Is pegylated interferon superior to interferon, with ribavarin, in chronic hepatitis C genotypes 2/3？

Over the past decade, significant improvements have been made in the treatment of chronic hepatitis C （CHC）, especially with the introduction of combined therapy using both interferon and ribavarin. The optimal dose and duration of treatment is still a matter of debate and, importantly, the efficacy of this combined treatment varies with the viral genotype responsible for infection. In general, patients infected with viral genotypes 2 or 3 more readily achieve a sustained viral response than those infected with viral genotype 1. The introduction of a pegylated version of interferon in the past decade has produced better clinical outcomes in patients infected with viral genotype 1. However, the published literature shows no improvement in clinical outcomes in patients infected with viral genotypes 2 or 3 when they are treated with pegylated interferon as opposed to nonpegylated interferon, both given in combination with ribavarin. This is significant because the cost of a 24-wk treatment with pegylated interferon in lessdeveloped countries is between six and 30 times greater than that of treatment with interferon. Thus, clinicians need to carefully consider the cost-versusbenefit of using pegylated interferon to treat CHC, particularly when there is no evidence for clinically measurable benefits in patients with genotypes 2 and 3 infections.     

ERCP wire systems： The long and the short of it

Guidewires are routinely used at the time of endoscopic retrograde cholangiopancreatography （ERCP） to gain and maintain access to the desired duct and aid in the advancement of various devices. Limitations of the traditional long-wire systems have led to the introduction of three proprietary short-wire systems. These systems differ in many respects but share two main principles： They lock a shorter wire in position to allow advancement or removal of various devices without displacement of the wire and they all allow for physician control of the wire. In this comprehensive review, we describe the key features of the three currently available short-wire systems： RX, Fusion and V systems. We also focus on the potential benefits and drawbacks that accompany the short-wire concept as a whole and each specific system in particular. Although the available data are limited, it appears that the use of the short-wire systems lead to reduced procedure, fluoroscopy and device exchange times, decreased sedation requirements, improved wire stability and increased endoscopist control of the wire. Furthermore, the physician-controlled wire-guided cannulation has the potential to decrease ampullary trauma and the rate of post-ERCP pancreatitis. The short guidewire systems appear to be an improvement over the traditional long-wire systems but further studies directly comparing the two approaches are needed.     

Is interferon-beta an alternative treatment for chronic hepatitis C？

The treatment of chronic hepatitis C (CMC) is still far from optimal, particularly for those subpopulations that do not respond to the standard combination therapy with Interferon-α(IFNα) plus ribavirin. Although in some cases the use of higher doses or longer treatment periods may be effective, these approaches are generally associated with a higher incidence of adverse events, which may either lead to a reduction in patient compliance or require drug withdrawal. IFNβcould represent an interesting alternative for treating CMC patients. Controversial data about IFNp efficacy in CMC exist, the main reason being that many results stem from pilot studies with small cohorts of patients. However, promising results have been obtained in some subgroups of patients that fail to respond to IFNa. Additionally, the good tolerability of IFNβrepresents an important advantage of the drug. The rates of dropouts in controlled clinical trials, as well as the need for dose reductions or treatment discontinuation are very low. It might be worth assessing the value of IFNβplus ribavirin in randomized studies with a larger cohort of patients, not eligible or not tolerating standard therapy, and for non-responders.     

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2： A project of the Kyushu University Liver Disease Study Group

AIM: To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus (HCV) of genotype 2, a multi-center study was retrospectively analyzed. METHODS: In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS: The overall sustained virological response (SVR), defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, (146/173) by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin (46.9% vs 92.9%), but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment (34.8% vs 92.0%). CONCLUSION: The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16 weeks.     

Psychological impact of chronic hepatitis C： Comparison with other stressful life events and chronic diseases

