Incidence of Hepatitis C Virus Infections Among Users of Human Immunodeficiency Virus Pre-exposure Prophylaxis

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慢性戊型肝炎相关研究进展

戊型肝炎散发于世界各地,多为急性自限性疾病,但近年来不断有文献报道在HIV感染者、器官移植和放化疗患者等免疫力低下人群中发现基因3型戊型肝炎病毒感染导致的戊型肝炎慢性化疾病,其临床表现类似急性戊型肝炎,但症状及肝功能损伤均较轻.目前研究发现,人群感染戊型肝炎病毒后肝炎慢性化的机制主要包括宿主因素和病毒因素.此文就慢性戊型肝炎的定义、临床表现、患者特征、感染慢性化的病毒因素及治疗等方面的进展进行综述.     

Inhibition of Fas-mediated Apoptosis by Antigen: Implications for Lymphomagenesis

Apoptotic deletion of expanded B cell populations is essential in avoidance of autoimmune disease and immune regulation of some B cell malignancies. The role of CD4+ T cells in B cell apoptosis is evident from the high incidence of B cell tumors and autoimmunity in patients with T cell diseases such as the acquired immune deficiency syndrome (AIDS). We have previously demonstrated that in Epstein-Barr Virus (EBV) negative Burkitt's lymphoma (BL), a tumor derived from proliferating centroblasts of the germinal center, the malignant lymphocytes can be induced to express Fas (CD95) by ligation of CD40 at the B cell surface. Upon CD40 engagement, BL cells are sensitized to T-cell derived death signals provided by Fas ligand (FasL, CD95L). HBL-3 is a cell line derived from an AIDS-related BL in which the tumor IgM binds the human erythrocyte "i" antigen. To determine whether Fas-mediated apoptosis of BL cells is reduced in the context of antigen to which the tumor IgM binds, we stimulated HBL-3 cells with CD40 ligand (CD40L, CD154) in the presence and absence of human erythrocytes expressing the "i" antigen, and measured Fas-mediated apoptosis upon exposure to an agonistic anti-Fas antibody. We observed that HBL-3 cells were sensitized to Fas-mediated death by exposure to CD40L. When i+ RBCs were present, Fas-mediated apoptosis in HBL-3 cells was reduced by greater than 30%. In contrast, there was no reduction in Fas-mediated apoptosis in the presence of i &#109 (I+) RBCs. These findings demonstrate that Fas-mediated deletion of BL cells is inhibited upon surface IgM engagement by antigen for which the malignant clone has affinity.     

Successful Treatment with Cyclosporine A of HCV-Driven Chronic Liver Disease Mimicking Autoimmune Hepatitis in a Patient with Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) is the commonest primary immunodeficiency disease characterized by defective antibody production and various degrees of T cell numbers abnormality or impaired proliferation to mitogens. Clinical features include recurrent bacterial sinopulmonary and gastrointestinal infections. Autoimmunity is very common in CVID, occurring in approximately 25% of the patients particularly with autoimmune thrombocytopenia, hemolytic anemia, inflammatory bowel disease, and rheumatoid arthritis. Persistent antigen stimulation, secondary to a defective eradication of pathogens followed by a compensatory exaggerated chronic inflammatory response, is the primary cause leading to autoimmunity. Here we describe a girl with CVID in whom a chronic liver disease mimicking autoimmune hepatitis developed after hepatitis C virus infection. The immunosuppressive treatment with cyclosporine A proved effective in reversing liver disease.     

Specialty training and specialization among physicians who treat HIV/AIDS in the United States

OBJECTIVE: To assess the association of specialty training and experience in the care of HIV disease with HIV-specific knowledge, referral patterns, and HIV-related education activities. DESIGN: Cross-sectional survey. SETTING: The United States. PARTICIPANTS: Physicians caring for patients in the HIV Costs and Service Utilization Study, a study of a probability sample of HIV-infected individuals in the United States. MEASUREMENTS AND MAIN RESULTS: Measures included physicians' reports of specialty training and HIV caseload, scores on an HIV-specific knowledge test, referral patterns, and attendance rates at HIV-related educational activities. Approximately 72% (379) of the eligible physicians completed a survey. Of these, 152 (40%) had infectious disease (ID) training, and 213 (56%) were generalists; 4% of ID-trained physicians and 37% of generalist physicians did not consider themselves HIV experts. The median current caseloads were 150 and 200 patients for ID experts and generalist experts, respectively. In contrast, the median caseload for non-expert generalists was 5. Mean scores on the knowledge scale were similar for ID and generalist experts (9.0 items correct out of 11 vs 8.5; P=not significant), but lower for generalist non-experts (6.5 items correct; P <.01). Experts had attended more local and national HIV meetings than non-experts (9.3 vs 2.7; P <.01, and 2.3 vs.40; P <.01, respectively) in the past year. Fewer ID experts ever referred than generalist experts (13.0% vs 27.3%; P=.01). In multivariable models that included specialty training and caseload, physicians with caseloads of 20 to 49 and >50 were more likely to have a high knowledge score (defined as 80% or more correct, odds ratio [OR], 2.8; P=.04 and OR, 5.7; P <.001, respectively), and the effect of specialty was attenuated (OR, 2.7; P=.02 decreased from OR, 7.8; P <.001 in a model without caseload). In the models predicting referral practices, both experience (OR,.25; P <.01 and OR,.17; P <.01 for caseloads of 20 to 49 and >50, respectively) and specialty (OR,.19; P <.01 and OR,.09; P <.01 for generalist and ID experts, respectively) were significant. CONCLUSIONS: In a national sample of physicians, HIV-specific knowledge was more strongly associated with HIV caseload than with specialty training. In addition, although referral practices were related to both experience and specialty, generalist experts and ID physicians reported similar behaviors. This suggests that generalist physicians, through clinical experience and self-education, can develop specialized knowledge in HIV care.     

