Hepatitis C-associated autoimmunity in patients coinfected with HIV.

Background: Hepatitis C virus (HCV) infection is associated with multiple extrahepatic manifestations. It is unclear to what extent extrahepatic manifestations occur in HIV/HCV coinfection. Methods: We prospectively assessed cross-sectional frequencies of autoimmune manifestations in HIV/HCV-coinfected patients (n=98), HIV-mono-infected (n=45) and HCV-mono-infected patients (n=78). Diagnostic vasculitis scores, HCV and HIV loads, CD4 cell counts, thyroid-, cardiolipin-, non-organ-specific tissue antibodies (nuclear, smooth muscle, anti-liver-kidney-microsome, neutrophil-cytoplasmic) and cryoglobulins were determined. Results: Synergistic effects of HCV and HIV infection were observed with respect to the prevalence of antibodies against thyroglobulin (HCV infection 15.4%, HIV infection 8.8%, HIV/HCV coinfection 30.6%; P<0.001) and cardiolipin antibodies (HCV infection 9.0%, HIV infection 31%, HIV/HCV coinfection 46%; P<0.001). Cryoglobulinemia type III, was significantly associated with HCV infection (HCV, 25.6%; HIV/HCV, 20.4%) but not with HIV infection (4.4%, P<0.05). Rheumatoid factor was commonly detected in patients with HCV infection (48%), but occurred considerably less frequently in patients with HIV infection (4.4%) or HIV/HCV coinfection (9.5%, P<0.01). Conclusion: HIV coinfection appears to differentially modulate the frequency of HCV-related autoimmunity. However, autoimmunity is rarely accompanied by clinical manifestations.     

Cryoglobulinaemia vasculitis in patients coinfected with HIV and hepatitis C virus

OBJECTIVE: To describe mixed cryoglobulinaemia (MC) vasculitis in patients coinfected with hepatitis C virus (HCV) and HIV. DESIGN: Retrospective multicentre study through the GERMIVIC Database of 4005 HIV/HCV-coinfected patients. METHODS: The characteristics and outcome of 11 HIV/HCV-coinfected patients with MC vasculitis were analysed and compared with those of 118 HCV-infected patients with MC vasculitis. RESULTS: The mean age was 46 years (SD, 14), with 82% male. The median initial CD4 cell count was 367 cells/microl (range, 252-846). After a mean follow-up of 44.4 months, two deaths (18%) were noted. Clinical manifestations of MC included polyneuropathy in seven (64%), purpura in four (36%), arthralgia in four (36%), and kidney involvement in three (27%). Six patients received combination treatment with interferon-alfa and ribavirin, three of whom had sustained HCV virological response and were complete clinical responders. Four patients received corticosteroids and two showed a partial clinical response. Regardless of the HIV virological response, antiretroviral therapy did not improve MC vasculitis. Compared with patients with HCV monoinfection, coinfected patients were younger (P < 0.001), more frequently male (P = 0.03), more frequently intravenous drug users (P < 0.001), had higher HCV viraemia (P = 0.004), higher liver necroinflammation (P = 0.03), higher gammaglobulinaemia (P < 0.001) and lower cryoglobulin level (P = 0.03). The clinical manifestations of MC vasculitis did not differ significantly between the two groups. CONCLUSION: There was a beneficial effect of anti-HCV therapy for HIV/HCV-coinfected patients with MC vasculitis.     

Mortality in siblings of patients coinfected with HIV and hepatitis C virus

BACKGROUND: Coinfection with hepatitis C virus (HCV) is a poor prognostic factor for human immunodeficiency virus (HIV)-infected patients. We examined whether the increased mortality in these patients is partly explained by a familial excess risk of death. METHODS: Danish HIV-infected patients who had had at least 1 HCV test were included (n=3531). In addition, 336,652 population control subjects matched for sex, age, and residency were identified from the Danish Civil Registration System. For both HIV-infected patients and population control subjects, we identified all siblings born after 1951, with dates of death or emigration. Siblings of HIV-infected patients were classified according to the patients' HCV serostatus. Survival after age 20 years was compared among the groups of siblings. RESULTS: We identified 437 siblings of HIV/HCV-coinfected patients, 1856 siblings of HIV-monoinfected patients, and 285,509 siblings of population control subjects. Mortality was substantially higher in siblings of HIV/HCV-coinfected patients than in either siblings of HIV-monoinfected patients (mortality rate ratio [MRR], 2.97 [95% confidence interval {CI}, 1.98-4.45]) or siblings of control subjects (MRR, 4.23 [95% CI, 3.09-5.79]). Siblings of HIV-monoinfected patients had slightly higher mortality (MRR, 1.43 [95% CI, 1.10-1.85]) than siblings of control subjects. CONCLUSIONS: HCV infection is a marker of familial factors that affect the survival of HIV-infected patients independently of the pathogenicity of HCV.     

