Management Of Portal Hypertension Research Articles

TIPS for management of portal-hypertension-related complications in patients with cirrhosis

Portal hypertension is primarily due to liver cirrhosis, and is responsible for complications that include variceal bleeding, ascites and hepatorenal syndrome. The transjugular intrahepatic portosystemic shunt (TIPS) is a low-resistance channel between the portal vein and the hepatic vein, created by interventional radiology, that aims to reduce portal pressure. TIPS is a potential treatment for severe portal-hypertension-related complications, including esophageal and gastric variceal bleeding. TIPS is currently indicated as salvage therapy in this setting when patients fail to respond to standard endoscopic and medical treatment. More recently, early TIPS has been shown to be effective in decreasing risk of rebleeding after variceal hemorrhage and mortality in Child-Pugh B patients with active hemorrhage at endoscopy, and in Child-Pugh C patients. TIPS is also an efficient treatment for refractory ascites and hepatic hydrothorax. In contrast, the role of TIPS in the hepatorenal syndrome has not been precisely defined. The aim of this review was to specifically describe the current role of TIPS in management of portal hypertension in patients with cirrhosis.

Cirrhotic patients and older people.

The global population is aging, and so the number of older cirrhotic patients is increasing. Older patients are characterised by a risk of frailty and comorbidities, and age is a risk factor for mortality in cirrhotic patients. The incidence of non-alcoholic fatty liver disease as an aetiology of cirrhosis is increasing, while that of chronic viral hepatitis is decreasing. Also, cirrhosis is frequently idiopathic. The management of portal hypertension in older cirrhotic patients is similar to that in younger patients, despite the greater risk of treatment-related adverse events of the former. The prevalence of hepatocellular carcinoma increases with age, but its treatment is unaffected. Liver transplantation is generally recommended for patients < 70 years of age. Despite the increasing prevalence of cirrhosis in older people, little data are available and few recommendations have been proposed. This review suggests that comorbidities have a considerable impact on older cirrhotic patients.

Management of portal hypertension and ascites in polycystic liver disease.

Patients suffering from polycystic liver disease may develop Hepatic Venous Outflow Obstruction, Portal Vein Obstruction and/or Inferior Caval Vein Syndrome because of cystic mass effect. This can cause portal hypertension, leading to ascites, variceal haemorrhage or splenomegaly. For this review, we evaluate the evidence to provide clinical guidance for physicians faced with this complication. Diagnosis is made with imaging such as ultrasound, computed tomography or magnetic resonance imaging. Therapy includes conventional therapy with diuretics and paracentesis, and medical therapy using somatostatin analogues. Based on disease phenotype various (non‐)surgical liver‐volume reducing therapies, hepatic or portal venous stenting, transjugular intrahepatic portosystemic shunts and liver transplantation may be considered. Because of complicated anatomy, use of high‐risk interventions and lack of empirical evidence, patients should be treated in expert centres.

Transjugular Intrahepatic Portosystemic Shunt Placement in Patients with Schistosomiasis-Induced Liver Fibrosis

PurposeEvaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) insertion on patients with schistosomiasis-induced liver fibrosis, and compare with that of patients with HBV-induced cirrhosis.Materials and MethodsThis was a retrospective study from November 2015 to December 2018 including 82 patients diagnosed with portal hypertension, one group of which is induced by schistosomiasis (n = 20), the other by hepatitis B virus (HBV) (n = 62). Both groups of subjects underwent TIPS placement for the management of portal hypertension complications.ResultsTIPS was inserted successfully in all patients (technical success 100%). After a median follow-up of 14 months following TIPS insertion, portal pressure gradient (PPG) value in both schistosomiasis-induced group and HBV-induced group underwent a significant decrease with no major difference between the two groups. There exists no significant difference demonstrated by Kaplan–Meier curves between two groups concerning cumulative rate of hepatic encephalopathy (HE) (log-rank p = 0.681), variceal rebleeding (log-rank p = 0.837) and survival (log-rank p = 0.429), and no statistically difference was found in terms of alleviation of portal vein thrombosis (PVT). In addition, splenectomy (HR 19, 95% CI 4–90, p < 0.001) was identified as independent predictor of PVT.ConclusionsTIPS placement is well-founded to be considered as a safe and effective treatment in patients with schistosomiasis-induced portal hypertension and relevant severe complications. We also found the risk of PVT is 19 times higher in patients who underwent splenectomy than in untreated patients.Level of EvidenceHistorically controlled studies, level 4.

