Virological Response In Hepatitis Research Articles

Achieving sustained virologic response in hepatitis C: a systematic review of the clinical, economic and quality of life benefits.

BackgroundThe goal of chronic hepatitis C treatment is to remove the virus to avoid progression of HCV-related disease. Sustained virologic response (SVR) is the most widely used efficacy endpoint in clinical studies of hepatitis C, and represents the eradication of HCV from the body. The aim of the current review was to examine the long-term clinical, economic and quality of life benefits associated with achieving SVR.MethodsA systematic literature review was performed using the PubMed, EMBASE and Cochrane library databases to identify articles examining the clinical, economic and quality of life benefits associated with SVR, published in English language from 2002–2013. For inclusion studies were required to enroll ≥100 patients and to report clinical endpoints including hepatocellular carcinoma, overall- or liver-related mortality, or progression of disease/complications (e.g. portal hypertension, esophageal varices). Review of economic studies on cost/cost-effectiveness of achieving SVR were focused on studies assessing boceprevir/telaprevir plus pegIFN and ribavirin as this represents the current standard of care in several jurisdictions worldwide. Quality of life evidence was required to use validated quality of life instruments and provide a quantitative analysis of the impact of SVR versus no treatment or treatment failure.ResultsSVR is durable with late relapse rates over 4–5 year periods being in the range of 1–2%. Patients who achieve SVR frequently demonstrate some regression of fibrosis/cirrhosis and have a substantially reduced risk for hepatocellular carcinoma (relative risk [RR] 0.1–0.25), liver-related mortality (RR 0.03–0.2) and overall mortality (RR 0.1–0.3) in comparison with no treatment or treatment failure. In the 5 years post-treatment, medical costs for patients achieving SVR are 13-fold lower than patients not achieving SVR. Patients who achieve SVR also have health state utility values that are 0.05 to 0.31 higher than non-responders to treatment.ConclusionsSVR represents the fundamental goal of antiviral treatment for patients infected with chronic HCV, so as to reduce risk of liver disease progression. Achievement of SVR has implications beyond those of clearing viral infection; it is associated with improved long-term clinical outcomes, economic benefits and improved health-related quality of life.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0748-8) contains supplementary material, which is available to authorized users.

The Importance of Occult Hepatitis B Infection Screening in Pre-Transplant Evaluation

Implication for health policy/practice/research/medical education: This paper argues the importance of occult hepatitis B infection screening in pre-transplant evaluation. It is applicable for those in the field of organ transplantation. Copyright © 2014, NewPub; Published by Kowsar Corp. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Occult hepatitis B virus infection (OHB) is defined based on the existence of hepatitis B virus (HBV) DNA in liver tissue or serum of the patients, in spite of negative antibody test result for hepatitis B surface antigen (1). Most of these patients have positive hepatitis B core antibody (HBc Ab) test result as the evidence of past HBV infection. Ramezani et al. recommended the evaluation of HBc Ab in hemodialysis patients for detection of OHB (2). There might be low titer of HBc Ab in minority of OHB patients due to immunosuppression. In the other word, all serological Ab panels for HBV might be negative in OHB setting. Searching for HBV DNA in serum is promising for determination of OHB in the immune deficiency state. However, this method could not be recommended in the routine screening due to its high expense. Therefore, defining the best diagnostic strategy for detection of OHB seems to be challenging in particular subgroups of patients. Although the precise clinical manifestations and pathogenesis of OHB are not clear, it is considered as a probable source of HBV infection via blood transfusion, hemodialysis, and organ transplantation. Reactivation of OHB in the post-transplantation phase could be fatal. It is wise to improve the yield of diagnostic tool for OHB screening in the pre-transplant phase to lower the liver-related morbidity and mortality in the transplant candidates. The important issues on OHB are the aggravation of chronic liver damage and concomitant fibrosis (3). Some studies showed that this condition causes progression of cirrhosis and development of hepatocellular carcinoma in chronic liver disease (4) OHB lowers the virologic response in hepatitis C infection (5) Song et al. declared that HBV transmission could occur via transfusion, hemodialysis, and organ transplantation (1). Considering the possibility of HBV reactivation, they suggested the screening of OBI in the post-transplantation phase. Furthermore, they mentioned the need for antiviral therapy in HBsAg-negative transplanted patients who are anti-HBc positive, to prevent the reactivation of HBV infection. HBV recurrence has occurred even two years after discontinuation of the immunosuppression (6). Fontenele et al. issued the role of OHB screening in hemodialysis patients to prevent the transmission of HBV and the consequent liver cell damage (7). Based on the current evidence, it seems reasonable to screen for OHB in the pre-transplantation phase and follow the patient carefully for early detection of OHB relapse. HBc Ab test is a practical screening method for OHB and is a surrogate marker of previous HBV infection in the immune competent patients. HBV DNA assay is an accepted alternative for OHB screening in the immunosuppressed individuals whose HBc Ab is in a low detectable titer.

