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 ...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.展开更多
AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter,...AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR.展开更多
AIM:To investigate the possibility of shortening the duration of peginterferon(Peg-IFN)plus ribavirin(RBV) combination therapy by incorporating interferon-β (IFN-β)induction therapy. METHODS:A one treatment arm,coho...AIM:To investigate the possibility of shortening the duration of peginterferon(Peg-IFN)plus ribavirin(RBV) combination therapy by incorporating interferon-β (IFN-β)induction therapy. METHODS:A one treatment arm,cohort prospective study was conducted on seventy one patients.The patients were Japanese adults with genotype 1b chronic hepatitis C,HCV-RNA levels of≥5.0 Log IU/mL or 100 KIU/mL,and platelet counts of≥90 000/μL.The treatment regimen consisted of a 2 wk course of twicedaily administration of IFN-βfollowed by 24 wk PegIFN plus RBV combination therapy.We prolonged the duration of the Peg-IFN plus RBV therapy to 48 wk if the patient requested it. RESULTS:The patients,including 44%males,were characterized by an median age of 63 years(range: 32-78 years),an median platelet count of 13.9(range: 9.1-30.6)×10 4 /μL,62%IFN-na?ve,and median HCV- RNA of 6.1(range:5.1-7.2)Log IU/mL.The sustained virologic response(SVR)rates were 34%(Peg-IFN:1-24 wk,n=61,95%confidence interval(CI): 24%-47%)and 55%(Peg-IFN:20-24 wk,n=31,95% CI:38%-71%,P<0.001;vs Peg-IFN:1-19 wk).TheSVR rate when the administration was discontinued early was 13%(Peg-IFN:1-19 wk,n=30,95%CI: 5%-30%),and that when the administration was prolonged was 50%(Peg-IFN:25-48 wk,n=10,95% CI:24%-76%,P<0.05;vs Peg-IFN:1-19 wk).In the patients who received 20-24 wk of Peg-IFN plus RBV,only the higher platelet count(≥130 000/μL) was significantly correlated with the SVR(odds ratio: 11.680,95%CI:2.3064-79.474,P=0.0024).In 45% (14/31)of the patients with a higher platelet count (≥130000/μL)before therapy,the HCV-RNA level decreased to below 3.3 Log IU/mL at the completion of IFN-β,and their SVR rate was 93%(13/14)after 20-24 wk administration of Peg-IFN plus RBV. CONCLUSION:These results suggest the possibilities of shortening the duration of Peg-IFN plus RBV combination therapy by actively reducing HCV-RNA levels using the IFN-βinduction regimen.展开更多
AIM: To assess the effi cacy of peginterferon alpha 2b at doses of 50 μg weekly and 80 μg weekly (based on body weight) plus ribavirin in HCV genotype 2 and genotype 3 chronic hepatitis C patients. METHODS: During t...AIM: To assess the effi cacy of peginterferon alpha 2b at doses of 50 μg weekly and 80 μg weekly (based on body weight) plus ribavirin in HCV genotype 2 and genotype 3 chronic hepatitis C patients. METHODS: During the study period of Jan 2002 to Dec 2003, all patients diagnosed as chronic hepatitis C or HCV related compensated cirrhosis were treated with peginterferon alpha 2b 50 μg S/C weekly (body weight < 60 kg) or 80 μg S/C weekly (body weight > 60 kg) plus ribavirin 800 mg/d for 24 wk. RESULTS: Overall 28 patients, 14 patients in each group (based on body weight) were treated during the period. Out of 28 patients, 75% were genotype 3, 18% were genotype 2 and 7% were genotype 1. The mean dose of peginterferon alpha 2b was 0.91 μg/kg in group 1 and 1.23 μg/kg in group 2 respectively. The end of treatment and sustained virologic response rates were 82% and 78% respectively. Serious adverse effects were seen in 3.5% patients. CONCLUSION: Low dose peginterferon alpha 2b in combination with ribavirin for 24 wk is effective in HCV genotype 2 and 3 chronic hepatitis C patients.展开更多
AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination the...AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. CONCLUSION: The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.展开更多