Low Prevalence of Hepatitis C Virus Infection Among HIV-Positive Patients: Data From a Large-Scale Cohort Study in Istanbul,Turkey

Background:

Rate of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) varies in different countries. This may be attributable to common transmission routes as well as social, economic, and cultural factors.

Objectives:

The purpose of this study was to investigate the prevalence and risk factors of HCV infection among HIV-positive patients in Istanbul, Turkey.

Patients and Methods:

Since January 2006 to November 2013, 949 HIV-positive patients that were enrolled in this study by ACTHIV-IST (Action Against HIV in Istanbul) Study Group, which consists of five centers to follow up HIV-positive patients in Istanbul. Epidemiologic and clinical data were collected retrospectively from medical records and were transferred to an HIV database system.

Results:

Among 949 patients, 84% were men and the mean age was 37.92 ± 11.54 years (range, 17-79). The most frequent route of transmission was heterosexual intercourse (48.8%), followed by men having sex with men (30.5%). Only nine patients (0.9%) had history of injection drug use (IDU). The prevalence of HIV/HCV coinfection was 0.9% (9:949). The IDU rate was 44.4% (4:9) in patients with HIV/HCV coinfection (three of them were not Turkish citizens), whereas this rate was only 0.6% (5:881) in patients with only HIV infection (P < 0.01). Genotypes 1b, 2a/2c, and 3 were determined in five, one, and two patients, respectively. Genotype could not be determined in one patient. History of residence in a foreign country (P < 0.01) and imprisonment (P < 0.01) were also considered as risk factors in terms of HIV/HCV coinfection.

Conclusions:

Prevalence of HIV/HCV coinfection is considerably low in Turkey. The extremely rare prevalence of IDU might have a role in this low prevalence.     

Risk factors and clinical profile of thrombotic thrombocytopenic purpura in systemic lupus erythematosus patients. Is this a distinctive clinical entity in the thrombotic microangiopathy spectrum?: A case control study

Introduction

The association of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE) is rare. It is associated with high morbidity and mortality. Information about risk factors and clinical outcomes is scant.

Material and Methods

A retrospective case-control study was performed in a referral center in Mexico City between 1994 and 2013. Patients were diagnosed with TTP if they fulfilled the following criteria: microangiopathic haemolytic anaemia, thrombocytopenia, high LDH levels, normal fibrinogen and negative Coombs’ test. Patients with SLE were diagnosed with ≥ 4 ACR criteria. We included three study groups: group A included patients with SLE-associated TTP (TTP/SLE; cases n = 22, TTP events n = 24); patients with non-autoimmune TTP (NA-TTP; cases n = 19, TTP events n = 22) were included in group B and patients with SLE without TTP (n = 48) in group C.

Results

After multivariate analysis, lymphopenia < 1000/mm3 [OR 19.84, p = 0.037], high SLEDAI score three months prior to hospitalisation [OR 1.54, p = 0.028], Hg < 7 g/dL [OR 6.81, p = 0.026], low levels of indirect bilirubin [OR 0.51, p = 0.007], and less severe thrombocytopenia [OR 0.98, p = 0.009] were associated with TTP in SLE patients. Patients with TTP/SLE received increased cumulative steroid dose vs. NA-TTP (p = 0.006) and a higher number of immunosuppressive drugs (p = 0.015). Patients with TTP/SLE had higher survival than NA-TTP (p = 0.033); however, patients hospitalised for TTP/SLE had a higher risk of death than lupus patients hospitalised for other causes

Conclusions

Lymphopenia is an independent risk factor for TTP/SLE. It is likely that patients with TTP/SLE present with less evident clinical features, so the level of suspicion must be higher to avoid delay in treatment.