Treatment Dilemma: A Case of Hepatitis C Virus Autoimmune Hepatitis (HCV-AIH) Overlap Syndrome

Abstract

Hepatitis C virus-autoimmune hepatitis (HCV-AIH) overlap syndrome is a challenging diagnosis that mandates clinical, immunological and histological manifestations of both diseases. Management is controversial and lacks consensus due to the discordant approach to treatment of each separate condition. A 57-year-old woman presented to the Emergency Room with a 2-day history of painless jaundice after her friends noticed her skin and eyes appeared yellow. At presentation her total bilirubin was 12.9 mg/dL and her direct bilirubin was 9.3 mg/dL. Her AST and ALT were 1631 and 1003 U/L, respectively, and her ALP was elevated to 183 U/L. Her Hep C Ab screen came back Grayzone with a reflex RNA PCR of 860,000 IU/mL. CT abdomen showed a normal-appearing liver without focal lesions, and a subsequent MRCP was negative for biliary obstruction. Ultrasound with Doppler was negative for any vascular occlusion. Further workup showed an elevated IgG to 2485 mg/dL, a positive ANA titer of 1:2560 and a positive anti-smooth muscle Ab to 1:320. The patient underwent a liver biopsy that showed lymphoplasmacytic infiltration along the portal ducts and within lobular parenchyma, consistent with autoimmune hepatitis and concomitant acute viral hepatitis vs. drug reaction. The patient denied recent ingestion of any hepatotoxic medications or alcohol. Her aggregate score based on the revised scoring system of the International Autoimmune Hepatitis Group was 17, placing her in the category of definite diagnosis. Prednisone was initiated prior to discharge and follow-up was arranged in clinic. At her follow-up appointment, her transaminitis had largely improved and her hyperbilirubinemia completely resolved. HCV-AIH overlap syndrome requires confirmation of diagnosis of each entity independently with a thorough workup. Management of this syndrome is controversial as treatment of one condition could exacerbate the other. One concept is to determine the predominant insult between the two at presentation and target this insult with initial therapy. This patient's histology lacked bile duct damage and steatohepatitis which is seen in acute HCV infection. Her immunologic markers combined with the biopsy results favored an autoimmune-predominant chronic HCV-AIH overlap syndrome, prompting initiation of immunosuppressive treatment with systemic steroids. The patient's subsequent rapid clinical improvement supports this strategy for initial treatment of HCV-AIH overlap syndrome.