Relationship Among Hepatic Inflammatory Changes, Circulating Levels of Cytokines, and Response to IFN-α in Chronic Hepatitis C

Fabris, Carlo; Soardo, Giorgio; Falleti, Edmondo; Toniutto, Pierluigi; Vitulli, Daniela; Federico, Edda; Forno, Monica Del; Mattiuzzo, M; Gonano, Fabio; Pirisi, Mario

doi:10.1089/jir.1998.18.705

Cited by 26 publications

(18 citation statements)

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“…More recent comprehensive work at animal models indicates that the synthesis of IL-6 and the activation of STAT3 within hepatocytes are critical functions of Kupffer cells and stimulation of EPO production. [40][41][42][43] Our study is in agreement with that of Lin et al, [44] who followed up 80 chronic HD patients (30 HCVpositive and 50 HCV-negative) in Taipei Medical University Hospital for one year and concluded that lessened anemia was observed in CHC. However, in his study, less erythropoietin was demanded in this group (HCV-positive), whereas our study demonstrated no significant difference of EPO dose between the two groups (HCV-positive and HCV-negative).…”

Section: Discussionsupporting

confidence: 90%

Effect of Hepatitis C Virus on Hemoglobin and Hematocrit Levels in Saudi Hemodialysis Patients

2009

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Background. Hepatitis C virus infection is common among patients undergoing hemodialysis, and HD patients are at high risk for infection with such virus. Recently, some studies and case reports indicated attenuated anemia in HD patients with HCV infection, and they previously considered this to be related to increased erythropoietin production after hepatic stimulation by chronic infection with hepatitis virus. Aim. The aim of our study is to investigate whether HCV-positive HD patients have higher hemoglobin (Hb) and hematocrit (HCT) values compared to HCV-negative patients. Methods. We retrospectively studied 83 chronic HD patients from Prince Salman Center for Kidney Disease, and monthly samples were collected between July 2007 and July 2008. The HCV status was determined by anti-HCV antibodies and confirmed with RNA polymerase chain reaction (PCR). Those with a history of blood transfusion or massive blood loss during the last six months were excluded from the study. Results. Thirty-three percent of our patients tested positive for anti-HCV antibody (51.8% were male). The mean age for HCV-positive group was 54.92 ± 15.61 years, while it was 51.01 ± 14.81 years for the HCV-negative group (p = 0.27). Mean Hb in the HCV-positive group was 11.18 ± 1.41gm/dL compared to 10.87 ± 1.29 gm/dL for the HCVnegative group (p = 0.05). Mean HTC values for the HCVpositive group was 34.4 ± 3.9, compared to 32.41 ± 3.41 for the HCV-negative group 12 months after starting hemodialysis. Eighty-one patients (27 HCV-positive and 54 HCVnegative) received erythropoietin (EPO) therapy. Seventytwo patients (25 HCV-positive and 47 HCV-negative) received IV iron (p = 0.28). Mean erythropoietin dose was (114.83 ± 84.92 IU/kg/week) for HCV-positive compared to (122.2 ± 91.46 IU/kg/week) for HCV-negative group (p = 0.74). Liver function tests were normal except for higher bilirubin level in the HCV-positive group, 7.74 ± 4.03 Umol/L compared to 5.47 ± 3.71 Umol/L in the HCV-negative group (p = 0.01). Conclusion. Our study showed that ESRD patients on HD with HCV infection have higher Hb and HCT levels compared with HCV-negative patients.

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Section: Discussionsupporting

confidence: 90%

Effect of Hepatitis C Virus on Hemoglobin and Hematocrit Levels in Saudi Hemodialysis Patients

2009

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“…Our study confirmed that the GG genotype of the TNF-α −238 gene promoter is implicated in the probability of liver cirrhosis, supporting our previous data [19] in a different and larger sample of HIV/HCV coinfected patients. Previous data have demonstrated the impact of TNF-α on liver fibrogenesis: increased concentrations of TNF-α have been detected in the liver of patients with chronic hepatitis C [45] and it has been observed that serum levels of this cytokine are correlated with the histological grading score of hepatitis [46]. Likewise, it has been observed that patients with increased serum levels of TNF-α or its receptors showed a reduced survival rate [47].…”

