Genetic markers may predict which hep C patients will not improve with treatment

By Liz Meszaros, MDLinx
Published August 27, 2017

Key Takeaways

In patients with advanced cirrhosis from hepatitis C virus (HCV), genotyping may help clinicians predict which are likely to improve after successful hepatitis C treatment, and thereby minimize the need for liver transplants, according to results presented at Digestive Disease Week (DDW) 2017.

"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," said lead author, Winston Dunn, MD, associate professor, University of Kansas Medical Center, Kansas City, KS.

Treatment with direct-acting antiviral agents (DAAs) will cure most patients with HCV, but some of those with more serious decompensated cirrhosis may fail to improve or may even experience further deterioration.

For both alcoholic liver disease and nonalcoholic fatty liver disease, the PNPPLA3 gene is the most important genetic risk factor. Dr. Dunn and colleagues focused on the Rs738409 single nucleotide polymorphism, a variation in the single base pair of DNA in the PNPLA3 gene. Patients have one of three genotypes: CC, CG, or GG.

To determine possible predictors of patients who will not fare well, Dr. Dunn and colleague followed 32 patients with decompensated cirrhosis who initially achieved sustained virologic response (SVR), and were virtually virus free after treatment with interferon-free DAAs. In these patients, they tracked changes in the Model for End-Stage Liver Disease (MELD) and Child-Pugh (CPT) scores at 12 to 48 weeks after SVR to assess the severity of their chronic liver disease.

In 5 of 16 patients with CG or GG genotypes had worse MELD or CPT scores, compared with only one patient with the CC genotype.

"These findings suggest 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," added Dr. Dunn.

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

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