Should aciclovir be given to all patients presenting with acute liver failure of unknown etiology

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Abstract

BACKGROUND

Herpes simplex virus (HSV) hepatitis is a rare complication in patients with HSV infection, but it often leads to acute liver failure (ALF), liver transplantation and death because of its nonspecific clinical presentation and a delay in diagnosis.

OBJECTIVE

To identify variables associated with survival, death or need for liver transplantation in patients with HSV hepatitis.

DESIGN AND INTERVENTION

This US, retrospective analysis involved a search of the PubMed and MEDLINE data-bases, and the electronic chart and pathology databases at the Northwestern Feinberg School of Medicine, Chicago, IL, to identify case reports of HSV hepatitis. Patients who were ≥ years old with evidence of hepatocellular injury and histologic evidence of HSV hepatitis were selected for inclusion in the study. Patients without liver histology evidence of HSV hepatitis were still included if their peak serum alanine aminotransferase level was >500 U/L, serology or biopsy of non hepatic tissue was consistent with a diagnosis of HSV infection, and there was no other cause of ALF. The records of eligible patients were examined to identify variables on presentation that were associated with survival, death or need for liver trans plantation. Variables considered included age, sex, immunosuppression, coagulopathy, hepatic encephalopathy, liver function, renal function, and antiviral therapy. Univariate and multivariate regression analyses were performed on these data.

OUTCOME MEASURES

The primary end point was the identification of variables associated with survival, liver transplantation or death.

RESULTS

A total of 137 patients (132 selected from the literature and 5 from the study institution) with HSV hepatitis were included in the analysis. Herpetic rash was seen at presentation in only 44% of patients, whereas fever, encephalopathy and coagulopathy were present in 98%, 80% and 84% of patients, respectively. Diagnosis of HSV hepatitis was made at autopsy in the majority (57.6%) of patients; disease was clinically suspected on the basis of patient history and presentation in only 23% of these patients. Death or liver transplantation occurred in 74% of the study population, and in significantly more patients who were left untreated compared with those who received aciclovir (also known as acyclovir in the US) treatment: 88% versus 51%, P = 0.03. Univariate analysis revealed that age >40 years, male sex, encephalopathy, coagulopathy, an immunocompromised state, serum alanine aminotransferase level >500 U/L, platelet count 75 × 103/L) and absence of aciclovir treatment were significantly associated with death or liver transplantation compared with spontaneous survival: odds ratio (OR) 2.9 (95% CI 1.2-7.5), OR 6.9 (95% CI 2.3-21.1), OR 11.0 (95% CI 2.9-41.5), OR 21.5 (95% CI 6.1-75.7), OR 2.3 (95% CI 1.4-5.0), OR 9.3 (95% CI 2.6-33.6), OR 15.5 (95% CI 3.6-67.3), and OR 0.14 (95% CI 0.06-0.33), respectively.

CONCLUSION

Empiric aciclovir therapy should be given to all patients presenting with ALF of unknown etiology until HSV hepatitis is excluded.

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