New Index Helps Predict Course of Early HCV Cirrhosis

By Lorraine L. Janeczko

September 04, 2014

NEW YORK (Reuters Health) - A genomic signature, combined with bilirubin and platelet tests, can help identify patients with early hepatitis C virus (HCV) cirrhosis who are at high risk for complications, new research suggests.

"This study provides additional evidence that a gene signature . . . can itself predict future clinical events for a patient with HVC-related cirrhosis. It helps predict downstream deterioration in terms of liver failure and deaths from liver failure or risk for hepatocellular carcinoma," said co-senior author Dr. Raymond T. Chung of Harvard Medical School in Boston, in a phone call with Reuters Health.

"The most important aspect of this is really to help stratify or identify patients who may need more intensive follow-up, but also to potentially identify candidates for possible interventions that might help slow the progression of liver disease. Our hope would be to apply this in patients with a longer run-up so they can be identified further in advance and potentially intervened and treated before complications occur," he said.

Could this test replace the MELD the score?

"No," Dr. Chung said. "The MELD score presupposes that these patients already have advanced disease. The MELD in anybody who doesn't have cirrhosis should be in the normal range. It's only when cirrhosis has deteriorated that the MELD score starts to rise. We would intend this index to be used well before one ever had to use a MELD score."

As reported online August 20 in Gut, the components of the new prognostic index are a digital transcript counting assay (NanoString nCounter) consisting of a 186-gene signature, the bilirubin level (>1 mg/dL), and the platelet count (<100,000/mm3).

In an independent training group of 216 Italian patients with HCV cirrhosis followed for a median of 10 years, the prognostic index was associated with hepatic decompensation (hazard ratio=2.71, p=0.003), 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 validation group consisted of 145 adults with compensated HCV cirrhosis who had liver biopsies over a 17-year period. Based on the prognostic index, the researchers stratified patients into groups at high-risk (16%), intermediate-risk (42%) or low-risk (42%).

The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), 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).

Co-senior author Dr. Yujin Hoshida of the Icahn School of Medicine at Mount Sinai in New York City wrote in an email, "Our prognostic index was strikingly predictive of a series of hepatitis C cirrhosis complications with hazard ratios as high as 7.36. The magnitude of association is outstanding compared with previously reported molecular prognostic markers (with hazard ratios generally below 2.0). It's kind of surprising that we keep seeing the high prognostic association across multiple patient cohorts and assay platforms."

"The gene signature could be assayed on archived fixed liver biopsy tissues. You could do this by using daily clinical specimens without any special preparation. We have some preliminary data indicating that the gene signature is prognostic also in hepatitis B virus and nonalcoholic steatohepatitis (NASH). We're now analyzing these etiologies and as well as alcohol on a larger scale with National Institutes of Health support," he added.

Several of the authors are named investigators on a pending patent application involving compositions, kits, and methods for detecting, characterizing, preventing, and treating hepatic disorders. NanoString has secured the option to an exclusive worldwide license, but has no role in the current study.


Gut 2014.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: