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A 14-year-old girl with type 1 diabetes mellitus, hypothyroidism, and amenorrhoea was referred with hepatomegaly that was detected incidentally on abdominal ultrasound. Her glycaemic control was poor during the preceding year, with HbA1c of 11%. She had raised transaminases on a few occasions during a period of 4 months, with levels returning to normal in between. Her growth and pubertal development were appropriate for age. Physical examination was normal apart from hepatomegaly palpable 2 cm below the costal margin. Serum caeruloplasmin, α1-antitrypsin, autoantibody screen, immunoglobulin levels, and hepatitis viral serology were normal. Liver biopsy showed features consistent with glycogenic hepatopathy (GH).
GH is a relatively underrecognized condition seen in poorly controlled type 1 diabetes mellitus. This occurs as a result of excessive accumulation of glycogen in hepatocytes, manifesting as hepatomegaly and flares of elevation in transaminases (1), which in some cases can be up to ≥10 times the upper limit of normal (2). Although abdominal pain is a frequent feature, this was not present in our patient.
Histology shows enlarged, pale plant cell–like hepatocytes with accentuated cell membranes, with or without mild fatty changes, and no or minimal necroinflammation. Glycogenated hepatocyte nuclei are also common. The excess amount of glycogen can be demonstrated with the periodic acid-Schiff stain resulting in a magenta staining pattern that disappears into a pale pink staining after diastase digestion (Fig. 1). The prognosis is usually good and symptoms are reversible with good glycaemic control.
The main differential diagnoses include nonalcoholic fatty liver disease, which shows significant steatosis, hepatocyte ballooning with or without Mallory hyaline, lobular and perivenular perisinusoidal fibrosis, and possible glycogen storage disease in children without hyperglycaemia (3). Although there appears greater cytoplasmic clumping of glycogen in glycogen storage disease, these features are nonspecific and a significant histological overlap exists with GH.
1. Van den Brand M, Elving LD, Drenth JP, et al. Glycogenic hepatopathy: a rare cause of elevated serum transaminases in diabetes mellitus. Neth J Med
2. Torbenson M, Chen YY, Brunt E, et al. Glycogenic hepatopathy: an underrecognized hepatic complication of diabetes mellitus. Am J Surg Pathol
3. Paradis V, Bedossa P. Definition and natural history of metabolic steatosis: histology and cellular aspects. Diabetes Metab