Anti-CGRP monoclonal antibodies offer long-term efficacy and safety in resistant chronic migraine

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Key clinical point: Anticalcitonin generelated peptide (anti-CGRP) monoclonal antibodies were effective and safe over a 12-month treatment period in patients with treatment-resistant chronic migraine (CM) and medication overuse.

 

Major finding: Among patients followed up for 12 months, a ≥50% reduction in monthly migraine days and Migraine Disability Assessment score was achieved by 36.4%-66.6% and 84.4%-100% of patients, respectively. No severe treatment-related adverse events were observed.

 

Study details: Findings are from a prospective, monocentric, cohort study including 203 patients with CM (most also reporting medication overuse) who were resistant to ≥3 preventive treatments and commenced preventive therapy with erenumab, galcanezumab, or fremanezumab.

 

Disclosures: The study did not receive any financial support. P Geppetti and FD Cesaris reported receiving personal fees and research grants from various sources along with serving as an advisory board member or founding scientist for some sources.

Source: Iannone LF et al. Long-term effectiveness of three anti-CGRP monoclonal antibodies in resistant chronic migraine patients based on the MIDAS score. CNS Drugs. 2022;36:191-202 (Feb 11). Doi: 10.1007/s40263-021-00893-y

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Key clinical point: Anticalcitonin generelated peptide (anti-CGRP) monoclonal antibodies were effective and safe over a 12-month treatment period in patients with treatment-resistant chronic migraine (CM) and medication overuse.

 

Major finding: Among patients followed up for 12 months, a ≥50% reduction in monthly migraine days and Migraine Disability Assessment score was achieved by 36.4%-66.6% and 84.4%-100% of patients, respectively. No severe treatment-related adverse events were observed.

 

Study details: Findings are from a prospective, monocentric, cohort study including 203 patients with CM (most also reporting medication overuse) who were resistant to ≥3 preventive treatments and commenced preventive therapy with erenumab, galcanezumab, or fremanezumab.

 

Disclosures: The study did not receive any financial support. P Geppetti and FD Cesaris reported receiving personal fees and research grants from various sources along with serving as an advisory board member or founding scientist for some sources.

Source: Iannone LF et al. Long-term effectiveness of three anti-CGRP monoclonal antibodies in resistant chronic migraine patients based on the MIDAS score. CNS Drugs. 2022;36:191-202 (Feb 11). Doi: 10.1007/s40263-021-00893-y

Key clinical point: Anticalcitonin generelated peptide (anti-CGRP) monoclonal antibodies were effective and safe over a 12-month treatment period in patients with treatment-resistant chronic migraine (CM) and medication overuse.

 

Major finding: Among patients followed up for 12 months, a ≥50% reduction in monthly migraine days and Migraine Disability Assessment score was achieved by 36.4%-66.6% and 84.4%-100% of patients, respectively. No severe treatment-related adverse events were observed.

 

Study details: Findings are from a prospective, monocentric, cohort study including 203 patients with CM (most also reporting medication overuse) who were resistant to ≥3 preventive treatments and commenced preventive therapy with erenumab, galcanezumab, or fremanezumab.

 

Disclosures: The study did not receive any financial support. P Geppetti and FD Cesaris reported receiving personal fees and research grants from various sources along with serving as an advisory board member or founding scientist for some sources.

Source: Iannone LF et al. Long-term effectiveness of three anti-CGRP monoclonal antibodies in resistant chronic migraine patients based on the MIDAS score. CNS Drugs. 2022;36:191-202 (Feb 11). Doi: 10.1007/s40263-021-00893-y

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Clinical Edge Journal Scan Commentary: Multiple Sclerosis April 2022

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Dr. Gudesblatt scans the journals, so you don’t have to!

Mark Gudesblatt, MD
The past several months' reviews have focused on issues related to the effect of COVID-19 infection, vaccine responses, and disease-modifying therapies on care of people with multiple sclerosis (MS). Although SARS-CoV-2 infection and its complications presently appear to be less important, we must keep our collective eyes on COVID-19 trends and how they might influence future treatment and disease management. Vaccination's effect on disease remains an issue of concern. A recent prospective study of vaccination vigilance (N = 194) noted that influenza vaccines were well tolerated in people with MS. Although some experienced short-term and nonserious adverse events following immunization (AEFI), the risk for MS relapse was not significantly different from that of people with MS who were not vaccinated (Maniscalco et al). Overall, 60.2% of people with MS did not experience any vaccine-related AEFI. The 39.8% who experienced nonserious short-term symptoms reported pain at the injection site (68.1%), headache (10.6%), flu-like symptoms (17%), and fatigue (4.3%). Long-term AEFI included flu-like symptoms, COVID-19, and MS relapse. The incidence of both infection and MS relapse (P = .65), and the cumulative survival rate (P = .21), were not significantly different between the vaccinated and unvaccinated people with MS groups. Another study exploring links between vaccination and the occurrence of MS included 400,563 individuals from the Québec Birth Cohort on Immunity and Health who were followed from 1983 to 2014 (Corsenac et al). This study concluded that bacillus Calmette-Guérin (BCG) vaccination was not associated with the incidence of relapsing-remitting MS during the entire follow-up period (adjusted hazard ratio [aHR] 1.01; 95% CI 0.85-1.20), but BCG vaccinations were positively associated with the incidence of MS diagnosed later in life (aHR 1.22; 95% CI 1.09-1.36). This vaccine relationship is less of an issue in the United States, where BCG vaccination for tuberculosis is uncommon.

