Development of Hepatocellular Carcinoma in Patients with Glycogen Storage Disease: a Single Center Retrospective Study

Abstract

Background: Glycogen storage disease (GSD) is an inherited disorder leading to abnormal glucose metabolism and glycogen accumulation, and is associated with various complications including hepatic adenoma and hepatocellular carcinoma. The aim of this study was to analyze the risk factors for hepatic adenoma and its malignant change, and the hepatocellular carcinoma-free survival rate in patients with GSD who developed adenoma. Methods: A total of 72 patients with GSD who were enrolled from March 1982 to September 2013 at Seoul National University Children's Hospital were retrospectively analyzed, and the median follow-up period was 19.2 years. Results: Thirty-two patients (44.4%) developed hepatic adenoma at an age range of 7.9-26.3 years (median, 14.3 years). Among the 32 patients with hepatic adenoma, 4 patients (12.5%) developed hepatocellular carcinoma on an average interval of 6.7 years between the diagnosis of adenoma and the development of hepatocellular carcinoma. GSD type I and portacaval shunt operation were found to be the risk factors for hepatic adenoma development. The hepatocellular carcinoma-free survival rate at 10 years from adenoma development was 82%. Conclusion:The present study found that portacaval shunt operation increases the risk of development of hepatic adenoma in GSD patients, especially in GSD type I. The hepatic adenoma in GSD patients has a potential of malignant transformation, which should be keep in mind in follow-up process of the disease.

"Bull’s eye” appearance of hepatocellular adenomas in patients with glycogen storage disease type I — atypical magnetic resonance imaging findings: Two case reports

“…, hemorrhage and malignant transformation) have been reported[ 6 - 9 ]. In a series of 32 GSD patients with HCAs, evolution of HCAs into hepatocellular carcinoma has been reported in about 12.5% of cases in a median interval time from the diagnosis of HCA to the diagnosis of hepatocellular carcinoma of 6.7 years[ 10 ]. In this series recently published by Jang et al [ 10 ], the radiological changes of HCAs in the 4 patients that developed hepatocellular carcinoma included an increase either in the number or size of HCA in two patients and an increase in both size and number in the remaining two patients.…”

“…In a series of 32 GSD patients with HCAs, evolution of HCAs into hepatocellular carcinoma has been reported in about 12.5% of cases in a median interval time from the diagnosis of HCA to the diagnosis of hepatocellular carcinoma of 6.7 years[ 10 ]. In this series recently published by Jang et al [ 10 ], the radiological changes of HCAs in the 4 patients that developed hepatocellular carcinoma included an increase either in the number or size of HCA in two patients and an increase in both size and number in the remaining two patients. The underlying etiology of HCAs in GSD is unknown; the most agreed hypothesis is that a chronic hepatic inflammation and underlying genetic may predispose these patients to develop HCAs[ 11 , 12 ].…”

Pediatric Primary Hepatic Tumors: Diagnostic Considerations

“…This occurs most commonly in GSD Type 1a (glucose-6-phosphatase deficiency) in the second to third decade of life [ 123 ]. The incidence of malignant transformation is estimated to be between 11% and 14% in various case series [ 142 , 143 ]. Appropriate metabolic control is reported to decrease the incidence of hepatic adenomas but appears to have no effect on occurrence of malignant transformation, and the pathophysiology has yet to be clearly described.…”

“…Patients with malignant transformation are likely to have a rapid increase in size and/or number of adenomas. Adenomas with hemorrhagic and necrotic changes are more suspicious for HCC, and patients who present with these findings are recommended to undergo contrast ultrasonography as well as biopsy or surgical resection [ 143 ].…”

Sex disparity in hepatocellular carcinoma owing to NAFLD and non-NAFLD etiology: epidemiological findings and pathobiological mechanisms

“…Certain inheritable metabolic disorders such as hemochromatosis, α-1 antitrypsin deficiency, tyrosinemia, glycogen storage diseases and several porphyrias also increase HCC risk, although they account for a negligible HCC risk globally [21,22] .…”