Humoral immune response to a yeast-derived hepatitis B vaccine in patients with type 1 diabetes mellitus.

The immune response following vaccination with a recombinant hepatitis B vaccine was investigated in 32 patients with Type 1 diabetes mellitus and compared with the outcome in 32 healthy age- and sex-matched volunteers. Participants were vaccinated at 0, 30, and 180 days and in vivo immune response was determined at 30, 60, 90, 180, and 210 days. The number of responders (anti-HBs greater than 1 IU l-1) was significantly lower (p less than 0.05) among patients at 30 (2 vs 11), 60 (17 vs 26), 90 (20 vs 28) and 180 (22 vs 29) days. The number of patients protected (anti-HBs greater than 10 IU l-1) was lower (p less than 0.05) than the number of protected volunteers at 60 (5 vs 14), 90 (10 vs 19), 180 (15 vs 24), and 210 days (24 vs 31). After the complete course of vaccination 8 out of 32 patients were still unprotected against hepatitis B (p less than 0.05). The anti-HBs titre of responders at 210 days was 251 (20, 3162) (geometric mean (-SD, +SD] IU l-1 in patients and 1259 (126, 12589) IU l-1 in control subjects (p less than 0.05). The HLA-antigen DQw1 frequency in the diabetic low responders (anti-HBs less than 100 IU l-1) was 0.27 compared with 0.86 in diabetic adequate responders. No relation between anti-HBs production and concentration of HbA1c could be demonstrated.     

慢性丙型肝炎病毒感染者2型糖尿病流行病学调查

目的研究慢性丙型肝炎病毒感染者2型糖尿病的发病情况。方法对221例慢性丙型肝炎感染者(其中肝硬化72例)2型糖尿病发病情况进行调查,并与慢性乙型肝炎病毒感染者660例(其中肝硬化220例)2型糖尿病发病情况进行对照。结果慢性丙型肝炎感染者2型糖尿病的发病率为21.2%(47/221),高于慢性乙型肝炎感染者的10.9%(72/660)(P<0.02);丙型肝炎病毒致肝硬化2型糖尿病的发病率为30.6%(22/72),明显高于慢性丙型肝炎患者2型糖尿病发病率23.4%(35/149),(P<0.05),并明显高于对照组乙型肝炎病毒致肝硬化2型糖尿病的发病率11.3%(25/220),(P<0.05)。结论肝硬化是慢性丙型肝炎感染者发生2型糖尿病的危险因素;肝硬化和丙型肝炎病毒共同作用导致了2型糖尿病危险性的增加。丙型肝炎病毒致肝硬化2型糖尿病的发病率明显高于乙型肝炎病毒致肝硬化。     

大鼠支气管哮喘模型γδT细胞Th1/Th2免疫应答模式的研究

目的　探讨γδT细胞在哮喘的免疫应答模式 ,认识γδT细胞亚群在哮喘发病机制中的作用。方法　Wistar大鼠 2 0只 ,随机分为健康对照组与哮喘组 (用鸡卵清蛋白致敏和刺激大鼠 ,制作哮喘模型 ) ,每组 10只。收集外周血单个核细胞 (PBMC)和支气管肺泡灌洗液 (BALF) ,用补体攻击法结合洗淘法选择性培养扩增γδT细胞 ,并用流式细胞术鉴定培养体系中的γδT细胞及其纯度 ,用原位杂交法测γδT细胞白细胞介素 (IL) 4mRNA和干扰素 (IFN)γmRNA的表达 ,用ELISA检测培养上清液中IL 4和IFN γ的浓度。结果　哮喘组大鼠PBMC和BALF中 ,γδT细胞培养上清液中IL 4浓度显著高于健康对照组 (P <0 0 1) ,IFN γ浓度低于健康对照组 (P <0 0 1) ;γδT细胞IL 4mRNA表达阳性率高于健康对照组 (P <0 0 1) ,IFN γmRNA表达阳性率低于健康对照组 (P <0 0 1)。结论γδT细胞或者γδT细胞亚群存在Th1/Th2模式 ,在大鼠哮喘模型呈Th2优势应答 ,γδT细胞参与了哮喘的发病过程。     

Prevalence of microalbuminuria in children with Type 1 (insulin-dependent) diabetes mellitus

Summary The prevalence of microalbuminuria was determined in children aged 7 to 18 years with Type 1 (insulin-dependent) diabetes of more than 2 years' duration. All patients (n =102) attending 2 diabetes clinics were asked to collect 2 overnight timed urine samples for albumin analysis by radioimmunoassay. Complete urine collection was obtained in 97 patients (95%). Overnight urinary albumin excretion rates were also measured in 36 healthy children matched for age and sex. Nineteen of the 97 patients (20%) had microalbuminuria, i. e. overnight urinary albumin excretion rates above the upper normal level (14 g/min) in both urine collections. Microalbuminuria was only demonstrated in patients aged 15 years, prevalence 37% (19/52 patients). Arterial blood pressure was elevated, mean 122/84±11/9mmHg, in the microalbuminuric group (19 patients) compared to the age-matched normoalbuminuric diabetic group (33 patients), mean 117/74±10/10 mm Hg,p < 0.001. The prevalence of simplex retinopathy was identical in these two groups, i. e. 25%. Glycosylated haemoglobin was slightly higher in the microalbuminuric patients,p < 0.10. Our cross-sectional study reveals a high prevalence (37%) of persistent microalbuminuria, a stage highly predictive of later development of diabetic nephropathy, in Type 1 diabetic children aged 15 years.     

Cytokine response to diabetic ketoacidosis (DKA) in children with type 1 diabetes (T1DM)

It has been suggested that cytokine release during DKA may result in capillary perturbation and thus may contribute to the development of its acute clinical complications (i.e.cerebral or pulmonary edema). We studied in 38 newly diagnosed T1DM children with DKA, aged 7.68±3.07 years, plasma levels of cytokines IL-1β (interleukin-1β), IL-2, IL-6, IL-8, IL-10, TNF-α (tumour necrosis factor-α) and also WBC (white blood cell count), hs-CRP (high sensitivity C-reactive protein), GH (growth hormone) and cortisol, prior to, during and 120h after DKA management, with the aim to monitor their levels at different time-points and in different degrees of DKA severity. Prior to DKA management the levels of IL-6, IL-8, IL-10, WBC and cortisol were elevated, but were all reduced within 120 h after DKA management. Then the patients were divided into two groups: a. moderate/severe: pH≤7.2, b. mild DKA: pH>7.2. In the group with moderate/severe DKA (ph≤7.2), IL-10 levels were the highest of all cytokines, but were significantly decreased after 6h (91.76 vs 18.04 pg/mL, p=0.008), with no further change, while IL-6 levels were decreased at 120 h (28.32 vs 11.9 pg/mL, p=0.003). The above were not observed in the group with mild DKA. In conclusion, in the children with DKA of our study, in the group with moderate/severe DKA the IL-10 levels were prematurely reduced at 6 hours, while the IL-6 levels remained high and were reduced at 120 hours after the DKA management. These changes may be responsible for increased capillary perturbation, which could lead to the subsequent development of acute DKA complications.     

Vaccination adherence to influenza,pneumococcal and hepatitis B virus in adult type 1 diabetes mellitus patients

AimTo document adherence to influenza, pneumococcal and hepatitis B virus (HBV) vaccination programme in adult type 1 diabetes mellitus (T1DM) patients.Materials and methodsObservational retrospective study using data obtained from computerized clinical records. We contacted all adult T1DM registered in our database from a tertiary diabetes care hospital. Primary efficacy outcome was to describe influenza, pneumococcal and HBV vaccination status.ResultsThree hundred patients were analyzed (male 53%). Mean age was 40.0 ± 14.4 years and T1DM duration was 19.7 ± 11.8 years. Thirty-five percent of the patients had complementary indications for studied vaccines. Adherence to vaccination program for influenza, pneumococcal and HBV was achieved by 55%, 18% and 17% of the patients, respectively. Only 3% of the subjects were vaccinated against the three microorganisms. Predictor of correct vaccination were: age, shorter diabetes duration, insulin pump treatment, better diabetes control and being a health professional. We detected 17 sick leaves, 127 lost working days and 3 hospitalizations due to flue during the follow-up.ConclusionsThe uptake of recommended vaccinations against influenza, pneumococcal and HBV in adult T1DM patients was below desirable levels. A special effort is required to all health professionals to implement immunization among adult people with T1DM. Clinical Trials NCT03478254.     

