肝衰竭合并真菌感染的诊断和治疗

<正>肝衰竭是由多种原因引起的严重肝功能损伤,病死率极高。由于存在严重免疫麻痹,易合并真菌感染。临床上广泛应用免疫抑制剂以及广谱抗菌药物,使肝衰竭患者发生真菌感染明显增加。肝衰竭合并真菌感染患者临床症状往往不典型,诊断缺乏有效手段。同时,由于肝功能失代偿以及相关并发症的存在,抗真菌药物及治疗时机的选择成为临床面临的难点问题。近年来,对于真菌感染的免疫治疗、营养治疗及肠道微生态治疗等新治疗策略研究进展迅速。本文将主要阐述肝衰竭合并真菌感染的     

终末期肝病合并感染诊治专家共识

终末期肝病(ESLD)发生发展中,感染可以诱发或加重ESLD肝功能失代偿的发生,亦是ESLD发展过程中最易出现的并发症之一。ESLD合并感染的规范诊疗需求迫切,国内外尚无针对ESLD合并感染性疾病的诊治指南、行业标准或专家共识,本共识旨在指导并提高临床医务工作者对ESLD合并感染疾病的综合诊治能力。     

终末期肝病合并感染诊治专家共识(2021年版)

终末期肝病(end-stage liver disease, ESLD)发生和发展中, 感染可以诱发或加重ESLD肝功能失代偿的发生, 亦是ESLD发展过程中较易出现的并发症之一。ESLD合并感染的规范诊疗需求迫切, 2018年7月中华医学会感染病学分会制订了我国第1部《终末期肝病合并感染诊治专家共识》, 基于2018年至今的循证医学数据及治疗方案, 进行本次修订。本共识旨在指导并提高临床医务工作者对ESLD合并感染疾病的综合诊治能力。     

终末期肝病合并感染诊治专家共识

终末期肝病(end-stage liver disease,ESLD)发生发展中,感染可以诱发或加重ESLD肝功能失代偿的发生,亦是ESLD发展过程中最易出现的并发症之一。ESLD合并感染的规范诊疗需求迫切,国内外尚无针对ESLD合并感染性疾病的诊治指南、行业标准或专家共识,本共识旨在指导并提高临床医务工作者对ESLD合并感染疾病的综合诊治能力。     

终末期肝病合并感染诊治专家共识(2021年版)

终末期肝病(end-stage liver disease,ESLD)发生发展中,感染可以诱发或加重ESLD肝功能失代偿的发生,亦是ESLD发展过程中最易出现的并发症之一。ESLD合并感染的规范诊疗需求迫切,2018年7月,中华医学会感染病学分会制订了我国第一部《终末期肝病合并感染诊治专家共识》,基于2018年至今的循证医学数据及治疗方案,进行本次修订。本共识旨在指导并提高临床医务工作者对ESLD合并感染疾病的综合诊治能力。     

糖尿病患者医院真菌感染的分析

糖尿病(DM)患者合并感染是威胁DM患者生命的重要并发症之一.回顾性分析34例DM合并真菌感染患者的临床资料,探讨DM合并真菌感染的临床特点及其危险因素,进一步预防和控制真菌感染.     

老年恶性肿瘤患者合并医院内真菌感染调查

目的 探讨老年恶性肿瘤患者合并医院真菌感染的特点和危险因素,为制定有效的感染防治措施提供依据. 方法 将219例老年恶性肿瘤患者,根据诊断分为真菌感染组和无真菌感染组,回顾性分析2组的一般临床资料及相关指标,先进行单因素比较,然后进行非条件Logistic多元回归分析. 结果 医院获得性真菌感染在肿瘤科发生率为26.94%,主要发生在呼吸道、口腔和肠道.2组单因素比较显示,在伴随基础疾病、年龄、日常活动能力(PS)评分、白细胞减少、抗菌素的使用以及住院时间等方面均存在显著性差异(P＜0.05);Logistic多元回归分析表明,住院天数、年龄、PS评分、白细胞减少、抗菌素的使用及合并基础疾病等因素与恶性肿瘤患者医院真菌感染密切相关.推测其是老年恶性肿瘤患者真菌感染的危险因素. 结论 在老年恶性肿瘤患者中,住院天数、年龄、PS评分、白细胞减少、合并基础疾病及抗菌素的使用6个因素可能是老年恶性肿瘤患者合并真菌感染的危险因素,在老年恶性肿瘤患者合并真菌感染的发生发展中起了重要作用.     

HBV感染的终末期肝病抗病毒治疗进展

引起终末期肝病（ESLD）的主要原因为HBV感染。HBV感染的ESLD患者肝功能极差,病情复杂多变,病死率高。目前治疗ESLD最有效的方法是肝移植,但由于供体器官来源有限、移植后昂贵的后续治疗费用等,大多数患者只能内科保守治疗。HBV感染的ESLD患者过去以全身支持治疗及针对并发症的综合治疗为主,近年来,抗病毒治疗越来越受到重视,被认为是阻止病情进展的重要治疗措施。现结合文献综述如下。     

COPD合并慢性呼吸衰竭患者院内肺部真菌感染30例临床分析

目的探讨慢性阻塞性肺病(COPD)合并慢性呼吸衰竭患者院内肺部真菌感染的危险因素、临床特点及防治对策。方法回顾性分析我院收治30例COPD合并慢性呼吸衰竭继发肺部真菌感染患者的临床资料,并与同期30例无院内真菌感染的COPD合并慢性呼吸衰竭患者对比分析。结果COPD合并慢性呼吸衰竭患者肺部真菌感染除与患者年龄、并发症有关外,还与长期住院、广谱抗生素和糖皮质激素的应用、各种侵入性操作等有密切关系,临床表现无特异性。结论合理使用抗生素和糖皮质激素,减少不必要的侵入性操作,尽快脱机,加强全身营养支持,警惕真菌感染,及早治疗,可以有效防治COPD合并慢性呼吸衰竭患者发生肺部真菌感染,改善其预后。     

系统性红斑狼疮合并深部真菌感染临床分析

目的 探讨系统性红斑狼疮(SLE)合并深部真菌感染的部位、菌种、诊断及预后.方法 回顾性分析北京协和医院2000-2006年住院治疗的1466例SLE患者中合并深部真菌感染的51例患者的临床资料. 结果 合并深部真菌感染51例SLE患者.感染的病原菌以白色念珠菌为主,其次为隐球菌和曲霉菌.感染最常见的部位是肺,其次为脑膜和血液.本组病例巾死亡10例,病死率达20%.曲霉菌感染者病死率高达4/5.低蛋白血症、多部位真菌感染、曲霉菌感染、真菌血症可能是导致SLE患者死亡的独立危险因素. 结论 SLE合并真菌感染的主要部位为肺,感染的病原菌以白色念珠菌为主;临床应重视早期诊断和曲霉菌感染.     

Spontaneous fungal peritonitis: Epidemiology,current evidence and future prospective

Spontaneous bacterial peritonitis is a complication of ascitic patients with end-stage liver disease(ESLD); spontaneous fungal peritonitis(SFP) is a complication of ESLD less known and described. ESLD is associated to immunodepression and the resulting increased susceptibility to infections. Recent perspectives of the management of the critically ill patient with ESLD do not specify the rate of isolation of fungi in critically ill patients,not even the antifungals used for the prophylaxis,neither optimal treatment. We reviewed,in order to focus the epidemiology,characteristics,and,considering the high mortality rate of SFP,the use of optimal empirical antifungal therapy the current literature.     

Impact of human immunodeficiency virus infection on progression to end-stage liver disease in individuals with hemophilia and hepatitis C virus infection

Hepatitis C virus (HCV) is the major cause of chronic liver disease in hemophiliacs. To determine the effect of human immunodeficiency virus (HIV) on the natural history of HCV infection, we evaluated end-stage liver disease (ESLD) in 157 hemophiliacs (85 HIV positive and 72 HIV negative) with HCV infection for an average of 24 years. After adjusting for age at HCV infection, past or current hepatitis B surface antigen positivity, and history of alcohol abuse, we determined that the rate of ESLD was significantly greater among HIV-positive than among HIV-negative hemophiliacs (relative risk [RR], 3.72; 95% confidence interval [CI], 1.25-11.09), as was the adjusted RR for death due to ESLD (RR, 3.81; 95% CI, 1.19-12.16). Among HIV-positive hemophiliacs, crude RR for ESLD was lower, but not significantly so, with antiretroviral treatment (RR, 0.19; 95% CI, 0.03-1.14; P=.069) and increased with each decade of HCV infection (RR, 2.26; 95% CI, 1.42-3.59; P=.0006) and HIV infection (RR, 2.18; 95% CI, 1.36-3.49; P=.0013). These findings suggest that HIV accelerates HCV disease progression.     

Non-ulcerative skin pathologies of the diabetic foot

Many of the complications of the diabetes are well studied but robust research documenting the cutaneous effects of the disease remains sparse. Various studies have suggested that the majority of patients with diabetes will suffer a skin disorder during the course of their disease and for some, the skin changes may even precede the diagnosis of diabetes. Cutaneous pathology of the diabetic foot and lower leg can arise as a result of the direct or indirect effects of diabetic complications. The most common manifestations include fungal and bacterial skin infection, nail disease and diabetic dermopathy. Other less commonly observed conditions include diabetic bullae, necrobiosis lipoidica diabeticorum (NLD), granuloma annulare and reddening of the soles. For many of the less common disorders, there is little in the way of effective treatment. However, much can be done in the clinical setting in the management of the more common manifestations such as bacterial and fungal infection. Fungal infection, in particular, although relatively inconspicuous, is a very common foot problem and if left untreated can threaten tissue viability in the diabetic foot leading to secondary bacterial infection and cellulitis. Management of fungal disease is often considered difficult due to high relapse and re-infection rates, although by introducing a combination of therapies including mechanical and pharmacological the success in treating this stubborn condition can be greatly improved.     

Histopathology of cryptococcosis and other fungal infections in patients with acquired immunodeficiency syndrome.

OBJECTIVE: To gain insight into the histopathologic characteristics of fungal infection in acquired immunodeficiency syndrome (AIDS). METHODS: A review was conducted of the histopathology for 162 patients with evident fungal infection. RESULTS: The microscopic appearance of esophageal candidiasis that was common in patients with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue. The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida infection. Eighteen patients had generalized cryptococcosis, representing the commonest generalized fungal disease. The essential histologic features of the disease consisted of yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. This was different from the manifestations of both Candida and Aspergillus infections. The two histologic patterns recognized in the pulmonary cryptococcal lesions could be graded with respect to the degree and type of inflammatory reaction. The milder one consisted of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response. Another pattern involved massive cryptococcal infection, which might be simply more extensive than that in the former. Capillary involvement of alveolar septa was an important common finding in all 18 patients.     

Hepatitis C virus load and survival among injection drug users in the United States

Persons chronically infected with hepatitis C virus (HCV), some of whom may be coinfected with HIV and human T-lymphotropic virus type II (HTLV-II), are at high risk for end-stage liver disease (ESLD). We evaluated whether ESLD death was associated with premorbid HCV RNA level or specific HCV protein antibodies among persons with or without HIV/HTLV-II coinfection in a cohort of 6,570 injection drug users who enrolled in 9 US cities between 1987 and 1991. We compared 84 ESLD descendents and 305 randomly selected cohort participants with detectable HCV RNA, stratified by sex, race, HIV, and HTLV-II strata. Relative hazard (RH) of ESLD death was derived from the proportional hazard model. Risk of ESLD death was unrelated to the intensity of antibodies against the HCV c-22(p), c-33(p), c-100(p), and NS5 proteins, individually or combined, but it increased with HCV RNA level (RH(adj) = 2.26 per log(10) IU/mL, 95% CI: 1.45-5.92). The association between HCV RNA level and ESLD death remained significant after adjustment for alcohol consumption (RH(adj) = 2.57 per log(10) IU/mL, 95% CI: 1.50-8.10). Deaths from AIDS (n = 45) and other causes (n = 43) were unrelated to HCV RNA (RH(adj)= 1.14 and 1.29 per log(10) IU/mL, respectively). HIV infection was not associated with ESLD risk in multivariate analyses adjusted for HCV RNA. Men had an increased risk of ESLD death in unadjusted analyses (RH = 1.92, 95% CI: 1.15-3.56) but not in multivariate analysis (RH(adj) = 0.98, 95% CI: 0.48-2.88). Non-black patients were at increased risk for ESLD death (RH(adj)= 2.76, 95% CI: 1.49-10.09). In conclusion, HCV RNA level is a predictor of ESLD death among persons with chronic HCV infection.     

End-stage liver disease in persons with hemophilia and transfusion-associated infections

