Management Of Portal Hypertension Research Articles

Update on the diagnosis and management of portal hypertension in cirrhosis according to the Baveno VII Consensus Conference recommendations.

Development of portal hypertension is the most critical hallmark in the natural history of advanced chronic liver disease, as it is responsible for most liver decompensations. Correct risk stratification allows the design of personalized treatment strategies. In addition, the dynamic nature of chronic liver disease requires a refinement of both invasive and non-invasive diagnostic methods at every stage. Treatment with non-selective beta blockers and suppression of the etiologic factor improve portal hypertension and decrease the probability of decompensation in high-risk patients. Patients admitted for variceal hemorrhage also benefit from personalized management, where insertion of a preventive TIPS plays a relevant role.

Indian College of Radiology and Imaging Evidence-Based Guidelines for Interventions in Portal Hypertension and Its Complications.

Portal hypertension is a complication of chronic liver disease. Various radiological interventions are being done to aid in the diagnosis of portal hypertension; further, an interventional radiologist can offer various treatments for the complications of portal hypertension. Diagnosis of portal hypertension in its early stage may require hepatic venous pressure gradient measurement. Measurement of gradient also guides in diagnosing the type of portal hypertension, measuring response to treatment and prognostication. This article attempts to provide evidence-based guidelines on the management of portal hypertension and treatment of its complications.

Portal hypertension and hepatocellular carcinoma: Des liaisons dangereuses….

Portal hypertension (PHT) and hepatocellular carcinoma (HCC) are major complication of cirrhosis which significantly contribute to morbidity and mortality. In this review, we aim to describe the consequences of both angiogenesis and inflammation in the pathogenesis of PHT and HCC, but also the difficulty to propose adapted treatment when PHT and HCC coexist in the same patients. Studies for review in this article were retrieved from the PubMed database using literature published in English until March 2021. Portal hypertension occurs secondary to an increase of intrahepatic vascular resistances, the opening of portosystemic collateral vessels and the formation of neovessels, related to vascular endothelial growth factor (VEGF). Recently, bacterial translocation-mediated inflammation was also identified as a major contributor to PHT. Interestingly, VEGF and chronic inflammation also contribute to HCC occurrence. As PHT and HCC often coexist in the same patient, management of PHT and its related complications as well as HCC treatment appear more complex. Indeed, PHT-related complications such as significant ascites may hamper the access to HCC treatment and the presence of HCC is also independently associated with poor prognosis in patients with acute variceal bleeding related to PHT. Due to their respective mechanism of action, the combination of Atezolizumab and Bevacizumab for advanced HCC may impact the level of PHT and its related complications and to date, no real-life data are available. Appropriate evaluation and treatment of PHT remains a major issue in order to improve the outcome of HCC patients.

Anesthesia in Children with Thrombocytopenia During Bypass Surgery for Extrahepatic Portal Hypertension (Review)

Portal hypertension syndrome is one of the most severe pediatric conditions causing gastroesophageal bleeding which can be fatal. The main challenge in the management of portal hypertension is prevention of bleeding from the portal vein system, which is achieved by vascular surgery, particularly portosystemic shunting. Epidural anesthesia, despite its advantages over the opioid one, is not always performed in children with extrahepatic portal hypertension, and still remains unsolved issue in pediatric anesthesiology.Aim of the review: to evaluate the scope of limitations of general anesthesia in bypass surgery for extrahepatic portal hypertension in children with thrombocytopenia. We searched PubMed, Medline, Elibrary.ru and other databases and used original clinical observations while performing anesthesiologic support of surgical correction of extrahepatic portal hypertension in children.We found that general anesthesia for portosystemic bypass surgery in children with thrombocytopenia requires the anesthetic support that does not include epidural anesthesia and high-dose opioid administration. This issue can be resolved by including the central selective alpha-2-adrenergic agonist dexmedetomidine with both analgesic and hypnotic effects in the anesthesia support. Due to its additive effects, this drug significantly reduces the need for hypnotics and opioid analgesics while maintaining a high level of neurovege-tative protection.Conclusion. In our opinion, optimizing anesthesia in children with thrombocytopenia during bypass surgery for extrahepatic portal hypertension is essential to minimize surgical stress and side effects of drugs.

