Early Virological Response Rates Research Articles

The expression of interleukin-1β in patients with chronic hepatitis B treated with pegylated-interferon-alpha combined with tenofovir disoproxil fumarate and monotherapy

BackgroundAnti-hepatitis B virus (HBV) treatment uses tenofovir disoproxil fumarate (TDF) along with Pegylated-interferon-alpha (Peg-IFN-α), which is more effective than TDF/Peg-IFN-α monotherapy. We have previously shown that interleukin-1beta (IL-1β) is related to the effectiveness of IFN-α treatment in chronic hepatitis B (CHB) patients. The aim was to investigate the expression of IL-1β in CHB patients treated with Peg-IFN-α combination with TDF and TDF/Peg-IFN-α monotherapy.MethodsHuh7 cells infected with HBV were stimulated by Peg-IFN-α and/or Tenofovir (TFV) for 24h. A single-center cohort study of prospective recruitment of CHB patients: untreated CHB (Group A), TDF combined with Peg-IFN-α therapy (Group B), Peg-IFN-α monotherapy (Group C), TDF monotherapy (Group D). Normal donors served as controls. The clinical datas and blood of patients were collected at 0, 12, and 24 weeks. According to the early response criteria, Group B and C were divided into two subgroups: the early response group (ERG) and the non-early response group (NERG). Stimulation of HBV-infected hepatoma cells with IL-1β to validate the antiviral activity of IL-1β. To test the blood sample, cell culture supernatant, and cell lysates and to assess the expression of IL-1β and HBV replication levels in various treatment protocols, Enzyme-Linked Immunosorbent Assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used. SPSS 26.0 and GraphPad Prism 8.0.2 software were used for statistical analysis. P values < 0.05 was considered to be statistically significant.ResultsIn vitro experiments, Peg-IFN-α plus TFV treatment group expressed higher IL-1β and inhibited HBV more effectively than monotherapy. Finally, 162 cases were enrolled for observation (Group A (n = 45), Group B (n = 46), Group C (n = 39), and Group D (n = 32)), and normal donors (n = 20) were enrolled for control. The early virological response rates of Group B, C, and D were 58.7%, 51.3%, and 31.2%. At 24 weeks, IL-1β in Group B(P = 0.007) and C(P = 0.034) showed higher than at 0 week. In Group B, the IL-1β showed an upward trend at 12w and 24w in the ERG. IL-1β significantly reduced HBV replication levels in hepatoma cells.ConclusionThe increased expression of IL-1β may enhance the efficacy of TDF combined with Peg-IFN-α therapy in achieving an early response for CHB patients.

Prevalence rate and prognostic value of the IL-28 gene polymorphism in hepatitis C patients in the Krasnodar territory

Objective. The study of the prevalence rate of the IL-28B genotype polymorphism in chronic hepatitis C (CHC) patients in the Krasnodar territory for the prediction of the effectiveness of various schemes of antiviral therapy. Materials and methods. There was executed the determination of single nucleotide polymorphisms (SNP) at loci rs8099917 and rs12979860 of the IL-28B gene in 833 CHC genotype 1 patients, aged of from 18 to 73 years, living in the Krasnodar Territory. In 260 cases the viral load has been determined. For genotyping IL-28B there was used the method of allele-specific PCR test system «AmpliSens Genoskrin IL28B-FL» in a amplifier with system of detection offluorescent signal in real-time mode “Rotor-Gene Q” (“Qiagen”, Germany). The investigation of the marker rs12979860 study was performed in combination with the marker rs8099917. Combinations of genotypic variants SNPIL-28B were compared with the rate of early virological response (EVR) and Sustained Virological Response (SVR) under antiviral therapy comprised of two components IFN/ ribavirin (20) andPEG-IFN/ribavirin (68 patients), as well as the "triple therapy": PEG-IFN/RBV/inhibitorsprotease 1 and 2 generations (16 cases). Results and discussion. In the Krasnodar territory in CHC genotype 1 patients there is prevailed heterozygous variant rs12979860 CTIL-28B (58.3%), potentially unfavorable in the prescription of "double" therapy. The detection rate of the protective allele CC is 2.1 times less often (27.7%). In the rs8099917 locus there is dominatedfavorable TTgenotype (53.4%), slightly exceeding the frequency of heterozygous risk genotype GT (41.2%). The frequency of combinations of various protective genotypes (CC+CT), less favorable (CT+TT), the most unfavorable for the prognosis (CT+GT) for two interleukin 28B gene loci is about the same accounting of from 26.3 to 32%. Patients with protective CC+TT alleles had the significantly higher viral load if compared with a group of patients with unfavorable TT+GG homozygotes. In the treatment of CHC patients with genotype CC+CT in investigated loci (rs12979860 and rs8099917) according to such schemes as IFN/RBV and Peg-IFN/RBV, EVR was observed in 100% and SvR - in 89.4-849% ofpatients respectively. The combination of CT+TT alleles of the IL28B gene significantly reduced the effectiveness of treatment of PEG-IFN/RBV to 50%; in this process a combination of CT+GT heterozygotes has the highest proportion while SVR does not exceed 33.3%."Triple" therapy with PEG-IFN/RBV/ protease inhibitors of 1st and 2nd generations eliminates the significance of the combination of unfavorable genotypes SNP of the interleukin 28B gene, allowing to achieve EVR in all the patients with the absence of protective alleles CC+TT, SVR - in 85.7% of cases. Conclusion. In choosing treatment regimens for CHC genotype 1 patients the differentiated approach is appropriate, with taking into account the favorable and unfavorable combinations of genotypic variants of the IL28B gene concerning rs12979860 and rs8099917. In patients with the presence ofprotective alleles CC+TT on these loci, a "double" combination therapy by as pegylated as well standard interferon preparations with ribavirin is highly effective and may be preferred; in the combination of less favorable alleles CT+TT, and particularly unfavorable heterozygotes CT+GT ofIL-28B gene, it is advisable to use a "triple" therapy with PEG-IFN/RBV/protease inhibitors of 1st and 2nd generations or non-interferon regimens. The study of the distribution of SNP genotypes of IL28B genes and their combinations in CHC patients C allowed to evaluate rationally the need of that cohort ofpatients for various, including expensive non-interferon, therapy schemes.

