Metabolic Factors and Chronic Hepatitis C: A Complex Interplay

Macaluso, Fabio Salvatore; Maida, Marcello; Minissale, Maria Giovanna; Vigni, Teresa Li; Attardo, S.; Orlando, Elisabetta; Petta, Salvatore

doi:10.1155/2013/564645

Cited by 31 publications

(20 citation statements)

References 164 publications

(177 reference statements)

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“…The natural history of any chronic liver disease is modulated by a number of emerging risk factors, 1,2 and recent evidence suggests a key role for the host genetic architecture. In particular, the C?G rs738409 variant in the PNPLA3 gene is a risk factor for non-alcoholic fatty liver disease (NAFLD), 3,4 for non-alcoholic steatohepatitis (NASH) severity, for significant liver fibrosis and for hepatocellular carcinoma.…”

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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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: 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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“…Interestingly, some of the features able to predict HCC development in viremic patients -such as advanced age, advanced fibrosis, degree of portal hypertension and elevated α-fetoprotein levels -have been identified as independent predictors of HCC also in SVR patients [48]. In addition, recent data have emphasized the potential role of metabolic and exogenous players, such as diabetes, obesity, insulin resistance and alcohol abuse, in promoting the development of HCC in SVR patients, acting as autonomous, nonviral carcinogenic factors [49,51]. In this line, a recent Taiwanese study [50], performed among 642 patients who achieved an SVR after pegylated-IFN plus Ribavirin therapy, showed that the strongest predictive factor of HCC occurrence in this cohort was liver cirrhosis, followed by age and gamma-glutamyl transpeptidase (GGT) levels -a well-known marker of metabolic syndrome review Macaluso, Calvaruso & Craxì future science group and its features, of liver fibrosis and its progression and of malignancies [52].…”

Section: The Residual Risk Of Hcc Among Svr Patientsmentioning

confidence: 99%

Residual Risk of Hepatocellular Carcinoma After HCV Eradication: more than meets the eye

Macaluso

Calvaruso

2015

Future Microbiol.

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Eradication of HCV in patients with advanced liver fibrosis or cirrhosis reduces, but does not altogether abolish, the risk of development of hepatocellular carcinoma. The reasons underlying this residual risk remain elusive. Even if HCV clearance eliminates its direct and indirect carcinogenic effects, the persistence of cirrhosis and the possible coexistence of metabolic factors (diabetes, obesity and insulin resistance) and of alcohol abuse can promote the development of hepatocellular carcinoma acting as autonomous, nonviral carcinogenic factors. Lessons learned in the IFN era may still assist in predicting the forthcoming scenario, when IFN-free regimens will obtain high rates of viral clearance even at the most advanced stages of liver disease. KeywordsHepatocellular carcinoma (HCC) is a challenging malignancy of global importance, being the second cause of cancer-related death worldwide [1]. The majority of HCCs occur in the context of chronic infection with HBV and HCV, and the cancer risk is directly related to the histological and clinical stage of the underlying liver disease [2]. In particular, HCV infection stands today as the leading risk factor for HCC in many industrialized countries [3], occurring at a rate between 3 and 8%, according to the geographic area, in patients with HCV-related cirrhosis [4]. On these assumptions, prevention of population exposure to HCV can be regarded as the most effective tool to reduce liver-related mortality from HCC due to chronic HCV infection. In the HCV scenario, where an effective vaccine is not currently available, antiviral treatments have stood as the real backbone of prophylaxis strategy in the prevention of HCC, of course together with all procedures implemented to prevent HCV transmission [5].However, the evidence that patients with chronic hepatitis C (CHC) are completely protected against occurrence of HCC by successful IFN-based treatments is controversial, mainly due to methodological limitations of available literature. All in all, HCC risk seems to be sharply attenuated, although not completely eliminated -especially in patients with advanced fibrosis -following eradication of HCV infection, and the causes for this residual HCC risk in patients who achieved a sustained virological response (SVR) remain receding. Moreover, the intrinsic limitations of the use of IFN to patients with less advanced liver disease have curtailed the potential benefit, due to the fact that HCC in HCV cirrhosis becomes more prevalent at the more advanced stages of liver disease.In this review, we discuss the available clinical evidence of the role of antiviral treatment against chronic HCV infection for the prevention of HCC, and the residual risk existing in patients successfully treated. In addition, we focus on the molecular mechanisms that might explain the pathophysiological rationale of the reduction, but not elimination, of HCC risk after HCV eradication. The lesson from the IFN era may be extremely useful to predict the near-future scenario, when For repri...

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“…KHC hastalarında %50 olguda steatoz olmasına karşılık, bu NAFLD'de bulunandan daha azdır. Ancak KHC'de demir birikimiyle steatoz arasında bir koşutluk olduğu göste-rilmiştir (197). KHB ve KHC'li hastalarda biyopsiyle gösterilen fibrozun metabolik sendromdan bağımsız olduğu gösterilmiş-tir (198).…”

Section: Karaciğer Yağlanması Ve Kronik Hepatit Cunclassified

Management of Chronic Hepatitis in Special Hosts and Special Situations: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases

Mıstık¹,

Aydın²,

Aksoy³

et al. 2015

Klimik Dergisi

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ÖzetTürk Klinik Mikrobiyoloji ve İnfeksiyon Hastalıkları Derneği Viral Hepatit Çalışma Grubu, özel konaklarda ve özel durumlarda kronik hepatit yönetimine ilişkin bir uzlaşı raporu hazırlamak üzere bir toplantı düzenlemiştir. Raporda konuyla ilgili literatür ve uluslararası kılavuzlar, hepatit B virusu (HBV) için sırasıyla kompanse ve dekompanse sirozlu hastalarda kronik hepatit B (KHB) tedavisi, karaciğer nakli sonrası HBV infeksiyonunun nüks etmesinden korunma ve nüks gelişen hastalarda tedavi, fülminan hepatit B tedavisi, hemodiyaliz hastalarında KHB teda- AbstractStudy Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases convened a meeting to develop a consensus report on management of chronic hepatitis in special hosts and special situations. Relevant literature and international guidelines were reviewed, and recommendations agreed are presented at the end of each section such as therapy of chronic hepatitis B (CHB) in patients with compensated and decompensated cirrhosis, prevention and therapy of recurrent hepatitis B after liver transplantation, management of fulminant

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Metabolic Factors and Chronic Hepatitis C: A Complex Interplay

Cited by 31 publications

References 164 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

Residual Risk of Hepatocellular Carcinoma After HCV Eradication: more than meets the eye

Management of Chronic Hepatitis in Special Hosts and Special Situations: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases

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