Active clinical trials for "Hypertension, Portal"

Minimal hepatic encephalopathy (MHE) is a subclinical cognitive impairment and represents the mildest type of hepatic encephalopathy (HE). Portal hypertension is the main complication of cirrhosis and is responsible of severe complications such as HE. The consequence of portal hypertension is the formation of the spontaneous portosystemic shunts (SPSS). The relationship between the SPSS and their characteristics and the prevalence of MHE in patient with cirrhosis is poorly known. The main objective of this study is to evaluate the MHE in patients with cirrhosis and portal hypertension.

Rationale: Hepatic encephalopathy (HE) is a major and common complication in patients with liver cirrhosis. HE can be classified in the extensive range of neurocognitive deterioration as minimal HE (MHE), covert HE (grade I), or overt HE (OHE, grade II-IV). Liver cirrhosis is the most common cause of portal hypertension (PH). Patients who develop complications of PH, like variceal bleeding or refractory ascites, can benefit from a Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement. Unfortunately, post-TIPS HE is a common and often severe complication. Incidence of new onset or worsening of HE after TIPS is approximately 20-45%. Currently there is no strategy to prevent post-TIPS HE.

This is an open-label, non-randomized trial that will be conducted at three clinical sites, Thomas Jefferson University (TJU), the Hospital of the University of Pennsylvania (HUP) and University of Bern (UB). Enrollment will be allocated into one of 4 different cohorts depending on the inclusion criteria for each cohort. Cohort 1: Patients scheduled for hepatic vein pressure gradient (HVPG) measurements will subsequently undergo two consecutive SHAPE (subharmonic aided pressure estimation) procedures using different ultrasound contrast agents (Definity [Lantheus Medical Imaging, N Bilerica, MA, USA] and Sonazoid [GE Healthcare, Oslo, Norway] in randomized order) to estimate portal pressures with a Logiq E10 scanner (GE Healthcare, Waukesha, WI, USA) and determine the reproducibility of the SHAPE algorithm. Cohort 2: Patients identified as having clinically significant portal hypertension (CSPH) will be monitored by SHAPE with Sonazoid for the duration of this project (18-24 months on average). These subjects will have follow-up ultrasound scans every 6 ± 2 months to check for hepatocellular carcinoma (HCC) (using the Barcelona-Liver Cancer staging system) as well as ascites and at those times a repeat SHAPE examination will be performed. Liver stiffness values will be measured with elastography as well. This cohort will examine if serial SHAPE can accurately predict development of ascites and other liver related events in patients with compensated cirrhosis undergoing routine HCC surveillance in a multi-center setting. Cohort 3: Subjects newly diagnosed with portal hypertension and starting treatment with non-selective β-blockers will be monitored with SHAPE and results compared to elastography measurements of liver stiffness with standard assessments (e.g., serum liver function tests and measurement of spleen size as well as platelet count). This cohort will establish if SHAPE can be used to monitor treatment response in patients identified with portal hypertension. Cohort 4: Patients with compensated advanced chronic liver disease scheduled for an endoscopy examination for screening of varices relative to the Baveno VI and the expanded-Baveno VI criteria as well as the AST to Platelet Ratio Index will undergo a SHAPE examination. This cohort will compare the predictive ability of SHAPE for allocating patients with compensated advanced chronic liver disease to screening of varices compared to the current standard of care.

