PT  - JOURNAL ARTICLE
AU  - King, Lindsay Y
AU  - Canasto-Chibuque, Claudia
AU  - Johnson, Kara B
AU  - Yip, Shun
AU  - Chen, Xintong
AU  - Kojima, Kensuke
AU  - Deshmukh, Manjeet
AU  - Venkatesh, Anu
AU  - Tan, Poh Seng
AU  - Sun, Xiaochen
AU  - Villanueva, Augusto
AU  - Sangiovanni, Angelo
AU  - Nair, Venugopalan
AU  - Mahajan, Milind
AU  - Kobayashi, Masahiro
AU  - Kumada, Hiromitsu
AU  - Iavarone, Massimo
AU  - Colombo, Massimo
AU  - Fiel, Maria Isabel
AU  - Friedman, Scott L
AU  - Llovet, Josep M
AU  - Chung, Raymond T
AU  - Hoshida, Yujin
TI  - A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration
AID  - 10.1136/gutjnl-2014-307862
DP  - 2015 Aug 01
TA  - Gut
PG  - 1296--1302
VI  - 64
IP  - 8
4099  - http://gut.bmj.com/content/64/8/1296.short
4100  - http://gut.bmj.com/content/64/8/1296.full
SO  - Gut2015 Aug 01; 64
AB  - 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/mm3), 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.