Pegylated interferon alfa and ribavirin for children with chronic hepatitis C

AIM:To study current treatment options for pediatric hepatitis C infection and their associated success rates.METHODS:We retrospectively reviewed charts of thirty children who had been treated with combination therapy of pegylated interferon alfa plus ribavirin for chronic hepatitis C infection.Patients had been treated with ribavirin(15 mg/kg per day) and either pegylated interferon alfa 2a(180 mg/m 2 once weekly) or pegylated interferon alfa 2b(1.5 mg/kg once weekly).Patients’ follow-up included subjective assessment of complaints,physical examination including weight and height,as well as laboratory evaluations for viral load [before treatment,at 12 wk,and 6 mo following treatment completion,as determined by sustained viral response(SVR)],complete blood count,liver enzymes,alkaline phosphatase,bilirubin,renal function tests,and thyroid function tests.For patients not achieving a two log decrease in viral load at treatment week 12,treatment was discontinued and the patient was considered a treatment non-responder.RESULTS:Thirty children aged 3-18 years were included in the study.Twenty patients(11 males,9 females) received pegylated interferon alfa 2b and ten patients(6 males,4 females) received pegylated interferon alfa 2a.Twenty-three patients were infected with genotype 1,six patients were infected with genotype 3,and one patient was infected with genotype 2.Twenty patients(67%) achieved SVR.Treatment success rates were 90% with pegylated interferon alfa 2a vs 55% with pegylated interferon alfa 2b.Although a trend was noted for improved outcomes in the group receiving pegylated interferon alfa 2a,there were no statistically significant outcome differences between the two treatment groups(P = 0.1).Treatment success was 56.5% for patients infected with genotype 1 virus,compared to 100% for patients infected with other genotypes(P = 0.064).There was no difference in treatment response between males and females.A cut-off age of twelve years was used to dichotomize younger vs older participants;however,no diff     

Pegylated interferon alfa-2b plus ribavirin in the retreatment of interferon-ribavirin nonresponder patients

BACKGROUND & AIMS: Inadequate data are available about retreatment of nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the efficacy and tolerability of a 48-week therapy with pegylated IFN-alpha-2b plus high-dose ribavirin in patients who have failed to respond to the combination. Treatment up to 48 weeks also in patients who have failed to clear hepatitis C virus (HCV) RNA by week 24 was also evaluated. METHODS: One hundred forty-one patients who previously did not respond to IFN and ribavirin, 86% with genotype 1 or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis, were retreated with pegylated IFN-alpha-2b 1.5 microg/kg per week and ribavirin 1000-1200 mg/day for 48 weeks and followed up for 24 weeks. RESULTS: By intent-to-treat analysis, 20% of patients achieved a sustained virologic response (SVR). SVR of genotype 1 patients was 19%. Independent predictors of SVR were low gamma-glutamyltransferase levels (OR, 22.9; 95% CI: 6.6-79.6) and low viral load (OR, 3.8; 95% CI: 1.1-12.6). Twelve (23%) out of 51 patients who were HCV RNA positive after 24 weeks of therapy achieved a late virologic response (after week 24) and 5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not associated with response (P = .2) or with early response (P = .3). CONCLUSIONS: Retreatment with pegylated IFN-alpha-2b and ribavirin of multi-experienced and "difficult to treat" nonresponder patients produced a very promising SVR. Accurate selection of patients, such as those with low viral load and low gamma-glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in HCV RNA-positive patients may further increase the rate of SVR.     

基因1型慢性丙型肝炎代偿期肝硬化患者抗病毒治疗后的长期随访研究

目的探讨基因1型慢性丙型肝炎代偿期肝硬化抗病毒治疗的长期疗效。方法采用平行对照回顾性队列研究,对基因1型慢性丙型肝炎代偿期肝硬化患者予聚乙二醇干扰素α-2a联合利巴韦林(PR)治疗,予以集落刺激因子对症治疗,5年长期随访并观察其转归。评估疗效、复发率,肝脏瞬时弹性超声成像检测肝脏硬度值(Stiffness值),比较持续病毒学应答(SVR)组和非持续病毒学应答(NSVR)组的临床事件(肝性脑病、腹水、消化道出血、肝癌或者死亡)发生。结果54例基因1型慢性丙型肝炎代偿期肝硬化患者接受了PR治疗,获得SVR的患者有35例。15例患者在第1次抗病毒治疗后获得SVR,9例、8例、2例、1例患者分别在第2、3、4、5次抗病毒治疗后获得SVR。仅有1例患者在获得SVR6周后出现复发。抗病毒治疗期间,患者的肝硬度值得到不同程度的改善,SVR组治疗后与基线值比较差异有统计学意义(P=0.0004)。结束治疗后的长期随访发现,SVR组患者的肝硬度值有进一步下降的趋势,并能保持在一个较低的水平。而NSVR组患者的肝硬度值没有改善。在平均为60个月的随访中,NSVR组新增3例肝癌患者,SVR组则无人发生。两组临床事件发生频率的差异有统计学意义[腹水:P=0.0168,RR=0.2353(95%CI 0.039~1.422),HCC:P=0.0391,RR=0.0000]。结论对于基因1型慢性丙肝代偿期肝硬化使用聚乙二醇干扰素α-2a联合利巴韦林能有效抑制病毒,应用集落刺激因子可提高患者治疗依从性。既往治疗失败患者,多次治疗及延长疗程能提高SVR率。获得SVR后的复发率低,能减少肝癌等临床事件的发生,缓解肝硬化进展。     