End treatment response and sustained viral response in hepatitis C virus genotype 3 among Pakistani population

BACKGROUND AND OBJECTIVESThis study aimed to determine the end treatment response (ETR) and sustained viral response (SVR) to interferon (IFN) and ribavirin in hepatitis C virus (HCV) genotype 3 in the Pakistani population.DESIGN AND SETTINGSThis is an interventional study conducted from January 2010 to December 2012 in Lyari General Hospital and Abbasi Shaheed Hospital, Karachi, outpatients department.METHODSAll patients with chronic hepatitis C genotype 3 infections were included. Patients with decompensated chronic liver disease, or having coexisting hepatitis B virus/human immunodeficiency virus were excluded. All patients received IFN alpha, 3 million international units (MIU), subcutaneously 3 times weekly and ribavirin >800 mg/d for a period of 6 months. Outcome parameters included ETR (negative polymerase chain reaction [PCR] at the end of therapy), SVR (negative PCR both at the end of treatment and 6 months later), and relapse (PCR negative at the end of treatment but positive 6 months later) were determined.RESULTSA total of 1170 patients were included with a female to male ratio of 1.64:1 and a mean age of 31.6 (8.4) years. Among 1170 patients, 985 completed the therapy as per the protocol, 119 were defaulted (treatment abandoned before completion), and 66 had to stop treatment due to side effects. ETR was 74.1%, SVR was 98%, relapse rate was 1.5%, and 10.1% were nonresponders. SVR was seen only in patients who had achieved an ETR (n=867). SVR was achieved in 848 patients (out of 867) (98%), relapse was seen in 13 (1.5%), and 6 (0.7%) patients lost follow-up after stopping treatment. Patients achieving ETR and SVR had a mean serum alanine aminotransferase of 71.3 (57.1) and 71.0 (56.5), respectively, which is approximately twice the upper normal limit.CONCLUSIONThe conventional IFN and ribavirin therapy in genotype 3 chronic HCV-infected patients gives an ETR and SVR of 74.1% and 98%, respectively.

Insulin resistance, telaprevir, and virological response in hepatitis C: The debate must go on

Insulin resistance, telaprevir, and virological response in hepatitis C: The debate must go on

Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance in HIV‐/HBV‐coinfected patients

The aim of this retrospective study was the identification of clinically useful viral determinants for the prediction of hepatitis B surface antigen (HBsAg) seroclearance and sustained virological response in hepatitis B virus/human immunodeficiency virus (HBV-/HIV)-coinfected patients receiving HBV-active combined antiretroviral therapy (cART). Quantification of HBsAg, HBeAg and HBV DNA before and after initiation of HBV-active cART in a cohort of 59 HIV-/HBV-coinfected patients was performed. Calculations of receiver operating characteristics (ROC) and Kaplan-Meier analysis were used for the identification of predictors of HBsAg seroclearance for HBeAg-positive [HBeAg(+); n = 36] and HBeAg-negative [HBeAg(-);n = 23] patients. HBeAg(+) patients with an HBsAg on-treatment decline ≥ 1 log IU/mL per year achieved higher HBsAg loss rates (P = 0.0294), whereas the quantification of HBeAg had no predictive value for HBsAg seroclearance. Among HBeAg(-) patients, a pretreatment baseline cut-off level of HBsAg ≤ 100 IU/mL was highly predictive for HBsAg seroclearance. No significant influence of the HBV genotype on HBsAg seroclearance was observed among the entire cohort. Quantitative determination of HBsAg provides a clinically useful viral parameter for the prediction of HBsAg seroclearance both in HBeAg(+) and HBeAg(-) HIV-/HBV-coinfected patients receiving HBV-active cART.

Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis

Background/aimsControversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. MethodsSystematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. ResultsThirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59–3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59–12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. ConclusionThis meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype.

