Etiologies and Outcomes of Transaminase Elevation > 1000 IU/L: A Systematic Review and Meta-Analysis.

Background: Among liver injury causes, few result in marked elevation of liver enzymes to a level > 1,000 international units per liter (IU/L). This review summarizes common etiologies of marked transaminase elevation and associated prognostic factors.

Methods: We performed a comprehensive search on PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through December 2022 using MOOSE guidelines for studies reporting frequency of etiologies of marked transaminase elevation. We used a proportion meta-analysis to pool frequencies with corresponding 95% confidence interval (CI). I was used to adjudicate heterogeneity. We used CMA software for statistical analysis.

Results: Seven relevant studies (n = 1608 patients) were included. The pooled frequency of ischemic hepatitis was 51% (95% CI 42-60%, I = 91%), viral hepatitis was 13.1% (95% CI 9.7-17.6%, I = 80%), toxins or drug-induced liver injury (DILI) was 13% (95% CI 8-18%, I = 85%), and pancreaticobiliary-related injury was 7.8% (95% CI 4.4-13.6%, I = 89%). Mortality was significantly higher in ischemic hepatitis versus other causes of marked transaminase elevation, with an odds ratio of 21 (95% CI 9.9-44.8, P value < 0.0001, I = 64% Q 11.1).

Discussion: This is the first meta-analysis to examine etiologies of marked transaminase elevation > 1000 IU/L. Liver ischemia is the most common cause, while other causes include DILI or toxins, viral hepatitis, and biliary pathologies. We found biliary pathologies to be the fourth most common cause. This is clinically relevant as it has been traditionally linked to a cholestatic pattern of liver injury. Being aware of this presentation may help prevent delayed or missed diagnoses and unnecessary testing.