Pegylated interferon alpha2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients

BACKGROUND: Hepatitis C virus (HCV) and HIV coinfection constitutes an important epidemiological and clinical problem. We evaluated the safety and efficacy of Pegylated interferon alpha2b (Peg-IFN) and a fixed dose of ribavirin in the treatment of chronic hepatitis C in HIV coinfection. METHODS: Open, prospective study in HCV-HIV coinfected patients with persistently elevated alanine aminotransferase (ALT) levels and a liver biopsy showing either portal or bridging fibrosis. Therapy included Peg-IFN (50 micro g weekly) with ribavirin 800 mg for 48 weeks. The primary end point was sustained virological response (SVR). Univariate and multivariate analyses were performed to determine factors associated with response. RESULTS: By intent-to-treat analysis, 11 of 35 patients (31%) reached SVR. SVR was significantly better for genotypes 2/3 than for genotype 1 (54% versus 21%; P < 0.05). By multivariate logistic regression analysis, only a non-1 genotype was an independent factor for SVR [odds ratio (OR), 6; 95% confidence interval (CI), 1.1-31.7; P < 0.005]. A decrease of at least 1.5 log10 HCV RNA at week 12 of therapy was highly predictive of SVR (OR, 49.9; 95% CI, 4.9-508.2; P < 0.001). Most patients developed adverse events, although only six patients (17%) discontinued treatment due to toxicity. CONCLUSIONS: The combination of low doses of Peg-IFN plus a fixed dose of ribavirin resulted in a rate of SVR similar to that obtained with higher doses of the drugs in HIV-infected patients and lower than those obtained in non-HIV patients. Response at week 12 may be useful to help guide therapy in HCV-HIV co-infected patients.     

Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta

Therapy of chronic hepatitis delta with standard interferon therapy has met with limited efficacy. This study was designed to examine the efficacy and safety of peginterferon with or without ribavirin. Thirty-eight serum hepatitis B surface antigen- and HDV RNA-positive patients with alanine aminotransferase (ALT) more than 1.5 times the upper normal limit received peginterferon alpha-2b (1.5 microg/kg) alone as monotherapy (n=16) or in combination with ribavirin (n=22), for 48 weeks. Thereafter, all the patients were maintained on peginterferon for 24 weeks and followed for 24 weeks off therapy. The primary end point studied was the virological and biochemical response at the end of follow-up. HDV RNA was determined by single or nested polymerase chain reaction assays. Twenty-seven patients (71%), 11 receiving monotherapy and 16 receiving the combination treatment, completed the follow-up. At the end of treatment, a virological response was observed in 3 of the patients treated with peginterferon (19%) and in 2 of the patients treated with combination therapy (9%), and a biochemical response was observed in 6 (37.5%) and 9 patients (41%), respectively. In nonresponders, ALT diminished from a mean of 174+/-53 to 86+/-41 IU/L. At the end of follow-up, serum HDV RNA was negative in 8 patients (21%), and a biochemical response was detected in 10 patients (26%). Treatment was discontinued in 25% of the patients, and dosing was modified in 58%. In conclusion, a prolonged course of peginterferon alpha-2b resulted in clearance of serum HDV RNA and ALT normalization in a fifth of patients with chronic hepatitis D, while ribavirin had no effect on the viral clearance rate. Overall tolerance of therapy was poor.     

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.     

