Life-threatening Variceal Bleeding Research Articles

S3065 Gunsight TIPS Technique as Salvage Therapy in Life Threatening Variceal Bleeding in a Non-Cirrhotic Patient

S3065 Gunsight TIPS Technique as Salvage Therapy in Life Threatening Variceal Bleeding in a Non-Cirrhotic Patient

Continuous vs. intermittent terlipressin infusion for portal hypertension: a systematic review and meta-analysis.

Portal hypertension, a major complication of chronic liver disease, often leads to life-threatening variceal bleeding, managed effectively with vasoactive drugs like terlipressin. However, the most optimal method of terlipressin administration, continuous versus intermittent infusion, remains a subject of debate, necessitating this systematic review and meta-analysis for evidence-based decision-making in managing this critical condition. This systematic review and meta-analysis adhered to the PRISMA standards and explored multiple databases until 6 April 2023, such as MEDLINE through PubMed, Scopus, Web of Science, and CENTRAL. Independent reviewers selected randomized controlled trials (RCTs) that met specific inclusion criteria. After assessing study quality and extracting necessary data, statistical analysis was performed using Review Manager (RevMan), with results presented as risk ratios (RR) or mean differences. Five RCTs (n=395 patients) were included. The continuous terlipressin group had a significantly lower risk of rebleeding (RR=0.43, P=0.0004) and treatment failure (RR=0.22, P=0.02) and fewer total adverse effects (RR=0.52, P<0.00001) compared to the intermittent group. However, there were no significant differences between the two groups in mean arterial pressure (P=0.26), length of hospital stays (P=0.78), and mortality rates (P=0.65). This study provides robust evidence suggesting that continuous terlipressin infusion may be superior to intermittent infusions in reducing the risk of rebleeding, treatment failure, and adverse effects in patients with portal hypertension. However, further large-scale, high-quality RCTs are required to confirm these findings and to investigate the potential benefits of continuous terlipressin infusion on mortality and hospital stays.

The Efficacy of Carvedilol in Comparison to Propranolol in Reducing the Hepatic Venous Pressure Gradient and Decreasing the Risk of Variceal Bleeding in Adult Cirrhotic Patients: A Systematic Review.

The most common cause of portal hypertension is liver cirrhosis. Portal hypertension causes many complications in cirrhotic patients; a significant complication is the formation of varices and the subsequent life-threatening variceal bleeding due to elevated portal venous pressures. Hepatic venous pressure gradient (HVPG) is the gold standard for measuring portal hypertension and guides management. Pharmacological treatments lower the HVPG, preventing the progression of varices and subsequent variceal bleeding. The pharmacological treatments frequently used in primary and secondary prophylaxis of a variceal bleed are nonselective beta (β)-adrenergic blockers. Propranolol was the first nonselective β-adrenergic blocker used for lowering HVPG and has been well studied. However, in the past decade, clinical trials have shown that carvedilol has been more effective. This study aims to establish whether carvedilol is more effective than propranolol in reducing the hepatic venous pressure gradient and decreasing the risk of variceal bleeding in adult cirrhotic patients. A systematic review has been conducted to gather relevant clinical trials comparing drugs and their effects on HVPG. Four databases: PubMed (Medical Literature Analysis and Retrieval System Online (MEDLINE)), Google Scholar, the Cochrane Library, and ScienceDirect, were analyzed, and records from January 1, 1999, to January 1, 2023, were chosen. There were a total of 1,235 potentially eligible records across the four databases. Using the eligibility criteria for this systematic review, seven studies of 533 patients were included. Across all seven clinical trials, it was found that carvedilol reduced HVPG more than propranolol and decreased the risk of variceal bleeding in adult cirrhotic patients.

The key role of hepatology providers in optimizing reproductive care in patients with liver disease: A call to action.

The key role of hepatology providers in optimizing reproductive care in patients with liver disease: A call to action.

Liver Elastography as a Predictor of Esophageal Varices in Patients With Cirrhosis.

IntroductionLiver cirrhosis is an advanced consequence of a long-standing liver disease that can lead to portal hypertension which subsequently can manifest as life-threatening variceal bleeding. The present study aimed to determine liver stiffness by shear wave elastography (SWE) to predict esophageal varices (EV) in patients with chronic liver diseases.MethodologyA prospective observational study was performed at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi between November 2020 and July 2021. Individuals aged between 18 and 50 years, irrespective of gender, with diagnosed chronic liver disease >6 months were eligible to partake in the study. Patients with concomitant renal failure, severe ascites, severe life-threatening co-morbidities including congestive heart failure NYHA-III and IV, acute asthmatic attack, and recent myocardial infarction (MI) were excluded from the study. SWE was determined in all patients to measure liver stiffness. Esophagogastroduodenoscopy (EGD) was performed to visualize the esophageal varices. All findings were recorded. A 2 × 2 table was applied to determine the sensitivity, specificity, positive, and diagnostic accuracy for SWE by taking endoscopy as the definitive test.ResultsA total of 204 patients were included in the study. Mean age of 40.37 ± 15.20 years was observed. The mean liver size of patients was 12.38 ± 2.06 cm and the mean liver stiffness of patients was 19.97 ± 8.6. The sensitivity and specificity of liver elastography were 44.90% and 51.90%, respectively. Furthermore, the positive and negative predictive values were 53.00% and 99.39%, respectively. The diagnostic accuracy of the test was 51.86%.ConclusionEven though the diagnostic gold standard for the detection of varices is EGD, liver elastography provides a less invasive procedure to assess for varices in patients with cirrhotic liver disease. The present study concluded that liver elastography is a non-invasive and indirect valuable tool to predict the presence of esophageal varices with sensitivity and specificity of 44.90% and 51.90%, respectively.

Gastrointestinal Bleeds.

Gastrointestinal Bleeds.

Combined Heart-Lung-Liver Transplantation for Patients With Cystic Fibrosis: The Australian Experience

Combined multivisceral transplantation has emerged as a therapeutic option for a select patient cohort; however, clinical decision-making remains complex and controversial. The aim of this study was to examine patient characteristics, operative complications, and long-term outcomes of all patients who have undergone combined heart-lung-liver transplantation (HLLTx) in Australia. In this study, we performed a retrospective analysis of all adult patients who have undergone combined HLLTx in Australia to date. Recipient clinical characteristics, waitlist, and transplant outcomes are described. Eight adult patients have received HLLTx at a single Australian transplant center. Recipients of HLLTx have typically been young (median age, 30.1 years; range, 24-37), underweight (median body mass index, 19.8 kg/m2; range, 16.2-30.4) patients with cystic fibrosis (n=8, 100%) with severe airflow obstruction (median forced expiratory volume in the first second of expiration, 24% predicted; range, 17%-48%) accompanied by liver cirrhosis confirmed on histopathology (n=8, 100%). Despite relative preservation of synthetic function and low model for end-stage liver disease scores (median, 8; range, 6-17), all recipients had complications of portal hypertension prior to transplantation, with many patients having suffered life-threatening variceal hemorrhage. In this cohort, HLLTx was associated with overall posttransplant survival of 87.5% at 30 days, 71.4% at 1 year, and 42.9% at 5 years. Listing for combined HLLTx was associated with prolonged waitlist times relative to bilateral sequential single-lung transplantation (median 556 vs 56 days, respectively), however waitlist mortality and/or delisting was comparable between groups. Taken together, these findings highlight the opportunities and challenges facing combined (heart-) lung and liver transplantation in patients with multiorgan failure.

Multivisceral Transplantation for Diffuse Portomesenteric Thrombosis: Lessons Learned for Surgical Optimization.

