Skip to main content

Jaime Bosch

University of Barcelona, MEDICINE, Faculty Member

Followers

95

Following

48

Co-authors

41

Public Views

Jaume Bosch, MD, PhDEmeritis Professor of Medicine, University of Barcelona (Spain), and Guest Professor of Hepatology at the University of Bern (Switzerland).My field of expertise is Cirrhosis of the liver and its complications related to portal hypertension. I have been active in this field since 1980, aftrer training with Prof RJ Groszmann at Yale University. My clinical and translational research has focused mainly in investigating new therapies, from experiemental studies to its clinical application. I have also developed a lab for studying the vascular biology of the liver and the mechanisms of its changes during cirrhosis develpment.My lsit of publications in Scopus includes 643, with an H factor of 112 (February 2021)

less

University of Barcelona

Juan García-Pagán

Bernardo Frider

Maimonides

Orfelina Campos Nuñez

Agustín Albillos

Universidad de Alcala

Interests

Uploads

Papers by Jaime Bosch

Anemia Worsens Hyperdynamic Circulation of Patients with Cirrhosis and Portal Hypertension

Digestive Diseases and Sciences, 1997

This retrospective cohort study was aimed atinvestigating the effects of anemia on the hemodynami... more This retrospective cohort study was aimed atinvestigating the effects of anemia on the hemodynamicdisturbances associated with portal hypertension. Inall, 202 consecutive nontreated portal-hypertensive patients referred for evaluation to our HepaticHemodynamic Laboratory were included. Compared to thenonanemic patients, anemic cirrhotic patients had anincreased cardiac output (7.9 ± 1.9 vs 7.1± 2 liters/min, P 5, P < 0.0001). Similar resultswere obtained when

Stenosis of the suprahepatic inferior vena cava as a complication of transjugular intrahepatic portosystemic shunt in Budd-Chiari patients

Liver Transplantation, 2001

Metabolomics Discloses Potential Biomarkers for the Noninvasive Diagnosis of Idiopathic Portal Hypertension

American Journal of Gastroenterology, 2013

Idiopathic portal hypertension (IPH) is a rare cause of portal hypertension that lacks a specifi ... more Idiopathic portal hypertension (IPH) is a rare cause of portal hypertension that lacks a specifi c diagnostic test. Requiring ruling-out other causes of portal hypertension it is frequently misdiagnosed. This study evaluates whether using high-throughput techniques there is a metabolomic profi le allowing a noninvasive diagnosis of IPH. METHODS : Thirty-three IPH patients were included. Matched patients with cirrhosis (CH) and healthy volunteers (HV) were included as controls. Metabolomic analysis of plasma samples was performed using UPLCtime-of-fl ight-mass spectrometry. We computed Student ' s P-values, corrected by multiple comparison and VIP score (Variable Importance in the Projection). The metabolites were selected with an adjusted Benjamini Hochberg P value < 0.05. We use markers with a greater VIP score, to build partial least squares projection to latent structures regression with discriminant analysis (PLS-DA) representative models to discriminate IPH from CH and from HV. The performance of the PLS-DA model was evaluated using R 2 and Q 2 parameter. An additional internal cross-validation was done. RESULTS : PLS-DA analysis showed a clear separation of IPH from CH with a model involving 28 metabolites (Q 2 = 0.67, area under the curve (AUC) = 0.99) and a clear separation of IPH from healthy subjects with a model including 31 metabolites (Q 2 = 0.75, AUC = 0.98). After cross-validation, both models showed high rates of sensitivity (94.8 and 97.5), specifi city (89.1 and 89.7), and AUC (0.98 and 0.98), reinforcing the strength of our fi ndings. CONCLUSIONS : A metabolomic profi le clearly differentiating patients with IPH from CH and healthy subjects has been identifi ed using subsets of 28 and 31 metabolites, respectively. Therefore, metabolomic analysis appears to be a valuable tool for the noninvasive diagnosis of IPH.

A prospective observational study on tolerance and satisfaction to hepatic haemodynamic procedures

Liver International, 2014

Understanding patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;am... more Understanding patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; attitudes to clinical experiences is essential for developing high-quality patient-centred healthcare, as a better knowledge of patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; tolerance and satisfaction might allow implementing measures that ameliorate comfort, care and use of resources. We aimed to describe patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; tolerance and satisfaction to invasive hepatic haemodynamic procedures, and to investigate which factors might influence patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; perspective in this field. Visual Analogue Scale (VAS) questionnaires regarding pain and duration (for tolerance), and comfort and general handling (for satisfaction) were prospectively administered to all consecutive patients (N = 327) submitted to hepatic haemodynamic procedures (N = 355) in a tertiary care setting during 2011. VAS scores ranged between 0 and 100 mm and items were defined as excellent if &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10 mm; good if 10-20 mm and inadequate if &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20 mm. Clinical and laboratory data were also collected. Satisfaction was excellent in &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;95% of cases (mean 2 ± 5 mm, median 0 mm) and average tolerance was good (15 ± 18 mm; median 6 mm). A percentage of 59% of patients had excellent tolerance, 9% good and 32% had inadequate tolerance. Duration and complexity of the procedure and limited operator&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s experience were associated with inadequate tolerance on univariate analysis; duration of the procedure remained the only independent factor associated with inadequate tolerance on multivariate analysis. Procedures lasting &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;35 min had a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;80% probability of being well tolerated. Satisfaction and tolerance to hepatic haemodynamic procedures are excellent and good respectively. Tolerance was decreased in long procedures; hence reducing as much as possible the duration of the procedures might further improve tolerance.