Treatment of hepatitis B virus infection in patients coinfected with HIV

This article highlights research into which treatments may be most effective for people with both hepatitis B virus infection and HIV. Studies from the era before highly active antiretroviral therapy and more recent studies are included.     

Treatment of the hepatitis C virus in patients coinfected with HIV

Hepatitis C virus (HCV) coinfection is common among individuals with HIV, and the progression of liver disease is accelerated in coinfected individuals compared with those with HCV alone. HCV coinfection also can decrease tolerability of highly active antiretroviral therapy. Additionally, the presence of HCV appears to increase morbidity and mortality in these individuals, and as such the management of both HCV and HIV in coinfected individuals requires careful consideration. Although coinfected patients should be considered for HCV therapy, the limited information to date indicates a lower rate of virologic response with current HCV therapies. Moreover, interactions between HCV and HIV antiviral medications may occur and potentially affect treatment efficacy. Thus, the decision to undertake HCV treatment must be individualized.     

Therapy insight: Management of hepatitis C in patients coinfected with HIV

Infection with HCV is common in HIV-infected patients and is an increasingly important public health problem. The medical management of hepatitis C in HIV-infected patients is complicated by immune suppression, potential drug interactions and toxicities, and the relative paucity of health-care providers with expertise in the management of both diseases. Nonetheless, there are now data to support the safety, tolerability and efficacy of hepatitis C treatment with peginterferon plus ribavirin in HIV-infected patients, and the impetus to treat these patients is, therefore, strong. Although the standard of care for the treatment of hepatitis C in HIV-infected patients has been more clearly defined, the delivery of care for hepatitis C remains inconsistent in many settings. The development and implementation of single-center multidisciplinary programs that combine the expertise of HIV specialists, hepatologists, gastroenterologists, psychiatrists, and addiction specialists, are needed to improve hepatitis C treatment outcomes in HIV-infected patients. This review considers the management of HCV infection in HIV-infected patients.     

Antitubercular therapy decreases nitric oxide production in HIV/TB coinfected patients

Background  

Nitric oxide (NO) production is increased among patients with human immunodeficiency virus (HIV) infection and also among those with tuberculosis (TB). In this study we sought to determine if there was increased NO production among patients with HIV/TB coinfection and the effect of four weeks chemotherapy on this level.     

HBV重叠HIV感染患者细胞免疫功能及临床特征的研究

目的：探讨HBV（乙肝病毒）重叠HIV（人类免疫缺陷病毒）感染患者的临床特征，以及细胞免疫功能损害情况。方法：回顾性分析我院2004—2007年收治的HBV重叠HIV感染的AIDS（获得性免疫缺陷综合征）患者30例的临床资料、免疫状态和转归，分析30例HBV重叠HIV感染者、50例单纯AIDS患者以及20例正常对照者的CD3、CIM、CD8细胞百分比以及CD4／CD8比值。结果：在30例HBV重叠HIV感染者中，6例死亡，均死于肝功能衰竭或肝硬化并发症。实验检查发现其肝功能以低蛋白血症为主要表现，转氨酶、胆红素轻度升高，透明质酸（HA）升高明显，HBV复制异常高拷贝。CIM、CD3的检测值，在3组之间两两比较差异有统计学意义，CD3及CIM细胞计数表现为HBV／HIV重叠感染组〈AIDS组〈正常对照组（P〈0．01），CD8细胞计数3组间两两比较差异无统计学意义。CD4／CD8比值降低，HBV／HIV重叠感染组、AIDS感染组均〈正常对照组（P〈0．01）。B超均显示肝回声增粗，弥漫性肝损害6例、腹水5例、肝肿大10例、脾大10例。结论：HBV重叠HIV感染者临床表现肝脏炎症反应较轻，但全身情况差，并发症多，增强了与HBV感染相关的终末期肝病风险，病死率也明显升高，同时CD4淋巴细胞衰减明显，细胞免疫损害明显。     

