心肺联合移植的临床研究(附1例报告)

目的 介绍成功开展心肺联合移植的经验.方法 2006-03-23对1例先天性心脏病室间隔缺损合并重度肺动脉高压、艾森门格综合征的患者,施行心肺联合移植术.受体采用心脏及两肺分别切除法,在隆突上作气管吻合,心脏作双腔静脉法吻合.结果 患者术后恢复顺利,1.5h神志清醒,22h拔除气管插管,第4日下床活动,术后未发生急性排斥反应,于术后第9周发生溶血葡萄球菌肺炎,经抗感染治愈,109d痊愈出院,至今生存7个月,可参加一般体育活动.结论 重视供受体人类白细胞抗原(human leucocyte antigen,HLA)配型、有效的心肺保护技术、细致的手术操作技术、合理有效的抗排斥及抗感染方案是心肺移植成功的关键.     

Long-term outcome following heart transplantation: current perspective

Heart transplantation keeps its leading position in the treatment of end-stage heart failure (HF). Survival rates and functional status following heart transplantation are excellent, particularly if compared to medical therapy. The process of acute and chronic transplant rejection, however, and the sequelae of immunosuppression, such as infection, malignancy and renal insufficiency, prevents even better results. Therapy with current mechanical circulatory support devices is associated with improving outcome and may become competitive to heart transplantation, at least in selected patients. But long-term results are not yet available.     

心脏移植术后急性排斥反应心肌内心电图监测的回顾性分析及临床意义

目的:研究心脏移植排斥反应发生时心肌内心电图的表现,探讨心肌内心电图(IMEG)各种数据监测急性排斥反应(AR)的临床意义。方法:回顾性分析141例次心脏移植后心肌活检结果,与同期描记的心肌内心电图数据。对移植物发生Ⅱ级(含)以上排斥反应时的心肌内心电图,分析其心率、心肌阻抗、QRS波幅、心室除极反应时间及心室除极反应T波降支最大斜率数据,并与其基础数据分析比较,判断排斥反应发生心肌内心电图的的表现,计算其变化率及在最佳诊断分割点的敏感度和特异性。回顾性分析各指标联合诊断敏感度、特异性和诊断准确率,绘制ROC曲线,检验诊断可靠性及因此可能避免的心肌活检次数和漏诊率。结果:Ⅱ级(含)以上排斥反应发生时,心肌内心电图的心率诊断的最佳分割点为+10%,其敏感度为82.8%,特异性为87.0%;心肌阻抗的诊断的最佳分割点为+15%,其敏感度为78.1%,特异性为96.1.%;QRS波幅诊断的最佳分割点为+15%,其敏感度为81.2%,特异性为92.2%;心室除极反应时间差异无统计学意义;以心室除极反应T波降支最大斜率降低10%为限,其诊断敏感度为84.3%,特异性为84.4%。如以4项指标联合诊断排斥反应,回顾性分析诊断敏感度可达95.3%,特异性为96.1%,其ROC曲线下面积为0.9237(95%CI为0.8132～0.9924)。采用心肌内心电图联合诊断可以避免52.5%心肌活检数量,将出现4.7%的漏诊率。采用IMEG监测AR的患者较未采用的患者,预计5年生存率高。结论:IMEG某些指标数据有较好的诊断排斥反应的敏感度和特异性,联合诊断将更加提高诊断的准确率,并可以减少心肌活检的次数,但也存在漏诊。连续的IMEG监测可以做为心脏移植后无创的、方便的及长期的排斥反应监测手段。     

Postmortem examination of the kidney in allogeneic hematopoietic stem cell transplantation recipients: possible involvement of graft-versus-host disease

To investigate the association between graft-versus-host disease (GVHD) and renal injury after allogeneic stem cell transplantation (allo-SCT), we compared autopsy findings of 26 consecutive allo-SCT recipients with two control groups: patients with hematologic malignancies who received cytotoxic chemotherapy alone (Control 1, n = 21) and those with non-hematologic diseases (Control 2, n = 12). We evaluated the following renal pathology; renal tubulitis, allograft glomerulitis, intimal arteritis, allograft nephropathy, and peritubular capillaritis. These changes were found in 11 allo-SCT recipients and 10 patients in Control 1, but none in Control 2. While overall frequency of renal impairments was similar between allo-SCT recipients and Control 1 (3/26 vs. 1/21), allo-SCT recipients were more likely to have renal tubulitis and peritubular capillaritis compared to Control 1 (5/26 vs. 1/21), but less likely to present with glomerulitis (1/26 vs. 6/21). Grade III–IV acute or extensive-type chronic GVHD were seen in all of the three patients with renal tubulitis and four of the five patients with peritubular capillaritis. Allo-SCT recipients with severe GVHD tended to have tubulitis and peritubular capillaritis. These findings have implications of some renal impairment attributable to GVHD.     

Intracranial hemorrhage following bone marrow transplantation: an autopsy study of 58 patients

Autopsy files of 180 patients were reviewed, who died after BMT between July 1987 and June 1998 and 58 (32.2%) cases, who had experienced intracranial hemorrhage (ICH) were selected. Age, sex, underlying disease, preparatory regimens, immunoprophylaxis, chronic and acute GVHD, survival of the patients and localization and size of hemorrhages were evaluated. There were 33 males and 25 females, with a mean age of 23.4 years. The main underlying disorders for which BMT was performed included SAA (n = 21), CML (n = 13) and AML (n = 10). Forty patients were found to have intraparenchymal hemorrhage, 35 had subarachnoid hemorrhage and eight patients had subdural hemorrhage. In 16 cases the CNS hemorrhage was so extensive that it was considered to be the main cause of death. There was no significant statistical difference concerning sex (P = 0.217), age (P = 0.296), underlying disease (P= 0.352), preparatory regimens (P = 0.07), immunoprophylaxis (P = 0.914), chronic and acute graft-versus-host disease (P = 0.107 and P = 0.631, respectively) and survival (P = 0.701) when comparing patients with or without ICH. However, the number of cases in which the CNS was defined as the main cause of death was higher among patients with ICH than in patients without ICH (n = 16 vs 15) (P = 0.011). We conclude that ICH is common and has a significant mortality rate following BMT.     

Liver transplantation for primary sclerosing cholangitis versus primary biliary cirrhosis: A comparison of complications and outcome

Abstract Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are the most common cholestatic disorders in adulthood requiring hepatic transplantation. Although they run similar courses, they may have different problems before and after transplantation. The aim of this study was to compare pre- and post-transplant complications and outcomes in these two similar but distinct patient groups. One hundred and seventeen adult patients underwent liver transplantation at our institution over a 6 year period, including 19 with PSC and 20 with PBC. Pre-transplant there were no significant differences in age, liver biochemistry, haematology or Child-Pugh scores between the two groups. The mean duration of disease before transplant was longer in PSC patients (11.7 vs 6.5 years; P < 0.05). The prevalence of septic cholangitis was greater in PSC (58 vs 5%; P < 0.01) as was the requirement for surgical or radiological interventional procedures, excluding cholecystectomy (53 vs 0%; P < 0.01). At transplantation, four patients with PSC had previously unrecognized cholangiocarcinoma. In the pre-transplant period these four patients had uncontrolled biliary sepsis at the time of transplant vs five of 15 PSC patients without cholangiocarcinoma. Postoperatively, PSC patients had a greater prevalence of intra-abdominal sepsis requiring surgical or radiological intervention (42 vs 5%; P < 0.05). In comparison, patients with PBC had a high prevalence of skeletal complications (30 vs 10%; P < 0.05) particularly avascular necrosis (15 vs 0%). The prevalence of chronic rejection was similar in both groups (15%). Overall survival was higher in PBC patients (85 vs 63%; P < 0.05). The prevalence of postoperative intra-abdominal sepsis requiring surgical or radiological intervention was higher in those patients with PSC who died (six of seven) compared to survivors (two of 12), (P < 0.001). Postoperative uncontrolled intra-abdominal sepsis directly contributed to more deaths in PSC patients (four of seven vs 0%). In conclusion, despite many similarities with PBC, PSC patients have higher prevalence of pre- and postoperative intra-abdominal sepsis that may contribute to poorer survival. In contrast PBC patients have excellent survival rates after a liver transplant, although bony complications are increased.     

Vitamin D and the risk of acute allograft rejection following human liver transplantation

Background: Vitamin D may act as an immune modulator in experimental and human organ transplantation, but these data are yet to be confirmed in human liver transplantation (LT). Aim: This study aimed to assess the relationship between acute liver allograft cellular rejection (ACR) and pretransplant serum vitamin D concentration or post‐transplant vitamin D supplementation. Method: We studied 133 LT recipients who underwent two per protocol allograft biopsies in the early post‐operative period, plus on‐demand biopsies as clinically indicated. ACR estimate was given according to the Banff scheme in biopsies obtained along two follow‐up periods: (a) from the transplant operation to the end of the second month (0–2 months); (b) and from the third month to the end of the eighth month (3–8 months) post‐LT. Results: The median pretransplant serum 25‐hydroxyvitamin D concentration was 12.5 ng/ml; 40 patients had concentrations ≤12.5 ng/ml, of whom six had ≤5.0 ng/ml. Seventy‐nine recipients received oral vitamin D₃ supplementation to treat post‐transplant osteoporosis. In the 0–2 months period, moderate‐to‐severe rejection episodes were independently associated with cytomegalovirus reactivation (P<0.005) and progressively lower pretransplant serum 25‐hydroxyvitamin D concentrations (P<0.02). Early vitamin D₃ supplementation was independently associated with a lack of ACR (P<0.05). Conclusions: These results suggest that vitamin D may favour immune tolerance towards the liver allograft.     

Famciclovir treatment of hepatitis B infection following liver transplantation: a long-term, multi-centre study

Abstract: Famciclovir is a novel guanosine nucleoside analogue with activity against herpes viruses and hepatitis B virus (HBV). Several preliminary reports have described efficacy of famciclovir in patients with recurrent hepatitis B after orthotopic liver transplantation (OLT). This report describes the largest study to date of long‐term famciclovir treatment in patients with de novo or recurrent hepatitis B post‐OLT. One hundred thirty patients with detectable serum HBV DNA after OLT received oral famciclovir 500 mg tid on a compassionate‐use basis. Safety analyses included all treated patients; efficacy was assessed in all patients and a subgroup of 73 patients with complete baseline HBV DNA and alanine aminotransferase (ALT) data who had received ≥6 months of treatment. Efficacy parameters included serum levels of HBV DNA, ALT, and anti‐HBe or anti‐HBs seroconversion rates. Of the 70 patients treated for ≥6 months who could be evaluated for response/non‐response to famciclovir, 52 (74%) were responders, defined as patients who experienced a 70% decrease or more in HBV DNA levels from baseline, or who became HBV DNA‐negative, for at least two consecutive visits. In famciclovir responders, HBV DNA levels decreased by a median of 91% after 12 weeks of treatment, 95% after 6 months and >99% after 18 months of treatment. Marked differentiation between responders and non‐responders could be made soon after the onset of treatment. Among anti‐HBe positive patients with evidence of HBV replication, 12/13 were responders. Patients with high baseline ALT levels experienced more rapid suppression of HBV DNA during therapy with famciclovir. Famciclovir therapy was safe and well tolerated; serious adverse events were reported infrequently. Famciclovir treatment may be beneficial in patients with hepatitis B infection post‐OLT.     

HLA配型相合的造血干细胞移植治疗重型再生障碍性贫血的临床研究

目的 评价HLA配型相合的异基因造血干细胞移植(allo-HSCT)治疗重型再生障碍性贫血(SAA)的疗效.方法 2000年1月至2008年11月采用allo-HSCT治疗SAA患者20例,其中同胞相合移植17例,非血缘关系移植3例.预处理采用环磷酰胺(Cy)50 mg·kg~(-1)·d~(-1)4 d加抗淋巴细胞免疫球蛋白(ATG)2.5 mg·kg~(-1)·d~(-1)或20 mg·kg~(-1)·d~(-1) d.移植物抗宿主病(GVHD)的预防方案为经典的环孢素A(CsA)联合短程甲氨蝶呤(MTX)及霉酚酸酯(MMF).同胞供者采集经重组人粒细胞集落刺激因子(G-CSF)动员的骨髓及外周血干细胞,非血缘供者单纯采集外周血干细胞.结果 回输单个核细胞中位数为7.89(4.00-14.21)×10~(8)/kg,所有患者均获供者造血重建,粒细胞植活中位时间14(11～20)d;血小板植活中位时间12(8～108)d.但1例患者发生晚期排斥,行另一供者二次移植后植活.21例次移植后共发生6例次急性GVHD(I度3例,Ⅱ度皮肤3例),发生率16%.19例生存期>100 d的患者中有7例发生慢性GVHD,其中4例为局限型,3例为广泛型.截至2009年2月28 日,经过中位18(2.0～106.8)个月的随访,共有17例患者无病生存,总生存率为82.5%.结论 采用Cy+ATG的预处理方案对SAA患者进行HLA配型相合HSCT,植活率高,可以获得良好的疗效.     

Favorable clinical outcome of nonalcoholic liver cirrhosis patients with coronary artery disease:A population-based study

AIM To elucidate the prevalence and risk of mortality of nonalcoholic liver cirrhosis(LC) patients with coronary artery disease(CAD).METHODS The study cohort included newly diagnosed nonalcoholic LC patients age ≥ 40 years old without a diagnosis of CAD from 2006 until 2011 from a longitudinal health insurance database. The mean follow-up period for the study cohort was 1152 ± 633 d. The control cohort was matched by sex, age, residence, and index date. Hazard ratios(HRs) were calculated using the Cox proportional hazard model and the Kaplan-Meier method. RESULTS After exclusion, a total of 3409 newly diagnosed nonalcoholic cirrhotic patients were identified from one million samples from the health insurance database. We found that CAD(5.1% vs 17.4%) and hyperlipidemia(20.6% vs 24.1%) were less prevalent in nonalcoholic LC patients than in normal subjects(all P 0.001), whereas other comorbidities exhibited an increased prevalence. Among the comorbidities, chronic kidney disease exhibited the highest risk for mortality(adjusted HR(AHR) = 1.76; 95%CI: 1.55-2.00, P 0.001). Ascites or peritonitis exhibited the highest risk of mortality among nonalcoholic cirrhotic patients(AHR = 2.34; 95%CI: 2.06-2.65, P 0.001). Finally, a total of 170 patients developed CAD after a diagnosis of nonalcoholic LC. The AHR of CAD in nonalcoholic LC patients was 0.56(95%CI: 0.43-0.74, P 0.001). The six-year survival rates for nonalcoholic LC patients with and without CAD were 52% and 50%, respectively(P = 0.012). CONCLUSION We conclude that CAD was less prevalent and associated with a reduced risk of mortality in nonalcoholic cirrhotic patients.     

Management of immunosuppressant agents following liver transplantation: Less is more

Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomitantly increasing as an issue for post-orthotopic liver transplantation patients;yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism.Current mainstay immunosuppression involves the use of calcineurin inhibitors;these are potent,but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver.Second,the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications.Finally,immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment,which undercut what used to be inevitable viral recurrence.Overall,while traditional immunosuppressive agents remain the most used,the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.     

Clinicopathological characteristics of hepatocellular carcinoma bearing Mallory bodies: an autopsy study

Abstract— Mallory bodies are known to occur in hepatocellular carcinoma. The simple question whether or not there are any clinicopathological features characterizing Mallory body-positive hepatocellular carcinoma remains unresolved to date. The present study of 200 consecutive autopsy cases of hepatocellular carcinoma showed several important differences between 49 cases bearing Mallory bodies and 151 cases bearing no Mallory bodies in carcinoma cells. The patients in the former group were older, showed a higher association rate of liver cirrhosis, and their liver weight was lighter. As to the gross pathology of hepatocellular carcinoma, the nodular type was relatively frequent in Mallory body-positive hepatocellular carcinoma, while the massive and diffuse types were relatively frequent in Mallory body-negative cases. The frequency of extrahepatic metastases in the Mallory body-positive group was lower than that in the Mallory body-negative cases. The reasons for these differences remain speculative.     

Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years

Background & Aims

Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH).

Methods

A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded.

Results

The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4–53.8). Median follow-up was 87.0 months (IQR, 43.5–168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4–6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2–5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5–5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4–6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2–3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0–3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2–3.5; p = 0.006) complications.

Conclusion

Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.