Extended treatment with lamivudine and adefovir dipivoxil in chronic hepatitis B patients with lamivudine resistance

Purpose

We and others have reported that adding adefovir dipivoxil (adefovir) to lamivudine results in virological and biochemical improvement in cases of lamivudine resistance. The current study assessed the efficacy and safety of combined therapy after 104 weeks of combined treatment and analyzed the frequency of persistent lamivudine resistant HBV.

Methods

A total of 78 patients with compensated CHB (Group A) were maintained on either adefovir 10 mg daily (n = 38) or placebo (n = 40) while continuing lamivudine. An additional 38 patients with decompensated cirrhosis or post liver transplantation (Group B) received lamivudine plus adefovir. The primary endpoint was HBV DNA response at year 2.

Results

At week 104 of therapy, a significantly greater proportion of patients in Group A on combination therapy (76%) had a decline in serum HBV DNA to ≤10⁵ copies or >2 log₁₀ reduction from baseline compared to those receiving lamivudine alone (13%; p < 0.001). Fifty-two percent of Group A patients on combination treatment continued to have the M204V/I HBV mutation compared to 92% receiving lamivudine alone (p = 0.0013). Virologic response occurred less frequently in patients expressing persistent lamivudine resistant HBV. In Group B, 87% of patients had HBV DNA response at week 104 (median change from baseline of −5.84 log₁₀ copies/mL).

Conclusions

The combination of lamivudine and adefovir for 2 years generally proved effective in lamivudine-resistant cases, but there was a persistently high rate of detection of lamivudine resistant mutants and impaired virologic response in compensated patients.     

De novo combination of lamivudine and adefovir versus entecavir monotherapy for the treatment of naïve HBeAg-negative chronic hepatitis B patients

Purpose

Either combination treatment or monotherapy using agents with a high genetic barrier are recommended for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). The aim of this study was to compare effect of naïve HBeAg-negative CHB patients with either de novo combination of lamivudine (LAM) and adefovir dipivoxil (ADV) or entecavir (ETV) monotherapy.

Methods

HBeAg-negative CHB patients (n = 71) with ALT levels between 2 and 10 times the upper normal limit and HBV DNA levels >10⁴ copies/mL were enrolled. Patients were treated with either LAM 100 mg plus ADV 10 mg per day (n = 31) or ETV 0.5 mg per day (n = 40) for 48 weeks.

Results

The average reduction in HBV DNA level compared with baseline were 5.16 ± 1.69 log in the LAM + ADV group and 5.36 ± 1.70 log in the ETV group by week 48 (P = 0.624). The virological response (VR) rates were 80.65 and 77.5%, the biochemical response (BR) rates were 93.55 and 90.00% at week 48 in the LAM + ADV and ETV groups, respectively. There was no significant difference in the VR and BR between the two groups. During the 48-week treatment period, virological breakthrough and serious side effects were not noted in any patient.

Conclusions

Both LAM + ADV combination therapy and ETV monotherapy are effective in naïve HBeAg-negative CHB patients, but further studies are needed to obtain long-term results.     

Beneficial effect of calcium channel blockers on home blood pressure variability in the morning in patients with type 2 diabetes

Aims/Introduction

Recent studies have shown the association between blood pressure variability and cardiovascular events. The present study was designed to investigate the relationship between antihypertensive drug class and home blood pressure variability in patients with type 2 diabetes.

Materials and Methods

We compared home blood pressure variability among patients treated with calcium channel blockers (n = 44), with angiotensin II receptor blockers and/or angiotensin‐converting enzyme inhibitors (n = 159), and with calcium channel blockers combined with angiotensin II receptor blockers and/or angiotensin‐converting enzyme inhibitors (n = 183). Next, we analyzed the effect of calcium channel blockers on morning blood pressure variability using multiple linear regression analysis.

Results

Coefficient variation of morning systolic blood pressure in patients treated with calcium channel blockers was significantly lower than that in patients treated with angiotensin II receptor blockers and/or angiotensin‐converting enzyme inhibitors (P = 0.036). Multivariate linear regression analyses showed that treatment with calcium channel blockers was significantly correlated with coefficient variation of morning systolic blood pressure (β = −0.264, P = 0.001).

Conclusions

The present study implies a possibility for validity on selecting calcium channel blockers in hypertensive patients with type 2 diabetes to reduce home blood pressure variability.     