Esophageal Hemorrhagic Syndromes

Esophageal bleeding is one of the most common medical emergencies. It takes the 3rd place among all digestive hemorrhages, and accounts for 14–16 % among all gastrointestinal bleeding. The most common cause of esophageal hemorrhages is Mallory – Weiss esophageal tear (10–12 %), less often – varicose veins of the esophagus in portal hypertension syndrome (up to 4 %) and, in some cases, is esophagitis of various etiologies (up to 1.6 %). The problem of esophageal bleeding is characterized by high incidence, high mortality rate due to constant increase of portal hyper tension cases, recurrences, difficulties in diagnosis, anatomical and physiological features of the esophagus, low efficiency of the main methods of hemostasis. There are various surgical and conservative methods of hemostasis, which show a variety of opinions in the solution to the problem of stopping esophageal bleeding. In Mallory – Weiss syndrome, endoscopic hemostasis is considered to be the preferred method of treatment. Management of portal hypertension is the most difficult task; a wide range of operations is used from the minimally invasive operations to the liver transplantation, as well as endoscopic hemostasis (ligation, sclerotherapy). In esophageal bleeding, due to reflux esophagitis, mainly conservative treatment is suggested, operations are performed with recurrences or complications. Each kind of esophageal hemorrhage is considered as a separate problem.

HVPG Measurements as a Surrogate of Clinical Events in Cirrhosis: Experience from Clinical Trials

Update current knowledge of the use of hepatic venous pressure gradient (HVPG) as a predictor of clinical events and of efficacy of therapy for portal hypertension. HVPG is a good predictor of clinical events. Decrease in HVPG during therapy is accompanied by a decreased incidence of complications from portal hypertension and improved survival. HVPG measurements are a valuable tool in the management of portal hypertension in cirrhosis. In addition of detecting and grading the severity of portal hypertension, HVPG measurements provide robust prognostic information on the risk of complications, disease progression/regression, and survival. Changes in HVPG in response to therapy predict the effects on clinical outcomes, both during treatment with beta-blockers and when treating HCV-related cirrhosis with specific antivirals. This has led to suggest that HVPG can be used as a surrogate for clinical events when developing new therapies for portal hypertension. Limitations of this approach are discussed.

Potential mechanisms linking gut microbiota and portal hypertension.

Gut microbiota is the largest collection of commensal micro-organisms in the human body, engaged in reciprocal cellular and molecular interactions with the liver. This mutually beneficial relationship may break down and result in dysbiosis, associated with disease phenotypes. Altered composition and function of gut microbiota has been implicated in the pathobiology of nonalcoholic fatty liver disease (NAFLD), a prevalent condition linked to obesity, insulin resistance and endothelial dysfunction. NAFLD may progress to cirrhosis and portal hypertension, which is the result of increased intrahepatic vascular resistance and altered splanchnic circulation. Gut microbiota may contribute to rising portal pressure from the earliest stages of NAFLD, although the significance of these changes remains unclear. NAFLD has been linked to lower microbial diversity and weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defence and inflammation. Moreover, disrupted host-microbial metabolic interplay alters bile acid signalling and the release of vasoregulatory gasotransmitters. These perturbations become prominent in cirrhosis, increasing the risk of clinically significant portal hypertension and leading to bacterial translocation, sepsis and acute-on-chronic liver failure. Better understanding of the gut-liver axis and identification of novel microbial molecular targets may yield specific strategies in the prevention and management of portal hypertension.

Computed tomography and magnetic resonance imaging features of regional portal hypertension

Computed tomography and magnetic resonance imaging features of regional portal hypertension

Long-term clinical outcomes in patients with viral hepatitis related liver cirrhosis after transjugular intrahepatic portosystemic shunt treatment

BackgroundTransjugular intrahepatic portosystemic shunt (TIPS) procedure has played a vital role in management of portal hypertension. Thus, we aimed to investigate the natural history, long-term clinical outcome, predictors of survival in viral hepatitis related cirrhotic patients post-TIPS.MethodA total of 704 patients with complete followed-up data were enrolled, and clinical characteristics of patients were collected and analyzed. Kaplan-Meier method was used to calculate survival, and comparisons were made by log rank test. A multivariate analysis of factors influencing survival was carried out using the Cox proportional hazards regression model.ResultsTIPS implatantion significantly decreased portal vein pressure with 9.77 cmH2O reduction, without influencing long-term liver functions. The total incidence rate of major complication post-TIPS, including HE and re-bleeding/bleeding, was 37.9% and 15.5%, respectively. Patients in Child-Pugh C stage revealed higher overt hepatic encephalopathy (HE) occurrence (65.6%), while patients receiving covered, 6 mm in diameter stents indicated notably lower incidence of HE in comparison with other groups (6.4%). The median survival was > 60 months, 27.0 months, and 11.5 months in cirrhotic patients with variceal bleeding, refractory ascites, and both complications, respectively. The cumulative 5-year survival was significantly higher in patients with variceal bleeding (75.6%) in comparison with either that in patients with refractory ascites (12.5%) or that in patients with both complications (1.96%) (P < 0.0001). Covered stents usage, baseline model for end-stage liver disease (MELD) score, and baseline Child-Pugh classification were predictive of survival (P < 0.001). Other variables including age, male gender, and pre-TIPS PVP were not emerged as significant predictors (P > 0.05).ConclusionTIPS was an effective and safe therapeutic method for decompression of portal hypertension and for treatment of its complications. Careful selection of patients with minimal liver dysfunction for TIPS implantation was essential for better long-term outcomes.

