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Gut. 2015 Aug;64(8):1296-302. doi: 10.1136/gutjnl-2014-307862. Epub 2014 Aug 20.

A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration.

Author information

1
Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
2
Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
3
Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Health System, Singapore.
4
Institute of Liver Sciences, King's College London, London, UK.
5
M. & A. Migliavacca Center for Liver Disease and 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
6
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, USA.
7
Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA.
8
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
9
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, USA.
10
Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA HCC Translational Research Laboratory, Barcelona Clinic Liver Cancer Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer Centro de Investigaciones en Red de Enfermedades Hepáticas y Digestivas, Hosptial Clínic Barcelona, Barcelona, Catalonia, Spain Institució Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Catalonia, Spain.

Abstract

OBJECTIVE:

The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression.

DESIGN:

We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1 mg/dL) and platelet count (<100,000/mm(3)), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10 years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8 years).

RESULTS:

In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001).

CONCLUSIONS:

A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions.

KEYWORDS:

CIRRHOSIS; GENE EXPRESSION; HEPATITIS C

PMID:
25143343
PMCID:
PMC4336233
DOI:
10.1136/gutjnl-2014-307862
[Indexed for MEDLINE]
Free PMC Article

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