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Chronic Hepatitis C Patients (chronic + hepatitis_c_patient)
Selected AbstractsHistological grading and staging in chronic hepatitis: Its practical correlationPATHOLOGY INTERNATIONAL, Issue 11 2002Miyuki Nakaji Although the histological features of various causes of chronic liver disease have been well described, usually the inflammatory activity of the disease is important after the cause has been established. Some patients have co-infection,or,concomitant,liver,disease,and on occasion it is difficult to decide the treatment. In order to clarify the histological differences, we investigated the inflammatory activity among autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC),,chronic,hepatitis C (CHC) and chronic hepatitis B (CHB) in a standardized way using the modified histological activity index (HAI). According to the modified HAI, inflammatory activity is divided into four categories; categories A/D explains portal/periportal inflammation and categories B/C explains lobular activity. The inflammatory score of AIH tended to be greater in all categories from the early stage of fibrosis, whereas scores of PBC were lower, except for portal inflammation. Chronic hepatitis C patients had portal or periportal inflammation, and their inflammatory scores were linked to the development of fibrosis. Chronic hepatitis B patients tended to have severe lobular injury, but did not have a relationship between the inflammatory score and their stage. To know the distribution of inflammation using the modified HAI scoring system may be helpful and convenient in evaluating patients with chronic inflammatory liver disease. [source] APRI-M6 for predicting long-term outcome of chronic hepatitis C patients after interferon-based therapy: More questions than answers,HEPATOLOGY, Issue 6 2007Tung-Hung Su M.D. No abstract is available for this article. [source] A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis CHEPATOLOGY, Issue 5 2003Frederik Nevens New treatments are needed for chronic hepatitis C patients in whom viral clearance cannot be achieved. Thirty-five chronic hepatitis C patients (genotype 1) were randomized to receive 20 ,g of recombinant HCV E1 (E1) (n = 26) or placebo (n = 9) intramuscularly at weeks 0, 4, 8, 12, and 24. Thirty-four then received open-label E1 vaccine at weeks 50, 53, 56, 59, 62, and 65. Twenty-four patients (12 men, 12 women; mean age, 52 y; 18 interferon-based treatment failures; mean baseline alanine aminotransferase [ALT] level, 118 IU/L) underwent a biopsy before and after 2 courses of E1, 17 months later. Liver histology was scored by 2 blinded pathologists according to the Ishak and Metavir systems. Postinjection reactions were similar to placebo (alum only). Nine of 24 patients (38%) had improvement of 2 points or more, 10 (41%) remained stable, and 5 (21%) showed worsening in total Ishak score. Nine patients (38%) improved both on Ishak and Metavir fibrosis scores. Plasma HCV-RNA levels remained unchanged, whereas ALT levels showed a trend toward a decrease during treatment. All but 3 patients developed a significant de novo E1-specific T-cell response. The increase in anti-E1 antibody levels correlated with the decrease in total Ishak score and with the relative decreases in both Ishak fibrosis score and ALT level (all P , .01). In conclusion, E1 therapeutic vaccination is well tolerated and the observed effects warrant further study. [source] Relationship of health-related quality of life to treatment adherence and sustained response in chronic hepatitis C patientsHEPATOLOGY, Issue 3 2002David Bernstein Interferon therapy may exacerbate health-related quality of life (HRQL) deficits associated with hepatitis C virus (HCV) early in the course of therapy. Treatment with polyethylene glycol,modified interferon (peginterferon) alfa-2a (40 kd) provides improved sustained response over interferon alfa-2a, but its effect on HRQL is unknown. The objective of this study was to (1) evaluate the effect of sustained virologic response on HRQL in patients with HCV and (2) determine whether impairment of HRQL during treatment contributes to early treatment discontinuation. Data consisted of a pooled secondary analysis of patients (n = 1,441) across 3 international, multicenter, open-label, randomized studies that compared peginterferon alfa-2a (40 kd) with interferon alfa-2a. ANCOVA was used to examine the effect of sustained virologic response on HRQL. Repeated-measures mixed-models ANCOVA was used to compare Fatigue Severity Scale (FSS) and SF-36 scores during treatment by treatment group. Logistic regression analysis was used to examine the association between changes at baseline in on-treatment HRQL and early treatment discontinuation. Sustained virologic response was associated with marked improvements from baseline to end of follow-up in all subjects, including patients with cirrhosis. During treatment, patients receiving peginterferon alfa-2a (40 kd) had statistically significantly better scores on both the SF-36 and FSS. Baseline to 24-week changes in fatigue and SF-36 mental and physical summary scores significantly predicted treatment discontinuation. In conclusion, sustained virologic response is associated with improvements in quality of life in patients with or without advanced liver disease. This parameter may be an important consideration in maximizing treatment adherence. [source] Relapse of hepatitis C in a pegylated-interferon-,-2b plus ribavirin-treated sustained virological responderHEPATOLOGY RESEARCH, Issue 6 2010Hideki Fujii A 41-year-old woman with chronic hepatitis C was treated with pegylated-interferon (PEG-IFN)-,-2b plus ribavirin for 24 weeks. She had hepatitis C virus (HCV) genotype 2a (1600 KIU/mL), and her liver histology showed mild inflammation and fibrosis. Four weeks after the start of the therapy, she achieved a rapid virological response (RVR) and then a sustained virological response (SVR). Serum alanine aminotransferase (ALT) levels remained within normal ranges and HCV RNA continued to be negative. However, ALT levels flared with the re-emergence of HCV RNA in the serum 1.5 years after discontinuation