丙型肝炎病毒与其合并人类免疫缺陷病毒感染者的病毒基因型差异

HCV与HIV具有相似的传播途径,都可以通过使用污染的血制品、注射用具、性接触及母婴传播,因此,HIV与HCV混合感染较常见.HIV感染改变HCV的自然病程,加速肝纤维化、肝硬化及肝细胞癌的进程已达成共识;HCV基因型对肝病的进程和预后亦起到重要作用.那么HCV基因型的分布在HⅣ/HCV混合感染与HCV单纯感染之间是否存在差异?各自的感染途径有何不同?值得我们作进一步的探讨.我们对昆明市第三人民医院收治的昆明地区85例HCV感染住院患者采用PCR等分子生物学方法研究了HIV/HCV感染与HCV单纯感染患者HCV基因型分布的差异.     

Serious ophthalmic pathology compromising vision in HCV/HIV co-infected patients treated with peginterferon alpha-2b and ribavirin

OBJECTIVE: To characterize the ocular changes associated with peginterferon alpha 2b (peg-IFN alpha-2b) and ribavirin therapy for chronic hepatitis C infection in HIV co-infected individuals. METHODS: A prospective, open-label trial treating HIV/hepatitis C (HCV) co-infected individuals with peg-IFN alpha-2b and ribavirin at the Warren Grant Magnusson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Twenty-three patients with a high mean CD4+ T-cell count were treated with peg-IFN alpha-2b and ribavirin and followed for 40 to 88 weeks. Ophthalmologic evaluations including visual acuity, visual field testing, color vision examination and indirect ophthalmoscopy were performed at baseline and every 3 months. RESULTS: Eight of the 23 patients (35%) developed ophthalmologic pathology, including cotton wool spots, cataracts, and two patients developed decreased color vision. These two patients regained their color vision, one after cessation of anti-HCV therapy. CONCLUSIONS: Although retinal pathologies have been reported in patients treated with interferon-alpha, they have not been reported during peg-IFN alpha-2b therapy nor in HIV/HCV co-infected patients. The incidence of serious ocular pathology associated with anti-HCV therapy may be very high and is probably associated with peg-IFN alpha-2b. Increased monitoring of patients treated with peg-IFN alpha-2b for retinal and visual changes is warranted.     

Glomerular lesions in lymphomas and leukemias

Renal lesions in lymphoid malignancies are rare, with most lesions observed in association with Hodgkin's disease. In two large series of patients with Hodgkin's disease, only 0.4 percent had minimal-change lesion whereas 0.1 percent had amyloidosis. The non-Hodgkin's lymphomas and leukemias comprise large and heterogeneous groups with equally diverse renal lesions. As in Hodgkin's disease, the most frequent lesion is minimal-change nephrotic syndrome. Also recognized are rare reports of renal disease associated with the atypical lymphoid proliferations of angioimmunoblastic lymphadenopathy, giant lymph node hyperplasia syndrome, and acquired immune deficiency syndrome. Broad generalizations regarding the pathogenesis of renal disease in these syndromes are difficult, partly due to the paucity and sporadic reporting of such cases. Mechanisms proposed to explain the renal pathologic findings include autologous nontumor antigens, tumor antigens, fetal antigen expression, immune complex deposition, viral antigens, and disordered T cell function.     

Glomerular function in neonates

Glomerular filtration rate is low in fetal and neonatal life. It increases after birth and reaches approximately 20 mL/min/1.73 m2 at 1 month of age in term and preterm neonates. Various methods have been used to measure glomerular filtration rate in neonates such as inulin clearance, creatinine clearance, and serum cystatin C. Serum creatinine concentrations are influenced by many factors. It is suggested to use other markers which are stable over time and are not affected by muscle mass or tubular reabsorption and secretion. Cystatin C incorporates these characteristics; however, there are some other limitations in the use of cystatin C as a marker of kidney function in neonates. Additionally, the numbers of studies focused on the use of cystatin C in neonates is limited. There is a need for further studies to determine cystatin C's normal range levels and investigate whether cystatin C can replace other tests such as serum creatinine as marker of kidney function in newborn babies. Assessment of newer kidney function tests is also warranted in newborn infants.     

HIV/HCV混合感染者与HCV感染者感染HCV基因型分析*

目的 使用二代测序技术检测广州地区人类免疫缺陷病毒（HIV）/丙型肝炎病毒（HCV）混合感染者和HCV感染者HCV基因型,了解本地区HCV基因型的流行特点。方法 在233例HCV感染者中,包括95例HIV/HCV混合感染者和138例HCV感染者,使用Illumina Miseq平台PE300模式对HCV Core和NS5B片段进行测序,采用生物信息学分析确定HCV基因型,对测序结果提示混合基因型感染的样本,使用NS5A基因型特异引物进行验证。结果 HIV/HCV混合感染者静脉吸毒感染构成比显著高于HCV感染者（77.7%对19.6% P<0.001）,HCV感染者输血感染的构成比显著高于HIV/HCV混合感染者（48.6%对3.2% P<0.001）;HIV/HCV混合感染者HCV Core基因片段平均数据量为（15456±6689） reads,HCV感染者为（14323±5321） reads,两组无显著差异（P>0.05）;HIV/HCV混合感染者HCV NS5B基因片段平均数据量为（16432±3467） reads,HCV感染者为（17611±5632） reads,也无显著差异（P>0.05）;本组228例（97.9%）HCV感染者为单一HCV基因型感染,HIV/HCV混合感染者HCV 6a型和3b型感染率显著高于HCV感染者（分别为47.4%对26.8%,P=0.001和13.7%对3.6%,P=0.005）,HCV 1b型感染率显著低于HCV感染者（20.0%对59.4%,P<0.001）;在233例入组的HCV感染者中,发现5例（2.1%）为混合基因型感染,其中4例为HIV/HCV混合感染者,1例为HCV感染者。结论 广州地区HIV/HCV混合感染者与HCV感染者感染HCV基因型构成比存在差异,其临床意义还需要探讨。     

