This study addresses the effects of shunt embolization on the recurrence of hepatic encephalopathy (HE) in patients with major portosystemic shunts. MEDLINE via PubMed, Google Scholar, and Scopus was searched to find the relevant full-text articles published from inception until August 2024. The primary outcome was the degree of HE or mental state change determined by the West-Heaven classification system. Dichotomous data were compared using odds ratios (OR). 95% confidence (CI) intervals were provided for each outcome in the report. The random-effects model was used to analyze the data. Trim and fill, Egger's regression and funnel plot were employed to evaluate publication bias in this body of literature. A total of 7 articles and 254 patients were included in the present meta-analysis. It was found that shunt embolization significantly reduced the recurrence of HE in patients with portosystemic shunts due to liver cirrhosis. Overall analysis showed that the pooled OR was 0.253 and the overall heterogeneity of the data was substantial (95% CI: 0.117-0.550, I 2=60.52% and P=0.001). The funnel plot was reasonably symmetrical and no study was trimmed to either side of the mean. Begg's (P=0.229) and Egger's tests (P=0.273) showed no significant risk of publication bias. Quality assessment showed that the majority of the included studies were of low quality. In conclusion, the present meta-analysis indicates that shunt embolization after portosystemic shunt significantly reduces the recurrence of HE in patients with liver cirrhosis. However, the findings should be interpreted with caution due to the low quality and low number of the included studies. Future research should prioritize higher-quality trials to validate these results and explore long-term outcomes.

Ammonia levels are orchestrated by a series of complex interrelated pathways in which the urea cycle has a central role. Liver dysfunction leads to an accumulation of ammonia, which is toxic and is strongly associated with disruption of potassium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation, hypoxaemia and dysregulation of neurotransmission. Hyperammonaemia is a hallmark of hepatic encephalopathy and has been strongly associated with liver-related outcomes in patients with cirrhosis and liver failure. In addition to the established role of ammonia as a neurotoxin in the pathogenesis of hepatic encephalopathy, an increasing number of studies suggest that it can lead to hepatic fibrosis progression, sarcopenia, immune dysfunction and cancer. However, elevated systemic ammonia levels are uncommon in patients with metabolic dysfunction-associated steatotic liver disease. A clear causal relationship between ammonia-induced immune dysfunction and risk of infection has not yet been definitively proven. In this Review, we discuss the mechanisms by which ammonia produces its diverse deleterious effects and their clinical relevance in liver diseases, the importance of measuring ammonia levels for the diagnosis of hepatic encephalopathy, the prognosis of patients with cirrhosis and liver failure, and how our knowledge of inter-organ ammonia metabolism is leading to the development of novel therapeutic approaches.

To compare clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) created with the single covered-uncovered stent (Viatorr TIPS Endoprosthesis) versus covered stent (Fluency) versus a combination of covered and uncovered stent.

From May 2016 and July 2019, a total of 180 liver cirrhosis patients with recurrent variceal bleeding underwent TIPS creation with single covered-uncovered stent (n = 63) or covered stent (n = 41) or a covered and uncovered stent combination (n = 76). Shunt dysfunction, rebleeding, overt hepatic encephalopathy and mortality was estimated using the Kaplan-Meier method and compared with the log-rank test.

The difference of baseline characteristics among these three groups were not significant. The included patients had a median age of 51 years (IQR 43-61), and 101 (56.1%) were men. The 1-year and 2-year shunt dysfunction rates were 1.6% and 3.2% in the single covered-uncovered stent group, 7.3% and 7.3% in the covered stent group and 5.3% and 6.6% in the combination group, respectively. There was no significant difference among groups [Hazard Ratio (HR) (95%CI): 1 vs 2.29 (0.38 - 13.72) vs 2.10 (0.41 - 10.83); P = 0.913]. No significant differences in the incidence of all-cause rebleeding were observed between the groups at 1 year (Viatorr vs Fluency vs combination: 11.1% vs 17.1% vs 10.5%) as well as 2 years (15.9% vs 17.1% vs 11.8%), with the HR (95%CI) being 1 vs 1.27 (0.5-3.21) vs 0.74 (0.30-1.82); P = 0.475). The 1-year and 2-year incidence of overt hepatic encephalopathy were 30.2% and 30.2% in the single covered-uncovered stent group, 22.0% and 22.0% in the covered stent group and 25.0% and 25.0% in the combination group, respectively. However, there was no significant difference among these three groups (P = 0.402). In addition, there was no significant difference in the 1-year and 2-year mortality (6.3% and 7.9% vs. 4.9% and 9.8% vs. 6.6% and 9.2%, P = 0.606).

No significant difference was observed among different stent groups. Fluency covered stent and the generic bare stent/Fluency covered stent was not an unreasonable alternative to the Viatorr stent for TIPS creation.

Hepatic encephalopathy (HE) after Trans-jugular intrahepatic portosystemic shunt (TIPS) is a common clinical problem. According to recent studies, Proton pump inhibitor (PPI) use can serve as an independent risk factor for HE. We performed a systematic review and meta-analysis to analyze the association between HE with PPI use versus without PPI use in patients undergoing TIPS.

We conducted a comprehensive literature search from inception through February 15th, 2022 on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases. Odds ratio (OR) was calculated when comparing dichotomous variables of patients with HE vs. no HE in PPI use versus no PPI use in post TIPS patients. A 95% confidence interval (CI) and P values (<0.05 considered significant) were also generated.

