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Viral Response (viral + response)
Terms modified by Viral Response Selected AbstractsPeginterferon alpha-2b plus ribavirin vs interferon alpha-2b plus ribavirin for chronic hepatitis C in HIV-coinfected patientsJOURNAL OF VIRAL HEPATITIS, Issue 4 2007M. Crespo Summary., Treatment of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients is associated with low response rates and high incidence of side effects. One hundred twenty-one hepatitis C virus (HCV),HIV-coinfected patients were randomized to receive interferon alpha-2b (3 MU thrice weekly; n = 61) or peginterferon alpha-2b (1.5 ,g/kg/week; n = 60), plus ribavirin (800 mg daily), for 24 (genotype 2 or 3) or 48 weeks (genotype 1 or 4). We assessed early virological response at 4, 8 and 12 weeks to predict sustained virological response (SVR). Safety assessment included frequent blood lactate measurement and relative quantitation of mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells. In intention-to-treat analysis, the SVR rate was higher in the peginterferon group (55%vs 26%; P = 0.002). The difference for HCV genotypes 1 and 4 was 45%vs 14% (P = 0.009) and 50%vs 27% (P = 0.387), respectively, and for genotype 2 or 3, 71%vs 43% (P = 0.12) Viral response at 4, 8 and 12 weeks of treatment was highly predictive of SVR. Among genotype 3 patients, 17 of 20 (85%) whose HCV RNA was already undetectable at 4 weeks had an SVR after 24 weeks of treatment. Hyperlactataemia occurred in 22 patients and was clinically significant in six, two of whom died. mtDNA decreased significantly 4,12 weeks after the start of treatment in patients developing clinically significant hyperlactataemia. Peginterferon alpha-2b plus ribavirin was more effective than interferon alpha-2b plus ribavirin in HIV-coinfected patients. Frequent monitoring of virological response may be very helpful to optimize treatment compliance, to tailor treatment duration and to minimize side effects. [source] HEPATITIS C AND ADDICTION: Retention rate and side effects in a prospective trial on hepatitis C treatment with pegylated interferon alpha-2a and ribavirin in opioid-dependent patientsADDICTION BIOLOGY, Issue 2 2009Nina Ebner ABSTRACT Hepatitis C viral (HCV) infection is present in 30 to 98% of intravenous drug users. Intravenous substance abuse represents the main route of HCV transmission in industrialized countries. A multi-centre, randomized, controlled, prospective study assessed sustained virological response (SVR), adverse events such as depressive episodes and retention rate of HCV treatment in opioid-dependent patients. Stabilized, opioid-dependent patients with chronic HCV infection (genotype 2 or 3) received pegylated interferon alpha-2a in combination with ribavirin 800 mg/day (Group A) or 400 mg/day (Group B). Participants were randomized, blocked and stratified by genotype and viral load. A standardized psychiatric assessment, Beck Depression Inventory (BDI) and Van Zerssen's list of complaints were administered at each study visit. In 31 months, 300 opioid-dependent patients were screened; 190 (63.3%) were hepatitis C antibody positive. According to study protocol, out of 75 ,potential-to-treat' patients with genotype 2 or 3, 17 stable patients (22.6%) were included in the study. All participants completed the study. Significant haemoglobin decreases occurred in both Groups A (P = 0.001) and B (P = 0.011). All the patients had an end-of-treatment (week 24) HCV RNA negativity. Fifteen (88.2%) achieved SVR at week 48. Overall, 52.9% developed depressive symptoms during treatment. Because of the prompt initiation of antidepressant medication at first appearance of depressive symptoms, no severe depressive episodes occurred. Our data show a high retention rate and reliability, and good viral response for both treatments. Hepatitis C treatment in stable opioid-dependent patients was efficacious, suggesting that addiction clinics can offer antiviral therapy in combination with agonistic treatment as part of multi-disciplinary treatment. [source] Treating hepatitis C in the prison population is cost-saving,HEPATOLOGY, Issue 5 2008Jennifer A. Tan The prevalence of chronic hepatitis C infection in U.S. prisons is 12% to 31%. Treatment of this substantial portion of the population has been subject to much controversy, both medically and legally. Studies have demonstrated that treatment of chronic hepatitis C with pegylated interferon (PEG IFN) and ribavirin is a cost-effective measure in the general population; however, no study has addressed whether the same is true of the prison population. The aim of this study was to determine the cost-effectiveness of hepatitis C treatment with PEG IFN and ribavirin in the U.S. prison population. Cost-effectiveness was determined via a decision analysis model employing Markov simulation. The cohort of prisoners had a distribution of genotypes and stages of fibrosis in accordance with prior studies evaluating inmate populations. The probability of transitioning from one health state to another, reinfection rates, in-prison and out-of-prison mortality rates, sustained viral response rates, costs, and quality of life weights were also obtained from the literature. Sensitivity analysis was performed. In