Favorable clinical outcome using a covered stent following transjugular intrahepatic portosystemic shunt in patients with portal hypertension

Aims

To compare retrospectively the clinical outcomes in patients treated with transjugular intrahepatic portosystemic shunt (TIPS) using the novel polytetrafluoroethylene-covered stents (Fluency) and bare stents.

Materials and methods

Sixty consecutive patients with portal hypertension treated with TIPS from April 2007 to April 2009 were included. TIPS creation was performed with Fluency stent grafts in 30 patients (group A) and with bare stents in 30 patients (group B). Liver function, TIPS patency and clinical outcomes were evaluated every 3 months after procedures.

Results

During hospitalization, there were no cases of hepatic encephalopathy (HE) and recurrence of variceal bleedings. Acute shunt occlusion was found in one patient in each group. Follow-ups were performed in group A with average time of 6.16 ± 3.89 months and in group B with 8.34 ± 4.42 months. The rates of recurrent bleeding, shunt occlusion, HE and mortality were 0.03, 0.0, 16.7 and 0% in group A, and 20.0, 30.0, 20.0 and 13.3% in group B, respectively. There was no difference of HE between group A and group B. The decrease of portal pressure and portosystemic pressure gradient, and the increase of portal flow were 34.1 and 23.3%, 60.0 and 52.8%, and 189.5 and 111.1% in group A and B, respectively. There were no differences of liver function between group A and B.

Conclusion

The Fluency stent graft is relatively safe and effective in TIPS creation, with a high patency rate compared with bare stents.     

��Ӳ���ž�����ѹ���Ʋ���

肝硬化患者因各种并发症而病死率高。内镜下食管曲张静脉结扎,生长抑素及其类似物均是处理出血的常用方法。近年美国肝病学会发布的指南中认为,当药物不能控制食管静脉曲张出血时,宜采用经颈静脉肝内门体分流术(TIPS)而不是外科手术。与其他方法比较,TIPS术后恰当的抗凝措施,可获得满意的长期预防食管静脉曲张出血的疗效。     

Effects of transjugular intrahepatic portasystemic shunt (TIPS) on splanchnic and systemic hemodynamics,and hepatic function in patients with portal hypertension

The purpose of this study was to evaluate the short-term splanchnic and systemic hemodynamics and hepatic function after TIPS creation. Fifteen cirrhotics with portal hypertension underwent TIPS placement for treatment of variceal hemorrhage, and extensive hemodynamic studies including right heart catheterization, portal pressure measurement, hepatic blood flow, and indocyanine green (ICG) clearance were performed before and 1 month after the procedure. Self-expandable metal stents (Strecker 11 mm diameter) were placed in all cases. Portasystemic gradient significantly diminished (18.3±4.2 vs 8±2.8; 54%±18 mm Hg) after the technique, mainly due to a decrease in portal pressure, and remained stable in the final study. Cardiac output and mean arterial pressure increased (6.2±1.4 vs 8.2±1.8 liters/min, 80.1±10.1 vs 91±11.2 mm Hg, respectively), and a decrease in systemic vascular resistance was registered (1018±211 vs 872±168 dyne/sec/cm⁵); the hepatic blood flow and ICG clearance also decreased significantly (1.5±0.7 vs 0.68±0.2 liters/min, 0.4±0.2 vs 0.24 ±0.06 liters/min, respectively). There was an increase in the preload at the final study, as evidenced by a marked increase in right atrial (3.1±1.6 vs 4.35±2.2 mm Hg, +15%,P<0.05), pulmonary arterial (12.2±2.4 vs 15.9±3.2 mm hg, +31.8%,P<0.001), and wedge pulmonary arterial pressures (6.9±2.4 vs 9.8±3.1 mm Hg, +53%,P<0.001). These results suggest that TIPS worsens the hyperdynamic syndrome associated to portal hypertension. Therefore, in patients with cardiac insufficiency, this procedure should be evaluated. TIPS also decreases the hepatic blood flow, inducing a mild worsening in liver function.Funded in part by the Fondo de Investigaciones Sanitarias de la Seguridad Social, grant 94/0240.     

