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terlipressin and hepatorenal syndrome: What is important for nephrologists and hepatologists

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World Journal of Gastroenterology 2010年第41期16卷 5139-5147页

作者： Ahmed A Magan Atif A Khalil Mohamed H Ahmed Department of Surgery Cambridge Uni-versity Hospital NHS foundation Trust Hills Road Cambridge CB2 0QQ United Kingdom Department of Nephrology Royal Liverpool and Broadgreen University Hospitals Liverpool L7 8XP United Kingdom Division of Acute Medicine James Cook University Hospital Marton Road Middlesbrough TS4 3BW United Kingdom

Hepatorenal syndrome (HRS) is a reversible form of functional renal failure that occurs with advanced hepatic cirrhosis and liver failure. Despite mounting research in HRS, its etiology and medical therapy has not been resolved. HRS encompasses 2 distinct types. Type 1 is characterized by the rapid development of renal failure that occurs within 2 wk and involves a doubling of initial serum creatinine. Type 2 has a more insidious onset and is often associated with ascites. Animal studies have shown that both forms, in particular type 1 HRS, are often precipitated by bacterial infections and cir-culatory changes. The prognosis for HRS remains very poor. Type 1 and 2 both have an expected survival time of 2 wk and 6 mo, respectively. Progression of liver cir-rhosis and the resultant portal hypertension leads to the pooling of blood in the splanchnic vascular bed. The ensuing hyperdynamic circulation causes an ineffective circulatory volume which subsequently activates neuro-hormonal systems. Primarily the sympathetic nervoussystem and the renin angiotensin system are activated, which, in the early stages of HRS, maintain adequate circulation. Both advanced cirrhosis and prolonged ac-tivation of neurohormonal mechanisms result in fatal complications. Locally produced nitric oxide may have the potential to induce a deleterious vasodilatory effect on the splanchnic circulation. Currently medical therapy is aimed at reducing splanchnic vasodilation to resolve the ineffective circulation and maintain good renal per-fusion pressure. terlipressin, a vasopressin analogue, has shown potential benefit in the treatment of HRS. It prolongs both survival time and has the ability to re-verse HRS in the majority of patients. In this review we aim to focus on the pathogenesis of HRS and its treatment with terlipressin vs other drugs.

关键词： Heptorenal syndrome terlipressin Kidney Liver

terlipressin improves pulmonary pressures in cirrhotic patients with pulmonary hypertension and variceal bleeding or hepatorenal syndrome

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Hepatobiliary & Pancreatic Diseases International 2012年第4期11卷 434-437页

作者： George N Kalambokis Konstantinos Pappas Epameinondas V Tsianos 1st Division of Internal Medicine and Hepato Gastroenterology UnitUniversity Hospital of IoanninaIoannina 45500Greece Department of Cardiology University Hospital of IoanninaIoannina 45500Greece

terlipressin has been shown to improve both pulmonary and systemic hemodynamics in stable cirrhotic patients with pulmonary hypertension,whereas other vasoconstrictors may cause pulmonary pressures to deteriorate We investigated the pulmonary and systemic hemodynamic effects of the first terlipressin dose(2 mg) in 7 cirrhotic patients with PH presenting with variceal bleeding(n=4) or hepatorenal syndrome(n=3).terlipressin decreased pulmonary vascular resistance(158.8±8.9 vs 186.5±13.9 dynes sec cm-5 ;P=0.003) together with an increase in systemic vascular resistance(2143± 126 vs 1643±126 dynes sec cm-5 ;Pterlipressin should be the vasoconstrictor treatment of choice when patients present with variceal bleeding or HRS.

关键词： terlipressin pulmonary hypertension cirrhosis variceal bleeding hepatorenal syndrome

Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats

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Hepatobiliary & Pancreatic Diseases International 2017年第5期16卷 506-511页

作者： Tom Florian Ulmer Anne Weiland Georg Lurje Christian Klink Anne Andert Hamid Alizai Christoph Heidenhain Ulf Neumann Department of General Visceral and Transplantation Surgery RWTH Aachen University Hospital Aachen Germany Department of Urology Helios Hospital Berlin-Buch Germany

BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70%partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups(n=24 in each group): 70% partial hepatectomy as control(PHC), 70% partial hepatectomy with splenectomy(PHS) or 70% partial hepatectomy with a micropump for terlipressin administration(PHT). Eight rats in each group were sacrificed on postoperative day(POD) 1,3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine(BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and 7.RESULTS: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups(PHT:8.13 ±1.55, 10.38±1.30, 6.25±0.89 cm H2O and PHS: 7.50±0.93,8.88 ±2.42, 5.75±1.04 cm H2O) was lower compared to the control group(PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1(Brd U: PHS vs PHC, 20.85% ±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96% ±11.69%). However, none of the differences were statistically significant.CONCLUSIONS: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration.

