Liver, Pancreas and Biliary Tract| Volume 54, ISSUE 9, P1215-1221, September 2022

Download started.


Characteristics and survival of patients with primary biliary cholangitis and hepatocellular carcinoma

Published:March 27, 2022DOI:



      Comprehensive and contemporary data pertaining large populations of patients with Primary Biliary Cholangitis (PBC) and hepatocellular carcinoma (HCC) are missing.


      To describe main characteristics and outcome of PBC patients with HCC diagnosed in the new millennium.


      Analysing the Italian Liver Cancer registry we identified 80 PBC patients with HCC diagnosed after the year 2000, and described their clinical characteristics, access to treatment and survival.


      Median age of patients was 71 years and 50.0% were males. Cirrhosis was present in 86.3% of patients, being well-compensated in 58.0%. Median HCC diameter was smaller in patients under surveillance (2.6 vs 4.0 cm, P = 0.007). Curative treatment, feasible in 50.0% of patients, was associated with improved survival compared to palliative and supportive care (42 vs 33 vs 6 months, P<0.0001). Surveillance was associated with a non-significant improved survival (36 vs 23 months), likely due to similar rate of curative treatment in patients under (51.4%) and outside surveillance (42.6%).


      PBC patients with HCC are often elderly males with well-preserved liver function. Feasibility of curative treatment is high and associated with improved prognosis. Description of these patients may help focus surveillance to identify earlier tumours, increase their curability, and improve prognosis.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Digestive and Liver Disease
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lleo A.
        • Leung P.S.C.
        • Hirschfield G.M.
        • et al.
        The pathogenesis of primary biliary cholangitis: a comprehensive review.
        Semin Liver Dis. 2020; 40: 34-48
        • Cavazza A.
        • Caballería L.
        • Floreani A.
        • et al.
        Incidence, risk factors, and survival of hepatocellular carcinoma in primary biliary cirrhosis: comparative analysis from two centers.
        Hepatology. 2009; 50: 1162-1168
        • Silveira M.G.
        • Suzuki A.
        • Lindor K.D.
        Surveillance for hepatocellular carcinoma in patients with primary biliary cirrhosis.
        Hepatology. 2008; 48: 1149-1156
        • Santi V.
        • Trevisani F.
        • Gramenzi A.
        • et al.
        Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival.
        J Hepatol. 2010; 53: 291-297
        • Natarajan Y.
        • Tansel A.
        • Patel P.
        • et al.
        Incidence of hepatocellular carcinoma in primary biliary cholangitis: a systematic review and meta-analysis. Dig Dis Sci 2021;66:2439-51.
        Correction in Dig Dis Sci. 2021; 66: 2842
        • Shibuya A.
        • Tanaka K.
        • Miyakawa H.
        • et al.
        Hepatocellular carcinoma and survival in patients with primary biliary cirrhosis.
        Hepatology. 2002; 35: 1172-1178
        • Imam M.H.
        • Silveira M.G.
        • Sinakos E.
        • et al.
        Long-term outcomes of patients with primary biliary cirrhosis and hepatocellular carcinoma.
        Clin Gastroenterol Hepatol. 2012; 10: 182-185
        • Boonstra K.
        • Beuers U.
        • Ponsioen C.Y.
        Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review.
        J Hepatol. 2012; 56: 1181-1188
        • Rong G.
        • Wang H.
        • Bowlus C.L.
        • et al.
        Incidence and risk factors for hepatocellular carcinoma in primary biliary cirrhosis.
        Clin Rev Allergy Immunol. 2015; 48: 132-141
        • Trivedi P.J.
        • Lammers W.J.
        • van Buuren H.R.
        • et al.
        Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study.
        Gut. 2016; 65: 321-329
        • Bucci L.
        • Garuti F.
        • Lenzi B.
        • et al.
        The evolutionary scenario of hepatocellular carcinoma in Italy: an update.
        Liver Int. 2017; 37: 259-270
        • Garuti F.
        • Neri A.
        • Avanzato F.
        • et al.
        The changing scenario of hepatocellular carcinoma in Italy: an update.
        Liver Int. 2021; 41: 585-597
        • Heathcote E.J.
        Management of primary biliary cirrhosis. The American association for the study of liver diseases practice guidelines.
        Hepatology. 2000; 31: 1005-1013
        • Pugh R.N.
        • Murray-Lyon I.M.
        • Dawson J.L.
        • et al.
        Transection of the oesophagus for bleeding oesophageal varices.
        Br J Surg. 1973; 60: 646-649
        • Giannini E.
        • Botta F.
        • Testa E.
        • et al.