Thymus-derived lymphocytes in type B acute viral hepatitis and healthy carriers of hepatitis B surface antigen (HBsAg)

To assess thymus-derived (T) lymphocyte function in hepatitis B infection, lymphocytes from patients with type B acute viral hepatitis and healthy carriers of the hepatitis B surface antigen, were compared to normal controls using phytohemagglutinin (PHA)-induced blast cell transformation and sheep-cell rosette formation. Overall cell (T lymphocyte)-mediated immune function was similar with thesein vitro assays in all three groups, except for decreases in total T cells in isolated patients with acute disease. Consequently, if a defect in cellular immunity exists in normal controls with persistent hepatitis B infection, it is probably specific for the antigens of the hepatitis B virus and not related to a generalized impairment of T-lymphocyte function.     

乙型肝炎和丙型肝炎与2型糖尿病的关系

乙型肝炎和丙型肝炎以及2型糖尿病(T2DM)均为全球性的严重公共卫生问题。分析了乙型和丙型肝炎与T2DM的关系。分析表明,一方面,乙型肝炎和丙型肝炎均促进T2DM发病,其发病机制涉及病毒感染抑制胰岛素信号转导和胰岛素靶细胞葡萄糖摄取以及糖原合成。另一方面,T2DM患者容易罹患乙型肝炎和丙型肝炎,这可能与糖尿病导致多种器官功能的破坏有关。     

Prevalence of hepatitis C infection in patients with type 2 diabetes mellitus

BACKGROUND: Recently, a possible epidemiological association between hepatitis C virus infection and diabetes mellitus has been suggested and a higher prevalence of HCV antibodies has been found among type 2 diabetic when compared with normal controls. AIM: To evaluate the prevalence of hepatitis C infection in diabetic patients in Curitiba, PR, Brazil. PATIENTS AND METHODS: A total of 145 type 2 and 104 type 1 diabetic patients attending the outpatient diabetic unit of an university hospital were consecutively tested for anti-HCV, using a fourth-generation enzyme-linked immunosorbent assay (ELISA). The control group was constituted by 16,720 volunteer blood donors attending the blood bank of the same hospital during the period of the study. Diabetic patients were also evaluated for clinical, biochemical (aminotransferase levels) and demographic variables and previous exposure to risk factors for hepatitis C infection. RESULTS: A higher prevalence of hepatitis C infection was observed in type 2 diabetic patients in comparison with blood donors. Although anti-HCV prevalence in type 2 diabetic patients was higher than found in type 1, it did not reach statistical significance. Both diabetic groups were predominantly female, and as expected, type 2 diabetic were older than type 1. Race distribution, duration of the disease, and previous exposure to hepatitis C risk factors were similar in both groups, but type 2 diabetic subjects had higher median levels of alanine aminotransferase than type 1. CONCLUSIONS: A higher prevalence of hepatitis C infection was detected in type 2 diabetic patients in comparison with blood donors in our region, in accordance with study data from different populations. If all type 2 diabetic patients should undergo regular screening for hepatitis C infection remains a question.     

Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States

BACKGROUND: Hepatitis C virus (HCV) infection may contribute to the development of diabetes mellitus. This relationship has not been investigated at the population level, and its biological mechanism remains unknown. OBJECTIVE: To examine the prevalence of type 2 diabetes among persons with HCV infection in a representative sample of the general adult population of the United States. DESIGN: Cross-sectional national survey. SETTING: The Third National Health and Nutrition Examination Survey, 1988-1994. PARTICIPANTS: 9841 persons older than 20 years of age for whom data on HCV infection and diabetes were complete. MEASUREMENTS: The presence of diabetes was ascertained by using American Diabetes Association guidelines based on fasting plasma glucose measurement and medication history. Presence of HCV infection was assessed by testing for serum HCV-specific antibodies (anti-HCV). RESULTS: Of the 9841 persons evaluated, 8.4% had type 2 diabetes and 2.1% were anti-HCV positive. Type 2 diabetes occurred more often in persons who were older, were nonwhite, had a high body mass index, and had low socioeconomic status. Type 2 diabetes was less common in persons who acknowledged previous illicit drug use. After adjustment for these factors, persons 40 years of age or older with HCV infection were more than three times more likely than those without HCV infection to have type 2 diabetes (adjusted odds ratio, 3.77 [95% CI, 1.80 to 7.87]). None of the 19 persons with type 1 diabetes were anti-HCV positive. CONCLUSION: In the United States, type 2 diabetes occurs more often in persons with HCV infection who are older than 40 years of age.     