Management of Portal Hypertension in the Pediatric Population: A Primer for the Interventional Radiologist.

Interventional radiology's role in the management of portal hypertension in the pediatric population differs from the management of adult portal hypertension. In the pediatric population, portal hypertension is frequently secondary to thrombosis and cavernous transformation of the extrahepatic portion of the portal vein. Transjugular intrahepatic portosystemic shunt can be utilized to manage portal hypertension in children with intrinsic liver disease that results in cirrhosis and portal hypertension, and is often used as a bridge to transplant. While technically feasible in extrahepatic portal vein occlusion, the sequelae of portosystemic shunting are less desirable in a child. The Meso-Rex bypass procedure, which represents the mainstay of management for pediatric portal hypertension, provides surgical relief of extrahepatic portal vein obstruction and restores mesenteric venous blood flow to the liver. This article aims to review management of portal hypertension in children as it pertains to the interventional radiologist, including preoperative assessment, postoperative evaluation, and the management of complications of the Meso-Rex bypass.

Clinical Assessment and Management of Portal Hypertension.

The development of portal hypertension in a patient with cirrhosis portends a poor prognosis. Untreated or progressive portal hypertension has serious clinical outcomes, which are often fatal. It is important to recognize portal hypertension early to delay progression and to treat complications of portal hypertension as they arise. This review will focus on the clinical assessment and management of portal hypertension.

Splanchnic Vein Thrombosis in the Myeloproliferative Neoplasms.

To review the epidemiology, diagnostic challenges, pathogenesis, and treatment strategies for patients with myeloproliferative neoplasm-associated splanchnic vein thrombosis. The epidemiology of myeloproliferative neoplasm-associated splanchnic vein thrombosis (MPN-SVT) has been well characterized. While typical MPN-associated thrombosis affects older patients and involves the arterial circulation, MPN-SVT mostly impacts younger women. An association with JAK2 V617F is well-known; recent studies have demonstrated only a weak association with CALR mutations. JAK inhibition may represent a novel treatment strategy, complementing anticoagulation, and management of portal hypertension. While the epidemiology has been well characterized, more work is needed to identify novel contributors to disease pathogenesis, beyond the JAK2 V617F mutation itself, and endothelial compromise. Testing for MPN mutations in the setting of non-cirrhotic SVT is commonplace; JAK2 V617F is the most likely to be identified. Testing for CALR or MPL mutations requires clinical judgement, though not unreasonable. The mainstay of therapy is indefinite anticoagulation; the role of direct oral anticoagulants is unclear. JAK inhibition may play a role in addressing associated splenomegaly and portal hypertension.

Management of portal hypertension before and after liver transplantation.

Orthotopic liver transplantation (OLT) represents a curative treatment option for end-stage liver disease (ESLD). Although epidemiology of ESLD has recently changed due to the rising prevalence of nonalcoholic fatty liver disease and the decreased burden of hepatitis C virus infections due to highly effective antiviral regimens, the management of portal hypertension (PHT) remains a clinical challenge in the pre- and post-OLT setting. The measurement of the hepatic venous pressure gradient represents the most reliable but invasive tool for assessment of the severity of PHT. Although novel liver ultrasound and magnetic resonance-based elastography methods have been developed, their value to screen for liver fibrosis and PHT in transplanted patients remains to be established. Nonselective beta-blockers represent the cornerstone of medical treatment of PHT, but more studies on their effects on clinical endpoints after OLT are needed. Statins are widely used to treat hyperlipidemia, which is a common condition after OLT. Although a growing body of evidence suggests that statins decrease portal pressure and PHT-related complications in ESLD, studies on potential benefits of statins after OLT are lacking. Finally, transjugular intrahepatic portosystemic shunts (TIPS) are effective in decreasing PHT and seem to decrease mortality on the OLT waiting list. Moreover, TIPS does not have an impact on liver function nor complicate the transplant surgical procedures. TIPS may also be used after OLT, but the evidence is limited. In conclusion, whereas the management of PHT in patients with ESLD is based on strong evidence, further data on the value of noninvasive monitoring tools as well as on medical and invasive treatment options in the post-OLT setting are needed to improve management strategies in patients with recurrent PHT after liver transplantation. Liver Transplantation 24 112-121 2018 AASLD.