Coadministration of ezetimibe with pegylated interferon plus ribavirin could improve early virological response in chronic hepatitis C obese Egyptian patients.

Ezetimibe has been reported to inhibit viral entry and to reduce BMI and has been proposed as a novel therapeutic agent for chronic hepatitis C (CHC), potentiating the effects of pegylated interferon and ribavirin (peg-IFN/RBV). The aim of the study was to assess the effects of ezetimibe coadministration with peg-IFN/RBV combination on the early virological response (EVR) rates in nonobese and obese patients with CHC genotype 4 (CHC-4). A total of 144 CHC-4 patients were divided into two groups; group 1 included nonobese patients (n=76) and group 2 included obese patients (n=68). Each group was further subclassified into equal control and treated groups. The control groups received peg-IFN/RBV combination for 24 weeks, and the treated groups received peg-IFN/RBV plus ezetimibe for 12 weeks and then only peg-IFN/RBV for the remaining 12 weeks. The study revealed that EVR significantly improved in the obese patients (85.3 vs. 64.7% in the treated and control groups, respectively, at P<0.05) without any significant improvement in the nonobese patients. Biochemical responses (defined as normalization of alanine aminotransferase at week 12) were markedly improved in the treated groups in both the nonobese and obese groups compared with their respective controls. The addition of ezetimibe to peg-IFN/RBV combination significantly improves EVR rates in obese patients compared with nonobese patients, and remarkably improves the biochemical responses in both obese and nonobese patients with CHC-4. This may shed light on a new strategy for the treatment of CHC, particularly in obese Egyptian patients.

Impact of Weight Loss in Overweight Patients Enrolled in Weight Management Program Prior to Hepatitis C Treatment on Early Virological Response

Background: Obesity is a risk factor for non-response to interferon-based hepatitis C therapy. We studied the effect of weight management program to induce weight loss in overweight patients prior to starting antiviral therapy on treatment response. Methods: Overweight patients received a weight loss brochure and a 6-week nutrition and exercise program prior to PEG-IFN + Ribavirin therapy (n=25). Early virological response rates (EVR) were compared between overweight subjects with and without ≥ 3% weight loss and control lean subjects (n=11). Results: Moderate to severe fibrosis was present in 41.7% and moderate to severe steatosis in 16.7% of patients. Most were Caucasians (90% and 72% for lean and overweight group, respectively). There was no statistical difference in age, sex or race between those who lost ≥ 3% of their body weight and those who didn’t among overweight group. Overweight subjects who lost ≥ 3% of body weight at week 12 of CHC therapy had higher EVR vs. those without ≥ 3% weight loss, 69.2% vs. 33.3%, p=0.036. Conclusion: Overweight patients enrolled into weight management program who achieved ≥ 3% body weight loss at 12 weeks of CHC therapy had higher EVR compared to those without 3% weight loss.

Retreatment of Chronic Hepatitis C Infection with Telaprevir: Preliminary Results in Turkey.