AIM: To examine the psychological impact of chronic hepatitis C (CHC) diagnosis in a large cohort of CHC patients as compared with other stressful life events and chronic diseases carrying a risk of life-threatening complications. METHODS: One hundred and eighty-five outpatients with compensated CHC were asked to self-grade, using a 100-mm visual analogue scale (VAS), the degree of stress caused by the learning of CHC diagnosis and the perceived severity of their disease. Diagnosis-related stress was compared to four other stressful life events and perceived CHC severity was compared to four other common chronic diseases. RESULTS: Learning of CHC diagnosis was considered a major stressful event (mean±SD scores: 72±25), significantly less than death of a loved-one (89±13, P< 0.0001) and divorce (78±23, P< 0.007), but more than job dismissal (68±30, P<0.04) and home removal (26±24, P< 0.0001). CHC was considered a severe disease (74±19), after AIDS (94±08, P< 0.001) and cancer (91±11, P< 0.001), but before diabetes (66±23, P<0.001) and hypertension (62±20, P<0.001). Perceived CHC severity was not related to the actual severity of liver disease, assessed according to Metavir fibrosis score. In multivariate analysis, diagnosisrelated stress was related to perceived disease severity (P< 0.001), trait anxiety (P< 0.001) and infection through blood transfusion (P< 0.001). CONCLUSION: Our results show the considerable psychological and emotional burden that a diagnosis of CHC represents, even in the absence of significant liver disease. They should be taken into account when announcing a diagnosis of CHC in order to reduce its negative effects.     

Four-week pegylated interferon a-2a monotherapy for chronic hepatitis C with genotype 2 and low viral load：A pilot,randomized study

AIM：To assess the efficacy and advantages of 4-wk pegylated interferon a-2a（peg-IFN-a2a） monotherapy for chronic hepatitis C patients with strong predictors of sustained virologic response（SVR）.METHODS：Patients（n = 33） with genotype 2 and low viral load（〈 100 KIU/mL）,who became HCV RNA negative after 1 wk of IFN treatment,were randomly allocated to receive a 4-or 12-wk treatment course at a ratio of 2：1,respectively,with a subsequent 24-wk follow-up period.Peg-IFN-a2a was administered subcutaneously at a dose of 180 μg or 90 μg once weekly.SVR was defined as absence of serum HCV RNA at the end of the follow-up period.RESULTS：All patients completed the treatment schedule,and more than half were symptom-free during the treatment.In the 4-wk treatment group,20 of 22（91%） patients achieved SVR.Two patients relapsed,but achieved SVR following re-treatment with peg-IFN-a2a alone.In the 12-wk treatment group,11 of 11（100%） patients attained SVR.CONCLUSION：Our results show that a 4-wk course of peg-IFN-a2a monotherapy can achieve a high SVR rate in ＂IFN-sensitive＂ patients,without negatively affecting outcome.     

Herbal medicine Ninjinyoeito ameliorates ribavirin-induced anemia in chronic hepatitis C： A randomized controlled trial

AIM: Ribavirin (RBV) shows a strong antiviral effect on hepatitis C virus when used in combination with interferon. However, RBV-induced anemia is a major problem in this therapy. It would be of great clinical importance to ameliorate the anemia without reducing the RBV dose. We report here that, Ninjinyoeito (NYT), a herbal medicine can reduce the RBV-induced anemia. METHODS: Twenty-three patients with chronic hepatitis C were treated with interferon alpha 2b plus RBV with (NYT group) or without (control group) NYT by a randomized selection. Eighteen patients completed the treatment schedule, and hemato-biochemical and virological effects were evaluated. RESULTS: There was no significant difference in biochemical and virological responses between the two groups. However, anemia was significantly reduced in the NYT group compared with the control group. The maximal decrease of Hb in the NYT group (2.59±1.10 g/dL) was significantly (P= 0.026) smaller than that in the control group (3.71±0.97 g/dL). There was no significant difference in serum glutathione peroxidase activity, serum RBV concentration, and Thl/Th2 balance between the two groups. There was no specific adverse effect in NYT administration. CONCLUSION: These results suggest that NYT could be used as a supportive remedy to reduce the RBV-induced anemia in the treatment of chronic hepatitis C.     

Patient education improves adherence to peg-interferon and ribavirin in chronic genotype 2 or 3 hepatitis C virus infection： A prospective, real-life, observational study

AIM： To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response （SVR） in a real-life setting in genotype 2/3 hepatitis C, as there are few adherence data in genotype 2/3 infection, even from randomized trials. METHODS： This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin. There was no intervention. Adherence wasself-reported over the past 4 wk （peg-interferon） or 7 d （ribavirin）. Adherence to bitherapy was defined as adherence to the two drugs for ≥ 20 wk. SVR was defined as undetectable RNA ≥ 12 wk after the end of treatment. RESULTS： 370/674 patients received education during the first 3 mo of treatment. After 6 too, adherence to bitherapy was higher in educated patients （61% vs 47%, P = 0.01）. Adherence to peg-interferon was 78% vs 69% （P=0.06）. Adherence to ribavirin was 70% vs 56% （P = 0.006）. The SVR （77% vs 70%, P = 0.05） and relapse （10% vs 16%, P = 0.09） rates tended to be improved. After adjustment for baseline differences, education improved adherence [Odds ratio （OR） 1.58, P = 0.04] but not the SVR （OR 1.54, P = 0.06）. CONCLUSION： In genotype 2/3 patients, therapeutic education helped maintain real-life adherence to bitherapy.     

Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype 1 relapsed after interferon monotherapy： A randomized controlled trial

INTRODUCTION Retreatment of hepatitis C patients who relapsed after recombinant interferon (rIFN) monotherapy has a fair rate of success when ribavirin is added to the original protocol. About 30% of patients infected with hepatitis C virus (HCV) genotype…     

Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C

AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for 65-85 kg; 1200 mg/d for 85-105 kg; 1400 mg/d for 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.     

The optimal dose of ribavirin for chronic hepatitis C: From literature evidence to clinical practice: The optimal dose of ribavirin for chronic hepatitis C

Approximately 170 million people worldwide are chronically infected by hepatitis C virus (HCV), which can result in progressive hepatic injury and fibrosis, culminating in cirrhosis and end-stage liver disease. The benchmark therapy for untreated HCV patients is a combination of pegylated interferon-alpha (PEG-IFN) and ribavirin (RBV). Several studies have suggested several potential new approaches to improve HCV therapy-optimization of the dose and duration of RBV therapy, accompanied by careful clinical management, is crucial in ensuring the greatest likelihood of a long response to therapy. RBV causes serious side effects, but in clinical practice, there are no alternatives for the treatment of HCV infection. Based on our results, weight-based doses of RBV are advantageous for genotype 1-infected patients, but its success in genotype 2- and 3-infected patients is unknown, particularly for shorter treatment durations.     

Efficacy of low dose peginterferon alpha-2b with ribavirin on chronic hepatitis C

INTRODUCTION The hepatitis C virus is a major cause of liver diseases affecting 170 million people worldwide[1]. In India, the estimated prevalence of hepatitis C virus infection is 1.8%. Genotypes 2 and 3 are predominant in Indian population[2]. Therapy …     

Study of pruritus in chronic hepatitis C patients

AIM: To investigate the occurrence and severity of pruritus in chronic hepatitis C patients treated with or without interferon (IFN) therapy.METHODS: A total of 89 patients with chronic hepatitis C and 55 control (non-hepatitis) patients were asked to rate their experience of diurnal and nocturnal pruritus in the preceding week using a visual analogue scale (VAS) and a five-point scale, respectively. Blood samples were taken and serum thymus and activation-regulated chemokine (TARC) levels were measured by enzyme-linked immunosorbent assay.RESULTS: A significantly greater proportion of chronic hepatitis C patients experienced nocturnal pruritus compared with control (58.4% vs 5.5%, P < 0.0001). Chronic hepatitis C patients also had more severe pruritus compared with control patients, indicated by the higher mean VAS scores in both the IFN-treated and non-IFN-treated groups. In particular, patients who received combined peginterferon alfa-2b and ribavirin had significantly higher mean VAS scores than those receiving peginterferon alfa-2a or no IFN treatment. Serum TARC levels did not correlate with pruritus scores, and no significant differences in TARC levels were observed between the IFN-treated and non-IFN-treated groups.CONCLUSION: Patients with chronic hepatitis C experience pruritus more than those without. Serum TARC levels do not correlate with pruritus severity in chronic hepatitis C patients.     

Desperately seeking hepatitis C virus

Spanish investigators described recently the so-called occult hepatitis C virus （HCV） infection, emphasizing the detection of genomic and antigenomic HCV RNA strands in liver and peripheral blood mononuclear cells. Therefore, the persistence of viral replication in occult HCV infection should be considered as a putative source of infection among family members and patients undergoing invasive procedures, transfusion or transplantation. Additionally, the most worrisome finding is that an occult HCV infection may persist in patients with sustained virological response.     

