Taiwanese patients with HBV and HCV co-infection are likely to experience HBV functional cure, but also HBV reactivation following direct-acting antiviral treatment for HCV

This study shows the outcomes after the direct acting antiviral (DAA) treatment in patients with chronic hepatitis B (HBV)/ hepatitis C (HCV) dual-infection, that including 10% of hepatitis B surface antigen (HBsAg) loss and 38% of HBV reactivation. Our findings published in the Journal of Hepatology provide new insights into understanding the viral interaction between HBV and HCV.

The research group led by Chair Professor Ming-Lung Yu from Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan, in collaboration with Professor Raymond T Chung from Massachusetts General Hospital, Boston; Department of Medicine, Harvard Medical School, reported a new insight into the viral interaction between HBV and HCV following DAA treatment and found it might be a blessing (HBsAg loss) in disguise (HBV reactivation) for patients. They also suggested the high risked cirrhotic patients to undergo HBV prophylaxis simultaneously.   

The new all-oral DAA regimens for HCV have greatly improved treatment efficacy with sustained virological response rates of > 95% for HCV monoinfected patients. Unfortunately, HBV reactivation and HBV-related clinical reactivation during or after DAA therapy were not infrequent, and might lead to mortality in HBV/HCV-coinfected patients, especially among those with cirrhosis.

This study enrolled 79 HBV/HCV-coinfected patients receiving DAA therapy to investigate their HBV-related outcomes. One exciting finding was that during one year post-DAA follow up, 8 (10.1%) patients experienced HBsAg loss (an ideal outcome of “HBV functional cure”) with a 12-month cumulative probability of 10.3%. Another new finding was the specific decline of HBsAg level during therapy, and rebound after stopping DAA.

Alternatively, up to 30 (38%) patients were found developing a HBV reactivation (means a rebound of HBV replication). Of them, 6 (20%) patients even experienced a HBV related clinical reactivation (means a clinical hepatitis) and 3 patients further developed hepatic failure with 2 died despite the immediate anti-HBV therapy. All these 2 patients had liver cirrhosis and were without an HBV prophylaxis before DAA. Thus prophylactic anti-HBV therapy is mandatory for cirrhotic patients, irrespective of baseline HBV DNA levels.

Pre-treatment HBsAg titer can be a surrogated marker to guide decision making. This study further found that using the pre-treatment HBsAg titer of less than 10 IU/mL could predict the higher chance of HBsAg loss and lower risk of HBV reactivation.

Researchers from Kaohsiung Medical University and Harvard Medical School also demonstrates a complex interaction among the host and the two viruses in determining HBV outcomes following the results from cytokines and micro RNAs experiments. 

Getting together, this study provides a new insight into the management of HBV/HCV-coinfected patients being treated with DAA.

Main researcher Intro.

Associate Professor Ming-Lun Yeh and Chair Professor Ming-Lung Yu are members of Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. They dedicate in the research and service of Liver diseases, including etiologies, epidemiology, pathogenesis, therapeutic modalities and prevention of hepatitis B, hepatitis C, steatohepatitis and liver cancers.

Author Email

fish6069@gmail.com; fishya@ms14.hinet.net

Paper cited from:

Yeh ML, Huang CF, Huang CI, Holmes JA, Hsieh MH, Tsai YS, Liang PC, Tsai PC, Hsieh MY, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL, Chung RT, Yu ML*. Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV co-infection. J Hepatol. 2020 Jul;73(1):62-71.

Research Paper available online on website

https://doi.org/10.1016/j.jhep.2020.01.027