Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension

Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://www.chictr.org.cn/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

A rabbit model of non- cirrhotic portal hypertension by repeated injections of E. coli through indwelling cannulation of the gastrosplenic vein

BACKGROUND: Non-cirrhotic portal hypertension is acommon cause of portal hypertension in developing coun-tries. To understand its etiopathogenesis we developed ananimal model by repeated portal endotoxemia inducedthrough the gastrosplenic vein.METHODS: Twenty-nine rabbits (1.5-2.0 kg) were divid-ed into control (group n = 13) and experimental ( groupn = 16) groups. Heat killed E. coli were injected throughan indwelling cannula into the gastrosplenic vein in pre-sensitized animals. The animals were sacriflced at 1, 3 and6 months.RESULTS: The mean portal pressure in group animalswas significantly (P < 0. 05) higher than in group at 1(17.5 ±3.4 vs 10.4±2.2 mmHg), 3 (17.8±1.3 vs7.2 +3.6mmHg), and 6 (19.8±3.1 vs 10.3±4.8 mmHg) months.Similarly, the mean splenic weight in group was signifi-cantly greater than in group (P <0.05). Histopathologi-cally, the spleen showed medullary congestion, hemosid-rin-laden macrophages and mild fibrosis. Histologically,the liver had normal parenchyma with mild portal lympho-cytic infiltrates and kupffer cell hyperplasia. No significantanomalies were detected by liver function tests.CONCLUSIONS: The rabbit model showed significantsplenomegaly with a persistent increase in portal pressureand mild fibrosis without hepatic parenchymal injury, quiteakin to non-cirrhotic portal fibrosis as seen in humans. Re-current intra-abdominal infection may play an importantrole in the pathogenesis of non-cirrhotic portal fibrosis.

Protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats

Objective:To observe the protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats.Methods:All rats were randomly divided into normal control group,cirrhosis and treatment group.Thioacetamide was used to establish rat model of cirrhotic portal hypertension.The necrotic tissue of gastric mucosa ulcer focus,degree of neutrophils infiltration at the ulcer margin,portal pressure,portal venous flow,abdominal aortic pressure,abdominal aortic blood flow at front end,gastric mucosal blood flow（GMBF）,glycoprotein（GP）of gastric mucosa,basal acid secretion,H’ back-diffusion,gastric mucosal damage index,NO,prostaglandin E2（PGE2） and tumor necrosis factor-α（TNF-α） were determined respectively,and the pathological changes of gastric mucosa were also observed by microscope.Results:Compared with cirrhosis group and the control group,the ulcer bottom necrotic material,gastric neutrophil infiltration and UI of the treatment group were all decreased significantly（P【0.01）,GMBF value,GP values,serum NO,PGE2,TNF- a were all significantly increased.Conclusions:Omeprazole has an important protective effect on gastric mucosal and it can increase gastric mucosal blood flow and related to many factors.

Pathological abnormalities in splenic vasculature in non-cirrhotic portal hypertension:Its relevance in the management of portal hypertension

BACKGROUND Portal hypertension(PH)is associated with changes in vascular structure and function of the portosplenomesenteric system(PSMS).This is referred to as portal hypertensive vasculopathy.Pathological abnormalities of PSMS has been described in the literature for cirrhotic patients.Raised portal pressure and hyperdynamic circulation are thought to be the underlying cause of this vasculopathy.In view of this,it is expected that pathological changes in splenic and portal vein similar to those reported in cirrhotic patients with PH may also be present in patients with non-cirrhotic PH(NCPH).AIM To investigate pathological abnormalities of splenic vein in patients with NCPH,and suggest its possible implications in the management of PH.METHODS A prospective observational study was performed on 116 patients with NCPH[Extrahepatic portal vein obstruction(EHPVO):53 and non-cirrhotic portal fibrosis(NCPF):63]who underwent proximal splenorenal shunt(PSRS),interposition shunt or splenectomy with devascularization in JIPMER,Pondicherry,India,a tertiary level referral center,between 2011-2016.All patients were evaluated by Doppler study of PSMS,computed tomography portovenogram and upper gastrointestinal endoscopy.An acoustic resonance forced impulse(ARFI)scan and abdomen ultrasound were done for all cases to exclude cirrhosis.Intraoperative and histopathological assessment of the harvested splenic vein was performed in all.The study group was divided into delayed and early presentation based on the median duration of symptoms(i.e.108 mo).RESULTS The study group comprising of 116 patients[77(66%)females and 39(34%)males]with NCPH had a median age of 22 years.Median duration of symptoms was 108 mo.The most common presentation in both EHPVO and NCPF patients was upper gastrointestinal bleeding(hematemesis and melena).The ARFI scan revealed a median score of 1.2(1.0-1.8)m/s for EHPVO and 1.5(0.9-2.8)m/s for NCPF.PSRS was performed in 84 patients(two of whom underwent interposition PSRS using a 10 mm Dacron graft);splenoadrenal shunt in 9;interposition mesocaval shunt in 5;interposition 1st jejunal to caval shunt in 1 patient and devascularization with splenectomy in 17 patients.Median presplenectomy portal pressure was 25(range:15-51)mm Hg.In 77%cases,the splenic vein was abnormal upon intraoperative assessment.Under macroscopic examination,wall thickening was observed in 108(93%),venous thrombosis in 32(28%)and vein wall calcification in 27(23%)cases.Upon examination under a surgical magnification loupe,21(18%)patients had intimal defects in the splenic vein.Histopathological examination of veins was abnormal in all cases.Medial hypertrophy was noted in nearly all patients(107/116),while intimal fibrosis was seen in 30%.Ninety one percent of patients with intimal fibrosis also had venous thrombosis.Vein wall calcification was found in 22%,all of whom had intimal fibrosis and venous thrombosis.The proportion of patients with pathological abnormalities in the splenic vein were significantly greater in the delayed presentation group as compared to the early presentation group.CONCLUSION Pathological changes in the splenic vein similar to those in cirrhotic patients with PH are noted in NCPH.We recommend that PH in NCPH be treated as systemic and pulmonary hypertension equivalent in the gastrointestinal tract,and that early aggressive therapy be initiated to reduce portal pressure and hemodynamic stress to avoid potential lethal effects.

Successful treatment of noncirrhotic portal hypertension with eculizumab in paroxysmal nocturnal hemoglobinuria: A case report

BACKGROUND Idiopathic non-cirrhotic portal hypertension(INCPH)is mainly associated with thrombophilia in Western countries.Paroxysmal nocturnal hemoglobinuria(PNH)is a rare hematologic disease that manifests with hemolytic anemia,thrombosis,and peripheral blood cytopenias.Portal and hepatic venous thrombosis were reported in PNH.A rare case of INCPH complicating PNH is described.CASE SUMMARY A 63-year old woman with a 2-year past medical history of PNH without treatment was admitted because of jaundice and refractory ascites requiring large volume paracentesis.Liver histology revealed portal venopathy with portal fibrosis and sclerosis,nodular regenerative hyperplasia,parenchymal ischemic changes,and focal sinusoidal and perivenular fibrosis without bridging fibrosis or cirrhosis,all indicative of INCPH.The flow cytometry confirmed PNH diagnosis and eculizumab treatment was initiated.Her condition was improved gradually,bilirubin was normalized 6 months following initiation of eculizumab,and 1 year later diuretics were stopped.CONCLUSION Eculizumab improved intravascular hemolysis and reversed clinical manifestations of INCPH in a patient with paroxysmal nocturnal hemoglobinuria.

Antibody and complement levels in patients with hypersplenism associated with cirrhotic portal hypertension and therapeutic principles

BACKGROUND Hypersplenism associated with cirrhotic portal hypertension is a common condition often resulting from hepatitis B-related cirrhosis.However,the levels of immunoglobulin(Ig)and complement in patients with hypersplenism associated with cirrhotic portal hypertension remain unclear.This study was undertaken to determine the levels of Ig and complement in these patients,the relationship between these levels and Child-Pugh class and their clinical significance.AIM To investigate the antibody(Ig)and complement levels in patients with hypersplenism associated with cirrhotic portal hypertension and their clinical significance.METHODS Clinical data of 119 patients with hypersplenism associated with cirrhotic portal hypertension were statistically analyzed and compared with those of 128 control patients.RESULTS IgA and IgG levels in patients with hypersplenism were significantly higher than controls(P<0.001).There was no significant difference in IgM between the two groups(P=0.109).C3 and C4 levels in patients with hypersplenism were significantly lower than controls(P<0.001).As liver function decreased,IgA and IgG levels increased(P<0.001),and C3 and C4 levels decreased(P<0.001).CONCLUSION Patients with hypersplenism associated with cirrhotic portal hypertension have significantly higher antibody(IgA and IgG)levels and significantly lower complement(C3 and C4)levels,which are both related to liver damage.Clinically,the administration of anti-hepatitis virus agents and protection of liver function should be strengthened.

Transjugular intrahepatic portosystemic shunt with radioactive seed strand for main portal vein tumor thrombosis with cirrhotic portal hypertension

BACKGROUND Patients with hepatocellular carcinoma complicated with main portal vein tumor thrombosis(mPVTT) and cirrhotic portal hypertension(CPH) have an extremely poor prognosis, and there is a lack of a clinically effective treatment paradigm.AIM To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS)combined with radioactive seed strand for the treatment of mPVTT patients with CPH.METHODS The clinical data of 83 consecutive patients who underwent TIPS combined with 125I seed strand placement for mPVTT and CPH from January 2015 to December 2018 were retrospectively reviewed. Procedure-related data(success rate, relief of portal vein pressure and CPH symptoms,and adverse events), PVTT response, and patient survival were assessed through a 2-year followup.RESULTS The success rate was 100.0% without perioperative death or procedure-related severe adverse events. The mean portal vein pressure was significantly decreased after the procedure(22.25 ± 7.33mmHg vs 35.12 ± 7.94 mmHg, t = 20.61, P < 0.001). The symptoms of CPH were all effectively relieved within 1 mo. The objective response rate of PVTT was 67.5%. During a mean follow-up of 14.5 ± 9.4 mo(range 1-37 mo), the cumulative survival rates at 6, 12 and 24 mo were 83.1%, 49.7%,and 21.8%, respectively. The median survival time was 12.0 ± 1.3 mo(95% confidence interval: 9.5-14.5). In multivariate Cox regression analysis, body mass index, Child-Pugh grade, cTNM stage,and PVTT response were independent prognostic factors(P < 0.05).CONCLUSION TIPS combined with radioactive seed strand might be effective and safe in treating mPVTT patients with CPH.

Systemic mastocytosis: A rare cause of non-cirrhotic portal hypertension

Mastocytosis is a clonal neoplastic disorder of the mast cells(MC) that can be limited to the skin(cutaneous mastocytosis) or involve one or more extracutaneous organs(systemic mastocytosis). The clinical manifestations of mastocytosis are heterogeneous ranging from indolent disease with a long-term survival to a highly aggressive neoplasm with survival of about 6 mo. Although liver involvement in aggressive systemic mastocytosis(ASM) is relatively common, the development of portal hypertension with or without cirrhosis is rare. We report a case of ASM without skin involvement in a 72-year-old caucasian male who presented with non-cirrhotic portal hypertension based on clinical, analytical, imagiological and endoscopic findings. Given the hematological picture, the correct diagnosis was established based on ancillary tests for MC using bone marrow aspirates and biopsy. Extensive involvement of the liver and gastrointestinal tract was histologically documented. The disease progressed rapidly and severe pancytopenia and recurrent upper gastrointestinal bleeding became the dominant problem. This case illustrates the challenge in establishing a diagnosis of ASM especially when the clinical picture is atypical and without skin involvement. Gastroenterologists should consider infiltrative disease, particularly systemic mastocytosis, as a differential diagnosis in a clinical case of portal hypertension of unknown etiology.

Portal hypertensive gastropathy:A systematic review of thepathophysiology,clinical presentation,natural history andtherapy

AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy(PHG) based on a systematic literature review.METHODS: Computerized search of the literature was performed via Pub Med using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG.PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepaticportosystemic-shunt or liver transplantation is highly successful ultimate therapies because they reduce the underlying portal hypertension.CONCLUSION: PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.

完全腹腔镜贲门周围血管离断术联合脾切除术对CPH的效果分析

目的:探究完全腹腔镜贲门周围血管离断术联合脾切除术治疗肝硬化门静脉高压症(CPH)患者的效果。方法:选取113例CPH患者,将其随机分为两组。对照组56例给予开腹贲门周围血管离断术联合脾切除术,观察组57例给予完全腹腔镜贲门周围血管离断术联合脾切除术,比较两组治疗效果。结果:观察组术后下床时间和住院时间均短于对照组;术中出血量、术后皮质醇、促肾上腺皮质激素、肾上腺素水平及并发症发生率均低于对照组;手术时间长于对照组,差异均有统计学意义(P<0.05)。术后两组患者ALT、AST、ALB、TBiL水平比较,差异均无统计学意义(P>0.05)。结论:完全腹腔镜贲门周围血管离断术联合脾切除术治疗肝硬化门静脉高压症可有效减少应激反应的发生和术中出血量,且并发症风险低。

TIPS治疗肝硬化门静脉血栓的临床疗效

目的 探讨经颈静脉肝内门体分流术(TIPS)治疗肝硬化合并门静脉血栓(PVT)的临床疗效。方法 选取17例肝硬化合并PVT,并有食管胃底静脉曲张破裂出血患者,对其进行TIPS治疗,术后进行随访6~25个月(平均16个月)。根据手术结果,分析手术治疗成功率、术后血管再通、曲张静脉缓解和再发出血情况。结果 17例患者TIPS手术成功14例,成功率82.3%。术前门静脉主干血栓9例,至随访结束1例未缓解,再通率88.9%,门静脉主干伴有分支血管血栓3例,2例部分缓解;2例伴有肠系膜上静脉血栓,术后均得到缓解。3例手术失败患者均未缓解。14例手术成功患者术后3个月、6个月再发出血分别为1例、2例,出血率为21.4%。术后10例曲张静脉转为轻度或消失,缓解率为76.9%。14例手术成功患者3例术后发生肝性脑病,治疗后好转。所有患者无严重并发症发生。结论 TIPS对于抗凝治疗失败的PVT患者具有非常好的技术成功率及临床疗效,明显提高了门静脉再通率,减少了门静脉高压相关并发症,疗效肯定,可作为一线治疗方法。

一组非肝硬化性门静脉高压症病因分析和诊断路径探讨

目的分析一组非肝硬化性门静脉高压(NCPH)患者的病因和诊断方法,归纳总结诊断路径。方法2020年9月~2022年3月广西医科大学第一附属医院收治的NCPH患者105例,常规临床检查和基因分析诊断。结果本组经综合检查,诊断肝前型69例(65.7%),肝内型21例(20.0%)、肝后型4例(3.8%)和未诊断11例(10.5);常见疾病为胰源性疾病22例(31.9%),门静脉阻塞15例(21.7%),血液性疾病15例(21.7%);主要诊断方法为影像学检查28例(40.6%),消化内镜检查14例(20.3%),骨髓穿刺活检术12例(17.4%);NCPH病因诊断前三位的方法依次为影像学检查(33.3%)、综合分析(18.1%)和消化内镜(13.9%)检查。结论NCPH以肝前型门静脉高压为常见,常规行实验室和影像学检查,必要时行消化内镜和骨髓穿刺活检术可明确诊断。对于常规检查仍不能诊断的,再考虑肝内型和肝后型门静脉高压,行肝穿刺活检或下腔静脉穿刺造影等检查往往能进一步明确诊断。

肝硬化心肌病的发病机制研究进展

肝硬化心肌病是一种在终末期肝病中出现的心肌功能障碍,它以收缩和舒张功能障碍、心脏结构改变和电生理异常为特征,是一种已知但了解不多的肝硬化并发症,其对肝硬化患者的生存和预后有不良影响。肝功能不全与门静脉高压下的全身炎症反应共同参与其发生发展。文章主要从肝功能不全导致的循环胆汁酸水平升高及门静脉高压下全身慢性炎症反应两方面对近年来肝硬化心肌病发病机制的研究进展进行综述。

ORIGINAL ARTICLES CALCIUM CHANNEL BLOCKERS IN CIRRHOTIC PATIENTS WITH PORTAL HYPERTENSION

Four calcium channel blockers, i.e. nifedipine, verapamil, cinnarizine and tetrandrine are currently available and used widely in treating cardiovascular diseases. To confirm the effects, if any, of calcium channel blockers on cirrhotic patients with portal hypertension, a study was performed on esophageal variceal pressure and rebleeding rate of esophageal varices after 2 years by using calcium channel blocker in 321 patients from some 23 hospitals. The results demonstrated that the calcium channel blockers could significantly reduce the esophageal variceal pressure and the portal blood flow in cirrhotic patients with portal hypertension. The proportion of patients with no recurrent gastrointestinal bleeding after 2 years medication of tetrandrine was 87.9% in tetrandrine group, significantly higher than those in the other 4 groups (P<0.05). It is suggested that tetrandrine should be more effective for cirrhotic patients with portal hypertension in preventing recurrent variceal bleeding.

