Refractory Hepatic Encephalopathy Research Articles

Transjugular Intrahepatic Portosystemic Shunt Reduction for Medically Refractory Hepatic Encephalopathy

Abstract Objective Transjugular intrahepatic portosystemic shunt (TIPS) is an established intervention for symptomatic portal hypertension, with many patients experiencing hepatic encephalopathy (HE) as an undesirable side effect. For medically refractory HE, TIPS reduction can decrease the burden of neurotoxic metabolites. This study aimed to evaluate the efficacy of TIPS reduction for the treatment of medically refractory post-TIPS HE. Methods A retrospective search using an institutional database yielded 45 patients who underwent TIPS reduction between 2011 and 2021. Four patients were excluded due to lack of post-TIPS HE, and 41 patients in total were included. The primary endpoint was improvement of HE after TIPS reduction as measured by the West Haven scores. Secondary endpoints included postreduction recurrence of ascites or gastrointestinal bleeding, procedural complications, and 30-day mortality. Results TIPS reduction was performed in all 41 patients with a 30-day mortality rate of 9.8%. No deaths were attributable to the procedure itself. Twenty-seven patients (65.9%) had improvement in HE and 10 patients (24.4%) proceeded to TIPS occlusion due to refractory HE. The average pre- and postreduction West Haven grades were 2.9 ± 0.5 and 1.9 ± 1.2 (p < 0.001), respectively. One patient (2.4%) had spontaneous TIPS thrombosis after reduction and developed arterial gastrointestinal bleeding, 15 patients (36.6%) experienced recurrent ascites, and there were no cases of variceal hemorrhage. Conclusions In this population, TIPS reduction improved medically refractory HE in 65.9% of patients with a 36.6% risk of recurrent ascites, no cases of variceal hemorrhage, and 9.8% 30-day mortality.

Endoscopic ultrasound sclerotherapy for refractory hepatic encephalopathy associated with rectal varices.

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An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab plus bevacizumab in patients with locally advanced unresectable or metastatic hepatocellular carcinoma.

TPS576 Background: Despite advances in treatment for unresectable hepatocellular carcinoma (HCC), long-term survival rates remain poor. The combination of atezolizumab (Atezo) plus bevacizumab (Bev) is approved frontline therapy for advanced HCC, but a minority of patients (pts) respond and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment (TME), mediated by activated immune checkpoint signaling and angiogenesis pathways, which may contribute to therapeutic resistance. RP3 is a genetically modified herpes simplex virus type 1 (HSV-1) that expresses the fusogenic gibbon ape leukemia virus glycoprotein with the R sequence deleted (GALV-GP-R–), an anti–CTLA-4 antibody-like molecule, CD40 ligand, and 4-1BB ligand. The direct oncolytic effect coupled with immune stimulation by RP3 in the TME is intended to provide systemic antitumor activity and synergize with anti–PD-1/PD-L1 agents, such as Atezo. Preclinical data have demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev, supporting the clinical combination of RP3 with Bev. This study will evaluate the safety and efficacy of RP3 combined with Atezo plus Bev as first- (1L) and second-line (2L) systemic therapies for unresectable and advanced HCC (NCT05733598). Methods: The 1L and 2L cohorts will each enroll up to 30 pts. Pts in the 1L cohort may not have received prior systemic treatment; pts in the 2L cohort must have progressed on or following 1 prior line of systemic therapy, which must have included a PD-1/PD-L1–directed agent. Key inclusion criteria include advanced unresectable HCC with ≥1 measurable tumor of ≥1 cm in longest diameter, Child-Pugh class A, and an Eastern Cooperative Oncology Group performance status of 0 to 1. Key exclusion criteria include untreated esophageal and/or gastric varices with bleeding or at high risk for bleeding and macroscopic invasion of the tumor into any major blood vessel(s) and/or main bile ducts. Pts with a history of medically refractory hepatic encephalopathy and/or hepato-renal syndrome are also excluded. Pts in the 1L cohort will receive Atezo 1200 mg and Bev 15 mg/kg every 3 weeks (Q3W) together with RP3 intratumorally Q3W for a total of up to 8 doses. Pts in the 2L cohort will receive RP3 every 2 weeks for 4 doses with Bev Q3W starting on cycle (C)1 day (D)1, then RP3 and Bev Q3W for up to 4 more doses with Atezo Q3W being added on C4D1. The primary endpoint is the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints are safety, ORR using HCC modified RECIST, duration of response, complete response rate, and progression-free survival. Clinical trial information: NCT05733598 .