Background: Multivisceral transplantation entails the en-bloc transplantation of stomach, duodenum, pancreas, liver and bowel following resection of the native organs. Diffuse portomesenteric thrombosis, defined as the complete occlusion of the portal system, can lead to life-threatening gastrointestinal bleeding, malnutrition and can be associated with liver and intestinal failure. Multivisceral transplantation is the only procedure that offers a definitive solution by completely replacing the portal system. However, this procedure is technically challenging in this setting. The aim of this study is to describe our experience, highlight the challenges and propose technical solutions.Materials and Methods: We performed a retrospective analysis of our cohort undergoing multivisceral transplantation for diffuse portomesenteric thrombosis at our institution from 2000 to 2020. Donor and recipient demographics and surgical strategies were reviewed in detail and posttransplant complications and survival were analyzed.Results: Five patients underwent MVTx. Median age was 47 years (23–62). All had diffuse portomesenteric thrombosis with life-threatening variceal bleeding. Major blood loss during exenteration was avoided by combining two techniques: embolization of the native organs followed by a novel, staged extraction. This prevented major perioperative blood loss [median intra-operative transfusion of 3 packed red blood cell units (0–5)]. Median CIT was 330 min (316–416). There was no perioperative death. One patient died due to invasive aspergillosis. Four others are alive and well with a median follow-up of 4.1 years (0.3–5.9).Conclusions: Multivisceral transplantation should be considered in patients with diffuse portomesenteric thrombosis that cannot be treated by any other means. We propose a standardized surgical approach to limit the operative risk and improve the outcome.

S1401 Malignant Mesenteric Venous Obstruction From Pancreatic Cancer, an Under-Recognized Condition Associated With Significant Morbidity, Can Be Treated With Venous Stenting

INTRODUCTION: Portal vein (PV) and superior mesenteric vein (SMV) stenosis can result from various pathologic processes including pancreatic cancer. Their clinical manifestations include portal hypertension (PH) with life-threatening variceal bleeding, refractory ascites, and mesenteric ischemia. In this abstract, 4 cases who underwent stenting are presented. CASE DESCRIPTION/METHODS: Case 1 is a 58-year-old woman with a history of pancreatic cancer status post Whipple resection, presented with worsening diarrhea, ascites, and malnutrition. Stool testing, colonoscopy with biopsies were negative. Ascitic fluid analysis was consistent with PH with no evidence of cirrhosis. Abdominal imaging showed ill-defined pancreatic body infiltrative mass with significant narrowing of the PV with resultant small bowel and colonic thickening. She underwent SMV/PV stenting which resulted in the resolution of diarrhea and bowel thickening. She went off total parenteral nutrition with 22 kg weight gain and was able to receive systemic anticancer therapy (SAT) and survived for 18 months afterward.Three other cases with similar preservations and varying degrees of refractory ascites, diarrhea, malnutrition, and bowel wall thickening on imaging. They all underwent PV or SMV stenting. Case 2 is a 68-year-old woman who experienced relief of symptoms but elected hospice care and passed away a month later, after developing SMV stent thrombosis despite oral anticoagulation. Case 3 is a 58-year-old woman who had PV and SMV stenoses. She developed refractory bleeding immediately after stenting and consequently died. Case 4 is a 66-year-old man who achieved symptoms resolution. His symptoms recurred due to stent thrombosis 6 weeks later. After thrombectomy, he improved and was alive at 4 months, on aspirin, enoxaparin, and SAT, with no recurrence of symptoms. DISCUSSION: PV and SMV stenosis caused by pancreatic cancer can result in varying degrees of bowel ischemia, malnutrition, refractory ascites and often leads to death. It is often unrecognized and clinical findings are attributed to the cancer itself. PV/SMV stenting is possible and can reverse PH, ascites, bowel ischemia, and malnutrition. Anticoagulation can decrease the risk of venous thrombosis associated with stenting but coexistent PH presents a challenge to anticoagulation. Further studies are needed to determine the targeted population that will benefit from stenting and when to start anticoagulation or antiplatelet therapy.Figure 1.: A) Abdominal CT scan showing PV stenosis B) PV stent placement process. Contrast failed to pass through the narrowed area.Figure 2.: C) Stent is successfully placed. D) Abdominal CT scan status post PV stent placement.

