HCV with and without Autoimmune Features: How do you Sort them out and Manage?

Chronic HCV infection is a common worldwide viral infection that has significant morbidity and mortality. Treatment with peginterferon alfa and ribavirin comprises the standard of care. Autoimmune hepatitis (AIH) is a progressive inflammatory hepatitis of uncertain aetiology that, if untreated, also has significant morbidity and mortality. Whereas the diagnosis of HCV is confirmed by HCV RNA positivity, the diagnosis of AIH is less precise but centred on autoantibody positivity (ANA, SMA and/or anti-LKM1) and characteristic hepatic histological findings. Clarification of the diagnosis is important since chronic HCV is treated with immunostimulatory medications and AIH is treated with immunosuppressive medications. In the setting of chronic HCV, autoantibody positivity is common, raising the question of chronic HCV with autoimmune features. Cross-sectional studies have suggested that ANA or SMA positivity in the setting of chronic HCV does not generally affect disease progression or response to interferon alfa-based medical regimens. Liver enzyme flares have been observed during treatment of HCV patients with anti-LKM1 positivity. Although ANA or SMA positivity is common in the setting of HCV and is usually unimportant from a clinical standpoint, occasionally HCV with autoimmune features may be present. High-titre ANA or SMA positivity perhaps with highly elevated liver enzymes should raise suspicion for this entity. Liver biopsy should be obtained prior to commencing antiviral therapy. If a histological picture suggestive of AIH is present, antiviral therapy should be deferred. If the biopsy is consistent with chronic HCV, plans for antiviral therapy should proceed.