Autopsy‐Proven Immune‐Mediated Hepatitis With Rapid Liver Atrophy Despite Minimal Aminotransferase Elevation After Durvalumab Plus Tremelimumab Therapy for Hepatocellular Carcinoma: A Case Report

Immune-mediated hepatitis caused by immune checkpoint inhibitors (ICIs) is typically suspected based on aminotransferase elevation; however, biochemical signals may be blunted in advanced cirrhosis, potentially delaying recognition. A 71-year-old woman with cirrhosis due to metabolic dysfunction-associated steatohepatitis and Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma refractory to transarterial chemoembolization started durvalumab plus tremelimumab therapy. The patient developed grade 3 immune-mediated colitis requiring high-dose corticosteroids, with sustained clinical remission. Despite only modest aminotransferase changes, serial non-contrast computed tomographic volumetry revealed progressive liver volume loss from 1.71 L pretreatment to 0.76 L at death, accompanied by jaundice and coagulopathy leading to fatal liver failure. In evaluating the subsequent liver dysfunction, the patient remained afebrile, and imaging revealed no biliary obstruction or vascular thrombosis. Autopsy revealed CD8-predominant T-cell infiltration with lobular hepatitis and patchy necrosis, consistent with immune-mediated hepatitis as the cause of death. The tumor burden was small without metastasis. This case highlights that ICI hepatitis can progress with minimal aminotransferase elevation in advanced cirrhosis, warranting multidimensional monitoring beyond aspartate aminotransferase/alanine aminotransferase, including bilirubin, coagulation parameters, clinical decompensation, and quantitative imaging.