The search strategy yielded a total of 27 articles. We finalized four studies with a total of 825 patients. There was statistically significant difference in TIPS patients with HE in PPI users versus non-PPI users (OR 3.39 [1.79-6.43], P<0.01, I2=55.5%). Pooled mean average days to hospitalization was 215.2 days to hospitalization for hepatic encephalopathy in non-PPI users compared to 139.5 days in PPI users.

Our study determines that there is a higher risk of post-TIPS HE in patients on PPI therapy vs. patients not receiving PPI therapy. We recommend using PPIs at a lower tolerable dose where necessary. Larger studies are needed to draw stronger conclusions.

Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.

To provide patients the chance of accepting curative transjugular intrahepatic portosystemic shunt (TIPS) rather than palliative treatments for portal hypertension-related variceal bleeding and ascites, we aimed to assess hepatic-associated vascular morphological change to improve the predictive accuracy of overt hepatic encephalopathy (HE) risks.

In this multicenter study, 621 patients undergoing TIPS were subdivided into training (413 cases from 3 hospitals) and external validation datasets (208 cases from another 3 hospitals). In addition to traditional clinical factors, we assessed hepatic-associated vascular morphological changes using maximum diameter (including absolute and ratio values). Three predictive models (clinical, hepatic-associated vascular, and combined) were constructed using logistic regression. Their discrimination and calibration were compared to test the necessity of hepatic-associated vascular assessment and identify the optimal model. Furthermore, to verify the improved performance of ModelC-V, we compared it with four previous models, both in discrimination and calibration.

The combined model outperformed the clinical and hepatic-associated vascular models (training: 0.814, 0.754, 0.727; validation: 0.781, 0.679, 0.776; p < 0.050) and had the best calibration. Compared to previous models, ModelC-V showed superior performance in discrimination. The high-, middle-, and low-risk populations displayed significantly different overt HE incidence (p < 0.001). Despite the limited ability of pre-TIPS ammonia to predict overt HE risks, the combined model displayed a satisfactory ability to predict overt HE risks, both in the low- and high-ammonia subgroups.

Hepatic-associated vascular assessment improved the predictive accuracy of overt HE, ensuring curative chances by TIPS for suitable patients and providing insights for cirrhosis-related studies.

We proposed a strategy for the creation of a 6-mm transjugular intrahepatic portosystemic shunt (TIPS) and to assess its effectiveness compared to a conventional 8-mm shunt for TIPS-induced hepatic encephalopathy (HE).

Patients were reviewed retrospectively using propensity score matching (1:1) and divided into 6-mm and 8-mm shunt groups based on shunt diameter. The stent patency, HE incidence, and rebleeding rate between the two groups were then compared.

From January 2018 to June 2021, both 6-mm shunt group and 8-mm shunt group included 58 patients. The 6-mm shunt group had significantly smaller liver volumes (879.3 ± 237.1 vs. 1008.8 ± 293.0; p = 0.010), and the median stent patency times were 30.7 and 33.8 months in the 6-mm and 8-mm groups, respectively (p = 0.124). No statistically significant difference was found between the two groups in the 1-year (8.6% vs. 3.4%; p = 0.242) and 2-year (17.2% vs. 12.1%; p = 0.242) rebleeding rates. The 1-year cumulative incidences of overt HE were 12.1% and 27.6% in the 6-mm and 8-mm groups, respectively (p = 0.040), and the 2-year cumulative overt HE incidences in these groups were 19.0% and 36.2%, respectively (p = 0.038). Notably, patients with a 6-mm shunt also experienced less hepatic impairment.

For patients with variceal bleeding and a small liver volume, the 6-mm shunt significantly reduced the incidence of overt HE, protected perioperative liver function, and did not affect stent patency or rebleeding rate.

For patients with variceal bleeding with small liver volume, the 6-mm transjugular intrahepatic portosystemic shunt (TIPS) significantly reduced the incidence of overt hepatic encephalopathy after TIPS, protected perioperative liver function, and did not affect stent patency and rebleeding rate.

• A strategy for the creation of a 6-mm transjugular intrahepatic portosystemic shunt for patients with variceal bleeding and a small liver volume was proposed. • The 6-mm transjugular intrahepatic portosystemic shunt significantly reduced the incidence of overt hepatic encephalopathy. • The 6-mm transjugular intrahepatic portosystemic shunt did not affect stent patency or rebleeding rate.

This meta-analysis was designed to evaluate the clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) conducted utilizing stents of different diameters, thus providing recommendations for more logical selections of covered stents for patients with portal hypertension, in particular for the Asian population.

Web of Science, PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure and Wan Fang were searched for randomized controlled trials and cohort studies from inception until February 2023. The meta-analysis was carried out using Revman 5.4 Software. Heterogeneity between researches was assessed by the χ2 test and I2 index. The outcomes evaluated were the incidence of post-TIPS hepatic encephalopathy (HE), variceal rebleeding, shunt dysfunction, 1-year overall survival and decrease in portal pressure gradient (PPG).

Eight appropriate clinical trials with 1246 patients were selected (638 and 608 patients in the experimental and control groups, respectively). In regards to preoperative PPG reduction, there was no discernible difference between the two groups [mean difference = 1.15, 95% confidence interval (CI) = -0.29-2.58, P = 0.12]. The rate of post-TIPS HE was significantly higher in patients in the 8 mm stent group than in the 6-7 mm stent group [odds ratio (OR) = 0.54, 95% CI = 0.42-0.70, P < 0.00001, I2 = 46%]. There were no significant differences in the rates of variceal rebleeding (OR = 1.05, 95% CI = 0.67-1.65, P = 0.84, I2 = 0%), shunt dysfunction (OR = 0.88, 95% CI = 0.53-1.47, P = 0.64, I2 = 0%) and 1-year overall survival (OR = 0.86, 95% CI = 0.50-1.50, P = 0.61, I2 = 0%).