The use of pegylated interferon alpha and ribavirin (PegIFN/RBV) for the retreatment of chronic hepatitis C virus (HCV) infection without a sustained virological response (SVR) prior to PegIFN/RBV treatment has resulted in low success rates. To investigate the efficacy and safety of telaprevir (TVR) in combination with PegIFN/RBV in patients infected with HCV genotypes 1 and 4 who were previously treated with PegIFN/RBV and failed to achieve SVR. Multi-center, retrospective, cross-sectional study. The study included 111 patients: 80 prior relapsers, 25 prior null responders, and six prior partial responders to PegIFN/RBV treatment. The patients were given TVR/PegIFN/RBV for 12 weeks, followed by a 12-week PegIFN/RBV treatment; virological response results were assessed at weeks 4, 12, and 24. Treatment was discontinued in patients with HCV RNA >1000 IU/mL at week 4 or with negative RNA results at week 4 but >1000 IU/mL at week 12. Rapid virological response (RVR), early virological response (EVR), extended rapid virological response (eRVR), and virological response at 24th week of treatment were evaluated. The side effects of combination therapy and the rates of treatment discontinuation were investigated. The mean age of the patients was 56.02±9.96 years and 45.9% were male. Ninety-one percent of the patients were infected with viral genotype 1, 69.6% with the interleukin (IL) 28B genotype CT and 20.2% were cirrhotic. The RVR rate was 86.3% in prior relapsers, 56% in prior null responders, and 50% in prior partial responders (p=0.002). EVR rates in those groups were 91.3%, 56%, and 83.3%, respectively (p<0.001). eRVR rates were 83.8% in prior relapsers, 48% in prior null responders, and 50% in prior partial responders (<0.001). The virological response at the 24th week of treatment was found to be the highest in prior relapsers (88.8%); it was 56% in prior null responders and 66.7% in prior partial responders (p<0.001). Common side effects were fatigue, headache, anorexia, malaise, anemia, pruritus, dry skin, rash, dyspepsia, nausea, pyrexia, stomachache, and anorectal discomfort. All treatments were discontinued due to side effects in 9.9% of patients. High virological response rates were obtained with TVR/PegIFN/RBV treatment. Although side effects were frequently observed, the discontinuation rate of combination therapy was low.

Impact of Interferon Lambda Gene Polymorphism on Treatment of HCV-4 Infection in Diabetic Patients

Background & Aim: IL28B polymorphisms are strongly associated with response to treatment for HCV infection. IL28B acts on interferon-stimulated genes via the JAK-STAT pathway, which has been implicated in development of insulin resistance. This study aimed to evaluate the Impact of interferon lambda gene polymorphism on treatment of HCV-4 infection in diabetic patients. Methods: Occurrence of variants at three IL28B-Related Single Nucleotide Polymorphisms (rs12979860, rs12980275, and rs8099917) was correlated with virologic response to combined treatment with pegylated interferon and ribavirin among 104 HCV -4 infected Egyptian patients (41 diabetic vs. 63 non-diabetic patients). Results: IL28B-Related Single Nucleotide Polymorphisms had significant impact on virologic responses to combined treatment among non-diabetic patients; CC subtype of rs12979860 and AA subtype of rs12980275 had the highest rapid virologic response rates (p=0.02 and 0.04 respectively). Early virologic response rates were significantly higher among non-diabetic patients with CC subtype of rs12979860 (p=0.005), AA subtype of rs12980275 (p=0.04) and TT subtype of rs8099917 (p=0.01).Significant higher percentage of sustained virologic response rates was found among non-diabetic patients with CC subtype of rs12979860 (p = 0.003) and AA subtype of rs12980275 (p = 0.004). Strikingly, all the subtypes of the three IL28B-Related Single Nucleotide Polymorphisms (rs12979860, rs12980275, and rs8099917) had no impact on virologic responses to combined treatment among diabetic patients. Conclusions: Non-diabetic patients with chronic hepatitis C-4 infection are more likely to benefit from the assessment of IL28B-related SNPs (rs12979860, rs12980275, rs8099917) in the prediction of virologic response to combined treatment than diabetic patients. Keywords: DM, SVR, HCV-4, IL28B, rs12979860, rs12980275, rs8099917. Read more →

The comparison of the efficacy of pegylated interferon α-2a and α-2b in chronic hepatitis C patients with genotype 1

The aim of this study was to assess the efficacy of treatment with pegylated interferon α-2a (Peg-INFα-2a) versus Peg-INFα-2b, plus ribavirin, in inducing rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR), and sustained virological response (SVR) in chronic hepatitis C. We reviewed 78 chronic hepatitis C patients with genotype 1 treated with 48 weeks of Peg-INFα-2a (n=35) and Peg-INFα-2b (n=43), plus ribavirin, between 2008 and 2011. The ETR and SVR of the patients were ascertained by assessing hepatitis C virus (HCV)-RNA levels at the end of the treatment and after 24 weeks of follow-up after the cessation of treatment. The RVR (31 vs. 26%), EVR (83 vs. 81%), ETR (74 vs. 63%), and SVR (46 vs. 51%) rates were similar for Peg-INFα-2a and Peg-INFα-2b groups. The overall SVR rate for these standard therapies was 48.7%. Multivariate analysis showed that HCV viral load was significantly associated with RVR, EVR, ETR, and SVR inversely (r=-0.25, P<0.05, and r=-0.34, r=-0.53, r=-0.42, P<0.01, respectively). In patients infected with HCV genotype 1, the rates of SVR did not differ significantly between the two available Peg-INF-ribavirin regimens, and HCV viral load was important in RVR, EVR, ETR, and SVR.

