Diagnosis and treatment for tuberculosis infection in liver transplant recipients: case reports

AIM: Tuberculosis (TB) infection after liver transplantation was described, diagnosed and treated herein. METHODS: We reviewed the clinical presentation, methods of diagnosis, and treatment of 2 cases of TB infection posttransplantation. RESULTS: Mycobacterium TB infection occurred in 2 of 110 (1.8%) patients undergoing liver transplantation between 2001 and 2006. Pyrexia, poor appetite, and weight loss were common presentations. The diagnosis was confirmed using lymph node biopsy and treated with standard antituberculous agents. One patient was suspected of having TB infection by clinical presentation, and tentative anti-TB drugs were used. The duration of treatment was 9 months. CONCLUSIONS: Early diagnosis and treatment are important in these patients. Careful monitoring of liver function and immunosuppressant levels are essential for patients who receive standard anti-TB drugs.     

Tuberculosis in liver transplant recipients: prophylaxis in an endemic area

Background

Tuberculosis (TB) has a high prevalence in Brazil. The scenario of liver transplantation (LT) creates challenges: atypical presentation, treatment hepatotoxicity, and increased mortality. The majority of TB cases after transplantation represent reactivation of latent infections; therefore, prophylaxis (PX) plays a major role. The aim of this study was to evaluate the benefits of PX after LT based on a pretransplantation tuberculin test (TT) in an endemic area.

Methods

Retrospective analysis of medical data from 376 adult cirrhotic patients undergoing OLT from 2001 to 2009.

Results

Among 191 selected patients, 137 (71%) showed a pretransplant TT including 41 (30%) with a TT ≥5 mm. The 17 (40%) of these patients who were prescribed PX did not experience TB. Prophylaxis was discontinued in 5 patients (20%) owing to suspicion of hepatotoxicity (medium serum alanine transaminase 175 U/L). In the group without PX, we diagnosed 1 case of pulmonary TB. The overall prevalence of anergic patients in the cirrhotic phase was 65% and prevalence of TB 1%.

Conclusions

The prevalence of TB was similar to that reported in the literature, but positivity to TT was higher (34% vs 25%), possibly because of the endemicity of the area. There was a lower prevalence of extrapulmonary disease and no mortality. No patient undergoing PX with isoniazid, although incomplete due to suspicion of hepatotoxicity displayed TB. One patient without PX was affected by TB. The drug was effective but not always safe.     

Mycobacterium tuberculosis infection in renal transplant recipients

Mycobacterium tuberculosis (TB) infection is more common among renal allograft recipients compared with the general population due to immunosuppression. The epidemiological risk in a country is an important determinant of transplant TB after transplantation. We retrospectively analyzed 283 renal transplant recipients who underwent renal transplantation between 1990 and 2004. We evaluated the incidence, patient and disease characteristics, prognosis, and outcome of TB infection. Tuberculosis developed in 10 (seven men and three women of mean age of 41+/-9 years) among 283 patients (3.1%). All patients were culture-positive for M tuberculosis. Although pulmonary TB was the most common presentation in the general population, 50% of patients in the study group developed extrapulmonary TB. The mean elapsed time from renal transplantation was 38 months. Three patients (1%) developed TB in the first year after transplantation. All patients were treated with a quartet of anti-TB therapy. One patient developed isoniazid-related reversible hepatotoxicity. No acute allograft rejection occurred during the anti-TB therapy. Two patients (20%) with pulmonary TB died due to dissemination of the disease. In conclusion, extrapulmonary presentations of TB are more common among renal transplant recipients with the increased risk of mortality.     

Hepatitis B virus infection in heart transplant recipients in a hepatitis B endemic area.

BACKGROUND: Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. It is almost impossible for us to reject organ donors or recipients with positive serum hepatitis B surface antigen (HBsAg). We report our experience with HBV infection in heart transplant recipients with particular attention to outcome of recipients who were HBsAg+ or who had received donor hearts from HBsAg+ donors. METHODS: We performed a retrospective review of medical records. RESULTS: In the study, we included 101 heart recipients with post-transplant survival of more than 6 months. According to pre-transplant HBV serology markers, we divided patients into 4 groups. Group 1 (n = 8) had been HBsAg+ at the time of heart transplantation. Of these, 6 patients had HBV reactivation in the post-transplant follow-up and needed lamivudine treatment. Complete response was achieved in all 6 patients; however, HBV recurrence occurred in 1 patient after 8 months of lamivudine treatment. The recurrence remained under partial control. Group 2 (n = 16) was HBV na?ve at the time of heart transplantation. Of these, 2 received HBsAg+ donor hearts under perioperative hepatitis B immunoglobulin prophylaxis. HBV infection was successfully prevented in 1 patient, but the other contracted HBV hepatitis, which was successfully treated with lamivudine. In Group 2, 10 patients received donor hearts from anti-HBs+ donors, and none contracted HBV hepatitis after transplantation. Group 3 (n = 55) had protective anti-HBs antibody at the time of heart transplantation either from previous HBV vaccination (n = 10) or from natural HGB infection (n = 45). HBsAg+ donor hearts were transplanted into 2 patients with anti-HBs from previous HBV vaccination, and into 8 patients with anti-HBs form natural HBV infection. However, none of these 10 patients who received HBsAg+ donor hearts had HBV hepatitis after transplantation. Group 4 (n = 22) was HBs-, anti-HBs-, and anti-HBc+ at the time of heart transplantation. Of these, 7 patients received HBsAg+ donor hearts. Six patients experienced no HBV hepatitis after heart transplantation, and serum HBV DNA by polymerase chain reaction (PCR) at the time of heart transplantation was negative in all 6 patients. One patient had HBV hepatitis after transplantation, and serum HBV DNA by PCR at the time of heart transplantation also was positive. CONCLUSION: HBV reactivation after the heart transplantation was common but usually well controlled with lamivudine treatment. Therefore, HBV carrier status should not contraindicate heart transplantation. HBsAg+ donor hearts were safely transplanted into anti-HBs+ recipients; therefore, HBsAg+ itself was not a contraindication to heart donation. Patients with HBsAg-, anti-HBs-, anti-HBc+, and negative HBV DNA in the serum by PCR could be protected from HBV infection from HBsAg+ donor hearts. However, patients with HBsAg-, anti-HBs-, anti-HBc+, and positive HBV DNA in the serum by PCR should be recognized as HBV carriers and closely followed for potential HBV flare-up after heart transplantation.     

肾移植受者肺外结核的发病及诊治特点分析

目的 探讨肾移植患者术后肺外结核的发病及诊治特点. 方法 1991年1月至2007年4月行肾移植手术2333例,术后发现结核病37例,经病理学和(或)影像学检查确诊肺外结核者19例(51%).其中累及移植肾5例、脑膜4例、胸膜4例、淋巴结3例、软组织2例,喉、肝、胸椎、肠道各1例,同时有2个肺外部位受累者3例.发病高峰期为术后1年(53%).治疗方案主要采用异烟肼、利福平、乙胺丁醇和吡嗪酰胺组合,疗程6～25个月. 结果 14例经抗结核治疗痊愈,随访1～161个月,患者均存活且无复发;5例患者治疗无效,继发多脏器功能衰竭死亡(26%).抗结核治疗中发生急性排斥反应8例(42%),肝功能损害4例(21%). 结论肾移植患者术后肺外结核发生率、病死率较高,应引起临床足够重视,使用抗结核药物时应注意兼顾抗结核与抗排斥反应2方面.     

Mycobacterium tuberculosis infection and laboratory diagnosis in solid-organ transplant recipients

Tuberculosis (TB) is an unusual infection in transplant recipients. We evaluated (i) the frequency of TB, (ii) the duration to develop the TB infection, and (iii) clinical consequences, in 380 solid-organ recipients from January 1995 to December 2000. A total of 10 (2.63%) patients (eight renal, two liver transplant recipients) were found to have post-transplantation TB. The frequency of TB in this patient population is 8.5-fold higher than the prevalance in the general Turkish population. Tuberculosis developed within 2-33 months after transplantation, with a median of 15 months. In all of these 10 patients, Mycobacterium tuberculosis (MTB) was isolated from the culture. All the patients continued to have low dose immunosuppressive treatment, and also quadriple antituberculosis treatment [isoniazid (INH), rifampin (RIF), pyrazinamide (PRZ) and ethambutol (ETB)] has been given. The two recipients had died of disseminated form of TB. Relapse was detected in one patient 6 months after the completion of the treatment. As post-transplant TB infection develops mostly within the first year after transplantation, clinicians should be more careful for early and fast diagnosis and treatment should be started immediately.     

实体器官移植受者感染新型冠状病毒的诊疗策略

实体器官移植受者（SOTR）由于长期服用免疫抑制药,属于各种病原体感染的高危人群,包括新型冠状病毒（新冠病毒）。另外,SOTR往往伴有高血压、糖尿病等慢性基础疾病,感染新冠病毒后重型率和病死率高于普通人群,因此得到移植领域专家的高度重视。奥密克戎株目前为全球范围内的主要流行毒株,快速扩散至全球100多个国家,引起广泛关注。根据最新的国际关于新冠病毒感染诊治指南和我国相关专家共识,结合目前新冠病毒感染疫情形势及我国《新型冠状病毒感染诊疗方案（试行第十版）》,本文从新冠病毒感染的流行病学、临床表现和预后、诊断和临床分型以及治疗方面进行简单述评。     

Safety of treatment of latent tuberculosis infection in compensated cirrhotic patients during transplant candidacy period

BACKGROUND: Treatment of latent tuberculosis infection with isoniazid (INH) or rifampin (RIF) is controversial in liver transplant candidates due to potential hepatotoxicity. In this study, treatment of latent tuberculosis during transplant candidacy period is explored, and relevant literature is reviewed. METHODS: Liver transplant candidates with latent tuberculosis infection by positive tuberculin skin test (>5 mm) were prospectively enrolled and treated with 9 months of INH or 4 months of RIF, and were monitored monthly for their liver enzyme profiles, adverse effects, compliance, and completion rate. RESULTS: Four of nine patients with INH had asymptomatic, mild elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) versus none of five patients in the RIF group. Two cases of elevations were attributed to INH. Two other cases were attributed to alcoholism or active chronic hepatitis B virus infection. Only one patient in the INH group experienced symptoms possibly attributed to INH hepatotoxicity. Compliance was 100% per patient reporting. Completion rates were 79% for INH and 100% for RIF. No fulminant hepatic failure or death was observed. CONCLUSION: Treatment of latent tuberculosis in liver transplant patients during their candidacy with INH or RIF appears to be a safe, viable option, if carefully monitored for adverse effects and liver enzymes.     

肝移植受者移植后淋巴组织增生性疾病的单中心诊疗经验

目的  总结肝移植受者移植后淋巴组织增生性疾病（PTLD）的发病情况和诊疗经验。方法  回顾性分析734例肝移植受者的临床资料,收集肝移植受者中PTLD的发病情况、临床症状、实验室数据及影像学资料;分析PTLD受者的病理学结果与治疗方式;分析PTLD受者的预后情况。结果  肝移植受者PTLD发生率为2.2%（16/734）, 中位术后发病时间为8（3, 46）个月。PTLD的临床表现主要为发热、淋巴结肿大,部分出现贫血、肝脾肿大、肝功能异常和消化系统症状等。16例PTLD受者中,1例他克莫司血药浓度异常升高;6例转氨酶升高;14例爱泼斯坦-巴尔病毒（EBV）DNA载量升高;5例巨细胞病毒（CMV）DNA载量升高。13例受者正电子发射计算机体层显像仪（PET/CT）检查提示相关肿大淋巴结¹⁸F-氟代脱氧葡萄糖代谢增高;2例受者颈部及腹部CT检查提示相应区域多发淋巴结肿大;1例受者仅超声提示淋巴结肿大。16例PTLD受者均行病理学检查, 其中13例受者原位杂交结果提示EBV编码的小RNA（EBER）阳性。降低免疫抑制剂水平是PTLD受者的基础治疗方案,根据不同病理类型的PTLD可联合利妥昔单抗靶向治疗及化学药物治疗;针对肿大淋巴结,给予手术及放射治疗。1例受者因PTLD治疗致移植肝衰竭死亡。结论  肝移植术后免疫抑制剂的使用可增加PTLD的患病风险,PTLD在儿童肝移植受者中发生率高于成人,尽早诊断和合理治疗可极大地改善PTLD受者的预后。     

Treating hepatitis C infection in liver transplant recipients.

Chronic infection with hepatitis C virus (HCV) is a growing problem worldwide, with up to 300 million individuals infected, and those with chronic infection are at risk for cirrhosis and hepatocellular carcinoma. HCV infection is the most common indication for liver transplantation in the United States and Europe. Unfortunately, although transplantation is effective for treating decompensated cirrhosis and limited hepatocellular carcinoma associated with hepatitis C, HCV reinfection is virtually the rule among transplant recipients. Reinfection of the graft is associated with more rapidly progressive disease, with a median time to cirrhosis of 8 to 10 yr. Unfortunately, treatment of chronic HCV in liver transplant recipients is suboptimal. Combination therapy with interferon (pegylated and nonpegylated forms) plus ribavirin appears to provide maximum benefits. Drug therapy is usually administered for recurrent disease. No prophylactic therapy is available. Preemptive regimens offer no distinctive advantages over treatments begun for recurrent disease. Overall, treatment is poorly tolerated, with frequent need for dose reductions, especially from cytopenias, and drug discontinuations in up to 50% of patients. Optimizing drug doses is important in maximizing sustained virological response rates. Future therapies may include ribavirin alternatives with lower rates of anemia, alternative interferons with lower rates of cytopenias, and new antiviral drugs that can be used alone or in combination with either interferon or ribavirin to enhance sustained virological response rates and improve tolerability. Liver Transpl 12:1192-1204, 2006. (c) 2006 AASLD.     

Diagnosis and treatment of allograft rejection in heart-lung transplant recipients

Six patients received heart-lung transplants between March, 1981, and January, 1982. There were four women and two men between 26 and 45 years of age, three with primary pulmonary hypertension and three with congenital heart disease and pulmonary hypertension (Eisenmenger's syndrome). Immunosuppression was primarily with cyclosporin-A, with additional corticosteroid, azathioprine, and rabbit antihuman thymocyte globulin. Six episodes of allograft rejection in four patients (10, 11, 21, 24, 53, and 86 days after transplantation) were detected by means of transvenous endomyocardial biopsy. All patients experienced pulmonary edema early after transplantation (reimplantation response), and two patients required mechanical ventilatory support for allograft rejection at 10 and 11 days. Treatment of rejection consisted of intravenous methylprednisolone (four episodes) or augmented oral prednisone (two episodes), with resolution. No episode thought to be pulmonary rejection has occurred in the absence of cardiac findings. Four patients are alive from 6 to 15 months after transplantation and are functionally normal. Early experience with heart-lung transplantation suggests (1) that allograft rejection can be detected by cardiac findings and successfully treated by augmented corticosteroids, (2) that lung rejection does not occur in the absence of cardiac findings, (3) that the frequency and severity of rejection episodes are not greater than with standard cardiac transplantation, and (4) that the frequency of rejection episodes is highest within the first 60 days after transplantation.     

肾移植术后带状疱疹的诊治

目的探讨肾移植术后并发带状疱疹的诊治方法。方法回顾性分析63例肾移植术后并发水痘带状疱疹病毒(VZV)感染患者的临床资料。结果肾移植患者并发VZV感染多发生在术后1～2年,根据患者的临床表现及体征即可诊断带状疱疹,必要时可取水疱液检查;63例患者在发生VZV感染后均根据血环孢素A(CsA)浓度谷值和峰值适当减少CsA用量,或调整免疫抑制剂联合用药方案。53例采用阿昔洛韦5～10mg·kg-1·d-1静脉滴注4～10d,治疗有效;另10例阿昔洛韦治疗效果不明显,6例改用更昔洛韦,4例加用更昔洛韦,剂量为5～6mg·kg-1·d-1,其中9例治愈,1例死于巨细胞病毒感染所致的呼吸衰竭。所有患者在抗VZV感染的同时均使用抗生素,以防止合并细菌感染,并给予止痛、神经封闭以及生物反馈等综合治疗。本组治疗的总有效率为98.4%(62/63)。结论肾移植术后VZV感染多发,诊断并不困难,治疗上合理用药非常重要,并相应调整免疫抑制治疗方案;阿昔洛韦和更昔洛韦对VZV感染有较好的疗效。     