Boceprevir plus peginterferon/ribavirin for treatment of chronic hepatitis C in Russia

AIM: to evaluate addition of boceprevir to peginterferon/ribavirin(PR) in Russian patients with chronic hepatitis C virus(HCV).METHODS: treatment-naive(t N) and treatmentexperienced(t E) patients(who had failed prior treatment with PR for ≥ 12 wk) with chronic HCV genotype 1 infection were enrolled in this placebocontrolled, double-blind study. All patients initially received PR for 4 wk. Patients randomized to control treatment then received PR for an additional 44 wk. t N patients randomized to triple therapy received boceprevir(800 mg three times daily) plus PR for 24 wk and then further therapy according to treatment week 8(t W8) HCV RNA levels. t E patients received boceprevir plus PR for 32 wk and then further therapy according to t W8 HCV RNA levels. treatment was discontinued for t N patients with detectable HCV RNA at t W24 and t E patients with detectable HCV RNA at t W12 because of futility. the primary efficacy end point was sustained virologic response(SVR) defined as undetectable HCV RNA 24 wk after completing all study therapy.RESULTS: SVR was 74.8% in the boceprevir plus PR arm compared with 46.2% in the control arm, with a stratification-adjusted treatment difference of 29.2%(95%CI: 16.4-41.5; P 0.0001). Rates of SVR were higher in the boceprevir arm in both t N and t E patient groups(t N 78.4% vs 56.3%; t E 69.4% vs 30.0%). Within t E patients, the rates of SVR were higher with boceprevir plus PR compared with PR, regardless of treatment failure type(null responder, partial responder, and relapser). Most patients receiving boceprevir plus PR in both t N(86%) and t E(71%) populations were eligible for reduced treatment duration. Anemia was increased in patients receiving boceprevir plus PR vs PR alone(47.2% vs 24.4%); there was a corresponding increase in ribavirin dose reduction and erythropoietin use. Among patients receiving boceprevir plus PR, SVR rates were similar in patients with anemia( 10 g/d L) and those without anemia(71.2% vs 77.4%).CONCLUSION: Regulatory approval has been obtained for boceprevir plus PR in Russian patients with HCV genotype 1 infection based on the results of this study.     

Sarcoidosis and chronic hepatitis C: A case report

Several case reports deal with the relationship between hepatitis C virus (HCV) infection and pulmonary or hepatic sarcoidosis. Most publications describe interferon α-induced sarcoidosis. However, HCV infection per se is also suggested to cause sarcoidosis. The present case report describes a case of biopsy-verified lung and liver sarcoidosis and HCV infection, and the outcome of antiviral therapy. In March 2009, a 25-year-old man presented with moderately elevated liver enzymes without any clinical symptoms. The patient was positive for HCV antibodies and HCV RNA of genotype 1b. Four months later the patient became dyspnoic and pulmonary sarcoidosis was diagnosed by lung biopsy and radiography. A short course of corticosteroid treatment relieved symptoms. Three months later, liver biopsy showed noncaseating granulomas consisting of epithelioid histiocytes and giant cells with a small amount of peripheral lymphocyte infiltration, without any signs of fibrosis. Chronic HCV infection with coexistence of pulmonary and hepatic sarcoidosis was diagnosed. Antiviral therapy with peginterferon α and ribavirin at standard doses was started, which lasted 48 wk, and sustained viral response was achieved. A second liver biopsy showed disappearance of granulomas and chest radiography revealed normalization of mediastinal and perihilar glands. The hypothesis that HCV infection per se may have triggered systemic sarcoidosis was proposed. Successful treatment of HCV infection led to continuous remission of pulmonary and hepatic sarcoidosis. Further studies are required to understand the relationship between systemic sarcoidosis and HCV infection.     

Hepatitis C virus： Virology, diagnosis and management of antiviral therapy

Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti- HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效观察

目的评价聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的临床疗效。方法使用聚乙二醇干扰素α-2a(派罗欣)联合利巴韦林(800~1200mg/d)治疗58例慢性丙型肝炎患者,疗程48周,分别于治疗12周、24周和48周及治疗结束后24周评价疗效,并观察药物副作用。结果基因1型和非基因1型患者早期应答率分别为57.1%和76.7%(P>0.05),持续应答率分别为53.6%和80.0%(P<0.05);HCV RNA高水平组和低水平组之间持续应答率分别为56.3%和80.8%,具有显著性差异(P<0.05)。结论在慢性丙型肝炎患者的治疗中,基因1型患者疗效低于非基因1型,HCV RNA低水平组的疗效优于高水平组。