We really appreciate the comments by Macaron et al. Indeed, the information that they have provided confirms the reported results indicating that the incidence of hepatocellular carcinoma (HCC) in patients with stage IV primary biliary cirrhosis (PBC) is approximately 1.5 to 1.8 cases per 100 person-years.1, 2 The commentary on the differences in the incidence of HCC in patients with advanced PBC and in patients with hepatitis C virus (HCV)–related cirrhosis should, however, be considered cautiously, particularly because some bias may have been incorporated into Macaron et al.'s analysis on account of factors such as the shorter period of follow-up (median = 3.6 years) and the lack of accurate information on the clinical characteristics and duration of cirrhosis in HCV-infected patients. Thus, the reported incidence of HCC in these latter patients with HCV cirrhosis is approximately 20% within a median of 3.6 years, whereas in most series assessed for longer periods, the incidence of HCC in patients with compensated HCV cirrhosis ranges from 4% to 7%.2, 3 In the recently published Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis study, the 5-year incidence of HCC was 7% for patients with cirrhosis.4 Among other factors, the shorter follow-up period in Macaron et al.'s analysis may explain the alleged differences between the two studies. Thus, in our study with a mean follow-up of 6.2 years, the cumulative incidence of HCC in patients with advanced PBC during the first 7 years was very low, but it then became similar to the incidence of HCC in an age-matched and sex-matched group of patients with HCV cirrhosis.2 A comparable trend was observed in Macaron et al.'s analysis, but there was only 15 months of follow-up (see Figure in Macaron et al.'s letter). Likewise, we would like to make a comment on the potential influence of treatments delaying the progression and severity of liver damage, such as antiviral therapy in patients with HCV-related cirrhosis and ursodeoxycholic acid in patients with PBC. Certainly, in a cohort of 389 patients with PBC followed for an average of 9.5 years, the probability of HCC development was significantly reduced for those patients receiving ursodeoxycholic acid therapy.5


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  • 1
    Cavazza A, Caballeria L, Floreani A, Farinati F, Bruguera M, Caroli D, et al. Incidence, risk factors, and survival of hepatocellular carcinoma in primary biliary cirrhosis: comparative analysis from two centers. HEPATOLOGY 2009; 50: 11621168.
  • 2
    Caballería L, Parés A, Castells A, Ginés A, Bru C, Rodés J. Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that in hepatitis C virus related-related cirrhosis. Am J Gastroenterol 2001; 96: 116011634.
  • 3
    Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004; 127: S35S50.
  • 4
    Lok AS, Seeff LB, Morgan TR, di Bisceglie AM, Sterling RK, Curto TM, et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 2009; 136: 138148.
  • 5
    Caballería L, Bruguera M, Parés A. Incidence and risk factors for hepatocellular carcinoma in primary biliary cirrhosis. J Hepatol 2008; 48: S328.

Albert Parés M.D.*, Llorenç Caballería M.D.*, * Liver Unit, Hospital Clinic, Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red en Enfermedades, Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain.