Case Presentation: A 64-year-old man with diet-controlled type 2 diabetes mellitus and hyperlipidemia presented to an academic center with painless jaundice. He was in his usual state of health until 2 weeks prior to presentation when he noticed dark urine. He then developed jaundice 4 days before his presentation. Initial laboratory testing was notable for alanine aminotransferase (ALT) 1219 IU/L and aspartate aminotransferase (AST) 1640 IU/L, total bilirubin 28 mg/dl (direct bilirubin 21 mg/dl), alkaline phosphatase 221 IU/L and INR 1.4. He denied any alcohol, acetaminophen or other drug ingestion. He had recently started taking a probiotic 2 weeks before presenting but denied taking any other over-the-counter supplements. He reported no nausea, vomiting, diarrhea, fevers, or abdominal pain. A right upper quadrant abdominal ultrasound and MRCP showed mild splenomegaly and cholelithiasis but no biliary dilatation, thrombus, or mass. Serological work-up was negative for acute viral hepatitis panel, acetaminophen, salicylate, ethanol, and ceruloplasmin levels. A urine toxicology screen was positive for cannabinoids. Alpha-1-antitrypsin testing was negative. Quantitative immunoglobulins (IgG and IgA) were elevated, as were κ free light chain (FLC) 16 mg/dl and λ FLC 5 mg/dl with a κ/λ ratio of 3.04 concerning for a possible autoimmune etiology. Serum protein electrophoresis showed a polyclonal pattern, and no M-protein detected. Antinuclear (ANA), antimitochondrial, anti-liver/kidney microsomal antibodies were negative. However, the anti-smooth muscle antibody (ASMA) was positive (titer >1:80). Subsequent liver biopsy showed autoimmune hepatitis. The patient was treated with prednisone, and his ALT and AST levels had decreased to 778 and 653 IU/L, respectively at the time of hospital discharge.
Discussion: Autoimmune hepatitis is a chronic, inflammatory disease of the liver that occurs predominantly in women (female-male ratio >4:1) in the first two decades of life (1). However, the disease can present at any age and in all ethnic groups. The pathogenesis of this disease is complex, but current data suggest there is immune dysregulation after encountering an environmental factor that leads to progressive, chronic destruction of the hepatic parenchyma. A genetic predisposition is also suspected. Characteristic laboratory abnormalities include elevations of AST and ALT exceeding 10-20 times the upper limit of normal (2), elevated gamma globulins, particularly IgG (3) and positive autoantibodies. The most commonly positive autoantibody is ANA, but ASMA has greater specificity for autoimmune hepatitis, especially when present in a titer greater than 1:80. The diagnosis is based upon characteristic serologic and histologic findings after excluding other forms of liver disease.
Conclusions: Although autoimmune hepatitis is typically identified in women during the first two decades of life, it can also occur in older men. Therefore, it is crucial to keep a broad differential when encountering a patient with markedly abnormal liver biochemical testing and no alternative readily apparent cause of acute or chronic liver disease.