Herpes Hepatitis Causing Acute Liver Failure in a Patient With Poorly Controlled Systemic Lupus Erythematosus

Introduction: Herpes simplex virus (HSV) hepatitis is a rare cause of acute liver failure (ALF), representing 1-2% of viral cases. The CDC estimates 572,000 new HSV-2 genital infections occur annually in the US. HSV hepatitis (HSVh) varies in presentation, but typically involves pregnant or immunocompromised patients who are anicteric with marked transaminitis. Case Description/Methods: A 31-year-old woman with a past medical history of SLE and prior stroke secondary to Moyamoya disease presented with nausea, vomiting and dizziness to an outside hospital, where she was found to have elevated transaminases. One week later, she was transferred to our ICU for liver transplant evaluation due to worsening transaminitis. She was tachycardic and tachypneic with mild abdominal distension, subtle asterixis, and vesicular lesions over the vulva and perineum. She was normotensive, afebrile, alert, and oriented, without hepatomegaly or tenderness to abdominal palpation. Initial labs suggested acute liver injury and DIC. She was prophylactically started on acyclovir and underwent extensive work-up for liver disease, significant for positive HSV-2 PCR in the blood and positive immunohistochemistry for HSV-1 in the liver. On admission, she was started on n-acetylcysteine, lactulose, and rifaximin. Urgent evaluation for liver transplant revealed she was not a candidate due to medical instability. Liver biopsy showed patchy hepatocyte necrosis affecting 50% of the tissue, with perivenular predominance. HSV stain was positive. The patient’s complicated ICU course resulted in her death on hospital day 18. She received 1 dose of foscarnet for possible acyclovir-resistant HSV as susceptibility testing pended. We later learned the sample was inadequate for processing. Discussion: This patient likely died from fulminant HSVh leading to liver failure, which is more common in patients with SLE, especially with significant corticosteroid therapy exposure. Females aged 30-40 are at higher risk. Most cases of HSVh present with fever and coagulopathy. HSV PCR of the serum is positive in most cases, however liver biopsy is the gold standard for diagnosis. Mortality without treatment approaches 90%. This patient had increased risk for acyclovir resistance, due to SLE and steroid exposure, which potentially contributed to the patient’s death despite prompt initiation of therapy. This case highlights the need to consider HSV hepatitis in high-risk patients and risk factors for increased mortality and acyclovir resistance (Figure 1, Table 1).Figure 1.: A. Low power image of an H&E stained section of the liver core biopsy showing an area of necrosis (between the arrows). B. Low power image of a section of the same liver core biopsy with IHC staining for HSV I. The area of necrosis shows brown staining consistent with HSV I infection (between the arrows). Table 1. - Initial Labs and Pertinent Negatives HSV-2 PCR (serum) Detected Hemoglobin (g/dL) 7.3 INR 7.39 D-dimer (mcg/mL) 60,195 Fibrinogen (mg/dL) 63 Haptoglobin (mg/dL) < 20 Creatinine (mg/dL) 2.1 Albumin (g/dL) 2.2 Total Bilirubin (mg/dL) 2.1 Alkaline Phosphatase (IU/L) 170 AST (IU/L) 8,668 ALT (IU/L) 1,894 CRP (mg/dL) 75 LDH (U/L) 33,367 GGT (U/L) 251 Pertinent Negative Tests HAV, HCV, HBV, CMV, Parvovirus, Acetaminophen, Salicylate, Alpha-1 Antitrypsin, Ceruloplasmin, AFP, CEA, CA 19-9, Varicella, EBV, Anti-Sm Ab