乙型肝炎肝硬化门脉高压症行脾切除联合门奇静脉断流术后影响预后的因素分析

目的分析影响乙型肝炎肝硬化门脉高压症行脾切除联合门奇静脉断流术后预后的主要因素。方法2014年6月~2015年6月我科行脾切除联合门奇静脉断流术治疗的乙型肝炎肝硬化门脉高压症患者74例,采用Cox回归分析影响术后预后的因素。结果术后随访3年,生存患者60例（81.1%）,死亡患者14例（18.9%）;单因素分析结果显示,死亡患者年龄≥50岁、合并疾病基础、CTP评分>10分、术前存在食管静脉曲张史、术中出血量>600 mL、术中输血量>500 ml、急诊手术、术后发生并发症、术后肝炎活动、治疗依从性差等显著高于生存患者（P<0.05）;多因素分析结果显示,患者术后发生并发症、合并基础疾病、肝硬化分级差、术后肝炎活动和患者对治疗依从性差等均为影响患者术后预后的危险因素（P<0.05）。结论影响乙型肝炎肝硬化门脉高压症患者术后预后的因素较多,应针对性地做好防治工作,提高患者生存率。     

Study of portal vein thrombosis in patients with idiopathic portal hypertension in Japan.

BACKGROUND/AIMS: The aim of this study was to elucidate the incidence and clinical manifestations of portal vein thrombosis (PVT) in patients with idiopathic portal hypertension (IPH) in Japan during long-term follow-up. PATIENTS AND METHODS: Twenty-two patients with IPH were examined for PVT by sonography during a follow-up of 12+/-6 years. Clinical manifestations and patient outcome related to PVT were studied. Seventy patients with liver cirrhosis were examined by sonography as an incidence control of thrombosis. RESULTS: Nine IPH patients had portal thrombosis (9/22, 41%), a higher incidence than in liver cirrhosis patients (7/70, 10%). Those with thrombosis showed ascites, marked hypersplenism, and low serum albumin. Four patients with thrombosis died. Patients without thrombosis showed less clinical problems after long-term follow-up. Plasma antithrombin III and protein C activity decreased in almost half of the patients. However, there were no differences in these parameters between patients with and without thrombosis. CONCLUSIONS: In Japan, IPH patients had a high incidence of portal thrombosis, a significant factor for poor prognosis. Whether the management of PVT contributes to an improvement of a clinical course of IPH or not should be clarified in further study.     

Management of portal hypertension based on portal hemodynamics

Portal hypertension is most commonly caused by chronic liver disease. As liver damage progresses, portal pressure gradually elevates and hemodynamics of the portal system gradually change. In normal liver, venous returns from visceral organs join the portal trunk and flow into the liver (hepatopetal blood flow). As portal pressure increases due to liver damage, congestion of some veins of the visceral organ occurs (blood flow to and from). Finally, the direction of some veins (the left gastric vein in particular) of the visceral organ change (hepatofugal blood flow) and develop as collateral veins (portosystemic shunt) to reduce portal pressure. Therefore, esophagogastric varices serve as drainage veins for the portal venous system to reduce the portal pressure. In chronic liver disease, as intrahepatic vascular resistance is increased (backward flow theory) and collateral veins develop, adequate portal hypertension is required to maintain portal flow into the liver through an increase of blood flow into the portal venous system (forward flow theory). Splanchnic and systemic arterial vasodilatations increase the blood flow into the portal venous system (hyperdynamic state) and lead to portal hypertension and collateral formation. Hyperdynamic state, especially around the spleen, is detected in patients with portal hypertension. The spleen is a regulatory organ that maintains portal flow into the liver. In this review, surgical treatment, interventional radiology, endoscopic treatment, and pharmacotherapy for portal hypertension (esophagogastric varices in particular) are described based on the portal hemodynamics using schema.     

