Secondary Prophylaxis Of Variceal Bleeding Research Articles

Indications and outcomes of transjugular intrahepatic portosystemic shunt insertion in two regional Australian hepatology centres.

Transjugular intrahepatic portosystemic shunt (TIPS) is an important therapy for complications of portal hypertension but remains underutilised in regional settings. The aim of this study is to explore the demographics, indications, outcomes and complications in patients undergoing TIPS in two regional hepatology centres. Retrospective analysis was undertaken of all patients undergoing TIPS at two regional centres between January 2017 and March 2023. The primary outcome measures were efficacy and complications of TIPS. Patient demographics (such as age, baseline liver severity scores and aetiology of liver disease) and indications for TIPS are detailed. Forty-eight patients underwent TIPS. Median age was 56 years (interquartile range (IQR): 46-65). The most common indications for TIPS were refractory ascites (n = 17) and failure of secondary prophylaxis of variceal bleeding (n = 13). Cumulative survival at 3 months and 1 year was 93% and 77% respectively. There was no significant difference in outcomes based on TIPS indication. The median number of paracenteses in patients undergoing TIPS for refractory ascites 1 year pre- and post-TIPS were 10 (IQR: 4.5-16) and 2 (IQR: 0-4) respectively (P < 0.001). There were no procedure-related deaths. Inpatient management of liver disease complications had a mean cost of $32 874.67 (SEM: 7779) in 1 year pre-TIPS compared with $12 304.70 (SEM: 3531.1) in 1 year post-TIPS (P < 0.001). TIPS is a safe and effective treatment to reduce complications of portal hypertension and can be performed successfully in the regional setting.

Management of Portal Hypertension in Patients with Hepatocellular Carcinoma on Systemic Treatment: Current Evidence and Future Perspectives.

The management of CSPH in patients undergoing systemic treatment for HCC has emerged as a critical concern due to the absence of reliable diagnostic criteria and uncertainties surrounding therapeutic approaches. This review aims to underscore the primary pathophysiological aspects linking HCC and PH, while also addressing the current and emerging clinical strategies for the management of portal hypertension. A review of studies from January 2003 to June 2023 was conducted using the PubMed database and employing MeSH terms, such as "hepatocellular carcinoma", "immune checkpoint inhibitors", "systemic therapy", "portal hypertension", "variceal bleeding" and "tyrosine kinase inhibitors". Despite promising results of tyrosine kinase inhibitors in animal models for PH and fibrosis, only Sorafenib has demonstrated similar effects in human studies, whereas Lenvatinib appears to promote PH development. The impact of Atezolizumab/Bevacizumab on PH remains uncertain, with an increasing risk of bleeding related to Bevacizumab in patients with prior variceal hemorrhage. Given the absence of specific guidelines, endoscopic surveillance during treatment is advisable, and primary and secondary prophylaxis of variceal bleeding should adhere to the Baveno VII recommendations. Furthermore, in patients with advanced HCC, refinement of diagnostic criteria for CSPH and guidelines for its surveillance are warranted.

B-Blockers in Liver Cirrhosis: A Wonder Drug for Every Stage of Portal Hypertension? A Narrative Review.

In cirrhotic patients, non-selective b-blockers (NSBBs) constitute the reference treatment of choice as monotherapy or combined with band ligation for the prevention of first variceal bleeding and rebleeding, respectively. Furthermore, the last Baveno VII guidelines recommended carvedilol, a b-blocker with additional anti-a1 receptor activity, in all compensated cirrhotics with clinically significant portal hypertension, to prevent liver decompensation. Interestingly enough, NSBBs have been reported to have a potentially positive impact on the short-term mortality of patients with acute-on-chronic liver failure. However, concerns remain about the use of b-blockers in the presence of severe complications, such as refractory ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, or established cirrhotic cardiomyopathy. In addition, it has not been verified yet whether carvedilol supersedes all the other NSBBs in every stage of liver disease, even when severe complications have developed. Therefore, this review aims to illustrate recent data regarding the potential role of b-blockers across all stages of liver disease, beyond the primary and secondary prophylaxis of variceal bleeding, and address the authors' proposals on the use of NSBBs concerning the severity of liver disease and the patient's performance status.

Outcomes of Transjugular Intrahepatic Portosystemic Shunt and Gastric Coronary Vein Embolization for Variceal Bleeding in Cirrhotic Portal Hypertension.

