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Portal Hypertension (portal + hypertension)

Distribution by Scientific Domains
Medical Sciences99%
Distribution within Medical Sciences
Hepatology37%
Transplantation16%
Gastroenterology & Hepatology15%
Surgery & Surgical Specialties5%
General & Internal Medicine2%
14 Other Subdomains21%

Kinds of Portal Hypertension

  • idiopathic portal hypertension
    		•
  • severe portal hypertension
    		•

    Selected Abstracts

    Current status of ectopic varices in Japan: Results of a survey by the Japan Society for Portal Hypertension

    HEPATOLOGY RESEARCH, Issue 8 2010
    Norihito Watanabe
    Aim:, The Clinical Research Committee of the Japan Society for Portal Hypertension has conducted a nationwide questionnaire survey to clarify the current status of ectopic varices in Japan. Methods:, A total of 173 cases of ectopic varices were collected. Results:, Duodenal varices were found in 57 cases, and most of them were located in the descending to transverse parts. There were 11 cases of small intestinal varices and 6 cases of colonic varices, whereas 77 patients had rectal varices, accounting for the greatest proportion (44.5%). Other sites of varices were the biliary tract, anastomotic sites, the stoma, and the diaphragm. Liver cirrhosis was the most frequent diseases (80.3%) underlying ectopic varices. It was noted that patients with rectal varices frequently had a history of esophageal varices (94.8%) and received endoscopic treatment (87.0%). The treatments for ectopic varices were as an emergency in 46.5%, elective in 35.4% and prophylactic in 18.2%. In emergency cases, endoscopic therapy was most frequent (67.4%), followed by interventional radiology (IVR; 15.2%), and endoscopy-IVR combination (6.5%). Elective treatment was performed by endoscopy in 34.3%, IVR in 28.6%, combined endoscopy-IVR in 5.7%, and surgical operation in 25.7%. The prophylactic treatment was endoscopic in 50.0%, IVR in 33.3%, combined treatments in 11.1%, and prophylactic surgery in none. The change of ectopic varices after treatment was disappearance in 54.9%, remnant in 35.4% and recurrence in 9.7%. The rate of disappearance was significantly lower in rectal varices (40.8%) than in duodenal varices (73.4%). The patient outcome did not differ among the various sites of the lesion. Conslusions:, Current status of ectopic varices in Japan has been clarified by a nationwide questionnaire survey. The authors expect that the pathophysiology of ectopic varices will be further elucidated, and that improved diagnostic modalities and treatment methods are established in the future. [source]

    New insights into the pathobiology of portal hypertension

    HEPATOLOGY RESEARCH, Issue 10 2009
    Praveen Guturu
    Portal Hypertension is a frequent complication of cirrhosis and causes significant morbidity and mortality. Increased intrahepatic resistance is the primary factor but portal hypertension is also associated with changes in systemic and porto-sytemic collateral circulation. Cirrhosis is a state of vasoregulatory imbalance with excess vasoconstrictors and less vasodilators in hepatic circulation and the reverse is true for systemic circulation. Multiple pathophysiologic mechanisms including endothelial dysfunction, sinusoidal remodeling and angiogenesis are involved in increasing resistance in hepatic vascular bed. Current evidence suggests that these changes in vasoreactivity contribute to a significant proportion of intrahepatic vascular resistance and that they are reversible, providing an attractive target for therapeutic intervention. [source]

    Left ventricular hypertrophy in rats with biliary cirrhosis

    HEPATOLOGY, Issue 3 2003
    Javier Inserte
    Portal hypertension induces neuroendocrine activation and a hyperkinetic circulation state. This study investigated the consequences of portal hypertension on heart structure and function. Intrahepatic portal hypertension was induced in male Sprague-Dawley rats by chronic bile duct ligation (CBDL). Six weeks later, CBDL rats showed higher plasma angiotensin-II and endothelin-1 (P < .01), 56% reduction in peripheral resistance and 73% reduction in pulmonary resistance (P < .01), 87% increase in cardiac index and 30% increase in heart weight (P < .01), and increased myocardial nitric oxide (NO) synthesis. In CBDL rats, macroscopic analysis demonstrated a 30% (P < .01) increase in cross-sectional area of the left ventricular (LV) wall without changes in the LV cavity or in the right ventricle (RV). Histomorphometric analysis revealed increased cell width (12%, P < .01) of cardiomyocytes from the LV of CBDL rats, but no differences in myocardial collagen content. Myocytes isolated from the LV were wider (12%) and longer (8%) than right ventricular myocytes (P < .01) in CBDL rats but not in controls. CBDL rats showed an increased expression of ANF and CK-B genes (P < .01). Isolated perfused CBDL hearts showed pressure/end-diastolic pressure curves and response to isoproterenol identical to sham hearts, although generated wall tension was reduced because of the increased wall thickness. Coronary resistance was markedly reduced. This reduction was abolished by inhibition of NO synthesis with N -nitro-L-arginine. Expression of eNOS was increased in CBDL hearts. In conclusion, portal hypertension associated to biliary cirrhosis induces marked LV hypertrophy and increased myocardial NO synthesis without detectable fibrosis or functional impairment. This observation could be relevant to patients with cirrhosis. [source]

    Underlying mechanism of portal hypertensive gastropathy in cirrhosis: A hemodynamic and morphological approach

