Tuesday, June 25, 2013

A Genetic Biomarker for Long-Term Prognosis of HCV-Related Cirrhosis

A Genetic Biomarker for Long-Term Prognosis of HCV-Related Cirrhosis

Profiling a 186-gene signature from needle-biopsy specimens could improve targeting of intensive surveillance to the highest-risk patients.

Hepatitis C virus (HCV)–related cirrhosis is a leading cause of liver-related morbidity and mortality. Identifying prognostic biomarkers of long-term outcomes might allow clinicians to risk-stratify their patients with cirrhosis and target high-risk patients for closer, more-intensive monitoring. In the current study, investigators assessed whether a 186-gene signature from liver tissue can predict death, progression of cirrhosis, or hepatocellular carcinoma (HCC) in HCV-infected patients with cirrhosis.

Researchers performed whole-genome gene expression profiling on archived liver biopsy tissue of 216 HCV-infected patients with Child-Pugh Class A cirrhosis (identified only by histology). The patients had been enrolled in a long-term, cohort study between 1985 and 1998 (N Engl J Med 1991; 325:675). During median follow-up of 10 years, 66 patients died (31%; 28 from HCC, 20 from liver failure, and 15 from non-liver–related causes), 71 (34%) developed hepatic decompensation, 66 (31%) progressed to Child-Pugh class B or C, 65 (30%) developed HCC (annual incidence, 2.9%), and 12 patients underwent liver transplantation.

Using the gene expression signature, patients were categorized by prognosis: poor (25%); intermediate (47%), or good (28%). In multivariate analysis, having a poor-prognosis signature was significantly associated with increased risk for death (P=0.004), liver disease progression (P<0.001), and HCC development (P=0.009). In the poor-, intermediate-, and good-prognosis groups, 10-year survival rates were 63%, 74%, and 85%, respectively, and annual HCC incidence rates were 5.8%, 2.2%, and 1.5%.

Comment: This study has significant clinical implications. First, such prognostic data will allow clinicians to advise patients with hepatitis C virus and early cirrhosis on their long-term prognoses. Second, these data will enable clinicians and public health programs to more appropriately target intensive surveillance practices to high-risk patients. Finally, genome-wide profiling can seemingly be performed on needle-biopsy specimens, thus allowing these important data to be gathered during routine clinical care. Once this 186-gene signature is further validated, it will become an important clinical tool.

Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology June 21, 2013

Hoshida Y et al. Prognostic gene expression signature for patients with hepatitis C–related early-stage cirrhosis. Gastroenterology 2013 May; 144:1024. (http://viajwat.ch/1c3YQqs)
Medline abstract (Free)

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