HLA‐B*35:01 and Green Tea Induced Liver Injury

Background Herbal supplements and particularly multi-ingredient products have become increasingly common causes of acute liver injury. Green tea is a frequent component in implicated products, but its role in liver injury is controversial. Methods Among 1414 patients enrolled in the U.S. Drug Induced Liver Injury Network who underwent formal causality assessment, 40 cases (3%) were attributed to green tea, 202 to dietary supplements without green tea, and 1142 to conventional drugs. The clinical features of green tea cases and representation of HLA class I and II alleles in cases and control groups were analyzed in detail. Results Patients with green tea-associated liver injury ranged in age from 17 to 69 years (median = 40) and developed symptoms 15 to 448 days (median = 72) after starting the implicated agent. The liver injury was typically hepatocellular (95%) with marked serum aminotransferase elevations and only modest increases in alkaline phosphatase. Most patients were jaundiced (83%) and symptomatic (88%). The course was judged as severe in 14 patients (35%), necessitating liver transplantation in 3 (8%), but rarely resulting in chronic injury (3%). In three instances, injury recurred upon re-exposure to green tea with similar clinical features but shorter time to onset. HLA typing revealed a high prevalence of HLA-B*35:01, found in 72% (95% CI: 58% to 87%) of green tea cases but only 15% (95% CI: 10% to 20%) caused by other supplements and 12% (95% CI: 10% to 14%) attributed to drugs, the latter rate being similar to population controls (95% CI: 11%: 10.5% to 11.5%). Conclusions Green tea-related liver injury has distinctive clinical features and close association with HLA-B*35:01 suggesting that it is idiosyncratic and immune-mediated.