Ribavirin Impairs Salivary gland function During Combination Treatment With Pegylated Interferon Alfa-2a In HEpatitis C patients

Background

Xerostomia is a common adverse event of unknown etiology observed during pegylated interferon (PegIFN)/Ribavirin (Rbv) treatment.

Objectives

To assess the frequency and mechanisms of xerostomia during PegIFN/Rbv therapy.

Patients and Methods

Thirty-one naïve patients with chronic hepatitis C consecutively received PegIFN-α2a (180 μg/week) plus Rbv (800–1200 mg/day). The controls were 10 patients with chronic hepatitis B who received PegIFN-α2a (180 μg/week). During treatment and follow-up, all patients underwent basal and masticatory stimulated sialometry,otorhinolaryngoiatric (ORL) examination, and a questionnaire survey to subjectively assess symptoms of oral dryness.

Results

Twenty-seven patients on PegIFN/Rbv and 4 on PegIFN (87% vs. 40%, P = 0.006) reported xerostomia. Thirty patients on PegIFN/Rbv combination therapy and 2 patients on monotherapy had ORL signs of salivary gland hypofunction (97% vs. 20%, P < 0.0001).Mean basal (A) and stimulated (B) salivary flow rates (mL/min) progressively decreased during PegIFN/Rbv treatment (A, 0.49 at baseline vs. 0.17 at the end of treatment, P < 0.0001; B, 1.24 at baseline vs. 0.53 at the end of treatment, P = 0.0004). At week 24 following PegIFN/Rbv treatment, salivary flow rates were similar to baseline (A, 0.53 at the end of follow-up vs. 0.49 at baseline; B, 1.19 at the end of follow-up vs. 1.24 at baseline). Salivary function was unaffected in monotherapy patients.

Conclusions

Rbv causes salivary gland hypofunction in hepatitis C patients receiving PegIFN/Rbv therapy, which promptly reverts to normal upon cessation of treatment.     

Efficacy of HBV Vaccination in Various Stages of Chronic Kidney Disease: Is Earlier Better?

Background

Despite improvement in hepatitis B infection prevention through national vaccination programs, implementation of compulsory and thorough blood donor screening, and reduction of transfusion numbers due to erythropoietin administration,hepatitis B remains a major concern in hemodialysis (HD) centers [1]. Compared to aresponse rate of over 90% in the normal population, only 50 to 60% of those with endstage renal disease (ESRD) achieve protective antibody levels following immunization against hepatitis B [2][3]. Various strategies have been developed to overcome the low seroconversion rate in ESRD patients, including co-administering zinc, gamma-interferon,thymopentin, interleukin-2, and levamisole as immunostimulants or adjuvants [3][4],changing the injection mode (intradermal versus intramuscular), or doubling the vaccine dose [5].

Objectives

Previous studies demonstrated that renal failure patients benefit from HBV vaccination; however, not all studies have demonstrated this. Therefore, we compared the rates of seroconversion (hepatitis B surface antibody [HBsAb] titer > 10 IU/mL) in patients at various stages of chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) who received HBV vaccination.

Patients and Methods

A total of 167 patients in 3 different stages of CKD were vaccinated against HBV. Each patient received the vaccine according to a standardized vaccination schedule consisting of 40 μg of the recombinant vaccine “Engerix” at 0, 1, and 6 months.Eight to 12 weeks after the last dose of vaccination, anti-HBsAb levels were measured.

Results

Mean age and eGFR were 57.4 ± 16.5 years and 26.7 ± 14.7 mL/min/1.73 m2, respectively.The overall seroconversion rate was 78%. Although a significant correlation between HBsAb titer and eGFR (r = 0.265, P = 0.001) was observed, in the multivariate analysis using age, CKD stage, diabetes mellitus, and gender as independent variables,the degree of renal function did not significantly contribute to seroconversion. In contrast,higher age (> 60 years) showed a significant negative correlation to seroconversion (odds ratio = 0.22; P = 0.004).

Conclousions

CKD patients of advanced age should be vaccinated against HBV. Although higher eGFR was not associated with improved seroconversion, the persistence of seroconversion was not evaluated; future studies should be conducted to develop recommendations for earlier or later vaccination.     

Antibiotic Susceptibility Profile of Helicobacter pylori Isolated from the Dyspepsia Patients in Tehran, Iran

Background/Aim:

Helicobacter pylori is an important pathogen for gastroduodenal diseases. Infection with H. pylori can be limited by regimens of multiple antimicrobial agents. However, antibiotic resistance is a leading cause of treatment failure. The aim of this study has been to determine the resistance patterns of H. pylori strains isolated from gastric biopsies of patients with dyspepsia by agar dilution method, in Tehran, Iran

Patients and Methods:

H. pylori isolates from patients with gastrointestinal diseases were evaluated for susceptibility testing by agar dilution method. Susceptibility testing was performed to commonly used antibiotics including clarithromycin, tetracycline, amoxicillin, metronidazole and ciprofloxacin.

Results:

Among 92 patients with dyspepsia, H. pylori strains were isolated from 42 patients. Seventeen (40.5%) of the isolates were resistant to metronidazole (MICs ≥ 8 μg/l), whereas one isolate (2.4%) was resistant to amoxicillin (MICs ≤ 0. 5 μg/ml) and ciprofloxacin (MICs ≤ 1μg/ml). The resistance rates to other antibiotics in H. pylori isolates are recorded as follows: clarithromycin 6 (14.3 %), tetracycline 2 (4.8%). In 5 of 42 resistant cases, combined resistance was found.

Conclusions:

These data suggest that metronidazole should be used among Iranian patients in first-line therapy with caution, and ciprofloxacin in association with amoxicillin and a proton pump inhibitor is more recommended.     

Effects of a short course of inhaled corticosteroids in noneosinophilic asthmatic subjects

BACKGROUND:

Noneosinophilic asthma has been regarded as a distinct phenotype characterized by a poor response to inhaled corticosteroids (ICS).

OBJECTIVE:

To determine whether noneosinophilic, steroid-naive asthmatic subjects show an improvement in asthma control, asthma symptoms and spirometry after four weeks of treatment with ICS, and whether they further benefit from the addition of a long-acting beta-2 agonists to ICS.

METHODS:

A randomized, double-blind, placebo-controlled, multicentre study comparing the efficacy of placebo versus inhaled fluticasone propionate 250 μg twice daily for four weeks in mildly uncontrolled, steroid-naive asthmatic subjects with a sputum eosinophil count ≤2%. This was followed by an open-label, four-week treatment period with fluticasone propionate 250 μg/salmeterol 50 μg, twice daily for all subjects.

RESULTS:

After four weeks of double-blind treatment, there was a statistically significant and clinically relevant improvement in the mean (± SD) Asthma Control Questionnaire score in the ICS-treated group (n=6) (decrease of 1.0±0.5) compared with the placebo group (n=6) (decrease of 0.09±0.4) (P=0.008). Forced expiratory volume in 1 s declined in the placebo group (−0.2±0.2 L) and did not change in the ICS group (0.04±0.1 L) after four weeks of treatment (P=0.02). The open-label treatment with fluticasone propionate 250 μg/salmeterol 50 μg did not produce additional improvements in those who were previously treated for four weeks with inhaled fluticasone alone.

CONCLUSION:

A clinically important and statistically significant response to ICS was observed in mildly uncontrolled noneosinophilic asthmatic subjects.     

Effects of cigarette smoke, nicotine and cotinine on red blood cell hemolysis and their -SH capacity

BACKGROUND:

Smoking is a leading cause of premature death. Red blood cell (RBC) membrane lipids are rich in polyunsaturated fatty acids; therefore, the effect of oxygen on RBC membranes is more prominent than on other body tissues. The attachment of peroxidants to RBC membranes can result in hemolysis.

OBJECTIVES:

The present study was conducted to assess the sensitivity of RBCs to 2,2′-azo-bis-(2-amidinopropane) dihydrochloride in smokers and nonsmokers. The effect of cigarette smoke, nicotine (1 μg/mL, 1.5 μg/mL and 2.5 μg/mL) and cotinine (1.25 μg/mL, 2.5 μg/mL and 5 μg/mL) on RBC hemolysis was also examined.

RESULTS:

RBC hemolysis in smokers was 21.6% higher than in non-smokers (P<0.05). Cigarette smoke increased 2,2′-azo-bis-(2-amidino-propane) dihydrochloride-induced RBC hemolysis by 281.7%. Nicotine inhibited RBC hemolysis by 36.7% at the highest concentration used, but increased RBC hemolysis at the lower concentrations. Cotinine caused a 13.8% increase in RBC membrane peroxidation at the highest concentration used and its effects were dose-dependent. At their highest concentrations, nicotine and cotinine decreased -SH groups by 50%.

CONCLUSIONS:

The present study confirms the results from previous studies of the oxidative and destructive effects of cigarette smoke, which are detrimental to the health of both active and passive smokers.     

Low-molecular-weight proteins as prognostic markers in idiopathic membranous nephropathy

Summary

Background

Accurate prediction of prognosis in idiopathic membranous nephropathy (iMN) allows restriction of immunosuppressive therapy to patients at high risk for ESRD. Here we re-evaluate urinary low-molecular-weight proteins as prognostic markers and explore causes of misclassification.

Design, setting, participants, & measurements

In a cohort of 129 patients with serum creatinine concentration <135 μmol/L and proteinuria ≥3.0 g/10 mmol, urinary α1- (uα1m) and β2-microglobulin (uβ2m) excretion rate was determined. Urinary α1m and uβ2m-creatinine ratio was also obtained. We defined progression as a rise in serum creatinine ≥50% or ≥25% and an absolute level ≥135 μmol/L.

Results

Median survival time was 25 months, and 47% of patients showed progression. The area under the receiver operating characteristic curve for uβ2m was 0.81 (95% CI: 0.73 to 0.89). Using a threshold value of 1.0 μg/min, sensitivity and specificity were 73% and 75%, respectively. Similar accuracy was observed for the uβ2m-creatinine ratio with sensitivity and specificity of 75% and 73%, respectively, at a threshold of 1.0 μg/10 mmol creatinine. Similar accuracy was found for uα1m and uα1m-creatinine ratio. Blood Pressure and cholesterol contributed to misclassification. Repeated measurements improved accuracy in patients with persistent proteinuria: the positive predictive value of uβ2m increased from 72% to 89% and the negative predictive value from 76% to 100%.

Conclusions

Urinary excretion of uα2m and uβ2m predict prognosis in iMN. A spot urine sample can be used instead of a timed sample. A repeated measurement after 6 to 12 months increases prognostic accuracy.     

Protective effect of flavonoids against red blood cell hemolysis by free radicals

BACKGROUND:

Flavonoids are polyphenolic substances with antioxidant properties, and they are found in different vegetables and fruits. Epidemiological studies have shown that the consumption of flavonoids reduces the prevalence of cardiovascular diseases. The use of synthetic antioxidants, however, has been limited because of their toxicity. Therefore, medical researchers have intensified their quest to find natural antioxidants.

OBJECTIVES:

To investigate the effect of several pure flavonoids, such as kaempferol, quercetin, morin and rutin, on red blood cell hemolysis and evaluate their -SH capacity as an indicator of membrane protection.

METHODS:

The rate of hemolysis and cell membrane -SH capacity were determined by spectrophotometry. Red blood cell peroxidation was induced using 2,2′-azo-bis-(2-amidinopropane) dihydrochloride. The effect of each flavonoid on hemolysis was examined at three concentrations (0.5 μg/mL, 5 μg/mL and 10 μg/mL), however, only the greatest concentration (10 μg/mL) of each flavonoid was used to study the effect on -SH groups.

RESULTS:

In all cases, the antioxidant activity was dose-dependent. Rutin showed the highest inhibitory effect on hemolysis among flavonoids (42.5%). The protective effect of kaempferol, rutin and morin against -SH group oxidation measured 7.7%, 23.3% and 26.4%, respectively.

CONCLUSIONS:

Results showed that flavonoids and flavonoid-containing plants can be used as natural antioxidants for the treatment and prevention of disease conditions, the pathogenesis of which is mediated by lipid peroxidation.     

Vitamin K1 supplementation to improve the stability of anticoagulation therapy with vitamin K antagonists: a dose-finding study

Background

Poor anticoagulant stability in patients using vitamin K antagonists is a risk factor for both bleeding and thrombosis. In previous studies supplementation with low dose vitamin K₁ was shown to improve the stability of anticoagulant control. We set up a study to confirm earlier reports and to determine the optimal daily dose of vitamin K₁ in preparation of a large study with clinical endpoints.

Design and Methods

Four hundred patients from two anticoagulation clinics starting with vitamin K antagonists, independently of a possible history of instable anticoagulation, were randomized to receive either placebo or 100, 150 or 200 μg of vitamin K₁ together with their treatment with vitamin K antagonists. The treatment was administered for 6 to 12 months. Anticoagulation stability, expressed as the percentage of time that the International Normalized Ratio was within the therapeutic range, was compared between the groups.

Results

After adjustment for age, sex, vitamin K antagonist used, anticoagulation clinic and interacting drugs as confounding factors the difference in percentage of time with the International Normalized Ratio within the therapeutic range between the placebo group and the vitamin K₁ groups was 2.1% (95% CI: −3.2% – 7.4%) for the group taking 100 μg, 2.7% (95% CI: −2.3% –7.6%) for the group taking 150 μg and 0.9% (95% CI: −4.5% – 6.3%) for the group taking 200 μg vitamin K₁ group, in favor of the vitamin K₁ groups. The patients from both the 100 μg group and the 150 μg group had a 2-fold higher chance of reaching at least 85% of time with the International Normalized Ratio within the therapeutic range. There were no differences in thromboembolic or hemorrhagic complications between the groups.

Conclusions

In patients starting vitamin K antagonists, supplementation with low dose vitamin K₁ resulted in an improvement of time that anticoagulation was within the therapeutic range. Differences between doses were, however, small and the improvement is unlikely to be of clinical relevance. For future studies we recommend selecting only patients with instable anticoagulant control. (This study was registered at www.isrctn.org as ISRCTN37109430)     

Ventricular pacing thresholds following high-energy implantable cardioverter defibrillator shocks in integrated bipolar defibrillation systems

BACKGROUND:

Increased ventricular pacing thresholds have been observed following monophasic implantable cardioverter defibrillator (ICD) shocks.

AIM:

To examine changes following high-energy biphasic shocks delivered by integrated bipolar ICD systems.

METHOD:

Ten episodes of ventricular fibrillation (VF) were induced at 10 min intervals in nine pigs with integrated ICD systems. After 10 s of each episode of VF, a 40 J biphasic shock was delivered, which successfully terminated VF (a total of 10 shocks). The bipolar pacing threshold at the right ventricular apex was measured before each shock and at 1 min intervals after each shock.

RESULTS:

The mean pacing threshold was 0.029±0.059 μJ before the first shock and gradually increased to 0.14±0.10 μJ after the 10th shock.

CONCLUSION:

It may be necessary to pace at a high-voltage output following biphasic shocks delivered by integrated bipolar ICD systems.     

Emergence of penicillin-resistant Streptococcus pneumoniae in southern Ontario, 1993�C94

Objective:

To determine the prevalence of resistance of Streptococcus pneumoniae to penicillin and other antimicrobial agents in metropolitan Toronto.

Design:

Consecutive pneumococcal isolates from different patients were obtained from two private community-based laboratories and from patients assessed in the emergency department of a tertiary-care teaching hospital in Toronto, Ontario between June and December 1993, and between March and October 1994. In vitro susceptibility testing was done by broth microdilution in accordance with National Committee for Clinical Laboratory Standards guidelines.

Results:

Twenty (7.3±3.1%) of 274 pneumococcal isolates were resistant to penicillin; six (30%) isolates had high-level resistance (minimal inhibitory concentration [mic] 2.0 μg/mL or greater); and 14 isolates had intermediate resistance (mic 0.1 to 1.0 μg/mL). Penicillin-resistant strains were also frequently resistant to tetracycline (55%), cotrimoxazole (50%), erythromycin (40%) and cefuroxime (35%). Resistant strains comprised several serotypes: 19F (six isolates), 9V (three), 23F (three), and one each of 6A, 6B, 14, and 19A; four isolates were nontypeable.

Conclusions:

There has been a recent emergence of penicillin-resistant S pneumoniae in southern Ontario. National and regional surveillance is warranted to determine the extent of the problem elsewhere in Canada.     

HIV virological suppression influences response to the AS03‐adjuvanted monovalent pandemic influenza A H1N1 vaccine in HIV‐infected children

Design

Children with HIV are especially susceptible to complications from influenza infection, and effective vaccines are central to reducing disease burden in this population. We undertook a prospective, observational study to investigate the safety and immunogenicity of the inactivated split-virion AS03-adjuvanted pandemic H1N1(2009) vaccine in children with HIV.

Setting

National referral centre for Paediatric HIV in Ireland.

Sample

Twenty four children with HIV were recruited consecutively and received two doses of the vaccine. The serological response was measured before each vaccine dose (Day 0 and Day 28) and 2 months after the booster dose. Antibody titres were measured using a haemagglutination inhibition (HAI) assay. Seroprotection was defined as a HAI titre ≥ 1:40; seroconversion was defined as a ≥ fourfold increase in antibody titre and a postvaccination titre ≥ 1:40.

Main outcome measures

The seroconversion rates after prime and booster doses were 75% and 71%, respectively. HIV virological suppression at the time of immunization was associated with a significantly increased seroconversion rate (P = 0·009), magnitude of serological response (P = 0·02) and presence of seroprotective HAI titres (P = 0·017) two months after the booster dose. No other factor was significantly associated with the seroconversion/seroprotection rate. No serious adverse effects were reported. Vaccination had no impact on HIV disease progression. The AS03-adjuvanted pandemic H1N1 vaccine appears to be safe and immunogenic among HIV-infected children. A robust serological response appears to be optimized by adherence to a HAART regimen delivering virological suppression.     

The Efficacy and Safety of Peginterferon-α-2a in Korean Patients with Chronic Hepatitis B: A Multicenter Study Conducted in a Real Clinical Setting

Background/Aims

Genotype C is the principal type of hepatitis B virus (HBV) in Koreans and is associated with poor prognosis for peginterferon α-2a therapy. The efficacy of and compliance to peginterferon α-2a therapy were investigated in Koreans with hepatitis B in a real clinical setting.

Methods

Hepatitis B patients treated with peginterferon α-2a from 2008 to 2011 at four university hospitals were consecutively enrolled.

Results

Eighty-eight patients were enrolled; 67 were hepatitis B e antigen (HBeAg)-positive. The mean treatment period was 36.1±15.2 weeks. In 26.1% of patients, treatment was discontinued due to insufficient antiviral effects and adverse events. At 24 weeks after treatment, 10/42 (23.8%) HBeAg-positive patients achieved both HBV DNA suppression to <2,000 IU/mL and HBeAg loss/seroconversion. For HBeAg-negative patients, 10/13 (76.9%) achieved HBV DNA suppression to <2,000 IU/mL at 24 weeks after treatment. During the follow-up period, 15 (30.6%) of the 49 patients who achieved HBV DNA suppression to 2,000 IU/mL developed a breakthrough HBV DNA level of >2×10⁶ IU/mL.

Conclusions

Peginterferon α-2a therapy in Koreans with hepatitis B in a real clinical setting resulted in a lower virologic response, as compared to Western individuals, but a favorable durability. There is a need to reduce the high rate of premature discontinuation compared to the controlled studies.     

Knowledge, attitudes and practice of Iranian medical specialists regarding hepatitis B and C

Background and Aims

Health care workers (HCWs) are at risk of contracting and spreading hepatitis B virus (HBV) and hepatitis C virus (HCV) to others. The aim of this study was to evaluate knowledge, attitudes and behavior of physicians concerning HBV and HCV.

Methods

A 29-item questionnaire (reliability coefficient = 0.7) was distributed at two national/regional congresses and two university hospitals in Iran. Five medical groups (dentists, general practitioners, paraclinicians, surgeons and internists) received 450 questionnaires in 2009, of which 369 questionnaires (82%) were filled out.