Acute Life-Threatening Complications of Portal Hypertension: a Review of Pathophysiology, Incidence, Management, and Cost

Portal hypertension represents a dysfunctional hemodynamic alteration within the portal venous system, usually due to cirrhosis. These altered hemodynamics play a direct role in the development of acute, life-threatening variceal hemorrhage and mark an important pathophysiologic step in the development of other sudden and life-threatening complications such as type 1 hepatorenal syndrome and spontaneous bacterial peritonitis. Many life-saving interventions in these patients are aimed at reducing portal venous pressure. The contribution of portal hypertension to the development of variceal hemorrhage, type 1 hepatorenal syndrome (known also by the name HRS-AKI), and spontaneous bacterial peritonitis in cirrhotic patients is discussed. This article reviews the pathophysiology and incidence of life-threatening complications of cirrhotic portal hypertension, with a discussion of management options and treatment costs.

Propranolol Reduces Portal Vein Diameter in Schistosomal Liver Disease with Portal Hypertension: A Prospective Cohort Study.

.Hepatosplenic schistosomiasis (HSS) complicates portal hypertension, leading to life-threatening variceal bleeding. Variceal bleeding is associated with increased portal vein diameter (PVD). Beta-blockers prevent variceal bleeding. It is unclear whether beta-blockers such as propranolol can reduce PVD in HSS. We aimed to explore the effect of propranolol on PVD in HSS. A longitudinal study was conducted at the University Teaching Hospital, Zambia, as an extension of a clinical trial of rifaximin undertaken to test the hypothesis that rifaximin could reduce bacterial translocation in HSS. We randomized 85 adults to either rifaximin and standard care, or propranolol-based standard care only for 42 days. We then followed up all the patients on propranolol up to day 180. We used ultrasound to measure PVD at baseline and day 180. The primary outcome was reduction in PVD. Beta-blockade and splenic size reduction were secondary outcomes. Portal vein diameter reduced after 180 days of propranolol therapy from median 12 mm (interquartile range (IQR): 11–14) to median 10 mm (IQR: 9–13) (P < 0.001). The pulse rate reduced from baseline median 70 beats/minute (IQR: 66–80) to 65 beats/minute (IQR: 60–70) by day 180 (P = 0.006). Hemoglobin levels improved from baseline median 8 g/dL (IQR: 6–11) to 12 g/dL (10–14) (P < 0.001). Splenic size remained unchanged. Propranolol led to the reduction in PVD over 180 days. This suggests that ultrasound could be useful in monitoring response and compliance to beta-blockers, especially in resource-constraint areas where portal hypertension measurement facilities are unavailable.

Precision Onion Skinning Technique for Transjugular Intrahepatic Portosystemic Shunt Revision

A transjugular intrahepatic portosystemic shunt is the standard of care for complications of portal hypertension, such as variceal bleeding, refractory ascites, and hepatic hydrothorax. Hepatic encephalopathy, hepatic insufficiency, and right heart failure are the major complications after shunt creation. If medical management is unsuccessful, the interventionalist is consulted to close/revise the shunt. Closure of the shunt results in a dangerously abrupt increase in portal pressure, increasing risk for life-threatening variceal bleeding. Methods for revising these shunts are reported, which result in coarse adjustments in shunt diameter, causing rapid changes in portosystemic gradients. Our method for shunt revision utilizes carefully sized covered stents deployed in a controlled “onion skin” fashion to produce a narrowing within the hepatic venous limb of the shunt to precisely calibrate the desired portosystemic gradient.

The Management of Pregnancy in Patients with Advanced Liver Disease Before and After Liver Transplantation

Pregnancy in cirrhotic women carries a significant risk of morbidity and mortality to both mother and fetus. Fetal complications include higher rates of spontaneous abortion, prematurity, and perinatal death. Maternal complications in a patient with established cirrhosis include portal hypertension, potentially life-threatening variceal hemorrhage, hepatic decompensation, postpartum hemorrhage, and splenic artery aneurysm rupture. Most of these adverse outcomes are associated with the severity of liver disease; however, physiologic hypervolemiain pregnancy leads to an additional increase in portal hypertension. Preconception liver transplantation mitigates some of these complications but also introduces added risks of hypertension/preeclampsia, gestational diabetes, and fetal growth restriction. Delaying conception by at least 1 year after transplantation minimizes fetal exposure to high doses of immunosuppressant medication and allows demonstration of good graft function prior to pregnancy. Thus, contraception counseling shortly after the transplant is imperative. Long-acting reversible contraception, which includes intrauterine devices and contraceptive implants, provides the most effective contraception for this population. Once pregnancy is planned and achieved, women need to maintain stable immunosuppression to prevent allograft rejection. Given the complexity of these patients, a multidisciplinary approach and close monitoring are essential to achieving successful outcomes.

