Systematic review and meta-analysis: Comparing hepatocellular and cholestatic patterns of drug-induced liver injury

Abstract

Background and aims

Drug-induced liver injury (DILI) is a leading cause of death from acute liver failure (ALF). Hy's law warns that a hepatocellular pattern of injury accompanied by jaundice and normal alkaline phosphatase (ALP) levels is associated with a 10% or greater chance of progression to transplant or liver-related death. This meta-analysis of DILI studies evaluates acute and chronic outcomes of DILI according to clinical pattern of injury.

Methods

We conducted a systematic search using electronic databases PubMed and EMBASE through to 8 March 2022. Our primary outcome was to compare acute outcomes including ALF, liver-related death, and liver transplant between patients experiencing hepatocellular, cholestatic, and mixed patterns of DILI. Our secondary outcome was to compare the rate of DILI chronicity between patients of these three differing patterns of injury. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model.

Results

Overall, 12 studies comprising 4290 patients were included. Patients with cholestatic DILI demonstrated similar rates of ALF (OR: 0.80, 95% CI: 0.46–1.40, p = 0.429) and liver-related death (OR: 0.92, 95% CI: 0.50–1.69, p = 0.792) compared to patients with hepatocellular DILI. Patients with cholestatic DILI were significantly more likely to experience chronicity compared to patients with hepatocellular DILI (OR: 2.53, 95% CI: 1.34–4.79, p = 0.004).

Conclusion

Hy's law conceives severe DILI as an exclusive consequence of hepatocellular pattern of injury. Our results demonstrate that cholestatic injury can be associated with similarly poor rates of ALF and liver-related fatality, as well as higher rates of chronic DILI.