生长抑制素14肽治疗肝硬化门脉高压并发食管胃底静脉曲张破裂出血的临床研究

目的探讨生长抑制素14肽治疗肝硬化门脉高压合并食管胃底静脉曲张破裂出血的临床效果。方法选取2010年4月至2013年2月在我院诊治的肝硬化门脉高压合并食管胃底静脉曲张破裂出血患者76例,按照随机数字表法随机分为对照组(n=38)和观察组(n=38)。两组患者进行常规基础治疗,对照组给予垂体后叶素治疗,观察组给予生长抑制素14肽治疗,比较两组的临床疗效及不良反应。结果观察组的总有效率(92.11%)显著高于对照组(73.68%),两组比较差异具有统计学意义(P<0.05),两组不良反应比较差异无统计学意义。结论生长素抑制素14肽治疗肝硬化门脉高压并发食管胃底静脉曲张破裂出血疗效显著,并且不良反应少,在临床上值得推广运用。     

Emerging therapies for portal hypertension in cirrhosis

Introduction: Counteracting splanchnic vasodilatation and increased portal-collateral blood flow has been the mainstay for the treatment of portal hypertension (PH) over the past three decades. However, there is still large room for improvement in the treatment of PH.

Areas covered: The basic mechanism leading to portal hypertension is the increased hepatic vascular resistance to portal blood flow caused by liver structural abnormalities inherent to cirrhosis and increased hepatic vascular tone. Molecules modulating microvascular dysfunction which have undergone preclinical and clinical trials are summarized, potential drug development issues are addressed, and situations relevant to design of clinical trials are considered.

Expert opinion: Experimental and clinical evidence indicates that molecules modulating liver microvascular dysfunction may allow for 30–40% reduction in portal pressure. Several agents could be utilized in the earlier stages of cirrhosis (antifibrotics, antiangiogenics, etiological therapies) may allow reduction of fibrosis and halt progression of PH. This ‘nip at the bud’ policy, by combining therapies with existing agents used in advanced phase of cirrhosis and novel agents which could be used in early phase of cirrhotic spectrum, which are likely to hit the market soon would be the future strategy for PH therapy.     

The role of vasoactive drugs in the treatment of oesophageal varices

Oesophageal varices are among the most important clinical consequences of portal hypertension. Recent progress in the knowledge of the pathophysiology of portal hypertension has led to the concept that it results from the increase of sinusoidal resistance and the increase in portal blood inflow consequent to splanchnic vasodilatation. Vasoactive drugs have therefore been evaluated, aiming to restore the imbalance between the increased intrahepatic and the decreased splanchnic vascular resistance. A large number of randomised, controlled trials have shown that vasoactive drugs in single or combination therapy, significantly reduce the risk of the first bleeding and rebleeding from oesophageal varices. Vasoactive drugs are also effective and safe in controlling acute variceal bleeding. Because of their high clinical efficacy, safety, ease of use and low cost, vasoactive drugs should be considered the first choice treatment for oesophageal varices.     

依贝沙坦治疗肝硬化大鼠门脉高压症实验研究

目的:探讨依贝沙坦对大鼠门脉高压症的治疗作用及副作用。方法:成年雄性Wistar大鼠门脉高压形成后,随机分为4组,即模型组(n=7)、依贝沙坦组(n=6)、普萘洛尔组(n=6),另取8只正常大鼠作为正常对照组。治疗14 d,分别从肝静脉、颈动脉插管测量肝静脉压力梯度(HVPG)、平均动脉压(MAP)。用放免法测定血清透明质酸(HA)、型前胶原(PC)含量。结果:与模型组相比,依贝沙坦组和普萘洛尔组的HVPG显著下降(P<0.05),两组间差别无统计学意义,依贝沙坦组的MAP显著下降(P<0.05)。与模型组相比,依贝沙坦组血清HA、PC显著下降(P<0.05)。结论:依贝沙坦具有一定降低大鼠肝硬化门脉压力的作用,但是该药物对全身血流动力学有较大的影响,可引起全身动脉压力的显著下降。     

术前光量子血氧疗法对肝硬化门静脉高压症的影响

目的 探讨术前光量子血氧疗法(UBIO)对肝硬化门静脉高压症的作用.方法 63例肝硬化门静脉高压症术前患者随机分成治疗组(32例)和对照组(31例),对照组采用常规的护肝治疗,治疗组在对照组治疗的基础上加用UBIO治疗.比较两组的肝功能指标和门静脉血流动力学指标在治疗前后的变化.结果 UBIO治疗后,患者的肝功能改善;脾脏厚度、门静脉宽度及门静脉血流量减少,门静脉血流速度增快.与对照组相比有显著差异(P＜0.05).结论 术前UBIO能改善肝硬化门静脉高压症患者的肝功能,改善门静脉高压和高动力循环状态.     

