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Gut. 2016 Feb;65(2):321-9. doi: 10.1136/gutjnl-2014-308351. Epub 2015 Jan 7.

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

Author information

1
National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit (BRU) and Centre for Liver Research, University of Birmingham, Birmingham, UK Liver Unit, Queen Elizabeth Hospital, Birmingham, UK.
2
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
3
Liver Unit, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.
4
Department of Surgical, Oncological and Gastroenterological, University of Padua, Padua, Italy.
5
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands Toronto Center for Liver Diseases, Toronto Western & General Hospital, University Health Network, Toronto, Ontario, Canada.
6
Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano (MI), Italy.
7
Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
8
Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, The Netherlands.
9
Center de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, APHP, Paris, France.
10
Department of Digestive and Liver diseases, UT Southwestern Medical Center, Dallas, Texas, USA.
11
The Sheila Sherlock Liver Center, The Royal Free Hospital, London, UK.
12
Department of Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
13
Division of Gastroenterology and Hepatology, University of Alberta, Edmonton, Alberta, Canada.
14
Liver Center of Excellence, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington, USA Liver Care Network, Swedish Medical Center, Seattle, Washington, USA.
15
Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA Arizona State University, Phoenix, Arizona, USA.

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.

KEYWORDS:

AUTOIMMUNE LIVER DISEASE; CHOLESTATIC LIVER DISEASES; PRIMARY BILIARY CIRRHOSIS

PMID:
25567117
DOI:
10.1136/gutjnl-2014-308351
[Indexed for MEDLINE]

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