Starting hemoglobin value predicts early phase prognosis after liver transplantation

Few studies have addressed the relationship between starting hemoglobin (Hb) value and early phase prognosis after liver transplantation (OLT). The aim of our study was to determine the relationship between the starting Hb value and the early phase prognosis after OLT by retrospectively reviewing the medical records of 102 consecutive recipients. Within this cohort, 47 patients had pulmonary complications after OLT, including eight cases of pulmonary edema, 12 cases of acute lung injury, six cases of acute respiratory distress syndrome, and 21 cases of pneumonia. According to whether the patients had pulmonary complications or not, they were categorized into the “no” versus the pulmonary complication groups. Twenty-two perioperative variables were analyzed in both groups to screen for variables that affected early pulmonary complications. A starting Hb ≤100 g/L was an independent risk factor for postoperative pulmonary complications. The duration to initial passage of flatus and the intensive care unit length of stay were significantly prolonged in patients with starting Hb values ≤100 g/L; these patients had poorer arterial blood gas analyses. The starting Hb value predicted the early phase prognosis after OLT for cirrhosis-associated hepatocellular carcinoma.     

肝癌患者射频消融后血清Th1、Th2型细胞因子的变化

目的 研究肝癌患者射频消融(RFA)治疗后血清Th1、Th2类细胞因子水平的变化,评价射频消融治疗对肝癌患者免疫状态的影响.方法 多极射频消融治疗仪(RFA-I)治疗肝癌患者28例,采用流式细胞术检测患者在射频消融前和治疗后1 d、21 d外周血,Th1细胞因子(IL-2、TNF-α)及Th2细胞因子(IL-4、IL-10).结果 肝癌患者治疗前外周血Th1细胞因子(IL-2、TNF-α)降低,Th2细胞因子(IL-4、IL-10)升高,与对照组相比,差异有统计学意义(P<0.05);RFA治疗后外周血Th1细胞因子(IL-2、TNF-α)升高,Th2细胞因子(IL-4、IL-10)降低,与治疗前相比,差异有统计学意义(P<0.05).结论 射频消融治疗可改善肝癌患者机体的免疫功能.     

Intraoperative cytokines production during orthotopic liver transplantation

In summary, we established that a significant production of the monokines interleukin-6, tumor necrosis factor apha, and interleukin-1 occurred during orthotopic liver transplantation whereas the lymphokines interferon gamma and interleukin-2 were not detected. Levels of interleukin-6 reached their maximum values before and especially at the end of the anhepatic phase. They remained high after the anhepatic phase, i. e. after reperfusion of the new livers. Tumor necrosis factor alpha and interleukin-1 reached their maximum values after the anhepatic phase. Not only were interleukin-6, tumor necrosis factor apha, and interleukin-1 present in the serum but they could also be detected in the bile produced by these new livers. Mechanisms of monokine production during orthotopic liver transplantation is multifactorial in origin and further studies will have to evaluate the relative contribution of the various factors involved. The possibility of an association between peroperative monokines and transplant outcome and their potential clinical implication will have to be elucidated.     

Factors influencing the concentration of cytokines during liver transplantation

Not only does the underlying disease that requires surgery constitute a significant stress to the human body, but also the surgery itself serves as a stressor. Cytokine secretion is activated in response to the surgical stress during liver transplantation. We examined 44 patients to compare cytokine levels, according to the underlying diseases causing liver failure (viral hepatitis vs alcoholic hepatitis), examining whether the values differed according to the model for end-stage liver disease (MELD) score [high (≥20) vs low (<20)]. Pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)1β, and IL-6 and anti-inflammatory cytokines IL-4 and IL-10 were quantified using sandwich enzyme- linked immunoassays at three times: (1) after inducing anesthesia, (2) 60 minutes after the start of the anhepatic period, and (3) 60 minutes after reperfusion. No difference in the level of any cytokine measured in our study was detected at any time point between the viral and the alcoholic hepatitis groups. Among the high MELD group, IL-1β and IL-4 contents were higher than in the low MELD group at all time points (P < .05). IL-10 concentrations at time 1 and TNF-α at time 2 were higher among the high MELD group (P < .05). In conclusion, the severity of the inflammatory and stress reactions expressed as cytokine concentrations did not differ according to the underlying liver disease, but did associate with the MELD score.     

大鼠肝移植免疫耐受过程Th细胞和Treg细胞因子及信号通路蛋白的变化研究

目的  探讨大鼠肝移植免疫耐受过程中,辅助性T细胞（Th）和调节性T细胞（Treg）细胞因子及相关信号通路蛋白的变化与免疫耐受的关系。方法  双袖套法建立原位肝移植模型,将大鼠分为3组：手术对照组（6只）,假手术不进行肝移植;短期组（10只）,术后存活10 d;耐受组（10只）,术后存活100 d,移植肝功能恢复正常。检测各组大鼠肝功能指标如丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）,Th1细胞因子[干扰素（IFN）-γ、白细胞介素（IL）-2、肿瘤坏死因子（TNF）-α],Th2细胞因子（IL-4、IL-5、IL-6、IL-13）,Th17细胞因子[粒细胞-巨噬细胞集落刺激因子（GM-CSF）、IL-17A],Treg细胞因子[IL-10、转化生长因子（TGF）-β、IL-12p]表达水平。对各组大鼠血清进行蛋白芯片检测。结果  与手术对照组比较,短期组AST明显降低,ALT明显升高（P < 0.05）。而耐受组与手术对照组的AST、ALT水平比较,差异均无统计学意义（均为P > 0.05）。各组大鼠的肝组织中,与手术对照组比较,短期组Th1细胞因子IFN-γ、IL-2表达水平明显升高（均为P < 0.05）;耐受组Th2细胞因子IL-4的表达水平明显低于手术对照组（P < 0.05）;短期组Th2细胞因子IL-5、IL-6、IL-13的表达水平明显低于手术对照组（P < 0.05）;耐受组IL-17A的表达水平明显高于手术对照组（P < 0.05）。耐受组IL-10、IL-12p的表达水平明显高于手术对照组（均为P < 0.05）,短期组TGF-β的表达水平明显高于手术对照组（P < 0.05）。与手术对照组比较,短期组细胞间黏附分子（ICAM）-1、前血小板碱性蛋白（Ppbp）、神经纤毛蛋白（Neuropilin）-2、Notch-2蛋白的表达水平明显升高（均为P < 0.05）;耐受组趋化因子配基17（CXCL17）、ICAM-1、Neuropilin-2蛋白的表达水平明显升高（均为P < 0.05）,而B7-1蛋白的表达水平显著减低（P < 0.05）。结论  在大鼠肝移植自然免疫耐受过程中,Treg类细胞因子（IL-10、TGF-β、IL-12p）,IL-6,IL-17以及细胞表面的跨膜信号通路分子（ICAM-1、Neuropilin-2、B7-1蛋白）在其中起到了重要的作用。     

受体性别对肝移植术后早期肝功能的影响

目的 探讨受体性别对肝移植术后早期肝功能的影响.方法 根据受体性别将21例肝移植病人分为2组:男性(M)和女性(F)组,比较两组术后7 d ALT、AKP,ALB的水平.结果 F组肝移植效果优于M组病人,两组术后7 d ALT及AKP水平有显著性差异(P＜0.05).术后7 d白蛋白(ALB)水平差异无统计学意义(P＞0.05).结论 性别对肝移植病人术后早期肝功能的恢复有重要影响.     

分娩镇痛对产妇血Th1/Th2型细胞因子平衡的影响

目的 探讨分娩镇痛对产妇血Th1/Th2型细胞因子平衡的影响.方法 50例足月产妇随机分为腰-硬联合阻滞(CSEA)分娩镇痛组(A组)和未行镇痛的对照组(C组),每组25例.A组行CSEA(0.1%罗哌卡因+2μg/ml芬太尼)分娩镇痛.两组产妇在宫口开至2～3 cm(T1)和胎儿娩出时(T2)采血3 ml,用放免法检测皮质醇、白细胞介素(IL)-1β,酶联免疫吸附(ELISA)法检测IL-10.记录产程、新生儿Apgar评分以及疼痛视觉模拟(VAS)评分.结果 T2时A组皮质醇、IL-1β、IL-10浓度明显低于C组(P＜0.05);A组第一产程活跃期明显短于C组(P＜0.05),新生儿Apgar评分组间比较差异无统计学意义.结论 CSEA有效地减轻疼痛等应激反应,缩短第一产程活跃期.CSEA分娩镇痛可有利于维持Th1/Th2型细胞因子平衡.     

大鼠肝移植术后早期肝脏损害与Ref-1蛋白的表达

目的 观察大鼠肝移植术后早期肝组织内氧化还原因子1(redox factor-1,Ref-1)蛋白表达与肝脏损伤的关系.方法 将150只Wistar大鼠动物分为三个组,肝移植组、假手术组和空白对照组.分别于肝移植术后3、6、9、12、24 h取材,采用免疫组织化学方法检测移植后各时间肝组织Ref-1蛋白表达,同时通过血清生化指标、组织病理学分析研究Ref-1蛋白表达的意义.结果 血清学检查显示,肝移植术后3 h AST、ALT显著升高,术后6 h降低.病理学分析显示:术后24 h内,部分肝组织结构不清,肝细胞变性,肝窦扩张充血,炎细胞明显浸润.肝损伤较重.免疫组化检测显示,肝移植后早期肝实质细胞内Refl蛋白增高.9h达高峰,以后逐渐下降.结论 肝移植术后发生肝损伤以术后6 h为最重,之后损伤程度逐渐减轻,这是由于移植术后缺血再灌注损伤,激活Ref-1的表达明显增加,修复了由于缺血再灌注损伤导致的细胞凋亡.     

Portopulmonary hypertension in the early phase following liver transplantation

BACKGROUND: Portopulmonary hypertension (PPH) is a severe complication of liver cirrhosis, which poses a high risk for postliver transplantation (LT) mortality. In most liver transplant centers, severe PPH is viewed as an absolute contraindication for LT, but recent reports challenge this. The purpose of our study was to determine the incidence of PPH, its influence on the 30-day mortality rate following LT and to determine the sensitivity and specificity of Doppler echocardiography and electrocardiography as noninvasive tools to determine PPH. METHODS: We studied 74 consecutive patients that underwent LT between February 2004 and November 2005. Pulmonary arterial pressure and cardiac index were repeatedly determined during surgery and postoperatively. PPH was defined as mild (mean pulmonary arterial pressure (MPAP) 25-35 mm Hg), moderate (MPAP of 35-45 mm Hg) and as severe (MPAP >45 mm Hg). RESULTS: The total incidence of PPH was 31% (16 mild, 5 moderate, and 2 severe). There was a tendency towards increased 30-day mortality rate in patients with PPH compared to controls (22% vs. 12%, P=0.1). However, the two patients with the most severe PPH survived. The duration of ventilation and total stay at the intensive care unit did not differ significantly between groups. The positive predictive value of Doppler echocardiography for PPH was 39% and the negative predictive value 90%. CONCLUSIONS: Mild pulmonary hypertension is common in patients with liver failure, whereas moderate and severe hypertension is not. Severe PPH should not be considered as absolute contraindication for LT.     

Influence of albumin supplementation on tacrolimus and cyclosporine therapy early after liver transplantation

Liver transplant recipients administered gelatin (GEL) rather than human albumin solution (HAS) can become profoundly hypoalbuminemic in the early postoperative period and often have hepatic dysfunction at this time. The combined effect of these two abnormalities could be an increase in the unbound (active) concentration of low-extraction highly albumin-bound drugs, such as tacrolimus (TAC). This may increase the efficacy and/or toxicity of such drugs. We prospectively compared the clinical outcome of 69 de novo liver transplant recipients randomized primarily to TAC or cyclosporine (CYA) and secondarily to HAS or GEL therapy during the first 14 days after liver transplantation. Antipyrine clearance on the 7th postoperative day was used as a measure of liver metabolic function. Serum albumin levels were significantly lower in both GEL arms than HAS arms during the first 14 days (P [lt ] .001). Although antipyrine clearance was similar in all four trial arms, it was intermediate between that found in historic healthy controls and patients with cirrhosis (P [lt ] .0001). Serum creatinine concentrations were significantly greater in the TAC plus GEL arm than the other three arms (P [lt ] .001). The linearized treated acute rejection rate was significantly greater in the TAC plus HAS arm than the other three arms (relative risk, 2.02; 95% confidence interval, 1.07 to 3.78; P = .03). These data indicate that excess nephrotoxicity can occur with TAC in liver transplant recipients with impaired hepatic metabolism who are administered GEL. In addition, supplementary albumin may reduce the efficacy of TAC in liver transplant recipients at a time when the risk for rejection is greatest. (Liver Transpl 2002;8:224-232.)     