Asian populations with portal hypertension may benefit more from TIPS with 6-7 mm covered stents because they can reduce the risk of postoperative HE while offering similar efficacy when compared to 8 mm covered stents.

Cirrhosis is a chronic disease characterized by chronic liver inflammation and diffuse fibrosis. A combination of vasoactive drugs, preventive antibiotics, and endoscopy is the recommended standard treatment for patients with acute variceal bleeding; however, this has been challenged. We compared the effects of early transjugular intrahepatic portosystemic shunt (TIPS), non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding.

The present network meta-analysis was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Assessing the methodological quality of systematic reviews guidelines. The review has been registered with the International Prospective Register of Systematic Reviews. The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and World Health Organization-approved trial registry databases were searched for randomized controlled trials (RCTs) evaluating early TIPS, non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding.

Twenty-four RCTs (1894 patients) were included in the review. Compared with standard treatment, early TIPS [odds ratio (OR), 0.53; 95% credible interval (Cr), 0.30-0.94; surface under the cumulative ranking curve (SUCRA), 98.3] had a lower risk of all-cause mortality (moderate-to-high-quality evidence), and early TIPS (OR, 0.19; 95% CrI, 0.11-0.28; SUCRA, 98.2) and non-early TIPS (OR, 0.30; 95% CrI, 0.23-0.42; SUCRA, 1.8) were associated with a lower risk of rebleeding (moderate-to-high-quality evidence). Early TIPS was not associated with a reduced risk of hepatic encephalopathy, and non-early TIPS (OR, 2.78; 95% CrI, 1.89-4.23, SUCRA, 0) was associated with an increased incidence of hepatic encephalopathy (moderate-to-high-quality evidence). There was no difference in the incidence of new or worsening ascites (moderate-to-high-quality evidence) among the three interventions.

Based on the moderate-to-high quality evidence presented in this study, early TIPS placement was associated with reduced all-cause mortality [with a median follow-up of 1.9 years (25th-75th percentile range 1.9-2.3 years)] and rebleeding compared to standard treatment and non-early TIPS. Although early TIPS and standard treatment had a comparable incidence of hepatic encephalopathy, early TIPS showed superiority over non-early TIPS in this aspect. Recent studies have also shown promising results in controlling TIPS-related hepatic encephalopathy. However, it is important to consider individual patient characteristics and weigh the potential benefits against the risks associated with early TIPS. Therefore, we recommend that clinicians carefully evaluate the patient's condition, considering factors such as severity of variceal bleeding, underlying liver disease, and overall clinical status, before making a treatment decision. Further well-designed RCTs comparing early TIPS with non-early TIPS are needed to validate these findings and provide more definitive guidance.

The association between the presence of sarcopenia in patients with cirrhosis and the onset of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) is yet to be established. We conducted a systematic review and meta-analysis to provide a thorough summary of the available evidence on this association.

A thorough search of the literature was performed in the PubMed, EMBASE, and Web of Science databases. The protocol was duly registered on PROSPERO (CRD42023398856). The hazard ratio (HR) and corresponding 95% confidence intervals (CIs) for the occurrence of HE after TIPS were extracted from studies comparing cirrhotic patients with and without sarcopenia. These data were then combined using a random-effect model.

A total of 1135 patients from seven cohort studies that met our eligibility criteria were included in the meta-analysis. Our findings indicate a significantly higher risk of post-TIPS HE among cirrhotic patients with sarcopenia compared to those without sarcopenia (HR, 2.35; 95% CIs 1.32-4.19; p = 0.004; I2 = 75%). The findings remained consistent across subgroups stratified by liver disease etiology, study location, and severity of hepatic dysfunction.

The study demonstrated that sarcopenia was strongly linked to an increased likelihood post-TIPS HE among cirrhotic patients.

Transjugular intrahepatic portosystemic shunt (TIPS) creation is effective in treating the sequelae of decompensated liver cirrhosis-including medically refractory ascites and variceal bleeding-by decompressing the portal venous system through a manmade portosystemic conduit within the liver. However, the altered physiology in which splenomesenteric blood bypasses intrahepatic portal venous perfusion can precipitate varying degrees of hepatic encephalopathy (HE). While the majority of post-TIPS HE cases can be treated medically, some require escalated management strategies, including endovascular interventions to modify the indwelling TIPS and/or occlude competitive physiologic spontaneous portosystemic shunts. This review article details the epidemiology, risk factors, diagnosis, classification, and treatment of post-TIPS HE.

In light of the global rise in the burden of chronic liver diseases and liver cirrhosis, the number of patients suffering from decompensation events is expected to increase. Transjugular intrahepatic portosystemic shunts (TIPSS) provide effective long-term symptom control and may prolong transplant-free survival in portal hypertension-driven recurrent ascites and variceal bleeding. New-onset or recurrent hepatic encephalopathy (HE) after TIPSS insertion (post-TIPSS HE) represents the most severe post-interventional complication.

To provide insight into the epidemiology and risk factors for post-TIPSS HE and scrutinize the current state of the art in treatment and drug therapy options.

We conducted a literature search on post-TIPSS HE in patients with liver cirrhosis.

Post-TIPSS HE occurs in up to 54.5% of cases and particularly early recurrent HE is associated with a dismal prognosis. In recent years, several risk factors for the development of post-TIPSS HE have been identified. These include not only parameters reflecting liver function (model for end-stage liver disease score/Child-Pugh score) as well as cognitive dysfunction caused by minimal HE but also extrahepatic factors such as sarcopenia and common medications such as proton pump inhibitors. In addition, new data on the benefit of rifaximin and of smaller stent grafts emerged and may improve the prevention of post-TIPSS HE.

