AIM: To describe our experience using a low-acceleratingdose regimen(LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis c virus(HcV) recurrence. METHODS: From 2003, a protocolized LADR st...
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AIM: To describe our experience using a low-acceleratingdose regimen(LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis c virus(HcV) recurrence. METHODS: From 2003, a protocolized LADR strategy was employed to treat liver transplant(LT) recipients with recurrent HcV at our institution. Medical records of 182 adult patients with recurrent HcV treated with LADR between 1/2003 and 1/2011 were reviewed. Histopathology from all post-LT liver biopsies were reviewed in a blinded fashion. Paired recipient and donor IL28 B status were assessed. A novel technique was employed to ascertain recipient and donor IL28B(rs12979860) Gt data using DNA extracted from archival FFPE tissue from explanted native livers and donor gallbladders respectively. The primary endpoint was SVR; secondary endpoints examined include(1) patient and graft survival;(2) effect of anti-viral therapy on liver histology(fibrosis and inflammation);(3) incidence of on-treatment development of AcR, cDR, or PcH;(4) association of recipient and donor IL28 B genotype with SVR; and(5) incidence of antiviral therapy-associated adverse events(anemia, leukopenia, thrombocytopenia, depression) and hepatic ***: The overall SVR rate was 38%(29% Gt1, 67% Gt2, 86% Gt3 and 58% Gt4). HcV Gt(P < 0.0001), donor age(P = 0.003), cytomegalovirus mismatch(P = 0.001), baseline serum bilirubin(P = 0.002), and baseline viral load(P = 0.04) were independent predictors for SVR. SVR rates were significantly higher in the recipient-cc/donor-non cc pairs(P = 0.007). Neither baseline fibrosis nor change in fibrosis stage after anti-viral therapy were associated with SVR. Fibrosis progressed in 72% of patients despite SVR. Median graft survival was 91 mo. Five-year patient survival was superior in patients who achieved SVR(97% vs 82%, P = 0.001). Pre-treatment ALP ≥ 150 U/L(P = 0.01), total bilirubin ≥ 1.5 mg/d L(P = 0.001) and creatinine ≥ 2 mg/d L(P = 0.001) were independently associated
AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis c virus(HcV) core protein in Hep G2 ***: HcV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cho...
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AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis c virus(HcV) core protein in Hep G2 ***: HcV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2(SREBP2) and the rate-limiting enzyme in cholesterol synthesis(HMGcR) was measured by quantitative real-time PcR and immunoblotting after transfection. The effects of core protein on the SREBP2 promoter and 3'-untranslated region were analyzed by luciferase assay. We used different target predictive algorithms, micro RNA(mi RNA) mimics/inhibitors, and site-directed mutation to identify a putative target of a particular mi ***: HcV core protein expression in Hep G2 cells increased the total intracellular cholesterol level(4.05 ± 0.17 vs 6.47 ± 0.68, P = 0.001), and this increase corresponded to an increase in SREBP2 and HMGcR m RNA levels(P = 0.009 and 0.037, respectively) and protein expression. The molecular mechanism studyrevealed that the HcV core protein increased the expression of SREBP2 by enhancing its promoter activity(P = 0.004). In addition, mi R-185-5p expression was tightly regulated by the HcV core protein(P = 0.041). Moreover, overexpression of mi R-185-5p repressed the SREBP2 m RNA level(P = 0.022) and protein expression. In contrast, inhibition of mi R-185-5p caused upregulation of SREBP2 protein expression. mi R-185-5p was involved in the regulation of SREBP2 expression by HcV core protein. cONcLUSION: HcV core protein disturbs the cholesterol homeostasis in Hep G2 cells via the SREBP2 pathway; mi R-185-5p is involved in the regulation of SREBP2 by the core protein.
Mdm2 285G>c and 344T>A Gene Variants and Their Association with Hepatocellular carcinoma: a Moroccan case-control Study. by Rebbani, Khadija; Ezzikouri, Sayeh; Marchio, Agnes; Kandil, Mostafa; Pineau, Pascal; Be...
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Mdm2 285G>c and 344T>A Gene Variants and Their Association with Hepatocellular carcinoma: a Moroccan case-control Study. by Rebbani, Khadija; Ezzikouri, Sayeh; Marchio, Agnes; Kandil, Mostafa; Pineau, Pascal; Benjelloun, Soumaya; published by
AIM: To evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis c patients in relation to interferon-λ(IFNL) polymorphisms. METHODS: This study enrolled patients with chronic hepatitis c referred t...
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AIM: To evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis c patients in relation to interferon-λ(IFNL) polymorphisms. METHODS: This study enrolled patients with chronic hepatitis c referred to the Tehran Blood Transfusion Hepatitis clinic in 2011. Patients were included in the study if they had no concomitant hepatic illness, were negative for human immunodeficiency virus antibodies, and had no prior history of treatment with any type ofpegylated interferon. Patients were treated with 180 μg pegylated interferon alpha-2a(Pegaferon®) weekly and 800-1200 mg ribavirin daily for 24 or 48 wk depending on weight and hepatitis c virus(HcV) genotype. Blood samples were collected from patients to obtain DNA for determination of IFNL rs12979860 and rs8099917 polymorphisms. The virologic response in patients was then evaluated and compared between the different IFNL ***: A total of 152 patients with a mean age of 41.9 ± 10.0 years were included in the study, of which 141/152 were men(92.8%). The most frequent HcV genotype was type-1, infecting 93/152(61.2%) patients. Sustained virologic response(SVR) was achieved in 81.9% of patients with HcV genotype-1 and 91.1% of patients with HcV genotype-3. Treatment success was achieved in 91.2%(52/57) of patients with the IFNL rs12979860 cc genotype and 82.1%(78/95) in those with other genotypes. Similar treatment response rates were also observed in patients with rs8099917 TT(39/45; 86.7%) and non-TT(61/68; 89.7%) genotypes. Univariate analyses identified the following factors which influenced treatment response for inclusion in a multivariate analysis: age, HcV RNA level, stage of liver fibrosis, rs12979860 cc genotype, and aspartate transaminase level. A logistic regression analysis revealed that only the rs12979860 cc genotype was significantly associated with achievement of SVR(OR = 6.2; 95%cI: 1.2-31.9; P = 0.03).cONcLUSION: The rs12979860 cc genotype was associated with SVR in patients
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