Portal hypertension and variceal bleeding in patients with liver cancer: Evidence gaps for prevention and management.

BACKGROUND AND AIMS: Portal hypertension (PHT) and HCC are 2 major complications of cirrhosis that often coexist in the same patient and impact the prognosis, especially in patients with acute variceal bleeding. In this review, we aim to discuss the best strategy for PHT screening and primary prophylaxis, as well as the management of acute variceal bleeding, to improve the management of PHT in HCC patients. RESULTS: Recent therapeutic advances observed in the management of HCC, notably through the advent of immunotherapy, have led to a clear improvement in the survival of patients. The prevention of complications related to underlying cirrhosis, such as PHT and acute variceal bleeding, is now part of the management of HCC patients. The Baveno VII conference recently redefined screening and prophylaxis in patients with cirrhosis. However, data regarding the applicability of these criteria in patients with HCC have been sparse. From our point of view, the Baveno criteria are not appropriate to exclude high-risk esophageal varices (EV) in HCC patients, and endoscopy should be performed except in HCC patients with a liver stiffness measurement (LSM) ≥25 kPa, who should benefit from nonselective beta-blockers (NSSBs) without performing endoscopy. We are also in favor of using NSBBs as primary prophylaxis in patients with EV regardless of the size and with gastric varices since these patients display clinically significant PHT. CONCLUSIONS: Appropriate evaluation and treatment of PHT remain major issues in improving the outcomes of HCC patients. Many questions remain unanswered, opening the field to many areas of research.

Pre-emptive TIPS in high-risk acute variceal bleeding. An updated and revised individual patient data meta-analysis.

BACKGROUND AND AIMS: A previous individual patient data meta-analysis (IPD-MA) showed that compared with drugs+endoscopy, the placement of transjugular portosystemic shunt within 72 hours of admission (pre-emptive transjugular intrahepatic portosystemic shunt: p-TIPS) increases the survival of high-risk patients (Child-Pugh B+ active bleeding and Child-Pugh C<14 points) with cirrhosis and acute variceal bleeding. However, the previous IPD-MA was not a two-stage meta-analysis, did not consider the potential risk of selection bias of observational studies, and did not include the most recent randomized clinical trial. We performed an updated and revised IPD-MA to reassess the efficacy of p-TIPS, addressing all previous issues. APPROACH AND RESULTS: We included all studies from the previous IPD-MA and searched for other possible eligible publications until September 2022. We performed a two-stage IPD-MA of data from 8 studies (4 randomized clinical trials and 4 observational). In addition, we performed a sensitivity analysis excluding those patients dying up to the first 72 hours after admission in the Drugs+Endoscopy arms of the 4 observational studies. The primary end point was the effects of p-TIPS versus Drugs+Endoscopy on 1-year survival.We identified 1389 patients (342 p-TIPS and 1047 Drugs+Endoscopy). The two-stage IPD-MA showed that p-TIPS significantly reduced the mortality in the overall population (HR=0·43, 95% CI: 0.32-0.60, p <0.001. This effect was observed in both subgroups of patients with Child-Pugh. The sensitivity analysis confirmed the survival benefit of p-TIPS. CONCLUSIONS: The updated two-stage IPD-MA confirms the significant survival advantage of p-TIPS in high-risk patients with cirrhosis and acute variceal bleeding. As a result, we recommend p-TIPS as the preferred first-choice treatment for these patients.

Direct-Acting Antivirals Reduce the De Novo Development of Esophageal Varices in Patients with Hepatitis C Virus Related Liver Cirrhosis.

The real-world benefits of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on the de novo occurrence and progression of esophageal varices (EV) remain unclear in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). This is a retrospective cohort study evaluating all patients with Child-Pugh class A HCV-related LC during 2013 to 2020 in the Chang Gung Medical System. A total of 215 patients fit the inclusion criteria and were enrolled. Of them, 132 (61.4%) patients achieved DAA induced-SVR and 83 (38.6%) did not receive anti-viral treatment. During a median follow-up of 18.4 (interquartile range, 10.1−30.9) months, the 2-year incidence of de novo EV occurrence was 8 (7.0%) in the SVR group and 7 (12.7%) in the treatment-naïve group. Compared to the treatment-naïve group, the SVR group was associated with a significantly lower incidence of EV occurrence (adjusted hazard ratio [aHR]: 0.47, p = 0.030) and a significantly lower incidence of EV progression (aHR: 0.55, p = 0.033). The risk of EV progression was strongly correlated with the presence of baseline EV (p < 0.001). To the best of our knowledge, this is the first study to demonstrate that DAA-induced SVR is associated with decreased risk of de novo EV occurrence and progression in the real world.

Sinistral Portal Hypertension Prediction During Pancreatoduodenectomy With Splenic Vein Resection.

BACKGROUND: Pancreaticoduodenectomy with porto-mesenterico-splenic confluence resection can cause sinistral portal hypertension (SPH), which may lead to gastrointestinal bleeding. Nevertheless, it remains difficult to predict SPH development during surgery. The aim of this study is to assess the feasibility of measuring splenic vein (SV) pressure to predict SPH. METHODS: The patients who underwent pancreaticoduodenectomy with porto-mesenterico-splenic confluence resection between January 2016 and December 2017 were included in this study. SV pressure was measured before SV clamping (SVP1) and after SV clamping (SVP2). SPH was defined as varicose vein formation detected by follow-up computed tomography. Incidence of SPH was assessed in patients who had no SV drainage after surgery. RESULTS: SV pressure was measured in 41 patients. Among them, 24 had no SV drainage (13 patients had occluded SV reconstruction, and 11 had SV ligation without an attempt at reconstruction) and were included for the analysis. SPH was observed in 16 of 24 patients (67%). The median ΔSVP (SPV2-SVP1) in patients with SPH was higher than that in patients without SPH (13.5 mmHg versus 7.5 mmHg, P = 0.0237). Most patients with SVP2 >20 mmHg (12/14 [86%]) or ΔSVP >10 mmHg (10/11 [91%]) developed SPH. CONCLUSIONS: For the patients with SV resection, high SV pressure after clamping (≥20 mmHg) and a large SV pressure difference (≥10 mmHg) before and after clamping are feasible indication criteria for SV reconstruction to prevent SPH.

CARVEDILOL AS PRIMARY PROPHYLAXIS FOR GASTRIC VARICEAL BLEEDING IN PORTAL HYPERTENSION MODEL IN RATS.

BACKGROUND: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy. AIM: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model. METHOD: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days. RESULTS: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups. CONCLUSION: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.

Endoscopic prophylaxis and factors associated with bleeding in children with extrahepatic portal vein obstruction / Profilaxia endoscópica e fatores associados ao sangramento em crianças com obstrução extra-hepática da veia porta

Abstract Objectives: This study aimed to evaluate factors associated with upper digestive hemorrhage and primary and secondary endoscopic prophylaxis outcomes in children with extrahepatic portal vein obstruction. Methods: This observational and prospective study included 72 children with extrahepatic portal vein obstruction who were followed from 2005 to 2017. Risk factors associated with upper digestive hemorrhage and the results of primary and secondary prophylaxis of these patients were evaluated. Results: Fifty patients (69.4%) had one or more episodes of bleeding during follow-up, with a median age at first hemorrhage of 4.81 years. The multivariate analysis showed that medium- to large-caliber esophageal varices were associated with an 18-fold risk of upper digestive hemorrhage (95% CI: 4.33-74.76; p < 0.0001). Primary prophylaxis was administered to 14 patients, with eradication in 85.7%; however, 14.3% of these patients had hemorrhages during the follow-up period and 41.7% had a relapse of varices. Secondary prophylaxis was administered to 41 patients. Esophageal varices were eradicated in 90.2% of patients. There were relapse and re-bleeding of esophageal varices in 45.9% and 34.1% of the children, respectively. Conclusion: Primary and secondary endoscopic prophylaxes showed high rates of esophageal varix eradication, but with significant relapses. Eradication of esophageal varices cannot definitively prevent recurrent upper digestive hemorrhage, since bleeding from alternate sites can occur. Medium- and large-caliber esophageal varices were associated with upper digestive hemorrhage in patients with extrahepatic portal vein obstruction. To the best of the authors' knowledge, this study is the first to evaluate bleeding risk factors in children with extrahepatic portal vein obstruction.

