Z Gastroenterol 2018; 56(05): e40
DOI: 10.1055/s-0038-1654639
POSTER
Hepatologie
Georg Thieme Verlag KG Stuttgart · New York

Mortality is increased in NAFLD patients with homozygosity for PNPLA3 risk allele

G Strebinger
1   Krankenhaus Oberndorf/Innere Medizin, Oberndorf, Austria
,
A Feldman
2   Uniklinikum Salzburg/Universitätsklinik für Innere Medizin 1, Salzburg, Austria
,
L Denkmayr
2   Uniklinikum Salzburg/Universitätsklinik für Innere Medizin 1, Salzburg, Austria
,
M Strasser
2   Uniklinikum Salzburg/Universitätsklinik für Innere Medizin 1, Salzburg, Austria
,
S Ruhaltinger
2   Uniklinikum Salzburg/Universitätsklinik für Innere Medizin 1, Salzburg, Austria
,
U Huber-Schönauer
1   Krankenhaus Oberndorf/Innere Medizin, Oberndorf, Austria
,
D Niederseer
3   Universitätsspital Zürich/Universitäres Herzzentrum Zürich, Zürich, Switzerland
,
L Stechemesser
2   Uniklinikum Salzburg/Universitätsklinik für Innere Medizin 1, Salzburg, Austria
,
S Zandanell
2   Uniklinikum Salzburg/Universitätsklinik für Innere Medizin 1, Salzburg, Austria
,
B Paulweber
2   Uniklinikum Salzburg/Universitätsklinik für Innere Medizin 1, Salzburg, Austria
,
C Datz
1   Krankenhaus Oberndorf/Innere Medizin, Oberndorf, Austria
,
E Aigner
2   Uniklinikum Salzburg/Universitätsklinik für Innere Medizin 1, Salzburg, Austria
› Author Affiliations
Further Information

Publication History

Publication Date:
09 May 2018 (online)

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Background and aims:

Several studies have shown the association of I148 M mutation in the PNPLA3 gene with hepatic steatosis, steatohepatitis and progression to fibrosis. The aim of this study was to investigate the association between PNPLA3 genotype and the outcome of NAFLD patients with regard to overall mortality and liver-related events.

Methods:

254 patients with a clinical and histological diagnosis of NAFLD (178 m; 76 f; 53 ± 14yrs) were genotyped for the I148 M variant in the PNPLA3 gene and stratified according to genotypes: II (n = 82), IM (n = 126); MM (n = 46). The clinical outcome data were obtained after a follow-up of 8.4 (± 4.1). years. The primary endpoint was defined as death of any cause or liver transplantation. Secondary endpoints were hepatic events, non-fatal cardiovascular events and extra hepatic malignancy. Clinical data was evaluated by Mann-Whitney-U-test. Event-free survival was estimated by Kaplan-Meier plots and assessed by log-rank test. Frequencies of primary and secondary endpoints were compared using chi-square test.

Results:

Clinical and biochemical characteristics were similar between groups at baseline. ALT levels were higher in carriers of at least one risk allele compared to wild type (p = 0.011 for MM; p = 0.037 for IM). The fatal primary endpoint was reached in 8 (17.4%) MM, 11 (8.7%) IM and 6 (7.3%) II subjects. Kaplan-Meier analysis showed a significantly decreased overall survival in MM compared to wild type (p = 0.033) and II/IM genotype patients combined (p = 0.021). Hepatic events occurred in 8 (17.4%) MM homozygous compared to 18 (8.7%; p = 0.077) non-homozygous (II/IM) patients.

Conclusion:

The overall mortality was significantly higher in subjects with PNPLA3 MM genotype compared to non-MM homozygotes. MM homozygous patients had a near-significant higher rate in hepatic events. PNPLA3 MM genotype may be a clinically useful tool to allocate NAFLD subjects to a close surveillance protocol for liver-related outcomes.