Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

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 treatm     

Anti-interferon-α neutralizing antibody is associated with nonresponse to pegylated interferon-α plus ribavirin in chronic hepatitis C

Summary. Pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment fails to achieve a sustained virological response (SVR) in approximately 20-50% of patients with chronic hepatitis C virus (HCV) infection. We assessed the contribution of an anti-IFN-α neutralizing antibody (NAb) on the nonresponse to treatment. NAbs were detected using an antiviral assay that assessed the neutralizing effects of serum samples against IFN. Serum samples were obtained at the end of the treatment and evaluated for the presence of NAbs using recombinant IFN-α as a standard. We studied 129 PEG-IFN-α/RBV-treated patients. In the 82 end-of-treatment responders, no NAbs were detected. Of the 47 patients who did not respond, seven (15%) were positive for NAbs. We also examined an additional 83 patients who had not responded to PEG-IFN-α treatment, and detected 12 with NAbs. Patients with good IFN-responsive characteristics, including HCV genotype 2/3 and major allele homozygotes for interleukin-28B, were included in the 19 patients with NAbs. No NAbs interfered with the antiviral activity of natural human IFN-β (nIFN-β) and re-treatement of patients with NAbs with nIFN-β/RBV achieved SVR. Our analyses revealed that the emergence of anti-IFN-α NAbs was a candidate causal factor of PEG-IFN-α-treatment failure. Therefore, these antibodies should be assayed in patients who do not respond to PEG-IFN-α therapy, and if detected, other effective treatments, i.e., medications that are not neutralized by anti-IFN-α NAbs, should be considered.     

Pegylated interferon ��-2b plus ribavirin for older patients with chronic hepatitis C

AIM:To analyze the efficacy and safety of a combination therapy of pegylated interferon(PEG-IFN) α-2b plus ribavirin(RBV) in older Japanese patients(65 years or older) infected with hepatitis C virus(HCV).METHODS:This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 wk.RESULTS:At 24 wk after the end of combination therapy,the overall sustained virologica...     

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

AIM:TT virus (TTV) is a newly described DNA virus relatedto postransfusion hepatitis that produces persistent viremiain the absence of clinical manifestations.PEG-IFN plusribavirin have been useful in the treatment of chronic hepatitisC infection.This study investigated the responses of TT virus(TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirintherapy.METHODS:Fifteen patients infected with HCV were treatedwith PEG-IFN(0.5 μg/body weight/week) and ribavirin(1000 mg-1 200 mg/daily) for 48 weeks,Blood samples weredrawn at the beginning and the end of the therapy.SerumTTV DNA and HCV RNA were quantified by real time PCR.RESULTS:At the beginning of treatment,TTV infection wasdetected in 10/15 (66.6%) of HCV-infected patients.Lossof serum TTV DNA at the end of therapy occurred in 6/10(60%) patients.Out of these 6 patients,4 (67%) becamepositive for TTV DNA after 6 months of therapy.RegardingHCV viremia,11/15 (73%) patients were negative for serumHCV RNA after 48 weeks of therapy,7/11 (64%) of thesecases also became negative for TTV DNA following thecombined treatment.In the 3/4 (75%) patients who werepositive for HCV RNA at the end of therapy,TTV DNA wasdetected as well.Sustained HCV response at 6 months aftertreatment was 53% (8/15).CONCLUSION:No TTV sustained response can be achievedin any patient after PEG-IFN plus ribavirin administration.     

Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis C

AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis C.METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus(HCV) were treated with responseguided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response(RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype(TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV subgenotype 2a or 2b.RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response(SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate(96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5%(P 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups(80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR(OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.     

Randomized trial of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin for chronic hepatitis C in Japanese patients

Background

Pegylated interferon (PegIFN) plus ribavirin is the standard therapy for patients with chronic hepatitis C genotype 1. Although several randomized clinical trials have compared PegIFNα-2a with PegIFNα-2b, these 2 regimens have not been directly compared in Asian patients. We, therefore, compared the safety and antiviral efficacy of these agents in Japanese patients.

Methods

A total of 201 PegIFN-na?ve, chronic hepatitis C patients were randomly assigned to once-weekly PegIFNα-2a (180?μg) or PegIFNα-2b (60–150?μg) plus ribavirin. We compared the sustained virological response (SVR) rates between the 2 regimens and analyzed their effects in relation to baseline characteristics, including single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene (rs8099917).

Results

PegIFNα-2a was associated with a higher SVR rate than PegIFNα-2b (65.3 vs. 51.0%, P?=?0.039). PegIFNα-2a and SNPs near IL28B independently predicted SVR (odds ratio 2.36; 95% confidence interval [CI] 1.19–15.50, and odds ratio 7.31; 95% CI 3.45–4.68, respectively) in logistic regression analysis. PegIFNα-2a was more effective than PegIFNα-2b (81.8 vs. 62.7%, P?=?0.014) in IL28B TT genotype patients, despite similarly low SVR rates in patients with TG or GG genotypes (36.4 vs. 35.9%). Patients weighing <60?kg, women, and patients aged >60?years had significantly higher SVR rates with PegIFNα-2a than with PegIFNα-2b (63.9, 61.3, and 67.3% vs. 43.8, 43.3,and 39.2%, respectively).

