Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin

BACKGROUND AND AIM: The therapeutic effect of pegylated interferon (peg-IFN)-alpha-2a combination with ribavirin on patients with chronic hepatitis C virus (HCV) infection is dependent on the rapidity of the virological response. The aim of this study was to investigate the predictive value of rapid virological response (RVR) and early virological response (EVR) on sustained virological response (SVR) in HCV patients treated with peg-IFN-alpha-2a and ribavirin. METHODS: The HCV genotypes of 105 patients with chronic hepatitis C were detected by enzyme-immunoassay. Patients received subcutaneous 180 microg peg-IFN-alpha-2a once weekly plus daily ribavirin. Patients with genotype 1 were treated for 48 weeks and patients with genotype 2 or 3 were treated for 24 weeks. HCV RNA was assessed by qualitative PCR at pretreatment, at weeks 4 and 12 during treatment, and at week 24 of follow-up. Virological response rates at different weeks were investigated, with RVR defined as serum HCV RNA undetectable after 4 weeks and EVR defined as HCV RNA either undetectable or decrease by >or=2 log(10) after 12 weeks. The effects of virological response rates at different weeks on SVR were analyzed. RESULTS: Of the 105 patients, 44 (41.9%) were genotype 1, 46 (43.8%) were genotype 2, and 15 (14.3%) were genotype 3. RVR rates (19.5%) of patients with genotype 1 were significantly lower than those (60.7%) of genotype 2 or 3 (chi(2) = 16.836, P = 0.000); and EVR rates (73.2%) of patients with genotype 1 were significantly lower than those (96.7%) of genotype 2 or 3 (chi(2) = 12.220, P = 0.000). The SVR rates (86.7%) of patients who had achieved RVR were significantly higher than those (43.9%) of patients who had not achieved RVR (chi(2) = 19.713, P = 0.000). The positive predictive value of RVR in all patients was higher than that of EVR, but there was no significant difference between RVR and EVR. The negative predictive value of RVR in all patients or with genotype 1 was significantly lower than that of EVR. In univariate analysis, HCV RNA level (P = 0.014), genotype (P = 0.001), RVR (P = 0.000) and EVR (P = 0.000) were associated with effect of treatment. However, in stepwise regression analysis, the independent factors associated with effect of antiviral therapy were RVR (OR = 6.501, P = 0.001), EVR (OR = 2.776, P = 0.003) and genotype (OR = 3.061, P = 0.024). CONCLUSIONS: The RVR and EVR rates of patients with genotype 1 were significantly lower than those of patients with genotype 2 or 3. RVR had a similar predictive value as EVR on SVR. Genotype, HCV RNA level, RVR and EVR were associated with SVR. Genotype, RVR and EVR were independent factors for predicting the effect of antiviral therapy.     

APRI as a predictor of early viral response in chronic hepatitis C patients

AIM: To evaluate the aspartate aminotransferase (AST) to platelet ratio index (APRI) as a predictive factor of early viral response in chronic hepatitis C naive patients.METHODS: We performed an ambispective casecontrol study. We enrolled chronic hepatitis C naive patients who were evaluated to start therapy with PEGylated interferon a-2b (1.5 mg/kg per week) and ribavirin (> 75 kg: 1200 mg and < 75 kg: 1000 mg). Patients were allocated into two groups, group 1: Hepatitis C patients with early viral response (EVR), group 2: Patients without EVR. Odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the relationship between each risk factor and the EVR in both groups.RESULTS: During the study, 80 patients were analyzed, 45 retrospectively and 35 prospectively. The mean ± SD age of our subjects was 42.9 ± 12 years; weight 70 kg (± 11.19), AST 64.6 IU/mL (± 48.74), alanine aminotransferase (ALT) 76.3 IU/mL (± 63.08) and platelets 209 000 mill/mm3 (± 84 429). Fifty-five (68.8%) were genotype 1 and 25 (31.3%) were genotype 2 or 3; the mean hepatitis C virus RNA viral load was 2 269 061 IU/mL (± 7 220 266). In the univariate analysis, APRI was not associated with EVR [OR 0.61 (95% CI 0.229-1.655, P = 0.33)], and the absence of EVR was only associated with genotype 1 [OR 0.28 (95% CI 0.08-0.94, P = 0.034)]. After adjustment in a logistic regression model, genotype 1 remains significant.CONCLUSION: APRI was not a predictor of EVR in chronic hepatitis C; Genotype 1 was the only predictive factor associated with the absence of EVR in our patients.     

Peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a monotherapy in early virological responders and peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a, ribavirin and amantadine triple therapy in early virological nonresponders: the SMIEC II trial in naïve patients with chronic hepatitis C

OBJECTIVE: The objective of this study was to compare the efficacy of anti-hepatitis C virus (anti-HCV) treatment schedules on the basis of an early virological response (EVR), defined as undetectable serum HCV-RNA (<50 IU/ml) after a 12-week induction course of peginterferon alpha-2a (PEG-IFN) 180 mcg/week. METHODS: A total of 210 interferon-na?ve patients (69% male; median age, 42 years) with histologically proven chronic hepatitis C infection (genotype 1: 62%) received PEG-IFN 180 mcg/week for 12 weeks. Patients with EVR (58%) were randomized to continue PEG-IFN monotherapy (n=64) or to add ribavirin (RBV), 800 mg/day (n=57), for 36 additional weeks. Patients without EVR (42%) were randomized to add RBV (n=42), or RBV plus amantadine, 200 mg/day (n=47), for 36 additional weeks. Sustained virological response (SVR, undetectable HCV-RNA 24 weeks after treatment completion) was compared among treatment groups. RESULTS: Patients with EVR: SVR rate was 60.3% in the PEG-IFN group versus 67.2% in the PEG-IFN+RBV group (NS). In genotypes 2/3, SVR rates were 66.7 versus 73.1% (NS); in genotypes 1/4, SVR rates were 51.6 versus 61.3%, respectively (NS). Patients without EVR: SVR was 16.7% in the PEG-IFN+RBV group versus 31.9% in the triple therapy group (P=0.07). In patients with genotypes 1/4, SVR rates were 9.4 versus 29.7% (P=0.041). CONCLUSION: In genotypes 1/4 patients without EVR, triple therapy results in higher SVR rates than standard dual therapy. This study confirms that addition of amantadine is beneficial in early-recognized 'difficult-to-treat' patients.     

干扰素治疗慢性丙型肝炎获得快速和早期病毒学应答的影响因素

目的:探讨慢性丙型肝炎患者应用聚乙二醇干扰素(pegylated interferon,PEG-IFN)联合利巴韦林治疗不同病毒学应答模式与疗效的关系及获得快速和早期病毒学应答的预测因素,为临床抗病毒治疗疗效判定和治疗方案的选择提供依据.方法:81例慢性丙型肝炎患者均给予pegylated interferon alpha-2a(PEG-IFNα-2a)135-180μg或PEG-IFNα-2b50-80μg,1次/wk皮下注射;利巴韦林800-1200mg/d,对所有患者进行治疗前、治疗4、12、24、48wk和停药后至少24wk的随访,详细记录患者的性别、年龄、丙型肝炎病毒(hepatitis C virus,HCV)RNA水平、肝硬化程度、脂肪肝、体质量指数(body mass index,BMI)、糖尿病史、饮酒史、输血史、既往抗病毒治疗史等等.根据治疗情况将患者分为快速病毒学应答(rapid virological response,RVR)组、早期病毒学应答(early virological response,EVR)组、无应答(no response,NR)组、复发(relapse,RL)组和持续病毒学应答(sustained virologic response,SVR)组.分别应用单因素分析和多因素Logistic逐步回归分析方法分析获得RVR和EVR的影响和预测因素.结果:81例患者中51例(62.9%)获得RVR,65例(80.2%)获得EVR,65例(80.2%)获得SVR,10例(12.3%)NR,6例(7.4%)FL.RVR组88.2%获得SVR,EVR组90.8%获得SVR.未获RVR和EVR的患者16人(19.8%),其中6人(37.5%)获得SVR,6人(100%)均未复发.3组SVR率的差异有统计学意义(?2=20.622,P<0.05),复发率差异无统计学意义(P>0.05).SVR、NR和RL组的RVR率分别为69.2%、0%、100.0%;EVR率分别为90.8%、0%、100.0%.3组RVR率及EVR率的差异有统计学意义.单因素分析结果显示:年龄≤40岁,HCVRNA载量<4×105,无肝硬化与快速病毒学应答有关;年龄≤40岁,HCVRNA载量<4×105,无肝硬化,BMI<24kg/m2与早期病毒学应答有关.将上述指标进行多因素Logistic逐步回归分析,结果表明:基线HCVRNA载量和肝硬化是预测RVR和EVR的独立影响因素.结论:RVR和EVR的获得是获得SVR的重要预测因素;未获得RVR和EVR的患者通过1年疗程的治疗,少部分患者仍可获得SVR;RVR和EVR不能预测复发.年龄、基线病毒载量、有无肝硬化和体质量指数与RVR和EVR的获得密切相关.基线病毒载量、有无肝硬化是预测RVR和EVR的独立因素.     

A comparison of physiology scores and morphology in a group of patients evaluated for endovascular repair of infrarenal aneurysms.

AIM: Endovascular repair (EVR) of abdominal aortic aneurysms (AAA) is an accepted alternative to open repair (OR). Anatomical suitability for EVR of 196 consecutive AAA referrals is analysed, according to aneurysm size and relative physiological fitness for OR. METHODS: Patients were evaluated for suitability according to 2 sets of arbitrary EVR anatomical criteria: flexible criteria (FC), and a subgroup, rigid criteria (RC) with few technical risks. Suitability was related to aneurysm size and operative risk (POSSUM). RESULTS: Eighty-eight patients (45%) were suitable by FC, 33 (17%) by RC, and 108 (55%) were unsuitable for EVR. Inadequate neck length (56%) and angulation (26%), were principle reasons for unsuitability. Mean AAA diameter was 60.5 mm for the whole group, 58.4 mm for those suitable by FC, 56.5 mm for those suitable by RC and 62.1 mm in those unsuitable (p<0.01). Median physiology scores (interquartile ranges) were 19 (17-21) overall, 18 (17-21) in those suitable FC, 18 (17-19) in those suitable by RC and 19 (18-21) for unsuitable patients (NS). High risk patients with large aneurysms. There were 133 larger aneurysms (=/>55 mm in diameter), of which there were 56 patients with physiology scores =/>20. Of these 16 (29%) and 4 (7%) were suitable by FC and RC, respectively. By comparison, of the remaining 77 with physiology scores of =/<19.35 (45%) were suitable for FC and 15 (19%) for RC (p<0.05). CONCLUSION: Unfit patients with significantly sized aneurysm; ironically those most likely to benefit, tend to be less suitable for EVR.     

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.     

Pegylated interferon plus ribavirin for genotype Ib chronic hepatitis C in Japan

AIM：To evaluate the efficacy of pegylated interferon α-2b（peg-IFNα-2b） plus ribavirin（RBV） therapy in Japanese patients with chronic hepatitis C（CHC） genotype Ib and a high viral load.METHODS：One hundred and twenty CHC patients（58.3% male） who received peg-IFNα-2b plus RBV therapy for 48 wk were enrolled.Sustained virological response（SVR） and clinical parameters were evaluated.RESULTS：One hundred（83.3%） of 120 patients completed 48 wk of treatment.53 patients（44.3%） achieved SVR.Early virological response（EVR） and end of treatment response（ETR） rates were 50% and 73.3%,respectively.The clinical parameters（SVR vs non-SVR） associated with SVR,ALT（108.4 IU/L vs 74.5 IU/L,P = 0.063）,EVR（76.4% vs 16.4%,P 〈 0.0001）,adherence to peg-IFN（≥ 80% of planned dose） at week 12（48.1% vs 13.6%,P = 0.00036）,adherence to peg-IFN at week 48（54.7% vs 16.2%,P 〈 0.0001） and adherence to RBV at week 48（56.1% vs 32.1%,P = 0.0102） were determined using univariate analysis,and EVR and adherence to peg-IFN at week 48 were determined using multivariate analysis.In the older patient group（〉 56 years）,SVR in females was significantly lower than that in males（17% vs 50%,P = 0.0262）.EVR and adherence to Peg-IFN were demonstrated to be the main factors associated with SVR.CONCLUSION：Peg-IFNα-2b plus RBV combination therapy demonstrated good tolerability in Japanese patients with CHC and resulted in a SVR rate of 44.3%.Treatment of elderly female patients is still challenging and maintenance of adherence to peg-IFNα-2b is important in improving the SVR rate.     

Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study

The aim of this study was to determine the efficacy of 14 weeks of treatment in patients infected with hepatitis C virus (HCV) genotype 2 or 3 who achieve early virological response (EVR). In a noncontrolled multicenter trial, 122 treatment-naive patients received 1.5 mug/kg pegylated interferon alfa-2b subcutaneously once weekly and 800 to 1,400 mg/d ribavirin based on body weight. Treatment was stopped at week 14 in patients with EVR, defined as undetectable HCV RNA at weeks 4 and 8. Patients without EVR were assigned to 24 weeks of treatment. The primary end point was sustained virological response (SVR), defined as undetectable HCV RNA 24 weeks after end of treatment. Among the 122 patients, 95 (78%) had EVR and received 14 weeks of treatment. The remaining 27 (22%) were treated for 24 weeks. SVR was obtained in 85 (90%) of 95 patients in the 14-week treatment group and 15 of (56%) 27 in the 24-week treatment group. Altogether, SVR was obtained in 100 of 122 patients (82%; 95% CI, 75%-89%). SVR after 14 weeks of treatment was achieved more frequently among genotype 3a patients with low viral load compared with high viral load (98% vs. 79%; P = .019). Logistic regression analysis showed that absence of bridging fibrosis/cirrhosis was the only independent predictor of SVR. In conclusion, patients with genotype 2 or 3 and EVR obtained a high SVR after 14 weeks of treatment. The results need to be confirmed in a randomized, controlled study before this treatment approach can be recommended, particularly for patients with genotype 3 and high viral load or severe fibrosis.     

Transcatheter aortic valve replacement using the new Evolut-Pro system: a prospective comparison with the Evolut-R device

BackgroundEvolut Pro (EVP) is a novel self-expandable aortic valve. This prosthesis consists of an external porcine pericardial wrap designed to reduce paravalvular leak (PVL), maintaining the benefits of its predecessor, the Evolut R (EVR). The aim was to compare the functional and clinical results in the short and medium term of the new EVP with the EVR system.MethodsConsecutive patients receiving either the EVR (n=50) or the EVP (n=33) from June 2015 to October 2018 were compared. Baseline characteristics, cardiovascular imaging, procedural outcomes, short and mid-term follow-up outcomes were prospectively collected and assessed.ResultsResidual mild PVL was common and comparable in the two groups (EVR 79% vs. EVP 70%; P=0.4). In the EVR group, the presence of PVL was directly related to prosthesis size, but this correlation was not observed in the EVP group. Conduction abnormalities were more prevalent with the EVP, but these did not translate into a higher need of permanent pacemaker implantation. Vascular and bleeding complications were infrequent in both groups. At mid-term clinical follow-up (median survival time: EVR 11±0.3 months, EVP 12±0.2 months), the 1-year rate of adverse events was similar (EVR: 24%, EVP: 33%; P=0.3).ConclusionsBoth protheses are effective for the treatment of severe aortic stenosis with excellent results at mid-term clinical follow up. The EVP remains associated with a significant rate of residual mild PVL that appears to be similar to that observed with EVR.     

Differential viral kinetics in treated genotype 4 chronic hepatitis C patients according to ethnicity

Summary.  Data concerning the efficacy of PEG-IFNα2a plus ribavirin treatment in treatment-naïve, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Hence the aim of this study was to investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. One hundred and twenty-three patients were retrospectively analysed. Early (EVR) and late virological response (LVR) was confirmed by undetectable (<50 IU/mL) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as 6 months later. Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively. EVR independently predicted SVR in Caucasian patients ( P  < 0.001) but not in Egyptian patients ( P  = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis ( P  = 0.004). LVR seems to be a better predictor of SVR than EVR in the vast majority of genotype 4-infected CHC patients, irrespective of ethnicity and all the other baseline parameters.     