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2009
    Lílian Amorim Curvêlo
    Abstract Background and Aim:, Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis. Methods:, Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis. Results:, The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 ± 5.9 mmHg) and severe PHG (16.9 ± 6.5 mmHg; P = 0.80) or between patients who did not have (15.2 ± 8.0 mmHg) and those who had PHG (16.3 ± 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index (P = 0.53 and 0.34, respectively), Child,Pugh classification (P = 0.73 and 0.78, respectively) or glucagon levels (P = 0.59 and 0.62, respectively). Conclusions:, The present data show no correlation between the presence or the severity of PHG and portal pressure, Child,Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors. [source]

    Increased heat-shock protein 90 expression contributes to impaired adaptive cytoprotection in the gastric mucosa of portal hypertensive rats

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2009
    Masayuki Tominaga
    Abstract Background and Aims:, Portal hypertensive (PHT) gastropathy results in an increased susceptibility to damage. Adaptive cytoprotection against ethanol-induced damage is impaired in the gastric mucosa of rats with portal hypertension. Excessive nitric oxide (NO) production occurs in portal hypertension and is mediated in part via heat-shock protein (Hsp)90 production. The aim of this study was to investigate the relation between adaptive cytoprotection after exposure to ethanol and gastric expression of Hsp90 in PHT rats. Methods:, Portal hypertension was induced in rats by staged portal vein occlusion. Adaptive cytoprotection to 70% ethanol was evaluated by assessing the injury index of the gastric mucosa with or without pretreatment with 10% ethanol. Expression of Hsp90 mRNA was evaluated by real-time polymerase chain reaction, and expression of Hsp90 protein was evaluated by western blotting. The effect of Hsp90 inhibition in PHT rats was evaluated by administration of geldanamycin. Results:, Gastric Hsp90 mRNA expression in PHT rats was significantly less than that in sham-operated (SO) controls. However, after 10% ethanol pretreatment, Hsp90 mRNA expression was significantly greater in PHT rats than in SO controls. In PHT rats, gastric Hsp90 protein expression after 10% ethanol pretreatment was significantly greater than that without the pretreatment. However, the pretreatment had no effect on the injury index compared to SO rats. Administration of geldanamycin prior to 10% ethanol pretreatment significantly decreased the injury index in response to 70% ethanol in the PHT rats. Conclusions:, These results show that 10% ethanol pretreatment markedly increases gastric Hsp90 expression in PHT rats. Excessive production of Hsp90 may contribute impaired adaptive cytoprotection. [source]

    Morphological features and clinical feasibility of thoracic duct: Detection with nonenhanced magnetic resonance imaging at 3.0 T

    JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2010
    Yu De-xin MD
    Abstract Purpose: To evaluate the detection of the thoracic duct using nonenhanced magnetic resonance imaging (MRI) and to determine the influence of some related disorders on the lymphatic duct. Materials and Methods: Highly fluid-sensitive sequence and fat-suppressed T2-weighted imaging (FS-T2WI) were performed in a total of 139 cases. The axial and coronal images were used to locate the thoracic duct and the measurement and evaluation of its dimensions were performed using a 3D maximum intensity projection (MIP) reconstruction image. The differences in the dimensions among control, portal hypertension, and common bile duct obstruction groups were compared using one-way analysis of variance. Results: The cisterna chyli was shown in 91% of cases on FS-T2WI, while the thoracic duct appeared in 70% of the MIP images. The common configuration of the cisterna chyli was tubular or saccular in 73%. Eighty thoracic ducts had a slight turn declining to the left at the level of T8,10. There was a significant difference in the transverse diameter of the thoracic duct between the portal hypertension group and other groups (F = 5.638, P = 0.005). Conclusion: Nonenhanced MRI is feasible for locating and depicting the morphological features of the thoracic duct. Portal hypertension may influence the dimension of the thoracic duct. J. Magn. Reson. Imaging 2010;32:94,100. © 2010 Wiley-Liss, Inc. [source]

    Childhood cirrhosis, hepatopulmonary syndrome and liver transplantation

    PEDIATRIC TRANSPLANTATION, Issue 3 2008
    Gokhan Tumgor
    Abstract:, Objectives:, The hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatatiton, and arterial hypoxemia. The aim of this study is to analyze outcome of children with HPS in liver transplant era. Methods:, Between September 1996 and November 2006, 172 cirrhotic patients (median age 5 years; range 0.2,22 years, M/F; 97/75) were followed at Ege University Pediatric Gastroenterology, Hepatology and Nutrition Unit. All patients were evaluated by chest radiography, arterial blood gas analysis, and alveolar-arterial oxygen tension difference, contrast echocardiography (CEE) after and before the liver transplantation. Results:, HPS was diagnosed in 33 patients (19%) by CEE. None of them had pulmonary hypertension. HPS was not found related to etiology of the liver disease. Portal hypertension was found related to the development of HPS (75.7% in patients with HPS and 54.6% in others, p = 0.02). 17 of 33 patients with HPS underwent liver transplantation. Preoperative and postoperative period of these patients was uneventful. Patients were extubated in the operating room except for two. Median follow up of transplanted children was 1.9 year (range; 0.75,10 years). Arterial blood gas analysis and CEE positivity regressed in all of them by postoperative 6th month. Conclusions:, HPS is a serious and important complication of cirrhotic children that leads to tissue hypoxia and central cyanosis. HPS seems reversible after liver transplantation in all patients. [source]

    Prospective Evaluation of Intraoperative Hemodynamics in Liver Transplantation with Whole, Partial and DCD Grafts

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010
    M. Sainz-Barriga
    The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered. [source]

    Dialysis Reduces Portal Pressure in Patients With Chronic Hepatitis C

    ARTIFICIAL ORGANS, Issue 7 2010
    Sandeep Khurana
    Abstract The purpose of this study was to characterize changes in hepatic venous pressures in patients with chronic hepatitis C. The histology and laboratory data from patients with chronic hepatitis C who underwent a transjugular liver biopsy (TJLB) and hepatic venous pressure gradient measurement were analyzed. Portal hypertension was defined as hepatic venous pressure gradient ,6 mm Hg. A single pathologist masked to hepatic venous pressure gradient scored liver sections for inflammation and fibrosis. The patients with high-grade inflammation (relative risk [RR] 2.82, P = 0.027, multivariate analysis) and late-stage fibrosis (RR 2.81, P = 0.022) were more likely to have a hepatic venous pressure gradient ,6 mm Hg, while the patients on dialysis (RR 0.32, P = 0.01) were less likely to have a hepatic venous pressure gradient ,6 mm Hg. The patients on dialysis (n = 58) had an elevated serum blood urea nitrogen and creatinine when compared with those who were not (n = 75) (47.6 ± 3.3 and 7.98 ± 0.4 vs. 25.9 ± 2.0 and 1.66 ± 0.22 mg/dL, respectively; P < 0.001). While the hepatic venous pressure gradient increased with the rising levels of liver fibrosis in the latter group (P < 0.01), it did not change in the patients on dialysis (P = 0.41). The median hepatic venous pressure gradient was especially low in late-stage fibrosis patients on dialysis when compared with the latter group (5 vs. 10 mm Hg, P = 0.017). In patients on dialysis, serum transaminases were low across all levels of fibrosis. Twenty-three of the 92 patients with early fibrosis had a hepatic venous pressure gradient ,6 mm Hg. In patients with chronic hepatitis C, concomitant TJLB and hepatic venous pressure gradient measurement identify those who have early fibrosis and portal hypertension. Long-term hemodialysis may reduce portal pressure in these patients. [source]

    Gastric mucosal resistance to acute injury in experimental portal hypertension

    BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2001
    Sara Calatayud
    The gastric mucosa of portal hypertensive rats exhibits important microvascular changes and a nitric oxide (NO)-dependent hyperemia. This study analyses whether portal hypertensive mucosa exhibits changes in its ability to withstand aggression. Portal hypertension was induced by partial portal vein ligation (PPVL) or common bile duct ligation (CBDL) and gastric damage was induced by oral administration of ethanol or aspirin. Experiments were performed in conscious or anaesthetized rats and some animals were pre-treated with the NO-synthesis inhibitor L -NAME. Conscious PPVL or CBDL rats showed an increased resistance to the damaging effects of ethanol. Oral administration of aspirin produced less gastric damage in PPVL conscious rats than in the control group. The protective effects of portal hypertension were maintained in animals anaesthetized with ketamine and absent when pentobarbital was employed. Pre-treatment with L -NAME restored the damaging effects of ethanol and aspirin in PPVL rats without modifying the level of damage in control animals. Gastric bleeding induced by oral aspirin, as measured by the luminal release of 51Cr-labelled erythrocytes, was significantly greater in PPVL rats than in control animals. Semi-quantitiative analysis by RT , PCR of the mRNA for endothelial NO-synthase (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) levels showed that the expression of iNOS was slightly increased in both the gastric mucosa and smooth muscle of PPVL rats. No changes were observed in eNOS and nNOS expression. Conscious portal hypertensive rats exhibit an enhanced resistance to acute gastric damage which is absent under the influence of some types of anaesthesia and seems related to an increased synthesis of nitric oxide. However, mucosal lesions in these animals show an augmented bleeding per area of injury. British Journal of Pharmacology (2001) 132, 309,317; doi:10.1038/sj.bjp.0703785 [source]

    GENERAL RULES FOR RECORDING ENDOSCOPIC FINDINGS OF ESOPHAGOGASTRIC VARICES (2ND EDITION)

    DIGESTIVE ENDOSCOPY, Issue 1 2010
    Takashi Tajiri
    General rules for recording endoscopic findings of esophageal varices were initially proposed in 1980 and revised in 1991. These rules have widely been used in Japan and other countries. Recently, portal hypertensive gastropathy has been recognized as a distinct histological and functional entity. Endoscopic ultrasonography can clearly depict vascular structures around the esophageal wall in patients with portal hypertension. Owing to progress in medicine, we have updated and slightly modified the former rules. The revised rules are simpler and more straightforward than the former rules and include newly recognized findings of portal hypertensive gastropathy and a new classification for endoscopic ultrasonographic findings. [source]

    ENDOSCOPIC MICROVASCULAR ARCHITECTURE OF THE PORTAL HYPERTENSIVE GASTRIC MUCOSA ON NARROW BAND IMAGING

    DIGESTIVE ENDOSCOPY, Issue 3 2007
    Seishu Hayashi
    Background:, We evaluated the endoscopic microvascular architecture of the gastric mucosa in portal hypertension patients using the prototype of narrow band imaging (NBI). Material and Methods:, The study included 103 Helicobacter pylori -negative patients with chronic liver disease (22 without portal hypertension (group 1), 81 with portal hypertension (group 2)). Results:, (i) Abnormality of collecting venules, reddening mucosa, red spots, a mosaic-like pattern, and gastric antral vascular ectasia (GAVE) were observed on the gastric mucosa, and an obscure change in collecting venules (73% vs 14%; P < 0.001), reddening mucosa (49% vs 5%; P < 0.001), red spots (36% vs 5%; P < 0.01) and a mosaic-like pattern (40% vs 5%; P < 0.01) were more frequently observed in group 2 than in group 1. (ii) On magnifying endoscopy with NBI, the mucosa with an obscure change in collecting venules was demonstrated as dilation of the capillaries surrounding the gastric pits in various degrees, and reddening mucosa was observed as extended and swollen gastric pits and various degrees of dilated and convoluted capillaries surrounding the gastric pits. Red spots were demonstrated as extended and swollen gastric pits, dilated and convoluted capillaries surrounding the gastric pits, and intramucosal hemorrhage around these capillaries. GAVE was recognized as partial and marked dilatation of the capillaries surrounding the gastric pits. Conclusion:, Abnormality of collecting venules, swelling of gastric pits, dilatation of capillaries surrounding the gastric pits, intramucosal hemorrhage around capillaries, and partial and marked dilatation of the capillaries were observed on the gastric mucosa in portal hypertension patients. [source]

