Abstract
Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12–3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23–6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01–11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.
Highlights
Chronic infection with hepatitis C virus (HCV) may lead to advanced liver fibrosis and endstage liver disease
The results obtained in this study support that the fatty liver disease (FLD)-related patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 genetic variant is associated with liver disease progression in HIV/HCV-coinfected patients
Others single nucleotide polymorphism (SNP) associated with FLD in the HIV-infected population such as SAMM50 rs738491 and LPPR4 rs12743824 do not seem to have a relevant role on liver disease evolution in these patients
Summary
Chronic infection with hepatitis C virus (HCV) may lead to advanced liver fibrosis and endstage liver disease. Several authors have analyzed whether the rs738409 genetic marker, located within the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, could be a risk factor for liver fibrosis progression in HIV/HCV-coinfected patients with controversial results [8,9,10,11]. This single nucleotide polymorphism (SNP) has been consistently associated with fatty liver disease (FLD) in both HCV-uninfected and HCV-infected individuals [12, 13]. Other SNPs that have been recently associated with FLD in the HIV-infected population [14] could have an impact on the faster liver fibrosis progression observed in the HIV/HCVcoinfected population, but this has not been explored so far
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
