Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: A multicentre international study

Palak J. Trivedi, Willem J. Lammers, Henk R. Van Buuren, Albert Parés, Annarosa Floreani, Harry L A Janssen, Pietro Invernizzi, Pier Maria Battezzati, Cyriel Y. Ponsioen, Christophe Corpechot, Raoul Poupon, Marlyn J. Mayo, Andrew K. Burroughs, Frederik Nevens, Andrew L. Mason, Kris V. Kowdley, Ana Lleo, Llorenç Caballeria, Keith D. Lindor, Bettina E. HansenGideon M. Hirschfield

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Objective Hepatocellular carcinoma (HCC) is an infrequent yet critical event in primary biliary cirrhosis (PBC); however, predictive tools remain ill-defined. Our objective was to identify candidate risk factors for HCC development in patients with PBC. Design Risk factor analysis was performed in over 15 centres from North America and Europe spanning >40 years observation period using Cox proportional hazards assumptions, logistic regression, and Kaplan- Meier estimates. Results Of 4565 patients with PBC 123 developed HCC, yielding an incidence rate (IR) of 3.4 cases/1000 patient-years. HCC was significantly more common in men (p<0.0001), and on univariate analysis factors at PBC diagnosis associated with future HCC development were male sex (unadjusted HR 2.91, p<0.0001), elevated serum aspartate transaminase (HR 1.24, p<0.0001), advanced disease (HR 2.72, p=0.022), thrombocytopenia (HR 1.65, p<0.0001), and hepatic decompensation (HR 9.89, p<0.0001). As such, nontreatment with ursodeoxycholic acid itself was not associated with cancer development; however, 12-month stratification by biochemical non-response (Paris-I criteria) associated significantly with future risk of HCC (HR 4.52, p<0.0001; IR 6.6 vs 1.4, p<0.0001). Nonresponse predicted future risk in patients with early stage disease (IR 4.7 vs 1.2, p=0.005), advanced disease (HR 2.79, p=0.02; IR 11.2 vs 4.4, p=0.033), and when restricting the analysis to only male patients (HR 4.44, p<0.001; IR 18.2 vs 5.4, p<0.001). On multivariable analysis biochemical non-response remained the most significant factor predictive of future HCC risk (adjusted HR 3.44, p<0.0001).

Original languageEnglish (US)
Pages (from-to)321-329
Number of pages9
JournalGut
Volume65
Issue number2
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Gastroenterology

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    Trivedi, P. J., Lammers, W. J., Van Buuren, H. R., Parés, A., Floreani, A., Janssen, H. L. A., Invernizzi, P., Battezzati, P. M., Ponsioen, C. Y., Corpechot, C., Poupon, R., Mayo, M. J., Burroughs, A. K., Nevens, F., Mason, A. L., Kowdley, K. V., Lleo, A., Caballeria, L., Lindor, K. D., ... Hirschfield, G. M. (2016). Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: A multicentre international study. Gut, 65(2), 321-329. https://doi.org/10.1136/gutjnl-2014-308351