of therapy. HCV RNA obtained from sera before therapy and after relapse shared a 98.6% homology with the E2 region, and phylogenetic analyses indicated that they were the same HCV strain. These results eliminated the possibility of a re-infection and strongly indicated a late relapse of the disease. Therefore, follow-up is necessary for chronic hepatitis C patients after SVR, even if they respond well to therapy, including RVR. [source] ,-Interferons and the single nucleotide polymorphisms: A milestone to tailor-made therapy for chronic hepatitis CHEPATOLOGY RESEARCH, Issue 5 2010Yasuhito Tanaka Type III interferons (IFN) (IFN-,1, -,2, -,3/interleukin [IL]-29, -28A, -28B) are cytokines with type I IFN-like antiviral activities. Most cells have expressed both type I and III IFN following Toll-like receptor (TLR) stimulation or viral infection, whereas the ability of cells to respond to IFN-, was restricted to a specific subset of cells. It was reported that signal transduction pathway of IFN-, was similar to that of IFN-,/, although a receptor adapted by IFN-, were distinct from that of IFN-,/,. However, the clinical significance and the role of each IFN-, were unclear. Recent genome-wide association studies (GWAS) of the human whole genome revealed several single nucleotide polymorphism sites (SNP) strongly associated with the response to pegylated IFN-, (PEG-IFN) plus ribavirin (RBV) treatment in chronic hepatitis C patients. The SNP, which are located near the IL-28B gene of chromosome 19, were discovered simultaneously by three independent studies opening a new prospective in hepatitis C research. The present review highlights significant insights that can be derived from the GWAS approach, and summarizes current knowledge of in vitro and in vivo study on the role of IFN-, in antiviral effect. [source] Low dose erythropoietin-beta improves anemia and maintains ribavirin dose in chronic hepatitis C patients receiving combination therapy with ribavirin plus pegylated interferon Alfa-2bHEPATOLOGY RESEARCH, Issue 6 2009Kuo-Chih Tseng Aim:, Anemia during combination therapy with pegylated interferon alfa-2b plus ribavirin (RBV) for chronic hepatitis C virus (HCV) patients usually leads to RBV dose reduction or discontinuation. This study evaluated the effect of erythropoietin-beta (EPO-,) to maintain RBV dose and hemoglobin (Hb) level in chronic HCV patients treated with antiviral combination therapy. Methods:, Eighty-eight chronic HCV patients who developed anemia during therapy were enrolled into this retrospective study: 55 in the EPO-, group and 33 in the untreated group. The study endpoints were to assess the RBV maintenance and the changes in Hb. Results:, A higher percentage of patients with RBV maintenance was observed in the EPO-, group compared with the untreated group (nadir Hb level <10.5 g/dL; 70% vs. 38%, P = 0.020; nadir Hb < 10 g/dL; 62% vs. 27%, P = 0.046). The mean Hb change from week 12 to week 20 was higher in the EPO-, group when compared with the untreated group, especially for patients receiving a total EPO-, dose of more than 16 000 U (+0.70 g/dL vs. ,0.32 g/dL, P = 0.023) and of 10 000 U-14 000 U (+0.60 g/dL vs. ,0.32 g/dL, P = 0.023). Conclusions:, Low-dose EPO-, can maintain RBV dose and increase Hb levels in anemic chronic HCV patients receiving combination therapy. [source] Liver steatosis in chronic hepatitis C: a morphological sign suggesting infection with HCV genotype 3HISTOPATHOLOGY, Issue 2 2001L Rubbia-Brandt Liver steatosis in chronic hepatitis C: a morphological sign suggesting infection with HCV genotype 3 Aims:,To identify factors associated with liver steatosis in chronic hepatitis C. Methods and results:,Occurrence and severity of liver steatosis in 254 chronic hepatitis C patients were compared with presence of alcohol abuse, body mass index (BMI) >26, history of intravenous drug addiction and hepatitis C virus (HCV) genotype. Steatosis was found in 109 (43%) patients. The occurrence of steatosis was significantly associated with ongoing alcohol abuse (P=0.03) or HCV genotype 3 (P= 0.003), but not with BMI >26. A moderate to severe steatosis was present in 60% of patients infected with HCV genotype 3, irrespective of the presence of alcohol abuse, BMI >26 or history of intravenous drug addiction. Using a multivariable stepwise logistic regression analysis, infection with genotype 3 had an odds ratio (OR) of 10 (95% confidence interval (CI)=4.56,22) for a liver steatosis, whereas the presence of a cirrhosis at histology had an OR=0.256 (95% CI=0.07,0.92). Conclusions:,A moderate to severe degree of steatosis of the liver is a morphological sign suggestive of infection with HCV genotype 3, independent of other risk factors of a fatty liver, but it may disappear at late stages of the disease. [source] The genetic differences with whole genome linkage disequilibrium mapping between responder and non-responder in interferon-, and ribavirin combined therapy for chronic hepatitis C patientsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2008P.-J. Chen Summary Interferon-, and ribavirin combined therapy has been a mainstream treatment for hepatitis C infection. The efficacy of this combined treatment is around 30% to 60%, and the factors affecting the responsiveness are still poorly defined. Our study is intended to investigate the genetic differences between responder and non-responder patients. The genome-wide linkage disequilibrium screening for loci associated with genetic difference between two patient groups was conducted by using 382 autosomal short tandem repeat (STR) markers involving 92 patients. We have identified 19 STR markers displaying different allele frequencies between the two patient groups. In addition, based on their genomic location and biological function, we selected the CD81 and IL15 genes to perform single nucleotide polymorphism genotyping. In conclusion, this study may provide a new approach for identifying the associated polymorphisms and the susceptible loci for interferon-, and ribavirin combined therapy in patients with chronic hepatitis C. [source] Genotype-specific mechanisms for hepatic steatosis in chronic hepatitis C infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2002Jason M Hui Abstract Background: Hepatic steatosis is common in hepatitis C, but the relative importance of host and viral factors is controversial. In the present prospective study, we examined metabolic factors associated with non-alcoholic fatty liver and viral genotype as predictors of steatosis and fibrosis in chronic hepatitis C infection. Methods: In 124 chronic hepatitis C patients, the association between liver histology and the following was investigated: demographic and anthropometric data, alcohol intake, alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein,cholesterol, high-density lipoprotein,cholesterol, triglyceride, transferrin saturation, ferritin, insulin, c-peptide, glucose and insulin resistance (homeostasis model). Results: By multivariate analysis, genotype 3 was associated with increased steatosis grade (P = 0.02). There were significant pairwise interactions between genotype 3 status and total cholesterol (P = 0.01), current alcohol intake (P = 0.04) and serum ALT (P = 0.01). This showed that the etiology of steatosis was different in patients with genotype 3 and those with non-genotype 3 chronic hepatitis C infection. In genotype 3 patients, the degree of steatosis was inversely associated with serum cholesterol (P = 0.005) and positively associated with serum triglyceride (P = 0.02). There was no association between body mass index (BMI) and the extent of steatosis. Among patients with other genotypes, the steatosis grade was strongly influenced by BMI (P < 0.0001) and serum ALT (P < 0.01). Independent predictors of fibrosis were age (P = 0.001), past alcohol intake (P = 0.04), ALT (P = 0.002), serum insulin (P = 0.001) and portal inflammation (P < 0.001). Conclusions: Hepatitis C genotype 3 may interfere with pathways of hepatic lipid metabolism, whereas increased BMI appears to be a more important pathogenic factor in other genotypes. Although steatosis and BMI were not associated with hepatic fibrosis, their relationship with serum insulin suggests that metabolic factors related to insulin action could influence fibrogenesis in hepatitis C. [source] Is delayed normalization of alanine aminotransferase a poor prognostic predictor in chronic hepatitis C patients treated with a combined interferon and ribavirin therapy?JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2002CHAO-HUNG HUNG Abstract Background and Aims : Decreased alanine aminotransferase (ALT) level is the accepted basic indicator of an interferon (IFN) therapeutic effect in chronic hepatitis C. This study assessed whether delayed normalization of ALT predicts a poor response to a combined therapy of IFN and ribavirin in patients with chronic hepatitis C virus (HCV) infection. Methods: Patients were treated with IFN-, 2b three times weekly and oral ribavirin for 24 weeks. The ALT values were assessed monthly and patterns of changes in ALT activity were analyzed. Serum HCV-RNA was checked at weeks 0, 12, 24, and 48. Results: A total of 103 patients completed therapy and 69 (67%) of them achieved a sustained viral response (SVR). There was no significant difference in the SVR between patients with or without early normalization (week 12) of ALT level (69 vs 56%). Of the sustained responders, nine patients (13%) with delayed ALT normalization had a SVR. Nine of the 12 patients (75%) with abnormal ALT and negative HCV-RNA at week 12 had a SVR compared with none of four patients who had positive HCV-RNA at week 12 (P = 0.0192). Conclusions: Lack of normalization of the ALT level at week 12 does not preclude successful virological outcome in hepatitis C patients receiving a combined therapy of IFN and ribavirin. Hepatitis C virus RNA at week 12 may be a useful predictor of treatment outcome in patients without early biochemical response. © 2002 Blackwell Publishing Asia Pty Ltd [source] ,Pseudo-aldosteronism' induced by intravenous glycyrrhizin treatment of chronic hepatitis C patientsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2001Tekla GJ Van Rossum Abstract Background and Aims: Treatment with intravenous glycyrrhizin reduces the progression of liver disease caused by chronic hepatitis C (HCV) infection. Glycyrrhetinic acid, a metabolite of glycyrrhizin, inhibits the renal conversion of cortisol to cortisone by inhibiting the enzyme 11,-hydroxysteroiddehydrogenase in the kidney. The resulting excess of cortisol subsequently stimulates the mineralocorticoid receptor, leading to pseudo-aldosteronism with hypertension, hypokalemia and eventually renin and aldosterone suppression. The aim of this study was to evaluate the occurrence of pseudo-aldosteronism after treatment of chronic hepatitis C (HCV) patients with increasing doses of intravenous glycyrrhizin. Methods: Forty-four HCV patients with chronic hepatitis or compensated cirrhosis were treated with intravenous glycyrrhizin 6 × 200 mg/week, 3 × 240 mg/week or 3 × 0 mg/week (placebo) for 4 weeks. In all patients, bodyweight, blood pressure and plasma concentrations of sodium, potassium, cortisol, DHEA-S (dehydroepiandrosterone sulfate), renin and aldosterone were measured before, and at 0 and 4 weeks after treatment. Results: Within the placebo group, no significant changes were observed. Within the 1200 mg group systolic blood pressure was significantly higher at the end of treatment, while aldosterone was significantly lower; at the end of the follow-up period these values had returned to baseline. The changes from baseline in systolic and diastolic blood pressure at the end of treatment were significantly higher in the 1200 mg group compared to the placebo group. The changes in aldosterone and potassium concentrations at the end of treatment increased with increasing dosage, although not significantly. Conclusion: Hepatitis C virus patients with chronic hepatitis or compensated cirrhosis show minor reversible symptoms of pseudo-aldosteronism after treatment with 1200 mg glycyrrhizin weekly for 4 weeks. [source] Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2010Marion Levast Abstract The prevalence of occult hepatitis B, defined by absence of HBsAg and HBV DNA, ranges widely in patients with hepatitis C. This