 

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

 

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

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Dr. Gudesblatt scans the journals, so you don’t have to!
Dr. Gudesblatt scans the journals, so you don’t have to!

Mark Gudesblatt, MD
The past several months' reviews have focused on issues related to the effect of COVID-19 infection, vaccine responses, and disease-modifying therapies on care of people with multiple sclerosis (MS). Although SARS-CoV-2 infection and its complications presently appear to be less important, we must keep our collective eyes on COVID-19 trends and how they might influence future treatment and disease management. Vaccination's effect on disease remains an issue of concern. A recent prospective study of vaccination vigilance (N = 194) noted that influenza vaccines were well tolerated in people with MS. Although some experienced short-term and nonserious adverse events following immunization (AEFI), the risk for MS relapse was not significantly different from that of people with MS who were not vaccinated (Maniscalco et al). Overall, 60.2% of people with MS did not experience any vaccine-related AEFI. The 39.8% who experienced nonserious short-term symptoms reported pain at the injection site (68.1%), headache (10.6%), flu-like symptoms (17%), and fatigue (4.3%). Long-term AEFI included flu-like symptoms, COVID-19, and MS relapse. The incidence of both infection and MS relapse (P = .65), and the cumulative survival rate (P = .21), were not significantly different between the vaccinated and unvaccinated people with MS groups. Another study exploring links between vaccination and the occurrence of MS included 400,563 individuals from the Québec Birth Cohort on Immunity and Health who were followed from 1983 to 2014 (Corsenac et al). This study concluded that bacillus Calmette-Guérin (BCG) vaccination was not associated with the incidence of relapsing-remitting MS during the entire follow-up period (adjusted hazard ratio [aHR] 1.01; 95% CI 0.85-1.20), but BCG vaccinations were positively associated with the incidence of MS diagnosed later in life (aHR 1.22; 95% CI 1.09-1.36). This vaccine relationship is less of an issue in the United States, where BCG vaccination for tuberculosis is uncommon.

 

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

 

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

Mark Gudesblatt, MD
The past several months' reviews have focused on issues related to the effect of COVID-19 infection, vaccine responses, and disease-modifying therapies on care of people with multiple sclerosis (MS). Although SARS-CoV-2 infection and its complications presently appear to be less important, we must keep our collective eyes on COVID-19 trends and how they might influence future treatment and disease management. Vaccination's effect on disease remains an issue of concern. A recent prospective study of vaccination vigilance (N = 194) noted that influenza vaccines were well tolerated in people with MS. Although some experienced short-term and nonserious adverse events following immunization (AEFI), the risk for MS relapse was not significantly different from that of people with MS who were not vaccinated (Maniscalco et al). Overall, 60.2% of people with MS did not experience any vaccine-related AEFI. The 39.8% who experienced nonserious short-term symptoms reported pain at the injection site (68.1%), headache (10.6%), flu-like symptoms (17%), and fatigue (4.3%). Long-term AEFI included flu-like symptoms, COVID-19, and MS relapse. The incidence of both infection and MS relapse (P = .65), and the cumulative survival rate (P = .21), were not significantly different between the vaccinated and unvaccinated people with MS groups. Another study exploring links between vaccination and the occurrence of MS included 400,563 individuals from the Québec Birth Cohort on Immunity and Health who were followed from 1983 to 2014 (Corsenac et al). This study concluded that bacillus Calmette-Guérin (BCG) vaccination was not associated with the incidence of relapsing-remitting MS during the entire follow-up period (adjusted hazard ratio [aHR] 1.01; 95% CI 0.85-1.20), but BCG vaccinations were positively associated with the incidence of MS diagnosed later in life (aHR 1.22; 95% CI 1.09-1.36). This vaccine relationship is less of an issue in the United States, where BCG vaccination for tuberculosis is uncommon.

 

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

 

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

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ACTRIMS 2022: Updates in Multiple Sclerosis Symptom Management

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ACTRIMS 2022: Updates in Multiple Sclerosis Symptom Management

Dr Enrique Alvarez, Associate Professor at the University of Colorado, reviews updates in symptom management that were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2022 meeting.

 

First, Dr Alvarez highlights two studies of nabiximols — a complex botanical mixture of tetrahydrocannabinol and cannabidiol — in patients with multiple sclerosis (MS). In both the GWSP0604 and SAVANT studies, patients taking nabiximols demonstrated significant spasticity improvement and reductions in spasm frequency.

 

Next, Dr Alvarez shares study results that compared patient responses to the responses of healthcare practitioners (HCPs) treating these patients for their MS. This analysis, which focused on cases of fatigue, mood, and cognition, found that patients reported significantly higher rates of these symptoms compared with HCP responses.

 

Another study assessed the importance of shared decision-making between HCPs and patients with MS, drawing from MEDLINE, EMBASE, and CINAHL databases. The researchers identified apparent challenges in patient education and access to information and recommended that shared decision-making be integrated into routine practice.

 

Dr Alvarez concludes with a review of new resources launched by the National Multiple Sclerosis Society, the goal of which is to inform and empower patients about dietary approaches for self-management and to support clinicians who are facilitating related discussions with their patients.