关键词： liver regeneration liver failure terlipressin splenectomy hepatectomy

terlipressin对肝大部切除术后早期门静脉高灌注综合征的保护性治疗研究

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中国普通外科杂志 2009年第7期18卷 717-722页

作者：任祖海叶启发余伟平黄文鹏陈晚平邢晓为蒋胜军孙亚冬中南大学湘雅三医院移植中心湖南长沙410013

目的探讨terlipressin对大鼠肝大部切除术后再灌注早期门静脉高灌注综合征的保护性治疗作用及其机制。方法将36只大鼠随机分为特利加压素(terlipressin)治疗组(Th组,n=18)及生理盐水治疗对照组(Ch组,n=18)。两组大鼠分别在给药前及再灌... 详细信息

目的探讨terlipressin对大鼠肝大部切除术后再灌注早期门静脉高灌注综合征的保护性治疗作用及其机制。方法将36只大鼠随机分为特利加压素(terlipressin)治疗组(Th组,n=18)及生理盐水治疗对照组(Ch组,n=18)。两组大鼠分别在给药前及再灌注后30min,1h,2h4个时点进行血流动力学观察,并依此各再分为3亚组:Th1/2,Th1,Th2及Ch1/2,Ch1,Ch2组,每亚组6只大鼠。另20只大鼠随机分为特利加压素治疗存活组(Ts组)10只及生理盐水治疗存活对照组(Cs组)10只。采用肝大部切除术(90%)加肝门阻断(30min)动物模型,将Th组及Ts组大鼠在肝门阻断前通过阴茎背静脉注射terlipressin,Ch组及Cs组用同法在相同的时间给予同等体积的无菌生理盐水。观察terli-pressin对小体积肝大鼠生存率及血流动力学的影响。结果所有大鼠存活超过24h;Ts组10d存活率(80.0%)明显高于Cs组(30.0%)(Pterlipressin能有效缓解门静脉高灌注状态,可以降低门静脉压力及血流量,能显著提高肝大部切除术后小体积肝存活率。

关键词：肝切除术小体积肝 terlipressin 血流动力学大鼠

terlipressin对肝大部切除术后早期小体积肝功能保护机制的研究

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中国普通外科杂志 2010年第7期19卷 756-762页

作者：任祖海叶启发余伟平黄文鹏陈晚平邢晓为蒋胜军孙亚冬中南大学湘雅三医院移植中心湖南长沙410013

目的探讨特利加压素(terlipressin)对大鼠肝切除术后早期残余肝脏功能的保护作用及其机制。方法建立肝大部切除(90%)术后小体积肝大鼠动物模型,将60只模型大鼠随机分为:特利加压素治疗组(T组)30只及生理盐水对照组(C组)30只。两组大鼠... 详细信息

目的探讨特利加压素(terlipressin)对大鼠肝切除术后早期残余肝脏功能的保护作用及其机制。方法建立肝大部切除(90%)术后小体积肝大鼠动物模型,将60只模型大鼠随机分为:特利加压素治疗组(T组)30只及生理盐水对照组(C组)30只。两组大鼠均分别在肝门阻断下行肝切除残肝复流后30 min,2,4,6,24 h 5个时点进行观察。即每组分为5个亚组:T1/2,T2,T4,T6,T24及C1/2,C2,C4,C6,C24。每亚组6只大鼠。将两组所有时点血清标本进行ALT、AST及TBIL测定。活体肝组织冷冻标本用于半定量RT-PCR检测mRNA水平残肝内A20及iNOS基因的表达。肝组织石蜡切片用于HE染色光镜下观察形态学改变;免疫组化法检测ET-1,A20及iNOS的细胞内表达以及TUNEL法原位检测凋亡细胞。结果两组ALT,AST及TBIL在再灌注后24h达高峰,其中T6及T24上述3个指标检测值明显低于C6和C24,(Pterlipressin不仅对肝大部切除术后小体积肝功能具有保护作用,可预防肝功能进行性损害,改善预后,还能改善残肝再灌注后早期炎性反应及减少肝细胞凋亡;通过减轻肝窦机械性损伤,维持微循环稳定。

