Journal Article

P242 Hepatocellular carcinoma incidence in adult patients with glycogen storage disease type III (GSD 3)

Sharma, Reena, Kuriakose, Kevin, Woodall, Alison, Green, Diane

2025

Overview

IntroductionGlycogen storage disease type III (GSD 3) is an inborn error of glycogen degradation caused by a deficiency of the glycogen debrancher enzyme. With improvements in medical care, patients are surviving longer into adulthood providing a better understanding of the condition’s long-term hepatic complications. Previous studies have demonstrated that individuals with GSD 3 are at risk of developing hepatocellular carcinoma (HCC). Our study is the first to assess HCC incidence in person-years at risk within the GSD 3 population.MethodsA retrospective analysis of clinical records was undertaken of all adult patients (alive and deceased) with GSD 3 at the Mark Holland Metabolic Unit, Salford Royal Hospital. Person-years at risk were calculated by measuring the time from age 18 years to one of the following outcomes: diagnosis of HCC, death, or end of follow-up (December 2024).ResultsA total of 19 patients with GSD 3 (58% male) were identified, with a median age of 33 years. The cohort had a median body mass index (BMI) of 31.9kg/m2 [IQR 25.6 – 40.8 kg/m2] and 47% had cirrhosis. 2 patients (11%) developed HCC. Both patients were male and aged 29 and 49 years at the time of diagnosis. Both had Child-Pugh A cirrhosis and were diagnosed with Barcelona Clinic Liver Cancer (BCLC) stage A (early stage) HCC managed with curative intent. Patient A (29 years) was initially treated with bridging trans-arterial chemoembolisation (TACE) with the intention to proceed to liver transplantation. However, he was later de-listed due to a rise in alpha-fetoprotein and instead, underwent surgical resection. Patient B (49 years) was managed directly with surgical resection. Both patients died due to complications of HCC recurrence and survived 49 and 48 months from diagnosis. A total of 330 person-years at risk were accumulated during the follow-up period providing an HCC incidence of 6.06 per 1,000 person-years at risk. Among GSD 3 patients with cirrhosis, the HCC incidence was 9.57 per 1,000 person-years at risk.ConclusionsOur study was drawn from the cohort at one of the largest adult metabolic centres in Europe. The findings demonstrate that patients with GSD are at risk of developing HCC. The cohort exhibits high levels of obesity providing a metabolic risk factor for cirrhosis. Existing literature also implicates abnormal glycogen in the pathogenesis of cirrhosis in GSD 3. However, despite the potential combined effects of these factors, the observed HCC incidence in cirrhotic patients with GSD is similar to the rates reported in metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis (10–15 per 1,000 patient-years). Given the rarity of GSD 3, larger multi-centre studies are essential to better understand and address the hepatic complications in this cohort.

• Publisher: BMJ Publishing Group LTD
• Subject: Body mass index / Cancer / Cirrhosis / Diagnosis / Enzymes / Glycogen / Hepatocellular carcinoma / Liver cancer / Liver cirrhosis / Liver diseases / Liver transplantation / Metabolism / Pathogenesis / Patients / Risk factors / Storage diseases / α-Fetoprotein