--

Enrique Alvarez, MD, PhD, Vice Chair of Clinical Research, Associate Professor, Department of Neurology, Division Neuroimmunology, University of Colorado, Rocky Mountain MS Center Anschutz Medical Center, Aurora, Colorado

 

Enrique Alvarez, MD, PhD, has disclosed the following relevant financial relationships:

 

Received research grant from: Biogen; Genentech/Roche; Novartis; TG Therapeutics; Patient-Centered Outcomes Research Initiative; National Multiple Sclerosis Society; National Institutes of Health; Rocky Mountain MS Center

 

Received income in an amount equal to or greater than $250 from: Actelion

 

 

 

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Dr Enrique Alvarez, Associate Professor at the University of Colorado, reviews updates in symptom management that were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2022 meeting.

 

First, Dr Alvarez highlights two studies of nabiximols — a complex botanical mixture of tetrahydrocannabinol and cannabidiol — in patients with multiple sclerosis (MS). In both the GWSP0604 and SAVANT studies, patients taking nabiximols demonstrated significant spasticity improvement and reductions in spasm frequency.

 

Next, Dr Alvarez shares study results that compared patient responses to the responses of healthcare practitioners (HCPs) treating these patients for their MS. This analysis, which focused on cases of fatigue, mood, and cognition, found that patients reported significantly higher rates of these symptoms compared with HCP responses.

 

Another study assessed the importance of shared decision-making between HCPs and patients with MS, drawing from MEDLINE, EMBASE, and CINAHL databases. The researchers identified apparent challenges in patient education and access to information and recommended that shared decision-making be integrated into routine practice.

 

Dr Alvarez concludes with a review of new resources launched by the National Multiple Sclerosis Society, the goal of which is to inform and empower patients about dietary approaches for self-management and to support clinicians who are facilitating related discussions with their patients.

--

Enrique Alvarez, MD, PhD, Vice Chair of Clinical Research, Associate Professor, Department of Neurology, Division Neuroimmunology, University of Colorado, Rocky Mountain MS Center Anschutz Medical Center, Aurora, Colorado

 

Enrique Alvarez, MD, PhD, has disclosed the following relevant financial relationships:

 

Received research grant from: Biogen; Genentech/Roche; Novartis; TG Therapeutics; Patient-Centered Outcomes Research Initiative; National Multiple Sclerosis Society; National Institutes of Health; Rocky Mountain MS Center

 

Received income in an amount equal to or greater than $250 from: Actelion

 

 

 

Dr Enrique Alvarez, Associate Professor at the University of Colorado, reviews updates in symptom management that were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2022 meeting.

 

First, Dr Alvarez highlights two studies of nabiximols — a complex botanical mixture of tetrahydrocannabinol and cannabidiol — in patients with multiple sclerosis (MS). In both the GWSP0604 and SAVANT studies, patients taking nabiximols demonstrated significant spasticity improvement and reductions in spasm frequency.

 

Next, Dr Alvarez shares study results that compared patient responses to the responses of healthcare practitioners (HCPs) treating these patients for their MS. This analysis, which focused on cases of fatigue, mood, and cognition, found that patients reported significantly higher rates of these symptoms compared with HCP responses.

 

Another study assessed the importance of shared decision-making between HCPs and patients with MS, drawing from MEDLINE, EMBASE, and CINAHL databases. The researchers identified apparent challenges in patient education and access to information and recommended that shared decision-making be integrated into routine practice.

 

Dr Alvarez concludes with a review of new resources launched by the National Multiple Sclerosis Society, the goal of which is to inform and empower patients about dietary approaches for self-management and to support clinicians who are facilitating related discussions with their patients.

--

Enrique Alvarez, MD, PhD, Vice Chair of Clinical Research, Associate Professor, Department of Neurology, Division Neuroimmunology, University of Colorado, Rocky Mountain MS Center Anschutz Medical Center, Aurora, Colorado

 

Enrique Alvarez, MD, PhD, has disclosed the following relevant financial relationships:

 

Received research grant from: Biogen; Genentech/Roche; Novartis; TG Therapeutics; Patient-Centered Outcomes Research Initiative; National Multiple Sclerosis Society; National Institutes of Health; Rocky Mountain MS Center

 

Received income in an amount equal to or greater than $250 from: Actelion

 

 

 

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HCC risk differs among various liver cirrhosis etiologies

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Key clinical point: The risk for hepatocellular carcinoma (HCC) varies with underlying etiologies, with active hepatitis C virus (HCV) cirrhosis posing the highest and alcoholic or nonalcoholic fatty liver disease (NAFLD) cirrhosis posing the lowest risk of developing HCC.

Major finding: Patients with active HCV (3.36%) showed the highest annual HCC incidence rate, followed by those with cured HCV (1.71%), alcoholic liver disease (1.32%), and NAFLD cirrhosis (1.24%). Patients with active HCV vs. NAFLD were at a 2.1-fold higher risk for HCC (adjusted hazard ratio 2.16; 95% CI, 1.16-4.04).

Study details: This multicenter, prospective cohort study analyzed data from two multiethnic cohorts enrolling a total of 2,733 patients with cirrhosis.