Careful selection of TIPSS candidates is of utmost importance to reduce the risk of post-TIPSS HE. In this narrative review, we provide a concise overview of the current epidemiology and risk factors of the treatment options for post-TIPSS HE.

Overt hepatic encephalopathy (HE) is a major complication of transjugular intrahepatic portosystemic shunt (TIPS). This study aimed to develop and validate prognostic models to identify patients at different risks of overt HE within 3 months after TIPS.

Two cohorts of patients with cirrhosis undergoing TIPS insertion were retrospectively included. In the derivation cohort of 276 patients, 3 models were established in increasing order of complexity: core model (age + Child-Pugh class), sarcopenia model (core model + sarcopenia), and full model (sarcopenia model + post-TIPS portal pressure gradient). All models were internally validated for discrimination and calibration and externally validated in an independent cohort of 182 patients.

During a 3-month follow-up period, 61 (22.1%) and 33 patients (18.1%) developed overt HE in the derivation and validation cohort, and sarcopenia was associated with increased risk of the outcome. In the derivation cohort, the core model showed a c-statistic of 0.68 (95% confidence interval [CI] 0.61-0.75), and discrimination improved in the sarcopenia model (c-statistic 0.73; 95% CI 0.66-0.80). The full model that extended the core model with inclusion of sarcopenia and post-TIPS portal pressure gradient showed a significant improvement in discriminative ability (0.77; 95% CI 0.71-0.83; P = 0.001). Both sarcopenia and full model yielded comparable performances in the validation cohort.

We developed and externally validated 2 prediction models applied before (sarcopenia model) and after TIPS (full model) to estimate the risk of post-TIPS overt HE. These tools could aid to select appropriate candidates for TIPS and guide postoperative management.

The Viatorr Controlled Expansion (VCX) stent-graft was designed to mitigate hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation.

To determine the incidence and degree of HE after VCX TIPS.

Thirty-three patients (M:F 17:16, mean age 58 years, mean MELD score 12) who underwent VCX TIPS between 2018 and 2019 were retrospectively studied. 11/33 (33%) patients had medically controlled pre-TIPS HE. TIPS indications included variceal hemorrhage (n = 12, 30%) and ascites (n = 21, 70%). Measured outcomes were post-TIPS HE (overall, recurrent, de novo) graded using the West Haven system, time-to-HE occurrence, HE-related hospitalization rate, and TIPS reduction rate.

VCX TIPS were 8 mm in 28/33 (85%) and 10 mm in 5/33 (15%). Mean final portosystemic pressure gradient was 6 mmHg. Cumulative HE incidence post-TIPS was 61% (20/33). 1-, 3-, 6-, and 12-month HE rates were 24%, 30%, 53%, and 61% over 247-day median follow-up. Median time-to-HE was 180 days. HE grades spanned grade 1 (n = 6), grade 2 (n = 8), and grade 3 (n = 6); 9 and 11 cases were recurrent and de novo HE, respectively. Medication non-compliance/infection was implicated in HE in 9/20 (45%) cases. Medical therapy addressed HE in 18/20 (90%) cases; however, HE still resulted in 39 hospitalizations among 13 patients, and median time to first hospitalization was 75 days. Shunt reduction was necessary in 2 (10%) cases of medically refractory HE.

The incidence of HE after VCX TIPS is high. Though HE symptoms may be medically controlled, hospitalization rates are high, and shunt reduction may be necessary.

Transjugular intrahepatic portosystemic shunt (TIPS) is created between a hepatic vein (HV) and the portal vein (PV) to alleviate the symptoms of portal hypertension. Despite high procedural success rates, a myriad of complications may occur at every step of TIPS creation. These complications may be attributable to the procedure itself or the shunt. Portal vein puncture is the most challenging and rate-limiting step, with extrahepatic portal vein puncture being the most devastating tabletop complication. Hepatic encephalopathy is the most common shunt-related complication after TIPS. Unlike bare metallic stents, covered stents have a longer patency rate and lower incidence of TIPS dysfunction. Most of the TIPS dysfunction that occurs with stent-grafts is due to technical errors and mechanical factors. TIPS revision often requires a combination of angioplasty, mechanical thrombectomy, and thrombolytics with a need for additional stenting in some cases. This review article focuses on procedure and shunt-related complications, as well as preventive and management strategies.

Transjugular intrahepatic portosystemic shunt (TIPS) is suggested as the salvage therapy for gastroesophageal variceal bleeding in cirrhosis. However, rebleeding might occur in some patients after TIPS. Currently, there is a lack of evidence in the endoscopic management of recurrent bleeding in these patients.

To evaluate the efficacy of endoscopic treatment in cirrhotic patients with recurrent bleeding after TIPS.

Cirrhotic patients with gastroesophageal varices who received endoscopic treatment for recurrent bleeding after TIPS were included.

6 patients were enrolled in this study. The median age of the patients was 47 years (range 27 to 65 years), and the duration of follow-up time was 346 (17-773) days. Stent stenosis or occlusion was found in 5 out of 6 patients after TIPS. Salvage endoscopic treatment, including esophageal variceal ligation (EVL), gastric variceal cyanoacrylate injection, esophageal variceal sclerotherapy, and balloon-occluded retrograde transvenous obliteration- (BRTO-) assisted endoscopic cyanoacrylate injection. Among included patients, 2 died shortly after EVL (14 and 19 days) due to variceal bleeding. Among other 4 patients, 2 had rebleeding episodes at 422 and 789 days, respectively.