Endoscopic Ultrasound-Guided Transgastric Shunt Obliteration for Recurrent Hepatic Encephalopathy.

Occlusion of spontaneous portosystemic shunts (SPSSs) in patients with cirrhosis may be required in recurrent or refractory hepatic encephalopathy. We describe a novel method for occlusion of SPSS using endoscopic ultrasound (EUS). EUS-guided transgastric shunt obliteration was performed by injecting glue and coils directly into SPSS. EUS-guided transgastric shunt obliteration was performed for 7 patients in 9 sessions. Complete cessation of Doppler flow was achieved in 6/7 cases. Adequate clinical response was observed in 6/7 patients. No procedure-related severe adverse events were seen. This novel technique is a potentially effective and efficient method for shunt obliteration.

Hepatic Encephalopathy following Transjugular Intrahepatic Portosystemic Shunt Placement.

Hepatic encephalopathy (HE) is a complex condition that arises as a complication of chronic liver disease and portosystemic shunting. Its pathophysiology involves several factors, including impaired ammonia metabolism, portosystemic shunting, sarcopenia, and systemic inflammation. The symptoms of HE can vary significantly, with manifestations ranging from subclinical signs to a comatose state. The West Haven classification system is most commonly used to grade the severity of HE. There is a broad differential for the presenting symptomatology of HE and other causes of altered mental status must be excluded during the workup. HE is a well-known complication of transjugular intrahepatic portosystemic shunt (TIPS) placement. Even though newer stent designs help reduce the risk of HE with smaller diameter shunts, it is essential that patients are counseled regarding this potential risk prior to the procedure. Once a diagnosis of HE has been confirmed, the mainstay of therapy is lactulose and rifaximin. In cases where a patient has received a TIPS placement and continues to experience refractory HE despite medical therapy, it may be necessary to consider shunt reduction or closure.

An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab and bevacizumab therapy in patients with locally advanced unresectable or metastatic hepatocellular carcinoma.

TPS4178 Background: Despite advances in treatment for unresectable hepatocellular carcinoma (HCC), long-term survival rates remain poor. The combination of bevacizumab (Bev) and atezolizumab (Atezo) is the preferred frontline therapy for advanced HCC, but a minority of patients (pts) respond, and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment, mediated by activated immune checkpoint signaling and angiogenesis pathways, which may contribute to therapeutic resistance. RP3 is a genetically modified herpes simplex virus type 1 (HSV-1) that expresses the fusogenic gibbon ape leukemia virus glycoprotein with the R sequence deleted (GALV-GP-R–), an anti–CTLA-4 antibody-like molecule, CD40 ligand, and 4-1BB ligand. The direct oncolytic effect coupled with immune stimulation by RP3 in the tumor microenvironment is intended to provide systemic antitumor activity and enhance therapeutic response to anti–PD-1/PD-L1 agents, such as Atezo. Preclinical data have demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev, supporting the clinical combination of RP3 with Bev. This study will evaluate the safety and efficacy of RP3 combined with Atezo and Bev as first- (1L) and second-line (2L) systemic therapies for unresectable and advanced HCC. Methods: The 1L and 2L cohorts will each enroll up to 30 pts. Pts in the 1L cohort may not have received prior systemic treatment; pts in the 2L cohort must have progressed on or following one prior line of systemic therapy, which must have included a PD-1/PD-L1−directed agent. Key inclusion criteria include advanced, unresectable HCC with ≥1 measurable tumor of ≥1 cm in longest diameter, Child-Pugh Class A, and Eastern Cooperative Oncology Group performance status of 0−1. Key exclusion criteria include untreated esophageal and/or gastric varices with bleeding or at high risk for bleeding and macroscopic invasion of tumor into any major blood vessel(s) and/or main bile ducts. Pts with a history of medically refractory hepatic encephalopathy and/or hepato-renal syndrome are also excluded. Pts in the 1L cohort will receive 1200 mg Atezo and 15 mg/kg Bev every 3 weeks (Q3W) together with RP3 intratumorally Q3W for a total of up to 8 doses. Pts in the 2L cohort will receive RP3 every 2 weeks for 4 doses with Bev Q3W starting on cycle (C) 1 day (D) 1, then RP3 and Bev Q3W for up to 4 more doses with Atezo Q3W being added on C4D1. The primary endpoint is overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints are safety, ORR using HCC modified RECIST, duration of response, complete response rate, and progression-free survival. Clinical trial information: NCT05733598 .

