肝移植治疗脾功能亢进相关终末期肝病*

背景：肝移植已成为治疗脾亢相关终末期肝病最理想的方法,行肝移植过程中保留脾脏,是否会出现移植后脾功能亢进相关问题,目前尚无统一的认识。 目的：观察肝移植治疗脾功能亢进相关终末期肝病移植后脾功能的恢复过程。 方法：纳入肝移植治疗终末期肝病患者63例,按有无脾功能亢进分为脾亢组和非脾亢组。比较两组移植后血小板计数、彩超测定脾脏上下径、厚度、门静脉直径及随访15个月的结果。 结果与结论：纳入患者63例,死亡8例,55例进入结果分析。其中,肝移植并行切脾者4例,仅1例存活。脾亢组移植手术结束时血小板较移植前明显降低,移植后3 d降至最低,而后逐渐上升,移植后7 d明显增加(P < 0.05),稳定至15个月;非脾亢组血小板移植后5 d降至最低,17 d达到移植前水平,两组比较差异均有显著性意义(P < 0.05)。移植后7 d脾脏上下径及厚度开始明显减小(P < 0.05),3个月脾静脉直径明显减小(P < 0.05),至15个月稳定,患者均无门静脉高压曲张静脉破裂出血史。说明肝移植过程中若无绝对切除脾脏的适应症,应尽量保留脾脏。 关键词：脾功能亢进;肝移植;终末期肝病;门静脉;临床观察 doi:10.3969/j.issn.1673-8225.2012.05.003     

肝硬化性脾功能亢进的外科治疗

脾功能亢进（脾亢）是肝硬化患者常见的临床综合征之一，表现为脾脏肿大、一种或几种血细胞（主要是血小板、白细胞）减少，其发生率高达50％-64％。肝硬化性脾亢的发生是多因素作用的结果：①肝细胞功能不全被认为是血小板减少的根源；②脾脏对血细胞（血小板为主）的阻留和破坏；③体内产生血小板抗体；④HBV或HCV抑制骨髓造血。以下把当前可选择的脾亢治疗措施和射频消融治疗脾亢的经验作一简单介绍。     

部分脾栓塞治疗肝硬化门脉高压并脾功能亢进

目的：探讨部分脾栓塞术的临床疗效。方法：采用Seldinger技术经股动脉穿刺置入导管至脾动脉，注入明胶海绵颗粒，栓塞脾动脉的部分小分支血管，治疗肝硬化门静脉高压并脾功能亢进患9例。结果：栓塞范围为30％～70％，术后患外周血象明显改善，上消化道再出血间期延长。无严重的并发症发生。结论：部分脾栓塞治疗肝硬化门脉高压并脾功能亢进是安全和有效的。     

终末期肝病模型动态评分评估HBV相关肝衰竭预后的价值

目的评估终末期肝病模型（MELD）评分及其变化率（△MELD）在预测HBV相关肝衰竭患者预后的价值。方法采用前瞻性研究,选取HBV相关肝衰竭患者98例,随访24周,收集相关临床资料,计算MELD、△MELD分值。比较不同时间点存活与死亡患者MELD及△MELD分值,应用ROC曲线下面积比较MELD及△MELD预测预后的准确性,以最佳临界值分组,比较不同组别不同时间点的病死率;绘制Kaplan-Meier生存曲线,运用生存分析方法比较各组生存率变化。结果98例患者24周内死亡52例,存活46例,死亡组与存活组间MELD、△MELD分值的差异有统计学意义（P〈0．01）;MELDI〉23组8、12、24周病死率均明显高于MELD〈23组,△MELD〉4．5组病死率也高于△MELD〈4．5组,差异有统计学意义（P〈0．001）;判断患者12、24周预后△MELD的AUC（0．823、0．815）明显大于MELD的AUC（0．680、0．684）（P〈0．05）;生存分析显示以最佳临界值分组,各组间累积存活率的差异有统计学意义（P=0．000）。结论终末期肝病模型评分系统适用于我国HBV相关肝衰竭患者预后的预测;△MELD评估预后的准确性要高于初始MELD,有着重要的临床应用价值。     

终末期肝病模型动态评分评估HBV相关肝衰竭预后的价值

目的 评估终末期肝病模型(MELD)评分及其变化率(△MELD)在预测HBV相关肝衰竭患者预后的价值.方法 采用前瞻性研究,选取HBV相关肝衰竭患者98例,随访24周,收集相关临床资料,计算MELD、△MELD分值.比较不同时间点存活与死亡患者MELD及△MELD分值,应用ROC曲线下面积比较MELD及△MELD预测预后的准确性,以最佳临界值分组,比较不同组别不同时间点的病死率;绘制Kaplan-Meier生存曲线,运用生存分析方法比较各组生存率变化.结果 98例患者24周内死亡52例,存活46例,死亡组与存活组间MELD、△MELD分值的差异有统计学意义(P ＜0.01);MELD≥23组8、12、24周病死率均明显高于MELD＜23组,△MELD＞4.5组病死率也高于△MELD＜4.5组,差异有统计学意义(P＜0.001);判断患者12、24周预后△MELD的AUC(0.823、0.815)明显大于MELD的AUC(0.680、0.684) (P ＜0.05);生存分析显示以最佳临界值分组,各组间累积存活率的差异有统计学意义(P =0.000).结论 终末期肝病模型评分系统适用于我国HBV相关肝衰竭患者预后的预测;△MELD评估预后的准确性要高于初始MELD,有着重要的临床应用价值.     

部分脾栓塞术对肝硬化脾功能亢进的介入治疗

目的:探讨和评价部分脾栓塞术(PSE)治疗肝硬化脾功能亢进的临床应用价值.方法:采用Seldinger技术对28例乙肝后肝硬化伴脾功能亢进患者用高压消毒明胶海绵颗粒共进行31次PSE.结果:28例手术中27例获得成功,栓塞范围为30%～60%,25位患者术后1周以内、1～2周及2周以上WBC和PLT均有不同程度的上升(P＜0.01),临床有效率为 92.6%.手术前后肝功能变化不大.全部病例均未发生严重并发症.结论:部分脾栓塞术对治疗肝硬化脾亢有明显疗效,可替代脾切除术.对肝功能的改善,近期疗效不明显.     

部分脾动脉栓塞术治疗肝硬化脾功能亢进患者的112例临床观察

目的分析与评价部分脾动脉栓塞术对肝硬化患者的各种临床影响。方法112例肝硬化合并脾功能亢进患者,其中男性71例,女性41例;年龄38～72岁,平均年龄52-3岁。采用Seldinger技术进行部分脾动脉栓塞术．观察其外周血细胞、肝功能、凝血酶原时间、白蛋白、肾功能、门静脉内径等。结果所有患者经过部分脾动脉栓塞术治疗5d后,外周血白细胞由（3．63±1．82）×10^9／L明显增高至（7．67±4．20）×10^9／L（P〈0．05）,血小板由（62．03±36．55）×109／L明显升高至（125．71±98．18）×10^9／L（P〈0．05）,凝血酶原时间由（17．68±3．44）s明显缩短至（16．68±2．92）s（P〈0．05）。肾功能中血尿素氮明显变化。血肌酐由（83．82±20．66）μmol／L明显升高至（90．54±19．15）μmol／L（P〈0．05）,4周后门静脉管径由（1．33±0．16）cm缩小至（1．16±0．16）cm（P〈0．05）,门静脉血液流速由（721．97±230．09）mL／min缩小至（492．30±174．67）mL／min（P〈0．05）。肝功能中观察了总胆红素、丙氨酸氨基转移酶、天冬氨酸氨基转氨酶、谷酰转肽酶等指标均无明显变化。结论部分脾动脉栓塞术对肝硬化患者不仅有缓解脾功能亢进,且能降低门静脉压,预防出血,对肝功能无明显影响。     

