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Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy.

ABSTRACT: HCV kinetic analysis and modelling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in three groups of patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease.Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to final effectiveness [?max]) was fitted to viral kinetic data.Baseline viral load and age were significantly associated with the severity of liver disease (P<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline in patients with less severe liver disease. The ?max was significantly (P?0.032) associated with increasing severity of liver disease (non-cirrhotic ?max [se]=0.86 [0.05], compensated cirrhotic ?max=0.69 [0.06] and decompensated cirrhotic ?max=0.59 [0.1]). The second phase decline slope was not significantly different among groups (mean 1.88 ±0.15 log10 IU/ml/week, P=0.75) as was the rate of change of SIL effectiveness (k=2.12/day [se=0.18/day]). HCV-infected cell loss rate (? [se]=0.62/day [0.05/day]) was high and similar among groups.The high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.

SUBMITTER: Canini L

PROVIDER: S-EPMC4262731 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy.

Canini Laetitia L DebRoy Swati S Mariño Zoe Z Conway Jessica M JM Crespo Gonzalo G Navasa Miquel M D'Amato Massimo M Ferenci Peter P Cotler Scott J SJ Forns Xavier X Perelson Alan S AS Dahari Harel H

Antiviral therapy 20140610 2

<h4>Background</h4>HCV kinetic analysis and modelling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in three groups of patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease.<h4>Methods</h4>Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. ...[more]

PMID: 24912382

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Project description:BackgroundThere is evidence that microRNA (MIR) 122 is a biomarker for various liver diseases in adults and children. To date, MIR122 has not been explored in children with intestinal failure-associated liver disease (IFALD, or hyperbilirubinemia associated with prolonged parenteral nutrition).ObjectivesThis study's purpose was to investigate changes in plasma miR-122, correlate miR-122 with serum liver function tests and enzymes, and investigate changes in whole blood transcripts including miR-122 targets in a group of children with IFALD who received pure intravenous fish oil (FO) as a treatment for cholestasis.MethodsThis was a prospective, observational study that enrolled children with IFALD who received intravenous FO (1 g/kg/d) and whose cholestasis resolved with FO. Plasma miR-122 was measured using reverse transcription-quantitative real-time PCR, and whole blood miR-122 targets were quantified using RNA sequencing.ResultsFourteen subjects with median age 6 mo (IQR: 3-65 mo) were enrolled. RNA sequence data were available for 4 subjects. When compared with the start of FO, median miR-122 concentrations at 6 mo of FO therapy decreased [1.0 (IQR: 1.0-1.0) compared with 0.04 (IQR: 0.01-0.6), P = 0.009]. At the start of FO, miR-122 correlated with conjugated bilirubin (r = 0.56; P = 0.038). At ∼3 mo of FO, miR-122 correlated with conjugated bilirubin (r = 0.56; P = 0.045). Reactive oxygen species, heme metabolism, coagulation, adipogenesis, IL-6-Janus kinase-signal transducer and activator of transcription (JAK-STAT) 3, IL-2-STAT5, transforming growth factor-β, TNF-α, inflammatory response, mammalian target of rapamycin gene families (normalized enrichment scores < -1.4), and miR-122 target genes were significantly downregulated with FO.ConclusionsIn this small cohort of young children with IFALD, miR-122 decreased with FO therapy and correlated with conjugated bilirubin. Key pathways involving oxidation, inflammation, cellular differentiation, and nutrient regulation were downregulated. Data from this study provide information about IFALD and FO. This trial was registered at www.clinicaltrials.gov as NCT00969332.

Project description:Reports of the role of host interleukin 28B (IL-28B) genetic variants in liver disease severity in patients with chronic hepatitis C (CHC) have obtained conflicting results. The impact of IL-28B in Asian patients with different viral genotypes remains elusive.We try to elucidate the effect of IL-28B genetic variants in a large Asian cohort with different viral genotypes.The association between the IL-28B rs8099917 genotype and liver fibrosis was investigated in 1288 patients with biopsy-proven CHC.Patients with hepatitis C virus genotype 1 (HCV-1) infection comprised 59.4% of the population. The remaining 40.6% (518 patients) did not have HCV-1 infection. Of the 1084 patients with the IL-28 genotype, 85.6% (928 patients) had the TT genotype. Univariate analysis revealed that, compared to patients without advanced liver fibrosis, patients with advanced liver fibrosis (Metavir fibrosis score 3-4) had an older age, a lower platelet count, a higher ?-fetoprotein level, a higher alanine aminotransferase level, a higher incidence of diabetes, and a higher frequency of rs8099917 non-TT genotype carriage.Logistic regression analysis revealed that factors significantly associated with advanced liver fibrosis included age (odds ratio [OR]/95% confidence interval [CI]: 1.023/1.009-1.037, P?=?.001), diabetes (OR/CI: 1.736/1.187-2.539, P?=?.004), ?-fetoprotein (OR/CI: 1.007/1.002-1.012, P?=?.009), platelet count (OR/CI: 0.991/0.988-0.993, P?<?.001), and carriage of the rs8099917 non-TT genotype (OR/CI: 0.585/0.400-0.856, P?=?.006). When patients were classified by viral genotype, factors that had significant independent associations with advanced liver fibrosis in patients with HCV-1 infection included diabetes (OR/CI: 2.379/1.452-3.896, P?=?.001), ?-fetoprotein (OR/CI: 1.023/1.012-1.035, P?<?.001), platelet count (OR/CI: 0.99/0.987-0.994, P?<?.001), and carriage of the rs8099917 non-TT genotype (OR/CI: 0.529/0.328-0.854, P?=?.009). In patients who had advanced liver fibrosis but not HCV-1 infection, factors that had significant independent associations with advanced liver fibrosis included age (OR/CI: 1.039/1.016-1.063, P?=?.001) and platelet count (OR/CI: 0.99/0.986-0.995, P?<?.001); additionally, IL-28B genetic variants were not associated with liver disease severity.Unfavorable IL-28B genetic variants were associated with advanced liver disease. The genetic effect is limited to patients with HCV-1 infection.

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Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy.

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Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy.

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