Glycogen accumulation in hepatocytes has been described in children with poorly-controlled diabetes mellitus, type 1 (DM1) as far back as the 1930s [1], [2], [3]. In the ensuing decades, this phenomenon has been reported numerous times in the clinical literature in children with poorly-controlled DM1 using a variety of terms, including “glycogen storage”, “glycogen-laden hepatomegaly”, “glycogen accumulation”, “hepatic glycogenosis”, “liver glycogenosis”, and “glycogen storage hepatomegaly” [4], [5], [6], [7], [8], [9], [10], [11]. However, it was not until a detailed clinical-pathological analysis by Torbenson and colleagues in 2006 that “glycogenic hepatopathy” became the standard name for this condition [12].

This landmark study demonstrated an association between glycogen accumulation and hepatomegaly and/or elevated aminotransferases. All of the patients had DM1, typically poorly-controlled. The key histological finding was marked hepatocellular glycogen accumulation with hepatocyte swelling but intact architecture. No more than mild steatosis, minimal inflammation, minimal acidophil bodies, and no significant fibrosis was seen. Megamitochondria were variably prominent. Given the lack of significant inflammation, the suspected mechanism of injury was that cytoplasmic swelling produced leakage of aminotransferases through cell membranes and compression of the sinusoids [12].

The vast majority of cases of glycogenic hepatopathy reported before and since 2006 has been in poorly-controlled DM1, often following aggressive insulin therapy. Although several large series are now published following such patients, numerous case reports continue to claim that glycogenic hepatopathy is underrecognized in DM1 [13], [14]. A much smaller number of cases of glycogenic hepatopathy has also been histologically confirmed in patients with diabetes mellitus, type 2 (DM2); non-diabetic patients on corticosteroids; and patients with nutritional deficiencies [10], [11], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24].

Despite the rarity of reported cases, multiple patients with glycogenic hepatopathy without DM1 were noted during routine clinical practice at a single acute care hospital, leading to the current study to assess the etiologies and clinical-pathological profiles of patients in this medical setting. It was hypothesized that in the modern era of insulin therapy, extreme hyperglycemia in DM1 may be a less common etiology for glycogenic hepatopathy than currently recognized.