Polypharmacy and Comorbidity Are Associated with a Lower Early Virologic Response in Hepatitis C Patients Treated with First Generation Protease Inhibitor Triple Therapy: A Preliminary Analysis

The protease inhibitors (PIs) boceprevir and telaprevir are currently standard treatment as part of triple therapy regimens (TTx) for chronic HCV genotype 1 (GT1) patients. In this preliminary analysis, we have compared demographic variables, polypharmacy, and Charlson's comorbid index (CCI) with Rapid Virological Response (RVR) and extended RVR (eRVR) rates in HCV GT1 patients receiving PI containing TTx. Retrospective descriptive cohort study. Among 74 HCV patients (46 M, 28 F; age: 54.43 ± 9.52 years; African Americans: 59.5 %) in this initial analysis, 44 % achieved RVR. All these RVR patients also achieved eRVR. Patients achieving RVR and eRVR were 50 ± 11.7 (mean ± SD) years old, compared to 58 ± 5.2 years without an RVR (p < 0.005). The average number of medications taken by patients achieving RVR and eRVR was 5 ± 2.7 compared to 9.24 ± 3.4 in patients not achieving RVR and eRVR (p < 0.005). Twenty-five percent of patients who were not on CYP3A4 inhibitors had an RVR and eRVR compared to 63.2 % who were taking CYP3A4 inhibitors (p = 0.001). Patients achieving RVR and eRVR had a lower CCI (1.61 ± 1.37) compared to those not achieving RVR and eRVR (2.8 ± 2.7; p = 0.02). Multivariate analysis also revealed a significant correlation between increased polypharmacy and CCI with lower RVR and eRVR rates. These preliminary treatment data demonstrate that increased polypharmacy and higher degrees of comorbidity decrease RVR and eRVR rates among patients receiving first generation PI-containing TTx regimens.

Closing in on the Target: Sustained Virologic Response in Hepatitis C Virus Genotype 1 Infection Response-Guided Therapy

Retrospective analyses of the boceprevir and telaprevir phase 3 trial data demonstrate the clinical relevance of detected but not quantifiable hepatitis C virus (HCV) genotype 1 RNA during treatment. These analyses illustrate the importance of using precise and standard terminology in reporting low-level HCV RNA results for consistent data collection across clinical trials, and to ensure optimal virologic response-guided treatment decision making in clinical practice. In the context of currently available quantitative HCV RNA assays, we clarify that unquantifiable HCV RNA should be classified as target detected or target not detected, as both have been shown to reflect clinically different qualitative HCV RNA levels during treatment. Additionally, use of terms such as "undetectable" or "below limit of detection" should be avoided as such terms are imprecise, not consistently defined, and often misinterpreted.

Antidepressant Prophylaxis Reduces Depression Risk but Does Not Improve Sustained Virological Response in Hepatitis C Patients Receiving Interferon Without Depression at Baseline: A Systematic Review and Meta-Analysis

Depression complicates interferon-based hepatitis C virus (HCV) antiviral therapy in 10% to 40% of cases, and diminishes patient well-being and ability to complete a full course of therapy. As a consequence, the likelihood of achieving a sustained virological response (SVR [ie, permanent viral eradication]) is reduced. To systematically review the evidence of whether pre-emptive antidepressant prophylaxis started before HCV antiviral initiation is beneficial. Inclusion was restricted to randomized controlled trials in which prophylactic antidepressant therapy was started at least two weeks before the initiation of HCV antiviral treatment. Studies pertaining to patients with active or recent depressive symptoms before commencing HCV antiviral therapy were excluded. English language articles from 1946 to July 2012 were included. The MEDLINE, Embase and Cochrane Central databases were searched. Where possible, meta-analyses were conducted evaluating the effect of antidepressant prophylaxis on SVR and major depression as well as on Montgomery-Asberg Depression Rating Scale and Beck Depression Index scores at four, 12 and 24 weeks. The Cochrane Collaboration tool was used to assess bias risk. Six randomized clinical trials involving 522 patients met the inclusion criteria. Although the frequency of on-treatment clinical depression was decreased with antidepressant prophylaxis (risk ratio 0.60 [95% CI 0.38 to 0.93]; P=0.02; I2=24%), no benefit to SVR was identified (risk ratio 1.08 [95% CI 0.74 to 1.57]; P=0.69; I2=58%). This practice is not justified to improve SVR in populations free of active depressive symptoms leading up to HCV antiviral therapy.