Colonic mucosa in patients with portal hypertension

BACKGROUND AND AIMS: To do a histomorphometric study of vascular changes in colonic mucosa of patients with portal hypertension (PHT) and to find their association with clinical and upper and lower gastrointestinal endoscopic observations. METHODS: Full length colonoscopy was carried out in 55 patients with portal hypertension and 25 controls. Hemorrhoids, anorectal varices and colopathy were carefully looked for and recorded. Two biopsies each were taken from the caecum, ascending colon, transverse colon, descending colon and rectum. Sections from all the five sites were examined for histopathological changes with special reference to changes in mucosal capillaries. Morphometric assessment of the diameter of the capillary and thickness of the capillary wall was performed. These histomorphometric changes were correlated with clinical parameters and findings of upper and lower gastrointestinal endoscopic findings. RESULTS: Dilated and congested capillaries as well as capillaries with irregular thickening of the wall were seen in a significantly higher number of sections from patients than controls in biopsies from all the five sites from caecum to rectum. On morphometry, the diameter of the capillaries and the thickness of the capillary wall in biopsies from all the five sites in patients was significantly higher than that in the control group. Apart from vascular changes, edema and inflammatory infiltrate in lamina propria were the other significant histological features noted. No significant association between clinical and endoscopic features and histomorphometric assessment was found. CONCLUSION: Dilated tortuous mucosal capillaries with irregular thickening of wall, edema of lamina propria and mild chronic inflammatory infiltrate are the major histopathological changes seen in colonic biopsies of patients with PHT, showing that PHT produces changes in the colonic mucosa similar to those seen in the mucosa of upper GI tract. However, the histological changes had no correlation with the clinical or endoscopic findings except that the thickness of the capillary wall was higher in patients who had undergone endoscopic sclerotherapy as opposed to those who had not received sclerotherapy.     

不同术式对活动性肝硬化门静脉高压症患者肝脏血流动力学和肝功能的影响

活动性肝硬化门静脉高压症患者 30例随机分为断流组和分流组。同期内科保守治疗的同类患者 30例为对照组。手术后分流组的门静脉血流量 (PVF)、自由门静脉压 (FPP)和肝总血流量 (HTF)显著下降 ,R15ICG明显增加 ,与断流组比较差异显著 (均P <0 0 5 )。治疗后 1年断流组的肝炎好转率优于分流组 (P <0 0 5 ) ,肝功能正常率显著高于其它两组 (均P <0 0 5 )。表明断流术有利于肝炎的恢复。     

21例特发性门脉高压临床及病理特点分析

目的分析特发性门脉高压(idiopathic portal hypertension,IPH)的临床及病理特点。方法回顾性分析2012年1月—2016年12月在解放军第三〇二医院住院治疗(资料完整)的21例IPH患者的临床及病理特点。结果 21例IPH患者中,男女比例6∶15,平均发病年龄(38.1±12.7)岁,临床以门脉高压症表现为主,肝功能无明显减退,主要并发症为上消化道出血及腹水。21例肝组织病理主要表现为肝细胞板排列基本正常,无假小叶形成,汇管区扩大,门静脉周围纤维化,门脉周围有不同程度的细胞浸润,血管紊乱,中央静脉及小叶间静脉扩张,肝窦扩张,窦周纤维化。结论 IPH患者门脉高压和肝功能损害不平行,门脉高压表现较重,确诊仍须病理学检查,治疗以防治并发症为主。     

Effect of laparoscopic splenectomy on portal hypertensive gastropathy in cirrhotic patients with portal hypertension

Aim:  This study investigated the relationship between portal hypertensive gastropathy (PHG) and splenomegaly, and the effect of laparoscopic splenectomy on PHG in cirrhotic patients with portal hypertension.
Methods:  Seventy patients with liver cirrhosis and portal hypertension were prospectively studied. Indication for laparoscopic splenectomy was bleeding tendency in 10 patients, induction of interferon in 45, treatment of hepatocellular carcinoma in seven, and treatment for endoscopic injection sclerotherapy-resistant esophagogastric varices in eight. The severity of PHG was classified into none, mild, or severe according to the classification by McCormack et al. The severity of liver disease was classified using the Child–Pugh score. All patients underwent upper gastrointestinal endoscopy before and 1 month after the operation.
Results:  The prevalence of PHG was significantly correlated with the severity of liver disease using the Child–Pugh score. The severity of PHG was significantly correlated with the resected spleen volume. One month after the operation, PHG was improved in 16 of 17 patients with severe PHG and in 12 of 32 with mild PHG. The Child–Pugh score showed a significant improvement (6.8 ± 1.4 to 6.2 ± 1.2) at 3 months after laparoscopic splenectomy ( P  < 0.0001).
Conclusions:  PHG may be associated with splenomegaly, and laparoscopic splenectomy may have a beneficial effect on PHG, at least for a short time.     