Portal hypertension (PH) is a group of syndromes characterized by abnormal changes in the portal blood flow system, mostly caused by cirrhosis. It is an important factor affecting the clinical prognosis of cirrhotic patients, and its severity determines the occurrence and development of cirrhotic complications. Clinically, measurement of portal venous pressure directly is highly invasive, and factors such as intra-abdominal pressure changes can interfere with the results, limiting its clinical application. Hepatic venous pressure gradient (HVPG) is the gold standard for assessing PH in cirrhosis. The normal range of HVPG is 3~5 mmHg, and HVPG ≥5 mmHg indicates the presence of PH. AASLD stated that HVPG ≥10 mmHg is defined as clinically significant portal hypertension (CSPH), and the risk of decompensation events is significantly increased at this stage. However, HVPG is an invasive test, which is unacceptable to some patients, such as being expensive, difficult to repeat, and poor patient compliance. Non-invasive tests for PH include serological tests, anatomical imaging and combination models. Imaging evidence of portal collateral circulation or hepatic blood flow in the portal venous system based on ultrasound Doppler, CT or magnetic resonance imaging techniques can assist to diagnose PH. In addition, elastography techniques such as transient elastography, point shear wave elastography, two-dimensional shear wave elastography and magnetic resonance elastography can be used to measure liver stiffness and spleen stiffness to assess PH. Some biochemical markers are also considered as non-invasive tests for PH. However, the available biomarkers are not yet a substitute for the HVPG accurately, and therefore, there is an urgent need for the development of biomarkers associated with HVPG in clinical practice. Metabolomics is a method to analyze the concentrated changes of endogenous small molecule metabolites under the combined effect of genetic, biological and environmental factors with the help of various high-throughput technologies. Metabolites are at the end of the biological information flow, and their changes are the ultimate expression of the information from the coordinated action of each group, objectively reflecting the overall changes of the organism. Currently, metabolomics techniques have been widely used in screening biomarkers of liver diseases. Wang et al. applied GC-TOF/MS and UPLC-QTOF/MS to study the urinary metabolomics of patients with hepatitis B cirrhosis and showed that α-hydroxymaurolate, tyrosine-betaine, 3-hydroxyisovaleric acid, knife-serine succinate, estrone and GUDCA were significantly altered in different Child-Pugh grades of cirrhosis, suggesting that these metabolites are potential biomarkers to identify different pathological stages of cirrhosis. Therefore, metabolomics is a reliable and valid tool for biomarker discovery. In conclusion, this study analyzed significantly altered metabolites in patients with hepatitis B cirrhosis using metabolomics to explore potential differential metabolites that are highly correlated with HVPG. Further, serological biomarkers were identified as an alternative to HVPG testing through model construction and validation.

The purpose of this study is to evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) plus Cadonilimab (a PD-1/CTLA-4 bispecific antibody) in advanced hepatocellular carcinoma (BCLC-C Stage) accompanied by tumor thrombosis-associated portal hypertension.

The main purpose of this exploratory study was to investigate the instant efficacy and safety of alverine oral administration in decreasing portal hypertension. Condition of disease: Cirrhotic portal hypertension Intervention/treatment: Drug: Alverine 60 mg (1 capsule), orally Drug: Alverine 120 mg (2 capsules), orally

Carvedilol has been shown to be more potent in decreasing portal hypertension to propranolol. But the efficacy of carvedilol to delay the growth of esophageal varices in chronic hepatitis B patients was unclear.

Hypothesis: The severity of portal hypertension in compensated advanced chronic liver disease (cACLD) can be assessed using vibration controlled transient elastography (VCTE) via the FibroScan® 502 Touch by measuring SS (splenic stiffness) Specific Aims: SS by VCTE will be measured in this single center clinical study comprising of 200 patients with cACLD (defined by LSM ≥10 kilopascals (kPa) according to the Baveno VI recommendations) who have not had a liver transplant and 100 subjects who are post-liver transplant. The association between baseline SS values will be examined in relation to the manifestations of portal hypertension such as esophageal or gastric varices. Specific Aim: To examine the relationship between SS and the presence of esophageal and gastric varices in patients with compensated advanced chronic liver disease (cACLD). Proposed Study Design: This is a cross sectional study that evaluates the relationship between SS by VCTE in patients with cACLD and manifestations of portal hypertension.

The worldwide obesity epidemic has led to an increase in the proportion of patients with chronic liver disease due to non-alcoholic fatty liver disease (NAFLD) and in the prevalence of obesity in patients with cirrhosis of all etiologies. The reported prevalence of obesity in patients with cirrhosis is of 30% which appears similar to that of the general population. Bariatric surgery is currently considered as the most effective and durable means for the management of morbid obesity as it is associated with the remission and/or improvement of many obesity associated comorbidities as well as improved quality and expectancy of life. However, the surgical risk is increased compared to individuals without cirrhosis, and determining the risk/benefit ratio of bariatric surgery in the setting of cirrhosis is a complex task further hampered by the lack of randomized controlled trials. The Nationwide Inpatient Sample study reported a slightly increased rate of mortality of bariatric surgery in the setting of compensated cirrhosis compared to individuals without cirrhosis (0.9% vs 0.3%). Interestingly, this risk was as high as 16.3% in individuals with decompensated cirrhosis (16.3%). However, this study has been published more than 10 years ago and the mortality of bariatric surgery has decreased significantly and is around 0.1%. Furthermore, the introduction of transient elastography in clinical practice has allowed the early identification of patients with chronic liver disease (CLD) at risk of developing clinically significant portal hypertension (CSPH). A few series including a limited number of patients have been published indicating that CSPH should not be considered as a formal contraindication for bariatric surgery. This study is meant to assess the outcomes of bariatric surgery in patients with morbid obesity and compensated advanced chronic liver disease (cACLD) (currently synonymous of the term "compensated cirrhosis'') associated with clinically significant portal hypertension (CSPH) in a large multicentric, multinational series.

Aim: To test if MRI can detect meaningful changes in portal pressure in the liver to assess whether treatment with beta-blockers has worked. Liver Disease: Most people with liver disease do not have symptoms. Over time they develop 'cirrhosis' - severe liver scarring. In the United Kingdom deaths due to cirrhosis have doubled over the last decade, because of increasing rates of alcohol consumption and obesity, while heart, kidney, lung diseases, strokes and cancer fatalities have fallen. Portal pressure: Cirrhosis causes increased pressure within the liver and changes in the circulation leading to the development of varicose veins in the gullet and stomach called 'varices'. Varices bleed easily, leading to emergency situations that can be life threatening. However, if the increased pressure within the liver (portal pressure) is detected early, then treatment can prevent variceal bleeding. The only test we have to predict prognosis and treatment success in someone with cirrhosis is by measuring the portal pressure. Measuring portal pressure: Currently the only existing test to measure portal pressure is to pass a pressure sensor through a vein in the neck, down into the liver. This is called the hepatic venous pressure gradient (HVPG) measurement. The HVPG measurement is disliked by patients because it is an invasive procedure. It is also expensive and not widely available. Hence, patients with cirrhosis need to have regular camera tests (endoscopies) to look for varices. How can you treat varices? Two options; With tablets to lower the pressure (beta-blockers) Endoscopy treatment (banding) Both have advantages and disadvantages; Beta-blockers only lower the portal pressure in about half of those that take them, with some evidence they may also have a protective effect against infections from the bowel by increasing the speed of bowel motion Treating the varices with endoscopy requires several endoscopies and can lead to life-threatening bleeding. Most patients are therefore given beta-blockers and monitored closely to see if they work. Why does it matter? Beta-blockers can cause side effects (e.g. fainting) that are unpleasant enough to make up to one third of patients stop taking them. Beta-blockers only reduce the portal pressure in half of patients. The remaining patients are exposed to potential side effects and possible harm in those with the most advanced liver disease. These patients may still have a life-threatening bleed as the varices have not been adequately treated. There is a desperate need to discover whether the portal pressure changes with treatment (such as with beta-blockers) without invasive tests across the NHS. Proposed study: Researchers in Nottingham have shown MRI can be used as an accurate marker of portal pressure with just one scan. To be useful to patients, doctors and researchers, this study will investigate whether MRI can detect meaningful changes in portal pressure after treatment with beta-blockers. This study has been designed with patient and public involvement (PPI) integrated throughout. A focus group shaped the study design and committed to collaborate in developing patient materials, recruitment, retention and dissemination. All patients who have HVPG will be given information about the study. Study Visit 1 One hour MRI scan Endoscopy to identify varices If varices are present the patient will be started on beta-blockers and invited to visit 2 If there are no varices, patients will return to regular follow up with the liver team Study Visit 2 (after one week) Assess side effects, blood pressure and pulse Increase dose of beta-blocker as appropriate Study Visit 3 (after 4-12 weeks) One hour MRI scan Repeat HVPG measurement Treatment success is determined by the second HVPG measurement. If beta-blockers are working they will be continued. If not, the patient will have treatment with endoscopy. This represents the ideal pathway which is more personalised than current standard care.