Platelet count and sustained virological response in hepatitis C treatment

To examine the epidemiological data, hematological safety and treatment responses of peginterferon-alpha 2a plus ribavirin therapy for hepatitis C. Between March 2008 and February 2011, 196 hepatitis C virus (HCV) genotype 1 infected Japanese (127 treatment-naive and 69 treatment-experienced patients) patients treated with peginterferon-alpha 2a plus ribavirin were enrolled. We examined the epidemiological data and treatment responses were retrospectively analyzed in terms of hematological safety. HCV RNA was measured by the COBAS TaqMan HCV test. Overall sustained virological response (SVR) rates of treatment-naive and treatment-experienced patients were 56% and 39%, respectively. Multivariate logistic regression analysis showed that SVR was attained independently of early virological response in both treatment-naive and treatment-experienced patients. SVR rates did not differ between the pretreatment hemoglobin < 13 g/dL and ≥ 13 g/dL groups. However, in treatment-naive patients, the SVR rate of the pretreatment platelet count < 130000/µL group was significantly lower than that of the pretreatment platelet count ≥ 130000/µL group. Attention should be paid to potential thrombocytopenia in the treatment of chronic hepatitis C patients.

A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis

Although annular fibrosis is the hallmark of cirrhosis, other microscopic changes that affect liver function such as sinusoid capillarization or loss of metabolic zonation are common. A sustained virological response (SVR) may halt fibrosis deposition in hepatitis C virus (HCV)-infected patients, but its impact on the other cirrhosis-associated lesions is unknown. The aim of this study was to assess the impact of an SVR on cirrhosis-related histopathological features. Paired pre- and posttreatment liver biopsies from 38 HCV patients with cirrhosis with an SVR were analyzed. Fibrosis was staged using the METAVIR scoring system, and the area of fibrosis was measured using morphometry. Ductular proliferation, metabolic zonation, sinusoid capillarization, and hepatic stellate cell activation were assessed by anti-cytokeratin-7, anti-glutamine synthetase (GS), anti-cytochrome P4502E1 (CYP2E1), anti-CD34, and anti α-smooth muscle actin (αSMA). After 61 months from an SVR, cirrhosis regression was observed in 61%, and the collagen content decreased in 89%. Although periportal and lobular necroinflammation vanished, portal inflammation persisted in 66%. Ductular proliferation decreased in 92%. Before treatment, metabolic zonation was lost, as shown by GS and CYP2E1, in 71% and 88%, respectively, with normalization in 79% and 73%, after an SVR. Conversely, no changes in sinusoidal capillarization were observed after treatment, as assessed by CD34 (P = 0.41) and αSMA (P = 0.95). Finally, no differences in all the immunohistochemical scores emerged whether or not cirrhosis persisted. Cirrhosis regression and decreased fibrosis are frequently observed among HCV patients with cirrhosis with an SVR. Despite ductular proliferation vanishing and lobular zonation restoration, portal inflammation and sinusoidal capillarization may not regress after viral eradication.

Do HIV/HCV co-infected patients need haematopoietic growth factors earlier than non-co-infected during HCV treatment?

BackgroundHepatitis C treatment (HCVt) with peg-interferon and ribavirin is limited by haematological side-effects. Haematopoietic growth factors (HGF) allow to maintain standard antiviral doses in order to achieve sustained virological response...

Implications of rapid virological response in hepatitis C therapy in the US veteran population

Early predictors of response to hepatitis C virus (HCV) therapy, such as rapid virological response, are valuable for the identification of patients with a higher likelihood of treatment success. To identify predictors of rapid virological response in a real world setting. Using the VA Clinical Case Registry, we identified patients with HCV mono-infection, without liver transplantation, who initiated peginterferon (PEG-IFN) and ribavirin (RBV) in 2007 or 2008 and had HCV RNA testing for RVR. Significant baseline characteristics from genotype specific univariate analyses were used in backwards stepwise models to identify significant independent predictors of RVR. The final cohort consisted of 2424 patients with genotype 1 (G1), 666 patients with genotype 2 (G2), and 419 patients with genotype 3 (G3). Rapid virological response rates were 15% for G1, 71% for G2 and 57% for G3. Sustained virological response rates were significantly higher in patients with rapid virological response than without, increasing from 18% to 52% in G1, 39% to 71% in G2, and 40% to 60% in G3 (P < 0.0001). A baseline HCV RNA < 500,000 IU/mL positively predicted RVR across all genotypes studied. In addition, for G1, Black race, Hispanic ethnicity, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≥ 0.6, ferritin ≥ 350 ng/mL, LDL< 100 mg/dL and diabetes; for G2, BMI ≥ 30 kg/m(2), platelets < 150 K/μL, LDL< 100 mg/dL and the use of PEG-IFN alfa-2b; and for G3, AST/ALT ≥ 1.0, all negatively predicted rapid virological response. We found several novel independent predictors of rapid virological response, including BMI, AST/ALT ratio, ferritin, platelets, LDL, diabetes and type of PEG-IFN prescribed, which may be useful in guiding treatment decisions in routine medical practice.

Meta‐analysis: insulin resistance and sustained virological response in hepatitis C

A higher baseline homeostasis model assessment of insulin resistance (HOMA-IR) score has sometimes predicted a poorer sustained virological response (SVR) rate to peginterferon/ribavirin therapy in treatment-naïve chronic hepatitis C patients. To perform a meta-analysis to evaluate the impact of HOMA-IR on SVR in hepatitis C. Relevant studies were identified by searching Medline and EMBASE. We identified 17 publications that addressed the influence of insulin resistance on SVR. The random effect model of Der Simonian and Laird method were used for heterogeneous studies using the Meta-Disc software 1.4, Madrid, Spain. Normal insulin sensitivity was associated with a higher rate of SVR [odds ratio (OR) 2.86 (95%CI: 1.97-4.16)] in comparison with insulin resistance. Moreover, in separate analysis by genotype selecting studies that used HOMA-IR > 2 as cut-off defining insulin resistance, SVR was higher in patients with HOMA-IR < 2 in all genotypes: HCV-1 [OR: 2.16 (95%CI: 1.51-3.08)], HCV-2&3 [OR: 3.06 (95%CI: 1.06-8.82)] and HCV-4 [OR: 6.65(95%CI: 2.51-17.61)]. Studies reporting no association between HOMA and SVR included easy-to-cure cohorts, analysed variables strongly related with insulin resistance like body mass index, steatosis, hyper γGT, age and fibrosis and reported differences in handling and interpretation of HOMA-IR. Elevated HOMA-IR was associated with a lower cure rate of patients with hepatitis C treated with Peg-IFN-α/ribavirin irrespective of genotype, and the more difficult-to-treat cohort, the better the HOMA-IR prediction. HOMA-IR is, as a surrogate marker of insulin resistance, susceptible to some biases derived from both handling and interpretation.

Telaprevir: Looking for a sustained virologic response in hepatitis C virus infection

Telaprevir, a hepatitis C virus (HCV) NS3/NS4A protease inhibitor, was recently approved by the U.S. Food and Drug Administration for the treatment of chronic HCV genotype 1 infection. When given in combination with pegylated interferon and ribavirin, it demonstrated improved efficacy over conventional pegylated interferon and ribavirin therapy. Improvement in efficacy was also noted in African American patients who traditionally respond less well to conventional anti-HCV treatment. While the role of telaprevir in the management of chronic HCV infection remains to be fully defined, its development and licensure represents an important milestone in anti-HCV therapeutics.

Insulin resistance and sustained virological response in hepatitis C: from bench to bedside

Insulin resistance and sustained virological response in hepatitis C: from bench to bedside

Secondary structure of the amino‐terminal region of HCV NS3 and virological response to pegylated interferon plus ribavirin therapy for chronic hepatitis C

The aim of the study was to identify a predictive marker for the virological response in hepatitis C virus 1b (HCV-1b)-infected patients treated with pegylated interferon plus ribavirin therapy. A total of 139 patients with chronic hepatitis C who received therapy for 48 weeks were enrolled. The secondary structure of the 120 residues of the amino-terminal HCV-1b non-structural region 3 (NS3) deduced from the amino acid sequence was classified into two major groups: A and B. The association between HCV NS3 protein polymorphism and virological response was analyzed in patients infected with group A (n = 28) and B (n = 40) isolates who had good adherence to both pegylated interferon and ribavirin administration (>95% of the scheduled dosage) for 48 weeks. A sustained virological response (SVR) representing successful HCV eradication occurred in 33 (49%) in the 68 patients. Of the 28 patients infected with the group A isolate, 18 (64%) were SVR, whereas of the 40 patients infected with the group B isolate only 15 (38%) were SVR. The proportion of virological responses differed significantly between the two groups (P < 0.05). These results suggest that polymorphism in the secondary structure of the HCV-1b NS3 amino-terminal region influences the virological response to pegylated interferon plus ribavirin therapy, and that virus grouping based on this polymorphism can contribute to prediction of the outcome of this therapy.

Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing

The impact of fibrosis stage on chronic hepatitis C virus (HCV) treatment response was explored in CHARIOT, a study of high dose peginterferon alfa-2a (PEG-IFNalpha-2a) induction therapy in treatment naïve genotype 1 infection. Eight hundred and ninety-six patients were randomised 1:1 to 360 microg (n=448) or 180 microg (n=448) PEG-IFNalpha-2a weekly with RBV 1000-1200 mg/day for 12 weeks followed by 36 weeks of 180 microg PEG-IFNalpha-2a weekly plus RBV 1000-1200 mg/day. Virological responses were assessed at week 4, 8, 12, 24, 48 (end of therapy), and 24 weeks following therapy (sustained virological response, SVR). As previously reported, there was no significant difference in SVR in the induction (53%) and standard (50%) arms, therefore the pooled study population was used for analysis of SVR and relapse. A marked step-wise decline in SVR was evident by fibrosis stage: F0 (70%); F1 (60%); F2 (51%); F3 (31%); F4 (10%) (p<0.0001). Early virological responses were lower among F3/4 patients, including rapid virological response (RVR) (21% vs. 34% for F3/4 and F0-2, respectively) (p=0.0072), and the RVR positive predictive value was also lower (63% vs. 80%). Virological relapse rates were similar in early disease stages (F0, 16%; F1, 23%; F2, 26%), but increased markedly in advanced fibrosis (F3, 50%; F4, 80%) (p<0.0001). Cumulative PEG-IFNalpha-2a and ribavirin doses were similar among patients with F3/4 and F0-2 within treatment arms through week 4, 8, 12, and week 24. Low virological response in hepatitis C genotype 1 patients with advanced fibrosis is not explained by inadequate cumulative PEG-IFN and ribavirin doses.

High rates of sustained virological response in hepatitis C virus-infected injection drug users receiving directly observed therapy with peginterferon alpha-2a (40KD) (PEGASYS) and once-daily ribavirin

This retrospective study evaluated the efficacy and tolerability of directly observed therapy with peginterferon alfa-2a and once-daily ribavirin (RBV) for chronic hepatitis C in 49 opioid-addicted injection drug users (IDUs) participating in a drug treatment program at a specialized outpatient center. Patients also received prophylactic citalopram to minimize the risk of interferon-induced depression. Patients had daily access to and support from specialist physicians, nurses and counseling services at the center, and a 24-hour helpline. Sustained virological response was achieved by 48 of 49 patients (98%) overall, including 20 of 21 (95%) hepatitis C virus (HCV) Genotype 1/4-infected patients and 28 of 28 (100%) Genotype 2/3-infected patients. Treatment was well tolerated, and no unexpected side effects of peginterferon treatment were seen. The safety profile of once-daily RBV was not different from twice-daily dosing. Decline in hemoglobin levels was similar to those reported in clinical trials including once-daily RBV and did not lead to dose reduction or treatment withdrawal. Our data demonstrate that HCV-infected IDUs on stable L-polamidone (methadone) or buprenorphine maintenance can be successfully and safely treated with peginterferon alfa-2a and RBV in an optimal substitution setting.

Predictive value of virological response on sustained virological response in hepatitis C patients

慢性HCV感染极易发展成肝硬化和肝癌,抗病毒治疗是惟一有可能延缓或阻止其进程的有效方法.目前最理想的抗病毒治疗方案为聚乙二醇干扰素(PEG-IFN)联介利巴韦林.获得持续病毒学应答(SVR)是评价其疗效的主婴指标,但多种宿主因索和病毒因素都可能影响其疗效.近年来有研究者认为治疗过程中病毒的应答情况能够综合反应这些因素的影响,可更好地预测其治疗效果~([1-2]).为了解不同基因型HCV感染者在抗病毒治疗过程中的病毒学应答情况对SVR的预测价值,为对不同基因型HCV感染者制定更加合理的个体化治疗方案提供参考,本研究对近年来在本院接受PEG-IFN联合利巴韦林治疗的慢性HCV感染者的相关资料做了回顾性分析。