HCV and extrahepatic diseases

Besides being a hepatotropic virus and a common cause of chronic hepatitis, hepatitis C virus (HCV) has been linked to a variety of extrahepatic immunological manifestations. The high prevalence of HCV infections in some of these conditions suggests an important pathogenetic role of the virus. The recent observation that HCV infects peripheral blood mononuclear cells, such as CD8+ T lymphocytes, CD19+ B lymphocytes and monocytes/microphages, has given an insight into the possible mechanisms of HCV associated autoimmunity. In the clinical practice it is recommended not only to search for symptoms and signs of autoimmune disorders in patients with chronic hepatitis C, but also to test for hepatitis C virus infection patients with extrahepatic conditions known to be related to HCV. Even if the occurrence of autoimmune disorders or the exacerbations of autoimmune diseases has been reported during interferon therapy, antiviral therapy is effective in treating some of the extrahepatic disorders associated with HCV, namely mixed cryoglobulinemia and membranoproliferative glomerulonephritis. The extrahepatic manifestations associated with hepatitis C virus infection are reviewed according to the available data and the option of interferon therapy is discussed.     

HBV and HCV therapy

One year of interferon therapy inhibits HBV replication in one third of the patients whereas long-term administration of oral nucleos(t)ide analogues is efficient in most of them, as long as early treatment adaptation in patients with partial virological response and resistance is provided. Following the demonstration of a more potent antiviral effect in terms of sustained virological response (SVR) rates, Pegylated-IFN coupled with Ribavirin has become the standard treatment for chronic hepatitis C, with nearly 65% of all treated patients achieving a SVR. Long-term suppression of HBV and eradication of HCV would halt the progression of chronic hepatitis to cirrhosis, hepatocellular carcinoma and liver decompensation.     

Glomerular size and structure in diabetes mellitus

Summary The present electron microscopic study shows that the kidney hyperfunction in early diabetes can be due to a significant morphological change: an increased glomerular filtration surface. Applying standard stereological methods, the area of the peripheral wall of the glomerular capillaries was measured in biopsy specimens obtained from 7 patients with early diabetes and 7 controls. — An 80 per cent enlargement of the capillary wall (the surface of the peripheral basement membrane) was found in the diabetics (2 p=0.0096). Also the total area of the interface between the tuft and the urinary space was increased by 70 per cent (2 p=0.029). Since the thickness of the peripheral basement membrane is known to be unchanged in patients with early diabetes the finding of an increased area of the membrane implies that an increased quantity of basement membrane material is present in these patients. The significance of this phenomenon for the understanding of the metabolism of the basement membrane is discussed, and a working hypothesis is advanced for the pathogenesis of the diabetic microangiopathy.     

Glomerular Filtration Rate and Initiation of Dialysis

The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis at higher glomerular filtration rate (GFR) has increased over the past decade. Recent data suggest that it may be associated with increased mortality. The goal of this analysis was to compare survival outcomes in patients with early and late start dialysis. We performed a retrospective analysis of hemodialysis (HD) incident patients from 1 January 2010 to 30 September 2014. Patients were classified into two groups by estimated GFR at dialysis initiation (eGFR ≥10: early start and <10 mL/min per 1.73m²: late start). Logistic regression was used to evaluate factors associated with early and late dialysis start, and Kaplan–Meier graphs and Cox regression models in survival analysis. In this total incident population (N = 235), 42 patients had an early dialysis start. Compared with the group with an eGFR of <10 mL/min per 1.73 m² at dialysis start, a Cox model showed an incremental increase in mortality associated with earlier dialysis start (P = 0.027). Independent factors (P < 0.05) associated with mortality in the multivariable Cox model in early dialysis start were: hypertension (HR 9.32, CI: 1.34–17.87), diabetes (HR 1.8, CI: 0.4–13.2) and albumin <3.5 g/dL (HR 1.5, CI: 0.8–6.2). Older patients (HR 0.084, CI: 0.008–0.863) with low phosphorus levels (HR 0.02, CI: 0.0–0.527) also had statistically significant results, although they showed a reduced risk of mortality. Early dialysis initiation was associated with an increased mortality risk, arguing against aggressive early dialysis initiation based primarily on eGFR alone.     

HCV and HIV Coinfection

Chronic hepatitis C (CHC) is estimated to affect about 20% of the 34 million individuals currently living with HIV worldwide, with greater rates (~ 75%) in intravenous drug users or persons exposed to blood products. Individuals who are coinfected with HIV and hepatitis C virus (HCV) show an accelerated course of liver disease, with faster progression to cirrhosis and its clinical complications. The combination of pegylated interferon plus ribavirin given for 6–18 months leads to sustained HCV clearance in no more than half of HIV-HCV coinfected patients. Thus, new direct anti-HCV drugs are eagerly awaited for this population. Appropriate diagnosis and monitoring of CHC, including the use of noninvasive tools for assessing liver fibrosis (eg, elastometry) as well as provision of therapy guided by early viral kinetics and IL28B genotyping, are improving the management of CHC in HIV-infected persons.