Pegylated interferon and ribavirin in re-treatment of responder-relapser HCV patients

BACKGROUND: The re-treatment of patients who relapse after a course of standard interferon and ribavirin with pegylated interferon alfa-2b plus ribavirin is an open issue. AIMS: To evaluate efficacy and safety of treatment with pegylated interferon alfa-2b plus ribavirin and the role of early HCV-RNA assessment as a predictor of sustained response. PATIENTS: Between May 2001 and December 2002, 242 consecutive patients with chronic hepatitis C were enrolled in an open, regional, multicentre study. Seventy-eight of them were responder-relapsers to a previous course of combination therapy. METHODS: Patients were treated with pegylated interferon alfa-2b (1 microg/kg/week) plus ribavirin (800-1200 mg daily). Qualitative HCV-RNA was performed at week 2. Genotypes 1-4 were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. RESULTS: We obtained an overall sustained virological response rate of 41.0% (78.6% for patients with genotypes 2-3). CONCLUSION: This treatment schedule prove to be safe and effective in relapsers with genotype non-1 while genotype 1-4 patients had a low rate of sustained virological response. Qualitative virological assessment after 2 weeks may identify patients who are more likely to reach sustained virological response, but it is not a valid tool for a stopping rule approach.     

Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response

A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-na?ve HCV RNA-positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon alpha-2b (1.5 microg/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, -0.1 to +13.9). CONCLUSION: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks.     

Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis patients

Standard therapy for chronic hepatitis C (HCV) is pegylated interferon in combination with ribavirin. There is limited experience with either drug in dialysis [end stage renal disease (ESRD)]. Six haemodialysis patients, four with HCV genotype 1, one with genotype 4 and one genotype 2 were treated with pegylated interferon-alfa-2b (n = 4) and pegylated interferon-alfa-2a (n = 2) for 24-48 weeks according to genotype with a dose of 50 or 135 mug/week respectively. All patients were given reduced ribavirin doses, initially 200-400 mg/day. Ribavirin trough plasma concentrations were measured with a HPLC method previously developed for earlier treatment studies, aiming at a target concentration of 10-15 micromol/L. Interferon related side-effects were common, in one patient peg-alfa-2b was permanently reduced to 50 mug every 9-10 days with improvement in tolerance. Average ribavirin dose was 170-300 mg/day. Ribavirin-induced anaemia was treated with high doses of erythropoietin and low doses of iron. Blood-transfusions were not needed. All patients became HCV-RNA-PCR negative during treatment which was completed or nearly completed in four patients. One patient terminated therapy prematurely due to pronounced interferon related side-effects and another died of myocardial infarction probably not related to therapy. Three patients have remained HCV-RNA negative with extended follow-up, two of whom have had a successful kidney transplant. Pegylated interferons are likely to become a valuable addition for HCV therapy in ESRD and are possible to combine with ribavirin. However the pharmacokinetics and tolerability of both peg-alfa-2a and 2b need to be studied more closely in prospective studies before definite dosing recommendations can be made.     

HCV-related advanced fibrosis/cirrhosis: randomized controlled trial of pegylated interferon alpha-2a and ribavirin

Summary. In patients with hepatitis C virus (HCV)‐related advanced fibrosis/cirrhosis, 30% of sustained HCV clearance has been reported with pegylated interferon α‐2a (PEG‐IFN) alone, but the efficacy and tolerability of the PEG‐IFN/ribavirin (RBV) combination remain poorly defined. A total of 124 treatment‐naïve patients with biopsy proved HCV‐related advanced fibrosis/cirrhosis (Ishak score F4–F6, Child–Pugh score ≤7) were randomized to 48 weeks of PEG‐IFN (180 μg sc weekly) and standard dose of RBV (1000/1200 mg po daily, STD) or PEG‐IFN (180 μg sc weekly) and low‐dose of RBV (600/800 mg po daily, LOW). Sustained virologic response (SVR) rates with PEG‐IFN/STD RBV (52%) were higher – albeit not significantly – than that with PEG‐IFN/LOW RBV (38%, P = 0.153). In multivariate analysis, genotype 2/3 and a baseline platelet count ≥150 × 10⁹/L were independently associated with SVR. The likelihood of SVR was <7% if viraemia had not declined by ≥2 log or to undetectable levels after 12 weeks. Nine adverse events in the STD RBV and 15 in the LOW RBV group were classified as severe (including two deaths); dose reductions for intolerance were required in 78% and 57% (P = 0.013), and treatment was terminated early in 23% and 27% of patients (P = n.s.). The benefit/risk ratio of treating compensated HCV‐cirrhotics with STD PEG‐IFN/RBV is favourable.     

Natural leukocyte interferon alpha (Alfaferone) combined with ribavirin in the treatment of patients with HCV-related cirrhosis: our experience

Background  

The aim of the study was to evaluate the efficacy and safety of combined treatment with natural leukocyte interferon alpha (Alfaferone) plus ribavirin in patients with HCV-related cirrhosis.