Viral and atypical bacterial aetiologies of infection in hospitalised patients admitted with clinical suspicion of influenza in Thailand,Vietnam and Indonesia

Background

Influenza constitutes a leading cause of morbidity and mortality worldwide. There is limited information about the aetiology of infection presenting clinically as influenza in hospitalised adults and children in South-East Asia. Such data are important for future management of respiratory infections.

Objectives

To describe the aetiology of infection presenting clinically as influenza in those hospitalised in South-East Asia.

Methods

Respiratory specimens archived from July 2008 to June 2009 from patients hospitalised with suspected influenza from Indonesia, Thailand and Vietnam were tested for respiratory viruses and atypical bacteria by polymerase chain reaction.

Results

A total of 1222 patients’ samples were tested. Of 1222, 776 patients (63·5%) were under the age of 5. Viruses detected included rhinoviruses in 229 of 1222 patients (18·7%), bocaviruses in 200 (16·4%), respiratory syncytial viruses in 144 (11·8%), parainfluenza viruses in 140 (11·5%; PIV1: 32; PIV2: 12; PIV3: 71; PIV4: 25), adenovirus in 102 (8·4%), influenza viruses in 93 (7·6%; influenza A: 77; influenza B: 16) and coronaviruses in 23 (1·8%; OC43: 14; E229: 9). Bacterial pathogens were Mycoplasma pneumoniae (n = 33, 2·7%), Chlamydophila psittaci (n = 2), C. pneumoniae (n = 1), Bordetella pertussis (n = 1) and Legionella pneumophila (n = 2). Overall, in-hospital case fatality rate was 29 of 1222 (2·4%).

Conclusion

Respiratory viruses were the most commonly detected pathogens in patients hospitalised with a clinical suspicion of influenza. Rhinovirus was the most frequently detected virus, and M. pneumoniae, the most common atypical bacterium. The low number of detected influenza viruses demonstrates a low benefit for empirical oseltamivir therapy, unless during an influenza outbreak.     

Characterization of hospital and community‐acquired respiratory syncytial virus in children with severe lower respiratory tract infections in Ho Chi Minh City,Vietnam, 2010

Background

Human respiratory syncytial virus (RSV) is an important community and nosocomial pathogen in developed countries but data regarding the importance of RSV in developing countries are relatively scarce.

Methods

During a 1-year surveillance study in 2010, we took serial samples from children admitted to the Emergency Unit of the Respiratory Ward of Children''s Hospital 1 in Ho Chi Minh City, Vietnam. RSV was detected within 72 hours of admission to the ward in 26% (376/1439; RSV A: n = 320; RSV B: n = 54; and RSV A and B: n = 2). Among those negative in the first 72 hours after admission, 6·6% (25/377) acquired nosocomial RSV infection during hospitalization (RSV A: n = 22; and RSV B: n = 3).

Results

Children with nosocomial RSV infection were younger (P = 0·001) and had a longer duration of hospitalization (P < 0·001). The rate of incomplete recovery among children with nosocomial RSV infection was significantly higher than among those without (P < 0·001). Phylogenetic analysis of partial G gene sequences obtained from 79% (316/401) of positive specimens revealed the co-circulation of multiple genotypes with RSV A NA1 being predominant (A NA1: n = 275; A GA5: n = 5; B BA3: n = 3; B BA9: n = 26; and B BA10: n = 7). The RSV A GA5 and RSV B BA3 genotypes have not been reported from Vietnam, previously.

Conclusion

Besides emphasizing the importance of RSV as a cause of respiratory infection leading to hospitalization in young children and as a nosocomial pathogen, data from this study extend our knowledge on the genetic diversity of RSV circulating in Vietnam.     

Decreased serum CA19‐9 is associated with improvement of insulin resistance and metabolic control in patients with obesity and type 2 diabetes after Roux‐en‐Y gastric bypass

Aims/Introduction

Patients with type 2 diabetes are known to show elevated serum levels of carbohydrate antigen 19-9 (CA19-9). The aim of the present study was to investigate the possible relationships of CA19-9 with metabolic control, insulin resistance (IR), and pancreatic β-cell function in patients with obesity and type 2 diabetes who underwent Roux-En-Y gastric bypass (RYGB).