        The 1-year and 3-month prognostic utility of the AST/ALT ratio and model for end-stage liver disease score in patients with viral liver cirrhosis.
        Am J Gastroenterol. 2002; 97: 2855-2860
        • Italian Association for the Study of the Liver (AISF); AISF Expert Panel; AISF Coordinating Committee
        Position paper of the Italian Association for the Study of the Liver (AISF): the multidisciplinary clinical approach to hepatocellular carcinoma.
        Dig Liver Dis. 2013; 45: 712-723
        • John B.V.
        • Aitcheson G.
        • Schwartz K.B.
        • et al.
        Male sex is associated with higher rates of liver-related mortality in primary biliary cholangitis and cirrhosis.
        Hepatology. 2021; 74: 879-891
        • Marzioni M.
        • Bassanelli C.
        • Ripellino C.
        • et al.
        Epidemiology of primary biliary cholangitis in Italy: evidence from a real-world database.
        Dig Liver Dis. 2019; 51: 724-729
        • Boccalini S.
        • Pellegrino E.
        • Tiscione E.
        • et al.
        Sero-epidemiology of hepatitis B markers in the population of Tuscany, Central Italy, 20 years after the implementation of universal vaccination.
        Hum Vaccin Immunother. 2013; 9: 636-641
        • Floreani A.
        • Cazzagon N.
        • Franceschet I.
        • et al.
        Metabolic syndrome associated with primary biliary cirrhosis.
        J Clin Gastroenterol. 2015; 49 (-6): 57
        • Borzio M.
        • Dionigi E.
        • Rossini A.
        • et al.
        External validation of the ITA.LI.CA prognostic system for patients with hepatocellular carcinoma: a multicenter cohort study.
        Hepatology. 2018; 67: 2215-2225
        • Muratori P.
        • Granito A.
        • Pappas G.
        • et al.
        Clinical and serological profile of primary biliary cirrhosis in men.
        QJM. 2007; 100: 534-535
        • Gerussi A.
        • Restelli U.
        • Croce D.
        • et al.
        Cost of illness of Primary Biliary Cholangitis - a population-based study.
        Dig Liver Dis. 2021; 53: 1167-1170
        • Lleo A.
        • de Boer Y.S.
        • Liberal R.
        • et al.
        The risk of liver cancer in autoimmune liver diseases.
        Ther Adv Med Oncol. 2019; 11 (1758835919861914)
        • Giannini E.G.
        • Cucchetti A.
        • Erroi V.
        • et al.
        Surveillance for early diagnosis of hepatocellular carcinoma: how best to do it?.
        World J Gastroenterol. 2013; 19: 8808-8821
        • Giannini E.G.
        • Sammito G.
        • Farinati F.
        • et al.
        Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: implications for its clinical use.
        Cancer. 2014; 120: 2150-2157
        • Vitale A.
        • Volk M.
        • Cillo U.
        Transplant benefit for patients with hepatocellular carcinoma.
        World J Gastroenterol. 2013; 19: 9183-9188
        • Cucchetti A.
        • Cescon M.
        • Trevisani F.
        • et al.
        What is the probability of being too old for salvage transplantation after hepatocellular carcinoma resection?.
        Dig Liver Dis. 2012; 44: 523-529
        • Vitale A.
        • Burra P.
        • Frigo A.C.
        • et al.
        Survival benefit of liver resection for patients with hepatocellular carcinoma across different Barcelona Clinic Liver Cancer stages: a multicentre study.
        J Hepatol. 2015; 62: 617-624
        • Pecorelli A.
        • Lenzi B.
        • Gramenzi A.
        • et al.
        Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma.
        Liver Int. 2017; 37: 423-433
        • Sangiovanni A.
        • Triolo M.
        • Iavarone M.
        • et al.
        Multimodality treatment of hepatocellular carcinoma: how field practice complies with international recommendations.
        Liver Int. 2018; 38: 1624-1634
        • Yen Y.H.
        • Cheng Y.F.
        • Wang J.H.
        • et al.
        Adherence to the modified Barcelona clinic liver cancer guidelines: results from a high-volume liver surgery center in east Asias.
        PLoS ONE. 2021; 16e0249194
        • Vitale A.
        • Finotti M.
        • Trevisani F.
        • et al.
        Treatment allocation in patients with hepatocellular carcinoma: need for a paradigm shift?.
        Liver Cancer Int. 2022; 3: 34-36
        • Pelizzaro F.
        • Vitale A.
        • Sartori A.
        • et al.
        Surveillance as determinant of long-term survival in non-transplanted hepatocellular carcinoma patients.
        Cancers (Basel). 2021; 13: 897
        • Carbone M.
        • Nardi A.
        • Flack S.
        • et al.
        Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score.
        Lancet Gastroenterol Hepatol. 2018; 3: 626-634