胰源性区域性门脉高压症的诊断与治疗

目的 探讨胰源性区域性门脉高压症诊断和治疗方法.方法 回顾性分析2003年1月-2013年2月南京市鼓楼医院收治的胰源性区域性门脉高压症患者28例的诊疗过程和随访资料.结果 28例患者中胰腺神经内分泌肿瘤4例,胰腺癌8例,胰腺假性囊肿10例,慢性胰腺炎6例,其中合并有呕血和（或）黑便史14例,所有患者均无肝硬化、腹水及肝功能异常等表现.纤维胃镜和超声内镜提示胃底静脉曲张20例,合并食管下段静脉曲张6例.28例患者均有脾肿大和脾功能亢进的表现.28例患者均采用手术治疗,手术均较顺利.8例胰体尾癌患者于术后3～9个月死亡.余20例患者中随访18例,随访时间为5个月～8年.定期复查内镜,食道下段及胃底周围曲张静脉明显改善或消失,均无再出血.结论 孤立性胃底静脉曲张、脾肿大和脾功能亢进、无肝硬化和肝功能正常及胰腺疾病病史是诊断胰源性区域性门脉高压症的基本要点.该疾病可通过脾切除术或联合胃底周围血管离断术治愈,应同时重视对胰腺原发疾病的治疗.     

Current approaches to the management of patients with liver cirrhosis who have acute esophageal variceal bleeding

Objective:

Esophageal variceal bleeding is the most dangerous complication in patients with liver cirrhosis, and it is accompanied by high mortality. Their treatment can be complex, and requires a multidisciplinary approach. This review examines current approaches to the management of patients with liver cirrhosis who have acute esophageal variceal bleeding.

Methods:

PubMed, Google Scholar, and Cochrane Systematic Reviews were searched for articles published between 1987 and 2015. Relevant articles were identified using the following terms: ‘esophageal variceal bleeding’, ‘portal hypertension’ and ‘complications of liver cirrhosis’. The reference lists of articles identified were also searched for other relevant publications. Inclusion criteria were restricted to the management of patients with liver cirrhosis who have acute esophageal variceal bleeding.

Results:

It is currently recommended to combine vasoactive drugs (preferable somatostatin or terlipressin) and endoscopic therapies (endoscopic band ligation as first choice, sclerotherapy if endoscopic band ligation not feasible) for the initial treatment of acute variceal bleeding. Antibiotic prophylaxis must be regarded as an integral part of the treatment. The use of a Sengstaken–Blakemore tube is appropriate only in cases of refractory bleeding if the above methods cannot be used. An alternative to balloon tamponade may be the installation of self-expandable metal stents. The transjugular intrahepatic portosystemic shunt is an extremely useful technique for the treatment of acute bleeding from esophageal varices. Although most current clinical guidelines classify it as second-line therapy, the Baveno VI workshop recommends early transjugular intrahepatic portosystemic shunt with expanded polytetrafluoroethylene-covered stents within 72?h (ideally <24?h) in patients with esophageal variceal bleeding at high risk of treatment failure (e.g. Child–Turcotte–Pugh class C?<?14 points or Child–Turcotte–Pugh class B with active bleeding) after initial pharmacological and endoscopic therapy. Urgent surgical intervention is rarely performed and can be considered only in case of failure of conservative and/or endoscopic therapy and being unable to use a transjugular intrahepatic portosystemic shunt. Among surgical operations described in the literature are a variety of portocaval anastomosis and azygoportal disconnection procedures.

Conclusions:

To improve the results of treatment for patients with liver cirrhosis who develop acute esophageal variceal bleeding, it is important to stratify patients into risk groups, which will allow one to tailor therapeutic approaches to the expected results.     