Section: Discussionmentioning

confidence: 98%

Liver Fibrosis, Host Genetic and Hepatitis C Virus Related Parameters as Predictive Factors of Response to Therapy against Hepatitis C Virus in HIV/HCV Coinfected Patients

et al. 2014

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ObjectiveTo establish the role of liver fibrosis as a predictive tool of response to pegylated interferon alpha (Peg-IFN) and ribavirin (RBV) treatment in human immunodeficiency (HIV)/hepatitis C virus (HCV) coinfected patients, in addition to recognized predictive factors (HCV load, HCV genotype, IL-28B polymorphism).Patients and MethodsA sample of 267 HIV/HCV coinfected patients was treated with Peg-IFN and RBV. Predictive factors of rapid (RVR) and sustained (SVR) virological response were analyzed. Independent variables were age, sex, IL28B, −238 TNF-α and −592 IL-10 polymorphisms, HCV genotype, HCV-RNA levels, significant fibrosis or cirrhosis and CD4+ T cell count.ResultsPatients infected by HCV genotype 1 (n = 187) showed RVR and SVR in 12% and 39% of cases, respectively. The parameters associated with RVR were IL28B genotype CC and plasma HCV-RNA levels <600000 IU/ml. Advanced liver fibrosis was negatively associated with SVR in patients without RVR. A SVR was obtained in 42% of subjects with HCV genotype 4, and the independent factors associated with SVR were IL28B genotype CC and an HCV-RNA <600000 IU/ml. A SVR was obtained in 66% of patients with HCV genotypes 2/3; in this case, the independent parameter associated with SVR was the absence of significant liver fibrosis. TNF-α and IL-10 polymorphisms were not associated with SVR, although a significantly higher percentage of −238 TNF-α genotype GG was detected in patients with significant liver fibrosis.ConclusionsIn HIV/HCV coinfected patients with HCV genotypes 1 or 4, RVR, mainly influenced by genotype IL28B and HCV-RNA levels, reliably predicted SVR after 4 weeks of therapy with Peg-IFN plus RBV. In patients infected by HCV genotype 3, an elevated relapse rate compromised the influence of RVR on SVR. Relapses were related to the presence of advanced liver fibrosis. Liver cirrhosis was associated with a −238 TNF-α polymorphism in these patients.

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“…There are inter-individual variations in detoxifying enzymes and cytokines that could be translated into differences in susceptibility for xenobiotic toxicity and treatment outcomes [13-17]. So in this study, we decided to investigate the association of polymorphisms in the enzymes involved in general oxidative stress defence including NAD(P)H:quinone oxidoreductase-1 (NQO1), Glutathione S-transferases (GST) M1 and T1, and microsomal epoxide hydrolase (EPHX1) enzymes and the two most important cytokines involved in the pathogenesis of liver disease with the basis of inflammation, namely tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) cytokines and the treatment outcome of silymarin in the subjects chronically exposed to H 2 S.…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective effect of silyamarin in individuals chronically exposed to hydrogen sulfide; modulating influence of TNF-α cytokine genetic polymorphism

et al. 2013

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Background and the purpose of the studySilymarin, a standardized extract of the milk thistle (Silybum marianum), is believed to exert some of its hepatoprotective effects though inhibition of free radicals and inflammation. In this study the effect of some pro- and anti-inflammatory cytokines and also antioxidant genes polymorphisms on the hepatoprotective effects of silymarin in the occupationally exposed individuals to hydrogen sulfide (H2S) in the sour natural gas refinery was investigated.MethodsWe genotyped seven polymorphisms in six genes reported by others as modifiers of oxidative stress (NQO1, mEPXH1, GSTT1 and GSTM1) and inflammation (TNF-α and TGF-β1) for an association in effect of decreasing in liver function tests (LFTs). The LFTs of 77 sour gas refinery workers were measured before and after administration of silymarin (140 mg, three times per day for 1 month).ResultsA significant reduction of blood AST, ALT and ALP was observed after 30 days of consumption (p < 0.001). The decreasing effect of silymarin on ALT in the subjects with high producer genotype (A allele carriers) was less than low producers. There were no significant associations between TGF-β1 and the studied genes of oxidative stress pathway and the effectiveness of silymarin.ConclusionThis is the first report about the effectiveness of silymarin in the subjects exposed chronically to H2S. Meanwhile, the modulatory effect of TNF-α on the effectiveness of silymarin might be used for individualize therapy.

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Relationship Among Hepatic Inflammatory Changes, Circulating Levels of Cytokines, and Response to IFN-α in Chronic Hepatitis C

Cited by 26 publications

References 30 publications

Effect of Hepatitis C Virus on Hemoglobin and Hematocrit Levels in Saudi Hemodialysis Patients

Effect of Hepatitis C Virus on Hemoglobin and Hematocrit Levels in Saudi Hemodialysis Patients

Liver Fibrosis, Host Genetic and Hepatitis C Virus Related Parameters as Predictive Factors of Response to Therapy against Hepatitis C Virus in HIV/HCV Coinfected Patients

Hepatoprotective effect of silyamarin in individuals chronically exposed to hydrogen sulfide; modulating influence of TNF-α cytokine genetic polymorphism

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