Results

Knowledge about routes of transmission of HBV and HCV, prevalence rate and seroconversion rates secondary to a needlestick injury was moderate to low. Concern about being infected with HBV and HCV was 69.4±2.1 and 76.3±2 (out of 100), respectively. Complete HBV vaccination was done on 88.1% of the participants. Sixty percent had checked their hepatitis B surface antibody (anti-HBs), and 83.8% were positive. Only 24% of the surgeons often used double gloves and 28% had reported a needlestick. There was no significant correlation between the different specialties and: concern about HBV and HCV; the underreporting of needlestick injuries; and correct knowledge of post-needlestick HBV infection.

Conclusions

Although our participants were afraid of acquiring HBV and HCV, knowledge about routes of transmission, prevalence, protection and post-exposure seroconversion rates was unsatisfactory. By making physicians aware of possible post-exposure prophylaxis, the underreporting of needlestick injuries could be eliminated. Continuous training about HBV and HCV transmission routes, seroconversion rates, protection, as well as hepatitis B vaccination and checking the anti-HBs level, is a matter of necessity.     

Comparison of adverse effects related to pegylated interferon-based therapy for patients with chronic hepatitis B and chronic hepatitis C in Taiwan

Purpose

Pegylated interferon (Peg-IFN)-based therapy is effective in treating chronic hepatitis B (CHB) and C (CHC) but frequently induces adverse events (AEs). This study was conducted to compare the incidence of Peg-IFN-based therapy-associated AEs in Taiwanese patients with CHB and CHC.

Methods

Fifty-six patients with CHB and 103 age-, sex- and treatment duration-matched patients with CHC were enrolled. Patients with CHB were treated with Peg-IFN-α-2a 180 μg/week for 24 weeks (HBeAg⁺, n = 31) or 48 weeks (HBeAg⁻, n = 25); patients with CHC were treated with Peg-IFN-α-2a 180 μg/week plus ribavirin 1,000–1,200 mg/day for 24 weeks (genotype 2/3, n = 57) or 48 weeks (genotype 1, n = 46).

Results

Significantly higher incidences of Peg-IFN-related AEs, especially neuropsychiatric symptoms, and ribavirin-associated skin manifestations were observed in patients with CHC compared with those with CHB, with either the 24- or 48-week regimen. Frequencies of laboratory abnormalities, except for anemia, were comparable in both groups. Neither group showed overt hepatic decompensation. Frequency of dose reduction was similar between the groups. Substantially higher rates of early termination and severe AEs were observed in patients with CHC.

Conclusions

Patients with CHB treated with Peg-IFN had fewer AEs than patients with CHC treated with Peg-IFN/ribavirin. All patients were treated safely.     

Serum levels of homocysteine in mice with malignant tumours

BACKGROUND:

Oxygen radicals and malondialdehyde (MDA) are tumourigenic. Homocysteine generates oxygen radicals. The possibility exists that hyperhomocysteinemia is a risk factor for cancer.

OBJECTIVE:

To investigate if serum levels of homocysteine and MDA are elevated in mice with malignant tumours.

METHODS:

Levels of serum homocysteine and MDA were estimated in 22 control and 22 tumour-bearing Balb/c mice.

RESULTS:

Serum homocysteine levels in control and tumour-bearing mice were 3.01±0.26 μmol/L and 4.05±0.46 μmol/L, respectively. The serum levels of MDA were 6.23±0.72 nmol/mL and 11.60±1.72 nmol/mL, respectively, in control and tumour-bearing mice.

CONCLUSION:

These results suggest that cancer in mice is associated with an increase in serum levels of homocysteine and the lipid peroxidation product MDA. It is, however, not known if this rise in homocysteine and MDA is due to cancer or if this rise causes cancer.     

Hepatitis B Virus Genotype B and High Expression of Interferon Alpha Receptor β Subunit are Associated With Better Response to Pegylated Interferon Alpha 2a in Chinese Patients With Chronic Hepatitis B Infection

Background

Hepatitis B virus (HBV) is one of leading causes of various hepatic diseases including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hundreds of million people worldwide are infected by HBV, chronically.

