Implications of <i><scp>PNPLA</scp>3</i> polymorphism in chronic hepatitis <scp>C</scp> patients receiving peginterferon plus ribavirin

Valenti, Luca; Aghemo, Alessio; Stättermayer, Albert Friedrich; Maggioni, P; Nicola, S. De; Motta, Benedetta Maria; Rumi, Maria Grazia; Dongiovanni, Paola; Ferenci, Péter; Colombo, Massimo

doi:10.1111/j.1365-2036.2012.05109.x

Cited by 37 publications

(43 citation statements)

References 38 publications

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“…The stronger effect of PNPLA3 in non-obese patients fits with a recent study showing that the amount of liver fat is similar in obese NAFLD compared to PNPLA3 rs738409 G-associated NAFLD. Our data confirmed the link reported in CHC between the severity of steatosis and the PNPLA3 rs738409 G variant, [8][9][10][11][12][13][14][15] but we were unable to confirm a direct association with the severity of fibrosis. Differences in clinical, metabolic and histological characteristics of studied populations, as well as in the analysis of data could explain this difference.…”

Section: Discussionsupporting

confidence: 70%

“…[5][6][7] Some studies on cohorts of mostly genotype 1 (G1) chronic hepatitis C (CHC) patients have reported an association between the PNPLA3 rs738409 G variant and the severity of both steatosis and fibrosis, the risk of fibrosis progression and HCC occurrence, and the response to pegylated interferon plus ribavirin therapy. [8][9][10][11][12][13][14][15] Bedossa et al, in liver biopsies from CHC patients, recently characterised the presence of histological features of steatohepatitis, showing that the occurrence of NASH in this setting not only was related to a poor atrisk metabolic profile but was also a risk factor for the severity of liver damage. 16 This study however did not investigate the impact of genetic background on the presence of steatohepatitis in the context of CHC.…”

Section: Introductionmentioning

confidence: 99%

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PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non‐obese subjects with hepatitis C

Petta

Vanni²,

Bugianesi³

et al. 2015

Aliment Pharmacol Ther

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SummaryBackgroundThe PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non‐alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC).AimTo test in genotype 1(G1)‐CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis.MethodsFour hundred and thirty‐four consecutively biopsied Caucasian G1‐CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of steatohepatitis in CHC were assessed using the Bedossa classification. Hepatic expression of PNPLA3 mRNA was evaluated in 63 patients.ResultsThe prevalence of steatohepatitis increased from 16.5% in patients with PNPLA3 CC, to 23.2% in CG and 29.2% in the GG genotype (P = 0.02). By multiple logistic regression, PNPLA3 genotype (OR 1.54, 95% CI 1.03–2.30, P = 0.03), together with age (OR 1.03, 95% CI 1.00–1.05, P = 0.02), BMI ≥ 30 (OR 2.06, 95% CI 1.04–4.10, P = 0.03) and homoeostasis model assessment (HOMA, OR 1.18, 95% CI 1.04–1.32, P = 0.006) were independently linked to steatohepatitis. When stratifying for obesity, PNPLA3 was associated with NASH in non‐obese patients only (12.0% in CC vs. 18.3% in CG vs. 27.3% in GG, P = 0.01), including after correction for metabolic confounders (OR 2.06, 95% CI 1.26–3.36, P = 0.004). We showed an independent association between steatohepatitis (OR 2.05, 95% CI 1.05–4.02, P = 0.003) and severe fibrosis. Higher liver PNPLA3 mRNA was associated both with the severity of steatosis (adjusted P = 0.03) and steatohepatitis after adjusting for gender, age, BMI and HOMA (P = 0.002).ConclusionIn patients with genotype 1 hepatitis C, the PNPLA3 G variant is associated with a higher risk of steatosis severity and steatohepatitis, particularly among non‐obese subjects.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non‐obese subjects with hepatitis C

Petta

Vanni²,

Bugianesi³

et al. 2015

Aliment Pharmacol Ther

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“…This suggests metabolic steatosis rather than genetic steatosis to be the reason for treatment failure in this cohort of patients. The lack of association between PNPLA3 genotype and SVR has been recently confirmed by a collaborative study conducted in Italy and Austria where 602 naïve patients of any HCV genotype were treated with PegIFNalfa plus Ribavirin [21]. Overall, in that study SVR rates were 51 % in rs738409 GG and 59 % in CG/CC patients.…”

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confidence: 64%

Understanding the Role of PNPLA3 Genetic Variants in Patients with Chronic Hepatitis C Infection

Aghemo

2012

Dig Dis Sci

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“…The prevalence of PNPLA3 148M homozygotes in the Italian population has been reported to be approximately 10% (8-14%) [75,78,81]. In contrast, the homozygote frequency in Germany appears to be lower (5.5%) [82].…”

Section: Patatin-like Phospholipase Domaincontaining 3 (Pnpla3) and Impmentioning

confidence: 78%

“…Furthermore, this association has been corroborated in the setting of alcoholic liver disease and hepatocellular carcinoma [73,74]. In patients with HCV infection, homozygotes for the PNPLA3 148M similarly has been reported to be associated with more steatosis, fibrosis, cirrhosis and hepatocellular carcinoma predominantly in Mediterranean populations [75][76][77][78].…”

Section: Patatin-like Phospholipase Domaincontaining 3 (Pnpla3) and Impmentioning

confidence: 83%

Impact of IL28B, ITPA and PNPLA3 Genetic Variants on Therapeutic Outcome and Progression of Hepatitis C Virus Infection

Rembeck

Lagging

2015

Pharmacogenomics

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Chronic HCV infection comprises a broad spectrum of liver disease, ranging from no or minimal activity to active hepatitis that in time may progress to severe liver fibrosis, cirrhosis and hepatocellular carcinoma if left untreated. This review describes the impact of genetic variants of interleukin 28B (IL28B; also known as interferon-lambda 3), inosine triphosphate pyrophosphatase (ITPA) and patatin-like phospholipase domain-containing 3 (PNPLA3) on therapeutic outcome and liver disease severity in HCV-infected patients.

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Implications of PNPLA3 polymorphism in chronic hepatitis C patients receiving peginterferon plus ribavirin

Abstract: SUMMARY BackgroundHomozygosity for the PNPLA3 p.I148M polymorphism influences steatosis and fibrogenesis in chronic hepatitis C (CHC).

Cited by 37 publications

References 38 publications

PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non‐obese subjects with hepatitis C

PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non‐obese subjects with hepatitis C

Understanding the Role of PNPLA3 Genetic Variants in Patients with Chronic Hepatitis C Infection

Impact of IL28B, ITPA and PNPLA3 Genetic Variants on Therapeutic Outcome and Progression of Hepatitis C Virus Infection

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