Percutaneous Retroperitoneal Splenorenal Shunt for Symptomatic Portal Vein Thrombosis After Liver Transplantation

Acute or recurrent bleeding from ectopic varices is a potentially life-threatening condition in rare patients with extrahepatic complete portal vein thrombosis (PVT) after liver transplantation (LT). In this setting, the role of interventional radiology is very limited and surgical shunts, in particular splenorenal shunts are usually used, despite the high associated mortality. We present the first reports of the clinical use of a new minimally invasive technique, percutaneous retroperitoneal splenorenal shunt (PRESS), in two LT recipients with life-threatening variceal hemorrhage secondary to PVT. Both patients had a successful PRESS using a transplenic approach with resolution of bleeding, avoiding the need for a potentially complicated laparotomy. The PRESS procedure is a useful addition to the interventional armamentarium that can be used in cases unsuitable for surgical shunt, and refractory to endoscopic management. In the future, this technique may be an alternative to surgical shunts as the standard procedure in patients with extra-hepatic PVT, just as the transjugular intrahepatic portosystemic shunt (TIPS) procedure has become for the management of portal hypertension in the absence of PVT. Longer-term follow-up will be needed to establish the long-term success of this procedure.

Liver diseases in pregnancy: Liver transplantation in pregnancy

Pregnancy in patients with advanced liver disease is uncommon as most women with decompensated cirrhosis are infertile and have high rate of anovulation. However, if gestation ensued; it is very challenging and carries high risks for both the mother and the baby such as higher rates of spontaneous abortion, prematurity, pulmonary hypertension, splenic artery aneurysm rupture, postpartum hemorrhage, and a potential for life-threatening variceal hemorrhage and hepatic decompensation. In contrary, with orthotopic liver transplantation, menstruation resumes and most women of childbearing age are able to conceive, give birth and lead a better quality of life. Women with orthotopic liver transplantation seeking pregnancy should be managed carefully by a team consultation with transplant hepatologist, maternal-fetal medicine specialist and other specialists. Pregnant liver transplant recipients need to stay on immunosuppression medication to prevent allograft rejection. Furthermore, these medications need to be monitored carefully and continued throughout pregnancy to avoid potential adverse effects to mother and baby. Thus delaying pregnancy 1 to 2 years after transplantation minimizes fetal exposure to high doses of immunosuppressants. Pregnant female liver transplant patients have a high rate of cesarean delivery likely due to the high rate of prematurity in this population. Recent reports suggest that with close monitoring and multidisciplinary team approach, most female liver transplant recipient of childbearing age will lead a successful pregnancy.

Spleno-adrenal shunt: A novel alternative for portosystemic decompression in children with portal vein cavernous transformation

