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For patients or death in a phase 3b, multicenter, open-label study.
“Although we observed increases in HBV DNA in most patients, these increases were [usually] not associated with ALT [alanine amino transferase] flares or clinical complications,” reported Chun-Jen Liu, MD, of National Taiwan University College of Medicine and Hospital, Taipei, and his associates. Although nearly two-thirds of patients developed HBV reactivation, less than 5% developed alanine aminotransferase rises at least twice the upper limit of normal, and only one patient had symptomatic HBV reactivation, which entecavir therapy resolved. This study was the first to prospectively evaluate the risk of HBV reactivation during HCV treatment, the researchers wrote in the March issue of Gastroenterology.
Because chronic hepatitis C virus infection tends to suppress HBV replication, peginterferon/ribavirin or direct-acting anti-HCV treatment can reactivate HBV infection, especially in patients who test positive for hepatitis B surface antigen (HBsAg). Left untreated, reactivated HBV can lead to fulminant hepatitis, liver failure, and death, as noted on recently mandated boxed warnings.
Accordingly, guidelines recommend testing patients for HBV infection before starting HCV treatment. The study enrolled 111 coinfected patients; about two-thirds were female, and 16% had compensated cirrhosis. All tested positive for HBsAg at screening, and all but one also tested positive at baseline. Mean baseline HBV DNA levels were 2.1 log10 IU/mL. Patients received 90 mg ledipasvir plus 400 mg sofosbuvir for 12 weeks, and levels of HCV RNA, HBV DNA, and HBsAg were tested at weeks 1, 2, 4, 8, 12, posttreatment week 4, and then every 12 weeks until posttreatment week 108.
In all, 70 (63%) patients developed HBV reactivation, including 84% of the 37 patients with undetectable HBV DNA at baseline. During treatment, none of these patients had ALT rise more than twice the upper limit of normal. By 48 weeks post treatment, however, 77% still had quantifiable HBV DNA, and two had marked ALT rises. Furthermore, by posttreatment week 53, one of these patients developed bilirubinemia and symptomatic HBV infection (malaise, anorexia, sclera jaundice, and nausea), which resolved after treatment with entecavir.
A total of 74 patients had quantifiable baseline HBV DNA (at least 20 IU/mL). Three received entecavir or tenofovir disoproxil fumarate based on confirmed HBV reactivation with a concomitant ALT rise of at least twice the upper limit of normal. All were asymptomatic. There were no cases of liver failure or death.
“Regardless of HBV DNA and/or ALT elevations, no patient had signs of liver failure,” the researchers wrote. “Our results support the recommendations put forth in clinical treatment guidelines: HCV-infected patients should be evaluated for HBV infection prior to HCV treatment with direct-acting antivirals. Those who are HBsAg positive should be monitored during and after treatment for HBV reactivation, and treatment should be initiated in accordance with existing guidelines.”
Gilead funded the study. Dr. Liu and 12 coinvestigators reported having no conflicts of interest. Nine coinvestigators reported being employees and shareholders of Gilead, and one coinvestigator reporting consulting for Gilead. The senior author disclosed ties to Roche, Bristol-Myers Squibb, Johnson & Johnson, Bayer, MSD, and Taiha.
SOURCE: Lui C-J et al. Gastroenterology. 2017 Nov 21. doi: 10.1053/j.gastro.2017.11.011.
For patients or death in a phase 3b, multicenter, open-label study.
“Although we observed increases in HBV DNA in most patients, these increases were [usually] not associated with ALT [alanine amino transferase] flares or clinical complications,” reported Chun-Jen Liu, MD, of National Taiwan University College of Medicine and Hospital, Taipei, and his associates. Although nearly two-thirds of patients developed HBV reactivation, less than 5% developed alanine aminotransferase rises at least twice the upper limit of normal, and only one patient had symptomatic HBV reactivation, which entecavir therapy resolved. This study was the first to prospectively evaluate the risk of HBV reactivation during HCV treatment, the researchers wrote in the March issue of Gastroenterology.
Because chronic hepatitis C virus infection tends to suppress HBV replication, peginterferon/ribavirin or direct-acting anti-HCV treatment can reactivate HBV infection, especially in patients who test positive for hepatitis B surface antigen (HBsAg). Left untreated, reactivated HBV can lead to fulminant hepatitis, liver failure, and death, as noted on recently mandated boxed warnings.
Accordingly, guidelines recommend testing patients for HBV infection before starting HCV treatment. The study enrolled 111 coinfected patients; about two-thirds were female, and 16% had compensated cirrhosis. All tested positive for HBsAg at screening, and all but one also tested positive at baseline. Mean baseline HBV DNA levels were 2.1 log10 IU/mL. Patients received 90 mg ledipasvir plus 400 mg sofosbuvir for 12 weeks, and levels of HCV RNA, HBV DNA, and HBsAg were tested at weeks 1, 2, 4, 8, 12, posttreatment week 4, and then every 12 weeks until posttreatment week 108.
In all, 70 (63%) patients developed HBV reactivation, including 84% of the 37 patients with undetectable HBV DNA at baseline. During treatment, none of these patients had ALT rise more than twice the upper limit of normal. By 48 weeks post treatment, however, 77% still had quantifiable HBV DNA, and two had marked ALT rises. Furthermore, by posttreatment week 53, one of these patients developed bilirubinemia and symptomatic HBV infection (malaise, anorexia, sclera jaundice, and nausea), which resolved after treatment with entecavir.