Endoscopic treatment may be an option for recurrent bleeding after TIPS in selected patients. Further studies are needed to carefully define the indication and efficacy of this option.

Complications of portal hypertension such as gastroesophageal variceal hemorrhage, ascites, and spontaneous bacterial peritonitis, as well as pulmonary complications, are often responsible for diminished quality of life, excess morbidity and mortality, increased health care resource use and expenditure, and dropout from the liver transplant (LT) waiting list. Therefore, the care of LT candidates on the waiting list must be centered on anticipation and prompt intervention for these complications.

The purpose of this study was to make a systematic review and meta-analysis to determine the stent diameter (8mm vs. 10mm) that conveys better safety and clinical efficacy for transjugular intrahepatic portosystemic shunt (TIPS).

Four databases were used to identify clinical trials published from inception until March 2020. Data were extracted to estimate and compare one-year and three-year overall survivals, hepatic encephalopathy, variceal rebleeding, and shunt dysfunction rates between patients with 8mm covered stents and those with 10mm covered stents.

Five eligible studies were selected, which included 489 patients (316 men, 173 women). The 8mm covered stent group had higher efficacy regarding one-year or three-year overall survival (odds ratio [OR], 2.88; P=0.003) and (OR, 1.81; P=0.04) and lower hepatic encephalopathy (OR, 0.69; P=0.04) compared with 10mm covered stent group. There were no significant differences in variceal rebleeding rate (OR 0.80; P=0.67). However, shunt dysfunction was lower in 10mm covered stent group (OR, 2.26; P=0.003).

Our results suggest that the use of 8mm covered stents should be preferred to that of 10mm covered stents for TIPS placement when portal pressure is frequently monitored.

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment tool in decompensated liver cirrhosis that has been shown to prolong transplant-free survival. Hepatic encephalopathy (HE) is a frequent complication of decompensated cirrhosis, eventually induced and/or aggravated by TIPS, that remains a clinical challenge especially in these patients. Therefore, patient selection for TIPS requires careful assessment of risk factors for HE. TIPS procedural parameters regarding stent size and invasive portosystemic pressure gradient measurements thereby have an important role. Endovascular shunt modification, in combination with a conservative medical approach, often results in a significant reduction of symptoms. This review summarizes HE molecular mechanisms and pathophysiology as well as diagnostic and therapeutic approaches targeting shunt-induced HE.

Portal hypertension is the main consequence of liver cirrhosis, leading to severe complications such as variceal hemorrhage, ascites or hepatic encephalopathy. As an attempt to decompress the portal venous system, portal flow is derived into the systemic venous system through spontaneous portosystemic shunts (SPSSs), bypassing the liver. In this review, we aim to provide an overview of the published reports in relation to the prevalence and physiopathology behind the appearance of SPSS in liver cirrhosis, as well as the complications derived from its formation and its management. The role of SPSS embolization is specifically discussed, as SPSSs have been assessed as a therapeutic target, mainly for patients with recurrent/persistent hepatic encephalopathy and preserved liver function. Furthermore, different aspects of the role of SPSS in liver transplantation, as well as in candidates for transjugular intrahepatic portosystemic shunt are reviewed. In these settings, SPSS occlusion has been proposed to minimize possible deleterious effects, but results are so far inconclusive.

To identify clinical variables, including use of newer Viatorr TIPS endoprosthesis with controlled expansion (VCX) that may affect the occurrence and risk of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt (TIPS) creation.

A total of 376 patients who underwent TIPS creation at our institution between 2003 and 2018 were retrospectively identified. Of these patients, 71 received a Viatorr controlled expansion endoprosthesis and 305 received a Viatorr TIPS endoprosthesis (older version without controlled expansion). Multivariate regression analysis was used to identify factors predicting the occurrence of hepatic encephalopathy after TIPS creation; a Cox proportional hazard model was used to assess risk of HE through time to HE onset RESULTS: A total of 194 patients (52%) developed hepatic encephalopathy after TIPS creation, including 28 of 71 patients (39%) who received a VCX endoprosthesis. Older patient age and the use of Viatorr endoprosthesis without controlled expansion were significantly associated with the development of hepatic encephalopathy overall. Pre-TIPS pressure variables, patient age, plasma international normalized ratio, and model for end-stage liver disease score were risk factors for time to hepatic encephalopathy.

Several variables are mild predictors of early hepatic encephalopathy development after TIPS creation, and the use of VCX endoprosthesis in TIPS creation is associated with a modest lower risk of hepatic encephalopathy. These preliminary findings should be considered in regard to patient selection, endoprosthesis selection, and post-transjugular intrahepatic portosystemic shunt creation monitoring for the development of hepatic encephalopathy.

Placement of a transjugular intrahepatic portosystemic shunt (TIPS) is a relatively common procedure used to treat complications of portal hypertension. However, only limited data exist regarding the hospital-readmission rate after TIPS placement and no studies have addressed the causes of hospital readmission. We therefore sought to identify the 30-day hospital-readmission rate after TIPS placement at our institution and to determine potential causes and predictors of readmission.

We reviewed our electronic medical-records system at our institution between 2004 and 2017 to identify patients who had undergone primary TIPS placement with polytetrafluoroethylene-covered stents and to determine the 30-day readmission rate among these patients. A series of univariable logistic-regression models were fit to assess potential predictors of 30-day readmission.

