An enlarging liver in a young diabetic male

A22-year-old man with history of type 1 diabe- tes mellitus, alpha-1-antitrypsin deficiency (ZZ phenotype), gastroesophageal reflux disease, hyperlipidemia, and depression presented to the hospital for increasing right upper quadrant pain and nausea for 2 weeks. The patient was a former heroin user and an active smoker, but denied significant alcohol use. The patient’s home medications included insulin, atorvastatin, dexlansoprazole, paroxetine, buprenor-phine, and trazodone. The patient had poorly controlled diabetes, requiring six hospitalizations for diabetic ketoaci-dosis within the last year.

Physical examination revealed a soft, nondistended abdomen
with diffuse tenderness and severe hepatomegaly without as-
cites, jaundice, spider angioma, or other stigmata of advanced
liver disease. Laboratory studies showed an alanine amino-
transferase of 223 U/L, aspartate aminotransferase of 331 U/L,
alkaline phosphatase of 223 U/L, total bilirubin of 0.3 mg/dL,
albumin of 3. 4 g/dL, platelet count of 302 U/L, International
Normalized Ratio of 0.9, and hemoglobin A1C of 14.6%. Hepati-
tis B and C serologies were negative and the alpha-1-antitryp-
sin level was less than 60 mg/dL. MRI revealed a significantly
enlarged liver with marked interval increase of 21. 2 to 25. 8 cm
from 8 months prior. No focal hepatic lesions were identified.
There was no intrahepatic or extrahepatic biliary ductal dila-
tation (Figures A, B). A core biopsy of the liver was performed
showing hepatocytes are swollen with cleared cytoplasm
(Figure C). Figures D and E show hepatocytes are strongly
and diffusely positive for periodic acid–Schiff stain and largely
negative for periodic acid–Schiff diastase stain, suggesting that
the hepatocytes were swollen with glycogen that was digested
with diastase. Periodic acid–Schiff diastase also highlights al-
pha-1-antitrypsin globules. n

Based on the clinical scenario, imaging, and pathologic
findings, what is the diagnosis?

Dr. Xu is in the Department of Medicine, Dr. Dhall is in the Department of Pathology and Laboratory Medicine, and Dr. Sundaram is in the Department of Gastroenterology and Hepatology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles.