The Association Between Hepatocellular Carcinoma and Gastrointestinal Adenocarcinoma: Is This a New Syndrome in Patients With Cirrhosis? A Case Series

Aim: This case series aimed to explore the occurrence of synchronous hepatocellular carcinoma (HCC) and gastrointestinal adenocarcinoma in cirrhotic patients and to propose a potential common pathogenic mechanism. Cases: We reviewed the available literature and retrospectively analyzed seven cases of cirrhotic patients with synchronous HCC and gastrointestinal adenocarcinoma (colon or gastric) identified in our center between March 2020 and June 2023. All patients underwent upper gastrointestinal endoscopy, abdominal ultrasound, computed tomography (CT) scan, and histological confirmation through biopsy or surgery. The mean age of the patients was 77.3 years (range 76–83), with five males and two females. Five patients had liver cirrhosis, and two had chronic hepatitis (one with HCV, one with MASLD). HCC was confirmed in all patients, with elevated alpha-fetoprotein levels (mean: 737.6 ng/mL). Colon adenocarcinoma was found in five patients, and gastric adenocarcinoma in one patient. Genetic and microsatellite instability analyses were performed in selected cases, revealing high microsatellite instability in one patient. We suggest that the Wnt/APC/β-catenin pathway might play a key role in the pathogenesis of both HCC and gastrointestinal malignancies. Conclusions: Synchronous HCC and gastrointestinal adenocarcinoma may be increasingly identified due to prolonged survival in cirrhotic patients. Alterations in the Wnt/APC/β-catenin pathway could represent a shared pathogenic mechanism. Regular surveillance through ultrasound and endoscopy is essential for early diagnosis in this high-risk population. Future research is needed to confirm these findings and explore targeted treatments.