AIM:To analyzed the association between inosine triphosphatase(ITPA)(rs1127354) genotypes and sustained virological response(SVR) rates in peginterferon(Peg-IFN)α + ribavirin(RBV) treatment.METHODS:Patients who under...AIM:To analyzed the association between inosine triphosphatase(ITPA)(rs1127354) genotypes and sustained virological response(SVR) rates in peginterferon(Peg-IFN)α + ribavirin(RBV) treatment.METHODS:Patients who underwent Peg-IFNα + RBV combination therapy were enrolled(n = 120) and they had no history of other IFN-based treatments.Variation in hemoglobin levels during therapy,cumulative reduction of RBV dose,frequency of treatment withdrawal,and SVR rates were investigated in each ITPA genotype.RESULTS:In patients with ITPA CC genotype,hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was < 60% of standard and/or treatment was withdrawn was significantly higher compared with CA/AA genotype.However,SVR rates were equivalent between CC and CA/AA genotypes,and within a subset of patients with Interleukin 28B(IL28B)(rs8099917) TT genotype,SVR rates tended to be higher in patients with ITPA CC genotype,although the difference was not significant.CONCLUSION:ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV dose.However,CC genotype was not inferior to CA/AA genotype for SVR rates.When full-length treatment is accomplished,it is plausible that more SVR is achieved in patients with ITPA CC variant,especially in a background of IL28B TT genotype.展开更多
Adverse effects associated with peginterferon and ribavirin during hepatitis C treatment are well known. Sudden hearing loss has rarely been reported. Possible mechanisms involved include direct ototoxicity of interfe...Adverse effects associated with peginterferon and ribavirin during hepatitis C treatment are well known. Sudden hearing loss has rarely been reported. Possible mechanisms involved include direct ototoxicity of interferon, autoimmunity, and hematological changes. Hearing loss is frequently fully resolved after discontinuation of antiviral therapy. We report a 47-year- old man with chronic hepatitis C, genotype 2 ac who developed sudden hearing loss 22 wk after starting therapy with peginterferon alpha 2a at a dose of 180 ~g per week and ribavirin 800 mg per day. Since symptoms did not worsen, antiviral therapy was continued for 2 wk, according to the patient＇s wish. Hearing loss resolved within 2 wk after the end of treatment. Serum liver alanine aminotransferase remained normal during and after the end of antiviral therapy. HCV RNA was undetectable at the end of therapy and remained negative 24 wk later. Thus, patients should be aware that hearing loss may occur with peginterferon therapy, but the decision whether to continue or to stop the treatment is based on the clinical judgment of the physician and the wishes of the patient.展开更多
Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved t...Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.展开更多
Peginterferon and ribavirin combination therapy for the treatment of hepatitis C virus （HCV） is well known to be associated with significant adverse effects. Sensorineural hearing loss, that in most cases is unilate...Peginterferon and ribavirin combination therapy for the treatment of hepatitis C virus （HCV） is well known to be associated with significant adverse effects. Sensorineural hearing loss, that in most cases is unilateral, has been reported as a consequence of therapy with both non-pegylabed and pegylated interferon （pegIFN） but is not a well-known adverse effect. We report a 45-year-old Caucasian woman who developed acute sensorineural hearing loss 2 mo after starting therapy with pegIFN-α 2b and ribavirin for the treatment of chronic HCV, genotype la. She did not report the hearing loss to the hepatitis clinic until 1 mo, later whereupon therapy was promptly discontinued. Although her serum alanine aminotransferase （ALT） normalized and her HCV-RNA became undetectable after 12 wk of pegIFN and dbavirin therapy, after discontinuation, her HCV-RNA became detectable with significant elevations of serum ALT. Four months after initial discontinuation, the patient re-commenced pegIFN and ribavirin combination therapy. After 44 of 48 wk of therapy, the patient＇s liver biochemistry has normalized and the HCV-RNA is undetectable. She has not developed worsening of her hearing loss and hearing on the left-side is unaffected. Both patients and physicians should be aware that sensorineural hearing loss may occur with pegIFN therapy. Our experience suggests that re-institution of therapy is not always associated with further hearing impairment.展开更多
BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations...BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations of this strategy unclear.AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-αregimens.METHODS This prospective,multicenter,observational study was conducted from November 2015 to June 2021 at three Chinese hospitals:The Second Affiliated Hospital of Xi’an Jiaotong University,Ankang Central Hospital,and The Affiliated Hospital of Yan’an University.Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus(HBV)markers,HBV DNA,and liver function.The primary outcome was HBV recurrence,defined as the reemergence of HBsAg,HBV DNA,or both,at least twice within 4-8 weeks of follow-up.RESULTS In total,121 patients who achieved HBsAg seroclearance were enrolled.After a median follow-up of 84.0(48.0,132.0)weeks,four subjects were lost to follow-up.HBsAg recurrence was detected in 16 patients.The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%.Multivariate logistic regression analysis demonstrated that consolidation time<12 weeks[odds ratio(OR)=28.044,95%CI:4.525-173.791]and hepatitis B surface antibody disappearance during follow-up(OR=46.445,95%CI:2.571-838.957)were strong predictors of HBsAg recurrence.HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.CONCLUSION HBsAg seroclearance following peg-IFN-αtreatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.展开更多
目的观察恩替卡韦(entecavir,ETV)单用及联合使用聚乙二醇干扰素(peginterferon,Peg-IFN)治疗高病毒载量慢性乙型肝炎(chronic hepatitis B,CHB)患者的疗效。方法该项前瞻性非随机队列研究纳入了2019年12月至2023年12月在南昌大学第一...目的观察恩替卡韦(entecavir,ETV)单用及联合使用聚乙二醇干扰素(peginterferon,Peg-IFN)治疗高病毒载量慢性乙型肝炎(chronic hepatitis B,CHB)患者的疗效。方法该项前瞻性非随机队列研究纳入了2019年12月至2023年12月在南昌大学第一附属医院等4家医院接受治疗的152例高病毒载量CHB患者。根据治疗方案将患者分为ETV组102例及Peg-IFN与ETV联合治疗组50例。主要结局指标为48周时乙型肝炎病毒(hepatitis B virus,HBV)表面抗原(hepatitis B virus s antigens,HBsAg)血清清除率。次要结局指标为48周HBsAg下降水平、HBV e抗原(hepatitis B virus e antigens,HBeAg)血清清除率、HBV-DNA阴转率及下降水平以及ALT下降水平。计量资料符合正态分布,两组间比较采用独立样本t检验,治疗前后组内比较采用重复测量方差分析。计数资料两组间比较采用卡方检验,治疗前后组内比较采用Cochran's Q检验多重比较进行统计分析。结果两组患者的ALT、HBV-DNA和HBsAg水平在整个48周治疗期间较治疗前均显著下降(P<0.001)。治疗48周时,ETV组丙氨酸氨基转移酶(30.82±9.86)U/L显著低于联合治疗组(37.57±19.84)U/L(P=0.027);ETV组HBV-DNA和HBsAg水平分别为(1.22±1.17)lg IU/mL和(3.65±0.85)lg IU/mL均显著高于联合治疗组(0.82±0.96)lg IU/mL和(2.62±1.45)lg IU/mL(P=0.034,P<0.001)。ETV组治疗48周时HBeAg和HBV-DNA清除率较治疗前均显著升高(P<0.001),而HBsAg清除率与治疗前差异无统计学意义(P=0.171)。联合治疗组治疗48周时HBsAg、HBeAg和HBV-DNA清除率较治疗前均显著升高(P<0.05)。治疗48周时,ETV组HBsAg和HBeAg血清清除率分别2.0%和13.7%均显著低于联合治疗组12.0%和38.0%(P=0.027,P=0.001);ETV组HBV-DNA清除率89.2%低于联合治疗组94.0%,差异无统计学意义(P=0.509)。结论Peg-IFN联合ETV治疗方案可作为高病毒载量CHB患者的首选治疗方案。展开更多
BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained viro...BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS: PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION: In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.展开更多
Before the advent of direct acting antiviral agents(DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the pres...Before the advent of direct acting antiviral agents(DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the present era of new potent DAAs, a place is still devoted to the drug. Ribavirin associated with sofosbuvir alone is efficient in the treatment of most cases of G2 infected patients. All options currently available for the last difficult-to-treat cirrhotic G3 patients contain ribavirin. Reducing treatment duration to 12 wk in G1 or G4 cirrhotic compensated patients is feasible thanks to ribavirin. Retreating patients with acquired anti NS5 A resistance-associated variants using ribavirin-based strategies could be useful. The addition of ribavirin with DAAs combinations however, leads to more frequent but mild adverse events especially in cirrhotic patients. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized even in difficult-totreat patients: The optimization of ribavirin dosage according to an early monitoring of blood levels has been suggested to be relevant in double therapy with peginterferon or sofosbuvir but not with very potent combinations of more than two DAAs.展开更多
AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chron...AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.展开更多
Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effe...Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.展开更多
文摘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.
