A 47-year-old woman comes to the emergency department due to jaundice. It started 3 days ago and is associated with fatigue, nausea, and itchiness but not confusion or drowsiness. Medical history is significant for celiac disease. The patient takes no prescription or over-the-counter medications. She rarely drinks alcohol and does not use illicit drugs. Family history is unremarkable. Temperature is 37.6 C (99.7 F), blood pressure is 125/80 mm Hg, pulse is 80/min, and respiratory rate is 12/min. Physical examination reveals scleral icterus. Cardiopulmonary examination is unremarkable. Asterixis is absent. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 14.2 g/dL |
| Platelets | 85,000/mm3 |
| Leukocytes | 7,000/mm3 |
| Liver function studies | |
| Total bilirubin | 4.2 mg/dL |
| Alkaline phosphatase | 210 U/L |
| Aspartate aminotransferase (SGOT) | 842 U/L |
| Alanine aminotransferase (SGPT) | 876 U/L |
Anti–smooth muscle antibody and antinuclear antibody titers are both markedly elevated. Which of the following would be the best next step in management?
Autoimmune hepatitis | |
Presentation |
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Laboratory |
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Histology |
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ALT = alanine aminotransferase; AST = aspartate aminotransferase. | |
This patient with fatigue, pruritus, jaundice, and elevated liver enzymes and autoantibody titers (ie, anti–smooth muscle, antinuclear) has autoimmune hepatitis (AIH). AIH is a chronic liver disease that occurs most commonly in middle-aged women with comorbid autoimmune disease (eg, autoimmune thyroiditis).
The initial presentation of AIH is variable, ranging from asymptomatic laboratory abnormalities to cirrhosis or acute liver failure. However, most patients have constitutional symptoms (eg, fatigue, weight loss, nausea), abdominal discomfort, pruritus, and jaundice. Laboratory evaluation typically demonstrates a hepatocellular pattern of liver injury with predominant elevations in transaminases (up to 20x the upper limit of normal) with variable elevations of bilirubin.
A variety of autoantibodies occur with AIH, leading to hypergammaglobulinemia and an elevated gamma gap (total protein − albumin = >4 g/dL). Antinuclear antibody is the most common antibody; however, the presence of anti–smooth muscle antibody is more specific for AIH. Management includes immunosuppression with glucocorticoids (eg, prednisone) with or without azathioprine.
(Choice A) N-acetylcysteine is used to treat acetaminophen overdose, which also presents with a hepatocellular patten of liver injury; however, elevated autoantibodies are unexpected. Furthermore, acetaminophen toxicity is typically more rapidly progressive, with markedly elevated transaminases (eg, >10,000 U/L) and hepatic failure (eg, asterixis, encephalopathy) occurring at ~72 hours. Pruritus and less significant transaminase elevations are more consistent with AIH.
(Choice B) Patients with AIH but without evidence of active inflammation (eg, normal aminotransferases, normal gamma globulin levels, minimal inflammatory changes on liver biopsy) can be observed without therapy; however, this symptomatic patient requires immunosuppression.
(Choice D) Liver transplant should be considered for patients with acute liver failure (ie, hepatic encephalopathy, prolonged PT, elevated transaminases) or decompensated cirrhosis (eg, ascites, variceal hemorrhage). Although transplantation could be considered if the patient's condition decompensates, immunosuppression may obviate this need in the future.
(Choice E) Ursodeoxycholic acid is used to treat primary biliary cholangitis, an autoimmune disorder characterized by a cholestatic pattern of liver injury (predominant elevations in alkaline phosphatase) and antimitochondrial antibody titers. This patient's hepatocellular pattern of injury and positive anti–smooth muscle antibody are more consistent with AIH.
Educational objective:
Autoimmune hepatitis is characterized by a hepatocellular pattern of liver injury with increased autoantibody titers (eg, anti–smooth muscle, antinuclear) and hypergammaglobulinemia. Typical manifestations include nausea, fatigue, pruritus, and jaundice. The mainstay of treatment is prednisone with or without azathioprine.