Efficacy of Ledipasvir and Sofosbuvir Treatment of HCV Infection in Patients Coinfected With HBV
Journal
Gastroenterology
Journal Volume
154
Journal Issue
4
Pages
989-997
Date Issued
2018
Author(s)
Chuang W.-L.
Sheen I.-S.
Wang H.-Y.
Chen C.-Y.
Tseng K.-C.
Chang T.-T.
Massetto B.
Yang J.C.
Yun C.
Knox S.J.
Osinusi A.
Camus G.
Jiang D.
Brainard D.M.
McHutchison J.G.
Hu T.-H.
Hsu Y.-C.
Lo G.-H.
Chu C.-J.
Chen J.-J.
Peng C.-Y.
Chien R.-N.
Abstract
Background & Aims: There have been reports of reactivation of hepatitis B virus (HBV) infection during treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents. We performed a prospective study of risks and outcomes of HCV infection treatment with ledipasvir and sofosbuvir in patients with HBV infection. Methods: We performed a phase 3b, multicenter, open-label study in Taiwan of 111 patients with HCV infection (61% HCV genotype 1, 39% HCV genotype 2 infection; 62% women, 16% with compensated cirrhosis) along with HBV infection. All but 1 were positive for the hepatitis B surface antigen (HBsAg); 1 patient who was HBsAg-positive at screening was found to be HBsAg-negative at baseline. Overall, 33% of participants had received prior treatment for HCV and 5% had previously been treated for HBV; no patient was on HBV therapy at the start of the study. All patients received a fixed-dose combination of 90 mg of the HCV NS5A inhibitor ledipasvir with 400 mg of the NS5B nucleotide analogue inhibitor sofosbuvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of therapy. Results: All 111 patients (100%) achieved a sustained virologic response. Of the 37 patients with baseline HBV DNA below 20 IU/mL, 31 (84%) had at least 1 episode of quantifiable HBV DNA through posttreatment week 12. Of the 74 patients with baseline HBV DNA levels of 20 IU/mL or more, 39 (53%) had increases of HBV DNA greater than 1 log10 IU/mL through posttreatment week 12. Overall, 5 patients had increased levels of HBV DNA concomitant with a level of alanine aminotransferase >2 times the upper limit of normal through posttreatment week 12. Of these, 3 patients started HBV treatment. In addition, 1 patient with HBV reactivation since week 8 and concomitant alanine aminotransferase elevation >2 times upper limit of normal at posttreatment week 48 started treatment at posttreatment week 53. This patient had clinical signs and symptoms associated with HBV reactivation. The most common adverse events were headache, upper respiratory infection, and fatigue. Conclusions: In a prospective study, the combination of ledipasvir and sofosbuvir for 12 weeks produced a sustained virologic response in 100% of patients with HCV infection who were coinfected with HBV. Most patients had an increase in level of HBV DNA not associated with signs or symptoms. ClinicalTrials.gov no: NCT02613871. ? 2018 AGA Institute
SDGs
Other Subjects
alanine aminotransferase; hepatitis B surface antigen; ledipasvir; sofosbuvir; triacylglycerol lipase; virus DNA; antivirus agent; benzimidazole derivative; fluorene derivative; hepatitis B antibody; hepatitis B surface antigen; hepatitis B(e) antigen; ledipasvir, sofosbuvir drug combination; uridine phosphate; virus RNA; abnormal laboratory result; adult; aged; Article; colon hemorrhage; compensated liver cirrhosis; drug efficacy; drug safety; duodenum ulcer; fatigue; female; headache; hepatitis B; Hepatitis B virus; hepatitis C; Hepatitis C virus genotype 1; Hepatitis C virus genotype 2; human; knee meniscus rupture; major clinical study; male; mixed infection; multicenter study; nonhuman; open study; optic neuritis; phase 3 clinical trial; priority journal; prospective study; side effect; sustained virologic response; Taiwan; treatment outcome; upper respiratory tract infection; analogs and derivatives; blood; clinical trial; complication; drug effects; genetics; Hepacivirus; hepatitis B; hepatitis C; immunology; middle aged; mixed infection; time factor; virus load; Adult; Aged; Antiviral Agents; Benzimidazoles; Coinfection; DNA, Viral; Female; Fluorenes; Hepacivirus; Hepatitis B; Hepatitis B Antibodies; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis C; Humans; Male; Middle Aged; Prospective Studies; RNA, Viral; Sustained Virologic Response; Taiwan; Time Factors; Treatment Outcome; Uridine Monophosphate; Viral Load
Publisher
W.B. Saunders
Type
journal article