Disclosures: The study received financial support from the National Cancer Institute; Cancer Prevention & Research Institute of Texas grant; and Center for Gastrointestinal Development, Infection, and Injury. No conflicts of interest were reported.

Source: Kanwal F et al. Risk factors for hepatocellular cancer in contemporary cohorts of patients with cirrhosis. Hepatology. 2022 (Mar 1). Doi: 10.1002/hep.32434

 

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Key clinical point: The risk for hepatocellular carcinoma (HCC) varies with underlying etiologies, with active hepatitis C virus (HCV) cirrhosis posing the highest and alcoholic or nonalcoholic fatty liver disease (NAFLD) cirrhosis posing the lowest risk of developing HCC.

Major finding: Patients with active HCV (3.36%) showed the highest annual HCC incidence rate, followed by those with cured HCV (1.71%), alcoholic liver disease (1.32%), and NAFLD cirrhosis (1.24%). Patients with active HCV vs. NAFLD were at a 2.1-fold higher risk for HCC (adjusted hazard ratio 2.16; 95% CI, 1.16-4.04).

Study details: This multicenter, prospective cohort study analyzed data from two multiethnic cohorts enrolling a total of 2,733 patients with cirrhosis.

Disclosures: The study received financial support from the National Cancer Institute; Cancer Prevention & Research Institute of Texas grant; and Center for Gastrointestinal Development, Infection, and Injury. No conflicts of interest were reported.

Source: Kanwal F et al. Risk factors for hepatocellular cancer in contemporary cohorts of patients with cirrhosis. Hepatology. 2022 (Mar 1). Doi: 10.1002/hep.32434

 

Key clinical point: The risk for hepatocellular carcinoma (HCC) varies with underlying etiologies, with active hepatitis C virus (HCV) cirrhosis posing the highest and alcoholic or nonalcoholic fatty liver disease (NAFLD) cirrhosis posing the lowest risk of developing HCC.

Major finding: Patients with active HCV (3.36%) showed the highest annual HCC incidence rate, followed by those with cured HCV (1.71%), alcoholic liver disease (1.32%), and NAFLD cirrhosis (1.24%). Patients with active HCV vs. NAFLD were at a 2.1-fold higher risk for HCC (adjusted hazard ratio 2.16; 95% CI, 1.16-4.04).

Study details: This multicenter, prospective cohort study analyzed data from two multiethnic cohorts enrolling a total of 2,733 patients with cirrhosis.

Disclosures: The study received financial support from the National Cancer Institute; Cancer Prevention & Research Institute of Texas grant; and Center for Gastrointestinal Development, Infection, and Injury. No conflicts of interest were reported.

Source: Kanwal F et al. Risk factors for hepatocellular cancer in contemporary cohorts of patients with cirrhosis. Hepatology. 2022 (Mar 1). Doi: 10.1002/hep.32434

 

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Active HCV infection worsens the prognosis of very early-stage HCC after ablation therapy

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Key clinical point: Active hepatitis C virus (HCV) infection negatively affects overall and recurrence-free survival in patients with very early-stage hepatocellular carcinoma (HCC) after curative radiofrequency ablation (RFA).

Major finding: Active HCV infection was a significant risk factor for shorter overall survival (adjusted hazard ratio [aHR] 2.17; P = .003) and early recurrence of HCC (aHR 1.47; P = .022). Patients with vs. without active HCV infection had a shorter median overall (66 months vs. 145 months) and recurrence-free (20 months vs. 31 months) survival (both P < .001).

Study details: Findings are from a single-center retrospective study including 302 patients with very early-stage HCC (Barcelona Clinic Liver Cancer stage 0) who underwent RFA and had follow-up of >6 months, of which 195 had HCV infection, including 132 active infection cases.

Disclosures: M Kurosaki and N Izumi declared funding support from the Japan Agency for Medical Research and Development and Japanese Ministry of Health, Welfare, and Labor, respectively, and along with K Tsuchiya, receiving lecture fees from several sources.

Source: Takaura K et al. The impact of background liver disease on the long-term prognosis of very-early-stage HCC after ablation therapy. PLoS One. 2022;17(2):e0264075 (Feb 23). Doi:  10.1371/journal.pone.0264075

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Key clinical point: Active hepatitis C virus (HCV) infection negatively affects overall and recurrence-free survival in patients with very early-stage hepatocellular carcinoma (HCC) after curative radiofrequency ablation (RFA).

Major finding: Active HCV infection was a significant risk factor for shorter overall survival (adjusted hazard ratio [aHR] 2.17; P = .003) and early recurrence of HCC (aHR 1.47; P = .022). Patients with vs. without active HCV infection had a shorter median overall (66 months vs. 145 months) and recurrence-free (20 months vs. 31 months) survival (both P < .001).

Study details: Findings are from a single-center retrospective study including 302 patients with very early-stage HCC (Barcelona Clinic Liver Cancer stage 0) who underwent RFA and had follow-up of >6 months, of which 195 had HCV infection, including 132 active infection cases.

Disclosures: M Kurosaki and N Izumi declared funding support from the Japan Agency for Medical Research and Development and Japanese Ministry of Health, Welfare, and Labor, respectively, and along with K Tsuchiya, receiving lecture fees from several sources.

