Portal vein thrombosis in cirrhosis: Controversies and latest developments

Portal vein thrombosis(PVT) is encountered in livercirrhosis, particularly in advanced disease. It has been a feared complication of cirrhosis, attributed to significant worsening of liver disease, poorer clinical outcomes and potential inoperability at liver transplantation; also catastrophic events such as acute intestinal ischaemia. Optimal management of PVT has not yet been addressed in any consensus publication.We review current literature on PVT in cirrhosis; its prevalence, pathophysiology, diagnosis, impact on the natural history of cirrhosis and liver transplantation,and management. Studies were identified by a search strategy using MEDLINE and Google Scholar. The incidence of PVT increases with increasing severity of liver disease: less than 1% in well-compensated cirrhosis, 7.4%-16% in advanced cirrhosis. Prevalence in patients undergoing liver transplantation is 5%-16%.PVT frequently regresses instead of uniform thrombus progression. PVT is not associated with increased risk of mortality. Optimal management has not been addressed in any consensus publication. We propose areas for future research to address unresolved clinical questions.

Historical overview and review of current day treatment in the management of acute variceal haemorrhage

Variceal haemorrhage is one of the most devastating consequences of portal hypertension,with a 1-year mortality of 40%.With the passage of time,acute management strategies have developed with improved survival.The major historical treatment landmarks in the management of variceal haemorrhage can be divided into surgical,medical,endoscopic and radiological breakthroughs.We sought to provide a historical overview of the management of variceal haemorrhage and how treatment modalities over time have impacted on clinical outcomes.A PubMed search of the following terms:portal hypertension,variceal haemorrhage,gastric varices,oesophageal varices,transjugular intrahepatic portosystemic shunt was performed.To complement this,Google?was searched with the aforementioned terms.Other relevant references were identified after review of the reference lists of articles.The review of therapeutic advances was conducted divided into pre-1970s,1970/80s,1990s,2000-2010 and post-2010.Also,a summary and review on the pathophysiology of portal hypertension and clinical outcomes in variceal haemorrhage was performed.Aided by the development of endoscopic therapies,medication and improved radiological interventions;the management of variceal haemorrhage has changed over recent de-cades with improved survival from an often-terminating event in recent past.

Role of early transjugular intrahepatic portosystemic stent-shunt in acute variceal bleeding:An update of the evidence and future directions

Variceal bleeding is a serious complication of cirrhosis and portal hypertension.Despite the improvement in management of acute variceal bleed(AVB),it still carries significant mortality.Portal pressure is the main driver of variceal bleeding and also a main predictor of decompensation.Reduction in portal pressure has been the mainstay of management of variceal bleeding.Transjugular intrahepatic porto-systemic stent shunt(TIPSS)is a very effective modality in reducing the portal hypertension and thereby,controlling portal hypertensive bleeding.However,its use in refractory bleeding(rescue/salvage TIPSS)is still associated with high mortality.“Early”use of TIPSS as a“pre-emptive strategy”in patients with AVB at high risk of failure of treatment has shown to be superior to standard treatment in several studies.While patients with Child C cirrhosis(up to 13 points)clearly benefit from early-TIPSS strategy,it’s role in less severe liver disease(Child B)and more severe disease(Child C>13 points)remains less clear.Moreover,standard of care has improved in the last decade leading to improved 1-year survival in high-risk patients with AVB as compared to earlier“early”TIPSS studies.Lastly in the real world,only a minority of patients with AVB fulfil the stringent criteria for early TIPSS.Therefore,there is unmet need to explore role of early TIPSS in management of AVB in well-designed prospective studies. In this review, we have appraised the role of early TIPSS, patient selection anddiscussed future directions in the management of patients with AVB.