PurposeChildren with portal vein cavernous transformation (PVCT) can develop life-threatening variceal hemorrhage from progressive portal hypertension. While spleno-renal shunt±splenectomy is the most common portosystemic decompression surgery performed in children, we have adopted a modified spleno-adrenal (SA) shunt for complicated PVCT. We describe our 10year experience focusing on technique evolution and treatment efficacy. MethodsBetween 2001 and 2011, 15 children (9 girls and 6 boys, ages 3–11years, median: 6years) with PVCT, portal hypertension, and hypersplenism were treated with SA shunt with splenectomy in Shanghai Children's Medical Center. All children in the study had endoscopy proven active esophageal variceal bleeding requiring multiple transfusions (mean: 4.2 units) with failed sclerotherapy (mean: 2.6 times). Greater omental vein pressure (GVP) approximating portal venous pressure was measured pre- and post-SA shunt. Pre- and post-operative ammonia levels were obtained. Follow-up ranged from 6months to 10years (mean: 4.2±2years). ResultsIntra-operative adrenal vein diameter and length ranged from 0.7 to 1.8cm and 2 to 3cm, respectively. Intra-operative GVPs pre-and post-SA shunt were (30±11) and (22±7) mmHg, respectively (p<0.01). On follow-up, there have been no recurrences of GI bleeding. Liver function tests remained normal in all children with the exception of elevated post-operative mean blood ammonia levels [Pre (18±7) mmol/L, post (60±17) mmol/L (p<0.05)] in all children. Ammonia levels normalized in all cases on outpatient follow-up. There have been no cases of hepatic encephalopathy, and all have normal age appropriate neurodevelopment (Bayley's assessment). Barium swallow and/or upper endoscopy showed interval resolution of esophageal varices in all children, and vascular ultrasound showed patent shunt anastomosis without stricture in 14 (93%). ConclusionsThe left adrenal vein is a viable conduit for effective selective portosystemic decompression. Similar to the more traditional spleno-renal shunt, SA appears also to have the advantage of preventing hepatic encephalopathy preserving neurodevelopment, although the rise in post-operative ammonia levels was unexpected. Longer follow-up is needed to look for late signs of encephalopathy assessing neurodevelopment long term.

Direct Measurement of Porto-systemic Gradient in a Failing Fontan Circulation

We describe the case history of a 42-year-old man with cardiac cirrhosis, portal hypertension, and life-threatening variceal bleeding after Fontan revision surgery. Direct pressure measurements in the portal vein, though high, demonstrated only a modest portosystemic gradient (PSG), 9 mm Hg. A transjugular intrahepatic portosystemic shunt procedure was performed. This reduced the PSG (3 mm Hg). His bleeding was controlled. The patient's histopathological findings were identical to that previously documented in Fontan patients, raising the question of whether these subdiaphragmatic hemodynamics are representative of the broader failing Fontan population.

Transjugular Intrahepatic Portosystemic Shunt for Variceal Hemorrhage due to Recurrent of Hereditary Hemorrhagic Telangiectasia in a Liver Transplant

Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) consists of vascular malformations associated with arteriovenous (AV), arterioportal, and/or portovenous shunting. Most patients with HHT have liver involvement. Symptoms, although rare, consist of cardiac failure, pulmonary hypertension, portal hypertension, portosystemic encephalopathy, cholangitis, and atypical cirrhosis. Reported treatments for symptomatic AV malformations have been associated with substantial morbidity and mortality. This report describes a case of hepatic HHT that required liver transplantation after hepatic artery embolization. Recurrent vascular malformations developed in the transplant, resulting in portal hypertension and life-threatening variceal hemorrhage that was controlled with transjugular intrahepatic portosystemic shunt creation.

Pregnancy and cirrhosis

As the treatment of cirrhosis improves, pregnancy in patients with cirrhosis is likely to become more common. Although maternal and fetal mortality is expected to similarly improve, pregnant patients with cirrhosis face unique risks. These include higher rates of spontaneous abortion and prematurity and a potential for life-threatening variceal hemorrhage, hepatic decompensation, splenic artery aneurysm rupture, and postpartum hemorrhage. Pregnancy outcome may be influenced by the underlying etiology of liver disease, as in viral and autoimmune hepatitis. Medications also impact the course of pregnancy, and must be tailored appropriately during this time.

Percutaneous Transsplenic Access in the Management of Bleeding Varices from Chronic Portal Vein Thrombosis

Three patients with life-threatening variceal hemorrhage secondary to portal vein (PV) thrombosis underwent endovascular treatment via the transsplenic route. The indications, techniques, and early outcomes are described. Each patient had successful portal/splenic vein recanalization with or without transjugular intrahepatic portosystemic shunt (TIPS) creation and variceal embolization with conventional catheter and wire techniques. The transsplenic approach is a useful addition to the interventional armamentarium that can be used in cases refractory to endoscopic management and unsuitable for surgical shunt procedures or conventional TIPS procedures. Longer-term follow-up will be needed to establish the durability of these procedures.