血栓性非硬化门脉高压症的遗传易感性研究进展

肝外型非硬化门脉高压症(NH-PH)是以肝外非硬化门静脉血栓形成和Budd-Chiari综合征(布加综合征)为代表的门脉高压疾病,二者的病因都归于内脏静脉血栓,具有多种共同的遗传易感因素。该文综述了血栓性NH-PH的遗传易感性研究进展,并对已报道的遗传易感基因及其突变位点进行整理分析,同时提示其他潜在的遗传易感基因靶点,以期为后续临床大样本验证提供筛选靶标,为NH-PH的早期诊断和发病机制研究提供新思路。

常规超声与超声造影定量评估肝硬化门静脉高压患者经颈静脉肝内门体静脉支架分流术后疗效的对比研究

目的应用常规超声与超声造影(CEUS)定量评估肝硬化门静脉高压(PHT)患者经颈静脉肝内门体静脉支架分流术(TIPS)后疗效,对比分析其临床价值。方法选取在我院接受TIPS治疗的PHT患者85例,均于TIPS前1 d及TIPS后1个月行常规超声检查和CEUS检查,获取门静脉内径(PVD)、脾静脉内径(SVD)、肠系膜上静脉内径(SMVD)、门静脉血流速度(PVV)、脾静脉血流速度(SVV)、肠系膜上静脉血流速度(SMVV),以及到达时间(AT)、达峰时间(TTP)、峰值强度(PI)、上升支斜率(AS);依据指南推荐方法检测TIPS前后门静脉压力梯度(PPG);比较PHT患者上述参数的差异。采用Pearson相关分析法分析PHT患者TIPS前常规超声及CEUS定量参数与TIPS后PPG的关系。结果常规超声检查结果显示,PHT患者TIPS前后PVD、SVD、SMVD、PVV、SVV、SMVV比较,差异均无统计学意义;CEUS检查结果显示,PHT患者TIPS后AT、TTP均较TIPS前缩短,PI、AS均较TIPS前增高,差异均有统计学意义(均P<0.05)。PHT患者TIPS前后PPG分别为(31.76±6.28)mmHg(1 mmHg=0.133 kPa)、(13.42±2.03)mmHg,差异有统计学意义(t=25.619,P<0.05)。Pearson相关性分析显示,PHT患者TIPS前AT、TTP与TIPS后PPG均呈正相关(均P<0.05),PI、AS与TIPS后PPG均呈负相关(均P<0.05);PHT患者TIPS前常规超声参数PVV、SVV、SMVV、PVD、SVD、SMVD与TIPS后PPG均无相关性。结论CEUS较常规超声可更准确地定量评估PHT患者TIPS前后门静脉压力变化,在TIPS后短期疗效评估中具有较好的临床价值。

光谱法研究天然牛磺酸与肝硬化门静脉高压大鼠的肝组织蛋白相互作用

目的:通过光谱法研究天然牛磺酸(Taurine)与肝硬化门静脉高压大鼠的肝组织蛋白相互作用并探讨其作用机制。方法:将120只大鼠按随机数字法分成正常组、模型组、心得安组、天然牛磺酸组四组,每组30只,除正常组外,其余组用四氯化碳(carbon tetrachloride, CCL4)制备肝硬化门脉高压大鼠模型,造模同时给药。心得安组喂心得安,天然牛磺酸组喂天然牛磺酸,模型组喂等量生理盐水,疗程10周,治疗后对比各组门脉高压数值,并测定不同温度下各组天然牛磺酸药物-大鼠肝组织蛋白体系荧光光谱和天然牛磺酸紫外吸收光谱,根据光谱数据进行分析。结果:天然牛磺酸组大鼠门脉血流量(portal vein flow, PVF)、门脉压力(portal vein pressure, PVP)、门脉阻力(PVR)较心得安组、模型组更低,平均动脉压(mean arterial pressure, MAP)较高。各组大鼠肝组织蛋白的Kq值均大于最大动态猝灭速率2.0×10^(10)L/(mol·s)。大鼠肝组织蛋白体系:焓变(△H):-8 707.633 6;熵变(△S):33.413 95。正常组吉布斯自由能变化(△G)、△H均为负值,△S为正值;天然牛磺酸组△G、△H均为正值,△S为负值,模型组无明显规律。正常组、模型组、天然牛磺酸组R值分别为1.77、2.35、2.28 nm, r值分别为1.24、1.31、6.56。结论:天然牛磺酸具有抗肝纤维化,减轻门脉高压的作用,其机制可能是改变了肝硬化门脉高压大鼠的肝脏组织蛋白结构,从而减轻肝损害。

腹腔镜辅助改良Sugiura手术与脾切除断流术对肝硬化门静脉高压症患者肝纤维化和凝血功能及再出血率的影响

目的探讨腹腔镜辅助改良Sugiura手术与脾切除断流术对肝硬化门静脉高压症(PHT)患者肝纤维化、凝血功能及再出血率的影响。方法选取2021年1月至2022年6月监利市第五人民医院收治的85例肝硬化PHT患者作为研究对象,根据手术方式不同分为断流组(n=39)与改良组(n=46)。断流组给予脾切除断流术治疗,改良组给予改良Sugiura手术治疗,比较两组手术情况及住院时间、门静脉血流动力学指标、肝纤维化指标、并发症发生情况及再出血率。结果两组手术时间、术中出血量及住院时间比较差异无统计学意义。术后,两组门静脉内径(Dpv)均短于术前,门静脉血流速度(Vpv)、门静脉血流量(Qpv)均慢于术前,且改良组Dpv短于断流组,Vpv、Qpv均慢于断流组,差异有统计学意义(P<0.05)。术后,两组透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)、Ⅳ型胶原(Ⅳ-C)水平均低于术前,且改良组低于断流组,差异有统计学意义(P<0.05)。术后,两组纤维蛋白原(Fg)水平均高于术前,凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)均短于术前,且改良组Fg水平高于断流组,PT、APTT均短于断流组,差异有统计学意义(P<0.05)。改良组并发症发生率、再出血率均低于断流组,差异有统计学意义(P<0.05)。结论与脾切除断流术相比,腹腔镜辅助改良Sugiura手术治疗肝硬化PHT治疗效果更佳,可显著改善患者肝功能,延缓肝纤维化进程,降低再出血率,安全性较佳。

特发性非肝硬化门静脉高压症的关键基因通路筛选与潜在中药预测

目的采用生物信息学方法对特发性非肝硬化门静脉高压症(idiopathic non-cirrhotic portal hypertension,INCPH)的基因芯片数据进行分析,获取疾病发生发展的关键基因和信号通路,预测治疗INCPH的潜在中药。方法从基因表达综合数据库(gene expression omnibus,GEO)数据库下载关于INCPH的基因芯片数据集GSE77627,利用R语言对数据进行标准化并筛选INCPH的差异基因(differential genes,DEGs),并利用Metascape数据库对所有DEGs进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析,并通过STRING数据库构建蛋白-蛋白互作网络;同时,利用CytoHubba插件筛选Degree值排名前15的DEGs作为关键基因。随后将关键基因与医学本体信息检索平台互相映射,以P<0.05为标准筛选治疗INCPH的潜在中药,并从TCMSP数据库中筛选潜在中药有效成分,导入Cytoscape软件构建中药相关网络图,并预测关键作用靶点。结果共获得1880个DEGs,其中表达上调的基因有1061个,表达下调的基因有819个。利用STRING数据库以及Cytoscape环境下的cytoHubba插件分析DEGs,筛选Dgree值排名15位的基因作为关键基因,分别是RPS27A、CDC42、EIF4E、MAPK1、PIK3R1、RPS6、RPS9、RPS8、RPL15、RPL27A、RPL24、RPL27、RPL26、RPL12和MAPK14。GO、KEGG分析显示DEGs主要参与配子生成、糖尿病并发症中的AGE-RAGE信号通路等信号通路。结论筛选得到干预INCPH的潜在中药为人参、丹参、黄芪等,可能成为INCPH治疗的潜在分子药物来源。

内镜及TIPS治疗特发性非肝硬化门脉高压并静脉曲张出血的长期效果及预后分析

目的探讨内镜及经颈静脉肝内门体分流术(transjugular intrahepatic portosystemic shunt,TIPS)治疗特发性非肝硬化门脉高压症(idiopathic non-cirrhotic portal hypertension,INCPH)患者静脉曲张出血后的长期临床效果及预后影响因素。方法回顾性分析2000年1月-2013年12月在西安市中心医院行内镜(内镜组)或TIPS(TIPS组)治疗的INCPH静脉曲张出血患者的临床资料,规律随访观察再出血及生存情况。结果在随访时间内,共有12例患者出现静脉曲张再出血,1年、2年、4年再出血率分别是5.0%、10.7%和38.3%,两组比较,差异无统计学意义(P=0.7445)。共有8例INCPH患者死亡,所有患者的1年、2年、4年生存率分别为97.4%、92.2%、78.2%,两组比较,差异无统计学意义(P=0.645)。年龄(HR=1.974,P=0.038)和Child-Pugh评分(HR=2.462,P=0.034)是预测患者生存的独立危险因素。结论内镜与TIPS可有效预防INCPH患者的静脉曲张再出血,且患者有较高的生存率。