Acute Hepatitis E Infection Accounts for Some Cases of Suspected Drug-Induced Liver Injury

Abstract

Background & Aims The diagnosis of drug-induced liver injury relies upon exclusion of other causes, including viral hepatitis A, B, and C. Hepatitis E virus (HEV) infection has been proposed as another cause of suspected drug-induced liver disease. We assessed the frequency of HEV infection among patients with drug-induced liver injury in the United States. Methods The drug-induced liver injury network (DILIN) is a prospective study of patients with suspected drug-induced liver injury; clinical information and biological samples are collected to investigate pathogenesis and disease progression. We analyzed serum samples, collected from patients enrolled in DILIN, for immunoglobulin (Ig)G and IgM against HEV; selected samples were tested for HEV RNA. Results Among 318 patients with suspected drug-induced liver injury, 50 (16%) tested positive for anti-HEV IgG and 9 (3%) for anti-HEV IgM. The samples that contained anti-HEV IgM (collected 2 to 24 weeks after onset of symptoms) included 4 that tested positive for HEV RNA, genotype 3. Samples from the 6-month follow-up visit were available from 4 patients; they were negative for anti-HEV IgM, but levels of anti-HEV IgG increased with time. Patients that had anti-HEV IgM were mostly from older men (89%; mean age, 67 years) and 2 were HIV positive. Clinical reassessment of the 9 patients with anti-HEV IgM indicated that acute hepatitis E was the most likely diagnosis for 7 and might be the primary diagnosis for 2. Conclusion HEV infection contributes to a small but important proportion of cases of acute liver injury that are suspected of being drug induced. Serologic testing for HEV infection should be performed—particularly if clinical features are compatible with acute viral hepatitis.

An Update on Drug-induced Liver Injury

“…36 A recently study highlights the small but important role of concomitant hepatitis E even in western countries; 3% (9 of 318) of patients with a diagnosis of DILI were found to have acute hepatitis E infection. 37 This finding has implications on treatment, such that same drug/drugs can be continued or restarted once the hepatitis episode has abated. Several causality assessment methods have been established as tools in the accurate diagnosis of DILI.…”

Hepatitis E: Epidemiology and Natural History

“…[83][84][85] A specific feature of HEV infection in low-endemicity areas is the occurrence of chronic HEV infection, defined as persistence of HEV RNA in a person's blood beyond 3 or 6 months, in immunosuppressed persons. 86 Such infection is associated with evidence of chronic liver injury, leading to fibrosis and even cirrhosis.…”

Idiosyncratic drug‐induced liver injury: A short review

“…In the initial report of the DILI Network (DILIN) prospective study, acute HCV infection masqueraded as iDILI in 1.3% of cases; therefore, that report recommended that acute HCV infection should be excluded by HCV RNA testing 16. Another published report from the DILIN showed that 3% of patients with suspected iDILI were positive for anti‐hepatitis E virus (anti‐HEV) immunoglobulin (Ig) M, and it was concluded that blood testing for acute HEV infection should be performed, especially if the clinical features are compatible with acute viral hepatitis 24. However, routine anti‐HEV IgM testing cannot be recommended owing to the uncertain performance of the currently available commercial tests 25.…”