非肝硬化门脉高压患者临床特点分析

目的 总结非肝硬化门脉高压症(NCPH)患者的临床特点和肝静脉压力梯度(HVPG)的变化.方法 2017年1月～2019年12月南京市第二医院住院的28例NCPH患者,采用Seldinger法穿刺右侧颈内静脉,使用一次性球囊导管测定肝静脉压力,计算HVPG,接受肝活检检查.结果 在本组28例NCPH患者中,诊断特发性门...     

非肝硬化性门静脉高压症的研究现状

肝硬化是门静脉高压的最常见原因,但仍有约20%的门静脉高压继发于非肝硬化因素,称为非肝硬化性门静脉高压症(NCPH),在发展中国家发病率较高。NCPH是一组异源性的肝脏血管疾病,临床上多见的是特发性门静脉高压(IPH)、肝外门静脉血管阻塞(EHPVO),以及布加综合征、先天性肝纤维化和结节再生性增生等少见病。此类患者常常具有门静脉高压的证据,如反复发生的静脉曲张出血和脾脏肿大,但肝功能保存尚好。目前尚无诊断NCPH的统一标准,对其诊断仍是一个挑战。临床上往往采用排除性诊断,必要时可行肝穿刺活组织检查来确诊。介绍了IPH和EHPVO的发病机制、病理表现、诊断方法及治疗策略的选择,若能有效控制上消化道出血,NCPH被认为是预后相对良好的一类疾病。     

门脉高压性胃病的进展

门脉高压性胃病（ponalhypertensivegastropathy，PHG）是指门脉高压症伴发的胃黏膜病变，主要发生于肝硬化门脉高压症病人，也见于非肝硬化门脉高压症病人，临床主要表现为消化道出血等症状，严重时危急生命。1984年Sarfeh等提出PHG与非PHG在形态、功能、治疗上都有不同，因其病理组织学上炎性改变依据不足，可称其为门脉高压性胃病。PHG常与食管静脉曲张同时存在，而PHG出血可占门脉高压消化道出血的10％～60％。食管胃底静脉曲张、肝功能损害越重，则门脉高压性胃病并发消化道出血的发生率越高。在上消化道出血患者，食管静脉曲张程度较轻者以PHG合并出血为主，食管静脉曲张程度较重者则以曲张静脉破裂出血为主。     

Natural history of patients with non cirrhotic portal hypertension: Comparison with patients with compensated cirrhosis

BackgroundThe knowledge of natural history of patients with portal hypertension (PH) not due to cirrhosis is less well known than that of cirrhotic patients.AimTo describe the clinical presentation and the outcomes of 89 patients with non-cirrhotic PH (25 with non-cirrhotic portal hypertension, INCPH, and 64 with chronic portal vein thrombosis, PVT) in comparison with 77 patients with Child A cirrhosis.MethodsThe patients were submitted to a standardized clinical, laboratory, ultrasonographic and endoscopic follow-up. Variceal progression, incidence of variceal bleeding, portal vein thrombosis, ascites and survival were recorded.ResultsAt presentation, the prevalence of varices, variceal bleeding and ascites was similar in the 3 groups. During follow-up, the rate of progression to varices at risk of bleeding (p < 0.0001) and the incidence of first variceal bleeding (p = 0.02) were significantly higher in non-cirrhotic then in cirrhotic patients. A PVT developed in 32% of INCPH patients and in 18% of cirrhotics (p = 0.02).ConclusionsIn the patients with non-cirrhotic PH variceal progression is more rapid and bleeding more frequent than in cirrhotics. Patients with INCPH are particularly prompt to develop PVT. This observational study suggests that the management of patients with non-cirrhotic PH should take into consideration the natural history of portal hypertension in these patients and cannot be simply derived by the observation of cirrhotic patients.     

