A Systematic Review of the Evidence Behind Use of Reduced Doses of Acetaminophen in Chronic Liver Disease

Acetaminophen is among the most commonly used nonopioid analgesics, but significant variation exists in its prescribing practices for cirrhosis patients. Our primary objective was to describe the quality of evidence supporting or refuting the use of acetaminophen in patients with hepatic dysfunction. A comprehensive literature review of PubMed, Cochrane Library, Web of Science, and International Pharmaceutical Abstracts using the search terms "acetaminophen," "paracetamol," "chronic liver disease," "cirrhosis," and "hepatic disease" for studies describing changes in acetaminophen metabolism in patients with hepatic dysfunction was conducted. Twelve studies and four abstracts were included. Ten studies and three abstracts were pharmacokinetic studies. Two studies and one abstract evaluated the association of acetaminophen use and decompensation in the cirrhotic patient. The level of certainty for dosing recommendations obtainable from reviewing the evidence is low due to a small number of studies meeting search criteria, small samples sizes, inadequate information regarding cirrhosis etiology and compensated versus uncompensated liver disease, and lack of information on patient centered health outcomes. High-quality trials are not available to support the use of decreased acetaminophen doses in compensated cirrhosis patients. Acetaminophen can be a safe analgesic in patients with compensated hepatic dysfunction after careful analysis of patient-specific factors.