Source: Takaura K et al. The impact of background liver disease on the long-term prognosis of very-early-stage HCC after ablation therapy. PLoS One. 2022;17(2):e0264075 (Feb 23). Doi:  10.1371/journal.pone.0264075

Key clinical point: Active hepatitis C virus (HCV) infection negatively affects overall and recurrence-free survival in patients with very early-stage hepatocellular carcinoma (HCC) after curative radiofrequency ablation (RFA).

Major finding: Active HCV infection was a significant risk factor for shorter overall survival (adjusted hazard ratio [aHR] 2.17; P = .003) and early recurrence of HCC (aHR 1.47; P = .022). Patients with vs. without active HCV infection had a shorter median overall (66 months vs. 145 months) and recurrence-free (20 months vs. 31 months) survival (both P < .001).

Study details: Findings are from a single-center retrospective study including 302 patients with very early-stage HCC (Barcelona Clinic Liver Cancer stage 0) who underwent RFA and had follow-up of >6 months, of which 195 had HCV infection, including 132 active infection cases.

Disclosures: M Kurosaki and N Izumi declared funding support from the Japan Agency for Medical Research and Development and Japanese Ministry of Health, Welfare, and Labor, respectively, and along with K Tsuchiya, receiving lecture fees from several sources.

Source: Takaura K et al. The impact of background liver disease on the long-term prognosis of very-early-stage HCC after ablation therapy. PLoS One. 2022;17(2):e0264075 (Feb 23). Doi:  10.1371/journal.pone.0264075

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Risk factors for recurrence after hepatic resection for early-stage HCC

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Key clinical point: Independent risk factors for postoperative recurrence among patients undergoing curative hepatic resection for early-stage hepatocellular carcinoma (HCC) include preoperative alpha-fetoprotein (AFP) level >400 µg/L, tumor size >5 cm, satellite nodules, multiple tumors, and microvascular invasion.

Major finding: Cirrhosis (adjusted hazard ratio [aHR] 1.49; P < .001), preoperative AFP level >400 µg/L (aHR 1.28; P = .004), tumor size >5 cm (aHR 1.74; P < .001), satellite nodules (aHR 1.35; P = .040), multiple tumors (aHR 1.63; P = .015), microvascular invasion (aHR 1.51; P < .001), and intraoperative blood transfusion (aHR 1.50; P = .013) were identified as independent risk factors associated with postoperative recurrence.

Study details: The data come from a large-scale, multicenter retrospective study including 1,424 adult patients who underwent curative hepatic resection for early-stage HCC (Barcelona Clinic Liver Cancer stage 0/A).

Disclosures: The study was supported by the National Natural Science Foundation of China. The authors reported no conflict of interests.

Source: Yao L-Q et al. Clinical features of recurrence after hepatic resection for early-stage hepatocellular carcinoma and long-term survival outcomes of patients with recurrence: A multi-institutional analysis. Ann Surg Oncol. 2022 Feb 22. Doi: 10.1245/s10434-022-11454-y

 

 

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Key clinical point: Independent risk factors for postoperative recurrence among patients undergoing curative hepatic resection for early-stage hepatocellular carcinoma (HCC) include preoperative alpha-fetoprotein (AFP) level >400 µg/L, tumor size >5 cm, satellite nodules, multiple tumors, and microvascular invasion.

Major finding: Cirrhosis (adjusted hazard ratio [aHR] 1.49; P < .001), preoperative AFP level >400 µg/L (aHR 1.28; P = .004), tumor size >5 cm (aHR 1.74; P < .001), satellite nodules (aHR 1.35; P = .040), multiple tumors (aHR 1.63; P = .015), microvascular invasion (aHR 1.51; P < .001), and intraoperative blood transfusion (aHR 1.50; P = .013) were identified as independent risk factors associated with postoperative recurrence.

Study details: The data come from a large-scale, multicenter retrospective study including 1,424 adult patients who underwent curative hepatic resection for early-stage HCC (Barcelona Clinic Liver Cancer stage 0/A).

Disclosures: The study was supported by the National Natural Science Foundation of China. The authors reported no conflict of interests.

Source: Yao L-Q et al. Clinical features of recurrence after hepatic resection for early-stage hepatocellular carcinoma and long-term survival outcomes of patients with recurrence: A multi-institutional analysis. Ann Surg Oncol. 2022 Feb 22. Doi: 10.1245/s10434-022-11454-y

 

 

Key clinical point: Independent risk factors for postoperative recurrence among patients undergoing curative hepatic resection for early-stage hepatocellular carcinoma (HCC) include preoperative alpha-fetoprotein (AFP) level >400 µg/L, tumor size >5 cm, satellite nodules, multiple tumors, and microvascular invasion.

Major finding: Cirrhosis (adjusted hazard ratio [aHR] 1.49; P < .001), preoperative AFP level >400 µg/L (aHR 1.28; P = .004), tumor size >5 cm (aHR 1.74; P < .001), satellite nodules (aHR 1.35; P = .040), multiple tumors (aHR 1.63; P = .015), microvascular invasion (aHR 1.51; P < .001), and intraoperative blood transfusion (aHR 1.50; P = .013) were identified as independent risk factors associated with postoperative recurrence.

Study details: The data come from a large-scale, multicenter retrospective study including 1,424 adult patients who underwent curative hepatic resection for early-stage HCC (Barcelona Clinic Liver Cancer stage 0/A).

Disclosures: The study was supported by the National Natural Science Foundation of China. The authors reported no conflict of interests.

Source: Yao L-Q et al. Clinical features of recurrence after hepatic resection for early-stage hepatocellular carcinoma and long-term survival outcomes of patients with recurrence: A multi-institutional analysis. Ann Surg Oncol. 2022 Feb 22. Doi: 10.1245/s10434-022-11454-y

 

 

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Inadequate ultrasound quality negatively influences HCC surveillance test performance

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Key clinical point: Hampered ultrasound visualization in patients with cirrhosis receiving hepatocellular carcinoma (HCC) surveillance is associated with worse test performance, negatively affecting both sensitivity and specificity of surveillance.

Major finding: Patients with cirrhosis and HCC having severely impaired ultrasound visualization before HCC diagnosis showed increased odds of false-negative results (adjusted odds ratio [aOR] 7.94; 95% CI 1.23-51.16), whereas those with only cirrhosis having moderately impaired visualization showed increased odds of false-positive results (aOR 1.60; 95% CI 1.13-2.27).

Study details: This was a retrospective cohort study involving 2,238 patients with cirrhosis, with (n = 186) or without (n = 2,052) HCC, who underwent at least one abdominal ultrasound examination.

Disclosures: The study was supported by the United States National Institute of Health. A Singal and D Fetzer declared serving as consultants or advisory board members of or having research agreements with various organizations.

Source: Chong N et al. Association between ultrasound quality and test performance for HCC surveillance in patients with cirrhosis: a retrospective cohort study. Aliment Pharmacol Ther. 2022;55(6):683-690 (Feb 15). Doi: 10.1111/apt.16779

 

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Key clinical point: Hampered ultrasound visualization in patients with cirrhosis receiving hepatocellular carcinoma (HCC) surveillance is associated with worse test performance, negatively affecting both sensitivity and specificity of surveillance.

Major finding: Patients with cirrhosis and HCC having severely impaired ultrasound visualization before HCC diagnosis showed increased odds of false-negative results (adjusted odds ratio [aOR] 7.94; 95% CI 1.23-51.16), whereas those with only cirrhosis having moderately impaired visualization showed increased odds of false-positive results (aOR 1.60; 95% CI 1.13-2.27).

Study details: This was a retrospective cohort study involving 2,238 patients with cirrhosis, with (n = 186) or without (n = 2,052) HCC, who underwent at least one abdominal ultrasound examination.

Disclosures: The study was supported by the United States National Institute of Health. A Singal and D Fetzer declared serving as consultants or advisory board members of or having research agreements with various organizations.

Source: Chong N et al. Association between ultrasound quality and test performance for HCC surveillance in patients with cirrhosis: a retrospective cohort study. Aliment Pharmacol Ther. 2022;55(6):683-690 (Feb 15). Doi: 10.1111/apt.16779

 

Key clinical point: Hampered ultrasound visualization in patients with cirrhosis receiving hepatocellular carcinoma (HCC) surveillance is associated with worse test performance, negatively affecting both sensitivity and specificity of surveillance.

Major finding: Patients with cirrhosis and HCC having severely impaired ultrasound visualization before HCC diagnosis showed increased odds of false-negative results (adjusted odds ratio [aOR] 7.94; 95% CI 1.23-51.16), whereas those with only cirrhosis having moderately impaired visualization showed increased odds of false-positive results (aOR 1.60; 95% CI 1.13-2.27).

Study details: This was a retrospective cohort study involving 2,238 patients with cirrhosis, with (n = 186) or without (n = 2,052) HCC, who underwent at least one abdominal ultrasound examination.

Disclosures: The study was supported by the United States National Institute of Health. A Singal and D Fetzer declared serving as consultants or advisory board members of or having research agreements with various organizations.

Source: Chong N et al. Association between ultrasound quality and test performance for HCC surveillance in patients with cirrhosis: a retrospective cohort study. Aliment Pharmacol Ther. 2022;55(6):683-690 (Feb 15). Doi: 10.1111/apt.16779

 

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MRE-based shear strain mapping may preoperatively predict microvascular invasion in HCC

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Key clinical point: Magnetic resonance elastography (MRE)-based shear strain mapping may serve as a noninvasive biomarker enabling the characterization of the tumor-liver interface and preoperative prediction of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC).

Major finding: The positive MVI vs. negative MVI group displayed a significantly higher octahedral shear strain (OSS) percentage of low-shear-strain length (pLSL) at three evaluation frequencies (60 Hz: 75% vs. 40%, 40 Hz: 85% vs. 40%, and 30 Hz: 70% vs. 20%; all P < .01). The peritumor OSS-pLSL area under the receiver operating characteristic curve (0.73-0.90) for MVI prediction was good/excellent at all frequencies.

Study details: The data are derived from a retrospective study of 59 patients with HCC, all of whom underwent the conventional 60 Hz MRE examination; of these, 29 patients also underwent 40 and 30 Hz MRE examinations.

Disclosures: The study was funded by the National Natural Science Foundation of China, among others. The authors declared no conflict of interests.