原发性肝癌父子两代肝硬化脾功能亢进性血小板减少症的部分性脾栓塞术治疗

对象与方法 一、对象：子,43岁。因黄疸,腹胀,尿少于2005年10月就诊。查体：轻度黄疸,心肺无异常,蛙腹,腹壁静脉曲张,肝大,剑突下4em,质硬,光滑,脾触及不满意,腹水征（＋）,下肢无水肿。CT检查肝内多发性占位,最大者位于肝左叶,约8．0cm×6．2cm,脾大,中等量腹水。AFP3592ng／ml。     

高强度聚焦超声（HIFU）治疗肝癌肝硬化脾功能亢进的疗效观察

目的：观察高强度聚焦超声(HIFU)治疗肝癌肝硬化脾功能亢进的疗效。方法收集我院消化内科的住院患者,收集时间为2011年11月~2013年12月,共计21例,所有研究对象均诊断为由于肝癌肝硬化脾功能亢进,男16例,女5例,平均年龄(54.2±17.5)岁,随机分为A组,B组,C组,分别接受高强度聚焦超声90次、60次、30次。结果研究对象中最多见的不良反应是发热,共计5例,体温(37.6±0.4)℃,4例研究对象在治疗后1天有局部红肿,蜕皮,在皮肤科治疗后症状消失,继续治疗。所有研究对象在治疗间期均无内出血、腹腔积液增多、胸腔积液、周围脏器受损、及血尿现象。我们发现A组接受高强度聚焦超声治疗最多90次,其组在0月、1月、2月、3月时的白细胞、血红蛋白以及血小板最高,肿瘤缩小最大,C组接受高强度聚焦超声治疗最少30次,其组在0月、1月、2月、3月时的白细胞、血红蛋白以及血小板最低,肿瘤缩小最小,差异有统计学意义(P<0.05)。结论随着高强度聚焦超声治疗次数的增加,肝癌肝硬化脾功能亢进患者白细胞、血红蛋白以及血小板恢复的越好,肿块缩小最大。     

部分脾栓塞在肝癌伴脾亢介入治疗中的应用

目的:对原发性肝癌(肝癌)伴脾功能亢进(脾亢)患者行部分脾栓塞,使其血细胞恢复正常,以便能进一步行肝动脉化疗。方法:对46例不能行手术切除、且血细胞明显低于正常的肝癌伴脾亢的患者行部分脾栓塞术,栓塞面积控制在50%-70%,栓塞前后测定血细胞数量,并作方差分析和t检验。结果:脾栓术后24小时、48小时、72小时、1周、2周、4周的血WBC和PLT均较栓塞前明显升高(P<0.05和P<0.01)。结论:部分脾栓塞能治疗脾功能亢进,提高血细胞数量,使肝癌伴脾亢患者的肝动脉化疗能正常进行。     

409例肝硬化和重型肝炎病例的MELD评分结果的构成分析

目的应用两种评分方法对409例肝硬化及重型肝炎患者进行评估比较，分析血清肌酐、血清胆红素及凝血酶原时间国际标准化比值（INR）对MELD评分结果的影响程度。方法统计409例肝硬化及重型肝炎患者的相关资料，应用Child和MELD评分法分别计算后应用Chiss软件进行统计学分析。结果随着A、B、C、D各个级别的病情的加重，MELD评分明显升高。各个级别的血清胆红素、INR之间存在明显差异；各个级别的血清肌酐之间无明显差异。结论血清胆红素及凝血酶原时间国际标准化比值（INR）的变化及不同能够明显影响到评分结果，而血清肌酐的结果对评分结果的影响不显著。MELD应与多因素分析及临床经验有机结合，才是符合临床实际的判断严重肝病预后的较科学手段。     

原发性肝癌与乙型肝炎肝硬化HBV DNA水平、HBV基因型的比较研究

目的 比较原发性肝癌与乙型肝炎肝硬化患者的血清HBV DNA水平、HBV基因型差别。方法 对210例原发性肝癌（HCC）患者及220例乙型肝炎肝硬化（HBV LC）患者的血清HBVDNA水平及HBV基因型进行分析,比较病毒学和基因型差异。结果 210例HCC患者和220例HBV LC患者HBV DNA检测阳性率分别为84.3％（177/210）、94.5％（ 208/220）;HBV DNA定量为（5.06±1.01） log10拷贝/ml和（5.36±1.13）log10拷贝/ml,HBV LC患者均高于HCC患者（P＜0.01）;HCC组和HBV LC组均以C基因型为主,两组B,C基因型分布无明显差异。结论 HCC患者血清HBV DNA水平低于HBV LC患者。两组HBV基因型分布无明显差异,均以C基因型为多。     

Comparison of the Child-Turcotte-Pugh classification and the model for end-stage liver disease score as predictors of the severity of the systemic inflammatory response in patients undergoing living-donor liver transplantation

The aim of this study was to evaluate and compare the Child-Turcotte-Pugh (CTP) classification system and the model for end-stage liver disease (MELD) score in predicting the severity of the systemic inflammatory response in living-donor liver transplantation patients. Recipients of liver graft were allocated to a recipient group (n = 39) and healthy donors to a donor group (n = 42). The association between the CTP classification, the MELD scores and perioperative cytokine concentrations in the recipient group was evaluated. The pro-inflammatory cytokines measured included interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α; the anti-inflammatory cytokines measured included IL-10 and IL-4. Cytokine concentrations were quantified using sandwich enzyme-linked immunoassays. The IL-6, TNF-α, and IL-10 concentrations in the recipient group were significantly higher than those in healthy donor group patients. All preoperative cytokine levels, except IL-6, increased in relation to the severity of liver disease, as measured by the CTP classification. Additionally, all cytokine levels, except IL-6, were significantly correlated preoperatively with MELD scores. However, the correlations diminished during the intraoperative period. The CTP classification and the MELD score are equally reliable in predicting the severity of the systemic inflammatory response, but only during the preoperative period.     

Efficacy of radiofrequency ablation of hepatocellular carcinoma associated with chronic liver disease without cirrhosis

Background. Hepatocellular carcinoma is one of the leading causes of death for compensated chronic liver disease.     

肝细胞癌和肝硬变中bcl-2蛋白表达与细胞凋亡的关系

目的：研究肝细胞癌和肝硬变中ｂｃｌ－２蛋白表达与细胞凋亡的关系。方法：应用原位脱氧核糖核酸末端转移酶标记法和Ｓ－Ｐ免疫组化技术检测２８例肝硬变和３５例肝细胞癌组织中凋亡细胞的分布、密度及ｂｃｌ－２蛋白的表达。结果：肝细胞癌组织中凋亡细胞密度显著低于肝硬变，且随其恶性程度的增高呈逐渐降低趋势；凋亡细胞在肝硬变中多分布于假小叶周边区域。ｂｃｌ－２蛋白在肝细胞癌组织中的表达强度明显高于肝硬变，但表达的阳性率差异不明显。结论：ｂｃｌ－２通过其表达产物调控肝硬变和肝细胞癌中的细胞凋亡，在肝细胞癌发生中起重要作用，但ｂｃｌ－２蛋白并非细胞凋亡的唯一调控因素     

Regenerative pattern of liver cells in primary biliary cirrhosis, alcoholic cirrhosis, posthepatitic cirrhosis (HBV-related) and hepatocellular carcinoma: Comparative analysis by computerized morphometry

