Severe hepatotoxicity associated with orlistat: clinical presentation, risk factors and outcomes

Orlistat, a widely prescribed anti-obesity agent, has been associated with rare but severe hepatotoxicity. The risk profile remains poorly characterised in vulnerable populations, particularly elderly individuals and those with concurrent alcohol use. This study presents a fatal case of OILI and systematically reviews published cases to delineate the clinical spectrum of the injury and highlight features that may be relevant to vulnerable populations.

We report a fatal case of OILI in a 66-year-old man with chronic alcohol use. A systematic literature review was conducted across PubMed, Web of Science, Embase and CNKI up to December 2025 to identify all published cases of OILI. Data on demographics, drug exposure, clinical presentation, laboratory values, and outcomes were extracted and analysed descriptively.

Ten cases were analyzed. The median age was 55.5 years (range: 15-66), with a female predominance (80%). Hepatocellular injury was the dominant pattern (nine out of ten). Severe outcomes, including acute liver failure, occurred in 60% (six out of ten) of patients, with a mortality rate of 20% (two out of ten) and 30% (three out of ten) requiring liver transplantation. Both fatalities were males aged ≥60 with alcohol use. Risk factors for severe outcomes included age ≥50 years, alcohol use, and duration of orlistat use >8 weeks. In patients with poor outcomes, transaminases often exceeded 5,000 U/L, bilirubin rose above 171 μmol/L, and INR was greater than 2.0.

OILI can present with acute liver failure, particularly in elderly patients with alcohol use. These observations suggest that close monitoring and prompt intervention may be important in high-risk patients, though larger studies are needed to confirm.