may influence the treatment of hepatitis C and the severity of liver disease. Sensitive and specific real-time PCR techniques are available commercially and can detect more reliably low HBV DNA levels. The aim of this study was to determine the prevalence of occult hepatitis B virus infection using the COBAS Taqman assay (Roche Diagnostics, Meylan, France) in the serum and liver of HBsAg negative patients with chronic hepatitis C and to evaluate its clinical consequences on liver pathology and its impact on the response to treatment with peg-IFN, and Ribavirin. HBV DNA detection was assessed retrospectively on 140 sera and 113 liver biopsies of HCV positive/HBsAg negative patients before treatment. A 4.4% (5/113) prevalence of occult hepatitis B was recorded in liver samples and in none of the sera. Anti-HBc was not detected in one, three of whom were sustained virological responders to treatment, one was relapsed responder and one was non-responder. Furthermore, in this cohort composed of 12% anti-HBs negative/anti-HBc positive and 20% anti-HBs positive/anti-HBc positive patients, anti-HBc was not associated with pre-therapeutic viral load, ALT serum levels, and histological activity or fibrosis. Using a commercial real-time PCR assay, we observed a low prevalence of occult B hepatitis. This, just as anti-HBC status, had no clinical impact in a large cohort of hepatitis C patients. It therefore does not appear useful to screen for occult hepatitis B in these patients with this test before beginning HCV treatment. J. Med. Virol. 82: 000,000, 2010. © 2010 Wiley-Liss, Inc. J. Med. Virol. 82: 747,754, 2010. © 2010 Wiley-Liss, Inc. [source] Increased frequency of IFN-,-producing peripheral CD8+ T cells with memory-phenotype in patients with chronic hepatitis CJOURNAL OF MEDICAL VIROLOGY, Issue 2 2002Masayuki Murata Abstract To identify the capacity for cytokine production and the phenotypic characteristics of peripheral CD8+ T cells in patients with chronic hepatitis C, 31 patients with chronic hepatitis C and 22 healthy controls were studied at the single cell level by three-color flow cytometry. Whole blood was stained with surface CD8, intracellular interferon-, (IFN-,), and interleukin-4 (IL-4), surface CD8, CD28, and intracellular IFN-, after stimulation with PMA plus ionomycin, and then surface CD8, CD45RA, and CD28. IFN-,-producing peripheral CD8+ T cells were found frequently in patients than in controls (P,<,0.05), whereas IL-4-producing peripheral CD8+ T cells were not. Although the frequency of peripheral CD28+CD8+ and CD28,CD8+ T cells in patients was not different from that of controls, CD28+CD8+ T cells exceeded CD28,CD8+ T cells in the capacity for IFN-,-production after mitogenic stimulation (P,<,0.01). In a more detailed analysis of the CD28+CD8+ T cells, CD45RA,CD28+CD8+ T cells, defined phenotypically as memory cells, were found frequently in patients than in controls (P,<,0.05). There were no significant correlations between the frequency of IFN-,-producing peripheral CD8+ T cells and hepatitis C virus RNA level or serum alanine aminotransferase level in patients. These data suggest that functionally T cytotoxic type 1 and memory CD8+ T cells are predominant in the peripheral blood of chronic hepatitis C patients and that such activated CD8+ T cells are associated with liver damage. J. Med. Virol. 67:162,170, 2002. © 2002 Wiley-Liss, Inc. [source] Sustained virological response to pegylated interferon and ribavirin is maintained during long-term follow-up of chronic hepatitis C patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010E. G. GIANNINI Aliment Pharmacol Ther,31, 502,508 Summary Background, There are few data in the literature regarding the long-term virological follow-up of chronic hepatitis C patients who obtain sustained virological response (SVR) to pegylated interferon (PEG-IFN) and ribavirin therapy. Aim, To assess the durability of SVR to PEG-IFN and ribavirin therapy during long-term follow-up of chronic hepatitis C patients. Methods, We evaluated a cohort of 231 chronic hepatitis C patients who had at least 48 weeks of follow-up after SVR to PEG-IFN and ribavirin treatment. Median duration of follow-up after SVR was 164 weeks, and exceeded 5 years in 30% of the cohort. Patients underwent consistent clinical, biochemical and virological evaluations every 6 months during follow-up. Results, Sustained virological response was maintained in 211 patients (91%) while HCV-RNA became positive in two patients (<1%) within 1 year after SVR, and in 18 patients (8%) serum HCV-RNA was transiently positive in at least one follow-up evaluation. Clinical outcome was not significantly different between patients with persistently negative and transiently positive serum HCV-RNA. Conclusions, Sustained virological response to PEG-IFN and ribavirin is maintained in 99% of patients during long-term follow-up. Late virological relapse occurred within 1 year after SVR and, from a clinical perspective, patients can be considered cured of infection after this period. [source] Presence of HCV-RNA after ultracentrifugation of serum samples during the follow-up of chronic hepatitis C patients with a sustained virological response may predict reactivation of hepatitis C virus infectionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009I. CASTILLO Summary Background, Concentration of viral particles by ultracentrifugation of serum prior to PCR allows detection of hepatitis C virus (HCV) RNA in patients with undetectable viral RNA by conventional PCR assays. Aim, To analyse if HCV-RNA is detected after serum ultracentrifugation in chronic hepatitis C patients with a sustained virological response to antiviral therapy (defined as serum HCV-RNA negativity by conventional assays 6 months after the end of therapy). Methods, HCV-RNA was tested using real-time PCR in ultracentrifuged sera collected during the post-treatment follow-up (mean: 42 ± 27 months) in 57 sustained virological responders (SVR). Results, After serum ultracentrifugation, HCV-RNA was detected on at least one occasion during the follow-up in 29/57 (51%) SVR. Thirteen (23%) of these 57 SVR suffered a reactivation 18 ± 8 months after the end