DNA immunization encoding the secreted nonstructural protein 3 (NS3) of hepatitis C virus and enhancing the Th1 type immune response

To induce a sustained and specific cellular immune response to hepatitis C virus (HCV), DNA immunization of mice was performed using plasmids containing the HCV nonstructural gene 3 (HCV/NS3). Plasmids were constructed such that the NS3 gene was expressed in a secreted form, a nonsecreted form or as a membrane-bound antigen. The plasmid encoding the secreted antigen induced the strongest humoral and cellular immunity and favoured the T-helper type 1 (Th1) pathway as shown by cytokine profiles and switching of antibody subclasses. Our study indicates that DNA immunization with a secreted form of HCV/NS3 is an effective means of inducing primary Th1 immune responses in the murine model.     

Ribavirin enhancement of hepatitis C virus core antigen-specific type 1 T helper cell response correlates with the increased IL-12 level

BACKGROUNDS/AIMS: Combination IFN-a and ribavirin therapy for hepatitis C virus-infected patients has been reported to improve the response rate up to 50%. In this study, we aimed to study further the role of ribavirin in hepatitis C virus-specific immune responses. METHODS: We immunized mice with hepatitis C virus core protein with or without different concentrations of ribavirin. Forty days after immunization, hepatitis C virus-specific immune responses were followed in these mice. RESULTS: We found that the mice immunized with core antigen once every 2 weeks and 0.5 mg ribavirin every day showed higher levels of core-specific IgG2 compared with those mice immunized with core antigen only. In addition, core antigen-stimulated spleen cells produced higher levels of T helper type 1 cytokines and the core-specific cytotoxic T cell activity also increased significantly. Furthermore, lipopolysaccharide-stimulated peritoneal cells produced higher levels of IL-12 in ribavirin-treated mice, and peritoneal cells isolated from naive mice also produced significantly higher level of IL-12 when cultured with ribavirin. CONCLUSIONS: Ribavirin may significantly promote the T helper type 1 immune response in vivo, and, furthermore, the effect of ribavirin on IL-12 level produced by accessory cells may contribute to the T helper type 1 enhancing effect.     

调节性T细胞和辅助性T细胞17的平衡变化在慢性乙型肝炎病毒感染中的作用

目的 研究调节性T细胞(Treg)和辅助性T细胞17(Th17)的平衡变化在慢性HBV感染中的作用.方法 应用ELISA法和流式细胞术分别对34例慢性乙型肝炎(CHB)患者、20例HBV相关慢加急性肝功能衰竭(ACHBLF)患者和20例健康对照者外周血中Treg和Th17分化相关细胞因子及外周血Th17和Treg细胞水平进行检测.计数资料应用Fisher's确切概率法,计量资料应用单因素方差分析和Tukey's多重比较检验.结果 ACHBLF组Th17分化相关因子IL-1β为(3.97±2.85) pg/mL,IL-6为(12.75±8.87)pg/mL,IL-21为(360.0±335.7)pg/mL,比健康对照组的IL-1β[(1.87±0.94)pg/mL,q=4.559,P＜0.01)、IL-6[(5.28±o.72)pg/mL,q=7.309,P＜0.01)和IL-21[(46.68±20.17) pg/mL,q=6.946,P＜0.01)均明显上调.ACHBLF组外周血Th17细胞比例明显高于健康对照组(q=3.972,P＜0.05).与健康对照组和ACHBLF组相比,CHB组Treg细胞分化相关因子TGF-β明显升高(q=4.536、5.323,均P＜0.01),外周血Treg比例也明显升高.ACHBLF组Th17细胞效应因子IL-17A水平最高,ACHBLF患者外周血Th17细胞比例与血清TBil水平呈正相关(γ=0.74,P＜0.01).结论 慢性HBV感染中,宿主免疫存在Th17和Treg失衡,ACHBLF组以Th17细胞活动为主,CHB组以Treg细胞活动为主.     

Interactions between human immunodeficiency virus-1, hepatitis delta virus and hepatitis B virus infections in 260 chronic carriers of hepatitis B virus.