A total of 74 patients had quantifiable baseline HBV DNA (at least 20 IU/mL). Three received entecavir or tenofovir disoproxil fumarate based on confirmed HBV reactivation with a concomitant ALT rise of at least twice the upper limit of normal. All were asymptomatic. There were no cases of liver failure or death.
“Regardless of HBV DNA and/or ALT elevations, no patient had signs of liver failure,” the researchers wrote. “Our results support the recommendations put forth in clinical treatment guidelines: HCV-infected patients should be evaluated for HBV infection prior to HCV treatment with direct-acting antivirals. Those who are HBsAg positive should be monitored during and after treatment for HBV reactivation, and treatment should be initiated in accordance with existing guidelines.”
Gilead funded the study. Dr. Liu and 12 coinvestigators reported having no conflicts of interest. Nine coinvestigators reported being employees and shareholders of Gilead, and one coinvestigator reporting consulting for Gilead. The senior author disclosed ties to Roche, Bristol-Myers Squibb, Johnson & Johnson, Bayer, MSD, and Taiha.
SOURCE: Lui C-J et al. Gastroenterology. 2017 Nov 21. doi: 10.1053/j.gastro.2017.11.011.
For patients or death in a phase 3b, multicenter, open-label study.
“Although we observed increases in HBV DNA in most patients, these increases were [usually] not associated with ALT [alanine amino transferase] flares or clinical complications,” reported Chun-Jen Liu, MD, of National Taiwan University College of Medicine and Hospital, Taipei, and his associates. Although nearly two-thirds of patients developed HBV reactivation, less than 5% developed alanine aminotransferase rises at least twice the upper limit of normal, and only one patient had symptomatic HBV reactivation, which entecavir therapy resolved. This study was the first to prospectively evaluate the risk of HBV reactivation during HCV treatment, the researchers wrote in the March issue of Gastroenterology.
Because chronic hepatitis C virus infection tends to suppress HBV replication, peginterferon/ribavirin or direct-acting anti-HCV treatment can reactivate HBV infection, especially in patients who test positive for hepatitis B surface antigen (HBsAg). Left untreated, reactivated HBV can lead to fulminant hepatitis, liver failure, and death, as noted on recently mandated boxed warnings.
Accordingly, guidelines recommend testing patients for HBV infection before starting HCV treatment. The study enrolled 111 coinfected patients; about two-thirds were female, and 16% had compensated cirrhosis. All tested positive for HBsAg at screening, and all but one also tested positive at baseline. Mean baseline HBV DNA levels were 2.1 log10 IU/mL. Patients received 90 mg ledipasvir plus 400 mg sofosbuvir for 12 weeks, and levels of HCV RNA, HBV DNA, and HBsAg were tested at weeks 1, 2, 4, 8, 12, posttreatment week 4, and then every 12 weeks until posttreatment week 108.
In all, 70 (63%) patients developed HBV reactivation, including 84% of the 37 patients with undetectable HBV DNA at baseline. During treatment, none of these patients had ALT rise more than twice the upper limit of normal. By 48 weeks post treatment, however, 77% still had quantifiable HBV DNA, and two had marked ALT rises. Furthermore, by posttreatment week 53, one of these patients developed bilirubinemia and symptomatic HBV infection (malaise, anorexia, sclera jaundice, and nausea), which resolved after treatment with entecavir.
A total of 74 patients had quantifiable baseline HBV DNA (at least 20 IU/mL). Three received entecavir or tenofovir disoproxil fumarate based on confirmed HBV reactivation with a concomitant ALT rise of at least twice the upper limit of normal. All were asymptomatic. There were no cases of liver failure or death.
“Regardless of HBV DNA and/or ALT elevations, no patient had signs of liver failure,” the researchers wrote. “Our results support the recommendations put forth in clinical treatment guidelines: HCV-infected patients should be evaluated for HBV infection prior to HCV treatment with direct-acting antivirals. Those who are HBsAg positive should be monitored during and after treatment for HBV reactivation, and treatment should be initiated in accordance with existing guidelines.”
Gilead funded the study. Dr. Liu and 12 coinvestigators reported having no conflicts of interest. Nine coinvestigators reported being employees and shareholders of Gilead, and one coinvestigator reporting consulting for Gilead. The senior author disclosed ties to Roche, Bristol-Myers Squibb, Johnson & Johnson, Bayer, MSD, and Taiha.
SOURCE: Lui C-J et al. Gastroenterology. 2017 Nov 21. doi: 10.1053/j.gastro.2017.11.011.
FROM GASTROENTEROLOGY
Key clinical point: Combination therapy with sofosbuvir/ledipasvir effectively treated chronic hepatitis C infection in hepatitis B coinfected patients.
Major finding: The rate of sustained viral response was 100% at 12 weeks. Most (63%) of patients had an increase in hepatitis B viral DNA, but only 5% of patients had a concomitant increase in alanine aminotransferase. There were no cases of liver failure or death.
Data source: A phase 3b, multicenter, single-arm, open-label study of 111 coinfected patients.
Disclosures: Gilead funded the study. Dr. Liu and 12 coinvestigators reported having no conflicts of interest. Nine coinvestigators reported being employees and shareholders of Gilead, and one coinvestigator reporting consulting for Gilead. The senior author disclosed ties to Roche, Bristol-Myers Squibb, Johnson & Johnson, Bayer, MSD, and Taiha.
Source: Lui C-J et al. Gastroenterology. 2017 Nov 21. doi: 10.1053/j.gastro.2017.11.011.