Medical Management of Portal Hypertension and Its Complications

AbstractPortal hypertension, most commonly caused by cirrhosis, is defined as an elevated hepatic venous pressure gradient that can lead to complications including ascites, hepatic, esophageal/gastric varices, hepatic encephalopathy, and hepatorenal syndrome. While these complications are initially managed by medical and endoscopic treatments, progressive decompensation of liver disease may lead to liver transplantation.

Novelties in the pathophysiology and management of portal hypertension: new treatments on the horizon

Portal hypertension (PH) is responsible for the most severe complications of cirrhosis and leading cause of death and liver transplantation. The standard pharmacological treatment available for PH currently consists of the use of a non-selective beta-blocker. However, a significant proportion of patients do not respond to pharmacological treatment. This has led to the development of identifiable targets for the discovery of new horizons in PH treatment. Recently, there has been significant progress in understanding the mechanism behind PH, which is a product of increased hepatic vascular resistance including structural changes and functional change due to endothelial dysfunction. Moreover, increased portal inflow is the outcome of dilation of splanchnic vessels and hyperdynamic circulation. Here, challenges in formulating potential pharmacological treatment as well as current potential targets for PH will be reviewed. During the past decades, there have been many efforts to explore new techniques to stimulate liver regeneration in addition to pharmacological treatment. The bone marrow (BM) stem cells which differentiate into mature hepatocytes are thought to contribute to liver regeneration and have been found to demonstrate great potential as regenerative medicine in different therapeutic applications. Based on these insights, we explore the current and potential novel therapeutic uses of BM stem cell therapy in PH.

Focusing on the diagnosis and management of portal hypertension in cirrhosis

Portal hypertension is one common complication with a high mortality in end-stage liver diseases. However, poor outcome has been shown with present therapeutic strategy, and the diagnosis and treatment of portal hypertension and its complications are research focuses. Therefore, it is necessary for clinicians and expert to regard diagnosis and treatment of portal hypertension patients, and to improve their clinical outcomes.

Multidisciplinary Non-Transplant Management of Confluent Porto-Mesenteric Thrombosis

Background: Confluent porto-mesenteric thrombosis (PMT) is a complex condition which can result in catastrophic variceal bleeding or refractory ascites secondary to portal hypertension (PHT). Management of PHT is challenging and often requires a multivisceral transplant (MVT). While short and medium term outcomes of MVT have improved, long term outcomes remain suboptimal.We report a single center experience of non-transplant management of confluent PMT, with specific focus on results of adopting a multi-D approach since 2012. End points were patient survival and re-bleeds. Method: Retrospective review of patients with PMT in a single center over a 10-year period. A dedicated multi-D team comprising of hepatology, transplant surgery, hematology and interventional radiology (IR) was developed over the last 5 years. All imaging was reviewed by TX surgery and IR to confirm confluent PMT. Patients who underwent MVT, non-confluent PMT or isolated superior mesenteric vein (SMV) thrombosis were excluded for this analysis. Results: Twenty patients met inclusion criteria (Table 1). 7 patients underwent ‘modified’ single stage Sugiura procedures (key Table1) and 13 had IR procedures for revascularization with additional thrombectomy in acute situations. 3 patients had percutaneous mesocaval shunts, while the other 10 had extended TIPS procedures. 3 patients re-bled after percutaneous procedures and 1 after a Sugiura. 7 of the 13 patients managed percutaneously had at least one re-intervention for complications. Reintervention was required in 7 out of 13 patients who had a percutaneous approach and in 1 patient post-Sugiura. 4 (2 surgical and 2 IR) of the 20 patients have died. Causes of death were: multiorgan failure in 2 patients with refractory re-bleed (1 acute, with intra-peritoneal bleeding post extended TIPS) and in 1, 9 months after a failed Sugiura. 1 patient had an infected TIPS and recurrent fungemias and 1 death was late after a Sugiura from unrelated cardiac causes. Conclusions: A multi-D approach may allow some patients with confluent PMT to avoid MVT. The considerable morbidity and even mortality in our experience emphasizes the need for very careful patient selection by an experienced team; while no patient in this cohort has required MVT, we believe rapid access to MVT may be a critical component of this approach. Despite the need for reinterventions in some patients, the avoidance of MVT and overall outcomes appear to justify our approach.Figure

Gender Linked Metric Analysis of Portal Vein: A Sonographic Appraisal.

