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

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, non-treatment 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). Non-response 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).

CONCLUSIONS:

This uniquely powered, internationally representative cohort robustly demonstrates that 12-month biochemical non-response is associated with increased future risk of developing HCC in PBC. Such risk stratification is relevant to patient care and development of new therapies.

• Authors: 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 Hansen, Gideon M Hirschfield, Global PBC Study Group
• Journal: Gut (Gut) Vol. 65 Issue 2 Pg. 321-9 (Feb 2016) ISSN: 1468-3288 [Electronic] England
• PMID: 25567117 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chemical References

• Ursodeoxycholic Acid
• Aspartate Aminotransferases

Topics

• Aspartate Aminotransferases (blood)
• Carcinoma, Hepatocellular (epidemiology, etiology)
• Europe (epidemiology)
• Female
• Humans
• Kaplan-Meier Estimate
• Liver Cirrhosis, Biliary (complications, epidemiology, metabolism)
• Liver Neoplasms (epidemiology, etiology)
• Logistic Models
• Male
• North America (epidemiology)
• Proportional Hazards Models
• Risk
• Risk Factors
• Sex Factors
• Thrombocytopenia (complications)
• Ursodeoxycholic Acid (therapeutic use)