文摘AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR.
文摘AIM:To investigate the possibility of shortening the duration of peginterferon(Peg-IFN)plus ribavirin(RBV) combination therapy by incorporating interferon-β (IFN-β)induction therapy. METHODS:A one treatment arm,cohort prospective study was conducted on seventy one patients.The patients were Japanese adults with genotype 1b chronic hepatitis C,HCV-RNA levels of≥5.0 Log IU/mL or 100 KIU/mL,and platelet counts of≥90 000/μL.The treatment regimen consisted of a 2 wk course of twicedaily administration of IFN-βfollowed by 24 wk PegIFN plus RBV combination therapy.We prolonged the duration of the Peg-IFN plus RBV therapy to 48 wk if the patient requested it. RESULTS:The patients,including 44%males,were characterized by an median age of 63 years(range: 32-78 years),an median platelet count of 13.9(range: 9.1-30.6)×10 4 /μL,62%IFN-na?ve,and median HCV- RNA of 6.1(range:5.1-7.2)Log IU/mL.The sustained virologic response(SVR)rates were 34%(Peg-IFN:1-24 wk,n=61,95%confidence interval(CI): 24%-47%)and 55%(Peg-IFN:20-24 wk,n=31,95% CI:38%-71%,P<0.001;vs Peg-IFN:1-19 wk).TheSVR rate when the administration was discontinued early was 13%(Peg-IFN:1-19 wk,n=30,95%CI: 5%-30%),and that when the administration was prolonged was 50%(Peg-IFN:25-48 wk,n=10,95% CI:24%-76%,P<0.05;vs Peg-IFN:1-19 wk).In the patients who received 20-24 wk of Peg-IFN plus RBV,only the higher platelet count(≥130 000/μL) was significantly correlated with the SVR(odds ratio: 11.680,95%CI:2.3064-79.474,P=0.0024).In 45% (14/31)of the patients with a higher platelet count (≥130000/μL)before therapy,the HCV-RNA level decreased to below 3.3 Log IU/mL at the completion of IFN-β,and their SVR rate was 93%(13/14)after 20-24 wk administration of Peg-IFN plus RBV. CONCLUSION:These results suggest the possibilities of shortening the duration of Peg-IFN plus RBV combination therapy by actively reducing HCV-RNA levels using the IFN-βinduction regimen.
文摘AIM: To assess the effi cacy of peginterferon alpha 2b at doses of 50 μg weekly and 80 μg weekly (based on body weight) plus ribavirin in HCV genotype 2 and genotype 3 chronic hepatitis C patients. METHODS: During the study period of Jan 2002 to Dec 2003, all patients diagnosed as chronic hepatitis C or HCV related compensated cirrhosis were treated with peginterferon alpha 2b 50 μg S/C weekly (body weight < 60 kg) or 80 μg S/C weekly (body weight > 60 kg) plus ribavirin 800 mg/d for 24 wk. RESULTS: Overall 28 patients, 14 patients in each group (based on body weight) were treated during the period. Out of 28 patients, 75% were genotype 3, 18% were genotype 2 and 7% were genotype 1. The mean dose of peginterferon alpha 2b was 0.91 μg/kg in group 1 and 1.23 μg/kg in group 2 respectively. The end of treatment and sustained virologic response rates were 82% and 78% respectively. Serious adverse effects were seen in 3.5% patients. CONCLUSION: Low dose peginterferon alpha 2b in combination with ribavirin for 24 wk is effective in HCV genotype 2 and 3 chronic hepatitis C patients.
基金Supported by Instituto de Investigacion La Princesa and CI-BERehd from Instituto de Salud Carlos Ⅲ, Madrid, Spain
文摘AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. CONCLUSION: The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.
