肝硬化门静脉高压上消化道黏膜病变内镜检查临床分析

目的探讨肝硬化门静脉高压上消化道黏膜病变内镜检查效果。方法将我院2016年1月—2018月1月收治的100例肝硬化门静脉高压上消化道黏膜病变患者作为研究对象,均进行内镜检查,观察上消化道病变类型,并根据肝硬化静脉曲张的程度将其分为轻度曲张、中度曲张和重度曲张,分析曲张程度与上消化道黏膜病变之间的关系。结果 100例患者中均出现不同程度的曲张,曲张位于食管有62例,曲张位于胃底有18例,曲张位于食管-胃底有20例。按照肝硬化静脉曲张的程度将其分为轻度曲张13例、中度曲张61例和重度曲张26例。随着静脉曲张程度升高,患者上消化道黏膜病变的发生率也相应升高。结论肝硬化门静脉高压上消化道黏膜病变内镜检查临床效果确切,可有效明确曲张静脉情况和消化道黏膜病变情况,准确判断病情,为治疗提供依据。

Effect of endotoxin on portal hemodynamic in rats

AIM: To study the effects of endotoxin on portal hemodynamic of normal and noncirrhotic portal hypertensive rats. METHODS: Normal rats were intraperitoneally injected with 0.1, 0.25, 0.5, 1.0, 2.0, 4.0mg.kg(-1) of lipopolysaccharide(LPS) respectively, portal vein ligation(PVL) and intrahepatic portal occlusion (IPO) rats as well as sham-operated rats were treated with an intraperitoneal injection of 1.0mg.kg(-1) of LPS, the portal vein pressure(PVP), portal venous flow(PVF), inferior vena cava pressure(IVCP) and portal vein resistance(PVR) were detected 4 hours after injection. RESULTS: PVF of the 5 groups of rats accepting intraperitoneal injection of LPS were increased from 14.0 to 18.0, 22.2, 26.2, 34.8, 39.6, 38.8 mL.min(-1) 4 hours after injection of LPS(P【0.01). PVP of the 4 groups of rats accepting more than 0.1mg/kg.b.w of LPS was increased from 1.04 to 1.25, 1.50, 1.80, 1.95, 2.05 kPa(P【0.01). The increments of PVF and PVP were in a dose-dependent manner of LPS. PVR of the 5 groups of rats was decreased from 51 to 42,44,48,45,44,47 kPa.min.L(-1) (P【0.05) and no dose-dependent manner was observed. PVF of PVL, IPO and sham-operated rats increased from 22.6 to 32.8, 22.0 to 28.0, 14.0 to 34.8 mL.min(-1) (P【0.01), and PVP increased from 1.86 to 2.24, 1.74 to 1.95, 1.04 to 1.80 kPa(P【0.01), PVR decreased from 71 to 61, 67 to 61, 52 to 44 kPa.min.L(-1) after intraperitoneal injection of 1mg.kg(-1) of LPS. The increments of PVF and PVP of PVL and IPO rats were significantly less than the sham-operated rats(P【0.01), There was no significant difference between the amounts of PVR decreased in the two groups of PHT model rats and sham-operated rats(P】0.05) after intraperitoneal injection 1mg.kg(-1) of LPS. CONCLUSION: Endotoxin could prompt portal hypertension of the normal and noncirrhotic portal hypertensive rats by increasing portal blood flow mainly.

Effect of transjugular intrahepatic portosystemic shunt on pulmonary gas exchange in patients with portal hypertension and hepatopulmonary syndrome

AIM: To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on pulmonary gas exchange and to evaluate the use of TIPS for the treatment of hepatopulmonary syndrome (HPS).METHODS: Seven patients, three of them with advanced HPS, in whom detailed pulmonary function tests were performed before and after TIPS placementat the University of Alabama Hospital and at the Hospital Clinic, Barcelona, were considered.RESULTS: TIPS patency was confirmed by hemodynamic evaluation. No changes in arterial blood gases were observed in the overall subset of patients. Transient arterial oxygenation improvement was observed in only one HPS patient, early after TIPS, but this was not sustained 4 mo later.CONCLUSION: TIPS neither improved nor worsened pulmonary gas exchange in patients with portal hypertension. This data does not support the use of TIPS as a specific treatment for HPS. However, it does reinforce the view that TIPS can be safely performed for the treatment of other complications of portal hypertension in patients with HPS.

