An Open-label Rollover Study in Chinese Patients After Finishing a 3-year Randomize Trial for Chronic Hepatitis B With High Serum Viral Load But Mild Elevated Aminotransferase

Background The indication to start NUCs remains controversial in non-cirrhotic compensated patients with chronic hepatitis B (CHB). Specifically, it has not been clarified whether high serum concentration of HBV DNA warrants treatment despite only mild elevation of serum alanine aminotransferase (ALT). In order to elucidate this unresolved issue, we've conducted a double blind placebo controlled randomized trial to investigate the efficacy of Tenofovir Disoproxil Fumarate (TDF) in CHB patients with high viral load but only mildly elevated serum ALT.

This open-label rollover study is an extension of the aforementioned randomized trial. For those who are initially randomized to placebo and later receive open-label TDF, there is a rare opportunity to study the efficacy of TDF by using the same patient as his/her own control. For those already randomized to TDF in the trial, the investigators will be able to closely monitor all aspects of therapeutic responses (i.e., biochemical, virological, serological, and histological) during a 6-year treatment course in an Asian cohort.

Regardless of their initial treatment assignment, these enrolled patients offer a unique opportunity to further explore the effectiveness of TDF in CHB in that they have paired biopsied liver tissue and comprehensive information.

Objectives:

The primary endpoint of this study is the evolution of liver fibrosis during the therapeutic course. The secondary endpoints are virological response including not only serum viral load but also intracellular HBV markers such as viral covalently closed circular (ccc) DNA, serological response including HBsAg seroconversion, HBeAg seroconversion, and quantification of HBsAg, biochemical response such as AST, ALT, and adverse reactions with particular attention to clinical events regarding bone and renal safety.