of therapy (reappearance of serum HCV-RNA detectable by conventional assays). Among reactivated patients, 11/13 (85%) had HCV-RNA in ultracentrifuged serum samples (detectable 10 ± 5 months before reactivation), while HCV-RNA was positive after ultracentrifugation in 18/44 (41%) long-term SVR (P = 0.01). Persistence of detectable HCV-RNA after serum ultracentrifugation was associated with reactivation (P = 0.001). Conclusions, Serum ultracentrifugation prior to PCR allows detection of HCV-RNA in SVR and its persistence may predict late reactivation. [source] Clinical trial: a randomized trial of pegylated-interferon-,-2a plus ribavirin with or without amantadine in treatment-naïve or relapsing chronic hepatitis C patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009P. LANGLET Summary Background, The combination therapy of pegylated-interferon-,2a plus ribavirin is considered as the standard of care for patients with chronic hepatitis C. A sustained viral response is obtained in 40,50% of naïve patients with genotype 1 and in around 80% of naïve patients with genotype 2 or 3. Aim, To assess whether amantadine, added to the conventional combination therapy, could improve the treatment efficacy. Methods, In all, 630 patients (intent-to-treat population) with chronic hepatitis C were randomized into two groups: 316 patients (treatment group) received pegylated-interferon-,2a (180 ,g once weekly) plus ribavirin (1000,1200 mg/daily) with amantadine (200 mg/daily); 314 patients (control group) received pegylated-interferon-,2a (180 ,g once weekly) plus ribavirin (1000,1200 mg/daily) without amantadine. The duration of the treatment was 48 weeks for genotypes 1, 4, 5 and 6, and 24 weeks for genotypes 2 and 3. Results, There was no statistically significant difference between treatments groups for any of the variables tested for. Subgroups of patients likely to take advantage of the addition of amantadine were not identified. Conclusions, This large study definitely excludes the role of amantadine in addition of conventional combination therapy in the treatment of chronic hepatitis C patients. [source] Enhanced ability of regulatory T cells in chronic hepatitis C patients with persistently normal alanine aminotransferase levels than those with active hepatitisJOURNAL OF VIRAL HEPATITIS, Issue 12 2009I. Itose Summary., In hepatitis C virus (HCV) infection, the Th1-type immune response is involved in liver injury. A predominance of immunosuppressive regulatory T cells (Treg) is hypothesized in patients with persistently normal alanine aminotransferase (PNALT). Our aim was to clarify the role of Treg in the pathogenesis of PNALT. Fifteen chronically HCV-infected patients with PNALT, 21 with elevated ALT (CH) and 19 healthy subjects (HS) were enrolled. We determined naturally-occurring Treg (N-Treg) as CD4+CD25high+FOXP3+ T cells. The expression of FOXP3 and CTLA4 in CD4+CD25high+ cells was quantified by real-time reverse transcriptase-polymerase chain reaction. Bulk or CD25-depleted CD4+ T cells cultured with HCV-NS5 loaded dendritic cells were assayed for their proliferation and cytokine release. We examined CD127,CD25,FOXP3+ cells as distinct subsets other than CD25+ N-Treg. The frequencies of N-Treg in patients were significantly higher than those in HS. The FOXP3 and CTLA4 transcripts were higher in PNALT than those in CH. The depletion of CD25+ cells enhanced HCV-specific T cell responses, showing that co-existing CD25+ cells are suppressive. Such inhibitory capacity was more potent in PNALT. The frequency of CD4+CD127,CD25,FOXP3+ cells was higher in CH than those in PNALT. Treg are more abundant in HCV-infected patients, and their suppressor ability is more potent in patients with PNALT than in those with active hepatitis. [source] Association of genetic polymorphisms with interferon-induced haematologic adverse effects in chronic hepatitis C patientsJOURNAL OF VIRAL HEPATITIS, Issue 6 2009M. Wada Summary., Interferon (IFN)-based combination therapy with ribavirin has become the gold standard for the treatment of chronic hepatitis C virus infection. Haematologic toxicities, such as neutropenia, thrombocytopenia, and anaemia, however, frequently cause poor treatment tolerance, resulting in poor therapeutic efficacy. The aim of this study was to identify host genetic polymorphisms associated with the efficacy or haematologic toxicity of IFN-based combination therapy in chronic hepatitis C patients. We performed comprehensive single nucleotide polymorphism detection in all exonic regions of the 12 genes involved in the IFN signalling pathway in 32 healthy Japanese volunteers. Of 167 identified polymorphisms, 35 were genotyped and tested for an association with the efficacy or toxicity of IFN plus ribavirin therapy in 240 chronic hepatitis C patients. Multiple logistic regression analysis revealed that low viral load, viral genotypes 2 and 3, and a lower degree of liver fibrosis, but none of the genetic polymorphisms, were significantly associated with a sustained virologic response. In contrast to efficacy, multiple linear regression analyses demonstrated that two polymorphisms (IFNAR1 10848-A/G and STAT2 4757-G/T) were significantly associated with IFN-induced neutropenia (P = 0.013 and P = 0.011, respectively). Thrombocytopenia was associated with the IRF7 789-G/A (P = 0.031). In conclusion, genetic polymorphisms in IFN signalling pathway-related genes were associated with IFN-induced neutropenia and thrombocytopenia in chronic hepatitis C patients. In contrast to toxicity, the efficacy of IFN-based therapy was largely dependent on viral factors and degree of liver fibrosis. [source] Longitudinal evaluation of a fibrosis index combining MMP-1 and PIIINP compared with MMP-9, TIMP-1 and hyaluronic acid in patients with chronic hepatitis C treated by interferon-alpha and ribavirinJOURNAL OF VIRAL HEPATITIS, Issue 10 2006C. Trocme Summary., We have recently described a fibrosis index combining serum procollagen type III N-terminal peptide (PIIINP) and matrix metalloproteinase 1 (MMP-1) concentrations for evaluating the amount of liver fibrosis in chronic hepatitis C patients. The aims of the present study were to