PNPLA3 Gene Polymorphisms in HCV/HIV-Coinfected Individuals

Sherman, Kenneth E.; Rouster, Susan D.; Kang, Min-Hee; Umbleja, Triin; Sterling, Richard K.; Butt, Adeel A.

doi:10.1007/s10620-018-5278-y

Cited by 4 publications

(5 citation statements)

References 18 publications

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“…While HCC development also reduced by DAA, HCV/HIV co-infected patients with advanced cirrhosis is still represent a risk group for this outcome, with the highest risk of HCC progression in DAA non-responders. Thus, the heterogenicity of these cirrhotic patients based on various co-morbidities, genetic polymorphism[87-89], late treatment initiation and altered response to treatment may affect the end-stage liver disease progression in coinfected patients.…”

Section: Hiv/hbv Co-infection-induced Liver Injurymentioning

confidence: 99%

Human immunodeficiency virus and hepatotropic viruses co-morbidities as the inducers of liver injury progression

Ganesan¹,

Poluektova²,

Kharbanda³

et al. 2019

WJG

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Hepatotropic viruses induced hepatitis progresses much faster and causes more liver- related health problems in people co-infected with human immunodeficiency virus (HIV). Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV, liver disease induced by hepatitis B virus (HBV) and hepatitis C virus (HCV) causes significant numbers of non-acquired immune deficiency syndrome (AIDS)-related deaths in co-infected patients. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease in HIV-HCV/HBV co-infection in the era of direct acting antivirals (DAA) and antiretroviral therapy (ART). We also review the novel therapeutics for management of HIV/HCV and HIV/HBV co-infected individuals.

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Section: Hiv/hbv Co-infection-induced Liver Injurymentioning

confidence: 99%

Human immunodeficiency virus and hepatotropic viruses co-morbidities as the inducers of liver injury progression

Ganesan¹,

Poluektova²,

Kharbanda³

et al. 2019

WJG

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“…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 [5–11]. The same allele was also identified as a risk factor for liver fibrosis and cirrhosis in HCV-monoinfected individuals [12–16] and in those with HCV/HIV coinfection [17–20] and it also turned out to be a predisposing factor of hepatocellular carcinoma (HCC) [21–24]. In a recent study, 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].…”

Section: Introductionmentioning

confidence: 99%

PNPLA3 rs738409 G allele carriers with genotype 1b HCV cirrhosis have lower viral load but develop liver failure at younger age

et al. 2019

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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.

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“…The methodology for determination of PNPLA3 SNPs, and its validation have been previously described [ 9 ]. Briefly, PBMCs (peripheral blood mononuclear cells) from the study participants were isolated from peripheral blood collected in CPTs (cell preparation tubes) (Becton Dickinson Co., Franklin Lakes, NJ, USA), according to the manufacturer’s directions.…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, some antiviral medications may enhance risk of liver injury by a variety of mechanisms including weight gain with increased insulin resistance [ 6 , 7 ]. There are relatively limited data regarding the role of PNPLA3 single nucleotide polymorphisms (SNPs) in the development of steatosis, liver injury and fibrosis among those with HIV infection [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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PNPLA3 Single Nucleotide Polymorphism Prevalence and Association with Liver Disease in a Diverse Cohort of Persons Living with HIV

Sherman

Rouster

Meeds

et al. 2021

Biology

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In persons living with HIV (PLWH), there are multiple sources of liver injury. Gene polymorphisms of PNPLA3 (patatin-like phospholipase domain-containing protein 3) have been identified as an important cofactor for increased disease severity in both alcoholic and non-alcoholic steatohepatitis (NASH). We utilized a well-characterized cohort of ethnically and racially diverse patients with HIV to define the prevalence of PNPLA3 SNPs (single nucleotide polymorphism) (rs738409), and to determine the relationship to hepatic steatosis and liver fibrosis. Steatosis was determined using MRI-PDFF (magnetic resonance imaging-determined proton density fat fraction) and fibrosis was estimated using MR Elastography (MRE). From the Miami Area HIV Study (MASH) cohort, 100 HIV positive participants and 40 controls (HCV/HIV = 20; HCV and HIV negative = 20) were evaluated. Nearly 40% of all participants carried the variant G allele associated with increased liver disease severity and 5% were homozygotic GG. The variant SNP occurred most frequently in those self-identified as Hispanic compared to white or Black participants. Hepatic steatosis (>5% fat) was present significantly more often in those without HIV vs. those with (p < 0.001). Putative NAFLD/NASH was found to be present in 6% of tested subjects, who were HIV monoinfected. BMI was lower in those that carried the G allele for PNPLA3. This finding suggests that PNPLA3 may be an independent component to NAFLD (non-alcoholic fatty liver disease)/NASH development and longitudinal follow-up of the cohort is warranted.

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PNPLA3 Gene Polymorphisms in HCV/HIV-Coinfected Individuals

Cited by 4 publications

References 18 publications

Human immunodeficiency virus and hepatotropic viruses co-morbidities as the inducers of liver injury progression

Human immunodeficiency virus and hepatotropic viruses co-morbidities as the inducers of liver injury progression

PNPLA3 rs738409 G allele carriers with genotype 1b HCV cirrhosis have lower viral load but develop liver failure at younger age

PNPLA3 Single Nucleotide Polymorphism Prevalence and Association with Liver Disease in a Diverse Cohort of Persons Living with HIV

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