选择性远端脾腔分流术治疗门静脉高压症

本文总结近8年来施行的42例选择性远端脾腔分流术的临床疗效和血流动力学效应以评价此术在肝硬变门静脉高压症中的治疗价值。本组门静脉高压症病人在分流术后仍维持术前的门静脉高压状态及门静脉向肝血流;而脾腔静脉吻合通畅率高,脾静脉压力显著下降。术后病人只有1例发生早期再出血,肝功能稳定,无肝性脑病发生,病人生活质量佳,本文结果表明,选择性远端脾腔分流术是一种较理想的选择性分流术式。     

The hypotensive effect of oral nitroglycerin on portal venous pressure in patients with cirrhotic portal hypertension

Abstract Nitroglycerin was administered orally to seven patients with cirrhosis and portal hypertension, to determine whether portal venous pressure (PVP) may be lowered without the systemic effects associated with its intravenous or sublingual use. PVP was measured via direct cannulation of the portal vein transhepatically using a Chiba needle. PVP decreased from 29 (s.d. = 4) to 22.7 (s.d. = 3.7) mmHg (22% mean fall) following 1.2 mg nitroglycerin with onset 7–15 min following ingestion, and the response persisted for up to 150 min. This was not associated with headache in any patient. Although a decrease in blood pressure was seen in most patients, this temporally followed the fall in PVP suggesting that it was a secondary response. Sublingual nitroglycerin was given to two patients without change in PVP yet both experienced severe headache. These findings support the hypothesis that oral nitroglycerin is delivered differentially to the portal venous bed with differential effects on PVP. Further studies are needed to evaluate this agent and this strategy for their potential role in long-term control of portal pressure.     

脾切除对门静脉高压症患者免疫功能的影响

目的:通过观察肝功能Child-Pugh A和B级门静脉高压症患者手术前后血清促/抗炎细胞因子和CD4+/CD25+百分比动态变化,探讨门静脉高压症患者手术前后免疫功能变化特点及脾切除对其的影响。方法:将2007年9月至2011年12月收治的36例门静脉高压症患者,依据肝功能分为Child-Pugh A级组和Child-Pugh B级组。在术前、术后7天、术后14天、术后1月、术后3月5个时间点动态观察患者肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、IL-10、IL-4及CD4+/CD25+百分比等相关指标的变化,并观察术前术后患者免疫功能变化特点及脾切除对它们的影响。结果:随着肝功能损害程度的加重,患者的手术时间延长,输血量增加,感染发生机会增多。术前患者肝功能越差,TNF-α和IL-6水平越低(P<0.05)。两组患者TNF-α和IL-6水平存在着一致性,此两项指标在术后7天增长到顶峰,随后逐渐下降;此两项指标在术后3个月时与术后1个月时比较,差异无显著性意义(P>0.05)。术前肝功能越差,IL-10和IL-4水平越低(P<0.05),两组患者IL-10和IL-4水平均在术后14天增长到顶峰,随后逐渐下降,在术后3月Child-Pugh B级组患者的IL-10、IL-4维持在较高水平(P<0.05)。两组患者CD4+/CD25+百分比水平均在术后14天增长到顶峰,随后逐渐下降,术后3月Child-Pugh B级组维持在较高水平(P<0.05)。结论:乙型肝炎肝硬化门静脉高压症患者处于免疫抑制状态,肝功能越差免疫水平越低;脾切除可以改善Child-Pugh B级患者的免疫状态。     

Liver pathology of idiopathic portal hypertension. Comparison with non-cirrhotic portal fibrosis of India The Japan idiopathic portal hypertension study*,+

ABSTRACT— Morphological changes of the liver were studied in 24 autopsy cases of noncirrhotic portal hypertension of unknown etiology (idiopathic portal hypertension, IPH), and in 123 surgical biopsies from such patients. For comparison, 15 whole-cut liver slices from autopsy cases of noncirrhotic portal fibrosis (NCPF) from India were also studied. Liver pathology was very similar in IPH and NCPF, characterized by phlebosclerotic changes and perivascular fibrosis of the portal vein system, and parenchymal atrophy perhaps secondary to portal circulatory insufficiency. The distribution of lesions was uneven, and despite marked fibrosis and occasional surface nodularity, there was no diffuse pseudonodule formation in the parenchyma. Surgical specimens showed similar changes except for more frequent portal cellular infiltrates, but the changes seen in one biopsy specimen were limited and not always diagnostic. It seems that IPH of Japan and NCPF of India are the same disease, and perhaps hepatoportal sclerosis elsewhere is also the same disease.