关键词：肝切除术/副作用 terlipressin 小体积肝肝功能保护机制

The Clinical Effects Study of Hepatic Failure by Intraperitoneal Injection of Antibiotics,Intravenous Injection of terlipressin,and Combined Therapy of Coloclysis and Plasma Exchange

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国际感染病学（电子版） 2012年第1期1卷 51-57页

作者： Hui Li Ya-ling Wang De-ying Tian Department of Liver Diseases No.3 Municipal People's Hospital of Kunming Department of Infectious Diseases Tongji HospitalTongji MedicalCollegeHuazhong University of Science and Technology

Objective To observe the therapeutic effects of intraperitoneal injection of antibiotics,intravenous injection of terlipressin,and combined treatment of coloclysis and plasma exchange on hepatic failure(HF),the subjects included 494 inpatient cases of hepatic failure who were treated in Department of Infectious Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China from 1997 to2008.Methods The patients that met the inclusion criteria were divided into intraperitoneal antibiotic injection group,intravenous terlipressin injection group,coloclysis group,plasma exchange group,combination group of coloclysis and plasma exchange in terms of treatment given and a control group was set up for each of the treatment group.In the intraperitoneal injection group,the prognosis and changes in clinical manifestations were observed in HF patients complicated with spontaneous peritonitis(SBP).In terlipressin injection group,HF patients complicated with hepatorenal syndrome(HRS) were observed for prognosis and changes in serum creatinine.In the combination group,the improvement in serum total bilirubin and prothrombin activity were observed.Results Two weeks after intraperitoneal injection of antibiotics,the ease ratios of abdominal pain,pressure pain and rebound tenderness were 87.64%,82.02%and 82.02%in the intraperitoneal injection group,respectively and the volume of ascites obviously decreased in 69 patients(77.53%).The survival rate in intraperitoneal injection group was significantly higher than in control group(P = 0.004).Four to eight days after the intravenous injection of terlipressin,the survival rate and the rate of serum creatinine decline of the treatment group were significantly higher than those in the control group(P = 0.003,P = 0.000).After 4 weeks of treatment,the ratio of clinical symptoms improvement(acratia,anorexia,abdominal distension,constipation) in coloclysis group were60.27%,57.53%,91.78%and 94.52%,in plasma exchange group were 71.83%,69.44%,75%and 72.2

关键词： Hepatic failure Intraperitoneal injection of antibiotics Elevation coloclysis terlipressin Plasma exchange

Position statement of Hepatology Society, Dhaka, Bangladesh, on the management of acute variceal bleeding in a resource-limited setting

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iLIVER 2022年第4期1卷 205-208页

作者： Tanvir Ahmad Shahinul Alam Saiful Islam Golam Azam Mahabubul Alam SKM Nazmul Hasan Golam Mustafa Motahar Hossain MdAkmat Ali Mobin Khan Kurmitola General Hospital DhakaBangladesh Department of Hepatology BSMMU General SecretaryHepatology SocietyDhakaBangladesh Department of Hepatology BSMMUBangladesh Department of Gastrointestinal-Hepatobiliary and Pancreatic Disorders(GHPD) BIRDEM HospitalBangladesh Department of Hepatology Shahid Syed Nazrul Islam Medical CollegeKishoregonjBangladesh Square Hospital Bangladesh Addin Medical College DhakaBangladesh

Variceal bleeding is one of the important signs of decompensation in patients with cirrhosis of the liver.It is always a medical emergency and sometimes results in death.Every year many patients die due to acute bleeding worldwide.The outcome depends on bleeding and its complications as well as the severity of the underlying liver disease.Careful volume resuscitation,administration of antibiotics and vasoactive drugs,and early endoscopic therapy prevent rebleeding and death.People living in rural areas are first referred to a district hospital from the Upazila health complex for any medical emergency.So,commencing the resuscitation process as well as administration of the vasoactive drug(terlipressin)at the first attending hospital before being referred to a higher center will decrease the mortality in patients presenting with acute variceal bleeding.

