Defying the Demographics: A “Triple Atypical” Presentation of Severe Autoimmune Hepatitis in an Older Adult Male

Background

Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver disease predominantly affecting young to middle-aged females with a 4:1 female-to-male ratio. Antimitochondrial antibodies (AMA), the serological hallmark of primary biliary cholangitis (PBC), occur in approximately 5% of patients with pure AIH without histological bile duct injury. AMA positivity may suggest AIH/PBC overlap syndrome per the Paris criteria; however, liver biopsy remains essential for definitive diagnosis. Severe acute liver injury in an older adult male represents a significant departure from the typical AIH phenotype and poses unique diagnostic challenges that risk delayed or incorrect treatment.

Case Presentation

An older adult male with hyperlipidemia and remote cholecystectomy presented with three months of progressive jaundice, dark urine, fatigue, nausea, and 35-pound unintentional weight loss. Liver tests several weeks prior had been normal. He developed severe hepatocellular injury with ALT 1789 U/L, AST 1380 U/L, total bilirubin 17.9 mg/dL, and coagulopathy (INR 2.0). Comprehensive viral and toxicologic workups were negative. Serological evaluation revealed dual positivity for anti-smooth muscle antibodies and AMA, ANA 1:320, anti-M2 positivity, and elevated IgG (1648 mg/dL), initially raising concern for AIH/PBC overlap syndrome. Percutaneous liver biopsy was performed after correction of coagulopathy, and empiric immunosuppression was initiated.

Findings

Liver biopsy demonstrated extensive lobular disarray, hepatocyte ballooning, interface hepatitis, confluent necrosis, hepatocyte rosettes, and dense portal inflammatory infiltrates rich in plasma cells. Critically, there was no marked bile duct injury, ductopenia, or florid duct lesion, excluding overlap syndrome and confirming pure AMA-positive AIH. The patient was treated with prednisone and azathioprine, remaining hemodynamically stable without hepatic encephalopathy or decompensation, consistent with severe acute liver injury rather than acute liver failure.

Discussion & Conclusion

This case illustrates a "triple atypical" presentation of AIH: older age, male sex, and severe acute onset with confounding AMA-positive serology. Although serological features partially met Paris criteria for overlap syndrome, histopathology confirmed pure AIH without bile duct pathology. AMA-positive AIH patients respond well to immunosuppressive therapy and do not evolve into PBC during long-term follow-up. A limitation is that this is a single case, and continued follow-up is needed to confirm sustained remission. This case reinforces that AMA positivity alone is insufficient to diagnose overlap syndrome and underscores the indispensable role of liver biopsy when clinical and serological features are discordant. Clinicians must maintain AIH in the differential diagnosis of severe acute liver injury regardless of atypical demographics, as early recognition and aggressive immunosuppression are critical to preventing progression to acute liver failure and the need for transplantation.