A large congenital and solitary intrahepatic arterioportal fistula in an old woman

Arterioportal fistula(APF)is a rare cause of portal hypertension and may lead to death.APF can be congenital,post-traumatic,iatrogenic(transhepatic intervention or biopsy)or related to ruptured hepatic artery aneurysms.Congenital APF is a rare condition even in children.In this case report,we describe a 73-year-old woman diagnosed as APF by ultrasonography,computed tomography,and hepatic artery selective arteriography.The fistula was embolized twice but failed,and she still suffered from alimentary tract hemorrhage.Then,selective arteriography of the hepatic artery was performed again and venae coronaria ventriculi and short gastric vein were embolized.During the 2-year follow-up,the patient remained asymptomatic.We therefore argue that embolization of venae coronaria ventriculi and short gastric vein may be an effective treatment modality for intrahepatic APF with severe upper gastrointestinal bleeding.

Laparoscopic and open splenectomy and azygoportal disconnection for portal hypertension

AIM： To compare the outcomes of laparoscopic and open splenectomy and azygoportal devascularization for portal hypertension. METHODS： From June 2006 to March 2009, laparoscopic splenectomy and azygoportal disconnection （LSD） were performed on 28 patients with cirrhosis, bleeding due to portal hypertension, and secondary hypersplenism. Success was achieved in 26 patients. Demographic, intraoperative, and postoperative variables of the patients were compared. RESULTS： Success of laparoscopic splenectomy and azygoportal disconnection was achieved in all but two patients （7.14%） who required open splenectomy and azygoportal devascularization （OSD）. The operation time was significantly longer in patients undergoing LSD than in those undergoing OSD （235 ± 36 min vs 178 ± 47 rain, P 〈 0.05）. The estimated intraoperative blood loss was much more in patients receiving OSD than in those receiving LSD （420 ± 50 mL vs 200 ± 30 mL, P 〈 0.01）. The proportion of patients undergoing laparoscopic and open splenectomy and azygoportal disconnection who received transfusion of packed red blood cells during or after the operation was 23.08% and 38.46%, respectively （P 〈 0.05）. The time of first oral intake was faster in patients after LSD than in those after OSD （1.5 ± 0.7 d vs 3.5 ± 1.6 d, P 〈 0.05）. The hospital stay of patients after LSD was shorter than that of patients after OSD （6.5 ± 2.3 d vs 11.7 ± 4.5 d, P 〈 0.05）. The pain requiring medication was less severe in patients after LSD than in those after OSD （7.69% vs 73.08%, P 〈 0.001）. The overall complication rate was lower in patients after LSD than in those after OSD （19.23% vs 42.31%, P 〈 0.05）.CONCLUSION： Laparoscopic splenectomy and azygoportal disconnection are the feasible, effective, and safe surgical procedure, and are advantageous over minimally invasive surgery for bleeding portal hypertension and hypersplenism.

Stability of a rat model of prehepatic portal hypertension caused by partial ligation of the portal vein

AIM： To study the stability of portal hypertension （PHT） caused by partial ligation of the portal vein ligation （PVL） in a rat model.METHODS： Thirty male adult Wistar rats were divided into two groups： 10 in Group Ⅰ received a sham operation; and 20 in Group Ⅱreceived partial PVL. Portal vein pressure （PVP） was measured at four time periods： before ligation, 2 wk, 6 wk and 10 wk postsurgery. Portal venography, blood sampling and liver and spleen pathological examinations were conducted at 10 wk after surgery.RESULTS： The PVP was 9.15± 0.58 cmH2O before ligation, and increased to 17.32 ±0.63 cmH2O 2 wk after PVL. By repeat measurement of the PVP in each rat, it was shown to remain elevated for 10 wk. There were no significant differences in the pressure measurements at 2 wk, 6 wk and 10 wk. Varices were found mainly in the mesenteric vein 2 wk after PVL, which were more obvious later, while these manifestations were similar at week 6 and week 10. Portal venography demonstrated the varices and collaterals. There was no significant change in liver pathology. The volume of the spleen was enlarged 2-fold after ligation, and the sinus of the spleen was enlarged due to congestion. Significant sinus endothelial cell proliferation was observed, but no evidence of hypersplenia was found on hemogram and biochemical examination.CONCLUSION： These findings suggest that a satisfactory prehepatic PHT rat model can be obtained by partial ligation of the portal vein, and this PHT rat model was stable for at least 10 wk.

Hyperammonemia,brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication

AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.

Adrenomedullin in cirrhotic and non-cirrhotic portal hypertension

AIM:Adrenomedullin (ADM) is a potent vasodilator peptide. ADM and nitric oxide (NO) are produced in vascular endothelial cells.Increased ADM level has been linked to hyperdynamic circulation and arterial vasodilatation in cirrhotic portal hypertension (CPH).The role of ADM in non-cirrhotic portal hypertension (NCPH) is unknown,plasma ADM levels were studied in patients with NCPH,compensated and decompensated cirrhosis in order to determine its contribution to portal hypertension (PH) in these groups. METHODS:There were 4 groups of subjects.Group 1 consisted of 27 patients (F/M:12/15) with NCPH due to portal and/or splenic vein thrombosis (mean age:41±12 years),group 2 consisted of 14 patients (F/M:6/8) with compensated (Child-Pugh A) cirrhosis (mean age:46±4), group 3 consisted of 16 patients (F/M:6/10) with decompensated (Child-Pugh C) cirrhosis (mean age:47±12). Fourteen healthy subjects (F/M:6/8) (mean age:44±8) were used as controls in Group 4.ADM level was measured by ELISA.NO was determined as nitrite/nitrate level by chemoluminescence. RESULTS:ADM level in Group 1 (236±61.4 pg/mL) was significantly higher than that in group 2 (108.4±28.3 pg/mL) and group 4 (84.1±31.5 pg/mL) (both P<0.0001) but was lower than that in Group3 (324±93.7 pg/mL) (P=0.002).NO level in group 1 (27±1.4 μmol/L) was significantly higher than that in group 2 (19.8±2.8 μmol/L) and group 4 (16.9±1.6 μmol/L) but was lower than that in Group 3 (39±3.6 μmol/L) (for all three P<0.0001).A strong correlation was observed between ADM and NO levels (r=0.827,P<0.0001). CONCLUSION:Adrenomedullin and NO levels were high in both non-cirrhotic and cirrhotic portal hypertension and were closely correlated,Adrenomedullin and NO levels increased proportionally with the severity of cirrhosis,and were significantly higher than those in patients with NCPH. Portal hypertension plays an important role in the increase of ADM and NO.Parenchymal damage in cirrhosis may contribute to the increase in these parameters.

Splenectomy with endoscopic variceal ligation is superior to splenectomy with pericardial devascularization in treatment of portal hypertension

AIM: To investigate the therapeutic efficacy and complications of splenectomy with endoscopic variceal ligation (EVL) and splenectomy with pericardial devascularization (i.e. Hassab’s operation) in patients with portal hypertension. METHODS: A total of 103 patients with liver cirrhosis and portal hypertension were randomly selected to receive either splenectomy with EVL (n = 53, group A) or Hassab’s operation (n = 50, group B). RESULTS: The portal blood flow volume, the presence of portal vein thrombosis, gastric emptying time and free portal venous pressure (FPP) before and after the operation were determined. Patients were followed up for up to 64 mo with an average of 45 mo, and the Dagradi classification of variceal veins and the grading of portal hypertension gastropathy (PHG) were evaluated. It was found that all esophageal varices were occluded or decreased to grade Ⅱ or less in both groups. There was little difference in the recurrence rate of esophageal varices (11.9% vs 13.2%) and the re-bleeding rate (7.1% vs 5.3%) between groups A and B. The incidence of complications and the percentage of patients with severe PHG after the operation were significantly higher in group B (60.0% and 52.0%) than in group A (32.1% and 20.8%, P < 0.05). No patients died of operation-related complications. There was no significant difference in gastric emptying time, FPP and portal blood flow volume between the two groups. CONCLUSION: The results suggest that splenectomy with EVL achieves similar therapeutic efficacy to that of Hassab’s operation in terms of the recurrence rate of esophageal varices and the re-bleeding rate, but theformer results in fewer and milder complications.

Portal hypertension due to portal venous thrombosis:Etiology, clinical outcomes

The thrombophilia in adult life has major implications in the hepatic vessels. The resulting portal vein thrombosis has various outcomes and complications. Esophageal varices, portal gastropathy, ascites, severe hypersplenism and liver failure needing liver transplantation are known well. The newly formed collateral venous circulation showing itself as pseudocholangicarcinoma sign and its possible clinical reflection as cholestasis are also known from a long time. The management strategies for these complications of portal vein thrombosis are not different from their counterpart which is cirrhotic portal hypertension, but the prognosis is unquestionably better in former cases. In this review we present and discuss the portal vein thrombosis, etiology and the resulting dinical pictures. There are controversial issues in nomenclature, management （including anticoagulation problems）, follow up strategies and liver transplantation. In the light of the current knowledge, we discuss some controversial issues in literature and present our experience and our proposals about this group of patients.

Nitroglycerine effects on portal vein mechanics and oxidative stress in portal hypertension

AIM:Тo examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension.METHODS:Thirty healthy controls and 39 patients with clinically verified portal hypertension and increasedvascular resistance participated in the study.Liver di-ameters,portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection.Cross-section area,portal flow and index of vascular resistance were calculated.In collected blood samples,superoxide anion radical (O 2-),hydrogen per-oxide (H 2 O 2),index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO 2-) were determined.Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration.RESULTS:Oxidative stress parameters changed sig-nificantly during the study.H 2 O 2 decreased at the end of study,probably via O 2-mediated disassembling in Haber Weiss and Fenton reaction;O 2-increased signifi-cantly probably due to increased diameter and tension and decreased shear rate level.Consequently O 2-and H 2 O 2 degradation products,like hydroxyl radical,initi-ated lipid peroxidation.Increased blood flow was to some extent lower in patients than in controls due to double paradoxes,flow velocity decreased,shear rate decreased significantly indicating non Newtonian char-acteristics of portal blood flow.CONCLUSION:This pilot study could be a starting point for further investigation and possible implemen-tation of some antioxidants in the treatment of portal hypertension.

Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

AIM： To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 dafer ligation when portal pressure is spontaneously normalized. METHODS： Adult male Wistar rats were divided into four groups： Group Ⅰ： Sham14d, sham operated; Group Ⅱ： PHil, portal vein stenosis, （both groups were used 14 days after surgery）; Group Ⅲ： Sham4od, Sham operated and Group Ⅳ： PH4od Portal vein stenosis （Groups Ⅱ and Ⅳ used 40 d afer surgery）. Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS： Forty days afer stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION： The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment.

Role of PGI_2 in the formation and maintenance of hyperdynamic circulatory state of portal hypertensive rats

AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCI4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitro-L-arginine (L-NNA)group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1mL of saline, L-NNA (3.3 mg/kg-d) and INDO (5 mg/kg·d) respectively through gastric tubes for one week/then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α, a stable hydrolytic product of PGI2, was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGFla (pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats (1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11, 75.21±6.89) were significantly higher than those in SO rats (725.53±105.54, 58.79±8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGFla and serum NO2/7NO3-in IHPH and PHPH rats (P<0.05) .Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased(P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto- concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.

Intraoperative pulmonary hypertension occurred in an asymptomatic patient with pre-existent liver cirrhotic and portal hypertension

Portopulmonary hypertension(PPH) is clinically defined as the development of pulmonary arterial hypertension complicated by portal hypertension,with or without advanced hepatic disease.Physical signs may be absent in mild to moderate PPH and only appear in a hyperdynamic circulatory state.Similar signs of advanced liver disease can be observed in severe PPH,with ascites and lower extremity edema.Pulmonary hypertension is usually diagnosed after anesthetic induction during liver transplantation(LT).We present intraoperative pulmonary hypertension in a 41-year-old male patient with hepatic cirrhosis.Since this patient had no preoperation laboratory data supporting the diagnosises of pulmonary hypertension and was asymptomatic for a number of years,it was necessary to send him to the intensive care unit after operation.Further study should be focued on the diagnosis and treatment of pulmonary arterial hypertension in order to reduce its mortality.

Percutaneous portal venoplasty and stenting for anastomotic stenosis after liver transplantation

AIM:To review percutaneous transhepatic portal venoplasty and stenting(PTPVS)for portal vein anastomotic stenosis(PVAS)after liver transplantation (LT). METHODS:From April 2004 to June 2008,16 of 18 consecutive patients(11 male and 5 female;aged 17-66 years,mean age 40.4 years)underwent PTPVS for PVAS.PVAS occurred 2-10 mo after LT(mean 5.0 mo). Three asymptomatic patients were detected on routine screening color Doppler ultrasonography(CDUS). Fifteen patients who also had typical clinical signs of portal hypertension(PHT)were identified by contrastenhanced computerized tomography(CT)or magnetic resonance imaging.All procedures were performed under local anesthesia.If there was a PVAS<75%, the portal pressure was measured.Portal venoplasty was performed with an undersized balloon and slowly inflated.All stents were deployed immediately following the predilation.Follow-ups,including clinical course, stenosis recurrence and stent patency which were evaluated by CDUS and CT,were performed. RESULTS:Technical success was achieved in all patients.No procedure-related complications occurred. Liver function was normalized gradually and the symptoms of PHT also improved following PTPVS.In 2 of 3 asymptomatic patients,portal venoplasty and stenting were not performed because of pressure gradients<5 mmHg.They were observed with periodic CDUS or CT.PTPVS was performed in 16 patients.In 2 patients,the mean pressure gradients decreased from 15.5 mmHg to 3.0 mmHg.In the remaining 14 patients,a pressure gradient was not obtained because of>75%stenosis and typical clinical signs of PHT.In a 51-year-old woman,who suffered from massive ascites and severe bilateral lower limb edema after secondary LT,PVAS complicated hepatic vein stenosis and inferior vena cava(IVC)stenosis. Before PTPVS,a self-expandable and a balloonexpandable metallic stent were deployed in the IVC and right hepatic vein respectively.The ascites and edema resolved gradually after treatment.The portosystemic collateral vessels resulting from PHT were visualized in 14 patients.Gastroesophageal varices became invisible on poststenting portography in 9 patients.In a 28-yearold man with hepatic encephalopathy,a pre-existing meso-caval shunt was detected due to visualization of IVC on portography.After stenting,contrast agents flowed mainly into IVC via the shunt and little flowed into the portal vein.A covered stent was deployed into the superior mesenteric vein to occlude the shunt. Portal hepatopetal flow was restored and the IVC became invisible.The patient recovered from hepatic encephalopathy.A balloon-expandable Palmaz stent was deployed into hepatic artery for anastomotic stenosis before PTPVS.Percutaneous transhepatic internal-external biliary drainage was performed in 2 patients with obstructive jaundice.Portal venous patency was maintained for 3.3-56.6 mo(mean 33.0 mo) and all patients remained asymptomatic.CONCLUSION:With technical refinements,early detection and prompt treatment of complications,and advances in immunotherapy,excellent results can be achieved in LT.

Bile duct ligation in rats: A reliable model of hepatorenal syndrome?

The two most widely used experimental models of advanced liver disease are the administration of carbon tetrachloride, and common bile duct ligation (BDL), however, neither has been systematically evaluated as a model of hepatorenal syndrome (HRS). The BDL model in rats, studied at diverse time points, induced a progressive renal dysfunction without structural changes in the kidney. The authors concluded that BDL is a good model for further studies of HRS and its treatment. However, the renal impairment observed at the acute phase of the BDL model is based on a different pathophysiology than that of HRS. Specifi cally, in acute obstructive jaundice, cholemia predominates over parenchymal liver disease (reversible at this stage without portal hypertension or cirrhosis) and independently induces negative inotropic and chronotropic effects on the heart, impaired sympathetic vasoconstriction response and profound natriuresis and diuresis that might lead to volume depletion. In addition, systemic endotoxemia contributes to the prerenal etiology of renal impairment and promotes direct nephrotoxicity and acute tubular necrosis. On the other hand, the renal failure observed in the chronic BDL model (with development of biliary cirrhosis, portal hypertension and ascites) shares pathophysiological similarities with HRS, but the accordance of the chronic BDL model to the diagnostic criteria of HRS (e.g. absence of spontaneous bacterial peritonitis, no renal function improvement after plasma volume expansion) should have been confirmed. In conclusion, we think that the BDL model is not suitable for the study of the natural history of HRS, but the chronic BDL model might be valid for the study of established HRS and its potential therapies.

Portal hypertensive colopathy is associated with portal hypertension severity in cirrhotic patients

AIM： To assess the prevalence of portal hypertension （PH） related colorectal lesions in liver transplant candidates, and to evaluate its association with the severity of PH. METHODS： Between October 2004 and December 2005, colonoscopy was performed in 92 cirrhotic liver transplant candidates. We described the lesions resulting from colorectal PH and their association with the grade of PH in 77 patients who underwent measurement of hepatic venous pressure gradient （HVPG）. RESULTS： Mean age was 55 years and 80.7% of patients were men. The main etiology of cirrhosis wasalcoholism （45.5%）. Portal hypertensive colopathy （PHC） was found in 23.9%, colonic varices in 7.6% and polyps in 38% of patients （adenomatous type 65.2%）. One asymptomatic patient had a well-differentiated adenocarcinoma. The manifestations of colorectal PH were not associated with the etiology of liver disease or with the Child-Pugh grade. Ninety percent of patients with colopathy presented with gastroesophageal varices （GEV）, and 27.5% of patients with GEV presented with colopathy （P = 0.12）. A relationship between higher values of HVPG and presence of colopathy was observed （19.9：1：6.2 mmHg vs 16.8 ± 5.4 mmHg, P = 0.045）, but not with the grade of colopathy （P = 0.13）. Preneoplastic polyps and neoplasm （P = 0.02） and spontaneous bacterial peritonitis （P = 0.006） were more prevalent in patients with colopathy. We did not observe any association between previous β-blocker therapy and the presence of colorectal portal hypertensive vasculopathy. CONCLUSION： PHC is common in cirrhotic liver transplant candidates and is associated with higher portal pressure.

Staging of portal hypertension and portosystemic shunts using dynamic nuclear medicine investigations

AIM： To explore portal hypertension and portosystemic shunts and to stage chronic liver disease （CLD） based on the pathophysiology of portal hemodynamics. METHODS： Per-rectal portal scintigraphy （PRPS） was performed on 312 patients with CLD and liver angioscintigraphy （LAS） on 231 of them. The control group included 25 healthy subjects. We developed a new model of PRPS interpretation by introducing two new parameters, the liver transit time （LTT） and the circu-lation time between right heart and liver （RHLT）. LTT for each lobe was used to evaluate the early portal hypertension. RHLT is useful in cirrhosis to detect liver areas missing portal inflow. We calculated the classical per-rectal portal shunt index （PRSI） at PRPS and the hepatic perfusion index （HPI） at LAS. RESULTS： The normal LTT value was 24 ± 1 s. Abnormal LTT had PPV = 100% for CLD. Twenty-seven noncirrhotic patients had LTT increased up to 35 s （median 27 s）. RHLT （42 ± 1 s） was not related to liver disease. Cirrhosis could be excluded in all patients with PRSI 〈 5% （P 〈 0.01）. PRSI 〉 30% had PPV = 100% for cirrhosis. Based on PRPS and LAS we propose the classification of CLD in 5 hemodynamic stages. Stage 0 is normal （LTT = 24 s, PRSI 〈 5%）. In stage 1, LTT is increased, while PRSI remains normal. In stage 2, LTT is decreased between 16 s and 23 s, whereas PRSI is increased between 5% and 10%. In stage 3, PRSI is increased to 10%-30%, and LTT becomes undetectable by PRPS due to the portosystemic shunts. Stage 4 includes the patients with PRSI 〉 30%. RHLT and HPI were used to subtype stage 4. In our study stage 0 had NPV = 100% for CLD, stage 1 had PPV = 100% for non-cirrhotic CLD, stages 2 and 3 represented the transition from chronic hepatitis to cirrhosis, stage 4 had PPV = 100% for cirrhosis. CONCLUSION： LTT allows the detection of early portal hypertension and of opening of transhepatic shunts. PRSI is useful in CLD with extrahepatic portosystemic shunts. Our hemodynamic model stages the evolution of portal hypertension and portosystemic shunts. It may be of use in the selection of patients for interferon therapy.

Oxidative stress in portal hypertension-induced rats with particular emphasis on nitric oxide and trace metals

AIM: To investigate the oxidative-stress-related changes in rats with portal hypertension with particular emphasis on nitric oxide (NO) and trace metals. METHODS: Cirrhosis was induced by partial portal vein ligation (PVL) in Wistar rats. The lipid peroxidation marker (malondialdehyde, MDA), antioxidant defense enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and agents known to have antioxidant features including nitric oxide (NO), zinc (Zn), copper (Cu) were determined both in serum and in liver tissue at 4 wk after surgery in PVL and sham-operated rats. Portal pressure of all experimental animals was measured. MDA was detected by thiobarbituric acid reactivity assay.SOD activity was determined by inhibition of nitroblue tetrazolium reduction with xanthine/xanthine oxidase used asa superoxide generator. CAT activity was determined by the breakdown of hydrogen peroxide. GSH concentrations were measured by using metaphosphoric acid for protein precipitation and 5'-5'-dithio-bis-2-nitrobenzoic acid for color development. NO was detected by the Griess method after reduction of nitrate to nitrite with nitrate reductase, and the concentrations of Zn and Cu were measured by a Shimadzu 680 AA atomic absorption spectrometer. Histopathological confirmation was done under light microscope. Statistical analyses were done by Student's t-test, and significance of the difference was tested by the unpaired Mann-Whitney test. P＜0.05 was considered statistically significant.RESULTS: Histopathological studies confirmed PVL induced cirrhotic changes. There was a statistically significant difference in portal pressure between PVL and control groups (P＜0.001). The results showed significant increases in the levels of MDA and NO in both tissue and serum (P＜0.05 and P＜0.001, respectively in tissue; P＜0.001 for each in serum), and Zn only in tissue (P＜0.001)in rats with PVL compared with sham-operated rats. Besides, PVL rats exhibited reduced plasma and tissue GSH, CAT, SOD (P＜0.001 for each). Serum and tissue Cu concentration did not change.CONCLUSION: Our findings suggest that PVL in rats induces important biochemical and molecular changes related to oxidative stress in the liver.

Delayed liver laceration following transjugular intrahepatic portosystemic shunt for portal hypertension

The transjugular intrahepatic portosystemic shunt(TIPS) is an acceptable procedure that has proven benefits in the treatment of patients who have complications from portal hypertension due to liver cirrhosis.Delayed liver laceration is a rare complication of the TIPS procedure.We describe a patient with portal hypertension due to liver cirrhosis,who suddenly presented with abdominal hemorrhage and liver laceration 8 d after TIPS.Few reports have described complications after TIPS placement.To the best of our knowledge,this is the first report describing delayed liver laceration.This potential and serious complication appears to be specific and fatal for TIPS in portal hypertension.We advocate careful attention to the technique to avoid this complication,and timely treatment is extremely important.