Abstract
BackgroundPNPLA3 rs738409 minor allele c.444G represents a risk factor for liver steatosis and fibrosis progression also in chronic hepatitis C (HCV). We investigated its impact on the timing of liver transplantation (LT) in patients with genotype 1b HCV cirrhosis.MethodsWe genotyped and evaluated 172 LT candidates with liver cirrhosis owing to chronic HCV infection, genotype 1b. One hundred patients needed LT for chronic liver failure (CLF) and 72 for a small hepatocellular carcinoma (HCC) in the cirrhotic liver without CLF. Population controls (n = 647) were selected from the Czech cross-sectional study MONICA.ResultsThe CLF patients were younger (53.5 ± 7.2 vs. 59.6 ± 6.6, P < 0.001) with more advanced liver disease than HCC patients (Child-Pugh’s score 9.1 ± 1.8 vs. 7.1 ± 1.9, P < 0.001, MELD 14.1 ± 3.9 vs. 11.1 ± 3.7, P < 0.001). PNPLA3 G allele increased the risk of LT for CLF in both allelic and recessive models (CG + GG vs. CC: OR, 1.90; 95% CI, 1.017–3.472, P = 0.045 and GG vs. CC + CG: OR, 2.94; 95% CI, 1.032–7.513, P = 0.042). Multivariate analysis identified younger age (P < 0.001) and the G allele (P < 0.05) as risk factors for CLF. The genotype frequencies between the CLF group and MONICA study significantly differed in both, allelic and recessive model (P = 0.004, OR 1.87, 95% CI 1.222–2.875; P < 0.001, OR 3.33, 95% CI 1.824–6.084, respectively). The OR values almost doubled in the recessive model compared with the allelic model suggesting the additive effect of allele G. In contrast, genotype frequencies in the HCC group were similar to the MONICA study in both models. Pretransplant viral load was significantly lower in GG than in CC + CG genotypes (median, IQR; 162,500 (61,550–319,000) IU/ml vs. 570,000 (172,000–1,595,000) IU/ml, P < 0.0009).ConclusionsOur results suggest that PNPLA3 rs738409 G allele carriage may be associated with a faster progression of HCV cirrhosis to chronic liver failure.
Highlights
Adequate timing of liver transplantation (LT) represents one of the main factors determining favourable posttransplant outcome
patatin-like phospholipase domain containing 3 (PNPLA3) G allele increased the risk of LT for chronic liver failure (CLF) in both allelic and recessive models (CG + GG vs. CC: odds ratio (OR), 1.90; 95% confidence interval (CI), 1.017–3.472, P = 0.045 and GG vs. CC + CG: OR, 2.94; 95% CI, 1.032–7.513, P = 0.042)
The genotype frequencies between the CLF group and MONICA study significantly differed in both, allelic and recessive model (P = 0.004, OR 1.87, 95% CI 1.222–2.875; P < 0.001, OR 3.33, 95% CI 1.824–6.084, respectively)
Summary
Adequate timing of liver transplantation (LT) represents one of the main factors determining favourable posttransplant outcome. The natural course of liver diseases may be altered by genetic factors. More than fifty studies demonstrating that the PNPLA3 rs738409 G allele is a risk factor for non-alcoholic steatohepatitis (NASH), liver cirrhosis in NASH or alcoholic liver disease have been published in the past decade [5,6,7,8,9,10,11]. The increased risk of HCC and PNPLA3 G allele was found only in alcoholic liver disease, but not in non-alcoholic fatty liver disease or viral hepatitis B and C [25]. PNPLA3 rs738409 minor allele c.444G represents a risk factor for liver steatosis and fibrosis progression in chronic hepatitis C (HCV). We investigated its impact on the timing of liver transplantation (LT) in patients with genotype 1b HCV cirrhosis
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