Portal hypertension in polycystic liver disease patients does not affect wait-list or immediate post-liver transplantation outcomes

AIM To establish the impact of portal hypertension(PH) on wait-list/post-transplant outcomes in patients with polycystic liver disease(PCLD) listed for liver transplantation. METHODS A retrospective single-centre case controlled study of consecutive patients listed for liver transplantation over 12 years was performed from our centre. PH in the PCLD cohort was defined by the one or more of following parameters:(1) presence of radiological or endoscopic documented varices from our own centre or the referral centre;(2) splenomegaly(> 11 cm) on radiology inabsence of splenic cysts accounting for increased imaging size;(3) thrombocytopenia(platelets < 150 × 109/L); or(4) ascites without radiological evidence of hepatic venous outflow obstruction from a single cyst. RESULTS Forty-seven PCLD patients(F: M = 42: 5) were listed for liver transplantation(LT)(single organ, n = 35; combined liver-kidney transplantation, n = 12) with 19 patients(40.4%) having PH. When comparing the PH group with non-PH group, the mean listing age(PH group, 50.6(6.4); non-PH group, 47.1(7.4) years; P = 0.101), median listing MELD(PH group, 12; non-PH group, 11; P = 0.422) median listing UKELD score(PH group, 48; non-PH group, 46; P = 0.344) and need for renal replacement therapy(P = 0.317) were similar. In the patients who underwent LT alone, there was no difference in the duration of ICU stay(PH, 3 d; non-PH, 2 d; P = 0.188), hospital stay length(PH, 9 d; non-PH, 10 d; P = 0.973), or frequency of renal replacement therapy(PH, 2/8; non-PH, 1/14; P = 0.121) in the immediate post-transplantation period. CONCLUSION Clinically apparent portal hypertension in patients with PCLD listed for liver transplantation does not appear to have a major impact on wait-list or peri-transplant morbidity.

Outcomes of pregnancy in patients with known Budd-Chiari syndrome

AIM To analyse the risk of pregnancy(a prothrombotic state) in patients with Budd-Chiari Syndrome(BCS). METHODS Retrospective study of pregnancy in women with known BCS at single center from January 2001 to December 2015. RESULTS Out of 53 females with BCS, 7 women had 16 pregnancies. Median age at diagnosis of BCS in these women was 25 years(range 21-34 years). At least one causal factor for BCS was identified in 6 women(86%). Six women had undergone radiological decompressive treatment. All patients had anticoagulation. Six fetuses were lost before 20 wk gestation in 2 women. There were 9 deliveries over 32 wk gestation and one delivery at 27 wk. All infants did well. Seven babies were born by emergency caesarean section. There were no cases of thrombosis. Two patients had notable vaginal(PV) bleeding in 3 pregnancies. None of the patients had variceal haemorrhage. Two patients were diagnosed with pulmonary hypertension, one during pregnancyand the other in the post-partum period. There was no maternal mortality.CONCLUSION Maternal outcomes in patients with treated BCS are favourable and fetal outcomes beyond 20 wk gestation are good. There has been increased rate of caesarean section. Pulmonary hypertension is an important finding that needs further validation. These patients should be managed in centers experienced in treating high-risk pregnancies.

Non-selective beta-blockers in cirrhosis:Current concepts and controversies

Non-selective beta-blockers(NSBBs) have been at the forefront in the management of portal hypertension in liver cirrhosis for the last three decades, a trusty component in the armamentarium of the Hepatologist. The role of beta-blockers has been cemented for years in cardiac disease including angina, hypertension and in heart failure, however NSBBs with their non-selective effects on β1 and β2 receptors have led to them fondly being termed "the hepatologist's aspirin". NSBBs' role in reduction of portal pressure in the setting of primary and secondary prophylaxis for variceal haemorrhage has been well established. NSBBs include propranolol, nadolol and carvedilol- with the latter having been shown to be effective in patients who often fail to demonstrate a haemodynamic response to propranolol. Recent observational studies however have served for the Hepatology community to question the beneficial role of NSBBs in portal hypertension, especially in advanced cases with refractory ascites. The deleterious effect in patients with refractory ascites in a few studies led to a U-turn in clinical practice, with some in the Hepatology community withdrawing their usage in patients with advanced cirrhosis. This also led to the "window hypothesis" suggesting there may be only be a finite time frame when NSBBs have a beneficial effect in portal hypertension. The window hypothesis proposed the window for the benefits of NSBBs is closed in early portal hypertension, opening as portal hypertension progresses with it closing in advanced liver disease. The window was proposed to close in conditions such as refractory ascites or spontaneous bacterial peritonitis when patients may not necessarily mount a compensatory haemodynamic response when on NSBBs. Some centres however have continued the practice of NSBBs in advanced cirrhosis with published data challenging the scepticisms of other groups who stop NSBBs. Thus the debate, like the window hypothesis has opened, with more questions to be answered about NSBB's mechanism of action not only in reducing portal hypertension but also their effects on systemic haemodynamics and on the pro-inflammatory pathways often activated in cirrhosis especially in advanced disease. This article serves to review the role of NSBBs in the management of portal hypertension/cirrhosis and concentrate on current concepts and controversies in this field.

Covered transjugular intrahepatic portosystemic stent-shunt vs large volume paracentesis in patients with cirrhosis: A real-world propensity score-matched study

BACKGROUND Refractory ascites has a 1-year survival rate of 50%.In selected patients,treatment options include liver transplantation(LT)or transjugular intrahepatic portosystemic stent shunt(TIPSS).AIM To assess the outcomes of patients who underwent a TIPSS compared to large volume paracentesis(LVP).METHODS Retrospective study of patients who underwent a covered TIPSS or LVP for refractory or recurrent ascites over 7 years.Primary outcome was transplant-free survival(TFS).Further analysis was done with propensity score matching(PSM).RESULTS There were 150 patients[TIPSS group(n=75),LVP group(n=75)].Seven patients in the TIPSS group underwent LT vs 22 patients in the LVP group.Overall median follow up,20(0.47-179.53)mo.In the whole cohort,there was no difference in TFS[hazard ratio(HR):0.80,95%confidence interval(CI):0.54-1.21];but lower de novo hepatic encephalopathy with LVP(HR:95%CI:0.20-0.96).These findings were confirmed following PSM analysis.On multivariate analysis albumin and hepatocellular carcinoma at baseline were associated with TFS.CONCLUSION Covered TIPSS results in similar TFS compared to LVP in cirrhotic patients with advanced liver failure.Liver transplant assessment should be considered in all potential candidates for TIPSS.Further controlled studies are recommended to select appropriate patients for TIPSS.

Current concepts in the management of non-cirrhotic non-malignant portal vein thrombosis

Non-cirrhotic non-malignant portal vein thrombosis(NCPVT)is an uncommon condition characterised by thrombosis of the portal vein,with or without extension into other mesenteric veins,in the absence of cirrhosis or intra-abdominal malignancy.Complications can include intestinal infarction,variceal bleeding and portal biliopathy.In this article,we address current concepts in the management of NCPVT including identification of risk factors,classification and treatment,and review the latest evidence on medical and interventional management options.

静脉曲张出血的最新治疗进展

急性胃食管静脉曲张破裂出血是肝硬化门脉高压患者最严重的并发症,常需急诊处理,有较高的并发症发生率和病死率。即便在最初的急性出血中幸存,这些患者再次出血及出现其他失代偿事件的风险仍然很高。过去30年治疗策略的不断演进,已大大提高了静脉曲张出血患者的生存概率。由于肝硬化具有多个病期,所以单一笼统的治疗模式已被摒弃,取而代之的是针对不同病期的患者采用不同的治疗方法以得到最佳治疗效果。这需要我们按疾病分期对肝硬化患者进行分层,然后方能针对个体化病例采用恰当的治疗方式并选择合理的治疗时机。与此同时,新的治疗方法不断涌现,而大量最新的证据仍然支持内镜和药物治疗的应用。本文中,我们对各个病期及止血失败后的治疗选择进行了总结。我们进行了细致的文献综述,呈现了所有的随机对照试验和meta分析结果,这些结果支持上述的治疗模式。