Resumo Objetivos: Este estudo visou avaliar fatores associados à hemorragia digestiva alta e resultados da profilaxia endoscópica primária e secundária em crianças com obstrução extra-hepática da veia porta. Métodos: Este estudo observacional e prospectivo incluiu 72 crianças com obstrução extra-hepática da veia porta acompanhadas de 2005 a 2017. Os fatores de risco associados à hemorragia digestiva alta e os resultados da profilaxia primária e secundária desses pacientes foram avaliados. Resultados: Dos pacientes, 50 (69,4%) apresentaram ≥ 1 episódio de sangramento durante o acompanhamento, com idade média da primeira hemorragia de 4,81 anos. A análise multivariada mostrou que varizes esofágicas de médio a grande calibre estavam associadas a um risco 18 vezes maior de hemorragia digestiva alta (IC de 95% 4,33-74,76; p < 0,0001). Foi administrada profilaxia primária em 14 pacientes, com erradicação em 85,7%; contudo, 14,3% desses pacientes apresentaram hemorragias durante o período de acompanhamento e 41,7% apresentaram recidiva de varizes. Foi administrada profilaxia secundária em 41 pacientes. As varizes esofágicas foram erradicadas em 90,2% dos pacientes. Houve recidiva e novos sangramentos de varizes esofágicas em 45,9% e 34,1% das crianças, respectivamente. Conclusão: As profilaxias esofágicas primárias e secundárias apresentaram altas taxas de erradicação de varizes esofágicas, porém com recidivas significativas. A erradicação de varizes esofágicas não pode prevenir de forma definitiva a hemorragia digestiva alta recorrente, pois pode ocorrer sangramento de outros locais. Varizes esofágicas de médio e grande calibre estavam associadas à hemorragia digestiva alta em pacientes com obstrução extra-hepática da veia porta. No melhor de nosso conhecimento, nosso estudo é o primeiro a avaliar os fatores de risco de sangramento em crianças com obstrução extra-hepática da veia porta.

Poor performance of noninvasive predictors of esophageal varices during primary prophylaxis surveillance in biliary atresia.

OBJECTIVE: Our objective was to analyze performance of noninvasive markers for significant esophageal varices in relation to outcomes of endoscopic surveillance and primary prophylaxis in biliary atresia (BA). METHODS: This was a prospective follow-up study of a national cohort of BA patients born between 1989 and 2017, including 72 consecutive patients who underwent variceal surveillance endoscopies. The risk for developing significant varices (grade ≥ 2) and variceal bleeding was compared between successful (postoperative total bilirubin ≤34 µmol/L) and failed portoenterostomy (PE) patients. AUROC analyses and Wilcoxon signed ranks test were used to assess accuracy of noninvasive measures to predict the presence of significant varices after successful PE. RESULTS: In total, 72 patients underwent 471 endoscopies during 427 follow-up years. Among 45 successful PE patients (63%), varices appeared later [at median age 1.6 (0.7-14) vs. 0.8 (0.4-1.9) years] and bled less often [7% vs. 41%, p < 0.001 for both] than after failed PE. Liver biochemistry, stiffness, and predictive scores showed poor accuracy for the presence of significant varices. After failed PE, lowered plasma albumin concentration predicted varices with an AUROC of 0.69 (95% CI 0.52-0.85, p = 0.030). After successful PE the varices prediction rule with AUROC 0.72 (95% CI 0.64-0.79) was the most accurate predictor. Individual predictors showed no meaningful changes between the two consecutive endoscopies leading to discovery of varices. CONCLUSION: Accurate targeting of endoscopies based on noninvasive predictors remains difficult during primary variceal prophylaxis protocol in BA. The differing prognoses after successful and failed PE should be considered in variceal surveillance and future studies. TYPE OF STUDY: Diagnostic/prognosis study. LEVEL OF EVIDENCE: Level II.

Risk of rebleeding from gastroesophageal varices after initial treatment with cyanoacrylate; a systematic review and pooled analysis.