Materials and Methods

The present study included 81 healthy volunteers, and 33 patients diagnosed with obesity and type 2 diabetes who underwent RYGB. Anthropometry, serum levels of CA19-9, glucose and lipid metabolic profiles, and serum insulin levels were determined at baseline and at 12 weeks after RYGB.

Results

Changes in CA19-9 were significantly and positively correlated with changes in fasting plasma glucose (r = 0.552, P = 0.001), 2-h post-challenge plasma glucose levels (r = 0.623, P = 0.000), glycated hemoglobin levels (r = 0.819, P = 0.000), glycated albumin levels (r = 0.711, P = 0.000), total cholesterol (r = 0.449, P = 0.009) and the Homeostasis Model of Assessment-IR index (r = 0.407, P = 0.019). Furthermore, a multiple stepwise regression analysis showed that the changes in serum levels of CA19-9 were independently and significantly associated with changes in glycated hemoglobin (β = 0.598, P = 0.000), fasting plasma glucose (β = 0.309, P = 0.000) and Homeostasis Model of Assessment-IR (β = 0.235, P = 0.010) after adjusting for confounding factors.

Conclusions

CA19-9 could be an effective indicator of IR, and glycemic and lipid metabolism in patients with obesity and type 2 diabetes after rapid metabolic control by RYGB. Additionally, CA19-9 might be a marker with which to evaluate the short-term effects of glycolipid toxicity on IR in these patients.     

Effects of Metabolic Syndrome on Fibrosis in Chronic Viral Hepatitis

Background/Aims

Metabolic syndrome, comprising diabetes, hypertension, central obesity, and dyslipidemia, is increasingly prevalent worldwide. We aimed to study the relationship between metabolic syndrome and the risk of liver fibrosis in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC).

Methods

In total, 954 patients (CHB, 850; CHC, 104 patients) with liver biopsy were included in the retrospective analysis. Extensive clinical and histological data were available. Metabolic syndrome was defined using the International Diabetes Federation definition of metabolic syndrome, 2006 criteria. Histological lesions were evaluated according to the histology activity index system.

Results

Metabolic syndrome was present in 6% of patients and significantly more prevalent in patients with CHC than in patients with CHB (5% vs 13%, p<0.001). Patients with metabolic syndrome were older among patients with CHB and patients with CHC, and, as expected, were mainly overweight or obese. Fibrosis was significantly more severe in patients with metabolic syndrome than in those without, regardless of whether they had CHB and CHC (CHB, 3.3±2.1 vs 2.4±1.3, p=0.025; CHC, 2.6±1.5 vs 1.3±0.7, p=0.006). Liver fibrosis (stages 3 to 4) was independently associated with increased age, higher transaminase level and metabolic syndrome (odds ratio, 2.421; p=0.017).

Conclusions

Metabolic syndrome is associated independently with severe fibrosis in patients with chronic viral hepatitis B and C.     

Response to the dipeptidyl peptidase‐4 inhibitors in Japanese patients with type 2 diabetes might be associated with a diplotype of two single nucleotide polymorphisms on the interleukin‐6 promoter region under a certain level of physical activity

Aims/Introduction

Muscle-derived interleukin-6 (IL-6) has been reported to promote glucagon-like peptide-1 (GLP-1) secretion, and we explored the association of single nucleotide polymorphisms (SNPs) in the human IL-6 promoter region with the responsiveness to dipeptidyl peptidase-4 inhibitors (DPP-4Is), drugs that increase circulating GLP-1.

Materials and Methods

The present observational study enrolled Japanese patients with type 2 diabetes who took a DPP-4I over 3 months, and most of the clinical information was collected retrospectively. We defined non-responders as those having less than a 0.2% decrease of the glycated hemoglobin level at 3 or 4 months after starting DPP-4I treatment. Physical activity was retrospectively estimated by the Japanese short version of International Physical Activity Questionnaire.

Results

We studied 316 patients whose physical activity corresponding to the season of the DPP-4I administration was estimated. The non-responder rate was 29.7%. We analyzed rs1800796 and rs2097677, both are suggested to be functional in Japanese. Multivariate analysis for all patients showed that the adjusted odds ratio for the non-responder risk of the diplotype rs1800796 G/*–rs2097677 A/* against C/C-G/G (OR_G*A*) was 0.445 (P = 0.068). When patients were stratified by the International Physical Activity Questionnaire into low (n = 149) and moderate/high (n = 167) activity groups, however, OR_G*A* in each group was 1.58 (P = 0.615) and 0.153 (P = 0.003), respectively.

