Z Gastroenterol 2014; 52 - KG109
DOI: 10.1055/s-0034-1386131

The adiponutrin (PNPLA3) variant increases the risk of developing end-stage liver cirrhosis but does not affect survival in patients with cirrhosis

M Krawczyk 1, A Bohner 1, C Reichel 2, F Lammert 1, F Grünhage 1
  • 1Saarland University Hospital, Department of Medicine II, Homburg, Germany
  • 2Rehabilitation Center Bad Brückenau, Clinic Hartwald, German Pension Insurance, Federal Office, Bad Brückenau, Germany

Background: The common adiponutrin (PNPLA3) variant (p.I148 M) has been associated with the development and progression of chronic liver disease such as NASH and ASH as well as HCC (Liu et al. J Hepatol 2014). Recently we have described that the p.I148 M mutation is also associated with increased liver stiffness (Krawczyk et al. J Hepatol 2011). Currently there is no data available on the effect of this variant and survival in patients with advanced liver disease. We therefore tested whether the p.I148 M polymorphism is associated with mortality in patients with advanced liver cirrhosis.

Patients and methods: The cohort consisted of 92 patients with advanced liver cirrhosis. The patients were followed prospectively for survival for at least 24 months. DNA was available in 80 patients. Kaplan-Meier curves for survival were generated and log rank tests were applied for differences in median survival times between carriers and non-carriers of the at risk genotype p. 148 M. In addition we performed testing for differences in survival in patients either homozygous for the wild-type or the mutant allele.

Results: Patients with liver cirrhosis in Child-Pugh stage B or C were overrepresented (52%). The median follow up time was 602 days (range 10 – 749 days). Overall 38/80 (48%) patients died, while 5 patients were transplanted during follow up. PNPLA3 genotype frequencies did not deviate from Hardy-Weinberg equilibrium (CC/CG/GG: 36%/43%/21%). The frequency of the risk variant was higher in this cohort as compared to individuals without cirrhosis (common OR = 2.25, P = 3.74 × 10-6) and patients with cirrhosis in general (common OR = 1.58, P = 0.025) from our previous publication (Krawczyk et al. J Hepatol 2011). There were no differences in allele and genotype distribution between survivors and non-survivors (P > 0.05). No differences in survival were detected between carriers and non-carriers or patients homozygous for either allele (log-rank > 0.05 respectively) after 6, 15 and 24 months.

Conclusion: The p.I148 M variant in the PNPLA3 gene promotes the progression of fatty liver disease and the development of cirrhosis. However, we could not detect an effect on short- or longer-term mortality secondary to infectious complications in our patients with advanced cirrhosis.