BACKGROUND: Cyanoacrylate alone or in combination with other interventions, can be used to achieve variable rates of success in preventing rebleeding. Our study aims to assess the pooled risk of gastric and esophageal varices rebleeding after an initial treatment with cyanoacrylate alone and/or in combination with other treatments, by a systematic review of the literature and pooled analysis. METHODS: PubMed, EMBASE, SCOPUS, and the Cochrane library were searched for studies that reported the risk of rebleeding during the follow-up period after treatment of gastric or esophageal varices with either cyanoacrylate alone or in combination with other treatments. Standard error, upper and lower confidence intervals at 95% confidence interval for the risk were obtained using STATA Version 15 which was also used to generate forest plots for pooled analysis. The random or fixed effect model was applied depending on the heterogeneity (I2). RESULTS: A total of 39 studies were found to report treatment of either gastric or esophageal varices with either cyanoacrylate alone or in combination with other treatments. When gastric varices are treated with cyanoacrylate alone, the risk of rebleeding during the follow-up period is 0.15(Confidence Interval: 0.11-0.18). When combined with lipiodol; polidocanol or sclerotherapy the rebleeding risks are 0.13 (CI:0.03-0.22), 0.10(CI:0.02-0.19), and 0.10(CI:0.05-0.18), respectively. When combined with percutaneous transhepatic variceal embolization; percutaneous transhepatic variceal embolization; endoscopic ultrasound guided coils; or with ethanolamine, the rebleeding risk are 0.10(CI:0.03-0.17), 0.10(CI:0.03-0.17), 0.07(CI:0.03-0.11) and 0.08(CI:0.02-0.14), respectively. When esophageal varices are treated with cyanoacrylate alone, the risk of rebleeding is 0.29(CI:0.11-0.47). When combined with percutaneous transhepatic variceal embolization; sclerotherapy; or band ligation, the risks of rebleeding are 0.16(CI:0.10-0.22), 0.12(CI:0.04-0.20) and 0.10(CI:0.04-0.24), respectively. When combined with a transjugular intrahepatic portosystemic shunt; or ethanolamine, the risks of rebleeding are 0.06(CI: - 0.01-0.12) and 0.02 (CI: - 0.02-0.05), respectively. CONCLUSION: In treating both gastric and esophageal varices, cyanoacrylate produces better results in terms of lower risk of rebleeding when combined with other treatments than when used alone. The combination of cyanoacrylate with ethanolamine or with endoscopic ultrasound guided coils produces the lowest risk of rebleeding in esophageal and gastric varices, respectively. We call upon randomized trials to test these hypotheses.

Cystic fibrosis-associated liver disease in children.

As improvements in nutritional and pulmonary care increase the life expectancy of cystic fibrosis (CF) patients, CF-associated liver disease (CFLD) is emerging as a cause of mortality. CFLD is the third leading cause of death in CF patients. We performed a search on PubMed and Google Scholar for published articles on CFLD. We reviewed the articles found in the literature search and gave priority to recent publications and studies with larger sample sizes. The prevalence of CFLD in the CF population is around 23% with a range of 2-62% and that prevalence increases linearly with age from 3.7% at age 5 to 32.2% at age 30. CFLD can present clinically in various ways such as hepatomegaly, variceal hemorrhage, persistent elevation of liver enzymes, and micro-gallbladder. Due to the focal nature of fibrosis in majority cases of CFLD, liver biopsies are sparsely performed for diagnosis or the marker of liver fibrosis. Although the mechanism of CFLD development is still unknown, many potential factors are reported. Some mutations of CFTR such as having a homozygous F508del mutation has been reported to increase the risk of developing CFLD and its severity. Having the SERPINA1 Z allele, a history of pancreatic insufficiency, a history meconium ileus, CF-related diabetes, or being male increases the risk of developing CFLD. Environmental factors do not appear to have significant effect on modulating CFLD development. Ursodeoxycholic acid is commonly used to treat or prevent CFLD, but the efficacy of this treatment is questionable.

Association between esophagogastric varices in hepatocellular carcinoma and poor prognosis after transarterial chemoembolization: A propensity score matching analysis.