HCV／HIV重叠感染患者血清HGF的表达及意义

目的研究血清肝细胞生长因子（HGF）在慢性丙型肝炎重叠免疫缺陷病毒（HCV／HIV）感染中的意义。方法检测36例HCV／HIV重叠感染患者血清HGF、HCV-RNA、生化及血浆HIV病毒载量水平,并与20例健康献血者对照。分析HGF水平与不同肝功能损害程度及HCV—RNA、HIV病毒载量间的关系。结果HCV／HIV重叠感染患者血清HGF水平高于对照组（P〈0．01）。重度肝功能损害患者HGF水平〉中度〉轻度〉对照组（P〈0．01）。HGF水平与HCV－RNA、HIV病毒载量呈正相关（P〈0．01）。结论血清HGF参与了HCV／HIV重叠感染的病理生理过程,与肝功能损害程度有关。     

Serum alpha-fetoprotein predicts virologic response to hepatitis C treatment in HIV coinfected patients

We explored the link between serum alpha-fetoprotein levels and virologic response in 383 HIV-hepatitis C virus coinfected patients. A low alpha-fetoprotein level (<5.0 ng/ml) was an independent predictor of sustained virologic response (odds ratio = 1.83; 95% confidence interval 1.05-3.20). Serum alpha-fetoprotein measurement should be integrated in the pretreatment assessment of prognostic factors of a virologic response.     

Hepatic compartmentalization of exhausted and regulatory cells in HIV/HCV‐coinfected patients

Accelerated intrahepatic hepatitis C virus (HCV) pathogenesis is likely the result of dysregulation within both the innate and adaptive immune compartments, but the exact contribution of peripheral blood and liver lymphocyte subsets remains unclear. Prolonged activation and expansion of immunoregulatory cells have been thought to play a role. We determined immune cell subset frequency in contemporaneous liver and peripheral blood samples from chronic HCV‐infected and HIV/HCV‐coinfected individuals. Peripheral blood mononuclear cells (PBMC) and biopsy‐derived liver‐infiltrating lymphocytes from 26 HIV/HCV‐coinfected, 10 chronic HCV‐infected and 10 HIV‐infected individuals were assessed for various subsets of T and B lymphocytes, dendritic cell, natural killer (NK) cell and NK T‐cell frequency by flow cytometry. CD8⁺ T cells expressing the exhaustion marker PD‐1 were increased in HCV‐infected individuals compared with uninfected individuals (P = 0.02), and HIV coinfection enhanced this effect (P = 0.005). In the liver, regulatory CD4⁺CD25⁺Foxp3⁺ T cells, as well as CD4⁺CD25⁺PD1⁺ T cells, were more frequent in HIV/HCV‐coinfected than in HCV‐monoinfected samples (P < 0.001). HCV was associated with increased regulatory T cells, PD‐1⁺ T cells and decreased memory B cells, regardless of HIV infection (P ≤ 0.005 for all). Low CD8⁺ expression was observed only in PD‐1⁺CD8⁺ T cells from HCV‐infected individuals and healthy controls (P = 0.002) and was associated with enhanced expansion of exhausted CD8⁺ T cells when exposed in vitro to PHA or CMV peptides. In conclusion, in HIV/HCV coinfection, ongoing HCV replication is associated with increased regulatory and exhausted T cells in the periphery and liver that may impact control of HCV. Simultaneous characterization of liver and peripheral blood highlights the disproportionate intrahepatic compartmentalization of immunoregulatory T cells, which may contribute to establishment of chronicity and hepatic fibrogenesis in HIV coinfection.     

HIV and HCV coinfected haemophilia patients: what are the best options of orthopaedic treatment?

Summary.  In the era of contemporary orthopaedics, haematology and internal medicine, it is obvious that surgery can be indicated in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected haemophilia patients suffering from severe and painful musculoskeletal problems. However, the expected high risk of infection and other postoperative complications is a concern due to the poor health status that many of these patients present. In a HIV and HCV coinfected haemophilia patient, the orthopaedic surgeon together with the multidisciplinary haemophilia team should weigh the risks and benefits carefully. Clinical and immunological status should be considered before suggesting a surgical procedure (specially a joint arthroplasty) in this group of patients. If a surgical procedure is contraindicated, conservative treatment could be an alternative, although many times with inferior results. Usually, surgical procedures can better relieve pain for several years and improve the quality of life in this cohort of patients. Regarding anaesthetics, drugs metabolized by the liver or the kidney should be avoided depending on every particular case. Rachianaesthesia is more recommendable than epidural anaesthesia in elderly patients in whom general anaesthesia sometimes could be dangerous, although in all ages we prefer general anaesthesia. The size of the needle should be small (size G-27), and we never use spinal catheters.