    HEMODYNAMIC MECHANISM OF ESOPHAGEAL VARICES

    DIGESTIVE ENDOSCOPY, Issue 1 2006
    Katsutoshi Obara
    We investigated the correlation between the collaterals around the esophagus and recurrence of esophageal varices in patients with portal hypertension who had undergone endoscopic injection sclerotherapy (EIS). In patients with portal hypertension, many types of collaterals around the esophagus were visualized by endoscopic ultrasonography (EUS). The collaterals outside the esophageal wall detected by EUS were divided into two groups according to the location of the veins: peri-esophageal collateral veins (peri-ECV) and para-esophageal collateral veins (para-ECV) Perforating veins are those that have penetrated the esophageal wall and have connected with either peri-ECV or para-ECV. We demonstrated that severe peri-ECV and large perforating veins play an important role in the development of esophageal varices in untreated patients with portal hypertension. The results of our investigation have shown that detection of peri-ECV and perforating veins by EUS and treatment of them by EIS appears to be important for the treatment of esophageal varices. The disappearance of peri-ECV by EIS is essential for reducing the recurrence rate of esophageal varices. To prevent variceal recurrence, a mucosal fibrosing method using argon plasma coagulation has been widely performed in Japan. If EUS abnormalities are associated with variceal recurrence, we recommend the use of the mucosal fibrosing method. In conclusion, the presence of severe peri-ECV and large perforating veins in the esophageal wall strongly correlate with the recurrence of esophageal varices in patients with portal hypertension. An understanding of these EUS abnormalities on the basis of hemodynamics around the esophagus is important for the management of esophageal varices in patients with portal hypertension. [source]

    Esophageal motility changes after endoscopic intravariceal sclerotherapy with absolute alcohol

    DISEASES OF THE ESOPHAGUS, Issue 2 2000
    Ghoshal
    Endoscopic sclerotherapy (EST) leads to structural and motility changes in the esophagus; the former are thought to be commoner after EST with absolute alcohol (AA), which is a commonly used sclerosant in India as it is cheap and effective. There are no previous studies on changes in esophageal motility after EST with AA. Accordingly, we studied patients with portal hypertension before (n = 24) and after (n = 22) variceal obliteration by EST with AA using a water perfusion esophageal manometry system. Contraction amplitude in the distal esophagus was reduced in the post-EST group compared with the pre-EST group (63.4 ± 24.9 vs. 18.2 ± 14.3 mmHg, p < 0.01). Duration of esophageal contraction in both the proximal and distal esophagus became prolonged in the post-EST compared with the pre-EST group (3.3 ± 0.8 vs. 5.4 ± 2.6 and 4.3 ± 1.1 vs. 6.6 ± 2.3 s, p < 0.001 for both). Lower esophageal sphincter (LES) pressure was reduced in the post-EST compared with the pre-EST group, although the difference was not significant statistically. Abnormal contraction waveforms were more frequent in the post-EST group. One patient in the post-EST group had persistent dysphagia in the absence of endoscopically documented stricture at the time of manometric study. This study shows frequent occurrence of esophageal dysmotility after EST with AA; however, esophageal dysmotility after EST was infrequently associated with motor dysphagia. [source]

    Bosentan treatment of portopulmonary hypertension related to liver cirrhosis owing to hepatitis C

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2006
    W. Grander
    Abstract Pulmonary arterial hypertension (PAH) with coexisting portal hypertension has been defined as portopulmonary hypertension (PPHTN). It is often related to liver cirrhosis of various aetiologies and is associated with a high mortality rate. Endothelin-1 (ET) is supposed to play an important role in the pathogenesis of PAH as well as portal hypertension. Therefore, therapy with an ETA/ETB receptor antagonist might be of use in the treatment of PPHTN. We report the case of a 76-year-old male with liver cirrhosis owing to chronic hepatitis C virus infection and PPHTN who was treated with the dual ETA/ETB receptor antagonist bosentan. The patient showed remarkable improvement of 6-min walking distance from 300 to 480 m after 2 weeks and to 540 m after 14 weeks, respectively. In addition, a significant decline of N-terminal pro B-type natriuretic peptide fraction (NT-proBNP) from 4928 ng mL,1 to 640 ng mL,1 was observed. Bosentan might be a promising new therapeutical option for patients suffering from PPHTN. [source]

    Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010
    Elena Mishchenko
    Abstract Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension. [source]

    Liver stiffness identifies two different patterns of fibrosis progression in patients with hepatitis C virus recurrence after liver transplantation,

    HEPATOLOGY, Issue 1 2010
    José A. Carrión
    Significant liver fibrosis (F , 2) and portal hypertension (hepatic venous pressure gradient [HVPG] , 6 mmHg) at 1 year after liver transplantation (LT) identify patients with severe hepatitis C recurrence. We evaluated whether repeated liver stiffness measurements (LSM) following LT can discriminate between slow and rapid "fibrosers" (fibrosis stage F2-F4 at 1 year after LT). Eighty-four patients who had undergone LT and who were infected with hepatitis C virus (HCV) and 19 LT controls who were not infected with HCV underwent LSM at 3, 6, 9, and 12 months after LT. All HCV-infected patients underwent liver biopsy 12 months after LT (paired HVPG measurements in 74); 31 (37%) were rapid fibrosers. Median LSM (in kilopascal) at months 6, 9, and 12 were significantly higher in rapid fibrosers (9.9, 9.5, 12.1) than in slow fibrosers (6.9, 7.5, 6.6) (P < 0.01 all time points). The slope of liver stiffness progression (kPa × month) in rapid fibrosers (0.42) was significantly greater than in slow fibrosers (0.05) (P < 0.001), suggesting two different speeds of liver fibrosis progression. Figures were almost identical for patients with HVPG , 6 mmHg or HVPG < 6 mmHg at 1 year after LT. Multivariate analysis identified donor age, bilirubin level, and LSM as independent predictors of fibrosis progression and portal hypertension in the estimation group (n = 50) and were validated in a second group of 34 patients. The areas under the receiver operating characteristic curve that could identify rapid fibrosers and patients with portal hypertension as early as 6 months after LT were 0.83 and 0.87, respectively, in the estimation group and 0.75 and 0.80, respectively, in the validation group. Conclusion: Early and repeated LSM following hepatitis C recurrence in combination with clinical variables discriminates between rapid and slow fibrosers after LT. (HEPATOLOGY 2009.) [source]

    Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management,

    HEPATOLOGY, Issue 1 2009
    Raj Vuppalanchi
    Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease in the western world. It is now recognized that these patients have myriad of important co-morbidities (e.g., diabetes, hypothyroidism and metabolic syndrome). The workup of patients with suspected NAFLD should consist of excluding competing etiologies and systemic evaluation of metabolic comorbidities. NAFLD is histologically categorized into steatosis and steatohepatitis, two states with fairly dichotomous natural history. While significant progress has been made in terms of noninvasively predicting advanced fibrosis, insufficient progress has been made in predicting steatohepatitis. Currently, liver biopsy remains the gold standard for the histological stratification of NAFLD. While sustained weight loss can be effective to treat NASH, it is often difficult to achieve. Foregut bariatric surgery can be quite effective in improving hepatic histology in selected patients without liver failure or significant portal hypertension. Thiazolidinediones have shown promise and the results from the ongoing, large multicenter study should become available soon. Large multicenter studies of CB, receptor anatagonists are also underway but their results will not be available for several years. Several recent studies have highlighted that cardiovascular disease is the single most important cause of morbidity and mortality in this patient population. Conclusion: Health care providers should not only focus on liver disease but also concentrate on aggressively modifying and treating their cardiovascular risk factors. (HEPATOLOGY 2009;49:306-317.) [source]

    Clinical risk factors for portopulmonary hypertension,

    HEPATOLOGY, Issue 1 2008
    Steven M. Kawut
    Portopulmonary hypertension affects up to 6% of patients with advanced liver disease, but the predictors and biologic mechanism for the development of this complication are unknown. We sought to determine the clinical risk factors for portopulmonary hypertension in patients with advanced liver disease. We performed a multicenter case-control study nested within a prospective cohort of patients with portal hypertension recruited from tertiary care centers. Cases had a mean pulmonary artery pressure > 25 mm Hg, pulmonary vascular resistance > 240 dynes · second · cm,5, and pulmonary capillary wedge pressure , 15 mm Hg. Controls had a right ventricular systolic pressure < 40 mm Hg (if estimable) and normal right-sided cardiac morphology by transthoracic echocardiography. The study sample included 34 cases and 141 controls. Female sex was associated with a higher risk of portopulmonary hypertension than male sex (adjusted odds ratio = 2.90, 95% confidence interval 1.20-7.01, P = 0.018). Autoimmune hepatitis was associated with an increased risk (adjusted odds ratio = 4.02, 95% confidence interval 1.14-14.23, P = 0.031), and hepatitis C infection was associated with a decreased risk (adjusted odds ratio = 0.24, 95% confidence interval 0.09-0.65, P = 0.005) of portopulmonary hypertension. The severity of liver disease was not related to the risk of portopulmonary hypertension. Conclusion: Female sex and autoimmune hepatitis were associated with an increased risk of portopulmonary hypertension, whereas hepatitis C infection was associated with a decreased risk in patients with advanced liver disease. Hormonal and immunologic factors may therefore be integral to the development of portopulmonary hypertension. (HEPATOLOGY 2008.) [source]

    Platelet count is not a predictor of the presence or development of gastroesophageal varices in cirrhosis,

    HEPATOLOGY, Issue 1 2008
    Amir A. Qamar
    Current guidelines recommend esophagogastroduodenoscopy (EGD) in patients with cirrhosis to screen for gastroesophageal varices (GEV). Thrombocytopenia has been proposed as a noninvasive test to predict the presence of GEV. There is no agreement regarding a specific platelet count (PLT) that can reliably predict GEV. The present longitudinal study aims to (1) further investigate the relationship between varices and PLT at the time of endoscopy, (2) investigate whether changes in PLT from the baseline over time can predict the development of GEV, and (3) investigate whether changes in PLT correlate with the hepatic venous pressure gradient (HVPG). A secondary analysis was conducted for 213 subjects with compensated cirrhosis with portal hypertension but without GEV enrolled in a randomized, placebo-controlled, double-blind trial of a nonselective beta-blocker used to prevent GEV. PLTs were obtained every 3 months, and HVPG measurements and EGD were done annually. The PLTs were compared between subjects who did and did not develop GEV. In a median follow-up of 54.9 months, 84 patients developed GEV. PLT was greater than 150,000 in 15% of patients at the development of GEV. A receiver operating curve did not show any PLT with high sensitivity or specificity for the presence of GEV. Subjects with clinically insignificant portal hypertension (HVPG < 10 mm Hg) whose PLT remained greater than 100,000 had a 2-fold reduction in the occurrence of GEV (P = 0.0374). A significant correlation was found between HVPG and PLT at the baseline, year 1, and year 5 (P < 0.0001). Conclusion: Cross-sectional or longitudinal evaluations of PLTs are inadequate noninvasive markers for GEV. Patients with mild portal hypertension whose PLT remains greater than 100,000 have significantly less risk of GEV. Although HVPG correlates somewhat with PLT, changes in PLT cannot be used as a surrogate for HVPG changes. (HEPATOLOGY 2008;47:153,159.) [source]

    Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats,

    HEPATOLOGY, Issue 4 2007
    Mercedes Fernandez
    Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) pathways are crucial to angiogenesis, a process that contributes significantly to the pathogenesis of portal hypertension. This study determined the effects of inhibition of VEGF and/or PDGF signaling on hyperdynamic splanchnic circulation and portosystemic collateralization in rats with completely established portal hypertension, thus mimicking the situation in patients. Portal vein,ligated rats were treated with rapamycin (VEGF signaling inhibitor), Gleevec (PDGF signaling inhibitor), or both simultaneously when portal hypertension was already fully developed. Hemodynamic studies were performed by transit-time flowmetry. The extent of portosystemic collaterals was measured by radioactive microspheres. The expression of angiogenesis mediators was determined by Western blotting and immunohistochemistry. Combined inhibition of VEGF and PDGF signaling significantly reduced splanchnic neovascularization (i.e., CD31 and VEGFR-2 expression) and pericyte coverage of neovessels (that is, ,-smooth muscle actin and PDGFR-, expression) and translated into hemodynamic effects as marked as a 40% decrease in portal pressure, a 30% decrease in superior mesenteric artery blood flow, and a 63% increase in superior mesenteric artery resistance, yielding a significant reversal of the hemodynamic changes provoked by portal hypertension in rats. Portosystemic collateralization was reduced as well. Conclusions: Our results provide new insights into how angiogenesis regulates portal hypertension by demonstrating that the maintenance of increased portal pressure, hyperkinetic circulation, splanchnic neovascularization, and portosystemic collateralization is regulated by VEGF and PDGF in portal hypertensive rats. Importantly, these findings also suggest that an extended antiangiogenic strategy (that is, targeting VEGF/endothelium and PDGF/pericytes) may be a novel approach to the treatment of portal hypertension. (HEPATOLOGY 2007.) [source]

    Increasing dimethylarginine levels are associated with adverse clinical outcome in severe alcoholic hepatitis,

    HEPATOLOGY, Issue 1 2007
    Rajeshwar P. Mookerjee
    Previous studies suggest reduced hepatic endothelial nitric oxide synthase activity contributes to increased intrahepatic resistance. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, undergoes hepatic metabolism via dimethylarginine-dimethylamino-hydrolase, and is derived by the action of protein-arginine-methyltransferases. Our study assessed whether ADMA, and its stereo-isomer symmetric dimethylarginine (SDMA), are increased in alcoholic hepatitis patients, and determined any relationship with severity of portal hypertension (hepatic venous pressure gradient measurement) and outcome. Fifty-two patients with decompensated alcoholic cirrhosis were studied, 27 with acute alcoholic hepatitis and cirrhosis, in whom hepatic venous pressure gradient was higher (P = 0.001) than cirrhosis alone, and correlated with ADMA measurement. Plasma ADMA and SDMA were significantly higher in alcoholic hepatitis patients and in nonsurvivors. Dimethylarginine-dimethylamino-hydrolase protein expression was reduced and protein-arginine-methyltransferase-1 increased in alcoholic hepatitis livers. ADMA, SDMA and their combined sum, which we termed a dimethylarginine score, were better predictors of outcome compared with Pugh score, MELD and Maddrey's discriminant-function. Conclusion: Alcoholic hepatitis patients have higher portal pressures associated with increased ADMA, which may result from both decreased breakdown (decreased hepatic dimethylarginine-dimethylamino-hydrolase) and/or increased production. Elevated dimethylarginines may serve as important biological markers of deleterious outcome in alcoholic hepatitis. (HEPATOLOGY 2007;45:62,71.) [source]

    A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis,,

    HEPATOLOGY, Issue 6 2005
    Wim Laleman
    Reduced intrahepatic endothelial nitric oxide synthase (eNOS) activity contributes to the pathogenesis of portal hypertension (PHT) associated with cirrhosis. We evaluated whether asymmetric dimethylarginine (ADMA), a putative endogenous NOS inhibitor, may be involved in PHT associated with cirrhosis. Two rat models of cirrhosis (thioacetamide [TAA]-induced and bile duct excision [BDE]-induced, n = 10 each), one rat model of PHT without cirrhosis (partial portal vein,ligated [PPVL], n = 10), and sham-operated control rats (n = 10) were studied. We assessed hepatic NOS activity, eNOS protein expression, plasma ADMA levels, and intrahepatic endothelial function. To evaluate intrahepatic endothelial function, concentration,effect curves of acetylcholine were determined in situ in perfused normal rat livers and livers of rats with TAA- or BDE-induced cirrhosis (n = 10) that had been preincubated with either vehicle or ADMA; in addition, measurements of nitrite/nitrate (NOx) and ADMA were made in perfusates. Both models of cirrhosis exhibited decreased hepatic NOS activity. In rats with TAA-induced cirrhosis, this decrease was associated with reduced hepatic eNOS protein levels and immunoreactivity. Rats with BDE-induced cirrhosis had eNOS protein levels comparable to those in control rats but exhibited significantly higher plasma ADMA levels than those in all other groups. In normal perfused liver, ADMA induced impaired endothelium-dependent vasorelaxation and reduced NOx perfusate levels, phenomena that were mimicked by NG -nitro- L -arginine-methyl ester. In contrast to perfused livers with cirrhosis induced by TAA, impaired endothelial cell-mediated relaxation in perfused livers with cirrhosis induced by BDE was exacerbated by ADMA and was associated with a decreased rate of removal of ADMA (34.3% ± 6.0% vs. 70.9% ± 3.2%). In conclusion, in rats with TAA-induced cirrhosis, decreased eNOS enzyme levels seem to be responsible for impaired NOS activity; in rats with biliary cirrhosis, an endogenous NOS inhibitor, ADMA, may mediate decreased NOS activity. (HEPATOLOGY 2005;42:1382,1390.) [source]

    A mouse model for cystic biliary dysgenesis in autosomal recessive polycystic kidney disease (ARPKD),

    HEPATOLOGY, Issue 5 2005
    Markus Moser
    Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of liver- and renal-related morbidity and mortality in childhood. Recently, PKHD1, the gene encoding the transmembrane protein polyductin, was shown to be mutated in ARPKD patients. We here describe the first mouse strain, generated by targeted mutation of Pkhd1. Due to exon skipping, Pkhd1ex40 mice express a modified Pkhd1 transcript and develop severe malformations of intrahepatic bile ducts. Cholangiocytes maintain a proliferative phenotype and continuously synthesize TGF-,1. Subsequently, mesenchymal cells within the hepatic portal tracts continue to synthesize collagen, resulting in progressive portal fibrosis and portal hypertension. Fibrosis did not involve the hepatic lobules, and we did not observe any pathological changes in morphology or function of hepatocytes. Surprisingly and in contrast to human ARPKD individuals, Pkhd1ex40 mice develop morphologically and functionally normal kidneys. In conclusion,our data indicate that subsequent to formation of the embryonic ductal plate, dysgenesis of terminally differentiated bile ducts occurs in response to the Pkhd1ex40 mutation. The role of polyductin in liver and kidney may be functionally divergent, because protein domains essential for bile duct development do not affect nephrogenesis in our mouse model. Supplementary material for this article can be found on the HEPATOLOGYwebsite (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005.) [source]

    Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis

    HEPATOLOGY, Issue 5 2003
    Luis Ruiz-del-Arbol M.D.
    Spontaneous bacterial peritonitis (SBP) is frequently associated with renal failure. This study assessed if systemic and hepatic hemodynamics are also affected by this condition. Standard laboratory tests, tumor necrosis factor , (TNF-,) in plasma and ascitic fluid, plasma renin activity (PRA) and norepinephrine (NE), and systemic and hepatic hemodynamics were determined in 23 patients with SBP at diagnosis and after resolution of infection. Eight patients developed renal failure during treatment. At diagnosis of infection, patients developing renal failure showed significantly higher values of TNF-,, blood urea nitrogen (BUN), PRA and NE, peripheral vascular resistance, and hepatic venous pressure gradient (HVPG) and lower cardiac output than patients not developing renal failure. During treatment, a significant reduction in cardiac output and arterial pressure and increase in PRA and NE, HVPG, and Child-Pugh score were observed in the first group but not in the second. Peripheral vascular resistance remained unmodified in both groups. Changes in PRA and NE correlated inversely with changes in arterial pressure and directly with changes in BUN, Child-Pugh score, and HVPG. Five patients in the renal failure group developed encephalopathy, and 6 died. In the group without renal failure, none of the patients developed encephalopathy or expired. In conclusion, patients with SBP frequently develop a rapidly progressive impairment in systemic hemodynamics, leading to severe renal and hepatic failure, aggravation of portal hypertension, encephalopathy, and death. This occurs despite rapid resolution of infection and is associated with an extremely poor prognosis. [source]

    Left ventricular hypertrophy in rats with biliary cirrhosis

    HEPATOLOGY, Issue 3 2003
    Javier Inserte
    Portal hypertension induces neuroendocrine activation and a hyperkinetic circulation state. This study investigated the consequences of portal hypertension on heart structure and function. Intrahepatic portal hypertension was induced in male Sprague-Dawley rats by chronic bile duct ligation (CBDL). Six weeks later, CBDL rats showed higher plasma angiotensin-II and endothelin-1 (P < .01), 56% reduction in peripheral resistance and 73% reduction in pulmonary resistance (P < .01), 87% increase in cardiac index and 30% increase in heart weight (P < .01), and increased myocardial nitric oxide (NO) synthesis. In CBDL rats, macroscopic analysis demonstrated a 30% (P < .01) increase in cross-sectional area of the left ventricular (LV) wall without changes in the LV cavity or in the right ventricle (RV). Histomorphometric analysis revealed increased cell width (12%, P < .01) of cardiomyocytes from the LV of CBDL rats, but no differences in myocardial collagen content. Myocytes isolated from the LV were wider (12%) and longer (8%) than right ventricular myocytes (P < .01) in CBDL rats but not in controls. CBDL rats showed an increased expression of ANF and CK-B genes (P < .01). Isolated perfused CBDL hearts showed pressure/end-diastolic pressure curves and response to isoproterenol identical to sham hearts, although generated wall tension was reduced because of the increased wall thickness. Coronary resistance was markedly reduced. This reduction was abolished by inhibition of NO synthesis with N -nitro-L-arginine. Expression of eNOS was increased in CBDL hearts. In conclusion, portal hypertension associated to biliary cirrhosis induces marked LV hypertrophy and increased myocardial NO synthesis without detectable fibrosis or functional impairment. This observation could be relevant to patients with cirrhosis. [source]

    Renal sodium retention in portal hypertension and hepatorenal reflex: From practice to science

    HEPATOLOGY, Issue 6 2003
    Manuel Jiménez-Sáenz M.D.
    No abstract is available for this article. [source]

    Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosis

    HEPATOLOGY, Issue 2 2003
    Lia Bellis
    Postprandial hyperemia is associated with a significant increase in portal pressure in cirrhosis, which may contribute to progressive dilation and rupture of gastroesophageal varices. In cirrhosis, an insufficient hepatic production of nitric oxide (NO) may impair the expected hepatic vasodilatory response to increased blood flow, further exaggerating the postprandial increase in portal pressure. This study was aimed at investigating whether low doses of an oral NO donor might counteract the postprandial peak in portal pressure. Twenty-three portal hypertensive cirrhotics, 8 of them under propranolol therapy, were randomized to receive orally 5-isosorbide mononitrate (ISMN; 10 mg; n = 11) or placebo (n = 12) and a standard liquid meal 15 minutes later. Hepatic venous pressure gradient (HVPG), mean arterial pressure (MAP), and hepatic blood flow (HBF) were measured at baseline and 15, 30, and 45 minutes after a meal. ISMN significantly attenuated the postprandial increase in portal pressure as compared with placebo (peak HVPG increase: 2.4 ± 1.4 mm Hg vs. 5.2 ± 2.1 mm Hg, P = .002). Percentual increases in HBF were similar in both groups. MAP decreased slightly in ISMN group (,7.5% ± .5%; P < .01 vs. baseline). These effects were also observed in patients on chronic propranolol therapy. In conclusion, hepatic NO supplementation by low doses of ISMN effectively reduces the postprandial increase of portal pressure in cirrhosis, with only a mild effect on arterial pressure. The same was observed in patients receiving propranolol. Our results suggest that therapeutic strategies based on selective hepatic NO delivery may improve the treatment of portal hypertension. [source]

    Increasing intra-abdominal pressure increases pressure, volume, and wall tension in esophageal varices

    HEPATOLOGY, Issue 4 2002
    Angels Escorsell
    Many daily activities cause acute elevations of intra-abdominal pressure (IAP). In portal hypertensive cirrhotic patients, increased IAP increases absolute portal pressure and azygos blood flow, suggesting that it may have detrimental consequences at the esophageal varices. The aim of this study was to investigate the effects of increased IAP on variceal pressure, size, and wall tension. Endosonography and a noninvasive endoscopic pressure gauge were used to measure variceal pressure, radius, wall tension, and volume in baseline conditions and after increasing IAP by 10 mm Hg using an inflatable girdle in 14 patients with cirrhosis and esophageal varices. Increasing IAP markedly increased variceal pressure (from 13.3 ± 4.2 to 17.4 ± 4.6 mm Hg; P = .0001) and radius (from 2.9 ± 1.0 to 3.9 ± 1.1 mm; P = .0001). Consequently, wall tension dramatically increased (from 38.7 ± 13.6 to 65.9 ± 23.8 mm Hg · mm, +78%; P = .0001). Variceal volume increased significantly from 1,264 ± 759 to 2,025 ± 1,129 mm3 (P = .0001). In conclusion, in portal hypertensive cirrhotic patients, increases in IAP have deleterious effects on variceal hemodynamics, markedly increasing the volume, pressure, and wall tension of the varices. Increases in IAP may contribute to the progressive dilatation that precedes the rupture of the varices in portal hypertension. [source]

    Hepatic arterial buffer response in patients with advanced cirrhosis

    HEPATOLOGY, Issue 3 2002
    Veit Gülberg
    Hepatic arterial buffer response (HABR) is considered an important compensatory mechanism to maintain perfusion of the liver by hepatic arterial vasodilation on reduction of portal venous perfusion. HABR has been suggested to be impaired in patients with advanced cirrhosis. In patients with hepatopetal portal flow, placement of a transjugular intrahepatic portosystemic shunt (TIPS) reduces portal venous liver perfusion. Accordingly, patients with severe cirrhosis should have impaired HABR after TIPS implantation. Therefore, the aim of this study was to investigate the effect of TIPS on HABR as reflected by changes in resistance index (RI) of the hepatic artery. A total of 366 patients with cirrhosis (Child-Pugh class A, 106; class B, 168; class C, 92) underwent duplex Doppler ultrasonographic examination with determination of RI and maximal flow velocity in the portal vein before and 1 month after TIPS placement. Portosystemic pressure gradient was determined before and after TIPS placement. In 29 patients with hepatofugal portal blood flow, RI was significantly lower than in 337 patients with hepatopetal flow (0.63 ± 0.02 vs. 0.69 ± 0.01; P < .001). TIPS induced a significant decrease of the RI in patients with hepatopetal flow (RI, 0.69 ± 0.01 before vs. 0.64 ± 0.01 after TIPS; P = .001) but not in patients with hepatofugal flow (RI, 0.63 ± 0.02 before vs. 0.63 ± 0.02 after TIPS; NS). This response was not dependent on the Child-Pugh class. In conclusion, our results suggest that some degree of HABR is preserved even in patients with advanced cirrhosis with significant portal hypertension. [source]