Liver Safety Assessment in Clinical Trials of New Agents for Chronic Hepatitis B

Robert J. Fontana; Mark I. Avigan; Harry L. A. Janssen; Arie Regev; Poonam Mishra; Anuj Gaggar; Nathaniel Brown; Cynthia Wat; Patricia Mendez; Ryan T. Anderson; Bruce Given; Veronica Miller; Maria Beumont


J Viral Hepat. 2020;27(2):96-109. 

In This Article


Various laboratory, clinical and histological criteria should be considered in the design of future phase 1 and 2/3 studies of investigational regimens for chronic HBV (Table 3). To adjudicate serum ALT flares encountered in these drug development programmes, a predefined protocol that specifies the testing of liver safety biomarkers prior to and during treatment should be established and followed (Table 4 and Table 5). Furthermore, investigation of individual cases of liver biomarker safety signals using a comprehensive and methodical approach is advisable. When a potential pattern of DILI events is identified in trials of new anti-HBV agents, an expert adjudication panel is recommended to help assess the overall preclinical, clinical and pharmacological liver safety data. Finally, molecular diagnostic assays that can reliably differentiate an enhanced host immune response to HBV antigens vs drug hepatotoxicity are in development and will hopefully improve our ability to develop safe and effective medications that increase the rate of HBsAg loss in the millions of patients with chronic HBV worldwide.