基金Supported by The Research Program of Intractable Disease provided by the Ministry of Health,Labor and Welfare of Japana Grant-in-Aid for Clinical Research from the National Hospital Organization of Japan
文摘AIM:To analyzed the association between inosine triphosphatase(ITPA)(rs1127354) genotypes and sustained virological response(SVR) rates in peginterferon(Peg-IFN)α + ribavirin(RBV) treatment.METHODS:Patients who underwent Peg-IFNα + RBV combination therapy were enrolled(n = 120) and they had no history of other IFN-based treatments.Variation in hemoglobin levels during therapy,cumulative reduction of RBV dose,frequency of treatment withdrawal,and SVR rates were investigated in each ITPA genotype.RESULTS:In patients with ITPA CC genotype,hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was < 60% of standard and/or treatment was withdrawn was significantly higher compared with CA/AA genotype.However,SVR rates were equivalent between CC and CA/AA genotypes,and within a subset of patients with Interleukin 28B(IL28B)(rs8099917) TT genotype,SVR rates tended to be higher in patients with ITPA CC genotype,although the difference was not significant.CONCLUSION:ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV dose.However,CC genotype was not inferior to CA/AA genotype for SVR rates.When full-length treatment is accomplished,it is plausible that more SVR is achieved in patients with ITPA CC variant,especially in a background of IL28B TT genotype.
文摘Adverse effects associated with peginterferon and ribavirin during hepatitis C treatment are well known. Sudden hearing loss has rarely been reported. Possible mechanisms involved include direct ototoxicity of interferon, autoimmunity, and hematological changes. Hearing loss is frequently fully resolved after discontinuation of antiviral therapy. We report a 47-year- old man with chronic hepatitis C, genotype 2 ac who developed sudden hearing loss 22 wk after starting therapy with peginterferon alpha 2a at a dose of 180 ~g per week and ribavirin 800 mg per day. Since symptoms did not worsen, antiviral therapy was continued for 2 wk, according to the patient＇s wish. Hearing loss resolved within 2 wk after the end of treatment. Serum liver alanine aminotransferase remained normal during and after the end of antiviral therapy. HCV RNA was undetectable at the end of therapy and remained negative 24 wk later. Thus, patients should be aware that hearing loss may occur with peginterferon therapy, but the decision whether to continue or to stop the treatment is based on the clinical judgment of the physician and the wishes of the patient.
文摘Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.
文摘Peginterferon and ribavirin combination therapy for the treatment of hepatitis C virus （HCV） is well known to be associated with significant adverse effects. Sensorineural hearing loss, that in most cases is unilateral, has been reported as a consequence of therapy with both non-pegylabed and pegylated interferon （pegIFN） but is not a well-known adverse effect. We report a 45-year-old Caucasian woman who developed acute sensorineural hearing loss 2 mo after starting therapy with pegIFN-α 2b and ribavirin for the treatment of chronic HCV, genotype la. She did not report the hearing loss to the hepatitis clinic until 1 mo, later whereupon therapy was promptly discontinued. Although her serum alanine aminotransferase （ALT） normalized and her HCV-RNA became undetectable after 12 wk of pegIFN and dbavirin therapy, after discontinuation, her HCV-RNA became detectable with significant elevations of serum ALT. Four months after initial discontinuation, the patient re-commenced pegIFN and ribavirin combination therapy. After 44 of 48 wk of therapy, the patient＇s liver biochemistry has normalized and the HCV-RNA is undetectable. She has not developed worsening of her hearing loss and hearing on the left-side is unaffected. Both patients and physicians should be aware that sensorineural hearing loss may occur with pegIFN therapy. Our experience suggests that re-institution of therapy is not always associated with further hearing impairment.
基金Supported by National Key Research and Development Program of China,No.2023YFC2308105.
文摘BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations of this strategy unclear.AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-αregimens.METHODS This prospective,multicenter,observational study was conducted from November 2015 to June 2021 at three Chinese hospitals:The Second Affiliated Hospital of Xi’an Jiaotong University,Ankang Central Hospital,and The Affiliated Hospital of Yan’an University.Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus(HBV)markers,HBV DNA,and liver function.The primary outcome was HBV recurrence,defined as the reemergence of HBsAg,HBV DNA,or both,at least twice within 4-8 weeks of follow-up.RESULTS In total,121 patients who achieved HBsAg seroclearance were enrolled.After a median follow-up of 84.0(48.0,132.0)weeks,four subjects were lost to follow-up.HBsAg recurrence was detected in 16 patients.The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%.Multivariate logistic regression analysis demonstrated that consolidation time<12 weeks[odds ratio(OR)=28.044,95%CI:4.525-173.791]and hepatitis B surface antibody disappearance during follow-up(OR=46.445,95%CI:2.571-838.957)were strong predictors of HBsAg recurrence.HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.CONCLUSION HBsAg seroclearance following peg-IFN-αtreatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.