Source: Li M et al. MR elastography-based shear strain mapping for assessment of microvascular invasion in hepatocellular carcinoma. Eur Radiol. 2022 (Feb 11). Doi: 10.1007/s00330-022-08578-w

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Key clinical point: Magnetic resonance elastography (MRE)-based shear strain mapping may serve as a noninvasive biomarker enabling the characterization of the tumor-liver interface and preoperative prediction of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC).

Major finding: The positive MVI vs. negative MVI group displayed a significantly higher octahedral shear strain (OSS) percentage of low-shear-strain length (pLSL) at three evaluation frequencies (60 Hz: 75% vs. 40%, 40 Hz: 85% vs. 40%, and 30 Hz: 70% vs. 20%; all P < .01). The peritumor OSS-pLSL area under the receiver operating characteristic curve (0.73-0.90) for MVI prediction was good/excellent at all frequencies.

Study details: The data are derived from a retrospective study of 59 patients with HCC, all of whom underwent the conventional 60 Hz MRE examination; of these, 29 patients also underwent 40 and 30 Hz MRE examinations.

Disclosures: The study was funded by the National Natural Science Foundation of China, among others. The authors declared no conflict of interests.

Source: Li M et al. MR elastography-based shear strain mapping for assessment of microvascular invasion in hepatocellular carcinoma. Eur Radiol. 2022 (Feb 11). Doi: 10.1007/s00330-022-08578-w

Key clinical point: Magnetic resonance elastography (MRE)-based shear strain mapping may serve as a noninvasive biomarker enabling the characterization of the tumor-liver interface and preoperative prediction of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC).

Major finding: The positive MVI vs. negative MVI group displayed a significantly higher octahedral shear strain (OSS) percentage of low-shear-strain length (pLSL) at three evaluation frequencies (60 Hz: 75% vs. 40%, 40 Hz: 85% vs. 40%, and 30 Hz: 70% vs. 20%; all P < .01). The peritumor OSS-pLSL area under the receiver operating characteristic curve (0.73-0.90) for MVI prediction was good/excellent at all frequencies.

Study details: The data are derived from a retrospective study of 59 patients with HCC, all of whom underwent the conventional 60 Hz MRE examination; of these, 29 patients also underwent 40 and 30 Hz MRE examinations.

Disclosures: The study was funded by the National Natural Science Foundation of China, among others. The authors declared no conflict of interests.

Source: Li M et al. MR elastography-based shear strain mapping for assessment of microvascular invasion in hepatocellular carcinoma. Eur Radiol. 2022 (Feb 11). Doi: 10.1007/s00330-022-08578-w

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Ramucirumab-mediated survival benefit in advanced HCC unperturbed by baseline prognostic covariates

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Key clinical point: Patients with advanced hepatocellular carcinoma (aHCC) and alpha-fetoprotein (AFP) levels ≥400 ng/mL experience a consistent survival benefit with ramucirumab therapy irrespective of baseline prognostic covariates.

Major finding: Ramucirumab vs. placebo improved overall survival in patients with viral (hazard ratio [HR] 0.76; 95% CI 0.60-0.97) and nonviral (HR 0.56; 95% CI 0.49-0.79) etiologies and in those with above-median AFP levels (≥4,081.5 ng/mL; HR 0.71; 95% CI 0.54-0.95).

Study details: Findings are from a post hoc meta-analysis of the phase 3 REACH and REACH-2 trials involving 542 patients with aHCC and AFP levels ≥400 ng/mL who were randomly assigned to receive ramucirumab (n = 316) or placebo (n = 226).

Disclosures: The study was sponsored by Eli Lilly and Company. JM Llovet, A Singal, A Villanueva, R Finn, M Kudo, P Galle, M Ikeda, and A Zhu reported receiving grants, personal/advisory board/consulting fees, or honoraria from various sources, including Eli Lilly. The other authors are employees or shareholders of Eli Lilly.

Source: Llovet JM et al. Prognostic and predictive factors in patients with advanced HCC and elevated alpha-fetoprotein treated with ramucirumab in two randomized phase III trial. Clin Cancer Res. 2022 (Mar 4). Doi: 10.1158/1078-0432.CCR-21-4000

 

 

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Key clinical point: Patients with advanced hepatocellular carcinoma (aHCC) and alpha-fetoprotein (AFP) levels ≥400 ng/mL experience a consistent survival benefit with ramucirumab therapy irrespective of baseline prognostic covariates.

Major finding: Ramucirumab vs. placebo improved overall survival in patients with viral (hazard ratio [HR] 0.76; 95% CI 0.60-0.97) and nonviral (HR 0.56; 95% CI 0.49-0.79) etiologies and in those with above-median AFP levels (≥4,081.5 ng/mL; HR 0.71; 95% CI 0.54-0.95).

Study details: Findings are from a post hoc meta-analysis of the phase 3 REACH and REACH-2 trials involving 542 patients with aHCC and AFP levels ≥400 ng/mL who were randomly assigned to receive ramucirumab (n = 316) or placebo (n = 226).

Disclosures: The study was sponsored by Eli Lilly and Company. JM Llovet, A Singal, A Villanueva, R Finn, M Kudo, P Galle, M Ikeda, and A Zhu reported receiving grants, personal/advisory board/consulting fees, or honoraria from various sources, including Eli Lilly. The other authors are employees or shareholders of Eli Lilly.