Conclusions

The diplotype rs1800796 G/*–rs2097677 A/* might contribute to responsiveness to DPP-4Is in Japanese patients with type 2 diabetes under a certain level of physical activity. However, further investigation is warranted to confirm this.     

Adherence to self‐care behavior and glycemic effects using structured education

Aims/Introduction

The purpose of the present study was to examine glycemic control in suboptimally controlled type 2 diabetes provided by a structured education group using the Diabetes Conversation Map™ (CM™) vs usual care in a university-based hospital primary care clinic.

Materials and Methods

This was a randomized, pragmatic clinical trial. Patients with type 2 diabetes were randomly assigned to structured education or usual care groups. The primary outcome was the difference in the mean change of glycated hemoglobin (HbA1c) from baseline to 12 months. Secondary outcomes included the percentage achieving therapeutic HbA1c goal and self-behavioral changes.

Results

A total of 245 patients were randomly assigned to two groups (CM™ group n = 121; usual care group, n = 116). The absolute reduction of HbA1c was significantly greater in the CM™ group at 3 and 6 months (Δ = −0.59% and Δ = −1.13%, P < 0.01), but the difference was no longer statistically significant at 9 and 12 months (Δ = −0.43% and Δ = −0.49%), based on an intention-to-treat analysis. A per-protocol analysis showed the significant change was maintained at 12 months (Δ = −0.67%). In the intervention group, greater percentages of patients achieved their American Association of Diabetes Educators Self-Care Behaviours™ framework (AADE7) behavioral goals at 3 months, in particular being active, problem-solving, reducing risk and health coping.

Conclusions

In type 2 diabetic patients with suboptimally controlled glucose, there were greater improvements in glucose control and self-care behavioral goals in those who underwent the CM™ education program compared with outcomes achieved in patients receiving usual care.     

Carbohydrate intake is associated with time spent in the euglycemic range in patients with type 1 diabetes

Aims/Introduction

Greater glycemic variability and lack of predictability are important issues for patients with type 1 diabetes. Dietary factors are one of the contributors to this variability, but how closely diet is linked to glycemic fluctuation on a daily basis has not been investigated. We examined the association between carbohydrate intake and glycemic excursion in outpatients.

Materials and Methods

A total of 33 patients with type 1 diabetes were included in the analyses (age 44.5 ± 14.7 years, diabetes duration 15.1 ± 8.3 years, 64% female, 30% using insulin pump, glycated hemoglobin 8.1 ± 1.3%). Time spent in euglycemia (70–180 mg/dL), hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) of consecutive 48-h periods of continuous glucose monitoring data were collected together with simultaneous records of dietary intake, insulin dose and physical activity. Correlation analyses and multiple regression analyses were used to evaluate the contribution of carbohydrate intake to time spent in the target glycemic range.

Results

In multiple regression analyses, carbohydrate intake (β = 0.53, P = 0.001), basal insulin dose per kg per day (β = −0.31, P = 0.034) and diabetes duration (β = 0.30, P = 0.042) were independent predictors of time spent in euglycemia. Carbohydrate intake (β = −0.51, P = 0.001) and insulin pump use (β = −0.34, P = 0.024) were independent predictors of time spent in hyperglycemia. Insulin pump use (β = 0.52, P < 0.001) and bolus insulin dose per kg per day (β = 0.46, P = 0.001) were independent predictors of time spent in hypoglycemia.

Conclusions

Carbohydrate intake is associated with time spent in euglycemia in patients with type 1 diabetes.     

Disparities in the Use of Internet and Telephone Medication Refills among Linguistically Diverse Patients

Background

Health systems are increasingly implementing remote telephone and Internet refill systems to enhance patient access to medication refills. Remote refill systems may provide an effective approach for improving medication non-adherence, but more research is needed among patients with limited English proficiency with poor access to remote refill systems.

Objective

To compare the use of remote medication refill systems among limited-English-proficiency (LEP) and English-proficient (EP) patients with chronic conditions.

Methods

Cross-sectional survey in six languages/dialects (English, Cantonese, Mandarin, Korean, Vietnamese, and Spanish) of 509 adults with diabetes, hypertension, or hyperlipidemia. Primary study outcomes were self-reported use of 1) Internet refills, 2) telephone refills, and 3) any remote refill system. LEP was measured by patient self-identification of a primary language other than English and a claims record of use of an interpreter. Other measures were age, gender, education, years in the U.S., insurance, health status, chronic conditions, and number of prescribed medications. Analyses included multivariable logistic regression weighted for survey non-response.

Results

Overall, 33.1 % of patients refilled their medications by telephone and 31.6 % by Internet. Among LEP patients (n = 328), 31.5 % refilled by telephone and 21.2 % by Internet, compared with 36.7 % by telephone and 52.7 % by Internet among EP patients (n = 181). Internet refill by language groups were as follows: English (52.7 %), Cantonese (34.9 %), Mandarin (17.4 %), Korean (16.7 %), Vietnamese (24.4 %), and Spanish (12.6 %). Compared to EP patients, LEP patients had lower use of any remote refill system (adjusted odds ratio [AOR] 0.18; p < 0.001),

Conclusions

LEP patients are significantly less likely than EP patients to use any remote medication refill system. Increased reliance on current systems for remote medication refills may increase disparities in health outcomes affecting LEP patients with poor access to telephone and Internet medication refills.Key Words: language barriers, minority health, survey research, disparities, adherence     

Are late-night eating habits and sleep duration associated with glycemic control in adult type 1 diabetes patients treated with insulin pumps?

Aims/Introduction

Little is known about the impact of sleep duration and late-night snacking on glycemic control in patients with type 1 diabetes using insulin pumps. The aim of the present study was to examine whether late-night eating habits and short sleep duration are associated with glycemic control in continuous subcutaneous insulin infusion-treated type 1 diabetic patients.

Materials and Methods

We included 148 consecutive adult type 1 diabetic subjects using an insulin pump (100 women and 48 men). Participants completed a questionnaire regarding sleep duration (classified as short if ≤6 h) and late-night snacking. Other sources of information included medical records and data from blood glucose meters. Glycemic control was assessed by glycated hemoglobin (HbA1c) levels and mean self-monitoring of blood glucose (SMBG) readings.

Results

The mean age of patients was 26 years, mean type 1 diabetes duration was 13.4 years and mean HbA1c level was 7.2%. In a univariate regression analysis, sleep duration was a predictor of both HbA1c (β = 0.51, P = 0.01) and SMBG levels (β = 11.4, P = 0.02). Additionally, an association was found between frequent late-night snacking and higher SMBG readings (often snacking β = 18.1, P = 0.05), but not with increased HbA1c levels. In the multivariate linear regression, independent predictors for HbA1c and SMBG were sleep duration and patient age. In a univariate logistic regression, sleep duration and frequency of late-night snacking were not predictors of whether HbA1c target levels were achieved.

Conclusions

Short sleep duration, but not late-night snacking, seems to be associated with poorer glycemic control in type 1 diabetic patients treated with continuous subcutaneous insulin infusion.     

Heel bone strength is related to lifestyle factors in Okinawan men with type 2 diabetes mellitus

Aims/Introduction

Although male diabetic patients have an increased risk of fracture, there is little information about this in the literature. The association between heel bone stiffness and the lifestyle of male patients with diabetes was evaluated.

Materials and Methods

The study included 108 participants with type 2 diabetes mellitus patients and 168 age-adjusted, healthy male volunteers. None of the participants had a history of osteoporosis or other severe diseases. Heel bone stiffness was examined by quantitative ultrasound, and each participant completed a health interview survey questionnaire. Bone stiffness was taken as an indicator of bone strength. Stepwise regression analysis was used to investigate associations between bone stiffness and lifestyle-related factors, such as sunlight exposure, intake of milk or small fish, regular exercise, cigarette smoking, consumption of alcohol, and number of remaining teeth.

Results

Bone stiffness showed a significant negative association with cigarette smoking [standardized coefficient (SC) = −0.297, F-value (F) = 10.059] and age (SC = −0.207, F = 7.565) in diabetic patients. Bone stiffness showed a significant negative association with age (SC = −0.371, F = 12.076) and height (SC = −0.193, F = 7.898), as well as a significant positive association with sunlight exposure (SC = 0.182, F = 9.589) and intake of small fish (SC = 0.170, F = 7.393) in controls.