彩色多普勒预测食管静脉曲张程度与出血风险的价值

目的通过彩色多普勒测定胃左静脉与门静脉直径、血流速度、血流量、血流方向等血流动力学指标,探讨其预测食管静脉曲张程度与出血风险的价值。方法肝硬化门静脉高压症86例,均接受彩色多普勒、电子胃镜及肝炎标志物、肝功能等常规检验/检查。以研究对象在24个月随访期内有出血史且经内镜检查确定为食道胃底静脉曲张破裂出血为出血风险的评价标准。对比分析出血组与非出血组的胃左静脉、门静脉血流动力学特点。结果随食管静脉曲张程度的加重,胃左静脉内径呈逐渐增宽的趋势,其中食管静脉中度曲张组与无曲张组、食管静脉重度曲张组与轻度曲张组比较有显著性差异（P〈0.05）;门静脉内径随食管静脉曲张程度的加重渐增宽,其中食管静脉中度曲张组与无曲张组、食管静脉重度曲张组与轻度曲张组、食管静脉中度曲张组与轻度曲张组比较有显著性差异（P〈0.05）。胃左静脉的离肝血流方向在出血组与非出血组间均存在显著性差异（χ^2=12.049,P=0.00）,这种显著性差异在Child分级的三级肝功能状态下均存在。不同肝功能状态下门静脉的离肝血流方向在出血组与非出血组间无显著性差异（P〉0.05）。以胃左静脉内径6mm、门静脉内径16mm为预测食管静脉曲张出血风险分层指标,出血患者中门静脉内径≥16mm与非出血组比较存在显著性差异（χ^2=4.21,P=0.04）。结论彩色多普勒测定胃左静脉血流方向、门静脉内径预测食管静脉曲张出血风险具有应用价值,在预测食管静脉曲张程度上胃左静脉、门静脉血流动力学参数均无显著价值。     

普萘洛尔治疗门脉高压患者的效果及门静脉宽度变化的意义

目的 探讨普萘洛尔治疗肝硬化失代偿期门脉高压患者的效果及门脉宽度测量的临床意义.方法 选择2013年1月至2015年12月收治的68例肝硬化失代偿期门脉高压患者进行回顾性分析,根据治疗方式分为普萘洛尔组(n=42)和对照组(n=26),2组患者均给予相同的基础治疗,普萘洛尔组加用普萘洛尔,观察2组患者的治疗效果差异及门脉宽度测量值变化.结果 治疗前,普萘洛尔组和对照组的静脉宽度、WHVP、FHVP、HVPG测定值差异无统计学意义(P>0.05);治疗后,2组患者的静脉宽度、WHVP、HVPG测定值较治疗前显著降低(P<0.05),普萘洛尔组患者的静脉宽度、WHVP、HVPG测定值均显著的低于对照组患者(P<0.05);对68例患者治疗前的门脉宽度测定值、HVPG测定值进行相关性分析(r=0.617,P<0.05);治疗后对68例患者治疗的门脉宽度测定值、HVPG测定值进行相关性分析(r=0.574,P<0.05).结论 普萘洛尔治疗肝硬化失代偿期门脉高压患者具有更加显著的效果,门脉宽度值抗炎药反应患者门脉高压变化情况,可以反映临床治疗效果.     

超声造影对门静脉高压重度食管静脉曲张的预测价值

目的探讨超声造影参数在预测重度食管静脉曲张中应用价值。方法回顾性分析了54例肝硬化门静脉高压行断流手术患者超声及超声造影参数与胃镜检查资料。应用ROC曲线下面积的值评价超声参数预测重度食管静脉曲张的价值。结果HV-HA,PV-HA,PVD,HAPI及HARI在重度EV组和非重度EV组间差异有显著性意义。HV-HA、HAPI、PV-HA的AUC值分别为0.822,0.763和0.704,以HV-HA≤8.4 s预测重度EV,其敏感性为73.7%,特异性为75.0%。结论超声造影在无创预测重度EV中有重要的应用前景。     

Sorafenib targets dysregulated Rho kinase expression and portal hypertension in rats with secondary biliary cirrhosis

Background and purpose

Extrahepatic vasodilation and increased intrahepatic vascular resistance represent attractive targets for the medical treatment of portal hypertension in liver cirrhosis. In both dysfunctions, dysregulation of the contraction-mediating Rho kinase plays an important role as it contributes to altered vasoconstrictor responsiveness. However, the mechanisms of vascular Rho kinase dysregulation in cirrhosis are insufficiently understood. They possibly involve mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)-dependent mechanisms in extrahepatic vessels. As the multikinase inhibitor sorafenib inhibits ERK, we tested the effect of sorafenib on haemodynamics and dysregulated vascular Rho kinase in rats with secondary biliary cirrhosis.

Experimental approach

Secondary biliary cirrhosis was induced by bile duct ligation (BDL). Sorafenib was given orally for 1 week (60 mg·kg⁻¹·d⁻¹). Messenger RNA levels were determined by quantitative real time polymerase chain reaction, protein expressions and protein phosphorylation by Western blot analysis. Aortic contractility was studied by myographic measurements, and intrahepatic vasoregulation by using livers perfused in situ. In vivo, haemodynamic parameters were assessed invasively in combination with coloured microspheres.

Key results

In BDL rats, treatment with sorafenib decreased portal pressure, paralleled by decreases in hepatic Rho kinase expression and Rho kinase-mediated intrahepatic vascular resistance. In aortas from BDL rats, sorafenib caused up-regulation of Rho kinase and an improvement of aortic contractility. By contrast, mesenteric Rho kinase remained unaffected by sorafenib.

Conclusions and implications

Intrahepatic dysregulation of vascular Rho kinase expression is controlled by sorafenib-sensitive mechanisms in rats with secondary biliary cirrhosis. Thus, sorafenib reduced portal pressure without affecting systemic blood pressure.     

肝硬化病人门静脉内径与侧支循环开放情况关系的分析

目的 探讨肝硬化病人门静脉内径与侧支循环开放情况的关系.方法 通过彩色多普勒超声、胃镜、CT等多种检查手段对586例肝硬化病人的门静脉内径与侧支循环开放情况进行检查观察.结果 肝硬化有侧支循环开放组病人门静脉内径[（1.18±0.166） cm]比无侧支循环开放组病人[（1.31±0.160） cm]显著减小;形成的侧支循环以食管胃底静脉曲张最为常见,脐静脉或脐旁静脉开放次之,胃左静脉扩张、脾胃静脉开放接排其后,其他交通支开放较少;门静脉内径越小侧支循环开放的通路就越多且各交通支开放的比例也越高.结论 综合应用彩色多普勒超声等检查方法观察门静脉内径和侧支循环形成状况对肝硬化性门脉高压的诊治、预后评定具有重要的参考价值和指导意义.     

Vapreotide: a somatostatin analog for the treatment of acute variceal bleeding

Background: Portal hypertension is a clinically important consequence of cirrhosis that can lead to morbidities such as variceal bleeding, hepatic encephalopathy and ascites. All of these outcomes carry high mortality rates. There have been several drugs created to assist with endoscopic therapy for the treatment of acute variceal bleeding. Recently, vapreotide has been studied in patients to evaluate its efficacy as treatment for acute variceal hemorrhage. Although no comparisons have been made between vapreotide and other somatostatin analogues, this drug has been shown to have efficacy in the control of acute variceal bleeding as well as reducing the risk of recurrent bleeding and death, especially when started prior to endoscopy. Objective: This paper reviews the literature regarding the basic science and clinical efficacy of vapreotide in acute variceal bleeding. Methods: We used a PubMed/Medline search in order to review the literature regarding the drug, vapreotide. Results/conclusions: Vapreotide appears to have benefit in the control of acute variceal bleeding. It is easy to administer and has few side effects, which are minor. These findings endorse the need for future trials to evaluate vapreotide and its use in acute variceal hemorrhage, a morbidity among patients with cirrhosis.     

胰源性区域性门脉高压症临床诊治

目的探讨胰源性区域性门脉高压症的诊断和治疗方法。方法回顾分析我院10年来共21例胰源性门脉高压的诊断和治疗措施及结果和随访。结果5例胰腺癌患者死于原发病复发转移,1例合并门脉血栓患者死于肠坏死,余无再出血。结论对于胰源性区域性门脉高压症,胰腺病史和胃镜、超声内镜及血管造影等检查发现胃底静脉曲张结合脾肿大及肝功能正常可协助明确诊断。胰源性门脉高压症可以通过脾切除术或同时结合贲门周围血管离断术治愈,但需结合原发胰腺疾病的治疗。     