validate this score in another cohort of patients and to assess its variations along those of TIMP-1, hyaluronic acid (HA) and MMP-9 during antiviral treatment. Seventy-nine patients treated by interferon-alpha and ribavirin for 24 or 48 weeks were included. A liver biopsy was performed within the 6 months before the start of treatment. Serum markers were measured in serum collected the day of the liver biopsy, at start of treatment, and every 3 months during treatment and a 6-month follow-up period. The PIIINP/MMP-1 index was significantly correlated to the METAVIR fibrosis (r = 0.68, P < 0.001). Its overall diagnostic value defined by the area under the receiver operating characteristics curves was 0.77 for discriminating F1 vs F2F3F4, and 0.81 for discriminating F1F2 vs F3F4, and was better than that observed for HA and TIMP-1. At the end of follow-up, the PIIINP/MMP-1 index significantly decreased in responders and remained stable in nonresponder patients. This decrease occurred early and continued regularly during the treatment period. This variation was because of both a decrease of PIIINP and an increase of MMP-1 concentrations. HA and TIMP-1 serum concentrations were also significantly lower at the end of follow-up in responder patients, but early changes were minimal and not influenced by the response to treatment. Our study shows that a noninvasive index combining PIIINP and MMP-1 is a useful tool to follow-up fibrosis change during and after antiviral therapy chronic hepatitis C patients. [source] Diagnostic accuracy of a fibrosis serum panel (FIBROSpect II) compared with Knodell and Ishak liver biopsy scores in chronic hepatitis C patientsJOURNAL OF VIRAL HEPATITIS, Issue 10 2006C. Christensen Summary., Liver biopsy is the primary method of assessing liver injury in hepatitis C patients. FIBROSpect II (FS), a diagnostic panel of three extracellular matrix remodelling markers, may be useful as a noninvasive alternative to this procedure. The purpose of this study was to correlate FS results with liver fibrosis scores to determine if this test is sufficiently accurate to be a viable alternative to liver biopsy. A total of 142 serum specimens were evaluated for fibrosis with FS and were compared with Knodell and Ishak fibrosis scores. FS reports an index score ranging from 0.1 to 1.0, which corresponds to the probability of progressive liver fibrosis. Using a FS index cut-off of 0.42, 50 of 54 patients with Ishak 3,6 were classified as having advanced fibrosis (METAVIR F2,F4) and 58 of 88 patients with Ishak 0,2 as having no/mild fibrosis (METAVIR F0,F1), resulting in a sensitivity of 93%, specificity of 66%, and an overall test accuracy of 76%. With a 38% prevalence of advanced fibrosis, the negative predictive value was 94% and positive predictive value was 63%. A biopsy length of ,2 cm was associated with higher concordance between FS results and liver fibrosis scores (P = 0.01). FS was clinically useful in ruling out advanced fibrosis in hepatitis C by identifying patients with mild disease in whom treatment could be deferred. The limitation of this test is its decreased sensitivity and specificity in the middle of the test's reporting range between scores of 0.42 and 0.80. [source] Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirinJOURNAL OF VIRAL HEPATITIS, Issue 7 2006C. Berg Summary., We conducted a randomized multinational study to determine whether 48 weeks of re-treatment with peginterferon-alpha-2a (40 kDa) plus ribavirin would induce a sustained virological response (SVR) in relapsed chronic hepatitis C patients. Patients who had previously relapsed during 24 weeks of untreated follow-up, after having achieved an end-of-treatment virological response with 24 weeks of peginterferon-alpha-2a (40 kDa)/ribavirin combination therapy, within a phase III trial, were studied. Although the recommended dosage was the same as that used at the end of the initial trial, adjustments were permitted. Data on serious adverse events, or adverse events that resulted in dose reductions or discontinuations, were collected. Following re-treatment, the overall SVR rate in the 64 patients was 55%. The SVR rates in patients infected with hepatitis C virus (HCV) genotype 1 and non-1 genotypes were 51% and 63%, respectively. Early (week 12) virological responses were seen in 39 patients (61%) and were predictive of an SVR. Re-treatment was well tolerated. The most frequent adverse events recorded were fatigue (5%) and abdominal pain (3%). Dosages of peginterferon-alpha-2a (40 kDa) and/or ribavirin were modified because of adverse events in 3% and 13% of patients, and because of laboratory abnormalities in 23% and 5% of patients, respectively. Thus, a 48-week course of peginterferon-alpha-2a (40 kDa) plus ribavirin induces an SVR in 55% of patients who relapsed during follow-up after 24 weeks of combination therapy. Physicians should not hesitate to offer re-treatment to patients who relapse after an initial, 24-week course of combination therapy, or who have prematurely stopped treatment because, for example, of laboratory abnormalities. [source] Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon ,-2b plus ribavirinALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009C.-J. CHU Summary Background, Cross-sectional studies suggest insulin resistance is strongly associated with hepatic steatosis and fibrosis in patients with chronic hepatitis C (CHC), which might affect the efficacy of antiviral therapy. Aim, To investigate retrospectively the impact of insulin resistance on treatment response in Chinese genotype 1 CHC patients receiving a 24-week course therapy with peginterferon ,-2b/ribavirin. Methods, A total of 133 biopsy-proven CHC patients were enrolled for analyses. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR). Hepatic fibrosis was graded by the METAVIR scoring system. Results, Mean HOMA-IR progressively elevated along with the severity of hepatic fibrosis (F1,F2 fibrosis: 2.55 ± 0.16 vs. F3,F4 fibrosis: 3.61 ± 0.20, P < 0.001). Compared with patients with sustained virological response (SVR), patients without SVR had significantly higher percentages of F3,F4 fibrosis (62.2% vs. 21.6%, P < 0.001) and baseline high viral load (,600 000 IU/mL; 64.4% vs. 35.6%, P = 0.038). In addition, patients without SVR had significantly higher plasma levels of insulin (15.03 ± 0.89 vs. 10.19 ± 0.55 ,U/mL, P < 0.001) and HOMA-IR values (3.76 ± 0.23 vs. 2.50 ± 0.15, P < 0.001). Multivariate analyses showed that F1,F2 fibrosis (odds ratio: 4.49, P = 0.001), HOMA-IR < 2 (odds ratio: 7.15, P = 0.005) and pre-treatment hepatitis C virus RNA < 600 000 IU/mL (odds ratio: 3.26, P = 0.012) were the independent factors associated with SVR. Conclusions, Insulin resistance is a major determinant of SVR in genotype 1 CHC patients receiving peginterferon ,-2b/ribavirin. Strategies to modify insulin resistance may be effective in enhancing SVR before or during anti-viral therapy. [source] Retreatment for 24 vs 48 weeks with interferon-,2b plus ribavirin of chronic hepatitis C patients who relapsed or did not respond to interferon aloneJOURNAL OF VIRAL HEPATITIS, Issue 6 2000J. Enríquez We assessed the efficacy of interferon (IFN) plus ribavirin over 24 or 48 weeks for the retreatment of patients with chronic hepatitis C who had relapsed or did not respond to a previous course of IFN. One-hundred and twenty patients (69 non-responders and 51 relapsers) were randomly assigned to receive IFN-,2b (3 million units thrice weekly) plus ribavirin (1000,1200 mg per day) for 24 weeks (group A: 58 patients) or 48 weeks (group B: 62 patients). Treatment was discontinued at week 12 if the alanine aminotransferase (ALT) level remained elevated. The rate of sustained response was 15.5% in group A and 37.1% in group B (P=0.013). Relapsers treated for 48 weeks had a sustained response rate of 66.6% compared with a sustained response rate of only 25% in those treated for 24 weeks (P=0.004). Moreover, a sustained response was seen in 14.3% of non-responders treated for 48 weeks and in 8.8% of those treated for 24 weeks (P=0.71). Fifty-three per cent of patients with a normal ALT level and undetectable hepatitis C virus (HCV) RNA at week 12 had a sustained response compared with 14% of those who were HCV RNA positive at week 12 (P < 0.001). Independent predictive factors of sustained response were: therapy for 48 weeks (P=0.0026), relapse after IFN treatment (P=0.0006), loss of HCV RNA at week 12 (P=0.0008) and HCV genotype non-1 (P=0.024). Hence, in patients with chronic hepatitis C who failed to respond to a previous course of IFN monotherapy, combination therapy with IFN plus ribavirin for 48 weeks seems to be more effective than IFN plus ribavirin for 24 weeks. [source] Apoptotic cell death does not parallel other indicators of liver damage in chronic hepatitis C patientsJOURNAL OF VIRAL HEPATITIS, Issue 3 2000Rodrigues The mechanisms of hepatocyte damage and the events that lead to high rates of chronic liver disease in hepatitis C virus (HCV) infection remain unclear. Recent in vitro studies have suggested that the HCV core protein may disrupt specific signalling pathways of apoptosis. This prompted us to study patients with chronic HCV infection to: determine the extent of apoptosis in the liver; evaluate whether clinical and biochemical data are correlated with histological findings; and to investigate if apoptosis is related to the histological activity of the disease. Twelve patients with chronic hepatitis C were included in the study. Liver histology was scored by using the histological activity index (HAI) of Knodell et al. DNA fragmentation was assessed in liver tissue by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) assay. Routine methods were used to determine serum markers of liver disease. Bile acids were measured in serum and liver by gas chromatography. Patients were placed, according to their HAI score, into group A (3.8 ± 0.3) or group B (7.8 ± 0.8) (P < 0.01). Liver enzymes tended to be higher in group B patients than in patients of group A. Levels of toxic bile acids in serum were greater in patients than in controls (P < 0.01). Chenodeoxycholic acid values were slightly higher in serum and liver of patients in group A. Liver biopsies with low HAI scores showed an increased rate of apoptosis (18.0 ± 4.0 apoptotic cells per field) compared to those with higher HAI scores (6.6 ± 2.1, P < 0.05) or to controls (3.5 ± 0.4, P < 0.01). Hence, less severe liver disease, associated with lower histological grades and biochemistries, as well as increased levels of chenodeoxycholic acid, induces an expanded apoptotic response. The lower apoptotic rate in advanced liver disease may be associated with the high incidence of hepatocellular dysplasia/neoplasia. [source] Evaluating the cost of sustained virologic response in naïve chronic hepatitis C patients treated à la carteALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2007M. BUTI Summary Background There is a tendency to individualize treatment in chronic hepatitis C patients depending on viral load and rapid clearance of HCV-RNA. Aim To evaluate the cost (,, 2006) per sustained virologic response in naïve patients with therapy à la carte compared with standard combination therapy. Methods A decision analysis model was used to compare standard therapy with peginterferon alpha and ribavirin for 24 weeks for genotype (G) 2/3, and 48 weeks for G1 and therapy à la carte with the same drugs but different durations: G1 high viral load for 48 weeks, G1 low viral load with rapid virologic response for 24 weeks, and without rapid virologic response for 48 weeks, and G2/3 with rapid virologic response for 12 weeks, and without rapid virologic response for 24 weeks. Results Sustained virologic response was similar in both strategies. The cost per successfully treated patient for standard therapy is ,17 812 and for therapy à la carte,12 313. Assuming that 13 309 patients with standard therapy and 14 450 patients with therapy à la carte achieve sustained virologic response, therapy à la carte has an overall cost-saving of ,59.13 million. Conclusion Therapy à la carte is a cost-saving strategy for chronic hepatitis C infection compared to standard therapy, with lower investment requirement per patient to achieve sustained virologic response. [source] Gene expression profile of Huh-7 cells