From the AGA Journals

Treatment with endoscopic submucosal dissection (ESD) is associated with higher rates of complete remission of dysplasia at 2 years, compared with cap-assisted endoscopic mucosal resection (cEMR) in patients with Barrett’s esophagus with dysplasia or early-stage intramucosal esophageal adenocarcinoma (EAC), according to study findings.

Despite the seeming advantage of ESD over cEMR, the study found similar rates of complete remission of intestinal metaplasia (CRIM) between the treatment groups at 2 years.

The study authors explained that ESD, a recent development in endoscopic resection, allows for en bloc resection of larger lesions in dysplastic Barrett’s and EAC and features less diagnostic uncertainty, compared with cEMR. Findings from the study highlight the importance of this newer technique but also emphasize the utility of both treatments. “In expert hands both sets of procedures appear to be safe and well tolerated,” wrote study authors Don Codipilly, MD, of the Mayo Clinic in Rochester, Minn., and colleagues in Clinical Gastroenterology and Hepatology.

Given the lack of comparative data on the long-term outcomes of cEMR versus ESD in patients with neoplasia associated with Barrett’s esophagus, Dr. Codipilly and colleagues examined histologic outcomes in a prospectively maintained database of 537 patients who underwent endoscopic eradication therapy for Barrett’s esophagus or EAC at the Mayo Clinic between 2006 and 2020. Only patients who had undergone either cEMR (n = 456) or ESD (n = 81) followed by endoscopic ablation were included in the analysis.

The primary endpoint of the study was the rate and time to complete remission of dysplasia (CRD), which was defined by the absence of dysplasia on biopsy from the gastroesophageal junction and tubular esophagus during at least one surveillance endoscopy. Researchers also examined the rates of complications, such as clinically significant intraprocedural or postprocedural bleeding that required hospitalization, perforation, receipt of red blood cells within 30 days of the initial procedure, and stricture formation that required dilation within 120 days of the index procedure.

Patients in the ESD group had a longer mean length of resected specimens (23.9 vs. 10.9 mm; P < .01) as well as higher rates of en bloc (97.5% vs. 41.9%; P < .01) and R0 resection (58% vs. 20.2%; P < .01). Patients were generally balanced on other basic baseline demographics, including age, sex distribution, and smoking status.

Over a median 11.2-year follow-up period, a total of 420 patients in the cEMR group achieved CRD. In the ESD group, 48 patients achieved CRD over a median 1.4-year follow-up period. The 2-year cumulative probability of CRD was lower in patients who received cEMR versus those who received ESD (75.8% vs. 85.6%, respectively). In a univariate analysis, the odds of achieving CRD were lower in cEMR versus ESD (hazard ratio, 0.41; 95% CI, 0.31-0.54; P < .01).

According to multivariate analysis, two independent predictors of CRD included ESD (hazard ratio, 2.38; P <.01) and shorter Barrett’s segment length (HR, 1.11; P < .01).

The investigators also assessed whether advancements made in cEMR technique have contributed to the findings in an analysis of patients who underwent cEMR (n = 48) with ESD (n = 80) from 2015 to 2019. In this analysis, the researchers found that the odds of CRD were lower than that of ESD (HR, 0.67; 95% CI, 0.45-0.99). Additionally, higher odds of achieving CRD in the cEMR group were observed in years between 2013 and 2019 (n = 129), compared with years 2006-2012 (n = 112) (HR, 2.09; 95% CI, 1.59-2.75; P < .01).

Demographic and clinical variables were incorporated into a Cox proportional hazard model to identify factors associated with decreased odds of CRD. This analysis found that decreased odds of CRD were associated with longer Barrett’s esophagus segment length (HR, 0.90; P <.01) and treatment with cEMR versus ESD (HR, 0.42; P < .01).

Over median follow-up periods of 7.8 years in the cEMR group and 1.1 years in the ESD group, approximately 78.5% and 40.7% of patients, respectively, achieved CRIM. While those in the ESD group achieved CRIM earlier, the cumulative probabilities of CRIM were similar by 2 years (59.3% vs. 50.6%; HR, 0.74; 95% CI, 0.52-1.07; P = .11). Shorter Barrett’s esophagus segment was the only independent predictor of CRIM (HR, 1.16; P < .01).

The researchers noted that the study population may have included patients with more severe disease than that in the general population, which may limit the generalizability of the findings. Additionally, the lack of a randomized design was cited as an additional study limitation.

In spite of their findings, the researchers explained that “continued monitoring for additional outcomes such as recurrence are required for further elucidation of the optimal role of these procedures in the management of” neoplasia associated with Barrett’s esophagus.”

The study was funded by the National Cancer Institute and the Freeman Foundation. The researchers reported no conflicts of interest with any pharmaceutical companies.

Treatment with endoscopic submucosal dissection (ESD) is associated with higher rates of complete remission of dysplasia at 2 years, compared with cap-assisted endoscopic mucosal resection (cEMR) in patients with Barrett’s esophagus with dysplasia or early-stage intramucosal esophageal adenocarcinoma (EAC), according to study findings.

Despite the seeming advantage of ESD over cEMR, the study found similar rates of complete remission of intestinal metaplasia (CRIM) between the treatment groups at 2 years.

The study authors explained that ESD, a recent development in endoscopic resection, allows for en bloc resection of larger lesions in dysplastic Barrett’s and EAC and features less diagnostic uncertainty, compared with cEMR. Findings from the study highlight the importance of this newer technique but also emphasize the utility of both treatments. “In expert hands both sets of procedures appear to be safe and well tolerated,” wrote study authors Don Codipilly, MD, of the Mayo Clinic in Rochester, Minn., and colleagues in Clinical Gastroenterology and Hepatology.

Given the lack of comparative data on the long-term outcomes of cEMR versus ESD in patients with neoplasia associated with Barrett’s esophagus, Dr. Codipilly and colleagues examined histologic outcomes in a prospectively maintained database of 537 patients who underwent endoscopic eradication therapy for Barrett’s esophagus or EAC at the Mayo Clinic between 2006 and 2020. Only patients who had undergone either cEMR (n = 456) or ESD (n = 81) followed by endoscopic ablation were included in the analysis.

The primary endpoint of the study was the rate and time to complete remission of dysplasia (CRD), which was defined by the absence of dysplasia on biopsy from the gastroesophageal junction and tubular esophagus during at least one surveillance endoscopy. Researchers also examined the rates of complications, such as clinically significant intraprocedural or postprocedural bleeding that required hospitalization, perforation, receipt of red blood cells within 30 days of the initial procedure, and stricture formation that required dilation within 120 days of the index procedure.

Patients in the ESD group had a longer mean length of resected specimens (23.9 vs. 10.9 mm; P < .01) as well as higher rates of en bloc (97.5% vs. 41.9%; P < .01) and R0 resection (58% vs. 20.2%; P < .01). Patients were generally balanced on other basic baseline demographics, including age, sex distribution, and smoking status.

Over a median 11.2-year follow-up period, a total of 420 patients in the cEMR group achieved CRD. In the ESD group, 48 patients achieved CRD over a median 1.4-year follow-up period. The 2-year cumulative probability of CRD was lower in patients who received cEMR versus those who received ESD (75.8% vs. 85.6%, respectively). In a univariate analysis, the odds of achieving CRD were lower in cEMR versus ESD (hazard ratio, 0.41; 95% CI, 0.31-0.54; P < .01).

According to multivariate analysis, two independent predictors of CRD included ESD (hazard ratio, 2.38; P <.01) and shorter Barrett’s segment length (HR, 1.11; P < .01).

The investigators also assessed whether advancements made in cEMR technique have contributed to the findings in an analysis of patients who underwent cEMR (n = 48) with ESD (n = 80) from 2015 to 2019. In this analysis, the researchers found that the odds of CRD were lower than that of ESD (HR, 0.67; 95% CI, 0.45-0.99). Additionally, higher odds of achieving CRD in the cEMR group were observed in years between 2013 and 2019 (n = 129), compared with years 2006-2012 (n = 112) (HR, 2.09; 95% CI, 1.59-2.75; P < .01).

Demographic and clinical variables were incorporated into a Cox proportional hazard model to identify factors associated with decreased odds of CRD. This analysis found that decreased odds of CRD were associated with longer Barrett’s esophagus segment length (HR, 0.90; P <.01) and treatment with cEMR versus ESD (HR, 0.42; P < .01).

Over median follow-up periods of 7.8 years in the cEMR group and 1.1 years in the ESD group, approximately 78.5% and 40.7% of patients, respectively, achieved CRIM. While those in the ESD group achieved CRIM earlier, the cumulative probabilities of CRIM were similar by 2 years (59.3% vs. 50.6%; HR, 0.74; 95% CI, 0.52-1.07; P = .11). Shorter Barrett’s esophagus segment was the only independent predictor of CRIM (HR, 1.16; P < .01).

The researchers noted that the study population may have included patients with more severe disease than that in the general population, which may limit the generalizability of the findings. Additionally, the lack of a randomized design was cited as an additional study limitation.

In spite of their findings, the researchers explained that “continued monitoring for additional outcomes such as recurrence are required for further elucidation of the optimal role of these procedures in the management of” neoplasia associated with Barrett’s esophagus.”

The study was funded by the National Cancer Institute and the Freeman Foundation. The researchers reported no conflicts of interest with any pharmaceutical companies.

Treatment with endoscopic submucosal dissection (ESD) is associated with higher rates of complete remission of dysplasia at 2 years, compared with cap-assisted endoscopic mucosal resection (cEMR) in patients with Barrett’s esophagus with dysplasia or early-stage intramucosal esophageal adenocarcinoma (EAC), according to study findings.

Despite the seeming advantage of ESD over cEMR, the study found similar rates of complete remission of intestinal metaplasia (CRIM) between the treatment groups at 2 years.

The study authors explained that ESD, a recent development in endoscopic resection, allows for en bloc resection of larger lesions in dysplastic Barrett’s and EAC and features less diagnostic uncertainty, compared with cEMR. Findings from the study highlight the importance of this newer technique but also emphasize the utility of both treatments. “In expert hands both sets of procedures appear to be safe and well tolerated,” wrote study authors Don Codipilly, MD, of the Mayo Clinic in Rochester, Minn., and colleagues in Clinical Gastroenterology and Hepatology.

Given the lack of comparative data on the long-term outcomes of cEMR versus ESD in patients with neoplasia associated with Barrett’s esophagus, Dr. Codipilly and colleagues examined histologic outcomes in a prospectively maintained database of 537 patients who underwent endoscopic eradication therapy for Barrett’s esophagus or EAC at the Mayo Clinic between 2006 and 2020. Only patients who had undergone either cEMR (n = 456) or ESD (n = 81) followed by endoscopic ablation were included in the analysis.

The primary endpoint of the study was the rate and time to complete remission of dysplasia (CRD), which was defined by the absence of dysplasia on biopsy from the gastroesophageal junction and tubular esophagus during at least one surveillance endoscopy. Researchers also examined the rates of complications, such as clinically significant intraprocedural or postprocedural bleeding that required hospitalization, perforation, receipt of red blood cells within 30 days of the initial procedure, and stricture formation that required dilation within 120 days of the index procedure.

Patients in the ESD group had a longer mean length of resected specimens (23.9 vs. 10.9 mm; P < .01) as well as higher rates of en bloc (97.5% vs. 41.9%; P < .01) and R0 resection (58% vs. 20.2%; P < .01). Patients were generally balanced on other basic baseline demographics, including age, sex distribution, and smoking status.

Over a median 11.2-year follow-up period, a total of 420 patients in the cEMR group achieved CRD. In the ESD group, 48 patients achieved CRD over a median 1.4-year follow-up period. The 2-year cumulative probability of CRD was lower in patients who received cEMR versus those who received ESD (75.8% vs. 85.6%, respectively). In a univariate analysis, the odds of achieving CRD were lower in cEMR versus ESD (hazard ratio, 0.41; 95% CI, 0.31-0.54; P < .01).

According to multivariate analysis, two independent predictors of CRD included ESD (hazard ratio, 2.38; P <.01) and shorter Barrett’s segment length (HR, 1.11; P < .01).

The investigators also assessed whether advancements made in cEMR technique have contributed to the findings in an analysis of patients who underwent cEMR (n = 48) with ESD (n = 80) from 2015 to 2019. In this analysis, the researchers found that the odds of CRD were lower than that of ESD (HR, 0.67; 95% CI, 0.45-0.99). Additionally, higher odds of achieving CRD in the cEMR group were observed in years between 2013 and 2019 (n = 129), compared with years 2006-2012 (n = 112) (HR, 2.09; 95% CI, 1.59-2.75; P < .01).

Demographic and clinical variables were incorporated into a Cox proportional hazard model to identify factors associated with decreased odds of CRD. This analysis found that decreased odds of CRD were associated with longer Barrett’s esophagus segment length (HR, 0.90; P <.01) and treatment with cEMR versus ESD (HR, 0.42; P < .01).

Over median follow-up periods of 7.8 years in the cEMR group and 1.1 years in the ESD group, approximately 78.5% and 40.7% of patients, respectively, achieved CRIM. While those in the ESD group achieved CRIM earlier, the cumulative probabilities of CRIM were similar by 2 years (59.3% vs. 50.6%; HR, 0.74; 95% CI, 0.52-1.07; P = .11). Shorter Barrett’s esophagus segment was the only independent predictor of CRIM (HR, 1.16; P < .01).

The researchers noted that the study population may have included patients with more severe disease than that in the general population, which may limit the generalizability of the findings. Additionally, the lack of a randomized design was cited as an additional study limitation.

In spite of their findings, the researchers explained that “continued monitoring for additional outcomes such as recurrence are required for further elucidation of the optimal role of these procedures in the management of” neoplasia associated with Barrett’s esophagus.”

The study was funded by the National Cancer Institute and the Freeman Foundation. The researchers reported no conflicts of interest with any pharmaceutical companies.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a two-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a two-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a two-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

While often linked to deleterious outcomes in certain disease states, the hepatocyte-produced inflammatory marker C-reactive protein (CRP) may be a checkpoint that protects against acetaminophen-induced acute liver injury, according to research findings.

Based on the study findings, researchers believe long-term suppression of CRP function or expression may increase an individual’s susceptibility to acetaminophen-induced liver injury. In contrast, CRP “could be exploited as a promising therapeutic approach to treat hepatotoxicity caused by drug overdose” wrote study authors Hai-Yun Li, MD, of the Xi’an Jiaotong University in Shaanxi, China, and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

According to Dr. Li and colleagues, a major cause of acute liver failure is acetaminophen-induced liver injury, but despite this risk, very few treatment options for this condition exist. The only approved treatment for this complication is N-acetyl cysteine (NAC).

Although CRP represents a marker for inflammation following tissue injury, a study from 2020 and one from 2018 suggest the protein regulates complement activation and may modulate responses of immune cells. The authors of the current study noted that few studies have explored what roles complement activation and modulated immune cell responses via CRP play in acetaminophen-induced acute liver injury.

To further elucidate the role of CRP in this setting, Dr. Li and researchers assessed the mechanisms of CRP action both in vitro as well as in CRP mice with Fcy receptor 2B knockout. The researchers suggested CRP may modulate immune cell responses via these receptors. Additionally, the investigators assessed CRP action in mice with C3 knockout, given previous studies suggesting C3 knockout may alleviate acetaminophen-induced liver injury in mice. The researchers also investigated hepatic expression of CRP mutants that were defective in complement interaction. Finally, the researchers sought to understand the therapeutic potential of the inflammatory marker by performing intraperitoneal administration of human CRP at 2 or 6 hours after induction of acetaminophen-induced acute liver injury in wild-type mice.

Injection of 300 mg/kg acetaminophen over 24 hours led to overt liver injury in wild-type mice, which was characterized by increased levels of circulating alanine transaminase and aspartate transaminase as well as massive necrosis of hepatocytes. The researchers noted that these manifestations were exacerbated significantly in the CRP knockout mice.

The intravenous administration of human CRP in the mice with the drug-induced liver injury rescued defects caused by mouse CRP knockout. Additionally, human CRP administration alleviated acetaminophen-induced acute liver injury in the wild-type mice. The researchers wrote that these findings demonstrate that endogenous and human CRP “are both protective,” at least in mouse models of acetaminophen-induced liver injury.

In a second experiment, the researchers examined the mechanisms involved in CRP protection in early phases of drug-induced liver injury. Based on the experiment, the researchers found that the knockout of an inhibitory Fcy receptor mediating the anti-inflammatory activities of CRP demonstrated only “marginal effects” on the protection of the protein in acetaminophen-induced liver injury. Overall, the investigators suggested that the inflammatory marker does not likely act via the cellular Fcy receptor 2B to inhibit early phases of acetaminophen-induced hepatocyte injury. Rather, the investigators explained that CRP may act via factor H, which is recruited by CRP in regulating complement activation, to inhibit overactivation of complement on injured hepatocytes. Ultimately, the researchers explained, this results in suppression of the late phase amplification of inflammation that is mediated by neutrophils’ C3a-dependent actions.

Finally, the researchers found that intraperitoneal administration of human CRP at 2.5 mg/kg in wild-type mice at 2 hours following induction of acetaminophen-induced liver injury led to “markedly reduced liver injury,” with an efficacy that was similar to that of 500 mg/kg N-acetylcysteine, the only available treatment approved for acetaminophen-induced liver injury.

The researchers noted that N-acetylcysteine is only effective during the early phases of the acetaminophen-induced liver injury and loses effectiveness at 6 hours following injury. In contrast, human CRP in this study was still highly effective at this time point. “Given that people can tolerate high levels of circulating CRP, the administration of this protein might be a promising option to treat [acetaminophen-induced liver injury] with minimal side effects,” the researchers wrote.

The study was funded by the National Natural Science Foundation of China. The researchers reported no conflicts of interest with any pharmaceutical companies.

This article was updated on Sep. 20, 2022.

While often linked to deleterious outcomes in certain disease states, the hepatocyte-produced inflammatory marker C-reactive protein (CRP) may be a checkpoint that protects against acetaminophen-induced acute liver injury, according to research findings.

Based on the study findings, researchers believe long-term suppression of CRP function or expression may increase an individual’s susceptibility to acetaminophen-induced liver injury. In contrast, CRP “could be exploited as a promising therapeutic approach to treat hepatotoxicity caused by drug overdose” wrote study authors Hai-Yun Li, MD, of the Xi’an Jiaotong University in Shaanxi, China, and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

According to Dr. Li and colleagues, a major cause of acute liver failure is acetaminophen-induced liver injury, but despite this risk, very few treatment options for this condition exist. The only approved treatment for this complication is N-acetyl cysteine (NAC).

Although CRP represents a marker for inflammation following tissue injury, a study from 2020 and one from 2018 suggest the protein regulates complement activation and may modulate responses of immune cells. The authors of the current study noted that few studies have explored what roles complement activation and modulated immune cell responses via CRP play in acetaminophen-induced acute liver injury.

To further elucidate the role of CRP in this setting, Dr. Li and researchers assessed the mechanisms of CRP action both in vitro as well as in CRP mice with Fcy receptor 2B knockout. The researchers suggested CRP may modulate immune cell responses via these receptors. Additionally, the investigators assessed CRP action in mice with C3 knockout, given previous studies suggesting C3 knockout may alleviate acetaminophen-induced liver injury in mice. The researchers also investigated hepatic expression of CRP mutants that were defective in complement interaction. Finally, the researchers sought to understand the therapeutic potential of the inflammatory marker by performing intraperitoneal administration of human CRP at 2 or 6 hours after induction of acetaminophen-induced acute liver injury in wild-type mice.

Injection of 300 mg/kg acetaminophen over 24 hours led to overt liver injury in wild-type mice, which was characterized by increased levels of circulating alanine transaminase and aspartate transaminase as well as massive necrosis of hepatocytes. The researchers noted that these manifestations were exacerbated significantly in the CRP knockout mice.

The intravenous administration of human CRP in the mice with the drug-induced liver injury rescued defects caused by mouse CRP knockout. Additionally, human CRP administration alleviated acetaminophen-induced acute liver injury in the wild-type mice. The researchers wrote that these findings demonstrate that endogenous and human CRP “are both protective,” at least in mouse models of acetaminophen-induced liver injury.

In a second experiment, the researchers examined the mechanisms involved in CRP protection in early phases of drug-induced liver injury. Based on the experiment, the researchers found that the knockout of an inhibitory Fcy receptor mediating the anti-inflammatory activities of CRP demonstrated only “marginal effects” on the protection of the protein in acetaminophen-induced liver injury. Overall, the investigators suggested that the inflammatory marker does not likely act via the cellular Fcy receptor 2B to inhibit early phases of acetaminophen-induced hepatocyte injury. Rather, the investigators explained that CRP may act via factor H, which is recruited by CRP in regulating complement activation, to inhibit overactivation of complement on injured hepatocytes. Ultimately, the researchers explained, this results in suppression of the late phase amplification of inflammation that is mediated by neutrophils’ C3a-dependent actions.

Finally, the researchers found that intraperitoneal administration of human CRP at 2.5 mg/kg in wild-type mice at 2 hours following induction of acetaminophen-induced liver injury led to “markedly reduced liver injury,” with an efficacy that was similar to that of 500 mg/kg N-acetylcysteine, the only available treatment approved for acetaminophen-induced liver injury.

The researchers noted that N-acetylcysteine is only effective during the early phases of the acetaminophen-induced liver injury and loses effectiveness at 6 hours following injury. In contrast, human CRP in this study was still highly effective at this time point. “Given that people can tolerate high levels of circulating CRP, the administration of this protein might be a promising option to treat [acetaminophen-induced liver injury] with minimal side effects,” the researchers wrote.

The study was funded by the National Natural Science Foundation of China. The researchers reported no conflicts of interest with any pharmaceutical companies.

This article was updated on Sep. 20, 2022.

While often linked to deleterious outcomes in certain disease states, the hepatocyte-produced inflammatory marker C-reactive protein (CRP) may be a checkpoint that protects against acetaminophen-induced acute liver injury, according to research findings.

Based on the study findings, researchers believe long-term suppression of CRP function or expression may increase an individual’s susceptibility to acetaminophen-induced liver injury. In contrast, CRP “could be exploited as a promising therapeutic approach to treat hepatotoxicity caused by drug overdose” wrote study authors Hai-Yun Li, MD, of the Xi’an Jiaotong University in Shaanxi, China, and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

According to Dr. Li and colleagues, a major cause of acute liver failure is acetaminophen-induced liver injury, but despite this risk, very few treatment options for this condition exist. The only approved treatment for this complication is N-acetyl cysteine (NAC).

Although CRP represents a marker for inflammation following tissue injury, a study from 2020 and one from 2018 suggest the protein regulates complement activation and may modulate responses of immune cells. The authors of the current study noted that few studies have explored what roles complement activation and modulated immune cell responses via CRP play in acetaminophen-induced acute liver injury.

To further elucidate the role of CRP in this setting, Dr. Li and researchers assessed the mechanisms of CRP action both in vitro as well as in CRP mice with Fcy receptor 2B knockout. The researchers suggested CRP may modulate immune cell responses via these receptors. Additionally, the investigators assessed CRP action in mice with C3 knockout, given previous studies suggesting C3 knockout may alleviate acetaminophen-induced liver injury in mice. The researchers also investigated hepatic expression of CRP mutants that were defective in complement interaction. Finally, the researchers sought to understand the therapeutic potential of the inflammatory marker by performing intraperitoneal administration of human CRP at 2 or 6 hours after induction of acetaminophen-induced acute liver injury in wild-type mice.

Injection of 300 mg/kg acetaminophen over 24 hours led to overt liver injury in wild-type mice, which was characterized by increased levels of circulating alanine transaminase and aspartate transaminase as well as massive necrosis of hepatocytes. The researchers noted that these manifestations were exacerbated significantly in the CRP knockout mice.

The intravenous administration of human CRP in the mice with the drug-induced liver injury rescued defects caused by mouse CRP knockout. Additionally, human CRP administration alleviated acetaminophen-induced acute liver injury in the wild-type mice. The researchers wrote that these findings demonstrate that endogenous and human CRP “are both protective,” at least in mouse models of acetaminophen-induced liver injury.

In a second experiment, the researchers examined the mechanisms involved in CRP protection in early phases of drug-induced liver injury. Based on the experiment, the researchers found that the knockout of an inhibitory Fcy receptor mediating the anti-inflammatory activities of CRP demonstrated only “marginal effects” on the protection of the protein in acetaminophen-induced liver injury. Overall, the investigators suggested that the inflammatory marker does not likely act via the cellular Fcy receptor 2B to inhibit early phases of acetaminophen-induced hepatocyte injury. Rather, the investigators explained that CRP may act via factor H, which is recruited by CRP in regulating complement activation, to inhibit overactivation of complement on injured hepatocytes. Ultimately, the researchers explained, this results in suppression of the late phase amplification of inflammation that is mediated by neutrophils’ C3a-dependent actions.

Finally, the researchers found that intraperitoneal administration of human CRP at 2.5 mg/kg in wild-type mice at 2 hours following induction of acetaminophen-induced liver injury led to “markedly reduced liver injury,” with an efficacy that was similar to that of 500 mg/kg N-acetylcysteine, the only available treatment approved for acetaminophen-induced liver injury.

The researchers noted that N-acetylcysteine is only effective during the early phases of the acetaminophen-induced liver injury and loses effectiveness at 6 hours following injury. In contrast, human CRP in this study was still highly effective at this time point. “Given that people can tolerate high levels of circulating CRP, the administration of this protein might be a promising option to treat [acetaminophen-induced liver injury] with minimal side effects,” the researchers wrote.

The study was funded by the National Natural Science Foundation of China. The researchers reported no conflicts of interest with any pharmaceutical companies.

This article was updated on Sep. 20, 2022.

The American Gastroenterological Association recently published a Clinical Care Pathway for screening, diagnosis, and treatment of patients with nonalcoholic fatty liver disease (NAFLD).

Recommendations are intended for a spectrum of clinical settings, including primary care, obesity medicine, gastroenterology, hepatology, and endocrinology practices, reported lead author Fasiha Kanwal, MD, of Baylor College of Medicine, Houston, and colleagues.

“Most patients with NAFLD and NASH [nonalcoholic steatohepatitis] are seen in primary care or endocrine clinics,” the authors wrote in Gastroenterology. “Although not all patients with NAFLD/NASH require secondary (i.e., hepatology) care, not knowing which patients might benefit from such care and when to refer them results in inconsistent care processes and possibly poor outcomes. Clinical Care Pathways, with careful explication of each step in screening, diagnosis, and treatment, have been shown to improve the quality of health care delivery in other areas of medicine, [and] are crucial to addressing the often inconsistent care processes characterizing current approaches to NAFLD/NASH.”

The guidance was drafted by a group of 15 multidisciplinary experts from around the world representing the AGA, the American Diabetes Association, the American Osteopathic Association, the Obesity Society, and the Endocrine Society. Recommendations were based on available literature and clinical experience.

The authors recommended a four-step screening process for NAFLD/NASH: Check for risk factors predicting clinically relevant fibrosis (stage F2 or higher), review history and perform relevant laboratory tests, conduct noninvasive liver fibrosis testing, and measure liver stiffness.

