Hepatitis is a rare complication of herpes simplex virus (HSV), often leading to acute liver failure (ALF), liver transplantation (LT), and/or death. Our aim was to identify variables associated with either survival or progression (death/LT), based on an analysis of cases in the literature and our institution. A total of 137 cases (132 literature, 5 institutional) of HSV hepatitis were identified. The main features at clinical presentation were fever (98%), coagulopathy (84%), and encephalopathy (80%). Rash was seen in less than half of patients. Most cases (58%) were first diagnosed at autopsy and the diagnosis was suspected clinically prior to tissue confirmation in only 23%. Overall, 74% of cases progressed to death or LT, with 51% in acyclovir-treated patients as compared to 88% in the untreated subjects (P = 0.03). Variables on presentation associated with death or need for LT compared to spontaneous survival: male gender, age >40 yr, immunocompromised state, ALT >5,000 U/L, platelet count <75 × 103/ L, coagulopathy, encephalopathy, and absence of antiviral therapy. In conclusion, HSV hepatitis has a high mortality and is often clinically unsuspected. Patients who are male, older, immunocompromised, and/or presenting with significant liver dysfunction are more likely to progress to death and should thus be evaluated for LT early. Based on the frequent delay in HSV diagnosis, low risk-benefit ratio, and significantly improved outcomes, empiric acyclovir therapy for patients presenting with ALF of unknown etiology is recommended until HSV hepatitis is excluded.
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