Congenital heart disease-associated liver disease: a narrative review.

Congenital heart diseases (CHD) can be associated with liver dysfunction. The cause for liver impairment can result out of a wide spectrum of different causes, including liver congestion, hypoxemia or low cardiac output. Fortunately, most CHD show a good long-term outcome from a cardiac perspective, but great attention should be paid on non-cardiac health problems that develop frequently in patients suffering from CHD. The treatment of liver dysfunction in CHD requires a close multidisciplinary management in a vulnerable patient collective. Unfortunately, structured recommendations on the management of liver dysfunction in patients with CHD are scarce. The objective of this review is to provide insights on the pathophysiology and etiologies of liver dysfunction as one of the most relevant non-cardiac problems related to CHD. Furthermore, we advise here on the management of liver disease in CHD with special attention on assessment of liver dysfunction, management of portal hypertension as well as on surveillance and management of hepatocellular carcinoma (HCC). A multidisciplinary perspective may help to optimize morbidity and mortality in the long-term course in these patients. However, as evidence is low in many aspects, we encourage the scientific community to perform prospective studies to gain more insights in the treatment of liver dysfunction in patients with CHD.

Porto Systemic Shunt Surgery - Case Series of 40 Cases Performed at a Single Tertiary Care Centre

Introduction: Portal hypertension is seen when there is pathological increase in hepatic venous pressure gradient. Portal hypertension is seen in a number of conditions like extra-hepatic portal venous obstruction, cirrhosis of liver, non cirrhotic portal fibrosis, portal vein thrombosis from various causes. Surgical Porto systemic shunts are a time proven modality for treating portal hypertension. These patients present as recurrent variceal bleeding, ascites, encephalopathy. This is a case series on Porto systemic shunting done in patients in a single tertiary care centre. Method: Retrospective study of 40 cases performed in a single tertiary care centre performed over 5 years from 2012 to 2016, along with comparison with the existing data on Porto systemic shunt surgeries. Results: From amongst the 40 patients cases of extra-hepatic portal venous obstruction were 75%, non cirrhotic portal fibrosis were 15%, portal vein thrombosis were 5%, cirrhotic patients were 5%. There was no immediate peri-operative mortality. 4 year shunt patency was 97%. Recurrent variceal bleeding was seen in 5%. Encephalopathy was seen in 1%. Re-intervention was required in 3%. 4 year survival was 96%. Conclusions: Surgical Porto systemic shunts remain time tested efficacious modality in management of portal hypertension. Porto systemic shunts have good long term survival benefit with symptomatic relief and improvement of quality of life.

Long-term clinical outcome and survival predictors in patients with cirrhosis after 10-mm-covered transjugular intrahepatic portosystemic shunt

Background and aimsTransjugular intrahepatic portosystemic shunts (TIPS) are successfully used in the management of portal hypertension (PH)-related complications. Debate surrounds the diameter of the dilation. The aim was to analyse the outcomes of and complications deriving from TIPS in patients with cirrhosis and identify predictors of survival. MethodsThis was a retrospective single-centre study, which included patients with cirrhosis who had a TIPS procedure for PH from 2009 to October 2018. Demographic, clinical and radiological data were collected. The Kaplan–Meier method was used to measure survival and predictors of survival were identified with the Cox regression model. ResultsA total of 98 patients were included (78.6% male), mean age was 58.5 (SD±/−9.9) and the median MELD was 13.3 (IQR 9.5–16). The indications were refractory ascites (RA), variceal bleeding (VB) and hepatic hydrothorax (HH). Median survival was 72 months (RA 46.4, VB 68.5 and HH 64.7) and transplant-free survival was 26 months. Clinical and technical success rates were 70.5% and 92.9% respectively. Age (HR 1.05), clinical success (HR 0.33), sodium (HR 0.92), renal failure (HR 2.46) and albumin (HR 0.35) were predictors of survival. Hepatic encephalopathy occurred in 28.6% of patients and TIPS dysfunction occurred in 16.3%. ConclusionsTIPS with 10-mm PTFE-covered stent is an effective and safe treatment for PH-related complications in patients with cirrhosis. Age, renal failure, sodium, albumin and clinical success are independent predictors of long-term survival.

Occurrence of Portal Hypertension and Its Clinical Course in Patients With Molecularly Confirmed Autosomal Recessive Polycystic Kidney Disease (ARPKD).

Purpose: Liver involvement in autosomal recessive polycystic kidney disease (ARPKD) leads to the development of portal hypertension and its complications. The aim of this study was to analyze the occurrence of the portal hypertension and its clinical course and the dynamics in patients with molecularly confirmed ARPKD in a large Polish center. Moreover, the available options in diagnostics, prevention and management of portal hypertension in ARPKD will be discussed.Materials and Methods: The study group consisted of 17 patients aged 2.5–42 years. All patients had ARPKD diagnosis confirmed by molecular tests. Retrospective analysis included laboratory tests, ultrasound and endoscopic examinations, transient elastography and clinical evaluation.Results: Any symptom of portal hypertension was established in 71% of patients. Hypersplenism, splenomegaly, decreased portal flow and esophageal varices were found in 47, 59, 56, and 92% of patients, respectively. Gastrointestinal bleeding occurred in four of 17 patients. Endoscopic variceal ligation (EVL) was performed at least once in nine patients with esophageal varices.Conclusions: Portal hypertension and its complications are present in a significant percentage of ARPKD patients. They should be under the care of multidisciplinary nephrology-gastroenterology/hepatology team. Complications of portal hypertension may occur early in life. Endoscopic methods of preventing gastroesophageal bleeding, such as endoscopic variceal ligation, are effective and surgical techniques, including liver transplantation, are required rarely.

Cirrhotic portal hypertension: From pathophysiology to novel therapeutics.

Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin II type receptor 1 blockers, which target the components of the classical renin angiotensin system (RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant off-target effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective -blockers (NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs. Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pathogenesis of portal hypertension and attempts to provide an update on currently available therapeutic approaches in the management of portal hypertension with special emphasis on how the alternate RAS could be manipulated in our search for development of safe, specific and effective novel therapies to treat portal hypertension in cirrhosis.

Recent Updates in Drugs Used in Management of Portal Hypertension

Portal hypertension is an expansion in the weight inside the gateway vein i.e., the vein that conveys blood from the stomach related organs to the liver. The expansion in pressure is brought about by a blockage in the blood course through the liver. The advancement of gateway hypertension in a patient with cirrhosis can cause genuine clinical results which can be lethal if untreated and dynamic. Along these lines it is essential to analyze portal hypertension to postpone the movement and to treat the serious difficulties of gateway hypertension. This survey centers around the ongoing updates in drugs utilized in the administration of portal hypertension.

Pharmacological management of portal hypertension: current status and future

Pharmacological management of portal hypertension: current status and future

Application and status of digestive endoscopy in the overall management of portal hypertension-related esophagogastric variceal bleeding

Portal hypertension-related esophagogastric variceal bleeding (EVB) is deadly. Therefore, multidisciplinary management involving hepatologists, digestive endoscopy, radiological intervention, and/or surgery is necessary. Digestive endoscopy is the core of the multidisciplinary approach to the overall management of portal hypertension. It plays an important role in the early warning, emergency treatment, and the prevention of the initial and re-bleeding of portal hypertension accompanied by esophagogastric varices. In addition, gastroscopy with endoscopic ultrasound scanning can enhance the management capabilities of ectopic varices.

The Clinical Efficacy and Safety of Simvastatin in the Management of Portal Hypertension in Cirrhotic Patients: A Systematic Review

Background: Variceal bleeding is a serious complication of portal hypertension in liver cirrhosis. Current guidelines recommend non-selective beta blockers (NSBBs) and endoscopic variceal ligation for primary prophylaxis of variceal bleeding. However, NSBBs are associated with low response rates and systemic adverse effects. Simvastatin has been shown to reduce portal hypertension in previous studies. Our aim was to assess its clinical efficacy and safety in reducing portal hypertension in cirrhotic patients. Method: We searched PubMed, The Cochrane Library, ScienceDirect, ProQuest, CINAHL, Scopus, and Clinicaltrials.gov, and manually browsed abstracts of major hepatology conferences for selection of studies. We selected randomized controlled trials with a population of cirrhotic patients, simvastatin as an intervention, HVPG change as an outcome, and English as the primary language. The quality of selected studies was assessed using the Cochrane Risk of Bias tool. We extracted change in HVPG from baseline to post-treatment as the principal summary measure, with safety as the secondary outcome.Results: Two full articles were included for qualitative analysis. Both studies reported reductions in HVPG from baseline to post-treatment in the simvastatin group, with this reduction being significantly higher as compared to the control group. Adverse effects were homogenously distributed in both groups, and good safety was reported by both studies. Simvastatin’s HVPG lowering effects are possibly additive to those of NSBBs. Conclusion: Simvastatin effectively reduces HVPG in cirrhotic patients with portal hypertension, although more clinical trials are needed to validate these results. Simvastatin could potentially be combined with NSBBs to achieve greater results.

Nonalcoholic fatty liver disease and portal hypertension.

Nonalcoholic fatty liver disease (NAFLD) is a substantial and growing problem worldwide and has become the second most common indication for liver transplantation as it may progress to cirrhosis and develop complications from portal hypertension primarily caused by advanced fibrosis and erratic tissue remodeling. However, elevated portal venous pressure has also been detected in experimental models of fatty liver and in human NAFLD when fibrosis is far less advanced and cirrhosis is absent. Early increases in intrahepatic vascular resistance may contribute to the progression of liver disease. Specific pathophenotypes linked to the development of portal hypertension in NAFLD include hepatocellular lipid accumulation and ballooning injury, capillarization of liver sinusoidal endothelial cells, enhanced contractility of hepatic stellate cells, activation of Kupffer cells and pro-inflammatory pathways, adhesion and entrapment of recruited leukocytes, microthrombosis, angiogenesis and perisinusoidal fibrosis. These pathological events are amplified in NAFLD by concomitant visceral obesity, insulin resistance, type 2 diabetes and dysbiosis, promoting aberrant interactions with adipose tissue, skeletal muscle and gut microbiota. Measurement of the hepatic venous pressure gradient by retrograde insertion of a balloon-tipped central vein catheter is the current reference method for predicting outcomes of cirrhosis associated with clinically significant portal hypertension and guiding interventions. This invasive technique is rarely considered in the absence of cirrhosis where currently available clinical, imaging and laboratory correlates of portal hypertension may not reflect early changes in liver hemodynamics. Availability of less invasive but sufficiently sensitive methods for the assessment of portal venous pressure in NAFLD remains therefore an unmet need. Recent efforts to develop new biomarkers and endoscopy-based approaches such as endoscopic ultrasound-guided measurement of portal pressure gradient may help achieve this goal. In addition, cellular and molecular targets are being identified to guide emerging therapies in the prevention and management of portal hypertension.

Role of Endoscopic Ultrasound to Assess and Manage Portal Hypertension

AbstractPortal hypertension leads to the development of varices along the gastrointestinal tract. Endoscopy plays an important role in the diagnosis and management of varices. Endosonography (EUS) enables visualization and permits access to varices and veins outside the gastrointestinal tract. EUS has emerged as an important tool, with the ability to identify vascular changes, treat gastric and ectopic varices, perform portal pressure measurements, portal venography, and intrahepatic shunt placement. This review discusses the role of endoscopy and the emerging role of EUS in evaluation and management of portal hypertension.

The role of a multidisciplinary team in the management of portal hypertension

BackgroundGastroesophageal variceal hemorrhage is the most severe complication of portal hypertension, with a high mortality rate. The current recommendations for gastroesophageal varices include pharmacological treatment, endoscopic treatment, transjugular intrahepatic portosystemic shunt (TIPS) placement, and splenectomy with devascularization surgery. Multidisciplinary team (MDT) comprises of a group of medical experts and specialists across a range of disciplines, providing personalized and targeted patient care tailored to each individual’s condition, circumstances, and expectations.MethodsPatients referred to the MDT clinic since its establishment in September 2014 were prospectively enrolled and followed-up for at least 12 months. Patient baseline characteristics, treatment methods, outcome and survival were compared to non-MDT patients retrieved from a prospectively maintained database with propensity score matching.ResultsPropensity-score matching (PSM) was carried out to balance available covariates, resulting in 58 MDT patients vs. 111 non-MDT patients. Overall survival and variceal rebleed was compared between the two groups. The rate of variceal rebleed was significantly higher in the non-MDT group, while no difference in overall survival was observed.ConclusionsThis study is the first to investigate the role of a multidisciplinary team in the management of gastroesophageal varices secondary to portal hypertension. Patients treated based on MDT clinic recommendations had a significantly lower risk for variceal rebleed.

Predictive Value of Abnormal Findings on Covered Transjugular Intrahepatic Portosystemic Shunt Baseline Doppler Sonography.

Doppler ultrasound (DUS) is frequently performed as a screening and diagnostic modality to evaluate the transjugular intrahepatic portosystemic shunt (TIPS) for short- and intermediate-term complications of the procedure. However, the clinical significance of initial frequently observed abnormalities in flow velocities, gradient, and direction in patients with covered TIPS is less studied. A retrospective study was performed between January 2005 and December 2014, and all patients undergoing covered TIPS procedure for the management of portal hypertension were included. Abnormal DUS findings were defined as intrashunt peak systolic velocities (PSVs) less than 90 or greater than 190 cm/s, intrashunt gradient greater than 50 cm/s, and abnormal flow direction in the main, right, and/or left portal veins. A total of 283 patients with adequate clinical follow-up and baseline TIPS DUS were included in the study. Median follow-up was 18.2 months. During the follow-up period, portal hypertension symptoms recurred in 83 patients who underwent TIPS angiography and/or revision. Of the 83, 57 had an elevated portosystemic gradient (>12 mm Hg) requiring angioplasty/stenting. With regard to baseline ultrasound, low PSVs were present in 88 patients (31.1%), high PSVs in 44 patients (15.5%), and elevated gradient in 98 patients (34.6%). The rate of developing TIPS stenosis in the future was not higher in patients with abnormal DUS parameters. For example, 26 (19.7%) of 132 patients with abnormal TIPS velocities developed stenosis compared with 31 (20.5%) of 151 patients with normal velocities (P = 0.9). Based on these results, abnormal DUS findings observed on baseline TIPS ultrasound examination have low predictive value for future covered TIPS dysfunction and failure.

Transjugular intrahepatic portosystemic stent-shunt in the management of portal hypertension

These guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of...

Peptide-based therapy in portal hypertension.

To summarize the use of gastrointestinal peptides in the management of portal hypertension. Vasoactive peptides are commonly used in the management of acute variceal hemorrhage and hepatorenal syndrome, which are portal hypertensive complications of cirrhosis. The main vasoactive peptides that are used are somatostatin and its long-acting analogue octreotide, and vasopressin and its analogue terlipressin. Early initiation of vasoactive peptides in the management of acute variceal hemorrhage and hepatorenal syndrome is associated with improved outcomes. Octreotide is the available vasoactive peptide in the Unites States. Recent developments and ongoing clinical trials may improve our understanding of hepatorenal syndrome and influence the use of vasoactive peptides, particularly terlipressin. Here, we review the literature on the use of vasoactive peptides in the management of acute variceal hemorrhage and hepatorenal syndrome.

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

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