Source: Llovet JM et al. Prognostic and predictive factors in patients with advanced HCC and elevated alpha-fetoprotein treated with ramucirumab in two randomized phase III trial. Clin Cancer Res. 2022 (Mar 4). Doi: 10.1158/1078-0432.CCR-21-4000

 

 

Key clinical point: Patients with advanced hepatocellular carcinoma (aHCC) and alpha-fetoprotein (AFP) levels ≥400 ng/mL experience a consistent survival benefit with ramucirumab therapy irrespective of baseline prognostic covariates.

Major finding: Ramucirumab vs. placebo improved overall survival in patients with viral (hazard ratio [HR] 0.76; 95% CI 0.60-0.97) and nonviral (HR 0.56; 95% CI 0.49-0.79) etiologies and in those with above-median AFP levels (≥4,081.5 ng/mL; HR 0.71; 95% CI 0.54-0.95).

Study details: Findings are from a post hoc meta-analysis of the phase 3 REACH and REACH-2 trials involving 542 patients with aHCC and AFP levels ≥400 ng/mL who were randomly assigned to receive ramucirumab (n = 316) or placebo (n = 226).

Disclosures: The study was sponsored by Eli Lilly and Company. JM Llovet, A Singal, A Villanueva, R Finn, M Kudo, P Galle, M Ikeda, and A Zhu reported receiving grants, personal/advisory board/consulting fees, or honoraria from various sources, including Eli Lilly. The other authors are employees or shareholders of Eli Lilly.

Source: Llovet JM et al. Prognostic and predictive factors in patients with advanced HCC and elevated alpha-fetoprotein treated with ramucirumab in two randomized phase III trial. Clin Cancer Res. 2022 (Mar 4). Doi: 10.1158/1078-0432.CCR-21-4000

 

 

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Meta-analysis underscores the need for improved HCC surveillance in NAFLD without cirrhosis

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Key clinical point: Compared with patients with hepatocellular carcinoma (HCC) due to other causes, a higher proportion of those with nonalcoholic fatty liver disease (NAFLD)-related HCC do not have cirrhosis and lack an indication for HCC surveillance, thus calling for surveillance strategies for patients with NAFLD without cirrhosis but at high risk for HCC.

Major finding: The proportion of patients without cirrhosis was higher among those with NAFLD-related HCC vs. HCC due to other causes (38.5% vs. 14.6%; P < .0001). Before cancer diagnosis, only 32.8% of patients with NAFLD-related HCC underwent HCC surveillance relative to 55.7% of those with HCC due to other causes (odds ratio 0.36; P < .0001).

Study details: This was a meta-analysis of 61 studies including 94,636 patients with HCC related to either NAFLD (n = 15,377) or other causes (n = 79,259).

Disclosures: No funding was received for the study. Some authors declared having stock options from, serving as paid/unpaid consultants or advisory board members for, and receiving royalties or research grants from various organizations.

Source: Tan DJH et al. Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis. Lancet Oncol. 2022 (Mar 4). Doi: 10.1016/S1470-2045(22)00078-X

 

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Key clinical point: Compared with patients with hepatocellular carcinoma (HCC) due to other causes, a higher proportion of those with nonalcoholic fatty liver disease (NAFLD)-related HCC do not have cirrhosis and lack an indication for HCC surveillance, thus calling for surveillance strategies for patients with NAFLD without cirrhosis but at high risk for HCC.

Major finding: The proportion of patients without cirrhosis was higher among those with NAFLD-related HCC vs. HCC due to other causes (38.5% vs. 14.6%; P < .0001). Before cancer diagnosis, only 32.8% of patients with NAFLD-related HCC underwent HCC surveillance relative to 55.7% of those with HCC due to other causes (odds ratio 0.36; P < .0001).

Study details: This was a meta-analysis of 61 studies including 94,636 patients with HCC related to either NAFLD (n = 15,377) or other causes (n = 79,259).

Disclosures: No funding was received for the study. Some authors declared having stock options from, serving as paid/unpaid consultants or advisory board members for, and receiving royalties or research grants from various organizations.

Source: Tan DJH et al. Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis. Lancet Oncol. 2022 (Mar 4). Doi: 10.1016/S1470-2045(22)00078-X

 

Key clinical point: Compared with patients with hepatocellular carcinoma (HCC) due to other causes, a higher proportion of those with nonalcoholic fatty liver disease (NAFLD)-related HCC do not have cirrhosis and lack an indication for HCC surveillance, thus calling for surveillance strategies for patients with NAFLD without cirrhosis but at high risk for HCC.

Major finding: The proportion of patients without cirrhosis was higher among those with NAFLD-related HCC vs. HCC due to other causes (38.5% vs. 14.6%; P < .0001). Before cancer diagnosis, only 32.8% of patients with NAFLD-related HCC underwent HCC surveillance relative to 55.7% of those with HCC due to other causes (odds ratio 0.36; P < .0001).

Study details: This was a meta-analysis of 61 studies including 94,636 patients with HCC related to either NAFLD (n = 15,377) or other causes (n = 79,259).

Disclosures: No funding was received for the study. Some authors declared having stock options from, serving as paid/unpaid consultants or advisory board members for, and receiving royalties or research grants from various organizations.

Source: Tan DJH et al. Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis. Lancet Oncol. 2022 (Mar 4). Doi: 10.1016/S1470-2045(22)00078-X

 

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