BACKGROUND/PURPOSE: Whether esophagogastric varices (EGV) can determine the outcome of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) remains unknown. This study aimed to assess the impact of EGV on the prognosis of HCC patients after TACE. METHODS: From 2007 to 2012, we retrospectively enrolled 251 treatment-naïve HCC patients who underwent TACE and received esophagogastroduodenoscopy when HCC was diagnosed. The prognostic factors were analyzed using a Cox proportional hazards model and propensity score-matching analysis. RESULTS: There were 120 (47.8%) patients with EGV. Compared to those without EGV, patients with EGV had worse liver functional reserve. After a median follow-up of 14.7 months (25th-75th percentiles, 6.4-35.6 months), 152 patients died. The cumulative 5-year overall survival (OS) rates were 11.2% and 38.8% in patients with and without EGV, respectively (p < 0.001). Multivariate analysis showed that presence of EGV, presence of ascites, tumor size >5 cm, serum alpha-fetoprotein >20 ng/mL, progressive disease by modified Response Evaluation Criteria in Solid Tumors, Assessment for Retreatment with TACE score ≥2.5, and higher albumin-bilirubin grades were the independent predictors of poor OS. Subgroup analysis also demonstrated that EGV was associated with poor OS in most of the subgroups. After propensity score matching, the EGV group still had a lower OS rate than their counterparts (p = 0.004). CONCLUSION: HCC patients with EGV had worse liver functional reserve compared to those without EGV. Moreover, EGV was an independent risk factor to predict poor prognosis in patients with HCC after TACE.

Use of fenestration to revise shunt dysfunction after transjugular intrahepatic portosystemic shunt.

PURPOSE: To explore the feasibility of fenestration in the treatment of shunt dysfunction after transjugular intrahepatic portosystemic shunt (TIPS). METHODS: Between February 2012 and December 2017, 12 TIPS patients with shunt dysfunction underwent fenestration to resolve recurrent portal hypertension with gastric variceal bleeding or ascites. The demographic data, operative data, postoperative recovery data, hemodynamic data, and complications were analyzed. RESULTS: Twelve patients underwent TIPS revision by fenestration, with a technical success rate of 100%. After stent reconstruction, the portal vein diameters decreased gradually with time (before the procedure: at 5 days/1 month/3 months/6 months; after procedure: 1.45 ± 0.11 cm/1.38 ± 0.06 cm/1.36 ± 0.05 cm/1.34 ± 0.05 cm/1.32 ± 0.06 cm, respectively, P = 0.057). Additionally, the blood flow velocity and blood flow rapidly increased in the portal veins and shunts after TIPS revision (P < 0.001). Surprisingly, after 3 months of stent reconstruction, the portal blood flow was 4607.99 ± 1304.10 mL/min which was even lower than the shunt flow at 4651.18 ± 612.74 mL/min. The mean pressure gradient (PSG) prior to TIPS revision was 36.71 ± 3.36 mmHg which decreased to 17.42 ± 3.37 mmHg after the procedure (P < 0.001). Clinical improvement was observed in all patients after the shunt reconstruction. Three patients (25%) had mild intra-abdominal hemorrhage at 1 week after the operation. After a mean 11.0 ± 1.24 months follow-up, ascites and bleeding were well controlled, and no stenosis of the stents was found. CONCLUSIONS: For patients with failed TIPS revision, fenestration to reconstruct the shunt provides an excellent alternative procedure, which is effective, safe, and has a certain clinical value, for continuing the treatment of portal hypertension.

Effect of Nonselective ß-Blockers on Mortality in Patients With End-Stage Cirrhosis.