文摘目的观察恩替卡韦(entecavir,ETV)单用及联合使用聚乙二醇干扰素(peginterferon,Peg-IFN)治疗高病毒载量慢性乙型肝炎(chronic hepatitis B,CHB)患者的疗效。方法该项前瞻性非随机队列研究纳入了2019年12月至2023年12月在南昌大学第一附属医院等4家医院接受治疗的152例高病毒载量CHB患者。根据治疗方案将患者分为ETV组102例及Peg-IFN与ETV联合治疗组50例。主要结局指标为48周时乙型肝炎病毒(hepatitis B virus,HBV)表面抗原(hepatitis B virus s antigens,HBsAg)血清清除率。次要结局指标为48周HBsAg下降水平、HBV e抗原(hepatitis B virus e antigens,HBeAg)血清清除率、HBV-DNA阴转率及下降水平以及ALT下降水平。计量资料符合正态分布,两组间比较采用独立样本t检验,治疗前后组内比较采用重复测量方差分析。计数资料两组间比较采用卡方检验,治疗前后组内比较采用Cochran's Q检验多重比较进行统计分析。结果两组患者的ALT、HBV-DNA和HBsAg水平在整个48周治疗期间较治疗前均显著下降(P<0.001)。治疗48周时,ETV组丙氨酸氨基转移酶(30.82±9.86)U/L显著低于联合治疗组(37.57±19.84)U/L(P=0.027);ETV组HBV-DNA和HBsAg水平分别为(1.22±1.17)lg IU/mL和(3.65±0.85)lg IU/mL均显著高于联合治疗组(0.82±0.96)lg IU/mL和(2.62±1.45)lg IU/mL(P=0.034,P<0.001)。ETV组治疗48周时HBeAg和HBV-DNA清除率较治疗前均显著升高(P<0.001),而HBsAg清除率与治疗前差异无统计学意义(P=0.171)。联合治疗组治疗48周时HBsAg、HBeAg和HBV-DNA清除率较治疗前均显著升高(P<0.05)。治疗48周时,ETV组HBsAg和HBeAg血清清除率分别2.0%和13.7%均显著低于联合治疗组12.0%和38.0%(P=0.027,P=0.001);ETV组HBV-DNA清除率89.2%低于联合治疗组94.0%,差异无统计学意义(P=0.509)。结论Peg-IFN联合ETV治疗方案可作为高病毒载量CHB患者的首选治疗方案。
文摘BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS: PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION: In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.
文摘Before the advent of direct acting antiviral agents(DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the present era of new potent DAAs, a place is still devoted to the drug. Ribavirin associated with sofosbuvir alone is efficient in the treatment of most cases of G2 infected patients. All options currently available for the last difficult-to-treat cirrhotic G3 patients contain ribavirin. Reducing treatment duration to 12 wk in G1 or G4 cirrhotic compensated patients is feasible thanks to ribavirin. Retreating patients with acquired anti NS5 A resistance-associated variants using ribavirin-based strategies could be useful. The addition of ribavirin with DAAs combinations however, leads to more frequent but mild adverse events especially in cirrhotic patients. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized even in difficult-totreat patients: The optimization of ribavirin dosage according to an early monitoring of blood levels has been suggested to be relevant in double therapy with peginterferon or sofosbuvir but not with very potent combinations of more than two DAAs.
文摘AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.
基金Supported by Brazilian government research foundations National Council for Research and Technology and Coordination for the Improvement of Higher Education Personnel with research grant and scholarships processNo.9028-11-0+2 种基金No.305064/2011-8 and No.232711/2014-3Sao Paulo Government agency Sao Paulo State Research Foundation withprocess No.2011/12448-0both granted to Andrade LEC and Keppeke GD
文摘Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.