a strategy without a pretreatment liver biopsy, treatment was cost-effective for all ages and genotypes. This model was robust to rates of disease progression, mortality rates, reinfection rates, sustained viral response rates, and costs. In a strategy employing a pretreatment liver biopsy, treatment was also cost-saving for prisoners of all ages and genotypes with portal fibrosis, bridging fibrosis, or compensated cirrhosis. Treatment was not cost-effective in patients between the ages of 40 and 49 with no fibrosis and genotype 1. Conclusion: Treatment of chronic hepatitis C with PEG IFN and ribavirin in U.S. prisons results in both improved quality of life and savings in cost for almost all segments of the inmate population. If the decision to treat hepatitis C is based on pharmaco-economic measures, this significant proportion of infected individuals should not be denied access to therapy. (HEPATOLOGY 2008.) [source] IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection,HEPATOLOGY, Issue 6 2006Martin Lagging Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-,-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P < .0001), even in those with body mass index (BMI) , 25 kg/m2 (P = .004) and with baseline viral load , 2 million IU/mL (P = .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P = .0002), including those having higher BMI (P < .05), higher viral load (P = .0005), and both higher BMI and viral load (P < .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1,infected patients, which was comparable with that observed using a reduction in HCV-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention. (HEPATOLOGY 2006;44:1617,1625.) [source] Correlation between beta-lipoprotein levels and outcome of hepatitis C treatment,HEPATOLOGY, Issue 2 2006Kavitha Gopal The low-density lipoprotein receptor (LDLR) has been proposed as a candidate receptor for the hepatitis C virus (HCV). Competitive inhibition of HCV binding to the LDLR by low-density lipoprotein (LDL) has been shown in vitro. If similar inhibition occurs in vivo, an elevated serum concentration of beta- lipoproteins may reduce the efficiency of infecting hepatocytes with HCV by competitively inhibiting HCV viral receptor binding. We investigated the role of baseline lipid values in influencing the outcome of HCV treatment. We conducted a retrospective chart review of patients treated with an interferon-based regimen at our liver and gastroenterology clinics between 1998 and 2004. Of 99 patients enrolled in the study, 49 (49.5%) had HCV genotype 1 (LDL 100.2 ± 30.2 mg/dL [mean ± SD]), and 50 patients (50.5%) had genotype 2 or 3 (LDL 110.1 ± 40 mg/dL) infection. Early viral response (EVR), end-of-treatment response (ETR), and sustained viral response (SVR) were documented in 99, 88, and 77 patients, respectively. LDL and cholesterol levels prior to treatment were found to be higher in patients with positive EVR, ETR, and SVR. This difference remained significant independent of age. Multivariate analysis controlling for genotype and age showed that the higher the cholesterol and LDL levels prior to treatment, the greater the odds of responding to treatment. In conclusion, having higher serum LDL and cholesterol levels before treatment may be significant prognostic indicators for treatment outcome of those with chronic hepatitis C infection, particularly in genotypes 1 and 2. (HEPATOLOGY 2006;44:335,340.) [source] High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C,HEPATOLOGY, Issue 2 2005Karin Lindahl Improved treatment regimens for patients with chronic hepatitis C, genotype 1 and high viral load are needed. Increasing the dose of ribavirin has increased the response rate, but experience with doses of more than 1,200 mg/day is limited. The aim of this study was to investigate the safety and tolerance to treatment with a high and individualized dose of ribavirin in combination with peginterferon. Ten patients with chronic hepatitis C, genotype 1 and high viral load were treated with peginterferon alfa-2a and ribavirin for 48 weeks in a prospective trial. The initial ribavirin dose was individualized and calculated from a pharmacokinetic formula based mainly on renal function. Ribavirin plasma concentrations were monitored, and the dose was adjusted to reach the target concentration. Hemoglobin was monitored, and patients were treated with erythropoietin and blood transfusions when indicated. After dose adjustments, the mean dose of ribavirin was 2,540 mg/day (range, 1,600-3,600) at week 24. The main side effect was anemia, which was controlled with erythropoietin. Two patients required blood transfusions. One patient was withdrawn at week 24 because of a lack of viral response, and one patient at week 39 because of side effects, primarily interferon associated. At follow-up (,24 weeks posttreatment), nine of ten patients had undetectable HCV RNA and thus were cured by standard definitions. In conclusion, a high dose of ribavirin according to an individualized schedule is feasible but associated with more frequent and serious side effects such as anemia. The viral response merits further evaluation. (HEPATOLOGY 2005;41:275,279.) [source] Introduction to therapy of hepatitis CHEPATOLOGY, Issue 5B 2002Karen L. Lindsay 1640 Marengo