Background: Data regarding safety of nonselective ß-blockers (NSBBs) in patients with end-stage cirrhosis are conflicting, making it difficult for practitioners to justify if benefits outweigh the risks. Objective: Evaluate the effect of NSBB use on mortality in patients with end-stage cirrhosis. Methods: We performed a dual-center retrospective study of patients who received octreotide for a variceal bleed. Patients were stratified into 2 groups based on whether or not a NSBB was prescribed at hospital discharge. The primary outcome was 24-month mortality. Multivariable logistic regression, with 24-month mortality as the dependent variable, was performed to identify independent risk factors for the primary outcome. Results: 255 patients met inclusion criteria; 24-month mortality was 32.8%. The NSBB and no-NSBB groups had similar mortality rates at 24 months (32.0% vs 38.5%, P = 0.51). Mortality at 3 months (11.6% vs 23.3%, P = 0.08) and 12 months (22.2% vs 30.0%, P = 0.36) were similar, and there were no differences in rate of variceal bleeding (22.7% vs 13.3%, P = 0.34) or cirrhosis-related cause of death (20.4% vs 23.3%, P = 0.81). In the multivariable model, age, model for end-stage liver disease with sodium and hepatocellular carcinoma were independent risk factors for 24-month mortality. NSBB therapy had no effect on 24-month mortality (adjusted odds ratio = 1.05; 95% CI = 0.32 to 3.40). Conclusion and Relevance: In patients with end-stage cirrhosis, use of NSBBs did not affect 24-month mortality. More research is needed to determine when, and if, NSBBs should be discontinued in end-stage cirrhosis.

Carvedilol as primary prophylaxis for gastric variceal bleeding in portal hypertension model in rats / Carvedilol como profilaxia de sangramento em varizes gástricas em modelo de hipertensão portal em ratos

ABSTRACT Background: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy. Aim: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model. Method: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days. Results: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups. Conclusion: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.

RESUMO Racional: A hipertensão portal (HP), medida indiretamente através do gradiente pressórico da veia hepática >5 mmHg, tem como principal causa etiológica a cirrose. Possui como complicações a ascite, disfunção hepática, disfunção renal e varizes esofagogástricas, que caracterizam o quadro de gastropatia. Objetivo: Avaliar o uso do carvedilol como profilaxia primária no desenvolvimento da circulação colateral em ratos submetidos ao modelo de ligadura parcial de veia porta (LPVP). Método: Estudo experimental qualitativo e quantitativo no qual foram utilizados 32 ratos Wistar, divididos em quatro grupos (n=8): grupo I - cirrose + carvedilol (LPVP+C); grupo II - cirrose + veículo (LPVP); grupo III - controle + carvedilol (SO - sham-operated+C); grupo IV - controle + veículo (SO - sham-operated). Após transcorridos sete dias do procedimento cirúrgico, foi administrado carvedilol (10 mg/kg) e veículo (1mL) para os respectivos grupos por sete dias consecutivos. Resultados: A análise histológica não mostrou alteração hepática em nenhum grupo e diminuição de edema e vasodilatação no grupo LPVP+C. A avaliação laboratorial da função hepática não mostrou alteração com significância estatística entre os grupos. Conclusão: Carvedilol mostrou ser fármaco com efeito positivo no sangramento das varizes gástricas e sem efeitos adversos significantes.

NSAID, antiaggregant, and/or anticoagulant-related upper gastrointestinal bleeding: Is there any change in prophylaxis rate after a 10-year period?

BACKGROUND/AIMS: Using proton-pump inhibitor (PPI) is a protective option for patients who require long-term non-steroidal anti-inflammatory drugs (NSAIDs) and antiaggregants. In our previous study, the rate of PPI use in prophylaxis was found to be 2%. Here we aimed to investigate whether there is a change in PPI use in prophylaxis in a similar patient group after 10 years. MATERIALS AND METHODS: The patients who followed up with upper gastrointestinal (GI) bleeding diagnosis between January 01, 2016 and December 31, 2017 were retrospectively evaluated. Patients who had malignancy or variceal hemorrhage were excluded. Ninety-six patients, who had taken NSAIDs, antiaggregants, or anticoagulants that were considered as the possible cause of bleeding, were included in the study. Risk groups for NSAID GI toxicity and PPI use rates in these patients were evaluated. RESULTS: Twenty (21%) of all patients with upper GI bleeding were using PPI. According to the pre-bleeding risk factor assessment, 86% of the patients were found to have moderate to high risk for NSAID-related GI bleeding, and 81% of these patients were not using PPI. PPI prophylaxis was not provided to 15 (75%) of the 20 patients with previous history of peptic ulcer bleeding. CONCLUSION: Despite many studies and recommendations on risk factors and prophylaxis for NSAID-related bleeding, prophylactic PPI use is still largely ignored by physicians. The rate of PPI use in the patient group of this study was found still quite insufficient.

