Clinical features and indicators of prognosis of herpes simplex and varicella-zoster hepatitis in non-pregnant patients

Abstract

Herpes simplex (HSV; type I and II) and varicella-zoster virus (VZV) form the alpha herpesvirus subfamily, characterized by latency in sensory nerve ganglia, a short replicative cycle, rapid cell to cell spread, characteristic skin lesions and, rarely, development of fulminant hepatitis. Dissemination of HSV type II from the genitourinary tract may explain the high frequency of this type in pregnant women with herpesvirus hepatitis. AIM: To characterize the clinical features of HSV and VZV hepatitis in a series of non-pregnant patients. METHODS: A retrospective review of cases diagnosed at the Mayo Clinic with HSV or VZV hepatitis by liver histopathology or culture techniques during life or at autopsy. RESULTS: From 1979 to 1996, 13 new cases (9 male, 4 female) ofHSV and VZV hepatitis were diagnosed with a mean age of 39 years (range 2-76). Most had fever (maximal temperature 38.4 _+ 0.3°C; Mean 4SE) and a low white cell count (nadir 3.2 _+ 1.0*109/L). All had evidence of severe hepatocellular necrosis (maximal AST 3400___ 1200 U/mL; maximal ALT 14004-500 U/mL). Cholestasis and jaundice were absent until late in the disease (maximal alkaline phosphatase 600_ 140 U/mL; maximal bilirubin 4.2_ 2.3 mg/dL) and renal function remained intact (maximal creatinine 1.6 40.5 mg/dL). Eight cases were due to HSV type I, 5 were due to VZV. Five patients survived (2/8 or 25% with HSV; 3/5 or 60% with VZV). None of the survivors had evidence of underlying immuno-compromise or malignancy. Six of the 8 (75%) nonsurvivors were immuno-compromised secondary to chemotherapy and died within days from liver failure or disseminated disease (5 patients had HSV; 1 VZV); the other 2 were not immuno-compromised and died from liver failure and a CVA complicating the hepatitis. Survivors differed from nonsurvivors in the maximal AST level (1100_+ 100 U/mL vs 4900_+ 1700; p=0.03) and the nadir of the white cell count (6.2 _+ 1.6109/L vs 1.4 _+ 0.6; p=0.005). CONCLUSIONS: 1) HSV and VZV hepatitis are characterized by fever, very high serum aminotransferase levels, a low white cell count and late, mostly mild, cholestasis; 2) HSV type II hepatitis is rare in non-pregnant patients; 3) HSV type I and immunocompromise are associated with high mortality; and 4) survival is associated with significantly lower transaminase levels and higher white cell counts.