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

作者：King Lindsay Y; Canasto Chibuque Claudia; Johnson Kara B; Yip Shun; Chen Xintong; Kojima Kensuke; Deshmukh Manjeet; Venkatesh Anu; Tan Poh Seng; Sun Xiaochen; Villanueva Augusto; Sangiovanni Angelo; Nair Venugopalan; Mahajan Milind; Kobayashi Masahiro; Kumada Hiromitsu; Iavarone Massimo; Colombo Massimo; Fiel Maria Isabel; Friedman Scott L; Llovet Josep M; Chung Raymond T; Hoshida Yujin^*

来源：Gut, 2015, 64(8): 1296-1302.

DOI：10.1136/gutjnl-2014-307862

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.

• 出版日期2015-8