Purpose: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with gastric coronary vein embolization (GCVE) for cirrhotic portal hypertensive variceal bleeding and compare outcomes of first-line with second-line treatment, coil with glue, and single-covered with double stents.Methods: Fifteen patients received TIPS plus GCVE as the first-line treatment for secondary prophylaxis of variceal bleeding, and 45 received it as second-line treatment. Preoperative and postoperative quantitative variables were compared using a paired t test. The incidence of survival rate, re-bleeding, hepatic encephalopathy, and shunt dysfunction were analyzed using the Kaplan-Meier method.Results: The portal venous pressure was significantly decreased from 39.0 ± 5.0 mm Hg to 22.5 ± 4.4 mm Hg (P≤0.001) after TIPS treatment. After 1, 3, 6, 12, 18, and 24 months re-bleeding rates were 1.6%, 3.3%, 6.6%, 13.3%, 0%, and 0%, respectively. Shunt dysfunction rates were 5%, 0%, 10%, 16.6%, 1.6%, and 5%, respectively. Hepatic encephalopathy rates were 3.3%, 1.6%, 3.3%, 6.6%, 0%, and 0%, respectively. And survival rates were 100%, 100%, 100%, 96.6%, 93.3%, and 88.3% respectively. In comparative analysis, statistically significant differences were seen in re-bleeding between the first-line and second-line treatment groups (26.6% vs 24.4%, log-rank P=0.012), and survival rates between single-covered and double stent (3.7% vs 16.1%, log-rang (P=0.043).Conclusion: The results suggest that TIPS combined with GCVE is effective and safer in the treatment of cirrhotic portal hypertensive variceal bleeding. The use of TIP plus GCVE as first-line treatment, may be preferable for high-risk re-bleeding, and more than 25 mm Hg portal venous pressure with repeated variceal bleeding. However, the sample size was small. Therefore, large, randomized, controlled, multidisciplinary center studies are needed for further evaluation.

Mortality after transjugular intrahepatic portosystemic shunt in older adult patients with cirrhosis: A validated prediction model.

Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) improves survival in patients with cirrhosis with refractory ascites and portal hypertensive bleeding. However, the indication for TIPS in older adult patients (greater than or equal to 70 years) is debated, and a specific prediction model developed in this particular setting is lacking. The aim of this study was to develop and validate a multivariable model for an accurate prediction of mortality in older adults. We prospectively enrolled 411 consecutive patients observed at four referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of variceal bleeding (derivation cohort) and an external cohort of 415 patients with similar indications for TIPS (validation cohort). Older adult patients in the two cohorts were 99 and 76, respectively. A cause-specific Cox competing risks model was used to predict liver-related mortality, with orthotopic liver transplant and death for extrahepatic causes as competing events. Age, alcoholic etiology, creatinine levels, and international normalized ratio in the overall cohort, and creatinine and sodium levels in older adults were independent risk factors for liver-related death by multivariable analysis. After TIPS implantation, mortality is increased by aging, but TIPS placement should not be precluded in patients older than 70 years. In older adults, creatinine and sodium levels are useful predictors for decision making. Further efforts to update the prediction model with larger sample size are warranted.

Carvedilol Achieves Higher Hemodynamic Response and Lower Rebleeding Rates Than Propranolol in Secondary Prophylaxis

Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective β-blockers (ie, propranolol). Limited data exist on the efficacy of carvedilol in secondary prophylaxis of variceal bleeding. Patients undergoing paired HVPG measurements for guiding secondary prophylaxis with either carvedilol or propranolol were included in this retrospective analysis. All patients also underwent band ligation. Changes in HVPG and systemic hemodynamics were compared between the 2 groups. Long-term follow-up data on rebleeding, acute kidney injury, nonbleeding decompensation, and liver-related death were analyzed applying competing risk regression. Eighty-seven patients (carvedilol/propranolol, n= 45/42) were included in our study. The median baseline HVPG was 21 mm Hg (interquartile range, 18-24 mm Hg), and 39.1%/48.3%/12.6% had Child-Turcotte-Pugh A/B/C cirrhosis, respectively. Upon nonselective β-blocker initiation, HVPG decreased more strongly in carvedilol users (median relative decrease, -20% [interquartile range: -29% to -10%] vs -11% [-22% to -5%] for propranolol; P= .027), who also achieved chronic HVPG response more often (53.3% vs 28.6%; P= .034). Cumulative incidences for rebleeding (Gray test, P= .027) and liver-related death (P= .036) were significantly lower in patients taking carvedilol compared with propranolol. Notably, ascites development/worsening also was observed less commonly in carvedilol patients (P= .012). Meanwhile, acute kidney injury rates did not differ between the 2 groups (P= .255). Stratifying patients by HVPG response status yielded similar results. The prognostic value of carvedilol intake was confirmed in competing risk regression models. Carvedilol induces more marked reductions in HVPG than propranolol in secondary prophylaxis of variceal bleeding, and thus is associated with lower rates of rebleeding, liver-related death, and further nonbleeding decompensation.