Meta‐analysis: pegylated interferon α‐2a achieves higher early virological responses than α‐2b in chronic hepatitis C

A Cochrane meta-analysis established that pegylated interferon α-2a is more effective than peginterferon α-2b in terms of sustained virological response (SVR) in the treatment of chronic hepatitis C. Rapid virological response (RVR) and early virological response (EVR) are crucial to reach SVR and to make clinical decisions. To compare RVR and EVR rates of peginterferon α-2a vs. peginterferon α-2b through a meta-analysis of previously published randomised control trials (RCT). MEDLINE, EMBASE and LILACS databases were systematically searched up to September 2011. Seven RCT that reported complete early virological response (cEVR) were selected. A meta-analysis focusing on RVR and cEVR outcomes was conducted and Relative Efficacy (RE) was calculated. Meta-analysis of cEVR included seven trials (n = 4359), and yielded an estimated effect in favour of peginterferon α-2a: Crude Efficacy (CEf) was 53.3% vs. 43.8%, RE = 1.118 (CI 95% = 1.039-1.203; P = 0.0028), heterogeneity Q = 8.959; I² = 33.0% (P = 0.1759). A sub-analysis of three studies with 3409 genotype-1 patients yielded CEf: 49.4% vs. 40.2%, RE = 1.151 (CI 95% = 0.968-1.369; P = 0.1124), Q = 9.802; I² = 79.6% (P = 0.0074). Meta-analysis of RVR included five trials (n = 3833) with an estimated effect in favour of peginterferon α-2a: CEf = 25.0% vs. 16.8%, RE = 1.151 (CI 95%:1.042-1.272; P = 0.0056), Q = 1.461;I² = 0.0% (P = 0.8335). Analysis of four studies reporting RVR including 3499 patients with genotypes 1 and 4 resulted in CEf: 18.3% vs. 12.7% RE = 1.206 (CI 95% = 1.059-1.374; P = 0.0048), Q = 1.116; I² = 0.0% (P = 0.7733). Peginterferon α-2a may be associated with a higher cEVR and RVR than peginterferon α-2b. These findings could help to achieve higher SVR rates and support clinical decision-making in the present scenario of triple combination therapy.

Review article: the treatment of genotype 1 chronic hepatitis C virus infection in liver transplant candidates and recipients

Recently, the therapeutic landscape with regard to anti-HCV therapy has changed dramatically. The new directly acting anti-virals (DAAs) have demonstrated improved sustained virological response (SVR) compared with pegylated-interferon and ribavirin. To examine and present the latest data with regard to anti-viral therapy in genotype 1 HCV-positive transplant candidates and recipients. An electronic search using Medline was performed. Search terms included 'HCV, DAA and protease inhibitor' in combination with 'treatment pre-transplantation' and 'treatment post-transplantation'. Patients with advanced fibrosis and cirrhosis have inferior SVR rates compared with patients with minimal fibrosis. A low accelerating dose regimen (LADR) of pegylated interferon and ribavirin (PR) appears to be a safe therapeutic option. Side effects also appear to be more pronounced in patients with advanced disease. Data from the large registration studies with triple therapy (boceprevir or telaprevir plus PR) demonstrated improved SVR rates even in patients with advanced disease, although virological relapse rates were highest amongst these patients. In transplant recipients, initial data are being reported on the use of triple therapy, and although no SVR data are available, promising results are accruing. The drug-drug interactions appear to be manageable. Side effects in particular anaemia appear to be markedly increased in the posttransplant setting. The use of the new DAAs in patients with advanced fibrosis/cirrhosis pretransplant and posttransplant appears possible, with manageable side effects and drug-drug interactions, and improved early virological response rates. We recommend that these patients are managed in centres with the appropriate expertise.