Many persons with hemophilia were infected with hepatitis C and B viruses (HCV, HBV) and HIV, but the consequences of these transfusion-acquired infections are poorly defined. We estimated the risk of HCV-related end-stage liver disease (ESLD) and the associations of age, HBV, and HIV with that risk. All 1816 HCV-seropositive hemophilic patients at 16 centers were followed for up to 16 years. Of these, 624 were HIV(-) and 1192 were HIV-coinfected; 135 had persistent HBV surface antigenemia, 1374 had resolved HBV infection, and 287 were HBV-uninfected. ESLD was defined as bleeding esophageal varices, hepatic encephalopathy, persistent ascites, or death excluding nonhepatic causes of these conditions. Competing risk models were used to estimate the annual hazard rate and cumulative incidence of ESLD. Proportional hazards models were used to estimate relative hazards of ESLD with covariates. ESLD developed in 127 of the HCV/HIV-coinfected participants, with an estimated 16-year cumulative incidence of 14.0% (95% confidence interval [CI], 11.6%-16.4%). Without HIV, 10 HCV-infected participants developed ESLD, for a significantly lower cumulative incidence of 2.6% (95% CI, 1.0%-4.3%, P <.0001). ESLD risk increased steeply with age in both groups. With HIV, ESLD risk was increased 8.1-fold (95% CI, 1.9-35.2) with HBV surface antigenemia, 2.1-fold (95% CI, 1.3-3.3) with fewer than 0.2 x 10(9)/L (200/microL) CD4(+) lymphocytes, and 1.04-fold (95% CI, 1.03-1.06) per year of age. Thus, HIV is associated with a markedly increased risk of HCV-related ESLD for persons with hemophilia, particularly with HBV infection, low CD4(+) lymphocytes, or older age.     

Lack of association of hepatitis C virus load and genotype with risk of end-stage liver disease in patients with human immunodeficiency virus coinfection

In hepatitis C virus (HCV) infection, virus load and the risk for HCV-related end-stage liver disease (ESLD) are increased among persons with human immunodeficiency virus (HIV) coinfection. To clarify these relationships, 42 hemophilic patients who developed ESLD and random samples from 164 hemophilic patients with HCV infection alone and 146 with HCV-HIV coinfection were tested for HCV load and genotype. HCV genotype was unrelated to HIV and age. In contrast, HCV load was higher with older age (P(trend)=.0001) and with HIV coinfection (6.2 vs. 5.9 log(10) genome equivalents/mL, P=.0001). During 16 years of follow-up of dually infected patients, ESLD risk was unrelated to HCV load overall (P(trend)=.64) or separately to HCV genotype 1 and genotypes 2 or 3 (P(trend)> or =.70). Irrespective of virus load, incidence of ESLD was marginally increased 2-fold (95% confidence interval, 0.8-5.6) with HCV genotype 1. Understanding the discordance between HCV load and ESLD, despite HIV's link to each of these, may help clarify the pathogenesis of HCV-related disease.     

Progression to end-stage liver disease in patients with inherited bleeding disorders and hepatitis C: an international, multicenter cohort study

Prior to 1990, many patients with inherited bleeding disorders were infected with hepatitis C virus (HCV). This study assessed the risk of end-stage liver disease (ESLD) in patients with hemophilia with chronic hepatitis C. Patients were infected between 1961 and 1990 and were followed up to August 2005. Of 847 anti-HCV(+) patients, 160 (19%) spontaneously cleared HCV and 687 (81%) developed chronic hepatitis C. Coinfection with HIV was present in 210 patients. After 35 years of infection the cumulative incidence of ESLD was 11.5% (95% CI, 8.2%-14.8%) in HIV(-) patients and 35.1% (95% CI, 29.2%-41.0%; P < .001) in patients coinfected with HIV. Independent risk factors of ESLD were HIV coinfection (hazard ratio 13.8; 95% CI, 7.5-25.3), older age at infection (hazard ratio 2.3 per 10 years; 95% CI, 2.0-2.8), alcohol abuse (hazard ratio 4.9; 95% CI, 2.5-9.6), and presence of HCV genotype 1 (hazard ratio 2.2; 95% CI, 1.1-4.2). With longer duration of HCV infection, the risk of developing ESLD is emerging in patients with inherited bleeding disorders. Risk factors for rapid progression to ESLD are alcohol abuse, coinfection with HIV, older age at infection, and presence of HCV genotype 1.     

Role of liver transplantation in human immunodeficiency virus positive patients

End-stage liver disease(ESLD) is a leading cause of morbidity and mortality amongst human immunodeficiency virus(HIV)-positive individuals. Chronic hepatitis B and hepatitis C virus(HCV) infection,drug-induced hepatotoxicity related to combined antiretro-viral therapy,alcohol related liver disease and non-alcohol related fatty liver disease appear to be the leading causes. It is therefore,anticipated that more HIV-positive patients with ESLD will present as potential transplant candidates. HIV infection is no longer a contraindication to liver transplantation. Key transplantation outcomes such as rejection and infection rates as well as medium term graft and patient survival match those seen in the non-HIV infected patients in the absence of co-existing HCV infection. HIV disease does not seem to be negatively impacted by transplantation. However,HIV-HCV coinfection transplant outcomes remain suboptimal due to recurrence. In this article,we review the key challenges faced by this patient cohort in the pre- and posttransplant period.