Patients at greatest risk for clinically significant fibrosis include those with two or more metabolic risk factors, those with type 2 diabetes, and those with incidentally detected steatosis and/or elevated aminotransferases.

“A recent retrospective cohort study found that patients with hepatic steatosis and elevated alanine aminotransferase had a significantly higher risk of progression to cirrhosis or hepatocellular carcinoma than patients with hepatic steatosis and persistently normal alanine aminotransferase,” the authors noted.

When any of the above risk factors are present, the authors recommended checking the patient’s history for excessive alcohol intake, conducting a complete blood count and liver function tests, and screening for other hepatic and biliary diseases, such as chronic hepatitis C virus infection and liver mass lesions.

If other liver diseases have been ruled out, the first step in liver fibrosis risk stratification involves noninvasive testing, with the authors favoring the Fibrosis-4 (FIB-4) score “because it has been shown to have the best diagnostic accuracy for advanced fibrosis, compared with other noninvasive markers of fibrosis in patients with NAFLD.”

The next step in risk stratification involves liver stiffness measurement (LSM) with FibroScan (vibration controlled transient elastography [VCTE]), or newer modalities, such as bidimensional shear wave elastography or point shear wave elastography, which offer “diagnostic performances at least as good as VCTE.”

According to the publication, patients with NAFLD at low risk of advanced fibrosis (FIB-4 less than 1.3 or LSM less than 8 kPa or liver biopsy F0-F1) can be managed by one provider, such as a primary care provider or endocrinologist, whereas indeterminate-risk patients (FIB-4 of 1.3-2.67 and/or LSM 8-12 kPa and liver biopsy unavailable) and high-risk patients (FIB-4 greater than 2.67 or LSM greater than 12 kPa or liver biopsy F2-F4) should be managed by a multidisciplinary team led by a hepatologist.

Lifestyle intervention, weight loss (if overweight or obese), and cardiovascular disease risk reduction are advised for patients of all risk categories.

“There are no large, long-term behavioral modification or pharmacotherapy studies regarding weight loss in individuals with NAFLD,” the authors wrote. “However, weight loss of any magnitude should be encouraged as beneficial.”

For patients with indeterminate and high risk, NASH pharmacotherapy is recommended, and if needed, diabetes care should involve medications with efficacy in NASH, such as pioglitazone.

“Although we recognize that knowledge is continuing to evolve and that recommendations may change accordingly over time, we believe this Pathway provides accessible, standardized, evidence-based, timely, and testable recommendations that will allow clinicians to care for a rapidly growing population of patients, most of whom are managed in primary care or endocrine clinics,” the authors concluded.

The article was supported by the American Gastroenterological Association, Intercept Pharmaceuticals, Pfizer, and others. The authors disclosed relationships with Novo Nordisk, Eli Lilly, Sanofi, and others.

The American Gastroenterological Association recently published a Clinical Care Pathway for screening, diagnosis, and treatment of patients with nonalcoholic fatty liver disease (NAFLD).

Recommendations are intended for a spectrum of clinical settings, including primary care, obesity medicine, gastroenterology, hepatology, and endocrinology practices, reported lead author Fasiha Kanwal, MD, of Baylor College of Medicine, Houston, and colleagues.

“Most patients with NAFLD and NASH [nonalcoholic steatohepatitis] are seen in primary care or endocrine clinics,” the authors wrote in Gastroenterology. “Although not all patients with NAFLD/NASH require secondary (i.e., hepatology) care, not knowing which patients might benefit from such care and when to refer them results in inconsistent care processes and possibly poor outcomes. Clinical Care Pathways, with careful explication of each step in screening, diagnosis, and treatment, have been shown to improve the quality of health care delivery in other areas of medicine, [and] are crucial to addressing the often inconsistent care processes characterizing current approaches to NAFLD/NASH.”

The guidance was drafted by a group of 15 multidisciplinary experts from around the world representing the AGA, the American Diabetes Association, the American Osteopathic Association, the Obesity Society, and the Endocrine Society. Recommendations were based on available literature and clinical experience.

The authors recommended a four-step screening process for NAFLD/NASH: Check for risk factors predicting clinically relevant fibrosis (stage F2 or higher), review history and perform relevant laboratory tests, conduct noninvasive liver fibrosis testing, and measure liver stiffness.

Patients at greatest risk for clinically significant fibrosis include those with two or more metabolic risk factors, those with type 2 diabetes, and those with incidentally detected steatosis and/or elevated aminotransferases.

“A recent retrospective cohort study found that patients with hepatic steatosis and elevated alanine aminotransferase had a significantly higher risk of progression to cirrhosis or hepatocellular carcinoma than patients with hepatic steatosis and persistently normal alanine aminotransferase,” the authors noted.

When any of the above risk factors are present, the authors recommended checking the patient’s history for excessive alcohol intake, conducting a complete blood count and liver function tests, and screening for other hepatic and biliary diseases, such as chronic hepatitis C virus infection and liver mass lesions.

If other liver diseases have been ruled out, the first step in liver fibrosis risk stratification involves noninvasive testing, with the authors favoring the Fibrosis-4 (FIB-4) score “because it has been shown to have the best diagnostic accuracy for advanced fibrosis, compared with other noninvasive markers of fibrosis in patients with NAFLD.”

The next step in risk stratification involves liver stiffness measurement (LSM) with FibroScan (vibration controlled transient elastography [VCTE]), or newer modalities, such as bidimensional shear wave elastography or point shear wave elastography, which offer “diagnostic performances at least as good as VCTE.”

According to the publication, patients with NAFLD at low risk of advanced fibrosis (FIB-4 less than 1.3 or LSM less than 8 kPa or liver biopsy F0-F1) can be managed by one provider, such as a primary care provider or endocrinologist, whereas indeterminate-risk patients (FIB-4 of 1.3-2.67 and/or LSM 8-12 kPa and liver biopsy unavailable) and high-risk patients (FIB-4 greater than 2.67 or LSM greater than 12 kPa or liver biopsy F2-F4) should be managed by a multidisciplinary team led by a hepatologist.

Lifestyle intervention, weight loss (if overweight or obese), and cardiovascular disease risk reduction are advised for patients of all risk categories.

“There are no large, long-term behavioral modification or pharmacotherapy studies regarding weight loss in individuals with NAFLD,” the authors wrote. “However, weight loss of any magnitude should be encouraged as beneficial.”

For patients with indeterminate and high risk, NASH pharmacotherapy is recommended, and if needed, diabetes care should involve medications with efficacy in NASH, such as pioglitazone.

“Although we recognize that knowledge is continuing to evolve and that recommendations may change accordingly over time, we believe this Pathway provides accessible, standardized, evidence-based, timely, and testable recommendations that will allow clinicians to care for a rapidly growing population of patients, most of whom are managed in primary care or endocrine clinics,” the authors concluded.

The article was supported by the American Gastroenterological Association, Intercept Pharmaceuticals, Pfizer, and others. The authors disclosed relationships with Novo Nordisk, Eli Lilly, Sanofi, and others.

The American Gastroenterological Association recently published a Clinical Care Pathway for screening, diagnosis, and treatment of patients with nonalcoholic fatty liver disease (NAFLD).

Recommendations are intended for a spectrum of clinical settings, including primary care, obesity medicine, gastroenterology, hepatology, and endocrinology practices, reported lead author Fasiha Kanwal, MD, of Baylor College of Medicine, Houston, and colleagues.

“Most patients with NAFLD and NASH [nonalcoholic steatohepatitis] are seen in primary care or endocrine clinics,” the authors wrote in Gastroenterology. “Although not all patients with NAFLD/NASH require secondary (i.e., hepatology) care, not knowing which patients might benefit from such care and when to refer them results in inconsistent care processes and possibly poor outcomes. Clinical Care Pathways, with careful explication of each step in screening, diagnosis, and treatment, have been shown to improve the quality of health care delivery in other areas of medicine, [and] are crucial to addressing the often inconsistent care processes characterizing current approaches to NAFLD/NASH.”

The guidance was drafted by a group of 15 multidisciplinary experts from around the world representing the AGA, the American Diabetes Association, the American Osteopathic Association, the Obesity Society, and the Endocrine Society. Recommendations were based on available literature and clinical experience.

The authors recommended a four-step screening process for NAFLD/NASH: Check for risk factors predicting clinically relevant fibrosis (stage F2 or higher), review history and perform relevant laboratory tests, conduct noninvasive liver fibrosis testing, and measure liver stiffness.

Patients at greatest risk for clinically significant fibrosis include those with two or more metabolic risk factors, those with type 2 diabetes, and those with incidentally detected steatosis and/or elevated aminotransferases.

“A recent retrospective cohort study found that patients with hepatic steatosis and elevated alanine aminotransferase had a significantly higher risk of progression to cirrhosis or hepatocellular carcinoma than patients with hepatic steatosis and persistently normal alanine aminotransferase,” the authors noted.

When any of the above risk factors are present, the authors recommended checking the patient’s history for excessive alcohol intake, conducting a complete blood count and liver function tests, and screening for other hepatic and biliary diseases, such as chronic hepatitis C virus infection and liver mass lesions.

If other liver diseases have been ruled out, the first step in liver fibrosis risk stratification involves noninvasive testing, with the authors favoring the Fibrosis-4 (FIB-4) score “because it has been shown to have the best diagnostic accuracy for advanced fibrosis, compared with other noninvasive markers of fibrosis in patients with NAFLD.”

The next step in risk stratification involves liver stiffness measurement (LSM) with FibroScan (vibration controlled transient elastography [VCTE]), or newer modalities, such as bidimensional shear wave elastography or point shear wave elastography, which offer “diagnostic performances at least as good as VCTE.”

According to the publication, patients with NAFLD at low risk of advanced fibrosis (FIB-4 less than 1.3 or LSM less than 8 kPa or liver biopsy F0-F1) can be managed by one provider, such as a primary care provider or endocrinologist, whereas indeterminate-risk patients (FIB-4 of 1.3-2.67 and/or LSM 8-12 kPa and liver biopsy unavailable) and high-risk patients (FIB-4 greater than 2.67 or LSM greater than 12 kPa or liver biopsy F2-F4) should be managed by a multidisciplinary team led by a hepatologist.

Lifestyle intervention, weight loss (if overweight or obese), and cardiovascular disease risk reduction are advised for patients of all risk categories.

“There are no large, long-term behavioral modification or pharmacotherapy studies regarding weight loss in individuals with NAFLD,” the authors wrote. “However, weight loss of any magnitude should be encouraged as beneficial.”

For patients with indeterminate and high risk, NASH pharmacotherapy is recommended, and if needed, diabetes care should involve medications with efficacy in NASH, such as pioglitazone.

“Although we recognize that knowledge is continuing to evolve and that recommendations may change accordingly over time, we believe this Pathway provides accessible, standardized, evidence-based, timely, and testable recommendations that will allow clinicians to care for a rapidly growing population of patients, most of whom are managed in primary care or endocrine clinics,” the authors concluded.

The article was supported by the American Gastroenterological Association, Intercept Pharmaceuticals, Pfizer, and others. The authors disclosed relationships with Novo Nordisk, Eli Lilly, Sanofi, and others.

A blood-based biomarker panel that includes DNA and protein markers featured a 71% sensitivity at 90% specificity for the detection of early-stage hepatocellular carcinoma (HCC) compared with the GALAD (gender, age, a-fetoprotein [AFP], Lens culinaris agglutinin-reactive AFP [AFP-L3], and des-gamma-carboxy-prothrombin [DCP]) score or AFP alone, according to research findings. The panel reportedly performed well in certain subgroups based on sex, presence of cirrhosis, and liver disease etiology.

Jezperklauzen/ThinkStock

The study, which included inpatients with HCC and controls without HCC but underlying liver disease, suggests the panel could be utilized in the detection of early stage disease in patients with well-established risk factors for HCC. Ultimately, this may lead to earlier treatment initiation and potentially improved clinical outcomes.

“A blood-based marker panel that detects early-stage HCC with higher sensitivity than current biomarker-based approaches could substantially benefit patients undergoing HCC surveillance,” wrote study authors Naga Chalasani, MD, of Indiana University, Indianapolis, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

HCC, which accounts for most primary liver cancers, generally occurs in patients with several established risk factors, including alcoholic liver disease or nonalcoholic fatty liver disease as well as chronic hepatitis B virus or hepatitis C virus infection. Current guidelines, such as those from the European Association for the Study of the Liver and those from the American Association for the Study of Liver Diseases, recommend surveillance of at-risk patients every 6 months by ultrasound with or without AFP measurement. When caught early, HCC is typically treatable and is associated with a higher rate of survival compared with late-stage disease. According to Dr. Chalasani and colleagues, however, the effectiveness of current recommended surveillance for very early stage or early stage HCC is poor, characterized by a 45% sensitivity for ultrasound and a 63% sensitivity for ultrasound coupled with AFP measurement.

The investigators of the multicenter, case-control study collected blood specimens from 135 patients with HCC as well as 302 age-matched controls with underlying liver disease but no HCC. Very early or early stage disease was seen in approximately 56.3% of patients with HCC, and intermediate, advanced, or terminal stage disease was seen in 43.7% of patients.

To predict cases of HCC, the researchers used a logistic regression algorithm to analyze 10 methylated DNA markers (MDMs) associated with HCC, methylated B3GALT6 (reference DNA marker), and 3 candidate proteins. Finally, the researchers compared the accuracy of the developed blood-based biomarker panel with other blood-based biomarkers – including the GALAD, AFP, AFP-L3, DCP – for the detection of HCC.