Portal hypertension is one of the most mystifying and disconcerting abdominal ailment. Ultrasonography (USG) is an effective diagnostic tool for its prompt management. Knowledge of normal calibre of portal vein in a local setting is essential as literature reports contrasting values in different regions. It helps in early diagnosis of portal hypertension even before it is clinically manifested thereby assisting clinicians and interventional radiologists in pertinent management. Study was aimed to evaluate the Portal Vein Diameter (PVD) and find its correlation with gender by using USG in North Indian population. A total of 300 healthy adults were included in the study. Portal vein diameter was measured in supine position and normal respiration by grey scale USG. The portal vein diameter was correlated with age and gender statistically using independent Student's t-test and ANOVA. Mean PVD of (9.49±1.03 mm) was observed in the present cross-sectional study. Male showed a significantly higher mean PVD (9.70±1.02 mm) as compared to females (9.10±0.94 mm). Scarcity of information concerning ultrasonographically measured standard portal vein diameter and inconstant values reported in literature necessitates the need for establishing local standard value. In the given subset of population the portal vein diameter was influenced by the gender. The information will be helpful in prompt diagnosis and management of portal hypertension.

Liver Stiffness Measurement in the Prediction of Clinical Significant Portal Hypertension and Related Complications

Hepatic cirrhosis is the end stage of chronic liver disease and leads to portal hypertension (PH) resulting in disease progression manifested with esophageal varices (EV) formation/bleeding, ascites formation and porto-systemic encephalopathy. The detection, prevention and management of portal hypertension and its complication are important for patient with cirrhosis. Hepatic venous pressure gradient (HVPG) has been the standard reference in portal pressure measurement and good predictor of prognosis and therapeutic effects for patients with PH. However, HVPG measurement is an invasive procedure requiring adequate equipment and needing a certain degree of expertise. Liver stiffness (LS) measured with transient elastography is a non-invasive method and in good correlation with portal pressure assessing with HVPG. Although there is also correlation between LS and presence of EV or high-risk EV, it was not as good as that for clinical significant PH. Most studies have demonstrated LS is useful in the prediction of PHT and its complication for patients with hepatic cirrhosis or advanced fibrosis. Clinically significant PH is >90% likely in patients with LS >20-25kPa. A proposed algorithm using LS, platelet count and abdominal sonography provided a useful strategy to detect early PHT. LS-based score incorporating LS, spleen size and platelet count demonstrated to be useful in identifying patients with clinical significant PHT or EV. Braveno VI consensus recommended avoiding screening scope for those patients with LS<20 kPa and platelet count >150000/mm3. Although useful in the EV prediction, LS measurement is not a replacement of scope in the diagnosis of varices for patients with hepatic cirrhosis.

Portal Hypertension Treatment with Candesartan plus Propranolol for Nine Months Restores Normal Portal Circulation Hemodynamic Pattern

Post HCV liver cirrhosis is one of the most prominent etiologies behind the abnormal portal circulation hemodynamics. It occurs as a result of distorted balance between portal venous flow (PVF) and intrahepatic resistances (IHR). PVF is partially controlled by using both specific and non-specific beta blockers (NSBBs) that have insignificant effects on IHR. Angiotensin recep- tor blockers (ARBs) inhibit the activated hepatic stellate cell (HSC) contraction and thought to reduce the dynamic portion of IHR. The study aimed to slow down the venous blood flow and to reduce the IHR of portal vein vasculature to control sequelae of the enhanced post cirrhosis portal venous turbulence. We evaluated the effects of Candesartan plus propranolol compared to each of them individually in management of portal hypertension (PH). Three groups of 25 patients each, presented with chronic HCV infection and grade II- III esophageal varices (OV), were randomly assigned to one of three treatment regimens: Propranolol or Candesartan or both. Subjects were screened every three month by Doppler Ultrasound for a total of nine months. Damping Index(DI),,pu1se Pulsatiity Index (P), Portal Venous Flow (PVF) Volume, Portal Venous Peak Velocity (PVPV), and Portal Vein Diameter (PVD) were evaluated once every.third month. Our study concluded that combined therapy (Propranolol + Candesartan) induced highly significant improvements that led to restoration of normal values of DI, PI, PVF volume & PVPV overtime compared to monotherapy regimens (P>O.001). Data strongly recommended using Propranolol plus Candesartan' in overtime management of portal hypertension.