Conclusions

PegIFNα-2a plus ribavirin resulted in higher SVR rates than PegIFNα-2b plus ribavirin in Japanese patients. PegIFNα-2a-based treatment should therefore be the preferred choice for women, older or low-weight patients, and those with the IL28B TT genotype.     

A case of deep venous thrombosis associated with pegylated interferon α2b plus ribavirin treatment of chronic hepatitis C

We present a case of deep venous thrombosis (DVT) during pegylated interferon (peg-IFN)-α2b plus ribavirin treatment of chronic hepatitis C (CHC). A 67-year-old man, who had been under treatment for hypertension and diabetes mellitus, was admitted to our hospital for peg-IFN-α2b plus ribavirin treatment for CHC. His serum hepatitis C virus (HCV) RNA level became undetectable 1 week after the initiation of peg-IFN-α2b plus ribavirin treatment. He suffered from severe pain, flare, and edema in both of his lower legs 6 weeks after the initiation of peg-IFN-α2b plus ribavirin treatment. He was diagnosed as having DVT because of the presence of a thrombus in the right soleus vein by ultrasonography. Peg-IFN-α2b plus ribavirin treatment was discontinued because a causal relationship between DVT and peg-IFN-α2b plus ribavirin treatment was suspected. DVT was not observed and the symptoms in both of his legs were improved after the administration of warfarin potassium. Subsequently, DVT has not recurred, and he has remained HCV-RNA negative.     

Pegylated interferon α-2b plus ribavirin for Japanese chronic hepatitis C patients with normal alanine aminotransferase

Aim: To investigate the efficacy and safety of a pegylated interferon (PEG‐IFN) α‐2b plus ribavirin (RBV) combination treatment for patients with chronic hepatitis C virus (HCV) infection who have persistently normal alanine aminotransferase (NALT). Methods: This multicenter study included 989 patients with HCV genotype 1 (114 with NALT and 875 with elevated ALT) who received weight‐based doses of PEG‐IFN α‐2b plus RBV for 48 weeks. We compared the sustained viral response (SVR) rates of patients with NALT and elevated ALT who received at least 80% or more of the target dosage of PEG‐IFN α‐2b and 60% or more of the target RBV (minimum acceptable dosage). Results: No significant difference was found in the overall SVR rate between the NALT (42.1%) and elevated ALT groups (37.3%). No significant difference in the SVR rates was found between NALT (63.3%) and elevated ALT group (61.6%) patients who received minimum acceptable dosage. Multivariate analysis showed that age (<65 years old) and total cholesterol (≧220 mg/dL) were significantly independent positive factors associated with an SVR in the NALT group. Twenty‐four weeks after treatment, an ALT increase above the normal range was observed for 34.0% (18 of 53) of the non‐responsive group of NALT patients. Conclusions: The efficacy and safety of PEG‐IFN α‐2b plus RBV combination therapy for patients with chronic HCV infection are similar for patients with NALT and those with elevated ALT levels. These results indicate that patients with NALT should be considered for treatment with PEG‐IFN α‐2b plus RBV.     

What is (cost) effective in patients with chronic hepatitis C virus infection?

Hepatitis C virus (HCV) infection often progresses to chronic hepatitis, cirrhosis, and possibly hepatocellular carcinoma. Chronic hepatitis C infection is a leading cause of chronic liver disease and the most common indication for liver transplantation. Combination therapy of interferon alpha and ribavirin is currently the standard regimen for chronic hepatitis C. This combination can achieve viral clearance in approximately 40% of patients, and improve histology and prognosis. The most cost-effective approach to guide duration of combination therapy is HCV genotyping. Cost effectiveness cannot be improved further by taking other well-defined predictive factors for sustained virological response into account. Recent insights into HCV kinetics and the correlation between initial viral decline and sustained virological response will allow us to optimize and individually tailor antiviral treatment Individualized treatment according to the initial viral decline, together with further improvements in drugs (e.g. by long-acting pegylated interferons), will have new impact on antiviral efficacy and cost effectiveness.     

Treatment of chronic hepatitis C with pegylated interferon plus ribavirin in treatment-naïve ‘real-life’ patients in India

Purpose/Aim

Results of treatment of chronic hepatitis C (CHC) with pegylated interferon plus ribavirin (PEG-RBV) are mainly available from well-designed clinical trials, and only few ‘real-life’ studies which give a true picture of success of therapy are available. Such data in Indian patients is scarce. This prospective study aimed to evaluate the efficacy, safety, and factors associated with sustained virological response (SVR) in Indian CHC patients treated with PEG-RBV in ‘real-life’ setting.

Material and Methods

All treatment-naïve patients with CHC/compensated cirrhosis treated with PEG-RBV between January 2004 and December 2010 were included.