A total of 566 patients were included in the analysis. The 30-day readmission rate after TIPS placement was 36%. The most common causes for readmission were confusion (48%), infection (15%), bleeding (11%), and fluid overload (7%). A higher Model for End-Stage Liver Disease (MELD) score corresponded with a higher rate of readmission (odds ratio associated with each 1-unit increase in MELD score: 1.06; 95% confidence interval: 1.02-1.09; P = 0.001). Other potential predictors, including indication for TIPS placement, were not significantly associated with a higher readmission rate.

The 30-day readmission rate after TIPS placement with covered stents is high, with nearly half of these readmissions due to hepatic encephalopathy-a known complication of TIPS placement. Novel interventions to help reduce the TIPS readmission rate should be prioritized in future research.

Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with cirrhosis. The impact of HE on the health care system is similarly profound. The number of hospital admissions for HE has increased in the last 10-year period. HE is a huge burden to the patients, care givers, and the health care system. HE represents a "revolving door" with readmission, severely affects care givers, and has effects on cognition that can persists after liver transplant. This article reviews the current literature to discuss the challenges and diagnostic and therapeutic approaches to HE.

The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists' consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy (HE) including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications in cirrhosis. Spontaneous portosystemic shunts (SPSSs) may increase the risk of post-TIPS complications and mortality. This study was done to evaluate the safety and efficacy of TIPS for treating variceal bleeding between patients with and without SPSSs.

The clinical data of 467 consecutive patients with cirrhosis who received TIPS for variceal bleeding from January 2012 to January 2018 were screened. A total of 33 patients with coexisting SPSSs were included as the SPSS group, and 33 patients without SPSSs were randomly selected as control. The procedure-related complications and long-term outcomes were compared between the two groups.

Both groups were successfully treated with TIPS. SPSSs were antegradely embolized before TIPS placement. In terms of safety, one patient in the SPSS group experienced an asymptomatic pulmonary embolism, and another patient experienced serious gastric ulcer bleeding. Overall, 23 (70.0%) patients in the SPSS group and 16 (51.5%) patients in the control group experienced different mild complications (P=0.131). During a median follow-up of more than 2 years, the rebleeding rates (7.1 vs. 3.7% at 1 year, P=0.508), overt hepatic encephalopathy occurrence rates (34.4 vs. 39.4% at 2 years, P=0.685), and orthotopic liver transplantation-free survival rates (73.2 vs. 70.7% at 2 years, P=0.557) were not significantly different between the two groups.

TIPS combined with antegrade embolization is safe, effective, and feasible for patients with SPSSs, with safety and long-term outcomes comparable to patients without SPSSs.

To investigate the role of early overt hepatic encephalopathy (OHE) as a clinical marker of prognosis in cirrhosis with a transjugular intrahepatic portosystemic shunt (TIPS) and to assess the relationship between recurrence of OHE and survival after TIPS.

From January 2012 to December 2013, a retrospective study of consecutive patients with cirrhosis and a TIPS was performed at a single institution. A total of 304 patients (196 males; mean age, 52 years) were enrolled during the study period. The mean Model for End-Stage Liver Disease (MELD) score was 11.6. Time-dependent Cox regression was applied to estimate the predictive ability of early OHE (within 3 months after TIPS) and the effect of its frequency on survival.

During a median follow-up of 28.3 months, 115 patients experienced OHE after the TIPS procedure; of these, 54 had at least 2 OHE episodes. Long-term survival worsened in patients with early OHE (hazard ratio [HR] = 2.75; 95% confidence interval [CI]: 1.75-4.32; P < .001). When early OHE was further divided into early-recurrent and single OHE, death was more common in patients with early-recurrent OHE (P < .001) than in patients with early-single OHE (P = .24). After adjustment by MELD score, ascites, serum albumin, indication for TIPS, and age, patients with early-recurrent OHE had a lower probability of survival (HR = 2.91; 95% CI: 1.04-4.89; P < .001). Furthermore, landmark and propensity score analyses confirmed the predictive value of early-recurrent OHE.

Early recurrence of OHE was associated with an increased risk of mortality for patients with cirrhosis who underwent TIPS.

Hepatic Encephalopathy (HE) is a neuropsychiatric syndrome that occurs in up to 30% of patients with cirrhosis. HE may be a consequence of pure liver failure, as in patients with fulminant hepatitis, or of the combination of liver failure and portal-systemic shunting, as in patients with liver cirrhosis. Several clinical and pathophysiologic observations suggest the importance of portal-systemic shunts in the development of HE. Episodes of HE are usually related to precipitating events, such as infections or gastrointestinal bleeding; a minority of cirrhotic patients experienced a chronic HE, refractory to standard medical treatment. This latter type of HE should be related to spontaneous or radiological (such as Transjugular Intrahepatic Portosystemic Shunt (TIPS)) portal systemic shunts, that could be restricted or occluded in patients with chronic HE. Both TIPS reduction and shunt occlusion are radiological procedures, safe and effective to ameliorate neurological symptoms in patients with refractory HE.

Whether pre-existing nonvariceal spontaneous portosystemic shunts (SPSSs) in cirrhotic patients affect outcomes after transjugular intrahepatic portosystemic shunt (TIPS) and whether they need to be closed remains unclear.

To assess the effects of the presence or embolization of SPSSs on outcomes after TIPS for cirrhosis.

From January 2004 to December 2014, 903 consecutive cirrhotic patients who underwent TIPS in a tertiary-care center were included, of which 715 patients had no SPSS (N-SPSS group), 144 patients had an SPSS without embolization (SPSS group), and 44 had an SPSS with embolization (SPSS + E group).

