Persistent Hepatitis a IgM Antibody: A Clue in the Diagnosis of Autoimmune Hepatitis

Abstract

Autoimmune hepatitis (AIH) is a condition characterized by persistent inflammation of the liver, associated with a T-cell mediated immune response directed against liver antigens. The presence of underlying genetic predisposition, failure of immune tolerance mechanisms, and the presence of exogenous precipitating stimulus have been linked to its pathophysiology. Hepatitis A (HAV) infection has been described as an environmental trigger associated with AIH development. We describe a patient with previously diagnosed acute HAV, presenting with persistent IgM antibody against Hepatitis A (anti-HAV IgM) who was subsequently diagnosed with AIH. A 56-year-old African-American lady presenting with two-week history of dark urine, pale stools, fatigue, lower extremity edema, and nocturnal pruritus. She had a well-documented prior history of HAV infection two years before, with subsequent resolution of symptoms and laboratory abnormalities. On physical examination, she appeared mildly ill with conjunctival icterus and jaundice. See Table 1 for laboratory results. Her MELD score was 21 upon presentation. Antinuclear antibody and anti-smooth muscle antibody titer were 1/640 and 1/1280, respectively. A liver biopsy demonstrated interface hepatitis with exuberant plasma cell infiltrate, and stage 4/4 fibrosis on trichrome stain, suggestive of AIH. The patient was diagnosed with AIH according to international diagnostic criteria for AIH (Score 17). She received treatment with oral steroids and azathioprine with later normalization of liver function and transaminases after three months of treatment. Anti-HAV IgM could be detected for up to three to six months after acute HAV infection. Our case illustrates the significance of late detection of Anti-HAV IgM more than six months after resolution of acute HAV infection. A study in children aged 6-14 years showed persistent Anti-HAV IgM in more than 20% of patients 12 to 18 months after initial infection. Several case reports (Table 2) have been published of AIH diagnosed seven to sixteen weeks after the initial acute HAV infection. In our case the time interval from initial acute HAV infection to the diagnosis of AIH is much longer, but the sustained anti-HAV IgM response indicates persistent antigenic stimuli, which could play a role in subsequent development of AIH, and facilitate its diagnosis.2265_A Figure 1. Laboratory values before and after treatment of AIH, including prior diagnosis of acute HAV and interval resolution2265_B Figure 2. Prior case reports of AIH diagnosed after documented acute HAV