Partial Splenic Embolization Is a Safe and Effective Alternative in the Management of Portal Hypertension in Children.

OBJECTIVE: There are multiple approaches to manage the clinical complications of portal hypertension (PHTN) to treat/prevent spontaneous hemorrhage by mitigating thrombocytopenia. No single approach is ideal for all patients given the heterogeneity of this population. Our goal was to determine whether partial splenic embolization (PSE) was safe and effective in the pediatric population. METHODS: This is a retrospective review of our single-center experience for all patients ages 0 to 21 who underwent PSE between January 2010 and August 2017. The embolized splenic volume targeted was 60% to 70%. RESULTS: Twenty-six patients underwent PSE due to thrombocytopenia and/or recurrent variceal bleeding. Patients ranged in age from 18 months to 20 years (mean 13.1 years). The median platelet count before PSE was 53.0 (×10/L). The platelet count improved after PSE with values >100,000 in 21 patients (80.8%). Children with prior esophageal varices showed improvement after PSE with only 9 (34.6%) requiring further endoscopic therapy. After PSE, patients developed transient abdominal pain, distention, fever, and perisplenic fluid collections. Serious complications such as splenic abscess, splenic rupture, bleeding, pancreatic infarction, opportunistic infection, or death were not observed. One patient experienced thrombotic complications after PSE and was later diagnosed with myelodysplastic syndrome. CONCLUSIONS: PSE is a safe and effective alternative in the management of pediatric PHTN in select populations. PSE may be a favorable alternative to splenectomy and portal systemic shunting because it preserves functional spleen mass and avoids postprocedure accelerated liver disease or encephalopathy.

Current and future pharmacological therapies for managing cirrhosis and its complications.

Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective beta-blockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective, haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore, statins are suggested to have protective effects upon fibrosis progression, decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.

Long-Term Results after Diversion Surgery in Extrahepatic Portal Vein Obstruction.

AIM: Extrahepatic portal vein obstruction (EHPVO) is a frequent cause of noncirrhotic portal hypertension in children. The aim of this study is to analyze long-term results after diversion surgery. PATIENTS AND METHODS: Retrospective review of EHPVO patients who underwent diversion surgery analyzing number of platelets, leukocytes, prothrombin activity, splenomegaly, and gastrointestinal bleeding 10 years after surgery. RESULTS: Thirty-three patients were evaluated, mostly males (64%) and presenting with gastrointestinal bleeding (46%). Mesoportal shunt (Rex) was performed in 19 patients, mesocaval in 7, distal splenorenal in 7, and proximal splenorenal in 3. While comparing mesoportal shunt to the other portosystemic shunts, an increase in platelets was found with every technique, but it was clearly higher in mesoportal shunt. The highest increase was 6 months after surgery (p = 0.0015) as well as prothrombin activity (p = 0.0003). Leukocytes level also increased without statistical significance. Spleen size (cm) and spleen size Z score (SSAZ) decreased significantly 6 months after mesoportal shunt (p = 0.0168). Before surgery, over 94% patients suffered gastrointestinal bleeding, which reduced significantly afterward with bleeding episodes in only four (12%) of them. CONCLUSION: Diversion surgery in EHPVO, especially mesoportal shunt of Rex, improves hepatic function (prothrombin activity), reduces hypersplenism (platelets, leukocytes, and spleen size), and decreases gastrointestinal bleeding episodes.

Non-invasive response prediction in prophylactic carvedilol therapy for cirrhotic patients with esophageal varices.