The multitarget HCC panel included 3 MDMs – HOXA1, EMX1, and TSPYL5. In addition, the panel included methylation reference marker B3GALT6 and the protein markers AFP and AFP-L3. The biomarker panel featured a higher sensitivity (71%; 95% confidence interval, 60-81) at 90% specificity for the detection of early stage HCC compared with the GALAD score (41%; 95% CI, 30-53) or AFP ≥ 7.32 ng/mL (45%; 95% CI, 33-57). The area under the curve for the novel HCC panel for the detection of any stage HCC was 0.92 vs. 0.87 for the GALAD and 0.81 for the AFP measurement alone. The researchers found that the performance of the test was similar between men and women in terms of sensitivity (79% and 84%, respectively). Moreover, the panel performed similarly well among subgroups based on presence of cirrhosis and liver disease etiology.

A potential limitation of this study was the inclusion of controls who were largely confirmed HCC negative by ultrasound, a technique that lacks sensitivity for detecting early stage HCC, the researchers noted. Given this limitation, the researchers suggest that some of the control participants may have had underlying HCC that was missed by ultrasound. Furthermore, the findings indicate that the cross-sectional nature of the study may also mean some of the control participants had HCCs that were undetectable at initial screening.

Despite the limitations of the study, the researchers reported that the novel, blood-based marker panel’s sensitivity for detecting early stage HCC likely supports its use “among at-risk patients to enhance HCC surveillance and improve early cancer detection.”

The study was funded by the Exact Sciences Corporation. The researchers reported conflicts of interest with several pharmaceutical companies.

A blood-based biomarker panel that includes DNA and protein markers featured a 71% sensitivity at 90% specificity for the detection of early-stage hepatocellular carcinoma (HCC) compared with the GALAD (gender, age, a-fetoprotein [AFP], Lens culinaris agglutinin-reactive AFP [AFP-L3], and des-gamma-carboxy-prothrombin [DCP]) score or AFP alone, according to research findings. The panel reportedly performed well in certain subgroups based on sex, presence of cirrhosis, and liver disease etiology.

Jezperklauzen/ThinkStock

The study, which included inpatients with HCC and controls without HCC but underlying liver disease, suggests the panel could be utilized in the detection of early stage disease in patients with well-established risk factors for HCC. Ultimately, this may lead to earlier treatment initiation and potentially improved clinical outcomes.

“A blood-based marker panel that detects early-stage HCC with higher sensitivity than current biomarker-based approaches could substantially benefit patients undergoing HCC surveillance,” wrote study authors Naga Chalasani, MD, of Indiana University, Indianapolis, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

HCC, which accounts for most primary liver cancers, generally occurs in patients with several established risk factors, including alcoholic liver disease or nonalcoholic fatty liver disease as well as chronic hepatitis B virus or hepatitis C virus infection. Current guidelines, such as those from the European Association for the Study of the Liver and those from the American Association for the Study of Liver Diseases, recommend surveillance of at-risk patients every 6 months by ultrasound with or without AFP measurement. When caught early, HCC is typically treatable and is associated with a higher rate of survival compared with late-stage disease. According to Dr. Chalasani and colleagues, however, the effectiveness of current recommended surveillance for very early stage or early stage HCC is poor, characterized by a 45% sensitivity for ultrasound and a 63% sensitivity for ultrasound coupled with AFP measurement.

The investigators of the multicenter, case-control study collected blood specimens from 135 patients with HCC as well as 302 age-matched controls with underlying liver disease but no HCC. Very early or early stage disease was seen in approximately 56.3% of patients with HCC, and intermediate, advanced, or terminal stage disease was seen in 43.7% of patients.

To predict cases of HCC, the researchers used a logistic regression algorithm to analyze 10 methylated DNA markers (MDMs) associated with HCC, methylated B3GALT6 (reference DNA marker), and 3 candidate proteins. Finally, the researchers compared the accuracy of the developed blood-based biomarker panel with other blood-based biomarkers – including the GALAD, AFP, AFP-L3, DCP – for the detection of HCC.

The multitarget HCC panel included 3 MDMs – HOXA1, EMX1, and TSPYL5. In addition, the panel included methylation reference marker B3GALT6 and the protein markers AFP and AFP-L3. The biomarker panel featured a higher sensitivity (71%; 95% confidence interval, 60-81) at 90% specificity for the detection of early stage HCC compared with the GALAD score (41%; 95% CI, 30-53) or AFP ≥ 7.32 ng/mL (45%; 95% CI, 33-57). The area under the curve for the novel HCC panel for the detection of any stage HCC was 0.92 vs. 0.87 for the GALAD and 0.81 for the AFP measurement alone. The researchers found that the performance of the test was similar between men and women in terms of sensitivity (79% and 84%, respectively). Moreover, the panel performed similarly well among subgroups based on presence of cirrhosis and liver disease etiology.

A potential limitation of this study was the inclusion of controls who were largely confirmed HCC negative by ultrasound, a technique that lacks sensitivity for detecting early stage HCC, the researchers noted. Given this limitation, the researchers suggest that some of the control participants may have had underlying HCC that was missed by ultrasound. Furthermore, the findings indicate that the cross-sectional nature of the study may also mean some of the control participants had HCCs that were undetectable at initial screening.

Despite the limitations of the study, the researchers reported that the novel, blood-based marker panel’s sensitivity for detecting early stage HCC likely supports its use “among at-risk patients to enhance HCC surveillance and improve early cancer detection.”

The study was funded by the Exact Sciences Corporation. The researchers reported conflicts of interest with several pharmaceutical companies.

A blood-based biomarker panel that includes DNA and protein markers featured a 71% sensitivity at 90% specificity for the detection of early-stage hepatocellular carcinoma (HCC) compared with the GALAD (gender, age, a-fetoprotein [AFP], Lens culinaris agglutinin-reactive AFP [AFP-L3], and des-gamma-carboxy-prothrombin [DCP]) score or AFP alone, according to research findings. The panel reportedly performed well in certain subgroups based on sex, presence of cirrhosis, and liver disease etiology.

Jezperklauzen/ThinkStock

The study, which included inpatients with HCC and controls without HCC but underlying liver disease, suggests the panel could be utilized in the detection of early stage disease in patients with well-established risk factors for HCC. Ultimately, this may lead to earlier treatment initiation and potentially improved clinical outcomes.

“A blood-based marker panel that detects early-stage HCC with higher sensitivity than current biomarker-based approaches could substantially benefit patients undergoing HCC surveillance,” wrote study authors Naga Chalasani, MD, of Indiana University, Indianapolis, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

HCC, which accounts for most primary liver cancers, generally occurs in patients with several established risk factors, including alcoholic liver disease or nonalcoholic fatty liver disease as well as chronic hepatitis B virus or hepatitis C virus infection. Current guidelines, such as those from the European Association for the Study of the Liver and those from the American Association for the Study of Liver Diseases, recommend surveillance of at-risk patients every 6 months by ultrasound with or without AFP measurement. When caught early, HCC is typically treatable and is associated with a higher rate of survival compared with late-stage disease. According to Dr. Chalasani and colleagues, however, the effectiveness of current recommended surveillance for very early stage or early stage HCC is poor, characterized by a 45% sensitivity for ultrasound and a 63% sensitivity for ultrasound coupled with AFP measurement.

The investigators of the multicenter, case-control study collected blood specimens from 135 patients with HCC as well as 302 age-matched controls with underlying liver disease but no HCC. Very early or early stage disease was seen in approximately 56.3% of patients with HCC, and intermediate, advanced, or terminal stage disease was seen in 43.7% of patients.

To predict cases of HCC, the researchers used a logistic regression algorithm to analyze 10 methylated DNA markers (MDMs) associated with HCC, methylated B3GALT6 (reference DNA marker), and 3 candidate proteins. Finally, the researchers compared the accuracy of the developed blood-based biomarker panel with other blood-based biomarkers – including the GALAD, AFP, AFP-L3, DCP – for the detection of HCC.

The multitarget HCC panel included 3 MDMs – HOXA1, EMX1, and TSPYL5. In addition, the panel included methylation reference marker B3GALT6 and the protein markers AFP and AFP-L3. The biomarker panel featured a higher sensitivity (71%; 95% confidence interval, 60-81) at 90% specificity for the detection of early stage HCC compared with the GALAD score (41%; 95% CI, 30-53) or AFP ≥ 7.32 ng/mL (45%; 95% CI, 33-57). The area under the curve for the novel HCC panel for the detection of any stage HCC was 0.92 vs. 0.87 for the GALAD and 0.81 for the AFP measurement alone. The researchers found that the performance of the test was similar between men and women in terms of sensitivity (79% and 84%, respectively). Moreover, the panel performed similarly well among subgroups based on presence of cirrhosis and liver disease etiology.

A potential limitation of this study was the inclusion of controls who were largely confirmed HCC negative by ultrasound, a technique that lacks sensitivity for detecting early stage HCC, the researchers noted. Given this limitation, the researchers suggest that some of the control participants may have had underlying HCC that was missed by ultrasound. Furthermore, the findings indicate that the cross-sectional nature of the study may also mean some of the control participants had HCCs that were undetectable at initial screening.

Despite the limitations of the study, the researchers reported that the novel, blood-based marker panel’s sensitivity for detecting early stage HCC likely supports its use “among at-risk patients to enhance HCC surveillance and improve early cancer detection.”

The study was funded by the Exact Sciences Corporation. The researchers reported conflicts of interest with several pharmaceutical companies.

In a new study, researchers stimulated immune cells to assemble into tertiary lymphoid structures that improved the efficacy of chemotherapy in a preclinical model of pancreatic cancer.

Overall, the evidence generated by the study supports the notion that induction of tertiary lymphoid structures may potentiate chemotherapy’s antitumor activity, at least in a murine model of pancreatic ductal adenocarcinoma (PDAC). A more detailed understanding of tertiary lymphoid structure “kinetics and their induction, owing to multiple host and tumor factors, may help design personalized therapies harnessing the potential of immuno-oncology,” Francesca Delvecchio of Queen Mary University of London and colleagues wrote in Cellular and Molecular Gastroenterology and Hepatology.

While the immune system can play a role in combating cancer, a dense stroma surrounds pancreatic cancer cells, often blocking the ability of certain immune cells, such as T cells, from accessing the tumor. As shown by Young and colleagues, this causes immunotherapies to have very little success in the management of most pancreatic cancers, despite the efficacy of these therapies in other types of cancer.

In a proportion of patients with pancreatic cancer, clusters of immune cells can assemble tertiary lymphoid structures within the stroma that surrounds pancreatic cancer. These structures are associated with improved survival in PDAC. In the study, Mr. Delvecchio and colleagues sought to further elucidate the role of tertiary lymphoid structures in PDAC, particularly the structures’ antitumor potential.

The investigators analyzed donated tissue samples from patients to identify the presence of the structures within chemotherapy-naive human pancreatic cancer. Tertiary lymphoid structures were defined by the presence of tissue zones that were rich in T cells, B cells, and dendritic cells. Staining techniques were used to visualize the various cell types in the samples, revealing tertiary lymphoid structures in approximately 30% of tissue microarrays and 42% of the full section.

Multicolor immunofluorescence and immunohistochemistry were also used to characterize tertiary lymphoid structures in murine models of pancreatic cancer. Additionally, the investigators developed an orthotopic murine model to assess the development of the structures and their role in improving the therapeutic effects of chemotherapy. While tertiary lymphoid structures were not initially present in the preclinical murine model, B cells and T cells subsequently infiltrated into the tumor site following injection of lymphoid chemokines. These cells consequently assembled into the tertiary lymphoid structures.

In addition, the researchers combined chemotherapy gemcitabine with the intratumoral lymphoid chemokine and injected this combination treatment into orthotopic tumors. Following injection, the researchers observed “altered immune cell infiltration,” which facilitated the induction of tertiary lymphoid structures and potentiated antitumor activity of the chemotherapy. As a result, there was a significant reduction in the tumors, an effect the researchers did not find following the use of either treatment alone.

According to the investigators, the antitumor activity observed following induction of the tertiary lymphoid structures within the cancer is associated with B cell–mediated activation of dendritic cells, a key cell type involved in initiating an immune response.

Based on the findings, the researchers concluded that the combination of chemotherapy and lymphoid chemokines might be a viable strategy for promoting an antitumor immune response in pancreatic cancer. In turn, the researchers suggest this strategy may result in better clinical outcomes for patients with the disease. Additionally, the researchers wrote that mature tertiary lymphoid structures in PDAC prior to an immune treatment could “be used as a biomarker to define inclusion criteria of patients in immunotherapy protocols, with the aim to boost the ongoing antitumor immune response.”

The study relied on a mouse model and for this reason, it remains unclear at this time if the findings will be generalizable to humans. In the context of PDAC, the researchers wrote that further investigation and understanding of the formation of tertiary lymphoid structures may support the development of tailored treatments, including those that take advantage of the body’s immune system, to combat cancer and improve patient outcomes.

The researchers reported no conflicts of interest with the pharmaceutical industry. No funding was reported for the study.

In a new study, researchers stimulated immune cells to assemble into tertiary lymphoid structures that improved the efficacy of chemotherapy in a preclinical model of pancreatic cancer.

Overall, the evidence generated by the study supports the notion that induction of tertiary lymphoid structures may potentiate chemotherapy’s antitumor activity, at least in a murine model of pancreatic ductal adenocarcinoma (PDAC). A more detailed understanding of tertiary lymphoid structure “kinetics and their induction, owing to multiple host and tumor factors, may help design personalized therapies harnessing the potential of immuno-oncology,” Francesca Delvecchio of Queen Mary University of London and colleagues wrote in Cellular and Molecular Gastroenterology and Hepatology.

