Genetic polymorphisms could help to determine outcomes in hepatitis C cirrhosis patients

Research presented at Digestive Disease Week®(May 6–9, Chicago, IL USA) has suggested that genotyping hepatitis C patients with advanced cirrhosis could help predict the likelihood of improvement after treatment, minimizing the need for liver transplants.

Lead author Winston Dunn (University of Kansas Medical Center, KS, USA) explained: “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.”

The majority of hepatitis C patients can now be cured by treatment with direct-acting antiviral agents, however some individuals with more serious cirrhosis or liver damage, don’t improve or present with further deterioration even after treatment.

This study investigated the significance of the Rs738409 single nucleotide polymorphism – a single base pair variation in the PNPLA3 gene, which has previously been established as an important risk factor in alcoholic liver disease and nonalcoholic fatty liver disease.

Individuals can have one of three genotypes of Rs738409; CC, CG or GG. The team investigated these in a cohort of 32 patients with decompensated liver cirrhosis. Initially all participants achieved a sustained virological response after treatment with direct-acting antiviral medication, effectively eliminating the virus.

The team followed up after 12–48 weeks, assessing the changes in two measures typically utilized to assess chronic liver disease; the Model for End-Stage Liver Disease (MELD) and the Child-Pugh (CPT) scores.

The researchers discovered that five of 16 patients who possessed CG or GG genotypes had worse MELD and CPT scores after the follow-up period, compared with only one patient from the CC genotype.

Dunn explained: “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. Until now, we have not had a method to distinguish between the individuals who would recover given equal severity in baseline disease.”

These findings could help practitioners predict a patient’s improvement after treatment, and minimize the need for liver transplants in the future. The team hope to carry out further research examining the underlying mechanisms for why CG and GG genotypes may lead to poor outcomes.



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