Genetic markers could identify patients with HCV and cirrhosis who will improve with treatment

Paul Basilio, MDLinx | May 08, 2017

New research shows that genotyping of patients who have advanced cirrhosis caused by hepatitis C virus (HCV) infection could help predict the likelihood of improvement after successful treatment. The study, which was recently presented at Digestive Disease Week 2017, could decrease the need for liver transplantation in such patients.

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Patients with HCV and serious decompensated cirrhosis may fail to improve or even experience further deterioration after treatment.

“Our findings further the move toward precision medicine, because we can potentially use a person’s genetic makeup to identify individuals who can benefit most from hepatitis C treatment, even at a very late stage in the progression of their liver disease,” said Winston Dunn, MD, the study’s lead author and Associate Professor at the University of Kansas Medical Center in Kansas City, KS.

While most patients with HCV can be cured with antiviral agents, patients with serious decompensated cirrhosis may fail to improve or even experience further deterioration after treatment.

Dr. Dunn’s team focused on the Rs738409 single nucleotide polymorphism (RSP)—a variation in a single base pair of DNA in the PNPLA3 gene, which is the the most important genetic risk factor for alcoholic liver disease and nonalcoholic fatty liver disease. Patients have one of three genotypes: CC, CG, or GG.

Thirty-two patients with decompensated cirrhosis who had initially achieved sustained virologic response (SVR) were followed at the University of Kansas Medical Center. The patients were essentially virus-free following interferon-free direct-acting antiviral medications such as sofosbuvir-ledipasvir and sofosbuvir-simeprevir.

Twelve to 48 weeks after achieving SVR, the researchers tracked changes in the patient’s Model for End-stage Liver Disease (MELD) and Child-Pugh (CPT) scores.

Results showed that 5 of 16 patients with genotypes CG or GG had worsening MELD or CPT scores following antiviral treatment. Only one of the patients with the CC genotype had worse scores.

“These findings suggest that screening for the Rs738409 CG and GG genotypes in hepatitis C patients with decompensated cirrhosis can help to identify individuals who are less likely to recover after achieving a ‘cure’ of their hepatitis C,” Dr. Dunn said. “Until now, we have not had a method to distinguish between the individuals who would recover given equal severity in baseline disease.”

Dr. Dunn’s team will now examine the underlying reasons why the presence of these genotypes leads to poor outcomes. In addition, they will look at how fatty liver and insulin resistance affect clinical recovery after treatment with direct-acting antiviral medications, and whether those findings correspond to Rs738409, the genetic marker for fatty liver.

Financial support for this study was provided by the Frontiers Pilot and Collaborative Studies Funding Program.