P517 Effects of Sapropterin on Portal and Systemic Hemodynamics in Patients with Cirrhosis and Portal Hypertension: A Bicentric Double-Blind Placebo Controlled Study

Journal of Hepatology, 2014

POSTERS hemodynamic data were collected. Pro-C5 was analysed as a single marker and combined in a... more POSTERS hemodynamic data were collected. Pro-C5 was analysed as a single marker and combined in a linear regression model with ALT, bilirubin, MELD, and Child score. Follow-up time was five year and mortality was analysed by log-rank. Pro-C5 was assessed in arterial plasma samples. Results: Pro-C5 clearly separated patients with a HVPG <10 mmHg or HVPG≥10 mmHg (p < 0.001, AUC=0.73) and controls (p < 0.0001, AUC=0.88). Pro-C5 correlated significantly with HVPG, ICGclearance, SVR and MAP (r = −0.68-0.33, p < 0.0001). A multiple regression analysis including Pro-C5, ALT, bilirubin MELD and Child improved the correlation to HVPG (r = 0.74, p < 0.0001). Moreover, Pro-C5 correlated with liver function markers and MELD (r = 0.31-0.68; p < 0.01-0.0001). Finally, there was a clear relation to increasing Child score A-C and plasma Pro-C5 (ANOVA p < 0.001) but no significant relation of Pro-C5 to mortality. Conclusions: Plasma Pro-C5 reflects both splanchnic and systemic hemodynamics in cirrhosis including PHT, liver function and stage of disease. A multimarker model in combination with clinical scores predicted HVPG and was able to diagnose clinical relevant HVPG non-invasively. Therefore Pro-C5 is a promising plasma marker of significant portal hypertension in cirrhosis.

Effects of propranolol on venous compliance in conscious rats with pre-hepatic portal hypertension

Journal of Hepatology, 2006

Background/Aims: The venous system is the primary capacitance region in the body. However, the in... more Background/Aims: The venous system is the primary capacitance region in the body. However, the influence of active changes in the venous system on the hemodynamic alterations of portal hypertension is poorly understood. To investigate venous compliance (VC) in conscious partial portal vein ligated rats (PPVL) and the effect of propranolol on VC. Methods: Venous compliance was derived from the relationship between changes in mean circulatory filling pressure (MCFP) and changes in blood volume (BV). Measurements were performed before and after i.v. propranolol (7.5 mg/Kg) or placebo in rats with portal hypertension due to PPVL and sham operated controls. Results: PPVL rats had an increased VC when compared to Sham (4.9G1.4 vs. 3.7G0.9 ml kg K1 mmHg K1 ; P!0.02). VC did not change after placebo but was significantly reduced by Propranolol in PPVL (K32.9G15.7%; P!0,007). Propranolol did not modify venous compliance in sham operated rats (C10.9G13.4%; PZns). Conclusions: Venous compliance is increased in portal hypertensive rats, suggesting that the venous system contributes to the profound circulatory changes encountered in portal hypertension. The increased venous compliance is markedly attenuated by propranolol, suggesting that this abnormality is related to increased adrenergic activity.

Total effective vascular compliance in patients with cirrhosis. Effects of propranolol

Journal of Hepatology, 2002

Background: Total effective vascular compliance (TEVC), may be increased in cirrhosis. However, i... more Background: Total effective vascular compliance (TEVC), may be increased in cirrhosis. However, its significance is unclear. Aims: To investigate TEVC in patients with cirrhosis, and the effects of propranolol. Methods: Seven patients without liver disease and 44 cirrhotic patients were studied before and after double-blind administration of propranolol (n ¼ 33) or placebo (n ¼ 11). Measurements: TEVC (right atrial pressure response to rapid central volume expansion), hepatic venous pressure gradient (HVPG) and systemic hemodynamics. Results: TEVC (ml mmHg 21 kg 21) was increased in cirrhotics (1.67^0.66 versus 1.33^0.32 in controls; P , 0:05). TEVC was not modified by placebo, but was markedly reduced by propranolol (from 1.74^0.75 to 1.33^0.56; P , 0:01). Propranolol decreased HVPG .10% in 20 patients ('responders': 220^9%) but ,10% in 13 'nonresponders'. TEVC was normalized by propranolol in HVPG 'responders' (from 1.76^0.88 to 1.21^0.51; P , 0:01), but not in 'non-responders' (1.69^0.48 to 1.52^0.59; NS). Reduction of TEVC in responders was accompanied by increased free hepatic vein pressure (121^20%, P ¼ 0:05; ,60% of the fall in HVPG), which was not observed in non-responders (13^11%, NS). Conclusions: TEVC is increased in cirrhosis. This abnormality is corrected by propranolol in patients exhibiting a .10% fall in HVPG, suggesting that changes in vascular compliance may influence the portal pressure response to propranolol.

766 Early lobular necrosis and living donor liver transplantation are strong predictors of severe HCV recurrence after liver

Hepatology, 2003

TIPS is a useful long-term derivative therapy for patients with Budd-Chiari syndrome uncontrolled by medical therapy

Hepatology, 2002

Patients with Budd-Chiari syndrome (BCS) may require treatment with portal decompressive surgery ... more Patients with Budd-Chiari syndrome (BCS) may require treatment with portal decompressive surgery or liver transplantation. Transjugular intrahepatic portosystemic shunt (TIPS) represents a new treatment alternative, but its long-term effect on BCS outcome has not been evaluated. Twenty-one patients with BCS consecutively admitted to our unit were evaluated. The mean follow-up was 4 +/- 3 years. Seven patients had nonprogressive forms and were successfully controlled with medical therapy; 1 case, with a short-length hepatic vein stenosis was successfully treated by angioplasty. All 8 patients are alive and asymptomatic. The remaining 13 patients, had a TIPS because of clinical deterioration (in one of them, because early TIPS thrombosis a successful side-to-side portacaval shunt [SSPCS] was performed) followed by an improvement in clinical condition. However, a patient with fulminant liver failure before TIPS insertion, died 4 months later and another patient with cirrhosis at diagnosis had liver transplantation 2 years later. The remaining 11 patients are alive and free of ascites. In 3 of these patients TIPS is patent after 3, 6, and 12 months. The remaining 8 patients developed late TIPS dysfunction. In two of these cases, after angioplasty and restenting, TIPS is patent after a follow-up of 9 and 80 months. In 5 other patients, recurring TIPS occlusion was not further corrected because no signs of portal hypertension were present. In conclusion, in patients with BCS uncontrolled with medical therapy, TIPS is a highly effective technique that is associated with long-term survival.

Multicenter Randomized Controlled Trial of Terlipressin Versus Sclerotherapy in the Treatment of Acute Variceal Bleeding: The TEST Study

Hepatology, 2000

Failure to control bleeding and early rebleeding account for the high mortality associated with v... more Failure to control bleeding and early rebleeding account for the high mortality associated with variceal hemorrhage in cirrhosis. We compared endoscopic sclerotherapy to terlipressin, a drug that effectively controls acute bleeding while reducing in-hospital mortality. This multicenter randomized controlled trial included 219 cirrhotic patients admitted for endoscopy-proven acute variceal bleeding and randomized to receive repeated injections of terlipressin during 6 days (n = 105) or emergency sclerotherapy (n = 114). Success was defined as obtaining control of bleeding (24-hour bleeding-free period during the first 48 hours) and lack of early rebleeding (any further bleeding from initial control to 5 days later) and survival during the study. Both groups were similar at inclusion. Failure rate for terlipressin was 33% and 32% for sclerotherapy (not significant [NS]). Early rebleeding was responsible for 43% and 44% of failures, respectively. This high efficacy was observed in both Child-Pugh class A + B and Child-Pugh class C patients. Both treatments were similar regarding transfusion requirements, in-hospital stay, and 6-week mortality (26 vs. 19 patients). Side effects appeared in 20% of patients receiving terlipressin and in 30% of those on sclerotherapy (P =.06); being serious in 4% and 7%, respectively (NS). In conclusion, terlipressin and sclerotherapy are equally highly effective therapies achieving the initial control of variceal bleeding and preventing early rebleeding. Both treatments are safe, but terlipressin is better tolerated. Therefore, terlipressin may represent a first-line treatment in acute variceal bleeding until the administration of elective therapy, especially in hospitals where a skilled endoscopist is not available 24 hours a day.

Noncirrhotic portal vein thrombosis exhibits neuropsychological and MR changes consistent with minimal hepatic encephalopathy

Hepatology, 2006

Hepatic encephalopathy can arise from portal-systemic shunting in the absence of intrinsic liver ... more Hepatic encephalopathy can arise from portal-systemic shunting in the absence of intrinsic liver disease. However, there are few descriptions of this form of encephalopathy. Portal vein thrombosis is an infrequent disease that causes portal-systemic shunting. Episodic hepatic encephalopathy has been described in patients with portal vein thrombosis, but it is not known if these patients develop minimal hepatic encephalopathy. We designed a study to investigate the neurological consequences of portal vein thrombosis in patients without cirrhosis and no clinical signs of encephalopathy. For this purpose, 10 patients underwent neuropsychological tests, an oral glutamine challenge test, and brain magnetic resonance (MR) imaging. The results were compared with those obtained in 10 healthy controls. Patients with portal vein thrombosis exhibited abnormalities in the results of neuropsychological tests, oral glutamine challenge test, and MR similar to those described in hepatic encephalopathy associated with cirrhosis. MR spectroscopy revealed a decrease in myoinositol and an increase in glutamine. The increase in glutamine correlated with an increase in ammonia following the oral glutamine challenge test, signs of increased brain water (decrease in magnetization transfer ratio), and impairment of attention tests. In conclusion, patients with noncirrhotic portal vein thrombosis develop subclinical neurological abnormalities compatible with minimal hepatic encephalopathy. These disturbances, which include signs of increase in brain water and a compensatory osmotic response (decrease in brain myo-inositol), appear to be secondary to brain exposure to ammonia induced by portal-systemic shunting.

Anemia increases gastric blood flow in noncirrhotic and cirrhotic patients

Gastrointestinal Endoscopy, 1995

Previous studies in rats have demonstrated that anemia induces a significant increment in gastric... more Previous studies in rats have demonstrated that anemia induces a significant increment in gastric mucosal blood flow. In the present study, we investigated whether chronic anemia induces similar changes in gastric blood perfusion in humans, and if this effect is also present in cirrhotic patients in whom gastric blood flow is usually increased in basal conditions. Gastric mucosal blood perfusion was assessed by means of laser-Doppler flowmetry and reflectance spectrophotometry applied through the endoscope. Anemia significantly increases laser-Doppler signal in cirrhotic (2.3 +/- 0.11 vs 2.9 +/- 0.22 volts, p &amp;amp;amp;amp;lt; 0.05) and noncirrhotic patients (1.71 +/- 0.15 vs 2.24 +/- 0.17, p &amp;amp;amp;amp;lt; 0.05). In anemic patients the index of hemoglobin concentration of the gastric mucosa, assessed by reflectance spectrophotometry, was significantly decreased in cirrhotic patients (107.6 +/- 4.7 vs 95.5 +/- 3.3, p &amp;amp;amp;amp;lt; 0.05) and noncirrhotic patients (93.9 +/- 4.1 vs 76.1 +/- 4.2, p &amp;amp;amp;amp;lt; 0.01), whereas the index of oxygen saturation was increased (36.7 +/- 0.7 vs 40.4 +/- 1.4, p = 0.05; and 36.4 +/- 1.1 vs 43.2 +/- 1.9, p &amp;amp;amp;amp;lt; 0.01, respectively). In conclusion, chronic anemia is associated with an enhanced gastric blood perfusion reflected by an increased laser-doppler signal and gastric mucosal oxygen index despite a decrease in gastric hemoglobin concentration. In cirrhotic patients, anemia promotes a further increment in its basal gastric hyperemia.

Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension

Gastroenterology, 2001

Clinical events after transjugular intrahepatic portosystemic shunt: Correlation with hemodynamic findings

Gastroenterology, 1998

Transjugular intrahepatic portosystemic shunt (TIPS) procedures are increasingly being used, but ... more Transjugular intrahepatic portosystemic shunt (TIPS) procedures are increasingly being used, but the relationship between the hemodynamic effects of TIPS and the clinical events on follow-up remains undefined. Hence, we have investigated the hemodynamic correlations of portal hypertension-related events after a TIPS procedure. Prospective follow-up of 122 cirrhotic patients who had a TIPS procedure performed because of variceal hemorrhage was conducted. The portacaval pressure gradient (PPG) significantly decreased after the TIPS procedure (from 19.7 +/- 4.6 to 8.6 +/- 2.7 mm Hg; P &amp;amp;amp;amp;amp;amp;gt; 0.001), but increased thereafter and at rebleeding (n = 25) was &amp;amp;amp;amp;amp;amp;gt; 12 mm Hg in all patients (18.4 +/- 4.6 mm Hg). Twenty-six patients developed ascites; the PPG (measured in 19) was always &amp;amp;amp;amp;amp;amp;gt; 12 mm Hg. Increasing the PPG to &amp;amp;amp;amp;amp;amp;gt; 12 mm Hg occurred very frequently (83% at 1 year). Within 1 year, 77% of patients underwent balloon angioplasty or restenting. However, 80% had again a PPG of &amp;amp;amp;amp;amp;amp;gt; 12 mm Hg 1 year after reintervention. Hepatic encephalopathy developed in 31% of patients at 1 year; 21 of 23 patients had a PPG of &amp;amp;amp;amp;amp;amp;lt; 12 mm Hg. Total protection from the risk of recurrent complications of portal hypertension after a TIPS procedure requires that the PPG be decreased and maintained &amp;amp;amp;amp;amp;amp;lt; 12 mm Hg. However, reintervention will be required in most patients within 1 year and again the second year. On the other hand, such portal decompression is associated with an increased risk of hepatic encephalopathy.

Isosorbide Mononitrate in the Prevention of First Variceal Bleed in Patients Who Cannot Receive β-blockers

Gastroenterology, 2001

Pathophysiology of variceal bleeding in cirrhotics

Patency of stents covered with polytetrafluoroethylene in patients treated by transjugular intrahepatic portosystemic shunts: long-term results of a randomized multicentre study

Liver International, 2007

An 80% dysfunction rate at 2 years limits the use of transjugular intrahepatic portosystemic shun... more An 80% dysfunction rate at 2 years limits the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of complications of portal hypertension. The use of covered stents could improve shunt patency; however, long-term effect and safety remain unknown. Eighty patients randomized to be treated by TIPS either with a covered stent (Group 1) or an uncovered prosthesis (Group 2) were followed-up for 2 years. Doppler US was performed every 3 months. Angiography and portosystemic pressure gradient measurement were performed every 6 months or whenever dysfunction was suspected. Actuarial rates of primary patency in Groups 1 and 2 were 76% and 36% respectively (P = 0.001). Clinical relapse occurred in four patients (10%) in Group 1 and 12 (29%) in Group 2 (P o 0.05). Actuarial rates of being free of encephalopathy were 67% in Group 1 and 51% in Group 2 (P o 0.05). Probability of survival was 58% and 45% at 2 years, respectively, in Groups 1 and 2 (NS). The mean Child-Pugh score improved only in Group 1 (from 8.1 AE 1.6 to 7 AE 2.2 at 2 years-P o 0.05). We also compared the Doppler-US parameters between patent and dysfunctioning shunts. In patent shunts, the mean velocity within the portal vein was significantly higher but the performance of Doppler-US was not accurate enough to predict shunt dysfunction. In conclusion, the improvement in TIPS patency by using covered prostheses is maintained over time with a decreased risk of encephalopathy, while the risk of death was not increased.

1 Lavina et al. SUPEROXIDE DISMUTASE GENE TRANSFER REDUCES PORTAL PRESSURE IN CCl4 CIRRHOTIC RATS WITH PORTAL HYPERTENSION

oxide synthase (eNOS), nitric oxide (NO), nitrotyrosine (NT), acetylcholine (Ach), mean arterial ... more oxide synthase (eNOS), nitric oxide (NO), nitrotyrosine (NT), acetylcholine (Ach), mean arterial pressure (MAP), reactive oxidative species (ROS), Adenovirus (Ad), β-galactosidase (βgal), carbon tetrachloride (CCl4), dihydroethidium (DHE), portal perfusion pressure (PP), methoxamine (Mtx). Background: Increased intrahepatic vascular tone in cirrhosis has been attributed to decrease hepatic nitric oxide (NO) secondary to disturbances in the posttranslational regulation of the enzyme eNOS. NO scavenging by superoxide (O2-) further contributes to reduce NO bioavailability in cirrhotic livers. Aim: To investigate whether removing increased O2- levels could be a new therapeutic strategy to increase intrahepatic NO, improve endothelial dysfunction and reduce portal pressure in cirrhotic rats with portal hypertension. Methods: Adenoviral vectors expressing extracellular SOD (AdECSOD) or ß-galactosidase (Adβgal) were injected intravenously in control and CCl4-induced cirrhotic rats. After 3...

Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction

Journal of Hepatology, 2021

Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to ... more Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acute-on-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure(s). The pathomechanisms involved in decompensation and disease progression are still not well understood, and as specific disease-modifying treatments do not exist, research to identify novel therapeutic targets is of the utmost importance. This review amalgamates the latest knowledge on disease mechanisms that lead to tissue injury and extrahepatic organ failure - such as systemic inflammation, mitochondrial dysfunction, oxidative stress and metabolic changes - and marries these with the classical paradigms of acute decompensation to form a single paradigm. With this detailed breakdown of pathomechanisms, we identify areas for future research. Novel disease-modifying strategies that break the vicious cycle are urgently required to improve patient outcomes.

Reply to: “First things first! Can bacterial infections be considered as decompensating events per se?”

Journal of Hepatology, 2021

Anemia Worsens Hyperdynamic Circulation of Patients with Cirrhosis and Portal Hypertension

Digestive Diseases and Sciences, 1997

This retrospective cohort study was aimed atinvestigating the effects of anemia on the hemodynami... more This retrospective cohort study was aimed atinvestigating the effects of anemia on the hemodynamicdisturbances associated with portal hypertension. Inall, 202 consecutive nontreated portal-hypertensive patients referred for evaluation to our HepaticHemodynamic Laboratory were included. Compared to thenonanemic patients, anemic cirrhotic patients had anincreased cardiac output (7.9 ± 1.9 vs 7.1± 2 liters/min, P 5, P < 0.0001). Similar resultswere obtained when

Stenosis of the suprahepatic inferior vena cava as a complication of transjugular intrahepatic portosystemic shunt in Budd-Chiari patients

Liver Transplantation, 2001

Metabolomics Discloses Potential Biomarkers for the Noninvasive Diagnosis of Idiopathic Portal Hypertension

American Journal of Gastroenterology, 2013

Idiopathic portal hypertension (IPH) is a rare cause of portal hypertension that lacks a specifi ... more Idiopathic portal hypertension (IPH) is a rare cause of portal hypertension that lacks a specifi c diagnostic test. Requiring ruling-out other causes of portal hypertension it is frequently misdiagnosed. This study evaluates whether using high-throughput techniques there is a metabolomic profi le allowing a noninvasive diagnosis of IPH. METHODS : Thirty-three IPH patients were included. Matched patients with cirrhosis (CH) and healthy volunteers (HV) were included as controls. Metabolomic analysis of plasma samples was performed using UPLCtime-of-fl ight-mass spectrometry. We computed Student ' s P-values, corrected by multiple comparison and VIP score (Variable Importance in the Projection). The metabolites were selected with an adjusted Benjamini Hochberg P value < 0.05. We use markers with a greater VIP score, to build partial least squares projection to latent structures regression with discriminant analysis (PLS-DA) representative models to discriminate IPH from CH and from HV. The performance of the PLS-DA model was evaluated using R 2 and Q 2 parameter. An additional internal cross-validation was done. RESULTS : PLS-DA analysis showed a clear separation of IPH from CH with a model involving 28 metabolites (Q 2 = 0.67, area under the curve (AUC) = 0.99) and a clear separation of IPH from healthy subjects with a model including 31 metabolites (Q 2 = 0.75, AUC = 0.98). After cross-validation, both models showed high rates of sensitivity (94.8 and 97.5), specifi city (89.1 and 89.7), and AUC (0.98 and 0.98), reinforcing the strength of our fi ndings. CONCLUSIONS : A metabolomic profi le clearly differentiating patients with IPH from CH and healthy subjects has been identifi ed using subsets of 28 and 31 metabolites, respectively. Therefore, metabolomic analysis appears to be a valuable tool for the noninvasive diagnosis of IPH.

A prospective observational study on tolerance and satisfaction to hepatic haemodynamic procedures

Liver International, 2014

Understanding patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;am... more Understanding patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; attitudes to clinical experiences is essential for developing high-quality patient-centred healthcare, as a better knowledge of patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; tolerance and satisfaction might allow implementing measures that ameliorate comfort, care and use of resources. We aimed to describe patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; tolerance and satisfaction to invasive hepatic haemodynamic procedures, and to investigate which factors might influence patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; perspective in this field. Visual Analogue Scale (VAS) questionnaires regarding pain and duration (for tolerance), and comfort and general handling (for satisfaction) were prospectively administered to all consecutive patients (N = 327) submitted to hepatic haemodynamic procedures (N = 355) in a tertiary care setting during 2011. VAS scores ranged between 0 and 100 mm and items were defined as excellent if &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10 mm; good if 10-20 mm and inadequate if &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20 mm. Clinical and laboratory data were also collected. Satisfaction was excellent in &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;95% of cases (mean 2 ± 5 mm, median 0 mm) and average tolerance was good (15 ± 18 mm; median 6 mm). A percentage of 59% of patients had excellent tolerance, 9% good and 32% had inadequate tolerance. Duration and complexity of the procedure and limited operator&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s experience were associated with inadequate tolerance on univariate analysis; duration of the procedure remained the only independent factor associated with inadequate tolerance on multivariate analysis. Procedures lasting &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;35 min had a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;80% probability of being well tolerated. Satisfaction and tolerance to hepatic haemodynamic procedures are excellent and good respectively. Tolerance was decreased in long procedures; hence reducing as much as possible the duration of the procedures might further improve tolerance.

P517 Effects of Sapropterin on Portal and Systemic Hemodynamics in Patients with Cirrhosis and Portal Hypertension: A Bicentric Double-Blind Placebo Controlled Study

Journal of Hepatology, 2014

POSTERS hemodynamic data were collected. Pro-C5 was analysed as a single marker and combined in a... more POSTERS hemodynamic data were collected. Pro-C5 was analysed as a single marker and combined in a linear regression model with ALT, bilirubin, MELD, and Child score. Follow-up time was five year and mortality was analysed by log-rank. Pro-C5 was assessed in arterial plasma samples. Results: Pro-C5 clearly separated patients with a HVPG <10 mmHg or HVPG≥10 mmHg (p < 0.001, AUC=0.73) and controls (p < 0.0001, AUC=0.88). Pro-C5 correlated significantly with HVPG, ICGclearance, SVR and MAP (r = −0.68-0.33, p < 0.0001). A multiple regression analysis including Pro-C5, ALT, bilirubin MELD and Child improved the correlation to HVPG (r = 0.74, p < 0.0001). Moreover, Pro-C5 correlated with liver function markers and MELD (r = 0.31-0.68; p < 0.01-0.0001). Finally, there was a clear relation to increasing Child score A-C and plasma Pro-C5 (ANOVA p < 0.001) but no significant relation of Pro-C5 to mortality. Conclusions: Plasma Pro-C5 reflects both splanchnic and systemic hemodynamics in cirrhosis including PHT, liver function and stage of disease. A multimarker model in combination with clinical scores predicted HVPG and was able to diagnose clinical relevant HVPG non-invasively. Therefore Pro-C5 is a promising plasma marker of significant portal hypertension in cirrhosis.

Effects of propranolol on venous compliance in conscious rats with pre-hepatic portal hypertension

Journal of Hepatology, 2006

Background/Aims: The venous system is the primary capacitance region in the body. However, the in... more Background/Aims: The venous system is the primary capacitance region in the body. However, the influence of active changes in the venous system on the hemodynamic alterations of portal hypertension is poorly understood. To investigate venous compliance (VC) in conscious partial portal vein ligated rats (PPVL) and the effect of propranolol on VC. Methods: Venous compliance was derived from the relationship between changes in mean circulatory filling pressure (MCFP) and changes in blood volume (BV). Measurements were performed before and after i.v. propranolol (7.5 mg/Kg) or placebo in rats with portal hypertension due to PPVL and sham operated controls. Results: PPVL rats had an increased VC when compared to Sham (4.9G1.4 vs. 3.7G0.9 ml kg K1 mmHg K1 ; P!0.02). VC did not change after placebo but was significantly reduced by Propranolol in PPVL (K32.9G15.7%; P!0,007). Propranolol did not modify venous compliance in sham operated rats (C10.9G13.4%; PZns). Conclusions: Venous compliance is increased in portal hypertensive rats, suggesting that the venous system contributes to the profound circulatory changes encountered in portal hypertension. The increased venous compliance is markedly attenuated by propranolol, suggesting that this abnormality is related to increased adrenergic activity.

Total effective vascular compliance in patients with cirrhosis. Effects of propranolol

Journal of Hepatology, 2002

Background: Total effective vascular compliance (TEVC), may be increased in cirrhosis. However, i... more Background: Total effective vascular compliance (TEVC), may be increased in cirrhosis. However, its significance is unclear. Aims: To investigate TEVC in patients with cirrhosis, and the effects of propranolol. Methods: Seven patients without liver disease and 44 cirrhotic patients were studied before and after double-blind administration of propranolol (n ¼ 33) or placebo (n ¼ 11). Measurements: TEVC (right atrial pressure response to rapid central volume expansion), hepatic venous pressure gradient (HVPG) and systemic hemodynamics. Results: TEVC (ml mmHg 21 kg 21) was increased in cirrhotics (1.67^0.66 versus 1.33^0.32 in controls; P , 0:05). TEVC was not modified by placebo, but was markedly reduced by propranolol (from 1.74^0.75 to 1.33^0.56; P , 0:01). Propranolol decreased HVPG .10% in 20 patients ('responders': 220^9%) but ,10% in 13 'nonresponders'. TEVC was normalized by propranolol in HVPG 'responders' (from 1.76^0.88 to 1.21^0.51; P , 0:01), but not in 'non-responders' (1.69^0.48 to 1.52^0.59; NS). Reduction of TEVC in responders was accompanied by increased free hepatic vein pressure (121^20%, P ¼ 0:05; ,60% of the fall in HVPG), which was not observed in non-responders (13^11%, NS). Conclusions: TEVC is increased in cirrhosis. This abnormality is corrected by propranolol in patients exhibiting a .10% fall in HVPG, suggesting that changes in vascular compliance may influence the portal pressure response to propranolol.

766 Early lobular necrosis and living donor liver transplantation are strong predictors of severe HCV recurrence after liver

Hepatology, 2003

TIPS is a useful long-term derivative therapy for patients with Budd-Chiari syndrome uncontrolled by medical therapy

Hepatology, 2002

Patients with Budd-Chiari syndrome (BCS) may require treatment with portal decompressive surgery ... more Patients with Budd-Chiari syndrome (BCS) may require treatment with portal decompressive surgery or liver transplantation. Transjugular intrahepatic portosystemic shunt (TIPS) represents a new treatment alternative, but its long-term effect on BCS outcome has not been evaluated. Twenty-one patients with BCS consecutively admitted to our unit were evaluated. The mean follow-up was 4 +/- 3 years. Seven patients had nonprogressive forms and were successfully controlled with medical therapy; 1 case, with a short-length hepatic vein stenosis was successfully treated by angioplasty. All 8 patients are alive and asymptomatic. The remaining 13 patients, had a TIPS because of clinical deterioration (in one of them, because early TIPS thrombosis a successful side-to-side portacaval shunt [SSPCS] was performed) followed by an improvement in clinical condition. However, a patient with fulminant liver failure before TIPS insertion, died 4 months later and another patient with cirrhosis at diagnosis had liver transplantation 2 years later. The remaining 11 patients are alive and free of ascites. In 3 of these patients TIPS is patent after 3, 6, and 12 months. The remaining 8 patients developed late TIPS dysfunction. In two of these cases, after angioplasty and restenting, TIPS is patent after a follow-up of 9 and 80 months. In 5 other patients, recurring TIPS occlusion was not further corrected because no signs of portal hypertension were present. In conclusion, in patients with BCS uncontrolled with medical therapy, TIPS is a highly effective technique that is associated with long-term survival.

Multicenter Randomized Controlled Trial of Terlipressin Versus Sclerotherapy in the Treatment of Acute Variceal Bleeding: The TEST Study

Hepatology, 2000

Failure to control bleeding and early rebleeding account for the high mortality associated with v... more Failure to control bleeding and early rebleeding account for the high mortality associated with variceal hemorrhage in cirrhosis. We compared endoscopic sclerotherapy to terlipressin, a drug that effectively controls acute bleeding while reducing in-hospital mortality. This multicenter randomized controlled trial included 219 cirrhotic patients admitted for endoscopy-proven acute variceal bleeding and randomized to receive repeated injections of terlipressin during 6 days (n = 105) or emergency sclerotherapy (n = 114). Success was defined as obtaining control of bleeding (24-hour bleeding-free period during the first 48 hours) and lack of early rebleeding (any further bleeding from initial control to 5 days later) and survival during the study. Both groups were similar at inclusion. Failure rate for terlipressin was 33% and 32% for sclerotherapy (not significant [NS]). Early rebleeding was responsible for 43% and 44% of failures, respectively. This high efficacy was observed in both Child-Pugh class A + B and Child-Pugh class C patients. Both treatments were similar regarding transfusion requirements, in-hospital stay, and 6-week mortality (26 vs. 19 patients). Side effects appeared in 20% of patients receiving terlipressin and in 30% of those on sclerotherapy (P =.06); being serious in 4% and 7%, respectively (NS). In conclusion, terlipressin and sclerotherapy are equally highly effective therapies achieving the initial control of variceal bleeding and preventing early rebleeding. Both treatments are safe, but terlipressin is better tolerated. Therefore, terlipressin may represent a first-line treatment in acute variceal bleeding until the administration of elective therapy, especially in hospitals where a skilled endoscopist is not available 24 hours a day.

Noncirrhotic portal vein thrombosis exhibits neuropsychological and MR changes consistent with minimal hepatic encephalopathy

Hepatology, 2006

Hepatic encephalopathy can arise from portal-systemic shunting in the absence of intrinsic liver ... more Hepatic encephalopathy can arise from portal-systemic shunting in the absence of intrinsic liver disease. However, there are few descriptions of this form of encephalopathy. Portal vein thrombosis is an infrequent disease that causes portal-systemic shunting. Episodic hepatic encephalopathy has been described in patients with portal vein thrombosis, but it is not known if these patients develop minimal hepatic encephalopathy. We designed a study to investigate the neurological consequences of portal vein thrombosis in patients without cirrhosis and no clinical signs of encephalopathy. For this purpose, 10 patients underwent neuropsychological tests, an oral glutamine challenge test, and brain magnetic resonance (MR) imaging. The results were compared with those obtained in 10 healthy controls. Patients with portal vein thrombosis exhibited abnormalities in the results of neuropsychological tests, oral glutamine challenge test, and MR similar to those described in hepatic encephalopathy associated with cirrhosis. MR spectroscopy revealed a decrease in myoinositol and an increase in glutamine. The increase in glutamine correlated with an increase in ammonia following the oral glutamine challenge test, signs of increased brain water (decrease in magnetization transfer ratio), and impairment of attention tests. In conclusion, patients with noncirrhotic portal vein thrombosis develop subclinical neurological abnormalities compatible with minimal hepatic encephalopathy. These disturbances, which include signs of increase in brain water and a compensatory osmotic response (decrease in brain myo-inositol), appear to be secondary to brain exposure to ammonia induced by portal-systemic shunting.

Anemia increases gastric blood flow in noncirrhotic and cirrhotic patients

Gastrointestinal Endoscopy, 1995

Previous studies in rats have demonstrated that anemia induces a significant increment in gastric... more Previous studies in rats have demonstrated that anemia induces a significant increment in gastric mucosal blood flow. In the present study, we investigated whether chronic anemia induces similar changes in gastric blood perfusion in humans, and if this effect is also present in cirrhotic patients in whom gastric blood flow is usually increased in basal conditions. Gastric mucosal blood perfusion was assessed by means of laser-Doppler flowmetry and reflectance spectrophotometry applied through the endoscope. Anemia significantly increases laser-Doppler signal in cirrhotic (2.3 +/- 0.11 vs 2.9 +/- 0.22 volts, p &amp;amp;amp;amp;lt; 0.05) and noncirrhotic patients (1.71 +/- 0.15 vs 2.24 +/- 0.17, p &amp;amp;amp;amp;lt; 0.05). In anemic patients the index of hemoglobin concentration of the gastric mucosa, assessed by reflectance spectrophotometry, was significantly decreased in cirrhotic patients (107.6 +/- 4.7 vs 95.5 +/- 3.3, p &amp;amp;amp;amp;lt; 0.05) and noncirrhotic patients (93.9 +/- 4.1 vs 76.1 +/- 4.2, p &amp;amp;amp;amp;lt; 0.01), whereas the index of oxygen saturation was increased (36.7 +/- 0.7 vs 40.4 +/- 1.4, p = 0.05; and 36.4 +/- 1.1 vs 43.2 +/- 1.9, p &amp;amp;amp;amp;lt; 0.01, respectively). In conclusion, chronic anemia is associated with an enhanced gastric blood perfusion reflected by an increased laser-doppler signal and gastric mucosal oxygen index despite a decrease in gastric hemoglobin concentration. In cirrhotic patients, anemia promotes a further increment in its basal gastric hyperemia.

Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension

Gastroenterology, 2001

Clinical events after transjugular intrahepatic portosystemic shunt: Correlation with hemodynamic findings

Gastroenterology, 1998

Transjugular intrahepatic portosystemic shunt (TIPS) procedures are increasingly being used, but ... more Transjugular intrahepatic portosystemic shunt (TIPS) procedures are increasingly being used, but the relationship between the hemodynamic effects of TIPS and the clinical events on follow-up remains undefined. Hence, we have investigated the hemodynamic correlations of portal hypertension-related events after a TIPS procedure. Prospective follow-up of 122 cirrhotic patients who had a TIPS procedure performed because of variceal hemorrhage was conducted. The portacaval pressure gradient (PPG) significantly decreased after the TIPS procedure (from 19.7 +/- 4.6 to 8.6 +/- 2.7 mm Hg; P &amp;amp;amp;amp;amp;amp;gt; 0.001), but increased thereafter and at rebleeding (n = 25) was &amp;amp;amp;amp;amp;amp;gt; 12 mm Hg in all patients (18.4 +/- 4.6 mm Hg). Twenty-six patients developed ascites; the PPG (measured in 19) was always &amp;amp;amp;amp;amp;amp;gt; 12 mm Hg. Increasing the PPG to &amp;amp;amp;amp;amp;amp;gt; 12 mm Hg occurred very frequently (83% at 1 year). Within 1 year, 77% of patients underwent balloon angioplasty or restenting. However, 80% had again a PPG of &amp;amp;amp;amp;amp;amp;gt; 12 mm Hg 1 year after reintervention. Hepatic encephalopathy developed in 31% of patients at 1 year; 21 of 23 patients had a PPG of &amp;amp;amp;amp;amp;amp;lt; 12 mm Hg. Total protection from the risk of recurrent complications of portal hypertension after a TIPS procedure requires that the PPG be decreased and maintained &amp;amp;amp;amp;amp;amp;lt; 12 mm Hg. However, reintervention will be required in most patients within 1 year and again the second year. On the other hand, such portal decompression is associated with an increased risk of hepatic encephalopathy.

Isosorbide Mononitrate in the Prevention of First Variceal Bleed in Patients Who Cannot Receive β-blockers

Gastroenterology, 2001

Pathophysiology of variceal bleeding in cirrhotics

Patency of stents covered with polytetrafluoroethylene in patients treated by transjugular intrahepatic portosystemic shunts: long-term results of a randomized multicentre study

Liver International, 2007

An 80% dysfunction rate at 2 years limits the use of transjugular intrahepatic portosystemic shun... more An 80% dysfunction rate at 2 years limits the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of complications of portal hypertension. The use of covered stents could improve shunt patency; however, long-term effect and safety remain unknown. Eighty patients randomized to be treated by TIPS either with a covered stent (Group 1) or an uncovered prosthesis (Group 2) were followed-up for 2 years. Doppler US was performed every 3 months. Angiography and portosystemic pressure gradient measurement were performed every 6 months or whenever dysfunction was suspected. Actuarial rates of primary patency in Groups 1 and 2 were 76% and 36% respectively (P = 0.001). Clinical relapse occurred in four patients (10%) in Group 1 and 12 (29%) in Group 2 (P o 0.05). Actuarial rates of being free of encephalopathy were 67% in Group 1 and 51% in Group 2 (P o 0.05). Probability of survival was 58% and 45% at 2 years, respectively, in Groups 1 and 2 (NS). The mean Child-Pugh score improved only in Group 1 (from 8.1 AE 1.6 to 7 AE 2.2 at 2 years-P o 0.05). We also compared the Doppler-US parameters between patent and dysfunctioning shunts. In patent shunts, the mean velocity within the portal vein was significantly higher but the performance of Doppler-US was not accurate enough to predict shunt dysfunction. In conclusion, the improvement in TIPS patency by using covered prostheses is maintained over time with a decreased risk of encephalopathy, while the risk of death was not increased.

1 Lavina et al. SUPEROXIDE DISMUTASE GENE TRANSFER REDUCES PORTAL PRESSURE IN CCl4 CIRRHOTIC RATS WITH PORTAL HYPERTENSION

oxide synthase (eNOS), nitric oxide (NO), nitrotyrosine (NT), acetylcholine (Ach), mean arterial ... more oxide synthase (eNOS), nitric oxide (NO), nitrotyrosine (NT), acetylcholine (Ach), mean arterial pressure (MAP), reactive oxidative species (ROS), Adenovirus (Ad), β-galactosidase (βgal), carbon tetrachloride (CCl4), dihydroethidium (DHE), portal perfusion pressure (PP), methoxamine (Mtx). Background: Increased intrahepatic vascular tone in cirrhosis has been attributed to decrease hepatic nitric oxide (NO) secondary to disturbances in the posttranslational regulation of the enzyme eNOS. NO scavenging by superoxide (O2-) further contributes to reduce NO bioavailability in cirrhotic livers. Aim: To investigate whether removing increased O2- levels could be a new therapeutic strategy to increase intrahepatic NO, improve endothelial dysfunction and reduce portal pressure in cirrhotic rats with portal hypertension. Methods: Adenoviral vectors expressing extracellular SOD (AdECSOD) or ß-galactosidase (Adβgal) were injected intravenously in control and CCl4-induced cirrhotic rats. After 3...

Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction

Journal of Hepatology, 2021

Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to ... more Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acute-on-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure(s). The pathomechanisms involved in decompensation and disease progression are still not well understood, and as specific disease-modifying treatments do not exist, research to identify novel therapeutic targets is of the utmost importance. This review amalgamates the latest knowledge on disease mechanisms that lead to tissue injury and extrahepatic organ failure - such as systemic inflammation, mitochondrial dysfunction, oxidative stress and metabolic changes - and marries these with the classical paradigms of acute decompensation to form a single paradigm. With this detailed breakdown of pathomechanisms, we identify areas for future research. Novel disease-modifying strategies that break the vicious cycle are urgently required to improve patient outcomes.

Reply to: “First things first! Can bacterial infections be considered as decompensating events per se?”

Journal of Hepatology, 2021