Treatment of hepatitis C in compensated cirrhotic patients is equally effective before and after liver transplantation

To investigate differences in tolerability and response to treatment in compensated cirrhotic patients affected by hepatitis C virus (HCV) infection before and after liver transplantation. Forty-three HCV non-liver transplanted (LT) cirrhotics (mean age 55 ± 8 years, 65.1% male, Child-Pugh-A, genotype 1-4: 65.1%, 2-3: 34.9%) and 17 LT recipients with recurrent HCV-related cirrhosis (mean age 57 ± 9 years, 88.2% male, Child-Pugh-A, genotype 1-4: 76.5%, 2-3: 23.5%) were included in the analysis from retrospective series. All patients received recombinant or pegylated interferon plus ribavirin at a standard dose and duration. Adverse events were recorded and classified according to the Common Terminology Criteria for Adverse Events. The mean duration of follow-up was of 4.3 ± 1.8 years after the end of the treatment. An early virological response (EVR) was achieved in 30/43 (69.8%) non-LT and in 8/17 (47.1%) LT cirrhotics, a sustained virological response (SVR) in 18/43 (41.9%) and 5/17 (29.4 %), respectively. No statistical difference was observed in EVR and SVR rates between the two groups. Among HCV non-LT cirrhotics, 6/43 (13.9%) discontinued the treatment prematurely, 11.6% of them receiving ≤ 80% of treatment; 8/17 (47%) LT cirrhotics withdrew the treatment, 35.2% of them receiving ≤ 80% of treatment. If compared with LT-ones (P = 0.015), an higher risk of treatment discontinuation could affect LT cirrhotics, who undergo more frequently ≤ 80% of treatment (P = 0.05). None of the non-LT cirrhotics died after the end of the treatment. With no regards to the achievement of SVR, LT cirrhotic patients showed a reduced survival in respect to non-LT ones (87% at 1 year, 76% at 3 and 5 years after the end of treatment). HCV antiviral treatment is equally effective in compensated cirrhotics both before and after LT, which patients show a higher risk of premature treatment withdrawal and a reduced survival, independently of the achievement of SVR.

No beneficial effect of all-trans retinoic acid in previous non-responder patients with chronic hepatitis C: The ATRACTION study, a phase II randomised trial

BackgroundPreclinical data suggested all-trans retinoic acid (tretinoin) as a potential antiviral agent against chronic hepatitis C infection. AimsTo assess efficacy, safety, and tolerability of tretinoin in combination with peg-interferon and ribavirin in genotype-1 infected patients with prior non-response. MethodWe performed an open-label multicentre clinical trial. Patients were randomised to either receive additional tretinoin (45mg/m2/day) for 12 weeks (arm A), or peg-interferon and ribavirin alone (arm B). Primary endpoint was the slope of the third phase of viral decline (Mδ) as determined in an established kinetic model known to correlate with treatment outcome. Secondary endpoints were additional kinetic parameters, viral response rates, safety, and tolerability. Results27 patients in arm A and 30 patients in arm B were treated per protocol until week 12. Viral kinetic parameters did not differ. Rates of early virological response (>2log10 drop at week 12) were similar (10/27 versus 11/30 patients). In arm A, patients experienced a higher rate and intensity of adverse events, most commonly skin and mucosal dryness, and headache. ConclusionAddition of tretinoin was safe and acceptably well tolerated. However, it did not influence viral kinetics and thus cannot be further considered as a treatment option.

The relationship of Genetic Polymorphisms of the MxA and HCV genotype with early virological response to interferon for HIV/HCV co-infection

Objective To explore the relationship of host single nucleotide polymorphisms( SNP )of the MxA gene and HCV genotype with early virological response ( EVR ) )to interferon for HIV/HCV coinfected patients.Methods 151 HIV/HCV co-infected patients were treated with interferon-2b ( INF-2b ) plus ribavirin( RBV ) for 24 weeks,then were divided into EVR group and non EVR ( NEVR )group.HCV genotype and SNP of the MxA promoter-88 site and -123 site were examined by polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP ) and the relationship of SNP of MxA and HCV genotype with EVR to IFN-2b were analysed.Results 12 cases were excluded because of no record of HCV genotype.Among the 139 patients,52 cases ( 34.4％ ) were genotype 1,87 cases ( 57.7％ ) were non-1 genotype.The rate of EVR in was higher in genotype 1 than in non-1 genotype ( x2=14.547,P ＜ 0.001 ); GT genotype at MxA promoter-88 responded better to INF treatment than GG and TT genotype,but the difference was not significant( x2=2.711,P ＞ 0.05 ).AT MxA promoter-123 site,the responses among CC,CA and AA genotype were not significantly different ( x2=0.453,P ＞ 0.05 ).In HCV non-1 genotype patients,the rate of EVR was higher in GT and TT genotype ( 91.5％ ) than in GG genotype ( 77.5％ ),but the difference was not significant ( x2=3.327,P=0.068 ).The rates of EVR in GT,GG and TT genotype of HCV genotype 1 patients were not significantly different.The rate of EVR in GT and TT genotype( 91.5％ )was higher in HCV genotype 1 patients than in non-1 genotype patients( 62.5％ ),and the difference was significant ( P ＜ 0.05 ).Conclusions Among HIV/HCV co-infected patients,those HCV non-1 genotype patients have a higher rate of EVR to INF than those genotype 1 ones,and those with GT genotype at MxA promoter-88 responds better to IFN treatment.It can be helpful in assessing the outcome and prognosis of IFN treatment. Key words: Chronic hepatitis C; Human Immune Deficiency Virus; Interferon; MxA