expressing hepatitis C virus genotype 1b or 3a core proteinsLIVER INTERNATIONAL, Issue 5 2009Valerio Pazienza Abstract Background: The liver disease expression in chronic hepatitis C patients is variable and may partially depend on the sequence of the infecting viral genotype. Aim: To identify some hepatitis C virus (HCV) genotype-specific virus,host interactions potentially leading to clinically significant consequences. Methods: We compared the gene expression profile of Huh-7 cells transiently expressing the core protein of HCV genotype 1b and 3a using microarray technology. Results: Thirty-two genes were overexpressed in Huh-7 transfected with the HCV genotype 1b core protein and 57 genes in cells transfected with the genotype 3a core protein. On the other hand, we found 20 genes downregulated by core 1b and 31 genes by core 3a. These included genes involved in lipid transport and metabolism, cell cycle, immune response and insulin signalling. Conclusion: The expression of HCV core proteins of different genotypes leads to a specific gene expression profile. This may account for the variable disease expression associated with HCV infection. [source] Predictors of a sustained virological response in patients with genotype 4 chronic hepatitis CLIVER INTERNATIONAL, Issue 8 2008Rita Raafat Gad Abstract Objectives: To determine the clinical, biological, virological and histological predictive factors associated with a sustained virological response (SVR) to combined interferon therapy among Egyptian patients infected by genotype 4 hepatitis C virus (HCV). Patients and Methods: Individual data from 250 patients with genotype 4 chronic hepatitis C, treated with different regimens of combined interferon, were analysed. The primary end point was SVR defined as undetectable HCV RNA by polymerase chain reaction (PCR) 24 weeks after the end of treatment. Multivariate logistic regression analysis was performed to select the independent prognostic parameters associated with SVR. Results: A sustained virological response was achieved among 137/250 (54.8%) patients. Baseline factors independently and negatively associated with SVR were serum ,-fetoprotein (AFP) level (above 0.3 upper limit of normal) [odds ratio (OR)=0.5, 95% confidence interval (CI): 0.2,0.8], severe fibrosis (Metavir score >F2) (OR=0.4, 95% CI: 0.2,0.8), presence of steatosis (OR=0.5, 95% CI: 0.3,0.97) and standard interferon treatment (OR=0.4, 95% CI: 0.2,0.8). Conclusions: Among genotype 4 chronic hepatitis C patients, severe fibrosis, severe steatosis, treatment with standard interferon and a high serum AFP level were all negatively associated with SVR. Pretreatment serum AFP level should be considered in the routine assessment of factors predictive of a treatment response. [source] Role of CYP2D6 polymorphism in predicting liver fibrosis progression rate in Caucasian patients with chronic hepatitis CLIVER INTERNATIONAL, Issue 3 2006Sigal Fishman Abstract: Objective: Previous studies have demonstrated that CYP2D6 polymorphism is associated with liver cirrhosis. The aim of the present study was to find out whether CYP2D6*4, the poor metabolizer allele can predict fibrosis progression rate. Methods: Seventy-five Caucasian patients with chronic hepatitis C infection were recruited. They were divided into two groups, ,fast fibrosers' and ,slow fibrosers', according to Poynard's fibrosis progression curves. Sixty-two patients underwent liver biopsy. Twenty healthy neonates were included as control population. DNA was extracted from peripheral blood and CYP2D6*4 was tested by polymer chain reaction using fluorescent hybridization probes in a lightCycler instrument. Results: Forty-two patients were classified as ,fast fibrosers' and 33 patients as ,slow fibrosers'. The frequency of CYP2D6*4 allele in the ,fast fibrosers' (34.5%) was significantly higher compared with the ,slow fibrosers' (15%) (P -value=0.007). There was no significant difference between the frequency of CYP2D6*4 in the ,slow fibrosers' (15%) compared with the controls (12.5%). Carrier state of CYP2D6*4 was the only covariate that was significantly positively correlated with fast progression to cirrhosis (odds ratio=6.5, P=0.01). Conclusion: This study indicates for the first time that CYP2D6 genotype might be a significant predictor of liver fibrosis progression rate in chronic hepatitis C patients. [source] Randomized trial of three different regimens for 24 weeks for re-treatment of chronic hepatitis C patients who failed to respond to interferon-, monotherapy in TaiwanLIVER INTERNATIONAL, Issue 6 2004Wan-Long Chuang Abstract: With the favorable result of interferon (IFN),ribavirin combination therapy for 24 weeks among naive Taiwanese chronic hepatitis C (CHC) patients, the optimal regimens of re-treatment for CHC patients who failed initial IFN monotherapy is not well-established. The study evaluated the effectiveness of re-treatment for 24 weeks with 3 different regimens and predictors for sustained virological response (SVR). Methods: Total 120 Taiwanese CHC patients (81 males, 70 relapsers, mean age: 48.6 years) who failed initial IFN monotherapy were enrolled. They were assigned randomly (with a ratio of 1:1:2) to receive one of the three regimens for re-treatment for 24 weeks; group A: IFN 6 million units (MU) monotherapy (N=30), group B: combination therapy with ribavirin and IFN 3 MU (N=30) or group C: combination therapy with ribavirin and IFN 6 MU (N=60). The intention-to-treat rate of sustained virological response (SVR) was 38.3%. The SVR rate in group C (53.3%) was significantly higher than group A (16.7%, P<0.005) and group B (30%, P<0.05). Drop-out rates were similar between the three groups. Patients achieving SVR had significant improvement histologically. Hepatitis C virus (HCV) genotype non-1b infection, lower pretreatment HCV RNA levels, combined with ribavirin and with higher IFN dose, and relapsers were independent predictors for SVR. Conclusion: We concluded that more than one-third Taiwanese CHC patients achieved SVR after 24 weeks re-treatment and combination therapy, especially with higher dose of IFN, yielded higher efficacy. [source] | ||||||||||||||||||||||||||||