部分脾动脉栓塞术联合内镜治疗门脉高压症合并中重度食管胃静脉曲张破裂出血的疗效分析

目的　研究内镜下食管静脉曲张套扎术（EVL）、胃静脉曲张硬化术（GVS）联合部分脾动脉栓塞术（PSE）对门脉高压症（PH）合并中重度食管胃静脉曲张（EGV）破裂出血的疗效、安全性及经济性。方法　纳入92例有明确EGV出血的肝硬化PH的住院患者。43例接受EVL/GVS联合PSE治疗为观察组,49例患者接受EVL/GVS治疗为对照组。比较2组患者中重度EGV的根治率、复发率、再出血率、住院天数、安全性及住院总费用。结果　观察组、对照组第1、3个月在EGV根治率、复发率、再出血率方面差异均无统计学意义（均P＞0.05）。第6、12个月观察组EGV根治率显著高于对照组（均P＜0.05）,复发率和再出血率显著低于对照组（均P＜0.05）,观察组住院总费用（万元：8.97 vs. 13.77）、住院总天数（d：27.0 vs. 43.0）显著低于对照组（均P＜0.01）。PSE常见并发症为发热、腹痛、腹腔积液、腹腔感染,严重并发症为脾脓肿。结论　内镜套扎、硬化联合部分脾动脉栓塞术治疗门脉高压症合并中重度EGV破裂出血中长期疗效与单纯内镜套扎、硬化术相比有较高的根治率,较低的复发率、再出血率、住院总费用及住院总天数。PSE并发症可控。     

肝硬化门脉高压症大鼠脾脏切除前后的肺泡巨噬细胞吞噬率变化的实验研究

目的：探讨脾切除术对肝硬化门脉高压症(PHT)的肺脏免疫功能影响,评估保脾手术对治疗PHT的优越性;方法：对模型大鼠及脾切除后的模型大鼠的肺泡巨噬细胞进行体外细胞培养;结果：脾切除术后的大鼠的肺泡巨噬细胞(PAM)的吞噬率显著低于对照组大鼠;结论：在治疗PHT时,从机体免疫角度来说保脾手术可能优于脾全切术。     

TIPS 和 PTVE 治疗肝硬化食管胃底静脉曲张破裂出血的 临床效果比较

摘要： 目的 探讨经颈静脉肝内门体分流术 （TIPS） 和经皮经肝胃冠状静脉栓塞术 （PTVE） 对肝硬化食管胃底静 脉曲张破裂出血的疗效。方法 回顾性分析因肝硬化食管胃底静脉曲张破裂出血就诊并实施介入治疗的 61 例患 者资料, 其中 PTVE 组 42 例, TIPS 组 19 例。比较 2 组治疗成功率、 再出血率、 曲张静脉缓解情况、 肝性脑病发生率、 生存率及肝功能变化等。结果 2 组手术均成功, TIPS 组术后门静脉压力明显下降, PTVE 组的再出血率为 78.6%, 高于 TIPS 组的 63.2%, PTVE 组术后食管胃底静脉曲张缓解的有效率为 50.0%, 明显低于 TIPS 组的 89.5%（均 P＜ 0.05）; PTVE 组和 TIPS 组肝性脑病发生率分别为 14.3%和 26.3%, 2 年累积生存率分别为 95.2%和 89.5%, 差异均无 统计学意义; PTVE 组术后各时期肝功变化与术前差异无统计学意义; TIPS 组术后 1、 3 个月肝功能较术前及 PTVE 术后同一时期下降, 术后 6、 12 个月肝功能变化与术前及 PTVE 术后同一时期相比差异无统计学意义。结论 TIPS 治疗肝硬化食管胃底静脉曲张破裂出血手术安全, 再出血率低, 食管胃底静脉曲张好转快, 术后中远期对肝功能影 响较小, 是一种理想的介入治疗方法。     

药物性肝硬化门脉高压症外科治疗23例临床分析

目的 总结药物性肝硬化门脉高压症的手术治疗方式及经验教训.方法 回顾分析23例手术治疗药物性肝硬化门脉高压症的临床资料.结果 本组治愈17例,好转5例,死亡1例(占4.35%).结论 以贲门周围血管离断术为主的手术是治疗药物性肝硬化门脉高压症较好的方法之一.     

胆石症合并门脉高压症手术方式探讨

目的探讨胆石症所致的门脉高压症手术时机和手术方式对患者预后的影响。方法对收治的42例胆石症合并门脉高压症患者,根据Child分级在不同的时间选择不同的手术方式进行手术或介入治疗。结果肝功Child A级的患者,无论行一期分流或断流均有较好的结局;Child B级根据不同病情选择不同的手术时机和方式,仍可以达到较满意的效果;Child C级的患者,即使行简单的外引流或二期手术,仍有半数以上的死亡率。结论胆石症性门脉高压与门脉高压性胆石症是2个完全不同的概念;在胆石症-胆道梗阻-肝纤维化-胆汁性肝硬化-门脉高压症这一疾病发展的不同过程中,Child A级的患者宜采用一期、根治性的手术;Child B、C级的患者,应遵循＂个体化治疗＂原则,以胆石症治疗为重点,尽可能缩小手术和创伤范围。