Warren Alpert Medical School of Brown University Providence, RI
Introduction: Among liver injury causes, only a few result in extreme liver enzyme rise, particularly alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 1000 international units per liter (IU/L). This review aims to summarize common etiologies of marked transaminitis.
Methods: We performed a comprehensive search on PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through April 2022 for relevant studies reporting the frequency of marked transaminitis etiologies (ALT or AST >1000 IU/L). We used a proportion meta-analysis to pool frequencies with the corresponding 95% confidence interval (CI). I2 was used to adjudicate heterogeneity. MetaXl software with the random-effects model was utilized for statistical analysis.
Results: Four relevant studies, comprising 1138 patients, were included in the analysis. The pooled frequency of ischemic hepatitis was 45% (95% CI 34-55%, I2=92%), of viral hepatitis was 16% (95% CI 3-34%, I2=98%), of toxin or drug-induced liver injury (DILI) was 13% (95% CI 8-18%, I2=85%), of acetaminophen-induced liver injury was 8% (95% CI 6-10%, I2=9%), of pancreaticobiliary causes was 6% (95% CI 1-16%, I2=96%) (Figure 1), of other causes (procedure-related, autoimmune, rhabdomyolysis, etc.) was 7% (95% CI 2-15%, I2=94%), and idiopathic was 6% (95% CI 4-7%, I2=14%). Ganga et al. reported a high prevalence of viral hepatitis (44.6%). This study was reported from South Asia and published as an abstract. In this study, Dengue, an endemic disease in India, was responsible for 52% of viral hepatitis cases; however, it was reported separately due to its multifactorial impact on the liver. A sensitivity analysis excluding this study resulted in a lower overall pooled frequency of viral hepatitis and a higher proportion of extrahepatic biliary obstruction (Tabel 1).
Discussion: This is the first meta-analysis to examine etiologies of marked transaminase elevation. Liver ischemia is the most common cause of ALT or AST above 1000 IU/L. Other common causes are DILI or toxins, viral hepatitis, and extrahepatic biliary obstruction. Etiologies such as rhabdomyolysis, procedural-related injury, and autoimmune hepatitis accounted collectively for only 7%. A notable finding of this review is the presence of extrahepatic biliary obstruction among the common causes of marked transaminitis. Interestingly, two studies reported it as the second and third most frequent etiology.