During a median follow-up period of 27.7 months, 368 (41%) patients experienced overt hepatic encephalopathy (OHE), 256 (28%) experienced clinical relapse, 164 (18%) developed shunt dysfunction, and 379 (42%) died. The SPSS group had a higher risk of OHE compared with the N-SPSS and SPSS + E groups (adjusted HR [95%CI]: N-SPSS vs SPSS vs SPSS + E: 1 vs 1.36 [1.06-1.75] vs 0.77 [0.46-1.29]; p = 0.027). In stratification analysis, a higher risk of OHE was only observed in patients with a large SPSS (SPSS diameter ≥6 mm) but not a small SPSS. Additionally, SPSS embolization was associated with a lower risk of OHE among patients with a large SPSS (adjust HR = 0.51; 95% CI: 0.29-0.91; p = 0.034). The risks of clinical relapse (p = 0.584), shunt dysfunction (p = 0.267), and mortality (p = 0.4743) did not significantly differ among groups.

Among cirrhotic patients undergoing TIPS, a pre-existing large SPSS was associated with a higher risk of OHE, which could be decreased by SPSS embolization. There was no clear association between the presence/embolization of an SPSS and post-TIPS clinical relapse, shunt dysfunction or mortality.

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

Treatment with proton pump inhibitors (PPIs) has been associated with development of hepatic encephalopathy (HE). As development of HE is a major complication after implantation of a transjugular intrahepatic portosystemic shunt (TIPS), we hypothesized that PPI treatment may be associated with a higher risk of post-TIPS HE.

We analyzed data of 397 patients with liver cirrhosis who received de novo TIPS implantation at the University Medical Center Freiburg, Germany. We assessed whether PPI medication and other patient characteristics are predictive factors for the development of post-TIPS HE.

Patients with PPI treatment at the time of TIPS implantation showed significantly higher rates of post-TIPS HE than those without PPI medication (30.4% vs 11.7%, p < 0.001). The rate of post-TIPS HE increased in a dose-dependent manner. However, PPI medication did not directly affect transplant-free survival. Remarkably, in 59.1% of patients who received PPIs there was no clear indication.

PPI treatment may be an independent risk factor for the development of post-TIPS HE and the risk increases with PPI dose. Indication for PPI treatment should be assessed carefully prior to TIPS implantation in patients with liver cirrhosis.

the aim of the study was to describe our 20-year experience with transjugular intrahepatic portosystemic shunt (TIPSS) procedures for children with resistant portal hypertension (PHTN).

Retrospective review of all children that had a TIPSS performed at Birmingham Children's Hospital from January 1, 1995 to January 1, 2015.

Forty children underwent 42 attempted TIPSS for resistant PHTN with recurrent variceal bleeding (n = 35), refractory ascites (n = 4), and hypersplenism (n = 1). Median age at operation was 12 years (range 7 months-17 years). Thirty-four procedures were elective and 8 were emergency cases. TIPSS was established in 33 cases (79%). Median portal venous pressure reduction was 10 mmHg. Variceal bleeding ceased in 27 (96%) and ascites improved in all. Clinical improvement following TIPSS enabled 7 children to be bridged to transplantation and 7 others to become suitable for transplantation. The 1-year and 5-year survival with TIPSS was 57% and 35%, respectively. Child-Pugh score C was an independent risk factor for adverse outcome (Likelihood ratio (LR) = 8.0; 95% confidence interval (CI) 2.7 to 23.5; P = 0.001). There were 6 major complications: hepatic artery thrombosis and infarction (n = 1), hepatic artery pseudoaneurysm (n = 1), bile leak (n = 1), and hepatic encephalopathy (n = 3). Encephalopathy was resistant to medical treatment in 2 cases, necessitating staged closure in 1. Ten patients (30%) required intervention to maintain TIPSS patency. The 1-year and 5-year freedom from reintervention was 71% and 55%, respectively.

A TIPSS is highly successful in controlling symptoms in children with resistant PHTN and facilitating liver transplantation. It is technically demanding and not without risk. Patients must be appropriately selected and counselled.

Post-TIPS hepatic encephalopathy (PSE) is a complex process involving numerous risk factors; the root cause is unclear, but an elevation of blood ammonia due to portosystemic shunt and metabolic disorders in hepatocytes has been proposed as an important risk factor.

The aim of this study was to investigate the impact of pathological features of mitochondrial ultrastructure on PSE via transjugular liver biopsy at TIPS implantation.

We evaluated the pathological damage of mitochondrial ultrastructure on recruited patients by the Flameng classification system. A score ≤2 (no or low damage) was defined as group A, and a score >2 (high damage level) was defined as group B; routine follow-up was required at 1 and 2 years; the incidence of PSE and multiple clinical data were recorded.

A total of 78 cases in group A and 42 in group B completed the study. The incidence of PSE after 1 and 2 years in group B (35.7% and 45.2%, respectively) was significantly higher than that in group A (16.7% and 24.4%, respectively); the 1- and 2-year OR (95% CI) were 2.778 (1.166-6.615) and 2.565 (1.155-5.696), respectively, for groups A and B. Importantly, group B had worse incidence of PSE than group A [P=0.014, hazard ratio (95%CI): 2.172 (1.190-4.678)].

Aggressive damage to mitochondrial ultrastructure in liver shunt predicts susceptibility to PSE. The registration number is NCT02540382.

Currently, there are no recommendations in guidelines concerning the preferred diameter of stents for transjugular intrahepatic portosystemic shunt (TIPS), owing to the lack of adequate evidence. We therefore compared 8mm stents with 10mm stents, to evaluate whether 8mm stents would achieve similar shunt function, with less hepatic encephalopathy (HE) and better liver function.

Cirrhotic patients were randomly assigned to receive TIPS with an 8mm or 10mm covered stent to prevent variceal rebleeding. The primary endpoint was shunt dysfunction. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival, their composite endpoint, overt HE (overall and spontaneous) and liver function were designated as the secondary endpoints.

From July 2012 to January 2014, 64 and 63 patients were allocated to the 8mm and 10mm groups, respectively. During a median follow-up of 27months in both arms, dysfunction rates (16% vs. 16% at two years, p=0.62), two-year rebleeding (16% vs. 17%, p=0.65), OLT-free survival (95% vs. 86%, p=0.37), and the composite endpoint (p=0.62) were not statistically different between the groups. Despite a marginal decrease in overall overt HE, there were significantly fewer spontaneous overt HE incidents in the 8mm group within two years (27% vs. 43%, p=0.03), with a risk reduction of 47%. Notably, patients receiving 8mm stents also developed less hepatic impairment.

TIPS with 8mm covered stents showed similar shunt function to TIPS with 10mm stents, but halved the risk of spontaneous overt HE and reduced hepatic impairment. Therefore, 8mm TIPS stents should be preferred for the prevention of variceal rebleeding in cirrhotic patients. Lay summary: The optimal diameter for transjugular intrahepatic portosystemic shunt (TIPS) remained uncertain. This study showed that TIPS with 8mm covered stents did not compromise shunt patency, or influence the efficacy of variceal rebleeding prevention compared to TIPS with 10mm stents, but reduced the risk of spontaneous overt hepatic encephalopathy and the incidence of severe encephalopathy. Moreover, liver function reserve was also better in the 8mm stents group, suggesting that 8mm TIPS stents should be preferred for the prevention of variceal rebleeding in cirrhotic patients.

To evaluate hepatic encephalopathy (HE) incidence after transjugular intrahepatic portosystemic shunt (TIPS) and classify by gravity and frequency.

This is a retrospective study of 75 patients with no previous episodes of HE who underwent TIPS between 2008 and 2014 with clinical follow-up after 6 and 12 months. Patient risk factors evaluated include age, INR (international normalized ratio), creatinine, bilirubin, and MELD score (Model for End-of-stage Liver Disease). HE was reported using two classifications: (1) gravity divided in moderate (West-Haven grades I-II) and severe (III-IV); (2) frequency divided in episodic and recurrent/persistent.

Overall HE incidence was 36% at 6 months, with 12 month incidence significantly decreased to 27% (p = 0.02). 13/75 (17%) patients had one episode of moderate HE, while 3/75 (4%) patients had severe recurrent/persistent HE. Age was the only pre-TIPS risk predictor. Post-TIPS bilirubin and INR showed variations from basal values only in the presence of diagnosed HE. Bilirubin significantly increased (p = 0.03) in correlation to HE severity, whereas INR changes correlated with temporal frequency (p = 0.04). HE distribution classified for severity is similar at 6 and 12 months, whereas when classified for frequency shows significant differences (p = 0.04).

A classification by gravity and frequency attests post-TIPS HE as a manageable risk. Monitoring of bilirubin and INR may help on clinical management risk stratification.

The hepatic venous pressure gradient (HVPG) could be used to stratify patients in different risk groups. No studies have reported the role of transjugular intrahepatic portosystemic shunt (TIPS) placement in a subgroup of patients with a high HVPG (≥20 mmHg) for secondary prophylaxis of variceal bleeding. This study was designed to evaluate the benefit of TIPS in cirrhotic patients with a high HVPG (≥20 mmHg) for rebleeding and survival.

We included 46 cirrhotic patients with a history of variceal bleeding and a high HVPG (≥20 mmHg) admitted to our hospital between January 2013 and June 2014 (TIPS group). Patients were matched by Child-Pugh scores to patients in our historical cohort hospitalized for prophylaxis of variceal rebleeding between April 2011 and December 2012 (propranolol + EVL group). The end points included time to significant rebleeding from portal hypertensive sources, 1-year survival, and time to the occurrence of hepatic encephalopathy (HE).

The 1-year actuarial probability of remaining free of variceal rebleeding was significantly higher in the TIPS group than in the propranolol + EVL group (85% vs. 54%, p = 0.01). The 1-year survival rates were not different between the two groups (85% vs. 89%, p = 0.591). The 1-year actuarial probability of remaining free of HE was significantly lower in the TIPS group than in the propranolol + EVL group (67% vs. 91%, p = 0.003).

TIPS was more effective than propranolol + EVL in preventing variceal rebleeding in cirrhotic patients with a high HVPG (≥20 mmHg). During the limited follow-up, survival was similar in the two groups.

Recent non-cirrhotic and non-malignant splanchnic vein thrombosis is now defined as extrahepatic portal vein thrombosis with or without involvement of the mesenteric vein according to the Baveno VI consensus from 2015. An early diagnosis is often challenging due to unspecific symptoms with abdominal pain or diarrhea but extremely important because of the potential acute and chronic complications, such as mesenteric ischemia and portal hypertension; therefore, rapid treatment is crucial. We present two cases of severe splanchnic vein thrombosis, which were treated with catheter-directed local thrombolysis and thrombus aspiration. These minimally invasive catheter-directed techniques have recently been successfully used in selected patients. A review of the literature is provided in this article. In summary, the management of splanchnic vein thrombosis must be individually planned for each patient and should be performed at experienced centers, which can provide all therapeutic options. In selected cases with the correct indications transjugular transhepatic catheter-directed local thrombolysis is a safe option with a good outcome.