Genetic marker may predict clinical recovery in advanced hep C cirrhosis

Last Updated: 2017-05-12

By Megan Brooks

NEW YORK (Reuters Health) - Researchers have identified a gene variant that may help predict clinical recovery after sustained virological response (SVR) to direct-acting antiviral therapy in patients with decompensated hepatitis C cirrhosis.

The vast majority of patients with HCV cirrhosis achieve virologic cure with direct-acting antiviral agents. "Unfortunately, about 5% of hepatitis C patients with the most serious form, decompensated cirrhosis, fail to clinically improve, or even worsen, after achieving SVR," said Dr. Winston Dunn from the Kansas University Medical Center in Kansas City, during a media briefing at Digestive Disease Week (DDW) 2017 where he presented his research May 6.

“It is important that we figure out a way to identify, in advance, the people with decompensated cirrhosis who may respond best to treatment and those who may not. The information will help us minimize the need for liver transplantations,” said Dr. Dunn.

The researchers hypothesized that a genetic risk factor for hepatic steatosis, namely rs738409 single nucleotide polymorphism (SNP) of the PNPLA3 gene, can predict clinical recovery after SVR in this patient population.

They followed 32 patients with decompensated cirrhosis who had initially achieved SVR with direct-acting antiviral drug therapy. Twelve to 48 weeks after SVR, they tracked changes in Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores to gauge the severity of chronic liver disease.

After SVR, improvement of at least one point in CTP score was seen in 81% of patients with the CC genotype and 56% of patients with either CG or GG genotypes. CTP scores worsened by at least one point in 6% of CC genotype patients and 13% of CG or GG genotype patients, Dr. Dunn reported.

At least a one point improvement in MELD scores occurred in 50% of CC genotype patients and 38% of CG or GG genotype patients. MELD scores worsened by at least a point in 6% of CC genotype patients and 19% in CG or GG genotype patients.

“These data suggest that a patient’s genotype in PNPLA3 gene should be a factor when considering which patient with decompensated cirrhosis should be evaluated for liver transplant,” said Dr. Dunn.

“Identifying this genetic marker continues to move toward precision medicine that we are seeing today, where health care providers can develop specific treatment plans based on the individual needs of patients,” he added.

“We are hoping to develop this test in the future for the treatment of patients with decompensated cirrhosis and hepatitis C,” said Dr. Dunn. His team is also conducting research to figure out the underlying mechanism that may explain why the presence of these genotypes lead to poorer health outcomes.

SOURCE: http://bit.ly/2q8QddR

Digestive Disease Week 2017.