Vitamin D supply and its relationship with nutritional status and survival in patients with liver cirrhosis

Annotation. Prognosis assessment is critical for liver cirrhosis (LC). Vitamin D deficiency is considered a possible unfavorable factor. The aim of the study was to assess the level of vitamin D in LC patients, to establish the prevalence of its deficiency, and to determine the relationship with the severity of LC, nutritional status, and patient survival. 95 LC patients, 61 men, and 34 women (age 50.1±1.15 years) were enrolled in the prospective study. The nutritional status was assessed using Onodera’s Prognostic Nutritional Index (Onodera’s PNI). The serum 25(OH)D3 was determined by enzyme immunoassay. Statistical analysis was performed in SPSS v 21.0. It was established that vitamin D insufficient supply was present in 9% of LC patients, deficiency – in 74%, and severe deficiency – in 15% of patients. LC decompensation was accompanied by a worsening of vitamin D deficiency. The serum 25(OH)D3 was correlated with Child-Turcotte-Pugh and Model For End-Stage Liver Disease (r= -0.481, -0.487, respectively, p˂0.001). The lowest 25(OH)D3 levels were in patients with severe and refractory ascites, hepatic encephalopathy, and significant hypoalbuminemia. Malnutrition was found in 34.7% of decompensated patients and was associated with severe vitamin D deficiency. The 25(OH)D3 was correlated with Onodera’s PNI (r=0.679, p˂0.001). The 25(OH)D3 had a good predictive value for the 1-year mortality (AUC 0.708, p=0.004). The 25(OH)D3 less than 12.5 ng/ml should be considered a marker of a poor prognosis. Thus, vitamin D deficiency is highly prevalent in LC patients. It is associated with the severity of liver disease, malnutrition, and poor prognosis. Further studies are needed to determine whether vitamin D supplementation can improve survival in LC patients.

An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab and bevacizumab therapy in patients with locally advanced unresectable or metastatic hepatocellular carcinoma.