关键词： Variceal bleeding Resource-limited setting terlipressin Cirrhosis Primary care physician

terlipressin decreases VEGF expression and improves PaO2/FiO2 in ARDS patient with shock

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Terlipressin decreases VEGF expression and improves PaO2/FiO...

The beneficial impacts of splanchnic vasoactive agents on hepatic functional recovery in massive hepatectomy porcine model

2011年第三十三届浙江省呼吸系病学术年会暨呼吸疾病诊...

作者： Department of Pulmonary Medicine,Zhongshan Hospital,Fudan University,180 Feng Lin Road,Shanghai 200032,People’ s Republic of China Feng Hua Lei Zhu Department of Pulmonary Medicine,Huzhou central Hospital,198 Hongqi Road,Zhejiang province 313000, People’ s Republic of China Feng Hua Enhai Cui Bing Wang

Recent clinical data suggest that terlipressin treatment may be advantageous for septic shock, compared with catecholamine.However,it is unknown whether terlipressin are effective for acute respiratory distress syndrome(ARDS) patient with shock.The aim of the present study was to compare the impact of terlipressin or dopamine on hemodynamic variables and vascular endothelial growth factor(VEGF) in ARDS patients with shock.Methods We studied 32 ARDS patients with shock despite fluid loading,enrolled to terlipressin(TP,n = 16) or dopamine(n = 16).TP was administered as continuous intravenous doses of 1.3μg/ kg/h and dopamine was administered with doses 20μg/ kg/min to maintain mean arterial pressure(MAP) at 70±5 mmHg for 48 h.Hemodynamic changes,Pa02/Fi02,VEGF were recorded prospectively.Results There was a significant correlation between plasma VEGF level and lung injury score LIS at baseline(r=0.387,P0.05 at 48 hours vs.baseline).However,there was no significant difference in TNF-αconcentration among groups.Conclusions:TP treatment has the potency to inhibit VEGF and improve oxygenation in early stage of ARDS with shock.

关键词： Acute respiratory distress syndrome Vascular?endothelial?growth?factor Oxygenation terlipressin Dopamine

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Hepatobiliary Surgery and Nutrition 2021年第3期10卷 325-336页

作者： Hye-Sung Jo Jae Hyun Han Yoon Young Choi Jin-I Seok Young-In Yoon Dong-Sik Kim Division of HBP Surgery and Liver Transplantation Department of SurgeryKorea University College of MedicineSeoulRepublic of Korea Department of Surgery St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulRepublic of Korea Department of Biomedical Science Korea University College of Medicine Graduate SchoolSeoulRepublic of Korea Division of Hepatobiliary Surgery and Liver Transplantation Department of SurgeryAsan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea

Background:Excessive portal pressure after massive hepatectomy can cause hepatic sinusoidal injury and have deleterious impacts on hepatic functional recovery,contributing to developing post-hepatectomy liver failure.This study aimed to assess the effects of splanchnic vasoactive agents on hepatic functional recovery and regeneration while clarifying the underlying mechanism,using a 70%hepatectomy porcine model.Methods:Eighteen pigs undergoing 70%hepatectomy were involved in this study and divided into three groups:control(n=6),terlipressin(n=6),and octreotide(n=6).terlipressin(0.5 mg)and octreotide(0.2 mg)were administered 3 times a day for each group with the first dose starting just before surgery until the 7th postoperative day,at which time the surviving pigs were sacrificed.During the period,portal pressure,liver weight,biochemical analysis,histological injury score,and molecular markers were evaluated and compared between groups.Results:The 7-day survival rates in the octreotide,terlipressin,and control groups were 100%,83.3%,and 66.7%,respectively.The portal pressures decreased in both terlipressin and octreotide groups than the control group at 30 minutes,1 hour and 6 hours after hepatectomy.The amount of regeneration measured by liver weight to body weight ratio at the time of sacrifice in the terlipressin group was smaller than that in the control group(117%vs.129%,P=0.03).Serum aspartate aminotransferase(AST)and total bilirubin levels at 1 and 6 hours after hepatectomy and prothrombin time/international normalized ratio(PT/INR)at 6 hours after hepatectomy were significantly improved in the terlipressin and octreotide groups compared to the control group.Serum endothelin-1(ET-1)was significantly lower in the terlipressin group than that in the control group 6 hours after hepatectomy(Pterlipressin group on the 7th postoperative day(Pterlipressin and

关键词： Hepatectomy portal pressure terlipressin somatostatin