FRI533 - Carvedilol is associated with superior hemodynamic response and rebleeding rates in comparison to propranolol in secondary prophylaxis of variceal bleeding

FRI533 - Carvedilol is associated with superior hemodynamic response and rebleeding rates in comparison to propranolol in secondary prophylaxis of variceal bleeding

Spleen Transient Elastography and Damping Index Identify a Subgroup of Patients Without an Acute or Chronic Response to Beta-Blockers.

Background and AimsMonitoring of acute or chronic response to beta-blockers in patients with liver cirrhosis is based on the measurement of the HVPG. Our aim was to evaluate the response to beta-blockers with non-invasive techniques.Patients and MethodsThis is a prospective observational study. Consecutive patients with an indication of primary or secondary prophylaxis of variceal bleeding who did not meet exclusion criteria were included. Acute response and chronic response were evaluated. Baseline and after acute and chronic response hepatosplenic measurements of TE and ARFI were obtained. Contrast-enhanced Doppler ultrasound was performed before and after acute and chronic responses.ResultsFrom June 2015 to May 2018, 55 patients (14 with exclusion criteria) were included. We analyzed 41 patients, mean age 57 (SD: 8), 82.9% men, alcohol 43.9%, children A/B/C 78%/17.1%/4.9%, and 87.8% on primary prophylaxis. In all, the acute response was performed and was positive in 68.3% (CI 95: 55–85%). The chronic response was performed in 30 (73.2%) and was positive in 36.7% (CI 95: 18–55%). Basal measurements significantly related to acute response were spleen TE [responders 58.4 (SD: 23.0) KPa vs. non-responders 75 (SD: 0) KPa; p = 0.02] and damping index [non-responders 0.96 (0.8) vs. responders 0.44 (0.4), p = 0.01], and with chronic response, the spleen TE [responders 58.1 (SD: 21.4) KPa vs. non-responders 73.2 (SD: 5.5) KPa; p = 0.02], and damping index [non-chronic responders 0.8 (0.7) vs. chronic responders 0.4 (0.4), p = 0.04]. A spleen TE ≥ 74 KPa had a high sensitivity of 100% and specificity of 60% and a high NPV100% for predicting poor acute response to beta-blockers. The damping index > 0.6 showed moderate sensitivity of 67% and specificity of 69% with a high NPV of 82% for predicting poor acute response to beta-blockers. The combination of both measurements for predicting poor acute response to beta-blockers had an AUC of 0.8 (CI 95: 0.5–0.9). A spleen TE ≥ 74 KPa had a high sensitivity of 87% and specificity of 71% with a high NPV of 71% for predicting poor chronic response to beta-blockers. A damping index > 0.6 had moderate sensitivity of 60%, specificity of 82%, and NPV of 56% for predicting poor chronic response to beta-blockers. The combination of both measurements for predicting poor chronic response to beta-blockers had an AUC of 0.8 (CI 95: 0.7–0.9).ConclusionSpleen TE and damping index can identify a subgroup of patients with poor acute or chronic response to beta-blockers.

Carvedilol versus endoscopic band ligation for secondary prophylaxis of variceal bleeding-long-term follow-up of a randomised control trial.

