Consensus Guidelines: Best Practices for Detection, Assessment and Management of Suspected Acute Drug-Induced Liver Injury During Clinical Trials in Adults with Chronic Viral Hepatitis and Adults with Cirrhosis Secondary to Hepatitis B, C and Nonalcoholic Steatohepatitis

作者：William R. Treem, Melissa Palmer, Isabelle Lonjon‐Domanec, Daniel W. Seekins, Lara Dimick‐Santos, Mark Avigan, JOHN F. MARCINAK, Ajit Dash, Arie Regev, Eric S. Maller, Meenal B. Patwardhan, James H. Lewis, Don C. Rockey, Adrian M. Di Bisceglie, James W. Freston, Raúl J. Andrade, Naga Chalasani · 发表于：Drug Safety · 年份：2020 · DOI：10.1007/s40264-020-01014-2 · 被引用次数：41 · 研究领域：Liver Disease Diagnosis and Treatment、Drug-Induced Hepatotoxicity and Protection、Hepatitis C virus research

With the widespread development of new drugs to treat chronic liver diseases (CLDs), including viral hepatitis and nonalcoholic steatohepatitis (NASH), more patients are entering trials with abnormal baseline liver tests and with advanced liver injury, including cirrhosis. The current regulatory guidelines addressing the monitoring, diagnosis, and management of suspected drug-induced liver injury (DILI) during clinical trials primarily address individuals entering with normal baseline liver tests. Using the same laboratory criteria cited as signals of potential DILI in studies involving patients with no underlying liver disease and normal baseline liver tests may result in premature and unnecessary cessation of a study drug in a clinical trial population whose abnormal and fluctuating liver tests are actually due to their underlying CLD. This position paper focuses on defining best practices for the detection, monitoring, diagnosis, and management of suspected acute DILI during clinical trials in patients with CLD, including hepatitis C virus (HCV) and hepatitis B virus (HBV), both with and without cirrhosis and NASH with cirrhosis. This is one of several position papers developed by the IQ DILI Initiative, comprising members from 16 pharmaceutical companies in collaboration with DILI experts from academia and regulatory agencies. It is based on an extensive literature review and discussions between industry members and experts from outside industry to achieve consensus regar...