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Randomized Controlled Trial
. 2011 Dec;21(12):851-60.
doi: 10.1097/FPC.0b013e32834c3e74.

Predicting cirrhosis and clinical outcomes in patients with advanced chronic hepatitis C with a panel of genetic markers (CRS7)

Teresa M Curto  1 , Robert J Lagier, Anna S Lok, James E Everhart, Charles M Rowland, John J Sninsky; HALT-C Trial group
Collaborators, Affiliations
Randomized Controlled Trial

Predicting cirrhosis and clinical outcomes in patients with advanced chronic hepatitis C with a panel of genetic markers (CRS7)

Teresa M Curto et al. Pharmacogenet Genomics. 2011 Dec.

Abstract

Objectives: Genetic factors may play a role in fibrosis progression in patients with chronic hepatitis C (CHC). A cirrhosis risk score (CRS7) with seven single nucleotide polymorphisms was previously shown to correlate with cirrhosis in patients with CHC. This study aimed to assess the validity of CRS7 as a marker of fibrosis progression and cirrhosis and as a predictor of clinical outcomes in patients with CHC.

Methods: A total of 938 patients (677 Caucasians, 165 African-Americans, and 96 Hispanic/Other) in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial were studied. CRS7 was categorized a priori as high risk (n=440), medium risk (n=310), or low risk (n=188). Patients were assessed for four possible outcomes: fibrosis progression, cirrhosis, clinical outcomes [decompensation or hepatocellular carcinoma (HCC)], or HCC alone.

Results: Twenty-nine percent (142/493) developed an increase in fibrosis score by greater than or equal to 2 points on follow-up biopsies, 58% had cirrhosis on one or more biopsies, 35% developed at least one clinical outcome, and 13% developed HCC. CRS7 (trend test) was associated with risk for fibrosis progression (P=0.04) with adjusted hazard ratio of 1.27 (95% confidence interval: 1.01-1.58) and with cirrhosis (P=0.05) with adjusted odds ratio of 1.19 (1.00-1.41). Rates of HCC and clinical outcomes were increased in patients with higher CRS7 scores, but were not statistically significant (P=0.12 clinical outcomes, and P=0.07 HCC). A single nucleotide polymorphism in AZIN1 was significantly associated with fibrosis progression.

Conclusion: CRS7 was validated as a predictor of fibrosis progression and cirrhosis among Hepatitis C Antiviral Long-term Treatment against Cirrhosis patients, who all had advanced fibrosis. CRS7 was not predictive of clinical outcome.

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Conflict of interest statement

Conflicts of Interest and Source of Funding: A. S. Lok is a consultant and receives research support from Hoffmann-La Roche, Inc. R. J. Lagier, C. M. Rowland, and J. J. Sninsky are employees and have equity interest with Celera Corporation. T. M. Curto and J. E. Everhart have no financial relationship related to this project.

Figures

Fig. 1
Fig. 1
Outcomes of all patients according to CRS7 Risk Group
Fig. 2
Fig. 2
Forest plots of individual SNPs and CRS7 risk groups for HALT-C patients – all outcomes
See this image and copyright information in PMC

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