While the immune system can play a role in combating cancer, a dense stroma surrounds pancreatic cancer cells, often blocking the ability of certain immune cells, such as T cells, from accessing the tumor. As shown by Young and colleagues, this causes immunotherapies to have very little success in the management of most pancreatic cancers, despite the efficacy of these therapies in other types of cancer.

In a proportion of patients with pancreatic cancer, clusters of immune cells can assemble tertiary lymphoid structures within the stroma that surrounds pancreatic cancer. These structures are associated with improved survival in PDAC. In the study, Mr. Delvecchio and colleagues sought to further elucidate the role of tertiary lymphoid structures in PDAC, particularly the structures’ antitumor potential.

The investigators analyzed donated tissue samples from patients to identify the presence of the structures within chemotherapy-naive human pancreatic cancer. Tertiary lymphoid structures were defined by the presence of tissue zones that were rich in T cells, B cells, and dendritic cells. Staining techniques were used to visualize the various cell types in the samples, revealing tertiary lymphoid structures in approximately 30% of tissue microarrays and 42% of the full section.

Multicolor immunofluorescence and immunohistochemistry were also used to characterize tertiary lymphoid structures in murine models of pancreatic cancer. Additionally, the investigators developed an orthotopic murine model to assess the development of the structures and their role in improving the therapeutic effects of chemotherapy. While tertiary lymphoid structures were not initially present in the preclinical murine model, B cells and T cells subsequently infiltrated into the tumor site following injection of lymphoid chemokines. These cells consequently assembled into the tertiary lymphoid structures.

In addition, the researchers combined chemotherapy gemcitabine with the intratumoral lymphoid chemokine and injected this combination treatment into orthotopic tumors. Following injection, the researchers observed “altered immune cell infiltration,” which facilitated the induction of tertiary lymphoid structures and potentiated antitumor activity of the chemotherapy. As a result, there was a significant reduction in the tumors, an effect the researchers did not find following the use of either treatment alone.

According to the investigators, the antitumor activity observed following induction of the tertiary lymphoid structures within the cancer is associated with B cell–mediated activation of dendritic cells, a key cell type involved in initiating an immune response.

Based on the findings, the researchers concluded that the combination of chemotherapy and lymphoid chemokines might be a viable strategy for promoting an antitumor immune response in pancreatic cancer. In turn, the researchers suggest this strategy may result in better clinical outcomes for patients with the disease. Additionally, the researchers wrote that mature tertiary lymphoid structures in PDAC prior to an immune treatment could “be used as a biomarker to define inclusion criteria of patients in immunotherapy protocols, with the aim to boost the ongoing antitumor immune response.”

The study relied on a mouse model and for this reason, it remains unclear at this time if the findings will be generalizable to humans. In the context of PDAC, the researchers wrote that further investigation and understanding of the formation of tertiary lymphoid structures may support the development of tailored treatments, including those that take advantage of the body’s immune system, to combat cancer and improve patient outcomes.

The researchers reported no conflicts of interest with the pharmaceutical industry. No funding was reported for the study.

In a new study, researchers stimulated immune cells to assemble into tertiary lymphoid structures that improved the efficacy of chemotherapy in a preclinical model of pancreatic cancer.

Overall, the evidence generated by the study supports the notion that induction of tertiary lymphoid structures may potentiate chemotherapy’s antitumor activity, at least in a murine model of pancreatic ductal adenocarcinoma (PDAC). A more detailed understanding of tertiary lymphoid structure “kinetics and their induction, owing to multiple host and tumor factors, may help design personalized therapies harnessing the potential of immuno-oncology,” Francesca Delvecchio of Queen Mary University of London and colleagues wrote in Cellular and Molecular Gastroenterology and Hepatology.

While the immune system can play a role in combating cancer, a dense stroma surrounds pancreatic cancer cells, often blocking the ability of certain immune cells, such as T cells, from accessing the tumor. As shown by Young and colleagues, this causes immunotherapies to have very little success in the management of most pancreatic cancers, despite the efficacy of these therapies in other types of cancer.

In a proportion of patients with pancreatic cancer, clusters of immune cells can assemble tertiary lymphoid structures within the stroma that surrounds pancreatic cancer. These structures are associated with improved survival in PDAC. In the study, Mr. Delvecchio and colleagues sought to further elucidate the role of tertiary lymphoid structures in PDAC, particularly the structures’ antitumor potential.

The investigators analyzed donated tissue samples from patients to identify the presence of the structures within chemotherapy-naive human pancreatic cancer. Tertiary lymphoid structures were defined by the presence of tissue zones that were rich in T cells, B cells, and dendritic cells. Staining techniques were used to visualize the various cell types in the samples, revealing tertiary lymphoid structures in approximately 30% of tissue microarrays and 42% of the full section.

Multicolor immunofluorescence and immunohistochemistry were also used to characterize tertiary lymphoid structures in murine models of pancreatic cancer. Additionally, the investigators developed an orthotopic murine model to assess the development of the structures and their role in improving the therapeutic effects of chemotherapy. While tertiary lymphoid structures were not initially present in the preclinical murine model, B cells and T cells subsequently infiltrated into the tumor site following injection of lymphoid chemokines. These cells consequently assembled into the tertiary lymphoid structures.

In addition, the researchers combined chemotherapy gemcitabine with the intratumoral lymphoid chemokine and injected this combination treatment into orthotopic tumors. Following injection, the researchers observed “altered immune cell infiltration,” which facilitated the induction of tertiary lymphoid structures and potentiated antitumor activity of the chemotherapy. As a result, there was a significant reduction in the tumors, an effect the researchers did not find following the use of either treatment alone.

According to the investigators, the antitumor activity observed following induction of the tertiary lymphoid structures within the cancer is associated with B cell–mediated activation of dendritic cells, a key cell type involved in initiating an immune response.

Based on the findings, the researchers concluded that the combination of chemotherapy and lymphoid chemokines might be a viable strategy for promoting an antitumor immune response in pancreatic cancer. In turn, the researchers suggest this strategy may result in better clinical outcomes for patients with the disease. Additionally, the researchers wrote that mature tertiary lymphoid structures in PDAC prior to an immune treatment could “be used as a biomarker to define inclusion criteria of patients in immunotherapy protocols, with the aim to boost the ongoing antitumor immune response.”

The study relied on a mouse model and for this reason, it remains unclear at this time if the findings will be generalizable to humans. In the context of PDAC, the researchers wrote that further investigation and understanding of the formation of tertiary lymphoid structures may support the development of tailored treatments, including those that take advantage of the body’s immune system, to combat cancer and improve patient outcomes.

The researchers reported no conflicts of interest with the pharmaceutical industry. No funding was reported for the study.

An American Gastroenterological Association clinical practice update for gastrointestinal pain in disorders of gut-brain interaction (DGBI), published in Clinical Gastroenterology and Hepatology, emphasizes patient-physician collaboration and improvement of patient understanding of the pathways and mechanisms of pain sensations. It is aimed at management of patients in whom pain persists after first-line therapies fail to resolve visceral causes of pain.

DGBIs include irritable bowel syndrome, functional dyspepsia, and centrally mediated abdominal pain syndrome, according to Laurie Keefer, PhD, AGAF, of the division of gastroenterology at Icahn School of Medicine at Mount Sinai, New York, and colleagues. Initial treatment usually focuses on visceral triggers of pain such as food and bowel movements, but this approach is ineffective for many.

Cognitive, affective, and behavioral factors can impact the treatment of these patients, making it a complex clinical problem that calls for a collaborative approach between the patient and clinician. Opioids and other drugs that could be misused should be avoided, according to the authors. Both pharmacologic and nonpharmacologic approaches can be considered, but the update did not address use of marijuana or other complementary or alternative therapies.

Effective management requires empathy and collaboration. The patient has often seen various other clinicians with suboptimal results, which has left them dissatisfied with their care. Cultural sensitivity is crucial because the understanding and interpretation of pain, and preferred management approaches, vary across cultures.

The first step is a nonjudgmental patient history using open-ended questions. Examples include: “How do your symptoms interfere with your ability to do what you want in your daily life?” or “How are these symptoms impacting your life the most?” These types of questions may identify patients who could benefit from behavioral health interventions.

Questions about symptom-related anxiety can improve understanding of patient concerns and offer an opportunity to address fears. Additional understanding of the patient’s perspective can come from questions like: “What do you think is causing your symptoms,” “Why are you coming to see me now?” and “What are you most concerned about with your symptoms?”

The initial assessment should ideally result in shared goals and expectations for pain management.

Providers should educate the patient about the pathogenesis of pain and how it can be modified. Pain signals can result from innocuous signals from the gut that are misinterpreted by the vigilant brain as it scans for injury or illness. That model might explain why some patients with similar diagnoses have widely differing pain experiences, and offers hope that a change in how one approaches pain might lead to improvements. Patients should be encouraged to avoid too much focus on the cause or a solution to pain, because it can interfere with acceptance of pain or, when needed, treatment.

Opioids should not be prescribed for these patients, and if they are already taking them on referral, it’s important to manage them within a multidisciplinary framework until the opioids can be discontinued. Long-term use of opioids can lead to narcotic bowel syndrome, which results in chronic and often heightened abdominal pain even with escalating opioid doses. Opioid stoppage often must be accompanied by behavioral and psychiatric therapies to ensure success.

Nonpharmacological therapies such as brain-gut psychotherapies should be brought up as potential options early in treatment, even though many patients won’t require this type of care. Early mention is likely to keep the patient more open to trying them because they’re less likely to think of it as a sign of failure or a “last-ditch” approach. Cognitive-behavioral therapy works to improve pain management skills and bolster skill deficits, with attention to pain catastrophizing, pain hypervigilance, and visceral anxiety through different techniques.

Gut-directed hypnotherapy deals with somatic awareness and the use of imagery and suggestion to reduce pain sensations. Mindfulness-based stress reduction has been shown to be effective in inflammatory bowel disease and musculoskeletal pain syndromes. The provider should be familiar with these available methods, but should leave choice of interventions to partner mental health providers.

It’s important to distinguish between gastrointestinal pain with visceral causes and centrally mediated pain. Central sensitization can cause intermittent pain to become persistent even in the absence of ongoing peripheral causes of pain.

Peripheral acting agents affect gastrointestinal pain, and a network meta-analysis identified the top three drugs for pain relief in irritable bowel syndrome as tricyclic antidepressants, antispasmodics, and peppermint oil.

Neuromodulator drugs are an option for DGBI pain because the gut nervous system shares embryonic developmental pathways with the brain and spinal cord, which helps explains some of the benefits of low-dose antidepressants, now termed gut-brain neuromodulators. These drugs should be started at a low dose and gradually titrated according to symptom response and tolerability.

The authors have financial relationships with various pharmaceutical companies.

An American Gastroenterological Association clinical practice update for gastrointestinal pain in disorders of gut-brain interaction (DGBI), published in Clinical Gastroenterology and Hepatology, emphasizes patient-physician collaboration and improvement of patient understanding of the pathways and mechanisms of pain sensations. It is aimed at management of patients in whom pain persists after first-line therapies fail to resolve visceral causes of pain.

DGBIs include irritable bowel syndrome, functional dyspepsia, and centrally mediated abdominal pain syndrome, according to Laurie Keefer, PhD, AGAF, of the division of gastroenterology at Icahn School of Medicine at Mount Sinai, New York, and colleagues. Initial treatment usually focuses on visceral triggers of pain such as food and bowel movements, but this approach is ineffective for many.

Cognitive, affective, and behavioral factors can impact the treatment of these patients, making it a complex clinical problem that calls for a collaborative approach between the patient and clinician. Opioids and other drugs that could be misused should be avoided, according to the authors. Both pharmacologic and nonpharmacologic approaches can be considered, but the update did not address use of marijuana or other complementary or alternative therapies.

Effective management requires empathy and collaboration. The patient has often seen various other clinicians with suboptimal results, which has left them dissatisfied with their care. Cultural sensitivity is crucial because the understanding and interpretation of pain, and preferred management approaches, vary across cultures.

The first step is a nonjudgmental patient history using open-ended questions. Examples include: “How do your symptoms interfere with your ability to do what you want in your daily life?” or “How are these symptoms impacting your life the most?” These types of questions may identify patients who could benefit from behavioral health interventions.

Questions about symptom-related anxiety can improve understanding of patient concerns and offer an opportunity to address fears. Additional understanding of the patient’s perspective can come from questions like: “What do you think is causing your symptoms,” “Why are you coming to see me now?” and “What are you most concerned about with your symptoms?”

The initial assessment should ideally result in shared goals and expectations for pain management.

Providers should educate the patient about the pathogenesis of pain and how it can be modified. Pain signals can result from innocuous signals from the gut that are misinterpreted by the vigilant brain as it scans for injury or illness. That model might explain why some patients with similar diagnoses have widely differing pain experiences, and offers hope that a change in how one approaches pain might lead to improvements. Patients should be encouraged to avoid too much focus on the cause or a solution to pain, because it can interfere with acceptance of pain or, when needed, treatment.

Opioids should not be prescribed for these patients, and if they are already taking them on referral, it’s important to manage them within a multidisciplinary framework until the opioids can be discontinued. Long-term use of opioids can lead to narcotic bowel syndrome, which results in chronic and often heightened abdominal pain even with escalating opioid doses. Opioid stoppage often must be accompanied by behavioral and psychiatric therapies to ensure success.

Nonpharmacological therapies such as brain-gut psychotherapies should be brought up as potential options early in treatment, even though many patients won’t require this type of care. Early mention is likely to keep the patient more open to trying them because they’re less likely to think of it as a sign of failure or a “last-ditch” approach. Cognitive-behavioral therapy works to improve pain management skills and bolster skill deficits, with attention to pain catastrophizing, pain hypervigilance, and visceral anxiety through different techniques.

