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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
prolekare.web.journal.doi_sk: 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:

Biology and life sciences – Genetics – Heredity – Genetic mapping – Medicine and health sciences – Microbiology – Gastroenterology and hepatology – Liver diseases – Cirrhosis – Oncology – Cancers and neoplasms – Virology – Viral transmission and infection – Viral load – Surgical and invasive medical procedures – Digestive system procedures – Gastrointestinal tumors – Transplantation – Organ transplantation – Carcinomas – Hepatocellular carcinoma – Liver transplantation – Variant genotypes – Liver fibrosis – Fatty liver


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