Th1/Th2细胞因子对器官移植排斥反应的影响

目的:研究Th1/Th2细胞因子对同种异系小鼠心脏移植存活时间的影响.方法:使用野生型BALB/c小鼠作为供体,野生型B6小鼠、IL-4基因去除B6小鼠及IFN-γ基因去除B6小鼠作为受体,行腹部异位小鼠心脏移植.部分IL-4基因去除小鼠、IFN-γ基因去除小鼠联合应用α-半乳糖神经酰胺(α-galactosylceramide,α-GalCer),以获得更强的Th1/Th2偏移.比较移植物存活时间.向野生型、IL-4基因去除及IFN-γ基因去除B6小鼠腹腔内注射供体小鼠脾细胞,提取受体小鼠脾脏CD8<'8>T细胞行淋巴细胞毒试验.结果:IFN-γ基因去除组小鼠的移植物存活时间为(6.40±0.55)d,联合应用α-GalCer组移植物存活时间为(8.00±1.15)d.IL-4基因去除组小鼠的移植物存活时间为(8.00±1.00)d,联合应用α-GalCer组移植物存活时间为(8.60±1.34)d.淋巴细胞毒试验显示IFN-γ基因去除小鼠的CD8+T细胞毒性明显增强.结论:Th1/Th2细胞因子与排斥反应之间并不存在简单的对应关系.     

抑制应激对烧伤血浆中LPS、前炎症细胞因子和TH1/TH2细胞因子的影响

目的 探讨抑制机体应激反应的措施,对严重烧伤后血浆中LPS、前炎症细胞因子和Th1/Th2细胞因子的影响。方法 将30％TBSA深Ⅱ度烧伤模型的SD大鼠分为烧伤立即复苏组（A）和烧伤立即复苏合剂组（B）,于伤后不同时相点取外周血分离血浆检测LPS、IL－1α、IL-6、TNFα、IL-8和IL－2、IFN－γ、IL－4、IL－10含量,另设假烧组作为对照（C）。结果 伤后LPS、IL－1α、IL－4、IL－10水平逐渐升高,IL－6、TNF－α、IL－8、IL－2和IFN－γ水平先升高后下降。A组炎症细胞因子和LPS升高幅度较大,其中IL－1α、IL－6和IL－4等升高时间（6h）较B组（12h）早。结论 及时液体复苏和采取抑制应激的措施,能延缓并减轻严重烧伤后炎症反应的发生,降低Th2细胞因子水平并使烧伤48h后Th1细胞因子得到部分恢复。     

Perioperative cytokines during orthotopic liver transplantation without venovenous bypass

Since most of studies investigating cytokine levels during human orthotopic liver transplantation used venovenous bypass (VVB), it may be difficult to distinguish between the increase in proinflammatory mediators induced by VVB, by ischemia-reperfusion injury or by splanchnic venous congestion in the anhepatic phase. The goal of this investigation was to assess the levels of interleukin-6 (IL-6) and soluble interleukin-2 receptors (sIL-2r) during OLT procedures routinely performed without VVB. PATIENTS AND METHODS: Twenty-one consecutive patients underwent OLT with cross clamping of the inferior caval vein without VVB. Soluble IL-2r concentrations were measured by means of luminescence enzyme immunometric assay and IL-6 by means of a sequential immunometric assay. Time points (TP) of sampling were before induction of anesthesia (TP1), after cross-clamping of the inferior vena cava (TP2), 15 minutes after reperfusion (TP3), and 24 hours after the transplant procedure (TP4). RESULTS: Soluble IL-2r increased significantly 24 hours after transplantation (P =.02) compared to TP1, TP2, and TP3. IL-6 increased significantly during the anhepatic period (TP2 vs TP1, P =.003) and again in the reperfusion period (TP2 vs TP3, P =.002). Twenty-four hours after surgery IL-6 declined significantly (TP3 vs TP4, P =.001), but remained significantly higher (P = 0.04) compared to TP1. Furthermore, we examined the relative changes (DeltaTP %) in perioperative levels of cytokines compared with those previously published in studies using VVB. We observed higher values of DeltaTP % of IL-6 in TP2 and TP4 among our group of patient without VVB. The data on sIL-2r were similar, suggesting no major effects of the operative technique on sIL-2r levels. CONCLUSION: The two interleukins showed different perioperative trends. Our data suggest that cross clamping contributes more to cell activation, namely, increased release of IL-6 in the anhepatic phase than the use of VVB. However, no major differences were observed during the reperfusion period. The extent of clinical effect on graft function of higher IL-6 levels in the anhepatic period among recipients not supported with VVB remains to be clarified.     