St. Since the 1997 National Institutes of Health Consensus Development Conference on management of hepatitis C there have been several important advances that significantly impact its therapy; notably the availability of sensitive, specific, and standardized assays for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SVR) is the optimal surrogate endpoint of treatment. Using pegylated interferon and ribavirin, virological response with relapse and nonresponse are less common, but remain poorly understood. Current studies are evaluating nonvirological endpoints of treatment, namely biochemical response and histological response. To date, definitive treatment trials have primarily been conducted in adult patients with elevated aminotransferase levels, clinically compensated chronic liver disease, and no other significant medical disorder. Limited data are available from studies of other patient populations, and the safety of interferon-based treatment has not yet been established in several patient groups. Future research is needed to elucidate the mechanisms of viral response and clearance, to develop effective therapies for interferon nonresponse or intolerance, to define the role of complementary and alternative medicine and other nonspecific therapies, and to develop strategies for the optimal management and treatment of special patient populations who probably represent the majority of persons with chronic hepatitis C in the United States. [source] Introduction to therapy of hepatitis CHEPATOLOGY, Issue S1 2002Karen L. Lindsay M.D. Since the 1997 National Institutes of Health Consensus Development Conference on management of hepatitis C there have been several important advances that significantly impact its therapy; notably the availability of sensitive, specific, and standardized assays for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SVR) is the optimal surrogate endpoint of treatment. Using pegylated interferon and ribavirin, virological response with relapse and nonresponse are less common, but remain poorly understood. Current studies are evaluating nonvirological endpoints of treatment, namely biochemical response and histological response. To date, definitive treatment trials have primarily been conducted in adult patients with elevated aminotransferase levels, clinically compensated chronic liver disease, and no other significant medical disorder. Limited data are available from studies of other patient populations, and the safety of interferon-based treatment has not yet been established in several patient groups. Future research is needed to elucidate the mechanisms of viral response and clearance, to develop effective therapies for interferon nonresponse or intolerance, to define the role of complementary and alternative medicine and other nonspecific therapies, and to develop strategies for the optimal management and treatment of special patient populations who probably represent the majority of persons with chronic hepatitis C in the United States. (HEPATOLOGY 2002;36:S114,S120). [source] Prevention of hepatocellular carcinoma complicating chronic hepatitis CJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2009Yoshiyuki Ueno Abstract Chronic hepatitis C virus (HCV) infection accounts for most cases of hepatocellular carcinoma (HCC) in Japan and is the second major cause in many other countries. Development of HCC takes a considerable time after onset of HCV infection, between 20,40 years in most cases, and usually develops after cirrhosis is established. Although only a minority of HCV infections reach this stage, the high prevalence of chronic HCV infection in many countries (1,3%) is such that HCC related to HCV infection poses a significant public health issue 20,50 years after the onset of HCV epidemics. Due to advances in testing, and accessibility of clean, disposable medical apparatus including syringes and needles, and particularly screening of donor blood for anti-HCV and by nucleic acid testing, new cases of HCV infection have decreased in most countries, except for continued transmission by injection drug users (IDU). A key difference between HBV and HCV infection is that HCV can be eradicated by effective antiviral treatment. Sustained eradication of HCV reverses hepatic fibrosis, thereby preventing progression to cirrhosis and risk of HCC. Further, it has been well demonstrated that interferon-based antiviral therapy suppresses development of HCC in high-risk patients, particularly when sustained viral response (SVR) is obtained. In summary, the two key approaches to prevent development of HCV-related HCC are primary prevention of HCV infection (adequate programs to screen donor blood, universal precautions to stop medical transmission of blood-borne viruses, curbing transmission by IDU) and potent antiviral therapy of chronic HCV infection. [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] Ribavirin dosage in patients with HCV genotypes 2 and 3 who completed short therapy with peg-interferon ,-2b and ribavirinALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2010A. MANGIA Aliment Pharmacol Ther,31, 1346,1353 Summary Background, The optimal dose of ribavirin to be used in combination with Peg-IFN in patients with HCV genotypes 2 and 3 undergoing short treatment