Impact of ribavirin dose reduction during treatment in chronic hepatitis C genotype 1 patients

Impact of ribavirin dose reduction during treatment in chronic hepatitis C genotype 1 patients

Efficacy of peginterferon and ribavirin is associated with the IL28B gene in Korean patients with chronic hepatitis C

Background/AimsSustained virologic response (SVR) for the treatment of chronic hepatitis C (CHC) may differ with ethnicity due to differences in genetic traits. This study evaluated the efficacy of peginterferon and ribavirin, and the association between IL28B genotypes and the treatment efficacy in Korean CHC patients.MethodsThis was a retrospective cohort study using data from medical records. Eighty-five CHC patients were eligible for assessment of the efficacy of antiviral therapy, and 47 patients were available for an IL28B genetic study, which was performed using the Multiplex tetra-primer PCR method for rs12979860.ResultsOverall, the early virologic response rate was 87.1%: 84.9% in HCV genotype 1 and 90.6% in genotype 2. The overall end-of-treatment virologic response rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. The overall SVR rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. For rs12979860, the frequencies of polymorphisms were 89% for the CC type, 11% for the CT type, and 0% for the TT type. Their overall SVR rate was 87% (39/47): 90.5% (38/42) for the CC type and 20% (1/5) for the CT type. For genotype 1, SVR rates were 88% (21/24) for the CC type and 0% (0/4) for the CT type. Multivariate analysis revealed that the IL28B-CC type was a good predictor for SVR.ConclusionsThe SVR of the combination therapy in Koreans was higher than that observed in Western countries. This finding might be attributable to the high prevalence of IL28B-CC type among Koreans, which may be a good predictor of SVR.

Efficacy of peginterferon α-2a and predictors of response in HBeAg-negative, genotype D-naive patients

BackgroundPeginterferon (PEG-IFN) α-2a has been shown to induce a sustained virologic response (SVR) in 20–30% of “hepatitis B e antigen (HBeAg)”-negative patients.AimTo determine the safety and efficacy of PEG-IFN α-2a in HBeAg-negative, genotype D-naive patients and to analyze the predictors of response.MethodsThis prospective, multicenter, open-label, nonrandomized trial was conducted at four hospitals. A total of 35 consecutive HBeAg-negative naive genotype D patients received PEG-IFN α-2a for 48 weeks.ResultsBased on a cutoff of hepatitis B virus (HBV) DNA <400 copies ml−1, an early virologic response (EVR) at week 12, end of treatment virologic response (ETVR) at week 48, and SVR at week 72 were achieved by 3 (9%), 9 (26%), and 8 patients (23%), respectively. The EVR rate improved to 43%, ETVR to 49%, and SVR to 57%, when a HBV DNA cutoff level of <20,000 copies ml−1 was used. Pretreatment HBsAg level was not a predictor for SVR on univariate analysis, but correlated with decline in HBV DNA levels at weeks 48 and 72. On multivariate logistic regression analysis, low body weight, high alanine aminotransferase (ALT), low HBV DNA, and low triglyceride levels were identified as baseline predictors of SVR.ConclusionHBeAg-negative genotype D-naive patients treated with PEG-IFN α-2a achieved SVR in 23 (HBV <400 copies ml−1) and 57% (HBV <20,000 copies ml−1) of patients, a better response than previously reported that might be related to the absence of drug resistance in these naive patients. Pretreatment predictors of SVR were low body weight, high ALT, low HBV DNA, and low triglycerides.

Rapid, early and sustained virological responses in a cohort of Irish patients treated with pegylated interferon and ribavirin for chronic hepatitis C virus infection

The response to the treatment with pegylated interferon (PEG IFN)-α combined with ribavirin in chronic hepatitis C virus (HCV) infection varies with some patients having a rapid or early response which is not sustained. To investigate the rates of rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) in an Irish cohort of HCV infected patients receiving IFN-α/ribavirin. Rates of RVR, EVR and SVR were examined in 123 patients undergoing standard treatment for chronic HCV infection between 2001 and 2007 at a Dublin Teaching Hospital. The rates of RVR, EVR and SVR in genotype 1 patients were 48, 68 and 50%, while in genotype 2/3 patients they were 87, 93 and 87%, respectively. The positive predictive values (PPV) of RVR for SVR in genotype 1 and genotype 2/3 patients were 90 and 92.4%, respectively. The rates of response to PEG IFN-α/ribavirin in Irish patients are consistent with other international reports. We support the regular monitoring of rapid and early virological response as a standard of care in treating chronic hepatitis C patients.