TPS623 Background: Despite advances in treatment for unresectable hepatocellular carcinoma (HCC), long-term survival rates remain poor. The combination of bevacizumab (Bev) and atezolizumab (Atezo) is the preferred frontline therapy for advanced HCC, but a minority of patients (pts) respond, and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment, mediated by activated immune checkpoint signaling and angiogenesis pathways, which may contribute to therapeutic resistance. RP3 is a genetically modified herpes simplex virus 1 (HSV-1) that expresses the fusogenic GALV-GP R- protein, an anti–CTLA-4 antibody-like molecule, CD40 ligand, and 4-1BB ligand. The direct oncolytic effect coupled with immune stimulation by RP3 in the tumor microenvironment is intended to provide systemic anti-tumor activity and reverse therapeutic resistance to anti-PD-1/PD-L1 agents. Pre-clinical data has demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev supporting the clinical combination of RP3 with Bev. RP3 combined with anti-PD1 therapy has demonstrated clinical activity and safety in pts with various malignant solid tumors. This study will evaluate the safety and efficacy of RP3 combined with Atezo and Bev as 1st (1L) and 2nd (2L) line systemic therapies for inoperable and advanced HCC. Methods: The 1L and 2L cohorts will each enroll up to 30 pts with advanced, unresectable HCC. Pts in the 1L cohort may not have received prior systemic treatment; pts in the 2L cohort must have progressed on or following one prior line of systemic therapy, which must have included a PD-(L)1 directed agent. Key inclusion criteria include advanced unresectable HCC with at least 1 measurable tumor of ≥1 cm in longest diameter, Childs-Pugh Class A, and ECOG Score of 0 or 1. Important exclusion criteria include untreated esophageal and/or gastric varices with bleeding or at high risk for bleeding, and macroscopic invasion of tumor into major blood vessels and/or main bile ducts. Pts with a history of medically refractory hepatic encephalopathy and/or hepato-renal syndrome are also excluded. Pts in 1L cohort will receive 1200 mg Atezo and 15mg/kg Bev Q3W together with RP3 intratumorally (IT) Q3W for a total of up to 8 doses. In 2L pts will receive RP3 Q2W for 4 doses with Bev Q3W starting on C1D1, then RP3 and Bev Q3W for up to 4 more doses with Atezo Q3W being added on C4D1. The primary endpoint includes overall response rate (ORR) by RECIST v1.1. Secondary endpoints are safety, ORR using HCC mRECIST, duration of response, complete response rate, and progression-free survival.

Transjugular intrahepatic portosystemic shunt reduction for refractory hepatic encephalopathy: a case series

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a therapeutic intervention for refractory ascites and variceal bleeding. However, the development of hepatic encephalopathy (HE) is a known complication. TIPS diameter can be reduced to decrease further HE episodes when refractory to pharmacotherapy. However, TIPS reduction for refractory hepatic encephalopathy (rHE) is poorly described. This case series identifies various characteristics and outcomes among this unique patient cohort. Case Presentation: In this cohort of 8 patients, 63% were male, 75% were Caucasian, and 38% had alcohol-associated cirrhosis. Following TIPS reduction, the number of HE-related admissions (mean, median) decreased from 2.1 and 2 to 1.6 and 0.5 while the number of non-HE admissions following TIPS reduction increased from 0.6 and 0 to 1 and 0.5. Conclusion: TIPS reduction reduced the number of hospitalizations for rHE but the total number of hospitalizations for all causes increased, demonstrating the high resource utilization for those with rHE following TIPS. Therefore, careful selection for initial TIPS placement remains a priority.

Functional recovery from refractory hepatic encephalopathy following angiographic obliteration of a large, spontaneous portal-umbilical portosystemic shunt: a case report

BackgroundHepatic encephalopathy (HE) as a consequence of cirrhosis with portal hypertension has a profound impact on quality of life for both patients and caregivers, has no gold-standard diagnostic test, and is a risk factor for mortality. Spontaneous portosystemic shunts (SPSS) are common in patients with cirrhosis, can be challenging to identify, and in some cases, can drive refractory HE. Cross-sectional shunt size greater than 83mm2 is associated with liver disease severity, overt HE, and mortality.Case presentationWe report a patient with refractory HE and frequent hospitalization in the context of an occult spontaneous portal-umbilical portosystemic shunt with an estimated cross-sectional area of 809mm2. Following identification and angiographic retrograde transvenous obliteration of the SPSS using plugs, coils and sclerosant, there was improvement in neurocognitive testing and no further hospitalization for HE.ConclusionSPSS in the context of cirrhosis with portal hypertension can contribute to the debilitating effects of refractory HE. This case highlights the opportunity to search for SPSS in patients with HE unresponsive to therapy as angiographic obliteration is usually safe, well-tolerated, and clinically effective.

Clinical Outcomes and Patency after Transjugular Intrahepatic Portosystemic Shunt Reduction for Overshunting Adverse Events

PurposeTo assess clinical outcomes and patency after transjugular intrahepatic portosystemic shunt (TIPS) reduction for overshunting adverse events. Materials and MethodsThis multicenter, retrospective observational study included 33 patients (male-to-female ratio, 20:13; mean age, 59 years; mean Model for End-Stage Liver Disease [MELD] score, 15) who underwent TIPS reduction between 2007 and 2020. Procedure indications included medically refractory hepatic encephalopathy (HE) (85%), post-TIPS hepatic insufficiency (HI) (12%), and heart failure (3%). The measured outcomes included improvement in HE (classified using the West Haven system) and HI, patency of reduced TIPS, and transplant-free survival (TFS). ResultsTIPS reductions were successfully performed using parallel stent (94%) or other (6%) techniques at a median of 120 days after TIPS creation (HE, median, 164 days; HI, median, 5 days). The portosystemic pressure gradient increased from a mean of 10 to 17 mm Hg (P < .001). The overall HE rate after TIPS reduction was 54%; HE was persistent, improved, and resolved in 21%, 32%, and 46% cases, respectively. In patients with HI, the MELD score increased from a mean of 22 before TIPS to 34 after TIPS (P = .061), but without improvement (0%) in HI after TIPS reduction (mean MELD score, 30; P = .266). Recurrent ascites occurred in 14% of the patients. The median shunt patency was 961 days (95% confidence interval, 476–1,447). The 30-day, 6-month, 1-year, and 3-year shunt patency rates were 92%, 81%, 74%, and 37%, respectively. The median TFS was not reached. The 30-day, 6-month, 1-year, and 3-year survival rates were 97%, 90%, 81%, and 60%, respectively. ConclusionsAlthough TIPS reduction may be an effective and durable approach to treat post-TIPS medically refractory HE, shunt reduction may not achieve meaningful benefit for HI.

Abstract No. 183 Transjugular intrahepatic portosystemic shunt reduction for medically refractory hepatic encephalopathy

Transjugular intrahepatic portosystemic shunt (TIPS) is an established intervention for symptomatic portal hypertension. Following TIPS creation, 25-45% of patients experience hepatic encephalopathy (HE), with symptoms ranging from impaired attention to coma (1). While HE can often be managed medically, refractory cases may require TIPS reduction which can redirect blood flow back through the hepatic parenchyma and decrease the burden of neurotoxic metabolites. The purpose of this study was to evaluate the efficacy of TIPS reduction for the treatment of medically refractory post-TIPS HE.

Symptom Management in Patients with Cirrhosis: a Practical Guide.

Purpose of the review Though it is well known that cirrhosis is associated with significant morbidity and mortality, management of symptoms in cirrhosis can be difficult. This review serves to offer practical guidance in the management of liver-specific symptoms of cirrhosis as well as other symptoms with special hepatic considerations.Recent findingsWe discuss liver-specific symptoms and management, including ascites and refractory ascites, hepatic encephalopathy, pruritus, and muscle cramping. We also discuss the challenges of treating more generalized symptoms in cirrhosis, including pain, depression/anxiety, appetite, and fatigue. Medication management is, especially complex in this population given the altered metabolism of drugs, and we consider some strategies to approach this.SummaryWith the right tools, provided throughout this review, hepatologists should be well equipped to manage the nuanced liver-specific and generalized symptoms in patients with cirrhosis.

Transjugular Intrahepatic Portosystemic Shunt Reduction for Medically Refractory Hepatic Encephalopathy

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is an established intervention for symptomatic portal hypertension. Following TIPS creation, 22-50% of patients experience hepatic encephalopathy (HE), with symptoms ranging from mild confusion to coma. While HE can be medically managed, refractory cases may require downsizing of the TIPS which can be accomplished by deploying a smaller caliber stent within the original shunt. Decreasing shunt diameter redirects blood flow back through liver parenchyma. The purpose of this study was to evaluate the efficacy of TIPS downsizing for the treatment of medically refractory post-TIPS HE.&#x0D; Methods: An IRB-approved, HIPAA compliant retrospective review was performed. A search of an institutional radiology database yielded 45 patients who underwent TIPS downsizing between 2011-2021. Four patients were excluded due to lack of post-TIPS HE, and a total 41 patients were included in the study. Clinical and serologic data were obtained for all 41 patients. The primary objective was to determine the efficacy of TIPS downsizing for reduction of HE as measured by the West Haven criteria. Secondary endpoints included post-downsize recurrence of ascites or gastrointestinal bleeding, procedural complications, and thirty-day mortality.&#x0D; Results: TIPS downsizing was performed in all 41 patients with a 9.8% thirty-day mortality rate. No deaths were attributable to the procedure itself. Of the remaining patients, twenty-seven patients (65.9%) had improvement in HE and 10 patients (24.4%) proceeded to TIPS occlusion due to refractory HE. The average pre-downsize and post-downsize West Haven grades were 2.9 ± 0.5 and 1.9 ± 1.2, respectively. One patient (2.4%) had spontaneous TIPS thrombosis after downsizing and developed gastrointestinal bleeding requiring embolization; 15 patients (36.6%) experienced recurrent ascites.&#x0D; Conclusion: In this population, TIPS downsizing improved medically refractory HE in 65.9% of patients with a 2.4% risk of recurrent gastrointestinal bleeding, 36.6% risk of recurrent ascites, and 9.8% thirty-day mortality.

Endovascular Management of Hepatic Encephalopathy

AbstractTransjugular intrahepatic portosystemic shunt (TIPS) and spontaneous portosystemic shunts (SPSS) may lead to new or worsening hepatic encephalopathy (HE), especially in patients with chronic liver disease. Patients with medically refractory HE (rHE) may benefit from endovascular interventions. In this review, we briefly describe the post-TIPS and SPSS vascular anatomy, pathophysiology, classification, factors associated with HE, and the medical management of HE. In addition, we will discuss current endovascular techniques for HE management, their advantages, disadvantages, and review of the current literature.

Retrograde Transvenous Obliteration of Gastric Varices using Sodium Tetradecyl Sulphate: Technical Considerations and Results from a Single Institution Retrospective Study

Abstract Introduction Retrograde transvenous obliteration (RTO) with the assistance of a balloon (BRTO) or a vascular plug (PARTO) is an established method for treating gastric varices (GVs) secondary to portal hypertension. Most of the available studies on RTO have used lipiodol along with sclerosing agents like ethanolamine oleate or sodium tetradecyl sulfate (STS). We evaluated the safety and efficacy of RTO for treating GVs using STS as a sclerosant without lipiodol. Materials and Methods Sixteen patients (nine men, age range 16–74 years) were included in this retrospective study. Twelve patients presented with acute bleeding, two with chronic bleeding, one with large varices without bleeding, and one with refractory hepatic encephalopathy (HE). BRTO was attempted in 14 patients and PARTO in 2 patients. The technical and clinical success and complications of RTO were studied. Results The RTO procedure was technically successful in 14 (14/16, 87.5%) patients, with 13 (13/14, 93%) obtaining clinical success. One patient died due to the early recurrence of bleeding. Three patients had minor intraprocedural complications. Conclusion Retrograde gastric variceal obliteration using STS is safe and technically feasible with high technical and clinical success and low complication rate.

Abstract No. 29 Percutaneous mesocaval shunt creation: a retrospective review of 5 patients with midterm outcomes

To evaluate the indication, approach, safety, and outcomes of percutaneous mesocaval shunt placement Institutional review board-approved retrospective review of the electronic medical records of patients with percutaneous mesocaval shunts was performed from January 2001 through March 2020 (n = 5). Indication for mesocaval shunt placement was refractory variceal hemorrhage in all 5 patients. All patients had extensive portal vein thrombosis (PVT) (1 intrahepatic, 4 extrahepatic) precluding transjugular intrahepatic portosystemic shunt placement. The underlying etiologies for PVT were non-alcoholic cirrhosis, primary sclerosing cholangitis, pancreatic cancer, post-surgical, and during pregnancy of indeterminate etiology. Post-procedurally, patients were followed for up to 10 years with clinical and laboratory assessment as well as CT or MRI imaging. Technical success was defined as placement of a stent from the superior mesenteric vein to the inferior vena cava. Clinical success was defined as cessation of refractory bleeding. Patient demographics, technical approach for placement, pre-procedure and post-procedure MELD scores, shunt patency, and complications were recorded. Technical and clinical success was achieved in 100% (5 of 5) of patients. Procedural imaging was available for 4/5 patients. To perform the inferior vena cava to superior mesenteric vein puncture, a combination of fluoroscopy and intravascular ultrasound was used in 25% (1/4), fluoroscopy and transabdominal ultrasonography was used in 25% (1/4), and fluoroscopy and intracardiac echocardiography was used in 50% (2/4). MELD scores (9 – 29) did not significantly deviate from pre-procedure to 30 days post-procedure in any patient. Mesocaval shunt primary unassisted patency was 5/5 (100%) at 6 months, 4/4 (100%) at 12 and 18 months, and 2/3 (67%) at 24 months. After 32 months, one patient underwent intentional mesocaval shunt closure for chronic, refractory hepatic encephalopathy (HE). The final patient maintained mesocaval shunt patency for greater than 10 years. No immediate complications occurred peri-procedurally. Two patients (40%) suffered HE, one of which resolved with medical optimization and the second required eventual shunt closure. Mesocaval shunt placement is an uncommonly performed procedure to treat complications of portal hypertension when a TIPS cannot be placed. In this cohort, outcomes were comparable to TIPS as it was safe, well tolerated, and remained patent in a majority of patients at 24 months.

Abstract No. 119 Transjugular intrahepatic portosystemic shunt for pediatric portal hypertension: a meta-analysis

The purpose of this study is to review and characterize the feasibility, safety and evidence supporting the use of TIPS shunt in the pediatric population by conducting a meta-analysis. Cochrane Database and PubMed were queried from establishment to April 2020 with the following keywords: “transjugular intrahepatic portosystemic shunt“ AND (“child” OR “pediatric”). The following criteria were adopted: 1. Patients< 18 years old received TIPS; 2. Sample size ≥5; 3. Studies with original data. The following data was extracted by two researchers: study name, year of publication, region, patient number, sex, age, indication of TIPS, portal HTN etiology, TIPS stent type, laboratory values, technical success, hemodynamic success, immediate clinical success, post-TIPS bleeding rate, survival/mortality, shunt patency, and complications. Statistical analysis was performed with STATA 15.1 (STATA Corp., College Station, TX). Pooled analysis was conducted. A random-effect model was used. Technical success, hemodynamic success, immediate clinical success, post-TIPS bleeding rate, survival, and shunt dysfunction were reported with 95% CI. Eleven observational studies totaling 210 subjects were included. The pooled technical success rate and hemodynamic success rate were 94% (95%CI: 86-99%) and 91% (95%CI: 82-97%), respectively; ongoing variceal bleeding resolved in 99.5% (95%CI: 97-100%); refractory ascites was improved in 96% (95%CI: 69-100%); post-TIPS bleeding rate was 14% (95%CI: 1-33%); 88% patients were alive or successfully received liver transplant (95%CI: 79-96%); Shunt dysfunction rate was 27% (95%CI: 17-38%). Hepatic encephalopathy occurred in 10.2% (19/187), though 84.2% (16/19) resolved with medical management. In conclusion, based on moderate level of evidence, TIPS is a safe and effective intervention that should be considered in pediatric patients with portal hypertensive complications. Our study demonstrates that TIPS is effective in achieving immediate clinical success and preventing future variceal bleeding in children. The risk of medically refractory hepatic encephalopathy is minimal. However, quality of published data is rather limited and future comparative studies are warranted.

Efficacy of TIPS Reduction for Refractory Hepatic Encephalopathy, Right Heart Failure, and Liver Dysfunction.

OBJECTIVE. The purpose of this study was to determine clinical outcomes of patients undergoing TIPS reduction. MATERIALS AND METHODS. In this institutional review board-approved, HIPAA-compliant study, all TIPS reductions performed at two institutions from January 1, 2008 to January 31, 2016, were retrospectively identified. Patients were divided into two groups according to pre-TIPS symptoms: volume overload due to ascites or hydrothorax (VO; n = 14) or variceal bleeding (VB; n = 12). Patient demographics, pre-TIPS model for end-stage liver disease score, pre- and post-TIPS portosystemic gradients, and clinical parameters were recorded. The primary endpoint was change in symptoms of hepatic encephalopathy (HE; West Haven criteria), right heart failure, or liver dysfunction. Secondary endpoints included paracentesis rate for the VO group and rebleeding for the VB group. RESULTS. The degree of HE increased in 24 of 26 patients (92%) after TIPS placement and decreased in 24 of 26 patients (92%) after TIPS reduction. Mean West Haven scores for the VO group decreased after TIPS reduction (from 2.57 ± 0.97 [SD] to 1.07 ± 0.70; p < .001). Mean West Haven scores for the VB group also decreased after TIPS reduction (from 2.45 ± 0.89 to 1.27 ± 0.86; p = .007). Right heart failure improved in two of three patients (67%), and total bilirubin improved in one of three patients (33%). Follow-up data were available up to median of 134 days (interquartile range, 44-286). TIPS reduction led to an increased paracentesis rate compared with before TIPS placement in four of 14 patients with VO (29%). One patient had a stable paracentesis rate after TIPS reduction compared with before TIPS placement. Variceal rebleeding did not occur in any patients with VB after TIPS reduction. At 54 days after TIPS reduction, one of the 12 patients with VB (9%) experienced hematemesis due to an endoscopically proven band-related ulcer. CONCLUSION. TIPS reduction successfully resolved HE and refractory right heart failure in most patients. In patients with VB, TIPS reduction with variceal embolization results in a low risk of short-term recurrent VB. However, in patients with VO, ascites may return or worsen after TIPS reduction despite improvement in HE.

Comparative study of the effect of neuromuscular electrical stimulation and oral administration of branched-chain amino acid on preventing sarcopenia in patients after living-donor liver transplantation: study protocol for an open-label randomized controlled trial

BackgroundLiver cirrhosis is the irreversible fibrosis of the liver and causes refractory ascites and hepatic encephalopathy, which might not respond to treatment. Living donor liver transplantation (LDLT) is an effective treatment for patients with cirrhosis. However, post-LDLT patients are prone to muscle atrophy and sarcopenia. Therefore, physiotherapy of post-LDLT patients is essential for preventing the progression of sarcopenia. Recently, rehabilitation using neuromuscular electrical stimulation (NMES) has been reported to be useful for preventing the progression of sarcopenia. Similarly, nutrition therapy is essential for post-LDLT patients because these patients frequently experience malnutrition. However, the effects of combined NMES and nutrition therapy on post-LDLT patients remain unknown.Methods/designThis open-label, randomized, parallel-group study will compare the effects of combined therapy with NMES and branched-chain amino acids (BCAA) with those of NMES alone in patients with decompensated cirrhosis after LDLT. After LDLT, 50 patients with decompensated cirrhosis will be randomly assigned to receive NMES with BCAA or NMES without BCAA. The duration of the intervention will be 3 months. To analyze the change in skeletal muscle mass, InBody 770 body composition and body water analysis and ultrasonography will be performed before LDLT and 4 weeks and 12 weeks post-LDLT. The primary endpoint is changes in the skeletal muscle mass from baseline to 3 months. Important secondary endpoints are the changes in the skeletal muscle mass from baseline to 1 month and changes in the quadriceps strength from baseline to 1 month.DiscussionThe results of this study are expected to provide evidence regarding the effect of NMES combined with BCAA therapy on the skeletal muscle of post-LDLT patients.Trial registrationJapan Registry of Clinical Research jRCTs071190051. Registered on February 26, 2020.