Herpes simplex virus (HSV) hepatitis occurs most commonly in the setting of immunocompromise, but has also been reported in immunocompetent adults, children, and pregnant women [1
]. To our knowledge, only seven cases of fulminant hepatitis due to HSV in immunocompetent adults have been reported. However, it is likely that many cases go undetected due to the nonspecific clinical and laboratory presentation. Patients with HSV hepatitis can present with a wide range of symptomatology, from mild constitutional symptoms to severe coagulopathy with loss of consciousness [4
]. Early diagnosis of HSV hepatitis is imperative in order to institute treatment in a timely manner. The mortality rate is high among untreated patients [5
]. In one review, only 23% of reported patients were diagnosed antemortem [6
]. Untreated herpes hepatitis is associated with mortality in 80% to 90% of cases [7
Early initiation of antiviral therapy, especially acyclovir, can improve chances of survival [8
There is no diagnostic pattern to the presentation of HSV hepatitis. Patients present with symptoms such as fever and abdominal pain in combination with rising ALT and AST titers [3
]. In a review of 137 cases of HSV hepatitis, the most common presenting features were fever (98%), coagulopathy (84%), and encephalopathy (80%). Rash was seen in less than half of patients [11
]. Over half of cases (58%) were first diagnosed at autopsy, and three-quarters of the cases (74%) progressed to death or liver transplantation. Other abnormalities that may be present in patients with HSV hepatitis include leukopenia, serological evidence of infection, and mucocutaneous lesions, but these factors are not present in all patients.
Fulminant HSV hepatitis is usually marked by significant elevations in transaminases, with AST typically higher than ALT, and a mild or absent hyperbilirubinemia. Serological testing for HSV-IgM and -IgG is often negative, however, it does not rule out HSV as the underlying etiology.
Definitive diagnosis is made by liver biopsy, with demonstration of hepatic necrosis, HSV cytopathic effects, and immunoreactivity to HSV [3
]. Viral blood cultures will not provide timely results, and real-time PCR testing for viremia, which can provide results in 3 hours [12
], is not available at every center.
Levels of ALT and AST correlate with survival. A greater than 100-fold increase in ALT and AST was associated with fatality in 100% of patients in one review [12
]. Liver biopsy and blood cultures should be performed, before initiation of antiviral therapy, but empiric therapy should be instituted immediately in patients with no other known reason for hepatic failure.
Biopsy will demonstrate diffuse hepatic necrosis with hemorrhage, and may demonstrate Cowdry type 1 and 2 inclusions. Collapse of the normal architecture with loss of the reticulin framework will be present. A lymphocytic infiltration may be seen, but is usually modest. Immunostaining for HSV will detect the presence of the virus within the hepatocyte cytoplasm. Blood cultures provide supportive evidence to the diagnosis.
A high index of suspicion is necessary when a patient presents with constitutional symptoms and elevating AST and ALT, and these findings should prompt immediate antiviral therapy with acyclovir. Risk factors for HSV hepatitis include third trimester pregnancy and immunosuppression. The degree of elevation of AST and ALT should be taken into account, because many viral illnesses, including primary HSV infection, can produce mild elevations in liver enzymes without progression to fulminant hepatitis. Serial evaluation of these values will show consistent increase when hepatic damage is severe, and should prompt immediate intervention. Even in the absence of direct evidence of acute HSV infection, administration of acyclovir is a relatively safe treatment. While fulminant hepatitis is only rarely due to HSV, the fact that this infection often responds to antivirals early in its course warrants empirical treatment. Despite this, there has been a report of acyclovir-resistant HSV hepatitis [13
Body piercing is a known risk factor for HSV infection. A review by Hayes and Harkness reported HSV infection and/or seroconversion to be associated with percutaneous needle exposure and body piercing [14
]. These findings indicate the need for public health intervention, including education and regulation of body piercing practices, in order to prevent transmission of HSV.