The effect of cryoglobulinemia on the antiviral therapy in patients with chronic hepatitis C

To investigate the possible influence of cryoglobulinemia on the antiviral effect in chronic hepatitis C patients, who were treated with combination therapy of pegylated interferon alpha-2a and ribavirin. Forty consecutive patients with chronic hepatitis C (CHC) were enrolled in the study. They received pegylated interferon alfa-2a (40kD, 180mug/w) along with ribavirin. Baseline cryoglobulins were detected in the sera by cryoprecipitation. Hepatitis C virus (HCV) genotyping was performed and HCV viral load was detected at baseline, and at 4, 12 weeks during treatment, 24 weeks after cessation of treatment. Eighteen (45.0%) patients infected with HCV were cryoglobulins positive at baseline. Mean serum HCV RNA level in cryoglobulins positive patients was higher than that in cryoglobulins negative patients (6.36+/-0.63 vs. 5.70+/-1.20, P = 0.032). The rapid virological response (RVR) rate was statically different between cryoglobulins positive patients and cryoglobulins negative ones (6/18, 33.3% vs. 15/22, 68.2%, P = 0.028). In contrast, no difference was found in early virological response (EVR) rate between the cryoglobulins positive patients and cryoglobulins negative ones (14/17, 82.4% vs. 18/21, 85.7%, P = 1.0). Sustained virological response (SVR) rate in cryoglobulins positive and cryoglobulins negative was different (0/3, 0 vs 6/6, 100%, P = 0.012). The rate of patients achieved RVR was different between the patients infected with HCV genotype 1 b of two groups (cryoglobulins positive: 2/13, 15.4% vs cryoglobulins negative 14/21; 66.7%, P = 0.005). However, the rate of EVR in patients infected HCV genotype 1 b was not statistically different (cryoglobulins positive: 9/12, 75.0% vs. cryoglobulins negative 17/20; 81.2%, P = 0.647). The rates of RVR and SVR achievement in cryoglobulinemia positive CHC patients are lower than those in cryoglobulinemia negative CHC patients.

Effect of An Induction Period of Pegylated Interferon-α2A and Ribavirin on Early Virological Response in HIV–HCV-Coinfected Patients: Results from the Coral-2 Study

It is uncertain whether a 4-week induction period of pegylated interferon and ribavirin increases early virological response (EVR) in HIV-HCV-coinfected patients. HIV and HCV genotype 1- and 4-coinfected subjects were randomized to receive pegylated interferon-α2a 270 μg/week plus ribavirin 1,600 mg daily and epoetin-β for 4 weeks, followed by pegylated interferon-α2a at standard dosages plus weight-based ribavirin (WBR) dosage for 8 weeks (induction arm [IA]), or pegylated interferon-α2a plus WBR for 12 weeks (standard therapy arm [SA]). HCV RNA was determined at weeks 0, 1, 2, 3, 4, 8 and 12. Ribavirin plasma trough concentrations were determined at weeks 4 (RBV-C(4)) and 12 (RBV-C(12)). A total of 67 patients were included; 33 in the SA and 34 in the IA. Overall, 25% received nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens. More patients achieved an HCV RNA decrease ≥1 log(10) at week 4 in the IA than in the SA (62% versus 38%; P=0.017), but EVR rates were similar in the two groups (74% versus 59% in the IA and SA, respectively; P=0.15). Independent predictors of faster HCV RNA decrease at 12 weeks were higher RBV-C(4) and younger age. RBV-C(4) were higher in patients allocated in the IA and in those receiving NRTIs (P=0.039). A 4-week induction with pegylated interferon-α2a plus ribavirin was associated with a greater decrease in HCV RNA at week 4; however, this did not translate into higher EVR rates. Higher RBV doses and avoidance of NRTI-sparing antiretroviral regimens might improve HCV treatment efficacy.