Carvedilol reduces rates of variceal bleeding and rebleeding by lowering portal pressure. However, an associated pleiotropic survival benefit has been proposed. We aimed to assess long-term survival in a cohort of patients previously randomised to receive either carvedilol or endoscopic band ligation (EBL) following oesophageal variceal bleeding (OVB). The index study randomised 64 cirrhotic patients with OVB between 2006 and 2011 to receive either carvedilol or EBL. Follow-up was undertaken to April 2020 by review of electronic patient records. The primary outcome was survival. Other outcomes including variceal rebleeding and liver decompensation events were compared. 26 out of 33 participants received carvedilol in the follow-up period and 28 out of 31 attended regular EBL sessions. The median number of follow-up days for all patients recruited was 1459 (SE=281.74). On the intention to treat analysis, there was a trend towards improved survival in the carvedilol group (p=0.09). On per-protocol analysis, carvedilol use was associated with improved long-term survival (p=0.005, HR 3.083, 95% CI 1.397-6.809), fewer liver-related deaths (0% vs 22.57%, p=0.013, OR ∞, 95%CI 1.565-∞) and fewer admissions with decompensated liver disease (12% vs 64.29%, p=0.0002, OR 13.2, 95% CI 3.026-47.23) compared to the EBL group. There was no statistically significant difference in variceal rebleeding rates. Following OVB in cirrhotic patients, carvedilol use is associated with survival benefit, fewer liver-related deaths and fewer hospital admissions with decompensated liver disease. Further studies are needed to validate this finding.

Carvedilol versus propranolol in the prevention of variceal rebleeding in hepatosplenic schistosomiasis: Efficacy and safety

Background and AimBeta blockers combined with endoscopic variceal band ligation (EVL) is the most effective means for the prevention of variceal rebleeding. No data are available on the efficacy of carvedilol in the secondary prophylaxis of variceal bleeding in hepatosplenic schistosomiasis. The aim of this study was to evaluate the efficacy and safety of carvedilol compared to propranolol as secondary prophylaxis of variceal bleeding in hepatosplenic schistosomiasis.MethodsThis was a prospective, randomized study over a period of 14 months from February 2019 to March 2020. All patients with portal hypertension due to schistosomiasis with at least one episode of variceal bleeding were included and randomized to the propranolol and carvedilol groups. EVL protocol was continued in both groups.ResultsSixty‐one patients were eligible and randomized to propranolol (n = 30) and carvedilol (n = 31) groups. There was no significant difference in hemorrhagic recurrence between the carvedilol (n = 1) and propranolol (n = 3) groups (3.33 vs 10%; P = 0.30). At 4 months, there was a significant reduction in mean arterial pressure (−4.13 mm Hg; 95% CI: −6.27 to −1.99; P < 0.05) and heart rate (−12.13 bpm; 95% CI: −13.92 to −10.35; P < 0.05) in the carvedilol group. There was no significant difference between the groups on the mean difference in arterial pressure. One patient in the carvedilol group had breathing difficulty. There were no adverse events in the propranolol group.ConclusionThere was no significant difference in the efficacy between carvedilol and propranolol. Carvedilol may be an alternative to propranolol for secondary prophylaxis of variceal rebleeding in hepatosplenic schistosomiasis.

Non-selective beta-blockers in patients with ascites: Thecomplex interplay among the liver, kidney and heart.

Non-selective beta-blockers (NSBBs) are the cornerstone of the primary and secondary prophylaxis of variceal bleeding in cirrhotic patients. They additionally prevent ascites development and death in compensated patients with clinically significant portal hypertension. After ascites onset, NSBBs remain beneficial for preventing further decompensations. However, as the cirrhosis progresses, the inflammation increases, systemic vasodilatation worsens, ascites turns refractory and cardiodynamic equilibrium becomes extremely fragile. In this scenario, NSBBs can critically impair the cardiac reserve and facilitate a haemodynamic breakdown, imperilling renal perfusion. Consequently, NSBB treatment should be carefully monitored or even avoided in such patients, and other options for portal hypertension management should be considered. In the present review, we explore the effects of NSBBs in patients with ascites and discuss the complex interplay among their hepatic, systemic and renal haemodynamic effects in this scenario.

Survival benefits of adding simvastatin to standard therapy for secondary prevention of bleeding esophageal varices in patients with hepatitis C-related liver cirrhosis

BackgroundThe combination of endoscopic band ligation and beta-blockers is the standard of care treatment for secondary prevention of variceal bleeding; however, rebleeding still occurs with associated high mortality. Simvastatin (a lipid-lowering agent) was found to reduce portal hypertension and decrease hepatic fibrosis. This study aimed to assess the effect of adding simvastatin to the standard therapy to prevent variceal rebleeding and its impact on survival in patients with liver cirrhosis.ResultsThis single-center randomized controlled clinical trial included 80 patients with cirrhosis receiving the standard secondary prophylaxis for variceal bleeding composed of endoscopic variceal ligation and non-selective β-blockers (either propranolol or carvedilol). Two weeks after the first attack of hematemesis, patients were randomized into two groups: group I who received the standard therapy (40 patients) and group II who administered simvastatin (20 mg daily for 2 weeks and 40 mg daily after that). Patients were followed up for 1 year. The primary endpoints were rebleeding and overall survival. Thirty patients of group I completed the study while ten patients died during the follow-up period. The simvastatin group showed a significantly better overall 1-year survival (3 deaths during follow-up) compared to the control group (37/40, 92.5% vs. 30/40; 75%) (p-value 0.034); however, this was lacking in Child C patients. No similar difference was present in rebleeding rates between the two groups (5/40, 12.5% vs. 3/40, 7.5%) (p-value 0.456) in groups I and II, respectively.ConclusionsAdding simvastatin to the standard therapy in secondary prevention of variceal bleeding could be associated with survival benefits in patients with Child A and B cirrhosis, while was incapable of reducing rebleeding.

Impact of variceal eradication on rebleeding and prognosis in cirrhotic patients undergoing secondary prophylaxis.

Endoscopic therapy has been widely applied to prevent variceal rebleeding, but data addressing the effect of endoscopic variceal eradication (VE) are lacking. We aimed to clarify the clinical impact of VE and reveal the long-term incidence and mortality of gastrointestinal rebleeding. This prospective study included 228 cirrhotic patients who underwent secondary prophylaxis for variceal bleeding and achieved VE through a systematic procedure we proposed as endoscopic sequential therapy (EST). Rebleeding rates before and after VE were compared and cumulative incidence of rebleeding and mortality were calculated using the Kaplan-Meier method. A logistic regression model and P for trend were used to investigate the optimal time limit for VE. During a median (interquartile range) follow-up duration of 33.0 (23.0-48.75) months, rebleeding was identified in 28 patients (12.3%) after VE and in 27 patients (11.8%) during endoscopic sessions. The cumulative incidence of rebleeding before and after VE was 8.4% and 1.8% at 6 months, and 14.9% and 4.0% at 1 year respectively (P<0.001). The long-term incidence of all-cause/variceal rebleeding following VE was 10.4%/9.1%, and 31.5%/23.5% at 2 and 5 years respectively. Eleven patients (4.8%) died and the 5-year mortality was 9.3%. VE achieved within 6 months was associated with fewer rebleeding events compared to VE achieved after 6 months (5.5% vs. 20.0%, P=0.002), while logistic regression revealed an overall increasing trend in the odds ratio of rebleeding (vs. patients with VE time ≤6 months) for patients with 6< VE time ≤12 months and VE time >12 months (P for trend <0.001). VE further reduces rebleeding based on routine endoscopic prophylaxis and improves long-term prognosis. VE within 6 months seems to be the optimal timing and should therefore be advocated.

Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival

Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an effective and safe treatment for complications of portal hypertension. Survival prediction is important in these patients as they constitute a high-risk population. Therefore, the aim of our study was to develop an alternative prognostic model for accurate survival prediction after planned TIPS implantation. A total of 1,871 patients with de novo TIPS implantation for ascites or secondary prophylaxis of variceal bleeding were recruited retrospectively. The study cohort was divided into a training set (80% of study patients; n= 1,496) and a validation set (20% of study patients; n= 375). Further, patients with early (preemptive) TIPS implantation due to variceal bleeding were included as another validation cohort (n= 290). Medical data and overall survival (OS) were assessed. A Cox regression model was used to create an alternative prediction model, which includes significant prognostic factors. Age, bilirubin, albumin and creatinine were the most important prognostic factors. These parameters were included in a new score named the Freiburg index of post-TIPS survival (FIPS). The FIPS score was able to identify high-risk patients with a significantly reduced median survival of 5.0 (3.1-6.9) months after TIPS implantation in the training set. These results were confirmed in the validation set (median survival of 3.1 [0.9-5.3] months). The FIPS score showed better prognostic discrimination compared to the Child-Pugh, MELD, MELD-Na score and the bilirubin-platelet model. However, the FIPS score showed insufficient prognostic discrimination in patients with early TIPS implantation. The FIPS score is superior to established scoring systems for the identification of high-risk patients with a worse prognosis following elective TIPS implantation. Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective treatment for patients with cirrhosis and clinically significant portal hypertension. However, risk stratification is a major challenge in these patients as currently available scoring systems have major drawbacks. Age, bilirubin, albumin and creatinine were included in a new risk score which was named the Freiburg index of post-TIPS survival (FIPS). The FIPS score can identify patients at high risk and may guide clinical decision making.

Comparison of the effectiveness of 11 mainstay treatments for secondary prophylaxis of variceal bleeding in patients with cirrhosis: A network meta-analysis.

The purpose of the present study was to compare the effectiveness of the transjugular intrahepatic portosystemic shunt (TIPS), endoscopic options, medications and mainstay combination therapies for patients with cirrhosis who have had at least one episode of variceal haemorrhage. The PubMed, Embase, Cochrane Library and Web of Science databases, as well as the reference lists of relevant articles, were searched to identify eligible studies. P-scores, that were based solely on the point estimates and standard errors of the network estimates, were performed to rank all treatments, on a scale from 0 (worst) to 1 (best). The odds ratio (OR) was determined to assess effects on mortality, treatment failure and bleeding from gastroesophageal ulcers. A total of 43 randomized controlled trials comprising 3,787 adult patients were included. In total, 26 (61%) trials adopted concealed randomization, while most studies did not specify blinding. The drug combination of nadolol and isosorbide mononitrate (ISMN) ranked first for lowering risks of overall mortality (P-score=0.8162), mortality due to liver failure (P-score=0.7536) and bleeding from gastroesophageal ulcers (P-score=0.7536). This combination was determined to be superior to endoscopic sclerotherapy (ES) alone (OR=0.63, 95% CI: 0.42-0.94) and TIPS alone in reducing overall mortality (OR=0.62, 95% CI: 0.40-0.96). ES was more likely to increase treatment failure compared with TIPS, endoscopic variceal ligation (EVL), ES plus EVL, EVL plus nadolol/propranolol plus ISMN and nadolol/propranolol plus ISMN. In conclusion, the present network meta-analysis suggested that for a decreased mortality due to variceal rebleeding in patients with cirrhosis, nadolol plus ISMN may be a preferable choice, while ES is associated with a higher risk of unfavourable treatment outcomes. Further well-controlled studies are required to further elucidate the appropriate treatment options.

Management of betablocked patients after sustained virological response in hepatitis C cirrhosis.

BACKGROUNDCurrent guidelines do not address the post–sustained virological response management of patients with baseline hepatitis C virus (HCV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option.AIMTo assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population.METHODSInclusion criteria were age > 18 years, HCV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after direct-acting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was < 12 mmHg, at the discretion of the attending physician.RESULTSSample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, Child-Pugh score A 77%, median platelets 77.000 × 103/µL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was < 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was ≥ 12 mmHg in 12/19 patients. The elastography area under receiver operating characteristic for HVPG ≥ 12 mmHg was 0.62. Betablockers were stopped permanently in 10/13 patients with gradient < 12 mmHg, with no bleeding episodes after a median follow-up of 68 wk.CONCLUSIONPortal hypertension dropped below the bleeding threshold in 39% of patients more than one year after antiviral treatment. Endoscopy and transient elastography are inaccurate for reliable detection of this change. Stopping betablockers permanently seems uneventful in patients with a gradient < 12 mmHg.

Non-Cirrhotic Portal Hypertension: A Case of Bleeding Gastro-Oesophageal Varices with Non-Cirrhotic Liver Reported in East Malaysia

Non-cirrhotic portal hypertension (NCPH) is clinically defined as the presence of portal hypertension in the background of non-cirrhotic liver. It is diagnosed by the findings in ultrasound of the hepatobiliary system and also oesophagogastroduodenoscopy (OGDS) that consistent with that of a portal hypertension, but otherwise has a relatively normal liver function and echotexture. The treatment mainly focuses on primary and secondary prophylaxis of variceal bleeding both pharmacologically like non-selective beta-blockers and octreotide, and non-pharmacologically like endoscopic band ligation of varices and sclerotherapy. In advance cases, sometimes surgery such as Porto-systemic shunt or splenectomy may be required especially in patients with uncontrolled variceal bleeding or with symptomatic hypersplenism. Here we report a case of a young man who presented with upper gastro-intestinal bleeding, which was initially thought from a bleeding ulcer but was found to be secondary to oesophageal and gastro-oesophageal varices. Apart from having mild ascites, he has no other features of portal hypertension. His liver biochemistry and echotexture were also normal. Unfortunately, the patient was lost to follow up while he was still in the early stage of investigating the condition. The purpose of this case report is to share an uncommon occurrence of NCPH in East Malaysia, where liver cirrhosis predominates the aetiology of portal hypertension. Also, to the best of our knowledge, there is a very limited reporting of a similar case in this region.

Role of band ligation for secondary prophylaxis of variceal bleeding.

AIMTo summarize and critically examine the role of band ligation in secondary prophylaxis of variceal bleeding in patients with cirrhosis.METHODSA literature review was performed using the MEDLINE and PubMed databases. The search terms consisted of the words “endoscopic band ligation” OR “variceal band ligation” OR “ligation” AND “secondary prophylaxis” OR “secondary prevention” AND “variceal bleeding” OR “variceal hemorrhage” AND “liver cirrhosis”. The data collected from relevant meta-analyses and from the most recent randomized studies that were not included in these meta-analyses were used to evaluate the role of endoscopic band ligation in an effort to demonstrate the most recent advances in the treatment of esophageal varices.RESULTSThis study included 11 meta-analyses published from 2002 to 2017 and 10 randomized trials published from 2010 to 2017 that evaluated the efficacy of band ligation in the secondary prophylaxis of variceal bleeding. Overall, the results proved that band ligation was superior to endoscopic sclerotherapy. Moreover, the use of β-blockers in combination with band ligation increased the treatment effectiveness, supporting the current recommendations for secondary prophylaxis of variceal bleeding. The use of transjugular intrahepatic portosystemic shunt was superior to combination therapy regarding rebleeding prophylaxis, with no difference in the survival rates; however, the results concerning the hepatic encephalopathy incidence were conflicting. Recent advances in the management of secondary prophylaxis of variceal bleeding have targeted a decrease in portal pressure based on the pathophysiological mechanisms of portal hypertension.CONCLUSIONThis review suggests that future research should be conducted to enhance current interventions and/or to develop innovative treatment options with improved clinical endpoints.

Betablockers do not increase efficacy of band ligation in primary prophylaxis but they improve survival in secondary prophylaxis of variceal bleeding.

Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non-selective beta-blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used. To assess (re-)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding. (Re-)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP. Seven hundred and sixty-six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n= 101 (35.6%) received EBL only, while n=180 (63.4%) received EBL+NSBBs. In 482 patients on SP, n=163 (33.8%) received EBL only, while n=299 (62%) received EBL+NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log-rank: P=0.353) nor mortality (log-rank: P=0.497) as compared to EBL alone. In SP, similar re-bleeding rates were documented in EBL+NSBB vs EBL alone (log-rank: P=0.247). However, EBL+NSBB resulted in a significantly lower mortality rate (log-rank: P<0.001). A decreased risk of death with EBL+NSBB in SP (hazard ratio, HR: 0.50; P<0.001) but not of rebleeding, transplantation or further decompensation was confirmed by competing risk analysis. Overall NSBB intake reduced 6-months mortality (HR: 0.53, P=0.008) in SP, which was most pronounced in patients without severe/refractory ascites (HR: 0.37; P=0.001) but not observed in patients with severe/refractory ascites (HR: 0.80; P=0.567). EBL alone seems sufficient for PP of variceal bleeding. In SP, the addition of NSBB to EBL was associated with an improved survival within the first 6months after EBL.

Non selective beta-blocker in cirrhosis: not ‘whether’ but ‘who and how’

Non selective beta-blockers (NSBBs) have been used for decades in patients with liver cirrhosis to reduce portal pressure and the risk for portal hypertensive bleeding (1-3). International guidelines recommend NSBB as primary and secondary prophylaxis for variceal bleeding in cirrhosis (4). Patients with liver cirrhosis and portal hypertension have a distinct pathophysiological feature dominated by a hyperdynamic circulation (5).