Results

Of 592 patients started on treatment, 524 (88.5 %) completed therapy (mean?±?SD age—42.0?±?12.1 years; 74.3 % males). Genotype 3 (73.6 %) was the commonest, followed by genotype 1 (19.3 %). In intention to treat analysis, SVR rates for ‘all’ patients, genotype 1 and genotype 3 patients were 72.3 % (428/592), 57 % (65/114), and 78.2 % (341/436), respectively (in per-protocol analysis—81.7 %, 69.1 %, and 85.3 %, respectively). Noncirrhotics had better SVR rates compared to cirrhotics treated for the same duration. About 20 % patients had both low viral load and achieved rapid virological response (RVR). Factors significantly associated with SVR were age <40 years, absence of cirrhosis, RVR, and no reduction in interferon dose.

Conclusion

SVR rates in CHC patients treated in ‘real-life’ setting in India were better than those reported in western population. Therapy should be prolonged for patients with cirrhosis, while one-fifth of patients may qualify for abbreviated therapy. Factors significantly associated with SVR were age <40 years, absence of cirrhosis, RVR, and no reduction in interferon dose.     

Efficacy of peg-interferon-α-2a plus ribavirin for patients aged 60 years and older with chronic hepatitis C in Korea

Background and Aim: In the present study, we evaluated the safety and efficacy of combination therapy with pegylated interferon and ribavirin for treating chronic hepatitis C (CHC) patients aged 60 years and older. Methods: A total of 314 CHC patients, who were treated with combination therapy, were classified into three groups according to age: (i) younger than 50 years (n = 137); (ii) 50–59 years (n = 109); and (iii) 60 years or older (n = 68). The sustained virological response (SVR) and discontinuation rates were compared between the three groups. Results: Discontinuation of therapy due to adverse event was more frequent in the older patient groups: 1%, 5%, and 10% for the < 50‐year, the 50–59‐year, and the ≥ 60‐year patient groups, respectively (P = 0.018). However, the older patient groups showed a SVR rate that was comparable to the SVR rates of the other age groups: 80%, 73%, and 75% for the < 50‐year, 50–59‐year, and ≥ 60‐year‐ patient groups, respectively (P = 0.420). A multivariate analysis showed that the aspartate aminotransferase : platelet ratio index (APRI) was an independent predictor of an SVR. An SVR was achieved in 95% (19/20) of the elderly patients with an APRI < 0.80. Conclusions: Although physicians must pay more attention to adverse events in the older patients, combination therapy can be considered for older patients, especially for patients with a low APRI.     

Immunogenicity of recombinant hepatitis B vaccine in treatment-naive and treatment-experienced chronic hepatitis C patients： The effect of pegylated interferon plus ribavirin treatment

AIM: To retrospectively evaluate the vaccination-induced anti-HBs seroconversion rates in treatment-naive and treatment-experienced chronic hepatitis C (CHC) patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon (PEG) plus ribavirin (RIB) treatment. METHODS: Seventy treatment-naive CHC patients (group A), 22 sustained virological responders-SVR following interferon (IFN) plus RIB treatment CHC patients (group B) and 121 healthy subjects (group C) had been participated in the same HBV vaccination schedule (20 microg, 0-1-6 mo). Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups: Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student's t-test and chi-square analysis (P < 0.05). RESULTS: Fifty-eight of 70 group A patients (82.85%), 20/22 group B (90.9%) and 112/121 healthy subjects (92.56%) had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients (P = 0.04). The corresponding rates were comparable between group A and group B CHC patients (P = 0.38). The vast majority of non-responders (10/14, 71.43%) had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1 (20% versus 26.7%, P = 0.67), mo 2 (46.7% vs 60%, P = 0.46) and mo 7 (86.7% versus 93.3%, P = 0.54) of follow-up. CONCLUSION: The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR following IFN plus RIB treatment does not affect the antibody response to HBV vaccine. Infection by genotype-1 seems to negatively influence the seroconversion rates. Vaccination against HBV during PEG plus RIB combination treatment is not beneficial in terms of anti-HBs seroconversion rates.     

A randomized controlled clinical study of lower-dose peginterferon alfa-2b in combination with ribavirin in the treatment of chronic hepatitis C

Objective To compare the efficacy and safety of lower-dose peginterferon alfa-2b plus ribavirin versus standard interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in China. Methods 192 patients with chronic hepatitis C were assigned peginterferon alfa-2b 0.5μg/kg each week plus ribavirin 750～1050 mg/d or standard interferon alfa-2b 3 MIU TIW plus ribavirin 750～1050 mg/d for 48-week treatment and 24-week fellow     

Intraocular complications of IFN-α and ribavirin therapy in patients with chronic viral hepatitis C

We report a panel of severe inflammatory and vascular intraocular disorders occurring during interferon-alpha (IFN-α) treatment in eight hepatitis C virus (HCV)-infected patients. These events include three cases of Vogt-Koyanagi-Harada like (VKH) disease (an association of panuveitis, retinal detachment, ear and meningeal detachment and skin and hair changes), two cases of central retinal vein occlusion, one case of central retinal artery occlusion, one case of severe hypertensive retinopathy and one case of bilateral ischemic optic neuropathy with severe visual impairment. Rare as they are, such severe ophthalmological complications require a close follow-up of HCV-infected patients under IFN-α treatment with ophthalmological monitoring if any ocular manifestation occurs.