PNPLA3 rs738409 G allele carriers with genotype 1b HCV cirrhosis have lower viral load but develop liver failure at younger age
Autoři:
Renata Senkerikova aff001; Sona Frankova aff001; Milan Jirsa aff002; Miluse Kreidlova aff004; Dusan Merta aff005; Magdalena Neroldova aff002; Klara Chmelova aff001; Julius Spicak aff001; Jan Sperl aff001
Působiště autorů:
Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
aff001; Charles University, First Faculty of Medicine, Prague, Czech Republic
aff002; Laboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
aff003; Institute of Medical Biochemistry and Laboratory Diagnostics First Faculty of Medicine Charles University and General University Hospital in Prague, Prague, Czech Republic
aff004; Anesthesiology, Resuscitation and Intensive Care Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
aff005
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0222609
Souhrn
Background
PNPLA3 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.
Methods
We 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.
Results
The 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).
Conclusions
Our results suggest that PNPLA3 rs738409 G allele carriage may be associated with a faster progression of HCV cirrhosis to chronic liver failure.
Klíčová slova:
Medicine and health sciences – Surgical and invasive medical procedures – Digestive system procedures – Transplantation – Organ transplantation – Liver transplantation – Oncology – Cancers and neoplasms – Carcinomas – Hepatocellular carcinoma – Gastrointestinal tumors – Gastroenterology and hepatology – Liver diseases – Liver fibrosis – Fatty liver – Cirrhosis – Biology and life sciences – Genetics – Heredity – Genetic mapping – Variant genotypes – Microbiology – Virology – Viral transmission and infection – Viral load
Zdroje
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