Conclusions

These findings suggest that cigarette smoking and age are negatively associated with bone stiffness in Okinawan male patients with type 2 diabetes mellitus.     

Detection and characterization of respiratory viruses causing acute respiratory illness and asthma exacerbation in children during three different seasons (2011–2014) in Mexico City

Background

Viral infections play a significant role in causing acute respiratory infections (ARIs) and exacerbations of chronic diseases. Acute respiratory infections are now the leading cause of mortality in children worldwide, especially in developing countries. Recently, human rhinovirus (HRV) infection has been emerged as an important cause of pneumonia and asthma exacerbation.

Objectives

To determine the role of several viral agents principally, respiratory syncytial virus, and HRV in children with ARIs and their relationship with asthma exacerbation and pneumonia.

Methods

Between October 2011 and March 2014, 432 nasopharyngeal samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were tested for the presence of respiratory viruses using a multiplex RT-qPCR. Clinical, epidemiological, and demographic data were collected and associated with symptomatology and viral infections.

Results

Viral infections were detected in at least 59·7% of the enrolled patients, with HRV (26·6%) being the most frequently detected. HRV infections were associated with clinical features of asthma and difficulty in breathing such as wheezing (P = 0·0003), supraesternal (P = 0·046), and xiphoid retraction (P = 0·030). HRV subtype C (HRV-C) infections were associated with asthma (P = 0·02).

Conclusions

Human rhinovirus was the virus most commonly detected in pediatric patients with ARI. There is also an association of HRV-C infection with asthma exacerbation, emphasizing the relevance of this virus in severe pediatric respiratory disease.     

The effect of antiviral therapy on serum cholesterol levels in chronic hepatitis C

Background/Aims

The aims of this study were to evaluate the effect of antiviral therapy on serum total cholesterol (TC) levels and to investigate the factors related to serum TC changes in chronic hepatitis C (CHC) patients.

Methods

A total of 94 CHC patients, the majority of whom were infected with genotype 1 or 2 and were receiving antiviral therapy, were consecutively enrolled. TC levels before treatment, at week 4, at the end of treatment (EOT), and at 24 weeks after the EOT were analyzed, along with factors related to pre- and post-treatment TC levels.

Results

Pretreatment TC levels in the sustained virologic response (SVR) group (167±3.6 mg/dL) and the non-SVR group (158±8.3 mg/dL) were similar, and both decreased during antiviral therapy. The TC levels at 24 weeks after the EOT significantly increased in the SVR group (183±4.7 mg/dL), but not in the non-SVR group (160±7.1 mg/dL, p=0.044) after adjusting for the pretreatment TC levels. The grade of hepatic fibrosis, as measured by the METAVIR score or the aspartate aminotransferase-platelet ratio index (APRI), but not viral load (p=0.119), was an independent variable associated with the pretreatment TC levels (METAVIR score, p=0.011; APRI, p=0.033). After adjusting for the presence of a SVR by longitudinal data analysis using generalized estimating equations, the independent variable APRI was associated with the serum TC level after antiviral therapy (p=0.014), whereas a SVR was associated with the serum TC level only with marginal statistical significance (p=0.084).

Conclusions

Serum TC levels increased in the SVR group after antiviral therapy for CHC; however, this was probably due to an improvement in liver fibrosis rather than the eradication of virus.     

Ezetimibe combined with standard diet and exercise therapy improves insulin resistance and atherosclerotic markers in patients with metabolic syndrome

Aims/Introduction

Ezetimibe lowers serum lipid levels by inhibiting intestinal absorption of dietary and biliary cholesterol. However, the effect of ezetimibe on insulin resistance remains unclear. The aim of the present study was to examine this issue in patients with metabolic syndrome in local-dwelling Japanese, who were not being treated with lipid-lowering drugs.

Materials and Methods

In 2009, 1,943 participants received a health examination in the Tanushimaru Study, a Japanese cohort of the Seven Countries Study, of whom 490 participants had metabolic syndrome. Among them, 61 participants (41 men and 20 women) were examined in the present study. They were treated with 10 mg of ezetimibe once a day for 24 weeks, combined with standard diet and exercise therapy.