Reply

We thank Matthews and Dore for agreeing with our suggestion to treat human immunodeficiency virus (HIV)-infected patients with acute hepatitis C by using combination therapy,1 although they advocate a 24-week duration because 85% of their patients with early virological response (EVR) but not rapid virological response (RVR) achieved sustained virological response (SVR) after a 24-week course in the recent ATAHC study.2 This is a key point, because the optimal duration would be the best compromise between reducing expense and toxicity on the one hand, and maximal efficacy on the other hand, given the faster and more severe evolution of HCV infection in HIV-infected patients. We agree that excluding patients who failed in the HEPAIG study to achieve RVR or EVR (n = 4) would enhance the SVR rate of 24-week course therapy. Indeed, the SVR rate in patients experiencing EVR, when assessed, was 88% (8/9), which is higher than that observed in ATAHC (74%)2 and close to the 92% obtained with a longer course in HEPAIG.1 However, the RVR rate in HEPAIG was high, particularly for the 14 patients treated for 24 ± 4 weeks (57%), compared with that observed in ATAHC (34%), whereas the EVR rate was lower (75% versus 91%). Because HCV therapy and doses were similar in these studies, this may be linked to differences in HCV genotype distribution (with a potential cluster effect), in the clinical presentation of acute hepatitis C, or in the characteristics of the patients (e.g., the HCV transmission route and perhaps the distribution in IL28B gene polymorphisms). Whatever the reasons, most patients with EVR in HEPAIG had RVR previously. Only two patients in HEPAIG experienced EVR but not RVR. Although both of these patients achieved SVR, this finding is not sufficient to draw conclusions, in contrast with the ATAHC study, where 17/20 patients with EVR but not RVR experienced SVR.2 Whether the three patients who did not experience SVR would have benefited from a longer course cannot be established from the ATAHC study. Recent cohort studies on acute hepatitis C in HIV-infected patients are quite supportive and complementary in helping to define the best strategy in treating acute hepatitis C in HIV-infected patients. They highlight the pivotal role of HCV kinetics assessment on the management of HCV therapy. From both the HEPAIG1 and ATAHC reports,2, 3 patients with RVR have to be treated for 24 weeks. For patients experiencing EVR but not RVR, SVR rate following a 24-week course ranges from 75% in the European Cohort Study4 (albeit including some patients with a 48-week course therapy) to 85% in ATAHC,2 compared with a hepatitis C virus (HCV) eradication rate of 100% (10/10) with a longer course in HEPAIG.1 Whether this mean difference of roughly 15%-20% is significant, relevant, or marginal may be debated and should only be addressed in randomized, controlled trials. Nevertheless, our conclusions parallel the recent recommendations of the NEAT consensus conference stating that it would be reasonable to aim for a 24-week course, with a longer duration reserved for those without RVR but with EVR.5 Finally, we also agree that new HCV therapies will probably lead to modifications in these propositions, not only by improving the success rate of retreatment of patients failing to respond to first line pegylated interferon–ribavirin therapy, but also as a first-line treatment of acute hepatitis C. Lionel Piroth*, Christine Larsen , Elisabeth Delarocque-Astagneau , Stanislas Pol§, * Infectious Diseases Department, University Hospital, and Université de Bourgogne, Dijon, France, Institut de Veille Sanitaire, Saint Maurice, France, Unité d'épidémiologie des maladies émergentes, Institut Pasteur, Paris, France, § Université Paris Descartes, Institut Cochin Inserm U1016 and service d'Hépatologie, APHP-Hôpital Cochin, Paris, France.

Twenty-four weeks of pegylated interferon plus ribavirin effectively treat patients with HCV genotype 6a

The optimal duration of treatment and expected response rate for hepatitis C virus genotype (HCV-6)-infected patients have not been determined. Our aims were to determine the treatment outcome with pegylated interferon (PEG-IFN) plus ribavirin for HCV-6a-infected patients at Southwest Hospital and assess the association of the on-treatment virological response with the sustained virological response (SVR). Medical records were reviewed retrospectively. Twenty-two HCV-6a-infected patients were treated for 24 weeks, and 21 (95.5%) achieved an early virological response (EVR), 20 (90.9%) an end-of-treatment response (ETR) and 18 (81.8%) a SVR. However, only 18 of the 22 HCV-6a-infected patients were tested for serum HCV RNA level at week 4 of treatment and 15 (83.3%) achieved a rapid virological response (RVR). The rates of SVR, RVR, EVR and ETR in these patients were all similar to those in HCV-2/3 treated for 24 weeks and higher than those in HCV-1b-infected patients treated for 48 weeks. A lower relapse rate (10.0%) was seen in HCV-6a compared with HCV-2/3 (12.5%) or HCV-1b-infected patients (23.3%). The positive predictive values of RVR and EVR for HCV-6a were comparable with those for HCV-2/3-infected patients (86.7%vs 90.9%, P = 0.683 and 85.7%vs 86.8%, P = 0.904, respectively). Of the 3 HCV-6a-infected patients who did not achieve a RVR, 2 achieved an EVR and went on to achieve a SVR. The patient who did not achieve an EVR did not achieve a SVR. In summary, our results indicate that 24 weeks of PEG-IFN plus ribavirin can effectively treat patients with HCV-6a chronic infection.