Changes in serum LECT 2 levels during the early period of liver regeneration after adult living related donor liver transplantation

We investigated changes in serum leukocyte cell-derived chemotaxin2 (LECT2) levels between donors and recipients in the early period during liver regeneration following adult living related donor liver transplantation (LRDLT). Five recipients (three women, two men; 37.0 +/- 15.8 years old), all of whom had end-stage liver failure, underwent LRDLT from healthy five donors (two women, three men; 41.6 +/- 14.3 years old) between June 2000 and February 2001. FK506 and methylprednisolone were used as immunosuppressants for recipients. Serum LECT2 levels decreased immediately after both the hepatectomy in all donors and the implantation of liver graft in all recipients. Donors showed a nadir at 3 to 12 hours, increasing at 24 to 48 hours. The nadir in recipients occurred several hours after the donors. The serum LECT2 levels of donors were significantly higher than those of recipients on day 5 (9.5 +/- 5.9 ng/mL vs 3.1 +/- 2.2 ng/mL, P = .04) and on day 7 (9.3 +/- 3.8 ng/mL vs 3.5 +/- 1.1 ng/mL, P = .04). Serum GPT and GOT levels were inversely proportionate to the serum LECT2 levels. The present studies suggest that LECT2 participates in liver regeneration and injury following hepatectomy.     

大鼠小体积肝脏移植后早期肝内细胞因子的变化

目的 研究不同冷缺血条件下大鼠小体积肝移植(30%标准体积)后早期肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)的变化,及其与肝脏再生的关系.方法 建立Lewis大鼠30%标准体积的原位肝移植模型.根据供肝在UW液中冷保存时间的不同,将受者分为3组:冷缺血1 h组、冷缺血8 h组和冷缺血16 h组,每组均为20只.观察受者存活情况至术后第7天,并分别在移植肝恢复血流后90 min、1 h、2 h、4 h和7 d收集样本,检测移植肝组织中TNF-α和IL-6表达情况,肝细胞DNA的合成情况,进行移植肝的形态学观察.结果 大鼠肝移植手术成功率均为100%.移植后第7天,冷缺血1 h和8 h组受鼠的存活率均为100%.冷缺血16 h组受鼠的存活率较低,移植后第7天无受鼠存活.冷缺血1 h组TNF-α和IL-6的表达水平较低,冷缺血8 h组和冷缺血16 h组TNF-α和IL-6的表达则高于冷缺血1 h组(F=58.81和F=184.12,P<0.05).冷缺血8 h组和冷缺血16 h组间TNF-α和IL-6的表达的差异无统计学意义.冷缺血1 h组增殖细胞数目明显高于冷缺血8 h组,差异有统计学意义(t=5.59,P<0.05).移植术后24h,冷缺血1 h组移植肝有轻度的组织学损伤;冷缺血8 h组移植肝有轻度的窦状隙扩张和轻度的炎症;冷缺血16 h组移植肝有局部淤血,存在肝细胞崩解和坏死等改变.结论 在小体积肝移植后早期,TNF-α和IL-6的上调表达对肝脏再生有重要意义.不同冷缺血时间的小体积肝脏移植物内存在早期启动肝脏再生的信号.     

原发性肝癌及癌旁组织中Th1/Th2类细胞因子表达模式

目的：观察人原发性肝癌（PHC）和癌旁组织中介Th1/Th2类细胞因子的影响。方法：以IFN-γ和IL-2代表Th1类细胞因子，IL-4和IL-10代表Th2类细胞因子，以逆转录聚合酶联反应检测肝癌和癌旁组织中Th1/Th2类细胞因子的表达。结果：PHC中7/11为Th1型细胞因子表达，4/11为Th0型细胞因子表达，癌旁组织中9/11为Th1型细胞因子表达，2/1为Th0型细胞因子表达。结论：原发性肝癌和癌旁组织中Th1类细胞因子强势表达。