Acute Liver Failure Due to Herpes Simplex Virus in an Immunocompetent Patient

Abstract

Purpose: A 48-year-old male with a history of sleep apnea and nephrolithiasis presented to an outside hospital with hepatitis, acute renal failure, hypotension, and pancytopenia. Five days earlier, he developed nausea, vomiting, night sweats, diarrhea, headache, intermittent fever, and chills. The patient did not use tobacco, alcohol, or illicit drugs. On transfer to our hospital on day 8 of his illness, he was febrile, tachypneic, tachycardic, and encephalopathic, but responsive. No icterus or asterixis was present. His abdomen was unremarkable. Petechia were present but no herpetic lesions. AST and ALT peaked at 9438 and 8230, respectively. Intial bilirubin and INR were normal. INR worsened, and bilirubin peaked at 4. He had hepatic steatosis and splenomegaly by CT. Hepatitis serologies, EBV, CMV, ANA, RF, anti-michochondrial antibodies, anti-smooth muscle antibodies, HIV, and HSV I/II IgM were negative. Blood, urine, and stool cultures were negative. The patient was intubated, started on hemodialysis for ARF, and begun on broad-spectrum antibiotics and doxycycline for possible rickettsial infection. However, over the course of the next 48 hours, the patient's condition deteriorated rapidly. He was taken for liver transplant but arrested and was not able to be resuscitated. Liver pathology showed herpes simplex hepatitis with massive hepatic necrosis with less than 10% viable hepatic parenchyma. Discussion: HSV hepatitis is a rare cause of acute liver failure (ALF) but occurs in immunocompromised and immunocompetent patients at a rate of 0.4%-1.4% of cases of ALF. The diagnosis is usually made post-mortem due to a lack of characteristic features and awareness. Common features of HSV hepatitis include fever, leucopenia, thrombocytopenia, elevated transaminases, encephalopathy, coagulopathy, and the absence of herpetic lesions or icterus. Both primary and secondary HSV-1 and HSV-2 infections are potential causes of hepatitis, and measurement of HSV IgM is often not helpful, as was the case in this patient. HSV PCR may be a more reliable method of diagnosis, as this has been found to be uniformly high in patients with HSV ALF. If HSV hepatitis is suspected, acyclovir should be started and transjugular biopsy should be undertaken to confirm diagnosis. Some recommend that all patients with ALF of unknown etiology be started on empiric acyclovir until a cause is determined. Liver transplant may be an option, although morbidity and mortality remain high post-transplant. A difficult diagnosis to make, clinicians should maintain a high index of suspicion for HSV infection in all cases of ALF even in immunocompetent patients and in the absence of herpetic lesions.