Association of fungal infection and increased mortality in liver transplant recipients

BACKGROUND: Invasive fungal infection is associated with increased morbidity and mortality following orthotopic liver transplantation (OLTx). Understanding the risk factors associated with fungal infection may facilitate identification of high-risk patients and guide appropriate initiation of antifungal therapy. OBJECTIVES: The aim of this study was to determine the incidence of fungal infections, identify the most common fungal pathogens, and determine the risk factors associated with fungal infections and mortality in OLTx recipients. METHODS: Medical records from 96 consecutive OLTx in 90 American veterans (88 males, 2 females; mean age 48 years, range 32 to 67) performed from January 1994 to December 1997 were retrospectively reviewed for fungal infection in the first 120 days after transplantation. Infection was defined by positive cultures from either blood, urine (<105 CFU/mL), cerebrospinal or peritoneal fluid, and/or deep tissue specimens. Superficial fungal infection and asymptomatic colonization were excluded from study. All patients received cyclosporine, azathioprine, and prednisone as maintenance immunosuppressive therapy. Fungal prophylaxis consisted of oral clotrimazole (10 mg) troches, five times per day during the study period. RESULTS: Thirty-five patients (38%) had documented infection with one or more fungal pathogens, including Candida albicans (25 of 35; 71%), C torulopsis (7 of 35; 20%), C tropicalis (2 of 35; 6%), non-C albicans (2 of 35; 6%), Aspergillus fumigatus (4 of 35; 11%), and Cryptococcus neoformans (1 of 35; 3%). The crude survival for cases with or without fungal infection was 68% and 87%, respectively (P <0.0001). The median intensive care unit stay and overall duration of hospitalization were significantly longer for patients with fungal infection (P <0.01). The mean time interval from transplantation to the development of fungal infection was 15 days (range 4 to 77) with a mean survival time from fungal infection to death of 21 days (range 3 to 64). Fungal infections occurred significantly more often in patients with renal insufficiency (serum creatinine >2.5 mg/dL), biliary/vascular complications, and retransplantation. CONCLUSIONS: Fungal infections were associated with increased morbidity and mortality following OLTx, with Candida albicans being the most common pathogen. Treatment strategies involving antifungal prophylaxis for high-risk patients and earlier initiation of antifungal therapy in cases of presumed infection are warranted.     

预防肝移植患者肺部感染的集束化护理管理

目的 探讨肝移植围术期预防肺部感染的集束化护理管理效果。 方法 将222例肝移植患者按住院时间分为对照组102例、观察组120例;对照组实施围术期常规护理,观察组实施预防肺部感染集束化护理管理。 结果 住院期间观察组肺部感染发生率显著低于对照组,肺部感染发生时间较对照组显著延迟（P＜0.05,P＜0.01）。观察组护理满意率高于对照组,但差异无统计学意义（P＞0.05）。 结论 实施预防肺部感染集束化护理管理可有效降低肝移植患者肺部感染发生率。     

Surveillance for CMV infection in orthotopic liver transplant recipients.

Infection with cytomegalovirus is a major cause of morbidity and mortality following orthotopic liver transplantation. In order that preventive strategies may be devised, a detailed assessment of risk factors for infection and disease is required. We have prospectively assessed 46 orthotopic liver transplant recipients for CMV excretion from multiple sites in order to determine incidence of, and risk factors for, CMV infection and disease. Risk factors for posttransplant CMV infection were donor CMV seropositivity, an increased volume of peritransplant whole-blood transfusion and an increased dose of extra steroid therapy to treat rejection episodes. These findings implicate, respectively, transfer of virus with donor organ, transfer of virus with blood transfusion, and stimulation of reactivation of latent virus in recipients through augmented immunosuppression. The possible ways of preventing or ameliorating these effects are discussed.