Computerized morphometrical measurements were made of liver cells and their nuclei taken from biopsy specimens of primary biliary cirrhosis (PBC), alcoholic cirrhosis, posthepatttic cirrhosis (HBV-related), and hepatocellular carcinoma (HCC). The specimens were stained with hematoxylln-eosin (HE), Mallory's stain for collagen fibers, orcein method, periodic acid Schiff (PAS) reaction, and silver impregnation. Light microscopic views were then selected and original liver cells were magnified × 1000. The size of liver cell nuclei, distance between corresponding liver cell nuclei and distribution pattern of hepatocytes were calculated by computer. Variation in regenerative activity among the four disease groups was noted. Regenerative features of liver cells were mild in degree in PBC. In alcoholic cirrhosis, regenerative features of liver cells were less prominent than in posthepatitic cirrhosis. In posthepatitic cirrhosis, regenerative liver cells were well developed, showing remarkable pleomorphlsm of liver cell nuclei and expansive arrangement of liver cell cords. This tendency towards regenerative activity suggests that the possibility of HCC occurring Is greater In posthepatitic cirrhosis than in PBC or alcoholic cirrhosis. It was concluded that morphologically, there is a greater possibility of occurrence of HCC in posthepatitic cirrhosis than in any other type of cirrhosis, because of its high regenerative hepatocytic activity. Also etiological factors of liver diseases are more important in the developement of liver cell regeneration. Furthermore, regenerative activity can be measured by computerized morphometry as an established methodology.     

Antifibrotic effect of edaravone in rat liver cirrhosis induced by dimethylnitrosamine

Edaravone (EDA), a newly synthesized free radical scavenger, has shown excellent results in the treatment of stroke. An overproduction of reactive oxygen species (ROS) causing oxidative DNA damage has been accounted as a major factor causing liver injury and fibrosis. Therefore, we examined its effect of EDA in rat model of liver cirrhosis induced by dimethylnitrosamine (DMN). Ten rats (DMN-group) were injected intraperitoneally with DMN (10 μg/g body weight) alone and another ten rats (EDA-group) were injected intraperitoneally with EDA (10 mg/kg body weight) 2 h after being injected with DMN. Both groups underwent their injection regimen three times a week for 4 weeks, after which the rats were sacrificed and their liver tissue sections were stained with Azan–Mallory for quantitative analyses of fibrosis development, using soft imaging and a previously published scoring system. Additionally, these sections were immunohistochemically stained using an antibody against α-smooth muscle actin (α-SMA). The total-bililubin in the EDA-group was found to be lower than that in the DMN-group. Quantitive analysis of liver fibrosis showed that the fibrotic area of the EDA-group was significantly smaller than that of the DMN-group. Additionally, the number of α-SMA positive cells in the EDA-group were significantly lower than that in the DMN-group. This study showed that EDA reduces liver fibrosis in a rat of cirrhosis induced by DMN. These data suggest that the reduction of liver fibrosis by EDA may be induced by the suppression of activated hepatic stellate cells.     

The refit model for end-stage liver disease-Na is not a better predictor of mortality than the refit model for end-stage liver disease in patients with cirrhosis and ascites

Background/Aims

The modification of the Model for End-Stage Liver Disease (MELD) scoring system (Refit MELD) and the modification of MELD-Na (Refit MELDNa), which optimized the MELD coefficients, were published in 2011. We aimed to validate the superiority of the Refit MELDNa over the Refit MELD for the prediction of 3-month mortality in Korean patients with cirrhosis and ascites.

Methods

We reviewed the medical records of patients admitted with hepatic cirrhosis and ascites to the Konkuk University Hospital between January 2006 and December 2011. The Refit MELD and Refit MELDNa were compared using the predictive value of the 3-month mortality, as assessed by the Child-Pugh score.

Results

In total, 530 patients were enrolled, 87 of whom died within 3 months. Alcohol was the most common etiology of their cirrhosis (n=271, 51.1%), and the most common cause of death was variceal bleeding (n=20, 23%). The areas under the receiver operating curve (AUROCs) for the Child-Pugh, Refit MELD, and Refit MELDNa scores were 0.754, 0.791, and 0.764 respectively; the corresponding values when the analysis was performed only in patients with persistent ascites (n=115) were 0.725, 0.804, and 0.796, respectively. The significant difference found among the Child-Pugh, Refit MELD, and Refit MELDNa scores was between the Child-Pugh score and Refit MELD in patients with persistent ascites (P=0.039).

Conclusions

Refit MELD and Refit MELDNa exhibited good predictability for 3-month mortality in patients with cirrhosis and ascites. However, Refit MELDNa was not found to be a better predictor than Refit MELD, despite the known relationship between hyponatremia and mortality in cirrhotic patients with ascites.