Incidence and risk factors of hepatocellular carcinoma in patients with primary biliary cirrhosis

Abstract

We read with great interest the article by Cavazza et al.,1 who demonstrated that an advanced histological stage was the only risk factor associated with the development of hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) from two European centers. Similar results were described in a Japanese multicenter study by Shibuya et al.2 Although these studies suggest screening for HCC in patients with advanced-stage PBC, it is still uncertain whether there is a significantly increased risk of HCC development in patients with stage IV PBC cirrhosis versus patients with cirrhosis of other etiologies. We assessed in a single-center study the incidence of HCC in North American patients with stage IV PBC or autoimmune hepatitis (AIH) cirrhosis and compared it to the incidence of HCC in patients with hepatitis C virus (HCV) cirrhosis. Three hundred fifteen patients with HCV cirrhosis, 49 patients with AIH cirrhosis, and 52 patients with stage IV PBC were evaluated at the Cleveland Clinic between 2001 and 2007. Stage IV PBC cirrhosis was diagnosed when patients had positive serological and histological findings of cirrhosis or biochemical and radiological evidence of portal hypertension. Cirrhosis due to AIH was defined by positive serological and histological findings of cirrhosis or biochemical and radiological evidence of portal hypertension. HCC-free survival was analyzed from the moment of the diagnosis of cirrhosis in HCV, AIH, and PBC patients until death or transplantation. During a median follow-up of 3.6 years (with 25th and 75th percentiles of 1.8 and 6.3, respectively), 64 of 315 patients (20.3%) with HCV cirrhosis, 2 of 49 patients (4.1%) with AIH cirrhosis, and 4 of 52 patients (7.7%) with PBC cirrhosis developed HCC. The annual cumulative incidence of HCC was 1.1% in patients with AIH cirrhosis, 1.5% in patients with PBC cirrhosis, and 4.0% in patients with HCV cirrhosis (Fig. 1). Incidence of HCC in patients with AIH, PBC, or HCV. This study has shown that although patients with stage IV PBC cirrhosis develop liver cancer, the risk is significantly lower in comparison with the risk for patients with HCV cirrhosis. The results of our study are discordant with a previously reported Spanish series in which the risks of HCC were similar in patients with late-stage PBC and in patients with HCV cirrhosis.3 We agree with Cavazza et al.1 that the low prevalence of PBC and the possible influence of geography on disease progression are confounding factors that may explain the divergent results in the literature. Future multicenter studies in North America with a longer follow-up period are necessary to validate these findings and better estimate the risk of HCC in PBC patients at an advanced histological stage. Carole Macaron M.D.*, Ibrahim A. Hanouneh M.D. , Nizar N. Zein M.D. , * Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH.