Glycogenic Hepatopathy

Abstract

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, a 1 -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.

Glycogenic hepatopathy: A narrative review

“…The hallmark of the GH is severe fluctuation in levels of glucose and administration of supraphysiologic levels of insulin to control the hyperglycemia. While first described in association with recurrent hyper- and hypoglycemia with ketoacidosis in T1DM, it has since been reported without ketosis or acidosis in patients with T2DM and with variable insulin requirements[ 3 , 4 , 8 - 16 , 42 ]. The excess glycogen accumulation has also been reported in diabetic patients without previous episodes of hypoglycemia[ 44 , 53 ].…”

Unusual glycogenic hepatopathy causing abnormal liver enzymes in a morbidly obese adolescent with well‐controlled type 2 diabetes: resolved after A1c was normalized by metformin

“…Glycogenic hepatopathy is a rare cause of hepatomegaly and elevated transaminases. All previously reported cases of diabetic patients with glycogenic hepatopathy were on insulin and had poorly controlled diabetes . Excess glucose from the hyperglycaemic stage enters hepatocytes freely and, in the presence of insulin, is converted to glycogen.…”

“…Excess glycogen accumulation in the liver leads to glycogen hepatopathy . This condition is reversible and treatable by controlling the diabetes . In contrast, NAFLD is the most common cause of chronic liver disease in paediatric patients; it is caused by fat accumulation in hepatocytes secondary to insulin resistance and hyperinsulinaemia .…”

Characteristics, clinical laboratory, histopathology, and outcomes of glycogenic hepatopathy in children

“…There is a scarcity of studies, case reports, and case series 4 , 5 , 6 , 7 , 8 in children with GH, so the pathophysiology of GH has not been well characterized in children. The aim of this study was to describe the clinical, biochemical, and histologic profile of children with GH.…”