Chun-Jen Liu1, Wan-Long Chuang2, I-Shyan Sheen3, Horng-Yuan Wang4, Chi-Yi Chen5, Kuo-Chih Tseng6, Ting-Tsung Chang7, Benedetta Massetto8, Jenny C Yang8, Chohee Yun8, Steven J Knox8, Anu Osinusi8, Gregory Camus8, Deyuan Jiang8, Diana M Brainard8, John G McHutchison8, Tsung-Hui Hu9, You-Chun Hsu10, Gin-Ho Lo11, Chi-Jen Chu12, Jyh-Jou Chen13, Cheng-Yuan Peng14, Ron-Nan Chien15, Pei-Jer Chen16. 1. Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan. Electronic address: cjliu@ntu.edu.tw. 2. Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 3. Chang Gung Memorial Hospital (CGMH), Taoyuan, Taiwan. 4. Mackay Memorial Hospital, Taipei, Taiwan. 5. Chia-Yi Christian Hospital, Chia-Yi, Taiwan. 6. Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan. 7. National Cheng Kung University Hospital, Tainan, Taiwan. 8. Gilead Sciences, Foster City, California. 9. Chang Gung Memorial Hospital (CGMH), Kaohsiung, Taiwan. 10. Changhua Christian Hospital, Changhua, Taiwan. 11. E-DA Hospital, Kaohsiung, Taiwan. 12. Taipei Veterans General Hospital, Taipei, Taiwan. 13. Chi Mei Hospital, Tainan, Taiwan. 14. China Medical University Hospital, Taichung, Taiwan. 15. Chang Gung Memorial Hospital, Keelung, Taiwan. 16. Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan. Electronic address: peijerchen@ntu.edu.tw.
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.
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.
Authors: Danielle J Smalls; Reagan E Kiger; LeAnn B Norris; Charles L Bennett; Bryan L Love Journal: Pharmacotherapy Date: 2019-11-03 Impact factor: 4.705
Authors: Ashwin Balagopal; Hyon S Hwang; Tanner Grudda; Jeffrey Quinn; Richard K Sterling; Mark S Sulkowski; Chloe L Thio Journal: J Infect Dis Date: 2020-04-07 Impact factor: 5.226