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PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis.
J Hepatol. 2013 Feb; 58(2):312-8.JH

Abstract

BACKGROUND & AIMS

Several studies have reported an association between the genetic variant rs738409 (G) in the PNPLA3 gene and the risk of cirrhosis in various liver diseases. Our purpose was to assess the influence of this polymorphism on the risk of hepatocellular carcinoma (HCC) occurrence in two distinct longitudinal cohorts of patients with cirrhosis as well as its possible usefulness in HCC-risk model prediction.

METHODS

PNPLA3 rs738409 genotypes were assessed in 279 patients with alcoholic- and 253 patients with HCV-related cirrhosis. These patients were followed-up and screened for the risk of HCC, and the influence of rs738409 on the occurrence of liver cancer was assessed using the Kaplan-Meier method, then according to the multivariate Cox model.

RESULTS

In patients with HCV-related cirrhosis, rs738409 genotypes did not influence the risk of HCC development (log-rank = 0.7) or death (log-rank = 0.2). Conversely, in patients with alcoholic cirrhosis, the rs738409 (GG) genotype was an independent risk factor for HCC occurrence (HR = 1.72 [1.21-2.45], log-rank = 0.002) as well as older age, male gender, and higher BMI. Combining these features enabled HCC-risk stratification of this population into three groups with the 6-year cumulative incidence ranging from 3.4% (low risk, n = 58), 12.2% (intermediate risk, n = 163), and 51.7% (high risk, n = 58), respectively (HR = 4.3 [2.7-6.4]; log-rank <0.0001).

CONCLUSIONS

This study provides key data that affirm the influence of the rs738409 (GG) genotype on the occurrence of HCC in patients with alcoholic cirrhosis. Its combination with clinical features refines the selection of patients at higher risk of liver cancer development.

Authors+Show Affiliations

University Paris 13-UFR SMBH/INSERM U698, Bobigny, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23069476

Citation

Guyot, Erwan, et al. "PNPLA3 Rs738409, Hepatocellular Carcinoma Occurrence and Risk Model Prediction in Patients With Cirrhosis." Journal of Hepatology, vol. 58, no. 2, 2013, pp. 312-8.
Guyot E, Sutton A, Rufat P, et al. PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis. J Hepatol. 2013;58(2):312-8.
Guyot, E., Sutton, A., Rufat, P., Laguillier, C., Mansouri, A., Moreau, R., Ganne-Carrié, N., Beaugrand, M., Charnaux, N., Trinchet, J. C., & Nahon, P. (2013). PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis. Journal of Hepatology, 58(2), 312-8. https://doi.org/10.1016/j.jhep.2012.09.036
Guyot E, et al. PNPLA3 Rs738409, Hepatocellular Carcinoma Occurrence and Risk Model Prediction in Patients With Cirrhosis. J Hepatol. 2013;58(2):312-8. PubMed PMID: 23069476.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis. AU - Guyot,Erwan, AU - Sutton,Angela, AU - Rufat,Pierre, AU - Laguillier,Christelle, AU - Mansouri,Abdellah, AU - Moreau,Richard, AU - Ganne-Carrié,Nathalie, AU - Beaugrand,Michel, AU - Charnaux,Nathalie, AU - Trinchet,Jean-Claude, AU - Nahon,Pierre, Y1 - 2012/10/13/ PY - 2012/04/03/received PY - 2012/09/18/revised PY - 2012/09/28/accepted PY - 2012/10/17/entrez PY - 2012/10/17/pubmed PY - 2013/7/24/medline SP - 312 EP - 8 JF - Journal of hepatology JO - J. Hepatol. VL - 58 IS - 2 N2 - BACKGROUND & AIMS: Several studies have reported an association between the genetic variant rs738409 (G) in the PNPLA3 gene and the risk of cirrhosis in various liver diseases. Our purpose was to assess the influence of this polymorphism on the risk of hepatocellular carcinoma (HCC) occurrence in two distinct longitudinal cohorts of patients with cirrhosis as well as its possible usefulness in HCC-risk model prediction. METHODS: PNPLA3 rs738409 genotypes were assessed in 279 patients with alcoholic- and 253 patients with HCV-related cirrhosis. These patients were followed-up and screened for the risk of HCC, and the influence of rs738409 on the occurrence of liver cancer was assessed using the Kaplan-Meier method, then according to the multivariate Cox model. RESULTS: In patients with HCV-related cirrhosis, rs738409 genotypes did not influence the risk of HCC development (log-rank = 0.7) or death (log-rank = 0.2). Conversely, in patients with alcoholic cirrhosis, the rs738409 (GG) genotype was an independent risk factor for HCC occurrence (HR = 1.72 [1.21-2.45], log-rank = 0.002) as well as older age, male gender, and higher BMI. Combining these features enabled HCC-risk stratification of this population into three groups with the 6-year cumulative incidence ranging from 3.4% (low risk, n = 58), 12.2% (intermediate risk, n = 163), and 51.7% (high risk, n = 58), respectively (HR = 4.3 [2.7-6.4]; log-rank <0.0001). CONCLUSIONS: This study provides key data that affirm the influence of the rs738409 (GG) genotype on the occurrence of HCC in patients with alcoholic cirrhosis. Its combination with clinical features refines the selection of patients at higher risk of liver cancer development. SN - 1600-0641 UR - https://www.unboundmedicine.com/medline/citation/23069476/PNPLA3_rs738409_hepatocellular_carcinoma_occurrence_and_risk_model_prediction_in_patients_with_cirrhosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(12)00776-3 DB - PRIME DP - Unbound Medicine ER -