Genetic marker predicts SVR failure in patients with HCV, cirrhosis

CHICAGO — A research team identified genetic markers that predict which patients with hepatitis C and cirrhosis will most likely improve with direct-acting antiviral agent and those who will fail to improve or possibly worsen, according to a presentation at Digestive Disease Week.

“The current generation of direct-acting antiviral agents provides virological cure for 90% to 95% of patients with hepatitis C cirrhosis. Unfortunately, about 5% of hepatitis C patients with ... cirrhosis, failed to clinically improve or even worsened after achieving virological response SVR,” Winston Dunn, MD, associate professor of gastroenterology at the University of Kansas Medical Center, said during a pre-conference press program. “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.”

The researchers analyzed the PNPLA3 gene, the most important genetic factor for both alcoholic liver disease and nonalcoholic fatty liver disease, according to Dunn, and specifically focused on the rs738409 polymorphism, a variation in a single base pair of DNA in the PNPLA3 gene. Patients will have either CC, CG or GG genotypes.

The study comprised 32 patients with decompensated cirrhosis who initially achieved SVR. The researchers tracked changes in MELD and Child-Pugh scores in the patients at 12, 24 and 48 weeks after SVR.

Child-Pugh scores improved by at least one point in 81% of the patients with CC genotype and by 56% of patients with either CG or GG genotypes. Child-Pugh scores worsened by at least one point in 6% of CC genotype patients and 13% of CG or GG genotype patients.

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

Mean difference in change in distribution of Child-Pugh scores and MELD scores from baseline to after SVR were 1.67 points and 1.7 points, respectively.

“These data suggest that a patient’s genotype in the PNPLA3 gene should be a factor when deciding which patient with decompensated cirrhosis should be evaluated for liver transplant. 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,” Dunn said in the press program. “As the next step, our team will be conducting research to possibly explain the underlying mechanism behind these findings.” – by Talitha Bennett

Reference: Dunn W, et al. Abstract Sa1535. Presented at: Digestive Disease Week; May 6-9, 2017; Chicago.

Disclosure: Healio.com/Hepatology was unable to determine Dunn’s relevant financial disclosures at the time of publication.