Objectives

This study in conducted to investigate the influence of Hepatitis B virus (HBV) genotypes and type I IFN-αreceptor β subunit (IFNAR2) expression in liver on response to treatment with pegylated IFN-α-2a (Peg-IFN-α-2a) for chronic hepatitis B infection.

Patients and Methods

In this study, 65 eligible patients with chronic hepatitis B disease were enrolled. HBV genotypes of these patients were analyzed by using PCR-RFLP of the surface gene of HBV. The expression of IFNAR2 in the liver was immune histochemically investigated using anti-IFNAR2 antibody. All immune histochemical slides were read semi-quantitatively by image analysis. Chronic hepatitis B patients were treated with Peg-IFN-α2a therapy for a 48-week period and followed up for 24 weeks. Baseline characteristics and sustained viral response (SVR) to Peg-IFN-α-2a therapy were evaluated.

Results

55 % of patients exhibited HBV genotype B and 31.7 % patients exhibited HBV genotypes C infections. After treatment with Peg-IFN-α-2a, SVR was achieved in 66.7 % of patients with HBV genotype B and in 26.3 % of patients with HBV genotype C (P = 0.009). Semiquantitative and the image analysis indicated by gray level values revealed a higher IFNAR2 expression in the group with severe inflammation (P < 0.001). Patients’ high IFNAR2 protein expression had a significant impact on SVR to Peg-IFN-α-2a therapy (P = 0.028).

Conclusions

HBV genotype B and high expression of IFNAR2 in the liver of chronic hepatitis B patients are closely associated with better response to Peg-IFN-α-2a therapy in chronic hepatitis B disease.     

European vs. Egyptian HCV-4 patients with elevated baseline HCV RNA, treated with PEG-IFN-α2a and ribavirin: the role of rapid and early virologic response

Background and Aims

Despite the recent spread of hepatitis C virus genotype 4 (HCV-4) into European countries, very little is known about the influence of ethnicity on treatment outcomes in patients with HCV-4. The aim of this study was to compare the virologic response (VR) rates of: rapid virologic response (RVR), early virologic response (EVR), VR at 24 weeks of treatment, at end of treatment (EoT), and sustained virologic response (SVR) of European and Egyptian HCV-4 patients.

Methods

Sixty (30 Europeans – Group A; and 30 Egyptians – Group B) chronic HCV-4 subtype A adult patients with elevated baseline viral load (>800 000 IU/m L) were treated for a fixed period of 48 weeks with pegylated interferon α2a (PEG-IFN- α2a) and ribavirin. During the study, HCV-RNA levels were measured at weeks 4,12,24,48 and 72.

Results

Baseline characteristics, including liver histology, were similar in the two groups. RVR, EVR and HCV-RNA at week 24 in Groups A and B were (RVR 26.7% vs. 30.0%) (EVR 23.3% vs. 16.7%) (in week 24 13.3% vs. 16.7%). Overall SVR rates were 36.7% (11/30) for Group A and 26.7% (8/30) for Group B (P = 0.59). For group B, RVR was the weakest indicator for SVR as compared with RVR of group A, where RVR was the best SVR indicator

Conclusions

The overall response to treatment was similar, but ethnic origin or previous history and treatment of schistosomiasis may influence intermediate response rates of chronic HCV-4a infected patients with elevated baseline HCV-RNA.     

Phase II,randomized, open,controlled study of AS03‐adjuvanted H5N1 pre‐pandemic influenza vaccine in children aged 3 to 9 years: follow‐up of safety and immunogenicity persistence at 24 months post‐vaccination

Background

An AS03-adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3–9 years.

Methods

In this follow-up of the Phase II study, we report immunogenicity persistence and safety at 24 months post-vaccination in children aged 3–9 years. The randomized, open-label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS03_A or AS03_B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune-mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination-inhibition assay 12 and 24 months after vaccination; cross-reactivity and cell-mediated responses were also assessed. ({"type":"clinical-trial","attrs":{"text":"NCT00502593","term_id":"NCT00502593"}}NCT00502593).

Results

The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine-related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell-mediated immunity was strong, and CD4⁺ T cells with a T_H1 profile were observed.

Conclusions

Two doses of an AS03-adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell-mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination.