Vascular events after liver transplantation: a long-term follow-up study

Long‐term follow‐up studies on the impact of vascular events (VE) and risk factors of liver transplant recipients are scarce. In this study, 311 recipients of a first isolated liver transplant who survived at least 1 year were followed up from 1979 to 2002. The median follow‐up duration was 6.2 (range1–22.7) years. Overall median survival was 18.7 [95% confidence interval (CI): 15.5–20.1] years and this was significantly lower compared with age‐ and sex‐matched controls. Eleven (21%) of the patients had a vascular cause of death and VE were the third cause of death. VE occurred later compared with other causes of death (mean 10.3 years vs. 4.5 years, P < 0.0001, 95% CI: 2.7–8.9). Systolic hypertension, systolic blood pressure, smoking, renal failure, age, hypertriglyceridemia, serum total cholesterol levels and hypercholesterolemia at the 1‐year follow‐up visit were associated with the occurrence of VE, but renal failure and age at 1 year after transplantation were the only independent risk factors for vascular death (hazard ratio 0.06, 95% CI: 0.01–0.41 and hazard ratio 1.17, 95% CI: 1.02–1.34, respectively). Finally, it was shown that the adequate treatment of hypertension was associated with a significant reduced risk of vascular death. Therefore, vascular risk factors should be treated aggressively to prevent VE in the long term.     

Steroid withdrawal after pediatric liver transplantation: a long-term follow-up study in 109 recipients

BACKGROUND: Steroids remain an important component of maintenance immunosuppression in liver transplantation, but when administered for a long period they may be associated with multiple severe side effects, particularly growth suppression in children. This study was conducted to clarify the balance of potential benefits and risks of steroid withdrawal (SW) in pediatric liver transplantation. METHODS: Between April 1984 and July 2000, 109 pediatric recipients with SW and at least 12 months of follow-up after SW were retrospectively reviewed and divided into three groups according to the type of anticalcineurin at SW: group I (cyclosporine, n=25), group II (cyclosporine microemulsion, n=25), and group III (tacrolimus, n=59). Steroids were withdrawn after a three-step reduction of steroid dosage (taper down to the substitution dose of 0.25 mg/kg/day, switch to alternate-day therapy, progressive SW). Patients were regularly followed up for clinical and biochemical monitoring. RESULTS: Median follow-up was 8.1 (range, 1.6-16.8) years. After SW, neither chronic rejection nor graft nor patient loss occurred. A trend toward lower anticalcineurin trough levels was observed in all groups. Glomerular filtration rate and fasting cholesterol were significantly better in group III (P<0.05). Median height z-score in all patients was -1.1 SD on alternate-day steroids versus -0.2 SD at the time of SW. Height z-score was slightly better in group III (NS). Early SW within 2 years after transplantation allowed a slightly better gain in growth. CONCLUSIONS: SW in pediatric liver transplantation is safe and may be beneficial to height outcome. Tacrolimus seems to offer several advantages in the long-term outcome.     

Prevalence of hepatic steatosis after islet transplantation and its relation to graft function

Islet allotransplantation can provide insulin independence in selected individuals with type 1 diabetes. The long-term effects of these transplants on the liver are unknown. Recently, two cases of periportal steatosis after islet transplantation have been described. In this study, we performed ultrasound and magnetic resonance imaging (MRI) in 30 C-peptide-positive islet transplant recipients to detect steatosis and to explore the association of the radiological findings with clinical and metabolic factors. Steatosis was observed on MRI in six (20%) subjects. Histological findings of hepatic steatosis concurred with the imaging findings. Steatosis completely resolved in one subject whose graft failed. More subjects with steatosis required supplementary exogenous insulin than not (67 vs. 21%; P < 0.05). The clinical features of subjects with and without steatosis were otherwise similar, although C-peptide levels were higher in insulin-independent subjects with steatosis (0.98 +/- 0.12 vs. 0.70 +/- 0.18 nmol/l; P = 0.05), despite similar blood glucose levels. Serum triglycerides and the use of exogenous insulin were associated with increased odds of steatosis in a logistic regression model (chi(2) [degrees freedom] = 13.6 [2]); P = 0.001). MRI-detected steatosis is a common finding; the steatosis appears to be due to a paracrine action of insulin secreted from intrahepatic islets. Hepatic steatosis may be associated with insulin resistance or graft dysfunction.     

Health-related quality of life after pancreatic islet transplantation: a longitudinal study

BACKGROUND: Pancreatic islet transplantation (PIT) has proven effective in achieving insulin independence, but to date, the impact of PIT on health-related quality of life (HRQL) has not been studied. METHODS: Ten patients who have undergone PIT at our institution were administered three HRQL questionnaires: the Hypoglycemia Fear Survey, the 36-Item Short Form Health Survey (SF-36), and a fatigue questionnaire. HRQL was assessed before PIT, then 3, 6, and 12 months after PIT. Responses were compared by analysis of variance and paired Student's t tests. RESULTS: Hypoglycemia Fear Survey responses demonstrated that hypoglycemia-related anxiety and hypoglycemia-related behavior modification occurred less frequently after PIT (P=0.003 and 0.0001, respectively). The total scores of the hypoglycemia questionnaire were also significantly improved after PIT, from a median score of 156 points before transplantation to 55 points 3 months after PIT (P=0.004), 38 points 6 months after PIT (P=0.001), and 69 points 12 months after PIT (P=0.04). The median scores of all SF-36 components also improved after PIT. No significant changes were seen in the fatigue symptoms as assessed by the fatigue questionnaire. CONCLUSION: PIT recipients have less anxiety about the symptoms and consequences of hypoglycemia. PIT recipients also indicate that their behavior requires significantly less modification to prevent or treat hypoglycemia after PIT compared with before PIT. Further investigation is needed to determine whether PIT improves generic measures of HRQL.     

脂肪变性供肝在背驮式肝移植中的应用

目的 探讨脂肪变性供肝(SLD)在背驮式肝移植中的应用.方法 将64例SLD进行了背驮式肝移植,其中脂肪变性程度分级为轻(S1级)、中(S2级)、重(S3级)者分别为22、25和17例,随机抽出同期80例供肝无脂肪变性者作为对照.观察手术当天受者的肝、肾功能,术后近期肝功能恢复情况,术后1个月的并发症发生情况,以及受者的死亡情况.结果 与对照组比较,手术当天各级脂肪变性组的肝、肾功能的差异均无统计学意义(P＞0.05).术后21 d,对照组95％受者的肝功能恢复正常,S1级组、S2级组和S3级组分别为90.9％、80.0％和70.6％,S3级组有2例(11.8％)发生移植物原发性无功能.S1、S2和S3组分别与对照组比较,出血、感染、肝动脉栓塞、腹水、败血症等并发症发生率的差异有统计学意义(P＜0.05).术后1年内,对照组死亡2例,S1级组死亡1例,S2级组死亡1例,S3级组死亡5例.结论 SLD可以用于移植,但对重度脂肪变性肝脏的移植,即使在目前供者紧张的情况下,也应审慎进行.     

Effect of graft steatosis on liver function and organ survival after liver transplantation

BACKGROUND: It was the aim to determine the effect of graft steatosis on intraoperative organ blood flow, postoperative liver function, and organ survival. METHODS: A total of 225 consecutive liver transplants were reviewed. Liver blood flow, hepatic function (AST, ALT, prothrombin time), and organ survival were determined. Donor liver grafts were categorized into 2 subgroups: mild (<30%) (n = 175) and moderate to severe (>/=30%) (n = 50) macrovesicular steatosis. RESULTS: Moderate to severe steatosis was associated with significantly increased AST and ALT levels and significantly diminished prothrombin time on the first and second postoperative day. By day 7 differences in liver function were no longer evident. Organ blood flow was not affected by steatosis. After adjustment for potential confounders, organ survival did not depend on the degree of donor steatosis (5-year-survival rates: 68% and 58% with steatosis <30%, or >/= 30%, respectively) (hazard ratio .754, confidence interval .458-1.242, P = .268). CONCLUSION: Steatotic livers can be transplanted safely with good results for long-term organ survival if other contraindications are absent.     

肝移植术后中长期管理应注意的问题

肝脏移植作为目前治疗终末期肝病的唯一有效手段已被社会各界所接受.随着近半个世纪以来肝移植手术技术和围手术期处理的日趋成熟以及新型免疫抑制药物的研发,肝移植患者术后的远期生存率和生活质量均已获得比较满意的效果(本中心肝移植术后患者生存时间最长已达10年以上).     

中度脂肪变性供肝肝移植的早期疗效与安全性研究

目的研究总结浙江大学医学院附属第一医院肝移植中心在脂肪变性供肝肝移植方面的经验并对其临床价值进行评估。方法分析2003年5月至2005年6月采用中度脂肪变性供肝（大泡性脂肪变性肝细胞占30％-60％）的24例成人肝移植受者（观察组）相关临床和随访数据,根据年龄、性别、终末期肝病模型评分和冷缺血时间进行匹配后,将24例采用无或轻度脂肪变性（大泡性脂肪变性肝细胞〈30％）供肝的肝移植受者作为对照组,将两组受者资料和移植肝相关数据进行分析比较。结果移植后1周内两组间肝肾功能变化差异无统计学意义（P〉0．05）,两组间早期移植物功能不全和早期急性肾损伤的发生率以及术后3个月、6个月及1年受者存活率差异均无统计学意义（均P〉0．05）。结论中度脂肪变性供肝在移植后早期可以发挥足够的功能,在排除其他危险因素的前提下可以安全地作为供肝系统的一部分。     

超声造影对移植肝局灶性病变的鉴别诊断价值

目的探讨超声造影对移植肝内局灶性病变的鉴别诊断价值。方法对67例肝移植术后确诊有移植肝内局灶性病变的患者进行超声造影检查,观察不同病变在动脉期、门静脉期和延迟期3个时相的造影剂灌注模式。以延迟期仍保持高增强或等增强或造影中始终无增强判定为良性病变,以延迟期消退为低增强或无增强判定为恶性病变,计算超声造影诊断良性病变与恶性病变的敏感度与假阴性率。结果与良性病变比较,在动脉期表现为高增强或等增强的病灶中,恶性病变在门静脉期或延迟期有显著的增强消退倾向(P0.01)。超声造影诊断良性病变的敏感度为90%(19/21),假阴性率为10%(2/21),2例假阴性均为肝脓肿;诊断恶性病变的敏感度为100%(46/46)。结论超声造影对移植肝内局灶性病变具有较高的鉴别诊断价值,有助于区别良、恶性病变。     

Experimental porcine orthotopic liver transplantation: a training protocol for transplantation in humans

The authors suggest that, prior to human liver transplantations, exhaustive training be undertaken on an animal model in order to acquire the expertise required for this delicate procedure. The pig has considerable anatomic similarities to man, as well as a comparable physiological and hemodynamic sensitivity, and has been used as a model by our experimental team to perfect our clinical liver transplantation technique. In particular, a surgical model representing the adult donor/child recipient situation has been developed. Anesthesia, extracorporeal bypass procedure and the full surgical protocol are described. This operative protocol was elaborated to mimic as closely as possible the clinical situation. Our model also allowed us to undertake several relevant physiological and pharmacological studies during the transplantation procedure.     

De novo malignancies following liver transplantation: a case-control study with long-term follow-up

BACKGROUND: Long-term survival data on de novo malignancy are limited following orthotopic liver transplantation (OLT) when compared with controls without malignancies. METHODS: Over a 12 yr period at our institution, 50 of 1043 patients (4.8%) who underwent OLT were identified to have 53 de novo malignancies. The clinical characteristics and survival of these patients were retrospectively reviewed and compared with a control cohort of 50 OLT recipients without malignancy matched with the incidence cases by age, year of OLT, sex, and type of liver disease. RESULTS: Chronic hepatitis C, alcohol and primary sclerosing cholangitis were the three leading causes of liver disease. Skin cancer was the most common malignancy (32%), followed by gastrointestinal (21%), including five small bowel tumors, and hematologic malignancies (17%). The cases and controls were not significantly different in the immunosuppressive regimen (p = 0.42) or the number of rejection episodes (p = 0.92). The five- and 10-year Kaplan-Meier survival rates for the cases were 77% and 34%, respectively, vs. 84% and 70%, respectively, for the controls (p = 0.02 by log-rank test). Patients with skin cancers had survival similar to the controls, but significantly better than non-skin cancers (p = 0.0001). The prognosis for patients with gastrointestinal tumors was poor, with a median survival of 8.5 months after the diagnosis. CONCLUSION: In this single institutional study, de novo malignancies after OLT were uncommon. Patients with non-skin cancer after OLT had diminished long-term survival compared with the controls. Our results differ from other reports in the high incidence of gastrointestinal malignancies with attendant poor prognosis.     

Everolimus in clinical practice in long-term liver transplantation: an observational study

Introduction

Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used in acute and chronic treatment of kidney and heart transplants. There is scarce information regarding its use in liver transplant recipients, although everolimus may be a useful alternative for selected cases.

Objective

The objective of this study was to study the clinical, biochemical, and pathological features of patients to whom everolimus was added based upon defined clinical profiles.

Study Design

This study was prospective observational ongoing study to evaluate the effectiveness and safety of everolimus alone or in combination with low doses of a calcineurin inhibitor (CNI). Chronic liver transplant recipients without contraindications to everolimus were defined based upon 7 profiles of complications. The initial everolimus dose (0.25 mg every 12 hours) was overlapped during conversion, measuring blood levels and evaluating clinical tolerance. Routine monitoring was performed to obtain immunosuppressant blood levels near the lower limit of the therapeutic range.

Results

The 35 patients' including 17 men and 18 women, had an overall mean age of 61 ± 10 years with a mean follow-up of 34 months. The everolimus treatment lasted 20 months (range, 6-60). The indication for everolimus conversion were as follows: renal insufficiency (45.7%), no response to hepatitis C virus (HCV) treatment (42.9%), autoimmune hepatitis associated with interferon (8.5%), de novo autoimmune hepatitis (25.5%), de novo tumor (37.1%), neurotoxicity (14.3%), or side effects to rapamycin treatment (5.7%). Patients may have presented more than one indication. Effectiveness was assessed based upon improved liver (48.6%) or renal function (31.25% with renal insufficiency) or withdrawal of prednisone (100% of 10 patients receiving prednisone). CNI was withdrawn from 48.6% of patients due to de novo tumors or neurotoxicity. The side effect were as follows: anemia, leukopenia, or thrombocytopenia (11.4%) or dyslipidemia (27.3%). The survival rate was 94.3%.

Conclusions

Administration of everolimus to chronic liver transplants enhanced therapeutic options in the long term recipients when applied for predefined clinical indications and administrated with dose adjustments based on serial monitoring of exposure.     

Herpes zoster infection after liver transplantation: a case-control study.

Prior case series have suggested that herpes zoster (HZ) after orthotopic liver transplantation (OLT) may lead to serious complications due to visceral involvement. We sought to determine the incidence, risk factors, and long term outcomes of HZ after OLT. Clinical data from September 1993 to April 2004 were collected on all cases of HZ after OLT, and at the same post-OLT time points in age, gender, and transplant-year-matched HZ-negative controls. Risk factors for HZ infection and long-term outcomes were compared between cases and controls. A total of 29 patients developed HZ at a median of 4.9 years (range .5-12.9) after OLT. All HZ infections except 1 were localized to a single dermatome. Only 8 (28%) were hospitalized and 16 (55%) were treated with oral antivirals alone. No patients developed visceral involvement or died of HZ infection. No risk factors for HZ infection were identified on multivariate analysis. Of the long-term outcomes, the estimated 10-year survival was lower (P = .05) for cases than controls. The lower survival in HZ cases was not directly attributable to HZ infection. In conclusion, this study is the largest series on HZ after OLT. HZ is neither a common nor a serious infection after OLT and can be managed with antiviral therapy with a low likelihood of visceral dissemination.