has not been established. Aim, To explore the relationship between starting ribavirin doses, expressed as mg/kg body weight and both rapid viral response at treatment week 4 (RVR) and sustained virological response (SVR) in patients treated for 12,14 weeks with peg-interferon ,-2b and ribavirin. Methods, A post hoc analysis of data collected from two multicenter clinical trials was performed. Multiple regression analyses were employed to identify independent baseline and on-treatment predictors of RVR and SVR. For each dose of ribavirin, the empirical estimated probability of response was computed and the continuous exposure index was dichotomized by using a recursive partitioning and amalgamation method. Results, A nonlinear relationship was ascertained between ribavirin dose and RVR, but not SVR. A dose of 15.2 mg/kg was selected as the best splitting value for discriminating RVR vs. non-RVR. Regression analysis identified low baseline viraemia, genotype 2 and high ribavirin dose as independent prognostic factors for RVR. The likelihood of an SVR was not correlated with baseline ribavirin dose, but was independently predicted by adherence to the full dose throughout treatment and normal platelet counts. Conclusions, Starting high ribavirin doses appears capable of increasing the rate of RVR in patients with HCV genotypes 2 and 3 undergoing short treatment. Maintenance of the full planned dose throughout treatment is essential for achieving optimal SVR rates. [source] Factors influencing long-term changes in mental health after interferon-alpha treatment of chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009F. SCHMIDT Summary Background, Antiviral treatment with interferon-alpha (IFN-,) is associated with several acute psychiatric side effects. Little is known about long-term effects on mental health after treatment independent from viral response and the influence of pre-existing psychiatric risk-factors. Aim, To evaluate long-term effects of antiviral treatment with interferon-alpha (IFN-,) on mental health in patients with psychiatric risk factors. Method, We prospectively investigated long-term mental health changes in 81 hepatitis C virus-infected patients. Psychiatric outcome was measured with the Montgomery,Asberg Depression Scale (MADRS), Brief Psychiatric Rating Scale, the Global Social Functioning Scale and the Global Clinical Impression Scale 6 months after the end of antiviral treatment with IFN-, and ribavirin. Results, Six months after antiviral therapy, 49% of the patients showed a worsening and 27.2% an improvement of depression scores. The most important predictor for a long-term improvement of depression scores was a pre-treatment MADRS score ,5 (OR 14.21, 95% CI: 2.51,81.30). Patients with pre-existing psychiatric disorders (OR = 0.117, 95% CI: 0.024,0.558), methadone substitution (OR = 0.20, 95% CI: 0.045,0.887) or genotype 2/3 (OR = 0.341, 95% CI: 0.138,0.845) were significantly less likely to show a long-term worsening of depressive symptoms. Conclusions, Pre-existing psychiatric risk factors increase the chance for a long-term improvement and reduce the risk for a long-term worsening of mental health after antiviral treatment of chronic hepatitis C with IFN-,. [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] Natural course of treated and untreated chronic HCV infection: results of the nationwide Hepnet.Greece cohort studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009E. K. MANESIS Summary Background, Interferon (IFN-,)-based regimens have been used with varying success in the treatment of chronic hepatitis C (CHC) for over two decades. The effect of such treatments on the natural course of CHC has been evaluated in small clinical trials with conflicting results. Aim, To investigate the natural course of IFN,-based -treated and untreated patients with CHC by analysing data from the HEPNET.GREECE study. Methods, We retrospectively analysed 1738 patients from 25 Greek Centres (median age 40.1; males 57.6%; cirrhosis 9.2%), 734 untreated and 993 treated with IFN,-based regimens [44.7% sustained viral response (SVR)], followed-up for median 25.2 and 46.8 months, respectively. Results During follow-up, 48 patients developed liver decompensation and 24 HCC. Older age was significantly related to disease progression (HR = 2.6 per 10 years of increasing age). Stratified by baseline cirrhosis, Cox analysis showed that patients with SVR, but not without SVR, had significantly lower hazard for events compared with nontreated patients (HR = 0.16; P < 0.001), whereas the detrimental effect of older age remained highly significant. Separate group analysis demonstrated that in cirrhosis, the beneficial effect of treatment was evident even without SVR. Treatment effect interacted significantly with age, indicating that older patients, mainly noncirrhotic, gained the most benefit. Conclusions IFN,-based treatment does alter the natural course of CHC. A protective effect is mostly present in patients with SVR, but older patients, at higher risk of events, gain the greatest benefit. In established cirrhosis, treatment carries a protective effect even among those without SVR. [source] Treatment of chronic hepatitis C in polytransfused thalassaemic patients: a meta-analysisJOURNAL OF VIRAL HEPATITIS, Issue 4 2010S.-M. Alavian Summary., Hepatitis C virus (HCV) infection is a major cause of liver-related morbidity and mortality among thalassaemic patients. In order to analyse the effect of the current anti-HCV treatment in this subset of HCV-infected patients, we conducted a systematic review with meta-analysis of the available literature. The outcome was sustained viral response. Both comparative [odds ratio (OR)] and non-comparative indeces (success rate) were used to run the meta-analytical procedure. Data encompassing 429 thalassaemic HCV-infected patients treated with conventional or pegylated interferon monotherapy or combination therapy with ribavirin were collected from 13 articles (10 prospective cohort studies, 1 randomized-controlled trial and 2 controlled trials). Pooled sustained viralogical response (SVR) was 44.7% (34.6,54.9). Pooled ORs of SVR for Genotype 1 vs non-Genotype 1 infected thalassaemic patients were 0.46 (95% CI: 0.22,0.95) in IFN monotherapy and 1.7 (95% CI: 0.46,6.04) in ribavirin combination therapy. Our meta-analysis shows that thalassaemic patients with Genotype 1 infection significantly benefit from the addition of ribavirin to their therapeutic regimen. It seems that using ribavirin in thalassaemic patients increases transfusion need by a median of 30,40%, but does not increase major adverse events or treatment withdrawal. Current literature is lacking sufficient evidence about the use of PEG-IFN as monotherapy or in combination with ribavirin in thalassaemic patients. [source] Modulation of the anti-inflammatory interleukin 10 and of proapoptotic IL-18 in patients with chronic hepatitis C treated with interferon alpha and ribavirinJOURNAL OF VIRAL HEPATITIS, Issue 4 2006E. Marín-Serrano Summary., The aim of this work was to analyse apoptosis rate, measured by the serum levels of proapoptotic interleukin (IL)-18 and of soluble Fas (sFas), as well as of anti-inflammatory IL-10, in patients with chronic hepatitis C, at baseline and after treatment with interferon alpha and ribavirin. Twenty-seven patients with biopsy-proven chronic hepatitis C were studied, at baseline and after treatment with interferon alpha (21 cases) or pegylated interferon (6 cases) plus ribavirin. A group of 15 healthy sex- and age-matched individuals was selected as control. Serum concentrations of sFas, IL-10 and IL-18 were determined by ELISA in sandwich. The relationship of these molecules to necro-inflammatory and fibrotic activity was evaluated. Evolution of the serum concentrations of these molecules was analysed after treatment. Significantly increased serum concentrations of sFas were detected in patients with chronic hepatitis, compared with controls. Levels of this molecule were significantly correlated with necroinflammatory activity. Likewise, concentrations of IL-10 were significantly increased in the group of patients, compared with controls. Treatment with interferon and ribavirin induced a significant decrease of IL-18 concentration independently of the viral response. In contrast, levels of sFas decreased only in those patients with sustained response to therapy. Finally, baseline levels of IL-10 were significantly increased in patients without response to treatment, compared with those with sustained response, but the concentration did not change with the treatment. Increased serum levels of IL-10 are a negative prognostic marker of response to hepatitis C treatment. A significant decrease of apoptotic rate, as determined by sFas, can be expected in patients with a response to therapy. [source] Serum concentrations of ribavirin and pegylated interferon and viral responses in patients infected with HIV and HCVJOURNAL OF MEDICAL VIROLOGY, Issue 9 2008Florence Nicot Abstract The hepatitis C virus (HCV) infects a substantial proportion of patients infected with human immunodeficiency virus (HIV). Patients infected with both HCV and HIV respond poorly to anti-HCV treatment with pegylated interferon alpha and ribavirin. But few data are available on the influence of ribavirin and interferon concentrations on treatment outcome for these patients. This study investigated the relationship between the serum pegylated interferon and ribavirin concentrations 3 and 6 months after treatment initiation, and treatment outcome in 35 HCV-HIV coinfected patients. The pegylated interferon and ribavirin concentrations at months 3 and 6 were similar. The pegylated interferon concentrations at 3 months in responders and nonresponders were similar. However, responders tended to have higher ribavirin concentrations (2,322 ng/ml) than nonresponders (1,833 ng/ml; P,=,0.08). Responders infected with HCV genotype 1 or 4 had higher ribavirin concentrations (2,672 ng/ml) than did similarly infected nonresponders (1,758 ng/ml; P,=,0.04). ROC curve analysis showed that a ribavirin concentration of 2,300 ng/ml was the best threshold for predicting a nonresponse (ROC area,=,0.80,±,0.12). Thus ribavirin concentrations influence treatment outcome in HIV patients infected with HCV genotype 1 or 4. Monitoring ribavirin concentrations could help adapt ribavirin concentrations and improve the sustained virological response. J. Med. Virol. 80:1523,1529, 2008. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||