Relationship between B-type natriuretic peptide levels and ventilatory response during cardiopulmonary exercise test in patients with chronic heart failure

AIM: Aim of the study was to evaluate if brain natriuretic peptide (BNP) levels, a cardiac neurohormone well correlated with prognosis in chronic heart failure (CHF), are associated with enhanced ventilatory response to exercise, in ambulatory patients with intermediate peak oxygen uptake (PVO2). METHODS: Resting BNP was measured in 129 consecutive stable CHF patients with mild to moderate heart failure (90% New York Heart Association (NYHA) class II or III) and intermediate (10-18 mL/kg/min) PVO2, assessed during cardiopulmonary exercise test. Mean (SD) left ventricular ejection fraction (EF) and pulmonary systolic pressure (PAP) were 41 +/- 3% and 47 +/- 14 mmHg, respectively. The enhanced ventilatory response to exercise (EVR) was assessed as a slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2 slope) > 35. RESULTS: Thirty-three over 129 patients (26%) had EVR. Mean BNP plasma level was 394 +/- 347 pg/mL. A significant correlation between BNP and EVR (r = 0.310; p < 0.01), was observed. In the logistic multivariate model, a BNP plasma level > 100 pg/mL had an independent predictive value for EVR (95% IC 1.68 to 10.5, Odds Ratio 4.23, p = 0.02). We found a significant correlation between BNP and PAP (r = 0.390; p < 0.001), and between PAP and EVR (r = 0.511; p < 0.01). CONCLUSIONS: In CHF patients with intermediate PVO2, plasma BNP is clearly related to the enhanced ventilatory response to exercise. In this subset, BNP levels could represent an effective alternative tool for the clinical assessment in patients with unreliable cardiopulmonary exercise test.     

Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels

BACKGROUND/AIMS: We showed previously that amino acid (aa) substitutions in the HCV core region (HCV-CR) are predictors of non-virological response (NVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy. Here, we determined the predictive factors of sustained virological response (SVR) and early virologic response (EVR) to this treatment. METHODS: We evaluated the response to 48-week PEG-IFN-RBV therapy in 114 Japanese adults infected with HCV genotype 1b and determined the predictors of EVR and SVR. RESULTS: EVR was achieved by 70% and SVR by 45% of patients. 64% of patients who achieved EVR also showed SVR, while none of non-EVR achieved SVR. Multivariate analysis identified low-density lipoprotein cholesterol (LDL-C) (>or=86 mg/dl), aa substitutions in HCV-CR (double-wild-type; arginine at aa 70/leucine at aa 91), gamma-glutamyl transpeptidase (GGT) (<109 IU/l), RBV dose (>or=11.0mg/kg), and leukocyte count (>or=4500/mm3) as significant determinants of EVR, and aa substitutions in HCV-CR (double-wild-type), LDL-C (>or=86 mg/dl), male gender, ICG R15 (<10%), GGT (<109 IU/l), and RBV dose (>or=11.0 mg/kg) as determinants of SVR. Prediction of response to therapy based on combination of these factors had high sensitivity, specificity, positive, and negative predictive values. CONCLUSIONS: Our study identified aa substitutions in the core region and serum LDL-C as predictors of response to PEG-IFN-RBV therapy in Japanese patients infected with HCV genotype 1b.     

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     

Short-term prolongation of pegylated interferon and ribavirin therapy for genotype 1b chronic hepatitis C patients with early viral response

Aim:  We tailored extended treatments using pegylated interferon (PEG IFN) and ribavirin (RBV) to viral responses after initiation of therapy and investigated the efficacy and safety of its therapy for chronic hepatitis C (CHC) patients.
Methods:  Eighty-two genotype 1b CHC patients were enrolled in the present study. All patients received PEG IFN-α-2b and weight-based RBV therapy. We defined a viral response in which serum HCV-RNA is undetectable at week 4 as rapid viral response (RVR), detectable at week 4 and undetectable by week 12 as early viral response (EVR), and detectable at week 12 and undetectable by week 24 as late viral response (LVR). We set the treatment duration depending on viral response; 48 weeks for RVR patients and 72 weeks for LVR. Furthermore, EVR patients received a short-term extension of treatment duration to 52–60 weeks. We prospectively investigated sustained viral response (SVR) rates of these groups.
Results:  Overall SVR rate for the total patient group was 57.3%. SVR rates of the RVR, EVR and LVR patients were 100%, 80.5% and 40.0%, respectively. Nine patients could not complete this treatment protocol. Baseline platelet count and mutation in the interferon sensitivity-determining region of NS5A were significant independent predictors of SVR, and amino acid substitution of the core region was a significant independent predictor of non-viral response by multivariate logistic regression analyses.
Conclusion:  The results indicate that short-treatment extension of PEG IFN plus RBV treatment protocols in EVR patients can improve overall SVR rates.     

Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4

SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.     

Early Virological Response in Children with Chronic Hepatitis C Treated with Pegylated Interferon and Ribavirin

Abstract Objective: Infection with hepatitis C virus (HCV) is widespread worldwide. It is estimated that this problem affects approximately 3% of global population. By introducing weekly doses of pegylated interferon (IFN) alfa in combination with ribavirin, given daily, to chronic hepatitis C (CHC) treatment one can achieve a full inhibition of HCV replication in 54–56% of adult patients. The aim of this study was to examine the relationship between prognostic factors and early virological response (EVR) after combination treatment with peginterferon alfa- 2a or alfa-2b and ribavirin in children with CHC. Methods: Twenty-three children with chronic HCV were treated with a combination of peginterferon alfa-2a or alfa-2b once a week and ribavirin twice a day. Assessment included age at the time of infection, the length of infection, HCV genotype, viral load in serum and HCV RNA level in peripheral blood mononuclear cells (PBMCs), alanine aminotransferase (ALT) activity and adherence to therapy. The efficacy endpoint was EVR defined as undetectable HCV RNA in serum or >2 log10 decrease in HCV RNA compared with baseline values. Results: An EVR was achieved in 15 out of 23 patients (65.3%) after 12 weeks of therapy. Conclusions: Lower HCV RNA viral load have positive influence on EVR. HCV RNA presence in PBMCs and lower ALT activity do not influence the achievement of EVR. Oncologic history does not bear any influence on EVR. Adherence to the therapy has an unclear influence on the achievement of EVR in children with CHC.     

Percutaneous AAA repair: is it safe?

PURPOSE: To assess if percutaneous insertion of large-bore sheaths is safe during endovascular repair (EVR) for abdominal aortic aneurysms (AAA). METHODS: Ninety-five AAA patients undergoing EVR had the endografts implanted percutaneously via 14-F to 20-F sheaths in a prospective nonrandomized study. Vascular sutures were applied bilaterally to the common femoral arteries using a vascular closure device; the sutures were tied after sheath withdrawal. Blood loss, operative time, and length of stay (LOS) were compared to 26 AAA patients undergoing EVR with bilateral femoral cutdowns before the percutaneous technique was available. Follow-up included duplex ultrasonography and clinical examination. RESULTS: Bilateral percutaneous closure of the femoral arteries was successful in 78 (82%) patients. Fifteen patients required arteriorrhaphy intraoperatively and 2 others within 24 hours. The failure rate was 20%, 0%, 3%, and 7% for the 20-F, 18-F, 16-F, and 14-F introducers, respectively. Blood loss was 400 mL (range 0-1800) in successful cases, 900 mL (range 0-3000) in failures (p<0.0001). One deep infection at the puncture site required thrombectomy and patchplasty; no other late complication occurred. There was no significant difference in operative time, blood loss, and LOS between patients treated with percutaneous EVR and those with primary femoral exposure. CONCLUSIONS: Percutaneous transfemoral EVR of AAA using large-bore introducer sheaths is safe. More than three quarters of the patients avoid femoral cutdown. Late complications are rare.     

Role of hepatitis C virus substitutions and interleukin‐28B polymorphism on response to peginterferon plus ribavirin in a prospective study of response‐guided therapy

Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity‐determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin‐28B (IL‐28B) locus affect the outcome of interferon (IFN)‐based therapies. We aimed to investigate the role of these factors on response to peginterferon plus ribavirin in a prospective study of response‐guided therapy. The aa sequences in core region and ISDR and rs12979860 genotypes were analysed in 115 HCV‐1 patients. The treatment was 24 weeks for patients achieving a rapid virological response (RVR), 48 weeks for those with an early virological response (EVR) and early terminated in those without an EVR. A sustained virological response (SVR) was achieved in 82% of 34 RVR patients, 45% of 74 EVR patients and 0% of seven non‐EVR patients. Logistic regression analysis showed that ISDR mutation (≥2) [odds ratio(OR): 6.024], double core 70/91 mutations (OR: 0.136), and platelet counts ≥ 15 × 10⁴/μL (OR: 3.119) were independent pretreatment factors associated with SVR. Apart from rs12979860 CC genotype, low viral load and ISDR mutation (≥2) were significant factors predictive of RVR. Combination of rs12979860 genotype and baseline viral characteristics (viral load and core/ISDR mutations) could predict RVR and SVR with positive predictive value of 100% and 91%, and negative predictive value of 80% and 54%, respectively. In conclusion, pretreatment screening rs12979860 genotype and aa substitutions in the core region and ISDR could help identifying patients who are good candidates for peginterferon plus ribavirin therapy.     

Efficacy of the regimen using twice-daily β-interferon followed by the standard of care for chronic hepatitis C genotype 1b with high viral load

Aim: In patients with refractory genotype 1b chronic hepatitis C with high viral loads, we retrospectively compared the efficacy of standard of care treatment (SOC: combined PEG‐IFN‐α‐2b/ribavirin for 48 weeks) and a regimen in which 2 weeks of SOC induction was replaced by twice‐daily β‐interferon alone (IFN‐β induction therapy). Methods: Seventeen patients received the IFN‐β induction therapy plus SOC (IFN‐β induction group) and 13 patients received SOC alone (SOC group). Results: In the IFN‐β induction group and SOC group, early virological response (EVR) rates were 88.2% and 53.8%, respectively. The end of treatment rates were 100.0% and 92.3%, and sustained virological response (SVR) rates were 70.6% and 53.8%, respectively. By induction with IFN‐β, even in refractory cases, the high virus negative conversion rate in the early treatment phase and actions of pegylated IFN‐α‐2b and ribavirin in the maintenance treatment phase led to an additive effect. In the analysis of contributing factors, only the achievement of EVR was associated with a significant difference in SVR (P = 0.0011). The univariate logistic regression analysis showed that only IFN‐β treatment was associated with a significant difference in EVR (P = 0.0492, odds ratio = 6.248, 95% confidence interval = 1.026–40.252), whereas no significant factors were found in the multivariate analysis due to small samples. Conclusion: IFN‐β induction therapy with higher EVR might be beneficial for protease inhibitor‐refractory chronic hepatitis C patients.     

Efficacy and tolerability of low-dose interferon-α in hemodialysis patients with chronic hepatitis C virus infection

AIM:To evaluate the efficacy and tolerability of lowdose standard or pegylated interferon(PEG-IFN)in hepatitis C virus(HCV)-positive hemodialysis patients.METHODS:In total,19 patients were enrolled in this study,of which 12 received PEG-IFNα-2a 67.5μg 1time/wk(Group 1)and 7 received standard interferonα-2b subcutaneously 1.5×106 U 3 times/wk(Group2).The treatment durations were 48 wk for patients infected with HCV genotype 1 and 24 wk for patients infected with HCV genotype 2/3.All patients were prospectively followed after the completion of therapy.The efficacy and tolerability of the treatment were evaluated based on the sustained virological response(SVR)and treatment-related drop-out rate.RESULTS:In Group 1,11 of the 12 patients completed the treatment.Early virological response(EVR)and sustained virological response(SVR)rates were 83.3%and 91.7%,respectively.One patient withdrew from treatment due to an adverse event(leukopenia).The drop-out rate was 8.3%in this group.In Group 2,5 of the 7 patients completed the treatment with an EVR and SVR of 85.7%and 71.4%,respectively.Two patients withdrew due to treatment-related adverse events(nausea and depression).In this group,the drop-out rate was 28.6%.In total,16 of the patients attained EVR,and 15 of them completed the treatment.The SVR rate for the patients who attained EVR was93.7%.Anemia was the most frequent side effect and was observed in 10/19 patients(55.5%),but could be effectively managed with erythropoietin.CONCLUSION:Low-dose interferon monotherapy,either with PEG-IFNα-2a or standard interferonα-2b,is an effective treatment option for hemodialysis patients with chronic hepatitis C.