To evaluate the factors determining the severity of chronic hepatitis B virus infection and the interactions of human immunodeficiency virus and hepatitis delta virus infections, we retrospectively analyzed 260 patients, 146 of whom were followed for a mean of 31.4 +/- 1.8 mo. Human immunodeficiency virus, hepatitis B virus, and hepatitis delta virus status and aminotransferase activities, histological activity index, alcohol consumption and the prevalence of cirrhosis were investigated. The patients included 54 homosexuals, 19 parenteral drug abusers and 187 subjects with other or unidentified risk factors for exposure to hepatitis B virus. Thirty-five patients (13%) were positive for antibody to human immunodeficiency virus; 27 were homosexual and 8 were drug abusers. The mean aminotransferase activities, histological activity index and the prevalence of cirrhosis were similar in the human immunodeficiency virus-positive and human immunodeficiency virus-negative subgroups. Actuarial survival was significantly lower in the human immunodeficiency virus-negative subgroups. Actuarial survival was significantly lower in the human immunodeficiency virus-positive group than in the human immunodeficiency virus-negative subjects (p = 0.004); the cause of death was clearly related to liver failure in four of the five human immunodeficiency virus-positive patients and two of the six human immunodeficiency virus-negative subjects who died. To evaluate the factors determining the severity of liver disease, we compared homogeneous subgroups of subjects. Among the homosexual patients, the prevalence of HBeAg and hepatitis B virus DNA, aminotransferase activities and the histological activity index did not differ according to human immunodeficiency virus antibody status.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus

Background: To examine the relationship between hepatitis C virus (HCV) infection and diabetes mellitus (DM) in Japanese populations, a retrospective study was done in 866 patients with chronic viral disease. Methods: The present study included 707 HCV-infected and 159 hepatitis B virus (HBV)-infected patients. The prevalences of HBV- and HCV-related cirrhosis were 32% and 33%, respectively. A case-control study was also conducted to determine the seroprevalence of HCV infection in a cohort of 459 diabetics. Results: The prevalence of DM was higher in HCV-infected patients (20.9%; P < 0.02) than in HBV-infected subjects (11.9%). In the cirrhotic patients, DM was observed in 30.8% of the subjects with HCV compared with 11.8% of those with HBV (P < 0.01). Multivariate analysis revealed that the major independent variables associated with type II DM were male sex (odds ratio, 1.54; p = 0.020) and cirrhosis (odds ratio, 1.97; P = 0.0007). The relative odds of the development of DM were calculated to be 3.2 times higher in HCV-infected cirrhotic patients than in HBV-infected ones. In the case-control study of the diabetic cohort, 10.5% of patients were infected with HCV compared with 1.1% with HBV (P < 0.0001). The results indicate that HCV infection is closely associated with DM, compared with HBV infection. Cirrhosis was an independent risk factor for DM. Conclusions: Taken together, the findings indicate that cirrhosis appears to be a more important predictor of glucose intolerance than HCV infection, and the combination of both factors increases the risk of DM in our populations. Received: April 18, 2002 / Accepted: October 25, 2002 Reprint requests to: S. Kakumu     

The prevalence of occult hepatitis B virus infection in type 2 diabetes mellitus patients

AIM: The prevalence of occult hepatitis B virus (HBV) infection is relatively frequent among patients with immune suppression. The impairment of the immune system is well demonstrated in diabetics. We aimed to investigate the prevalence of occult HBV infection among hepatitis B core antibody (HbcAb)+/- hepatitis B surface antibody (anti-HBs) positive type 2 diabetes mellitus patients. MATERIALS AND METHODS: The study involved 100 HBcAb+/-anti-HBs type 2 diabetes mellitus patients and 100 age and sex matched, HBcAb+/-anti-HBs healthy blood donors. Exclusion criteria were positive serology for HBsAg, hepatitis C virus or HIV, diagnosis of malignancy or earlier organ transplantation history, use of immunosuppressive therapy. All patients were questioned about their past medical history and were tested for serum alanine aminotransferase and HBV DNA level. RESULTS: The diabetic patients did not differ significantly from healthy controls in terms of sex and age. HBV DNA was detected in 11% of the diabetic patients (1 x 10-5 x 10 copies/ml) and in 3% of the controls (4 x 10-1 x 10 copies/ml). The difference between groups was statistically significant (P<0.05). The history of blood transfusion, surgery, and vaccination for HBV and alcohol use were similar in both groups (P>0.05). The serum alanine aminotransferase levels in diabetic patients were close to those of controls (26.2+/-16.4 IU/l vs. 23.9+/-9.7 IU/l; P>0.05). CONCLUSION: These data suggest that the prevalence of occult HBV infection is higher in diabetics compared with healthy controls and this may contribute to the increased prevalence of primary hepatocellular carcinoma in diabetics.