Gut-directed hypnotherapy deals with somatic awareness and the use of imagery and suggestion to reduce pain sensations. Mindfulness-based stress reduction has been shown to be effective in inflammatory bowel disease and musculoskeletal pain syndromes. The provider should be familiar with these available methods, but should leave choice of interventions to partner mental health providers.

It’s important to distinguish between gastrointestinal pain with visceral causes and centrally mediated pain. Central sensitization can cause intermittent pain to become persistent even in the absence of ongoing peripheral causes of pain.

Peripheral acting agents affect gastrointestinal pain, and a network meta-analysis identified the top three drugs for pain relief in irritable bowel syndrome as tricyclic antidepressants, antispasmodics, and peppermint oil.

Neuromodulator drugs are an option for DGBI pain because the gut nervous system shares embryonic developmental pathways with the brain and spinal cord, which helps explains some of the benefits of low-dose antidepressants, now termed gut-brain neuromodulators. These drugs should be started at a low dose and gradually titrated according to symptom response and tolerability.

The authors have financial relationships with various pharmaceutical companies.

An American Gastroenterological Association clinical practice update for gastrointestinal pain in disorders of gut-brain interaction (DGBI), published in Clinical Gastroenterology and Hepatology, emphasizes patient-physician collaboration and improvement of patient understanding of the pathways and mechanisms of pain sensations. It is aimed at management of patients in whom pain persists after first-line therapies fail to resolve visceral causes of pain.

DGBIs include irritable bowel syndrome, functional dyspepsia, and centrally mediated abdominal pain syndrome, according to Laurie Keefer, PhD, AGAF, of the division of gastroenterology at Icahn School of Medicine at Mount Sinai, New York, and colleagues. Initial treatment usually focuses on visceral triggers of pain such as food and bowel movements, but this approach is ineffective for many.

Cognitive, affective, and behavioral factors can impact the treatment of these patients, making it a complex clinical problem that calls for a collaborative approach between the patient and clinician. Opioids and other drugs that could be misused should be avoided, according to the authors. Both pharmacologic and nonpharmacologic approaches can be considered, but the update did not address use of marijuana or other complementary or alternative therapies.

Effective management requires empathy and collaboration. The patient has often seen various other clinicians with suboptimal results, which has left them dissatisfied with their care. Cultural sensitivity is crucial because the understanding and interpretation of pain, and preferred management approaches, vary across cultures.

The first step is a nonjudgmental patient history using open-ended questions. Examples include: “How do your symptoms interfere with your ability to do what you want in your daily life?” or “How are these symptoms impacting your life the most?” These types of questions may identify patients who could benefit from behavioral health interventions.

Questions about symptom-related anxiety can improve understanding of patient concerns and offer an opportunity to address fears. Additional understanding of the patient’s perspective can come from questions like: “What do you think is causing your symptoms,” “Why are you coming to see me now?” and “What are you most concerned about with your symptoms?”

The initial assessment should ideally result in shared goals and expectations for pain management.

Providers should educate the patient about the pathogenesis of pain and how it can be modified. Pain signals can result from innocuous signals from the gut that are misinterpreted by the vigilant brain as it scans for injury or illness. That model might explain why some patients with similar diagnoses have widely differing pain experiences, and offers hope that a change in how one approaches pain might lead to improvements. Patients should be encouraged to avoid too much focus on the cause or a solution to pain, because it can interfere with acceptance of pain or, when needed, treatment.

Opioids should not be prescribed for these patients, and if they are already taking them on referral, it’s important to manage them within a multidisciplinary framework until the opioids can be discontinued. Long-term use of opioids can lead to narcotic bowel syndrome, which results in chronic and often heightened abdominal pain even with escalating opioid doses. Opioid stoppage often must be accompanied by behavioral and psychiatric therapies to ensure success.

Nonpharmacological therapies such as brain-gut psychotherapies should be brought up as potential options early in treatment, even though many patients won’t require this type of care. Early mention is likely to keep the patient more open to trying them because they’re less likely to think of it as a sign of failure or a “last-ditch” approach. Cognitive-behavioral therapy works to improve pain management skills and bolster skill deficits, with attention to pain catastrophizing, pain hypervigilance, and visceral anxiety through different techniques.

Gut-directed hypnotherapy deals with somatic awareness and the use of imagery and suggestion to reduce pain sensations. Mindfulness-based stress reduction has been shown to be effective in inflammatory bowel disease and musculoskeletal pain syndromes. The provider should be familiar with these available methods, but should leave choice of interventions to partner mental health providers.

It’s important to distinguish between gastrointestinal pain with visceral causes and centrally mediated pain. Central sensitization can cause intermittent pain to become persistent even in the absence of ongoing peripheral causes of pain.

Peripheral acting agents affect gastrointestinal pain, and a network meta-analysis identified the top three drugs for pain relief in irritable bowel syndrome as tricyclic antidepressants, antispasmodics, and peppermint oil.

Neuromodulator drugs are an option for DGBI pain because the gut nervous system shares embryonic developmental pathways with the brain and spinal cord, which helps explains some of the benefits of low-dose antidepressants, now termed gut-brain neuromodulators. These drugs should be started at a low dose and gradually titrated according to symptom response and tolerability.

The authors have financial relationships with various pharmaceutical companies.

A newly updated version of the Model for End-Stage Liver Disease (MELD) score was effective for predicting short-term mortality in patients with end-stage liver disease and addressed important determinants of wait list outcomes that haven’t been addressed in previous versions, according to findings from a recent study. The new model, termed MELD 3.0, includes new variables such as female sex, serum albumin, and updated creatinine cutoffs.

Thomas Northcut/Getty Images

“We believe that the new model represents an opportunity to lower wait list mortality in the United States and propose it to be considered to replace the current version of MELD in determining allocation priorities in liver transplantation,” wrote study authors W. Ray Kim, MD, of Stanford (Calif.) University and colleagues in Gastroenterology.

In patients with end-stage liver disease, the MELD score was shown to be a reliable predictor of short-term survival, according to the researchers. The original version of MELD consists of international normalized ratio of prothrombin time and serum concentrations of bilirubin and creatinine; MELDNa consists of the same with the addition of serum concentrations of total sodium. Since 2016, MELDNa has been utilized in the United States to allocate livers for transplant.

Despite the utility of the current MELD score, questions have been raised concerning the accuracy of the tool’s ability to predict mortality, including a study by Sumeet K. Asrani, MD, MSc, and colleagues. Changes in liver disease epidemiology, the introduction of newer therapies that alter prognosis, as well as increasing age and prevalence of comorbidities in transplant-eligible patients are several drivers for these concerns, according to Dr. Kim and colleagues. Also, there is an increasing concern regarding women and their potential disadvantages in the current system: At least one study has suggested that serum creatinine may overestimate renal function and consequently underestimate mortality risk in female patients, compared with men with the same creatinine level.

Dr. Kim and colleagues sought to further optimize the fit of the current MELD score by considering alternative interactions and including other variables relevant to predicting short-term mortality in patients awaiting liver transplant. The study included patients who are registered on the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files newly wait-listed from 2016 through 2018. The full cohort was divided 70:30 into a development set (n = 20,587) and a validation set (n = 8,823); there were no significant differences between the sets in respect to age, sex, race, or liver disease severity.

The investigators used univariable and multivariable regression models to predict 90-day survival following wait list registration. The 90-day Kaplan-Meier survival rate in the development set was 91.3%. Additionally, model fit was tested, and the investigators used the Liver Simulated Allocation Model to estimate the impact of replacing the current version of the MELD with MELD 3.0.

In the final MELD 3.0 model, the researchers included several additional variables such as female sex and serum albumin. Additionally, the final model was characterized by interactions between bilirubin and sodium as well as between albumin and creatinine. Also, an adjustment to the current version of MELD lowering the upper bound for creatinine from 4.0 mg/dL to 3.0 mg/dL.

The MELD 3.0 featured significantly better discrimination, compared with the MELDNa (C-statistic = 0.8693 vs. 0.8622, respectively; P < .01). In addition, the researchers wrote that the new MELD 3.0 score “correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women.” The MELD 3.0 score with albumin also led to fewer wait-list deaths, compared with the MELDNa, according to the Liver Simulated Allocation Model analysis (P = .02); the number for MELD 3.0 without albumin was not statistically significant.

According to the investigators, a cause of concern for the MELD 3.0 was the addition of albumin, as this variable may be vulnerable to manipulation. In addition, the researchers note that, while differences in wait list mortality and survival based on race/ethnicity were observed in the study, they were unable to describe the exact root causes of worse outcomes among patients belonging to minority groups. “Thus, inclusion in a risk prediction score without fully understanding the underlying reasons for the racial disparity may have unintended consequences,” the researchers wrote.

“Based on recent data consisting of liver transplant candidates in the United States, we identify additional variables that are meaningfully associated with short-term mortality, including female sex and serum albumin. We also found evidence to support lowering the serum creatinine ceiling to 3 mg/dL,” they wrote. “Based on these data, we created an updated version of the MELD score, which improves mortality prediction compared to the current MELDNa model, including the recognition of female sex as a risk factor for death.”

The researchers reported no conflicts of interest with the pharmaceutical industry. No funding was reported for the study.

A newly updated version of the Model for End-Stage Liver Disease (MELD) score was effective for predicting short-term mortality in patients with end-stage liver disease and addressed important determinants of wait list outcomes that haven’t been addressed in previous versions, according to findings from a recent study. The new model, termed MELD 3.0, includes new variables such as female sex, serum albumin, and updated creatinine cutoffs.

Thomas Northcut/Getty Images

“We believe that the new model represents an opportunity to lower wait list mortality in the United States and propose it to be considered to replace the current version of MELD in determining allocation priorities in liver transplantation,” wrote study authors W. Ray Kim, MD, of Stanford (Calif.) University and colleagues in Gastroenterology.

In patients with end-stage liver disease, the MELD score was shown to be a reliable predictor of short-term survival, according to the researchers. The original version of MELD consists of international normalized ratio of prothrombin time and serum concentrations of bilirubin and creatinine; MELDNa consists of the same with the addition of serum concentrations of total sodium. Since 2016, MELDNa has been utilized in the United States to allocate livers for transplant.

Despite the utility of the current MELD score, questions have been raised concerning the accuracy of the tool’s ability to predict mortality, including a study by Sumeet K. Asrani, MD, MSc, and colleagues. Changes in liver disease epidemiology, the introduction of newer therapies that alter prognosis, as well as increasing age and prevalence of comorbidities in transplant-eligible patients are several drivers for these concerns, according to Dr. Kim and colleagues. Also, there is an increasing concern regarding women and their potential disadvantages in the current system: At least one study has suggested that serum creatinine may overestimate renal function and consequently underestimate mortality risk in female patients, compared with men with the same creatinine level.

Dr. Kim and colleagues sought to further optimize the fit of the current MELD score by considering alternative interactions and including other variables relevant to predicting short-term mortality in patients awaiting liver transplant. The study included patients who are registered on the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files newly wait-listed from 2016 through 2018. The full cohort was divided 70:30 into a development set (n = 20,587) and a validation set (n = 8,823); there were no significant differences between the sets in respect to age, sex, race, or liver disease severity.

The investigators used univariable and multivariable regression models to predict 90-day survival following wait list registration. The 90-day Kaplan-Meier survival rate in the development set was 91.3%. Additionally, model fit was tested, and the investigators used the Liver Simulated Allocation Model to estimate the impact of replacing the current version of the MELD with MELD 3.0.

In the final MELD 3.0 model, the researchers included several additional variables such as female sex and serum albumin. Additionally, the final model was characterized by interactions between bilirubin and sodium as well as between albumin and creatinine. Also, an adjustment to the current version of MELD lowering the upper bound for creatinine from 4.0 mg/dL to 3.0 mg/dL.

The MELD 3.0 featured significantly better discrimination, compared with the MELDNa (C-statistic = 0.8693 vs. 0.8622, respectively; P < .01). In addition, the researchers wrote that the new MELD 3.0 score “correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women.” The MELD 3.0 score with albumin also led to fewer wait-list deaths, compared with the MELDNa, according to the Liver Simulated Allocation Model analysis (P = .02); the number for MELD 3.0 without albumin was not statistically significant.

According to the investigators, a cause of concern for the MELD 3.0 was the addition of albumin, as this variable may be vulnerable to manipulation. In addition, the researchers note that, while differences in wait list mortality and survival based on race/ethnicity were observed in the study, they were unable to describe the exact root causes of worse outcomes among patients belonging to minority groups. “Thus, inclusion in a risk prediction score without fully understanding the underlying reasons for the racial disparity may have unintended consequences,” the researchers wrote.

“Based on recent data consisting of liver transplant candidates in the United States, we identify additional variables that are meaningfully associated with short-term mortality, including female sex and serum albumin. We also found evidence to support lowering the serum creatinine ceiling to 3 mg/dL,” they wrote. “Based on these data, we created an updated version of the MELD score, which improves mortality prediction compared to the current MELDNa model, including the recognition of female sex as a risk factor for death.”

The researchers reported no conflicts of interest with the pharmaceutical industry. No funding was reported for the study.

A newly updated version of the Model for End-Stage Liver Disease (MELD) score was effective for predicting short-term mortality in patients with end-stage liver disease and addressed important determinants of wait list outcomes that haven’t been addressed in previous versions, according to findings from a recent study. The new model, termed MELD 3.0, includes new variables such as female sex, serum albumin, and updated creatinine cutoffs.

Thomas Northcut/Getty Images

“We believe that the new model represents an opportunity to lower wait list mortality in the United States and propose it to be considered to replace the current version of MELD in determining allocation priorities in liver transplantation,” wrote study authors W. Ray Kim, MD, of Stanford (Calif.) University and colleagues in Gastroenterology.

In patients with end-stage liver disease, the MELD score was shown to be a reliable predictor of short-term survival, according to the researchers. The original version of MELD consists of international normalized ratio of prothrombin time and serum concentrations of bilirubin and creatinine; MELDNa consists of the same with the addition of serum concentrations of total sodium. Since 2016, MELDNa has been utilized in the United States to allocate livers for transplant.

Despite the utility of the current MELD score, questions have been raised concerning the accuracy of the tool’s ability to predict mortality, including a study by Sumeet K. Asrani, MD, MSc, and colleagues. Changes in liver disease epidemiology, the introduction of newer therapies that alter prognosis, as well as increasing age and prevalence of comorbidities in transplant-eligible patients are several drivers for these concerns, according to Dr. Kim and colleagues. Also, there is an increasing concern regarding women and their potential disadvantages in the current system: At least one study has suggested that serum creatinine may overestimate renal function and consequently underestimate mortality risk in female patients, compared with men with the same creatinine level.

Dr. Kim and colleagues sought to further optimize the fit of the current MELD score by considering alternative interactions and including other variables relevant to predicting short-term mortality in patients awaiting liver transplant. The study included patients who are registered on the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files newly wait-listed from 2016 through 2018. The full cohort was divided 70:30 into a development set (n = 20,587) and a validation set (n = 8,823); there were no significant differences between the sets in respect to age, sex, race, or liver disease severity.

The investigators used univariable and multivariable regression models to predict 90-day survival following wait list registration. The 90-day Kaplan-Meier survival rate in the development set was 91.3%. Additionally, model fit was tested, and the investigators used the Liver Simulated Allocation Model to estimate the impact of replacing the current version of the MELD with MELD 3.0.

In the final MELD 3.0 model, the researchers included several additional variables such as female sex and serum albumin. Additionally, the final model was characterized by interactions between bilirubin and sodium as well as between albumin and creatinine. Also, an adjustment to the current version of MELD lowering the upper bound for creatinine from 4.0 mg/dL to 3.0 mg/dL.

The MELD 3.0 featured significantly better discrimination, compared with the MELDNa (C-statistic = 0.8693 vs. 0.8622, respectively; P < .01). In addition, the researchers wrote that the new MELD 3.0 score “correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women.” The MELD 3.0 score with albumin also led to fewer wait-list deaths, compared with the MELDNa, according to the Liver Simulated Allocation Model analysis (P = .02); the number for MELD 3.0 without albumin was not statistically significant.

According to the investigators, a cause of concern for the MELD 3.0 was the addition of albumin, as this variable may be vulnerable to manipulation. In addition, the researchers note that, while differences in wait list mortality and survival based on race/ethnicity were observed in the study, they were unable to describe the exact root causes of worse outcomes among patients belonging to minority groups. “Thus, inclusion in a risk prediction score without fully understanding the underlying reasons for the racial disparity may have unintended consequences,” the researchers wrote.

“Based on recent data consisting of liver transplant candidates in the United States, we identify additional variables that are meaningfully associated with short-term mortality, including female sex and serum albumin. We also found evidence to support lowering the serum creatinine ceiling to 3 mg/dL,” they wrote. “Based on these data, we created an updated version of the MELD score, which improves mortality prediction compared to the current MELDNa model, including the recognition of female sex as a risk factor for death.”

The researchers reported no conflicts of interest with the pharmaceutical industry. No funding was reported for the study.

A clinical update from the American Gastroenterological Association focuses on bleeding and thrombosis-related questions in patients with cirrhosis. It provides guidance on test strategies for bleeding risk, preprocedure management of bleeding risk, venous thromboembolism (VTE) prophylaxis, screening for portal vein thrombosis (PVT), and anticoagulation therapies. It is aimed at primary care providers, gastroenterologists, and hepatologists, among other health care providers.

In cirrhosis, there are often changes to platelet (PLT) counts and prothrombin time/international normalized ratio (PT/INR), among other parameters, and historically these changes led to concerns that patients were at greater risk of bleeding or thrombosis. More recent evidence has led to a nuanced view. Neither factor necessarily suggests increased bleeding risk, and the severity of coagulopathy predicted by them does not predict the risk of bleeding complications.

Patients with cirrhosis are at greater risk of thrombosis, but clinicians may be hesitant to prescribe anticoagulants because of uncertain risk profiles, and test strategies employing PT/INR to estimate bleeding risk and track treatment endpoints in patients receiving vitamin K antagonists may not work in cirrhosis patients with alterations in procoagulant and anticoagulant measures. Recent efforts to address this led to testing of fibrin clot formation and lysis to better gauge the variety of abnormalities in cirrhosis patients.

The guideline, published in Gastroenterology, was informed by a technical review that focused on both bleeding-related and thrombosis-related questions. Bleeding-related questions included testing strategies and preprocedure prophylaxis to reduce bleeding risk. Thrombosis-related questions included whether VTE prophylaxis may be useful in hospitalized patients with cirrhosis, whether patients should be screened for PVT, potential therapies for nontumoral PVT, and whether or not anticoagulation is safe and effective when atrial fibrillation is present alongside cirrhosis.

Because of a lack of evidence, the guideline provides no recommendations on visco-elastic testing for bleeding risk in advance of common gastrointestinal procedures for patients with stable cirrhosis. It recommends against use of extensive preprocedural testing, such as repeated PT/INR or PLT count testing.

The guideline also looked at whether preprocedural efforts to correct coagulation parameters could reduce bleeding risk in patients with cirrhosis. It recommends against giving blood products ahead of the procedure for patients with stable cirrhosis without severe thrombocytopenia or severe coagulopathy. Such interventions can be considered for patients in the latter categories who are undergoing procedures with high bleeding risk after consideration of risks and benefits, and consultation with a hematologist.

Thrombopoietin receptor agonists (TPO-RAs) are also not recommended in patients with thrombocytopenia and stable cirrhosis undergoing common procedures, but they can be considered for patients who are more concerned about reduction of bleeding events and less concerned about the risk of PVT.

Patients who are hospitalized and meet the requirements should receive VTE prophylaxis. Although there is little available evidence about the effects of thromboprophylaxis in patients with cirrhosis, there is strong evidence of benefit in acutely ill hospitalized patients, and patients with cirrhosis are believed to be at a similar risk of VTE. There is evidence of increased bleed risk, but this is of very low certainty.

PVT should not be routinely tested for, but such testing can be offered to patients with a high level of concern over PVT and are not as worried about potential harms of treatment. This recommendation does not apply to patients waiting for a liver transplant.

Patients with non-umoral PVT should receive anticoagulation therapy, but patients who have high levels of concern about bleeding risk from anticoagulation and put a lower value on possible benefits of anticoagulation may choose not to receive it.

The guideline recommends anticoagulation for patients with atrial fibrillation and cirrhosis who are indicated for it. Patients with more concern about the bleeding risk of anticoagulation and place lower value on the reduction in stroke risk may choose to not receive anticoagulation. This is particularly true for those with more advanced cirrhosis (Child-Turcotte-Pugh Class C) and/or low CHA2DS2-VASC scores.

Nearly all of the recommendations in the guideline are conditional, reflecting a lack of data and a range of knowledge gaps that need filling. The authors call for additional research to identify specific patients who are at high risk for bleeding or thrombosis “to appropriately provide prophylaxis using blood product transfusion or TPO-RAs in patients at risk for clinically significant bleeding, to screen for and treat PVT, and to prevent clinically significant thromboembolic events.”

The development of the guideline was funded fully by the AGA. Members of the panel submitted conflict of interest information, and these statements are maintained at AGA headquarters.

A clinical update from the American Gastroenterological Association focuses on bleeding and thrombosis-related questions in patients with cirrhosis. It provides guidance on test strategies for bleeding risk, preprocedure management of bleeding risk, venous thromboembolism (VTE) prophylaxis, screening for portal vein thrombosis (PVT), and anticoagulation therapies. It is aimed at primary care providers, gastroenterologists, and hepatologists, among other health care providers.

In cirrhosis, there are often changes to platelet (PLT) counts and prothrombin time/international normalized ratio (PT/INR), among other parameters, and historically these changes led to concerns that patients were at greater risk of bleeding or thrombosis. More recent evidence has led to a nuanced view. Neither factor necessarily suggests increased bleeding risk, and the severity of coagulopathy predicted by them does not predict the risk of bleeding complications.

Patients with cirrhosis are at greater risk of thrombosis, but clinicians may be hesitant to prescribe anticoagulants because of uncertain risk profiles, and test strategies employing PT/INR to estimate bleeding risk and track treatment endpoints in patients receiving vitamin K antagonists may not work in cirrhosis patients with alterations in procoagulant and anticoagulant measures. Recent efforts to address this led to testing of fibrin clot formation and lysis to better gauge the variety of abnormalities in cirrhosis patients.

The guideline, published in Gastroenterology, was informed by a technical review that focused on both bleeding-related and thrombosis-related questions. Bleeding-related questions included testing strategies and preprocedure prophylaxis to reduce bleeding risk. Thrombosis-related questions included whether VTE prophylaxis may be useful in hospitalized patients with cirrhosis, whether patients should be screened for PVT, potential therapies for nontumoral PVT, and whether or not anticoagulation is safe and effective when atrial fibrillation is present alongside cirrhosis.

Because of a lack of evidence, the guideline provides no recommendations on visco-elastic testing for bleeding risk in advance of common gastrointestinal procedures for patients with stable cirrhosis. It recommends against use of extensive preprocedural testing, such as repeated PT/INR or PLT count testing.

The guideline also looked at whether preprocedural efforts to correct coagulation parameters could reduce bleeding risk in patients with cirrhosis. It recommends against giving blood products ahead of the procedure for patients with stable cirrhosis without severe thrombocytopenia or severe coagulopathy. Such interventions can be considered for patients in the latter categories who are undergoing procedures with high bleeding risk after consideration of risks and benefits, and consultation with a hematologist.

Thrombopoietin receptor agonists (TPO-RAs) are also not recommended in patients with thrombocytopenia and stable cirrhosis undergoing common procedures, but they can be considered for patients who are more concerned about reduction of bleeding events and less concerned about the risk of PVT.

Patients who are hospitalized and meet the requirements should receive VTE prophylaxis. Although there is little available evidence about the effects of thromboprophylaxis in patients with cirrhosis, there is strong evidence of benefit in acutely ill hospitalized patients, and patients with cirrhosis are believed to be at a similar risk of VTE. There is evidence of increased bleed risk, but this is of very low certainty.

PVT should not be routinely tested for, but such testing can be offered to patients with a high level of concern over PVT and are not as worried about potential harms of treatment. This recommendation does not apply to patients waiting for a liver transplant.

Patients with non-umoral PVT should receive anticoagulation therapy, but patients who have high levels of concern about bleeding risk from anticoagulation and put a lower value on possible benefits of anticoagulation may choose not to receive it.

The guideline recommends anticoagulation for patients with atrial fibrillation and cirrhosis who are indicated for it. Patients with more concern about the bleeding risk of anticoagulation and place lower value on the reduction in stroke risk may choose to not receive anticoagulation. This is particularly true for those with more advanced cirrhosis (Child-Turcotte-Pugh Class C) and/or low CHA2DS2-VASC scores.

Nearly all of the recommendations in the guideline are conditional, reflecting a lack of data and a range of knowledge gaps that need filling. The authors call for additional research to identify specific patients who are at high risk for bleeding or thrombosis “to appropriately provide prophylaxis using blood product transfusion or TPO-RAs in patients at risk for clinically significant bleeding, to screen for and treat PVT, and to prevent clinically significant thromboembolic events.”

The development of the guideline was funded fully by the AGA. Members of the panel submitted conflict of interest information, and these statements are maintained at AGA headquarters.

A clinical update from the American Gastroenterological Association focuses on bleeding and thrombosis-related questions in patients with cirrhosis. It provides guidance on test strategies for bleeding risk, preprocedure management of bleeding risk, venous thromboembolism (VTE) prophylaxis, screening for portal vein thrombosis (PVT), and anticoagulation therapies. It is aimed at primary care providers, gastroenterologists, and hepatologists, among other health care providers.

In cirrhosis, there are often changes to platelet (PLT) counts and prothrombin time/international normalized ratio (PT/INR), among other parameters, and historically these changes led to concerns that patients were at greater risk of bleeding or thrombosis. More recent evidence has led to a nuanced view. Neither factor necessarily suggests increased bleeding risk, and the severity of coagulopathy predicted by them does not predict the risk of bleeding complications.

Patients with cirrhosis are at greater risk of thrombosis, but clinicians may be hesitant to prescribe anticoagulants because of uncertain risk profiles, and test strategies employing PT/INR to estimate bleeding risk and track treatment endpoints in patients receiving vitamin K antagonists may not work in cirrhosis patients with alterations in procoagulant and anticoagulant measures. Recent efforts to address this led to testing of fibrin clot formation and lysis to better gauge the variety of abnormalities in cirrhosis patients.

The guideline, published in Gastroenterology, was informed by a technical review that focused on both bleeding-related and thrombosis-related questions. Bleeding-related questions included testing strategies and preprocedure prophylaxis to reduce bleeding risk. Thrombosis-related questions included whether VTE prophylaxis may be useful in hospitalized patients with cirrhosis, whether patients should be screened for PVT, potential therapies for nontumoral PVT, and whether or not anticoagulation is safe and effective when atrial fibrillation is present alongside cirrhosis.

Because of a lack of evidence, the guideline provides no recommendations on visco-elastic testing for bleeding risk in advance of common gastrointestinal procedures for patients with stable cirrhosis. It recommends against use of extensive preprocedural testing, such as repeated PT/INR or PLT count testing.

The guideline also looked at whether preprocedural efforts to correct coagulation parameters could reduce bleeding risk in patients with cirrhosis. It recommends against giving blood products ahead of the procedure for patients with stable cirrhosis without severe thrombocytopenia or severe coagulopathy. Such interventions can be considered for patients in the latter categories who are undergoing procedures with high bleeding risk after consideration of risks and benefits, and consultation with a hematologist.

Thrombopoietin receptor agonists (TPO-RAs) are also not recommended in patients with thrombocytopenia and stable cirrhosis undergoing common procedures, but they can be considered for patients who are more concerned about reduction of bleeding events and less concerned about the risk of PVT.

Patients who are hospitalized and meet the requirements should receive VTE prophylaxis. Although there is little available evidence about the effects of thromboprophylaxis in patients with cirrhosis, there is strong evidence of benefit in acutely ill hospitalized patients, and patients with cirrhosis are believed to be at a similar risk of VTE. There is evidence of increased bleed risk, but this is of very low certainty.

PVT should not be routinely tested for, but such testing can be offered to patients with a high level of concern over PVT and are not as worried about potential harms of treatment. This recommendation does not apply to patients waiting for a liver transplant.

Patients with non-umoral PVT should receive anticoagulation therapy, but patients who have high levels of concern about bleeding risk from anticoagulation and put a lower value on possible benefits of anticoagulation may choose not to receive it.

The guideline recommends anticoagulation for patients with atrial fibrillation and cirrhosis who are indicated for it. Patients with more concern about the bleeding risk of anticoagulation and place lower value on the reduction in stroke risk may choose to not receive anticoagulation. This is particularly true for those with more advanced cirrhosis (Child-Turcotte-Pugh Class C) and/or low CHA2DS2-VASC scores.

Nearly all of the recommendations in the guideline are conditional, reflecting a lack of data and a range of knowledge gaps that need filling. The authors call for additional research to identify specific patients who are at high risk for bleeding or thrombosis “to appropriately provide prophylaxis using blood product transfusion or TPO-RAs in patients at risk for clinically significant bleeding, to screen for and treat PVT, and to prevent clinically significant thromboembolic events.”

The development of the guideline was funded fully by the AGA. Members of the panel submitted conflict of interest information, and these statements are maintained at AGA headquarters.

The diagnostic performance of optical evaluation for submucosal invasive cancer (SMIC) in patients with large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) may be dependent on lesion morphology. While optical evaluation featured excellent performance in the assessment of flat lesions, the assessment only featured decent performance in nodular lesions, underscoring the need for additional evaluation algorithms for these lesions.

Endoscopists rely on the accuracy of real-time optical evaluation to facilitate appropriate selection of treatment; however, in studies focusing on LNPCPs, the performance of optical evaluation is modest.

The stratification of optical evaluation by lesion morphology may enable more accurate “implementation of a selective resection algorithm by identifying lesion subgroups with accurate optical evaluation performance characteristics,” first authors Sergei Vosko, MD, and Neal Shahidi, MD, of the department of gastroenterology and hepatology, Westmead Hospital, Sydney, and colleagues wrote in Clinical Gastroenterology and Hepatology.

Given the potential importance of stratification in optical evaluation, Dr. Vosko and colleagues assessed the performance of the optical assessment modality based on lesion morphology in a prospective cohort of 1,583 LNPCPs measuring at least 20 mm in patients (median age, 69 years) referred for endoscopic resection.

In the observational cohort, centers performed optical evaluation before endoscopic resection. The optical prediction of SMIC was based on several different established features, including Kudo V pit pattern, depressed morphology, rigidity/fixation, and ulceration. The researchers calculated optical evaluation performance outcomes, which were reported by the dominant morphology, namely nodular (Paris 0–Is/0– IIaDIs) versus flat (Paris 0–IIa/0–IIb).

Across the overall cohort, the median lesion size was 35 mm. The investigators identified a total of 855 flat LNPCPs and 728 nodular LNPCPs, with 63.9% of LNPCPs considered granular. Additionally, the researchers reported submucosal invasive cancer in 146 LNPCPs (9.2%).

According to the investigators, the overall sensitivity of optical evaluation to diagnose submucosal invasive cancer was 67.1% (95% confidence interval, 59.2%-74.2%), while the overall specificity was 95.1% (95% CI, 93.9%-96.1%). The investigators reported significant differences between flat vs. nodular LNPCPs in terms of sensitivity (90.9% vs. 52.7%, respectively; P <.001) and specificity (96.3% vs. 93.7%; P =.027).

Overall, the SMIC miss rate was 3.0% (95% CI, 2.3%-4.0%). There was a significant difference in the SMIC miss rate between flat and nodular LNPCPs (0.6% vs. 5.9%, respectively; P < .001).

Independent predictors of missed SMIC on optical evaluation, as identified in the multiple logistic regression analysis, included nodular morphology (odds ratio, 7.2; 95% CI, 2.8-18.9; P < .001), rectosigmoid location (OR, 2.0; 95% CI, 1.1-3.7; P =.026), and size of at least 40 mm (OR, 2.0; 95% CI, 1.0-3.8; P =.039).

Based on the findings, the researchers suggested that all flat lesions, in the absence of optical features consistent with submucosal invasive cancer, should subsequently be removed by high-quality endoscopic mucosal resection, in conjunction with the application of “site-specific modifications and ancillary techniques where needed.”

One limitation of this study is how lesion morphology was classified, which can in some cases be subjective.

The researchers added that additional refinement is required “to robustly apply a selective resection algorithm irrespective of lesion morphology” given the modest performance value of optical evaluation in nodular lesions. “Nevertheless, it is imperative that all endoscopists embrace optical evaluation in everyday clinical practice, thus harnessing its proven ability to influence resection technique selection and the associated clinical and economic ramifications,” they concluded.

The study received financial support the Cancer Institute of New South Wales, in addition to funding from the Gallipoli Medical Research Foundation. One author reported receiving research support from Olympus Medical, Cook Medical, and Boston Scientific. The remaining authors disclosed no conflicts.

The diagnostic performance of optical evaluation for submucosal invasive cancer (SMIC) in patients with large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) may be dependent on lesion morphology. While optical evaluation featured excellent performance in the assessment of flat lesions, the assessment only featured decent performance in nodular lesions, underscoring the need for additional evaluation algorithms for these lesions.

Endoscopists rely on the accuracy of real-time optical evaluation to facilitate appropriate selection of treatment; however, in studies focusing on LNPCPs, the performance of optical evaluation is modest.

The stratification of optical evaluation by lesion morphology may enable more accurate “implementation of a selective resection algorithm by identifying lesion subgroups with accurate optical evaluation performance characteristics,” first authors Sergei Vosko, MD, and Neal Shahidi, MD, of the department of gastroenterology and hepatology, Westmead Hospital, Sydney, and colleagues wrote in Clinical Gastroenterology and Hepatology.

Given the potential importance of stratification in optical evaluation, Dr. Vosko and colleagues assessed the performance of the optical assessment modality based on lesion morphology in a prospective cohort of 1,583 LNPCPs measuring at least 20 mm in patients (median age, 69 years) referred for endoscopic resection.

In the observational cohort, centers performed optical evaluation before endoscopic resection. The optical prediction of SMIC was based on several different established features, including Kudo V pit pattern, depressed morphology, rigidity/fixation, and ulceration. The researchers calculated optical evaluation performance outcomes, which were reported by the dominant morphology, namely nodular (Paris 0–Is/0– IIaDIs) versus flat (Paris 0–IIa/0–IIb).

Across the overall cohort, the median lesion size was 35 mm. The investigators identified a total of 855 flat LNPCPs and 728 nodular LNPCPs, with 63.9% of LNPCPs considered granular. Additionally, the researchers reported submucosal invasive cancer in 146 LNPCPs (9.2%).

According to the investigators, the overall sensitivity of optical evaluation to diagnose submucosal invasive cancer was 67.1% (95% confidence interval, 59.2%-74.2%), while the overall specificity was 95.1% (95% CI, 93.9%-96.1%). The investigators reported significant differences between flat vs. nodular LNPCPs in terms of sensitivity (90.9% vs. 52.7%, respectively; P <.001) and specificity (96.3% vs. 93.7%; P =.027).

Overall, the SMIC miss rate was 3.0% (95% CI, 2.3%-4.0%). There was a significant difference in the SMIC miss rate between flat and nodular LNPCPs (0.6% vs. 5.9%, respectively; P < .001).

Independent predictors of missed SMIC on optical evaluation, as identified in the multiple logistic regression analysis, included nodular morphology (odds ratio, 7.2; 95% CI, 2.8-18.9; P < .001), rectosigmoid location (OR, 2.0; 95% CI, 1.1-3.7; P =.026), and size of at least 40 mm (OR, 2.0; 95% CI, 1.0-3.8; P =.039).

Based on the findings, the researchers suggested that all flat lesions, in the absence of optical features consistent with submucosal invasive cancer, should subsequently be removed by high-quality endoscopic mucosal resection, in conjunction with the application of “site-specific modifications and ancillary techniques where needed.”

One limitation of this study is how lesion morphology was classified, which can in some cases be subjective.

The researchers added that additional refinement is required “to robustly apply a selective resection algorithm irrespective of lesion morphology” given the modest performance value of optical evaluation in nodular lesions. “Nevertheless, it is imperative that all endoscopists embrace optical evaluation in everyday clinical practice, thus harnessing its proven ability to influence resection technique selection and the associated clinical and economic ramifications,” they concluded.

The study received financial support the Cancer Institute of New South Wales, in addition to funding from the Gallipoli Medical Research Foundation. One author reported receiving research support from Olympus Medical, Cook Medical, and Boston Scientific. The remaining authors disclosed no conflicts.

The diagnostic performance of optical evaluation for submucosal invasive cancer (SMIC) in patients with large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) may be dependent on lesion morphology. While optical evaluation featured excellent performance in the assessment of flat lesions, the assessment only featured decent performance in nodular lesions, underscoring the need for additional evaluation algorithms for these lesions.

Endoscopists rely on the accuracy of real-time optical evaluation to facilitate appropriate selection of treatment; however, in studies focusing on LNPCPs, the performance of optical evaluation is modest.

The stratification of optical evaluation by lesion morphology may enable more accurate “implementation of a selective resection algorithm by identifying lesion subgroups with accurate optical evaluation performance characteristics,” first authors Sergei Vosko, MD, and Neal Shahidi, MD, of the department of gastroenterology and hepatology, Westmead Hospital, Sydney, and colleagues wrote in Clinical Gastroenterology and Hepatology.

Given the potential importance of stratification in optical evaluation, Dr. Vosko and colleagues assessed the performance of the optical assessment modality based on lesion morphology in a prospective cohort of 1,583 LNPCPs measuring at least 20 mm in patients (median age, 69 years) referred for endoscopic resection.

In the observational cohort, centers performed optical evaluation before endoscopic resection. The optical prediction of SMIC was based on several different established features, including Kudo V pit pattern, depressed morphology, rigidity/fixation, and ulceration. The researchers calculated optical evaluation performance outcomes, which were reported by the dominant morphology, namely nodular (Paris 0–Is/0– IIaDIs) versus flat (Paris 0–IIa/0–IIb).

Across the overall cohort, the median lesion size was 35 mm. The investigators identified a total of 855 flat LNPCPs and 728 nodular LNPCPs, with 63.9% of LNPCPs considered granular. Additionally, the researchers reported submucosal invasive cancer in 146 LNPCPs (9.2%).

According to the investigators, the overall sensitivity of optical evaluation to diagnose submucosal invasive cancer was 67.1% (95% confidence interval, 59.2%-74.2%), while the overall specificity was 95.1% (95% CI, 93.9%-96.1%). The investigators reported significant differences between flat vs. nodular LNPCPs in terms of sensitivity (90.9% vs. 52.7%, respectively; P <.001) and specificity (96.3% vs. 93.7%; P =.027).

Overall, the SMIC miss rate was 3.0% (95% CI, 2.3%-4.0%). There was a significant difference in the SMIC miss rate between flat and nodular LNPCPs (0.6% vs. 5.9%, respectively; P < .001).

Independent predictors of missed SMIC on optical evaluation, as identified in the multiple logistic regression analysis, included nodular morphology (odds ratio, 7.2; 95% CI, 2.8-18.9; P < .001), rectosigmoid location (OR, 2.0; 95% CI, 1.1-3.7; P =.026), and size of at least 40 mm (OR, 2.0; 95% CI, 1.0-3.8; P =.039).

Based on the findings, the researchers suggested that all flat lesions, in the absence of optical features consistent with submucosal invasive cancer, should subsequently be removed by high-quality endoscopic mucosal resection, in conjunction with the application of “site-specific modifications and ancillary techniques where needed.”

One limitation of this study is how lesion morphology was classified, which can in some cases be subjective.

The researchers added that additional refinement is required “to robustly apply a selective resection algorithm irrespective of lesion morphology” given the modest performance value of optical evaluation in nodular lesions. “Nevertheless, it is imperative that all endoscopists embrace optical evaluation in everyday clinical practice, thus harnessing its proven ability to influence resection technique selection and the associated clinical and economic ramifications,” they concluded.

The study received financial support the Cancer Institute of New South Wales, in addition to funding from the Gallipoli Medical Research Foundation. One author reported receiving research support from Olympus Medical, Cook Medical, and Boston Scientific. The remaining authors disclosed no conflicts.