Results

Bodyweight (P < 0.001), body mass index (P < 0.001), systolic blood pressure (P = 0.003), diastolic blood pressure (P < 0.001), triglycerides (P = 0.002), non-high-density lipoprotein cholesterol (P = 0.001), low-density lipoprotein cholesterol (P < 0.001) and homeostasis model assessment of insulin resistance (P = 0.011) significantly decreased after the observational period. There were no statistically significant differences in the effects of ezetimibe between men and women. Univariate analysis showed that the reduction of homeostasis model assessment of insulin resistance was not associated with the improvement of other metabolic components.

Conclusions

Ezetimibe combined with standard diet and exercise therapy improves not only bodyweight and atherogenic lipid profiles, but also insulin resistance, blood pressure and anthropometric factors in metabolic syndrome in local-dwelling Japanese. Interestingly, the improvement of insulin resistance had no correlation with other metabolic components.     

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.     

Efficacy and tolerability of peginterferon alpha plus ribavirin in the routine daily treatment of chronic hepatitis C patients in Korea: a multi-center, retrospective observational study

Background/Aims

We aimed to evaluate the efficacy and safety of peginterferon plus ribavirin for chronic hepatitis C (CHC) patients under real life setting in Korea.

Methods

We retrospectively analyzed the medical records of 758 CHC patients treated with peginterferon plus ribavirin between 2000 and 2008 from 14 university hospitals in the Gyeonggi-Incheon area in Korea.

Results

Hepatitis C virus (HCV) genotype 1 was detected in 61.2% of patients, while genotype 2 was detected in 35.5%. Baseline HCV RNA level was ≥6×10⁵ IU/mL in 51.6% of patients. The sustained virological response (SVR) rate was 59.6% regardless of genotype; 53.6% in genotype 1 and 71.4% in genotype 2/3. On multivariate analysis, male gender (p=0.011), early virological response (p<0.001), genotype 2/3 (p<0.001), HCV RNA <6×10⁵ IU/mL (p=0.005) and adherence to the drug >80% of the planned dose (p<0.001) were associated with SVR. The rate of premature discontinuation was 35.7%. The main reason for withdrawal was intolerance to the drug due to common adverse events or cytopenia (48.2%).

Conclusions

Our data suggest that the efficacy of peginterferon and ribavirin therapy in Koreans is better in Koreans than in Caucasians for the treatment of CHC, corroborating previous studies that have shown the superior therapeutic efficacy of this regimen in Asians.     

Noninvasive assessment of liver fibrosis with the aspartate transaminase to platelet ratio index (APRI): Usefulness in patients with chronic liver disease: APRI in chronic liver disease

Background

The aspartate aminotransferases (AST) to platelet ratio index (APRI) may serve as a noninvasive marker to assess liver fibrosis.

Objectives

To assess the diagnostic ability of the APRI for prediction of fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD).

Patients and Methods

This retrospective study included 207 patients with CHB, 108 with CHC, and 140 patients with NAFLD. The APRI was calculated as (AST level/upper normal limit for AST)/platelet counts (109/L) × 100. The stage of liver fibrosis in patients with chronic viral hepatitis was graded using the METAVIR scale. The Kleiner system for grading fibrosis was used in patients with NAFLD.

Results

Bivariate correlation analyses showed that the APRI was significantly associated with fibrosis scores in patients with CHC (p = 0.2634, p = 0.0059) and NAFLD (p = 0.2273, p = 0.0069), but not in those with CHB (p = 0.1005, p = 0.1495). Receiver operating characteristic (ROC) curves were used for assessing the ability of the APRI as a predictor of the absence or presence of liver fibrosis (fibrosis score of 0 vs fibrosis scores of 1-4). In patients with CHC, the APRI showed a sensitivity of 72.7% and a specificity of 62.4% for detection of fibrosis (p<0.01). In the NAFLD group, the APRI showed a sensitivity of 60.0% and specificity of 73.3% for detection of fibrosis (p<0.01). In patients with CHB, the APRI showed a sensitivity of 55.0% and a specificity of 75.4% for fibrosis (p=NS).

Conclusions

The APRI shows an acceptable accuracy for the assessment of liver fibrosis in patients with CHC and NAFLD, but not in those with CHB.     

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.