BACKGROUND & AIMS: Non-selective beta-blockers (NSBBs) are the mainstay of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. We investigated whether non-invasive markers of portal hypertension correlate with hemodynamic responses to NSBBs in cirrhotic patients with esophageal varices. METHODS: In this prospective cohort study, 106 cirrhotic patients with high-risk esophageal varices in the derivation cohort received carvedilol prophylaxis, and completed paired measurements of hepatic venous pressure gradient, liver stiffness (LS), and spleen stiffness (SS) at the beginning and end of dose titration. LS and SS were measured using acoustic radiation force impulse imaging. A prediction model for hemodynamic response was derived, and subject to an external validation in the validation cohort (63 patients). RESULTS: Hemodynamic response occurred in 59 patients (55.7%) in the derivation cohort, and in 33 patients (52.4%) in the validation cohort, respectively. Multivariate logistic regression analysis identified that ΔSS was the only significant predictor of hemodynamic response (odds ratio 0.039; 95% confidence interval 0.008-0.135; p <0.0001). The response prediction model (ModelΔSS = 0.0490-2.8345 × ΔSS; score = (exp[ModelΔSS])/(1 + exp[ModelΔSS]) showed good predictive performance (area under the receiver-operating characteristic curve [AUC] = 0.803) using 0.530 as the threshold value. The predictive performance of the ModelΔSS in the validation set improved using the same threshold value (AUC = 0.848). CONCLUSION: A new model based on dynamic changes in SS exhibited good performance in predicting hemodynamic response to NSBB prophylaxis in patients with high-risk esophageal varices. LAY SUMMARY: Non-selective beta-blockers are the mainstay of primary prophylaxis to prevent variceal bleeding in patients with cirrhosis and high-risk esophageal varices. This prospective study showed that a prediction model based on changes in spleen stiffness before vs. after dose titration might be a non-invasive marker for response to prophylactic non-selective beta-blocker (carvedilol) therapy in patients with cirrhosis and high-risk esophageal varices. ClinicalTrials.gov Identifier: NCT01943318.

Transjugular intrahepatic portosystemic shunt as a bridge to liver transplant: Current state and future directions.

Liver transplantation is one of the mainstays of treatment for liver failure due to severe chronic liver disease. Bridging therapies, such as placement of a transjugular intrahepatic portosystemic shunt (TIPS), are frequently employed to control complications of portal hypertension such as ascites, hydrothorax, and variceal bleeding, and thereby reduce morbidity in patients awaiting transplant. There is no significant difference seen in either graft survival or patient survival between those receiving TIPS pre-transplant and those who do not, although those receiving TIPS placement on average have a longer waiting time on the transplant waitlist. Locoregional therapies, such as thermal ablation or chemoembolization, can be efficacious in patients with HCC and pre-existing TIPS; however there is a risk for increased adverse events in patients receiving these therapies who have TIPS compared to those who do not. In summary, TIPS is a safe, effective treatment that can be used to ameliorate the complications that are sequelae of portal hypertension. While it does not appear to improve survival post-transplant, TIPS placement pre-transplant may increase survival time to transplant, thus improving overall survival as well as quality of life.

Recanalization of Chronic Extrahepatic Portal Vein Obstruction in Pediatric Patients Using a Minilaparotomy Approach.

PURPOSE: Extrahepatic portal vein obstruction (EHPVO) is the most frequent cause of portal hypertension in children. Some patients are not amenable to meso-Rex bypass and alternative surgeries do not restore physiologic flow. We aim to demonstrate the feasibility and safety of minilaparotomy for recanalization of chronic EHPVO. METHODS: This 2013-2015 single-center, retrospective review included pediatric patients with chronic EHPVO who underwent minilaparotomy, mesenteric vein access, and attempted recanalization of the occluded portal vein. Outcomes included portal patency, resolution of variceal bleeding, size and number of varices, spleen size, and platelet count. RESULTS: There were 6 EHPVO patients. The median age was 9.9 years and median duration of EHPVO was 7 years (3-16 years). EHPVO etiologies were liver transplantation (50%), idiopathic (33%), and umbilical vein catheterization (17%). Four patients (67%) had successful portal vein recanalization and stenting. At last follow-up [median 3.1 years (2.2-4.3 years)] all successfully recanalized patients had patent portal vein stents and resolution of varices and variceal bleeding. The median reduction in spleen size was 26%, with improvement in platelet counts (50-310/µL). The 2 patients with an idiopathic etiology may have never had a main extrahepatic portal vein based on imaging, and both were unable to be recanalized. CONCLUSIONS: Recanalization and stenting of a prolonged occlusion of the portal vein via a minilaparotomy approach is feasible, safe, and may provide an alternative to shunt surgery or endoscopic therapy in selected patients.