post-TIPS 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.

Post-Transjugular Intrahepatic Portosystemic Shunt (TIPS) Hepatic Encephalopathy-A Review of the Past Decade's Literature Focusing on Incidence, Risk Factors, and Prophylaxis.

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for portal hypertension and its' complications in liver cirrhosis, yet the development of hepatic encephalopathy (HE) remains a significant concern. This review covers the reported incidence, risk factors, and management strategies for post-TIPS HE over the past decade. Incidence varies widely (7-61%), with factors like age, liver function, hyponatremia, and spontaneous portosystemic shunts influencing risk. Procedural aspects, including TIPS timing, indication, and stent characteristics, also contribute. Pharmacological prophylaxis with lactulose and rifaximin shows promise, but current evidence is inconclusive. Procedural preventive measures, such as shunt embolization and monitoring portal pressure gradients, are explored. Treatment involves pharmacological options like lactulose and rifaximin, and procedural interventions like stent diameter reduction. Ongoing studies on novel predictive markers and emerging treatments, such as faecal microbiota transplant, reflect the evolving landscape in post-TIPS HE management. This concise review provides clinicians with insights into the multifaceted nature of post-TIPS HE, aiding in improved risk assessment, prophylaxis, and management for patients undergoing TIPS procedures.

Effectiveness and prognosis of covered stents with different diameters in transjugular intrahepatic portosystemic shunt: a meta-analysis.

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.

Prediction of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt Based on CT Radiomic Features of Visceral Adipose Tissue

To evaluate the performance and clinical utility of CT radiomic features of visceral adipose tissue (VAT) in the prediction of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS). This multi-center study was retrospectively designed. Patients with cirrhosis who underwent TIPS were recruited from January 2015 to December 2020. Pre-TIPS contrast-enhanced CT images were collected for VAT segmentation and radiomic feature extraction. Least absolute shrinkage and selection operator regression with ten-fold cross-validation was performed to reduce dimension. Logistic regression with regularization, support vector machine, and random forest were used for model construction. A total of 130 patients (90 men; mean age, 54±11 years) were finally enrolled. The cohort was split into 85 patients for the training set (58 men; mean age, 53±12 years) with 19 HE, 21 patients for the internal test set (17 men; mean age, 53±11 years) with 5 HE, and 24 patients for the external test set (15 men; mean age, 55±11 years). Ten radiomic features and C-reactive protein constituted radiomic-clinical models with the best performance. The average area under the receiver operating characteristic curve is 0.97 in the training set and 0.84 in the test sets. For a fixed sensitivity of 0.90, the specificity and negative predictive value of the model is 0.63 and 1.00, respectively; while for a fixed specificity of 0.90, the sensitivity and positive predictive value is 0.60 and 0.75, respectively. Machine learning models based on CT radiomic features extracted from VAT can predict post-TIPS HE with satisfactory performance. Our machine learning models based on CT radiomic features of visceral adipose tissue in patients with cirrhosis may assist in predicting hepatic encephalopathy after transjugular intrahepatic portosystemic shunt, indicating its potential in patient selection and clinical decision-making. Radiomics of visceral adipose tissue provide great help in predicting hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. The clinical-radiomic models showed satisfactory performance with an average area under the receiver operating characteristic curve of 0.84. The model can hypothetically provide 90% sensitivity and 100% negative predictive value for guiding patients who are considering transjugular intrahepatic portosystemic shunt.

Hepatic encephalopathy with proton pump inhibitor use in post tips patients: a systematic review and meta-analysis.

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.

Primary prevention of hepatic encephalopathy post-TIPS: A systematic review and meta-analysis.

Transjugular intrahepatic portosystemic shunt (TIPS) can be an effective treatment for cirrhotic patients who develop variceal bleeding and ascites. However, TIPS placement is associated with an increased risk of developing hepatic encephalopathy (HE). Recently, there have been efforts to use the typical medical therapies prophylactically in patients undergoing TIPS placement to prevent post-TIPS HE. We conducted literature searches in MEDLINE, Embase, CINAHL, Scopus, and Cochrane to examine studies that use prophylactic medical therapy for preventing post-TIPS HE. A narrative synthesis and grading of recommendations assessment assessment were done for all studies. Meta-analysis was performed for eligible studies using the Mantel-Haenszel method random-effects model. Nine hundred twenty-one articles were screened and 5 studies were included in the study after 2 levels of screening. The medications studied were rifaximin, lactulose, lactitol, L-Ornithine-L-aspartate (LOLA), albumin, and combination therapies. Narrative results showed that lactulose, lactitol, LOLA and albumin prophylaxis were not associated with reduction in HE occurrence or mortality. A combination of rifaximin and lactulose was found to be associated with lower occurrence of HE, and the results were not different when LOLA was added. Meta-analysis (n = 3) showed that rifaximin treatment was not associated with changes in HE occurrences. In conclusion, a vast majority of medications were not found to be effective post-TIPS HE prophylaxis when used alone. A rifaximin and lactulose combination therapy may be beneficial. Overall, there is significant limitation in the current data and more studies are needed to yield more robust meta-analysis results in the future.

TIPS: indications, Contraindications, and Evaluation.

This review summarizes the current and emerging indications, contraindications, and evaluation for TIPS. In the last three decades of use, there have been substantial changes and progress in this field, including the use of controlled-expansion, covered stents, which has broadened the clinical uses of TIPS. Recent findings have rapidly expanded the indications for TIPS, including emerging uses in hepatorenal syndrome, hepatopulmonary syndrome and before abdominal surgery. The widespread use of controlled-expansion, covered stents has decreased rates of post-TIPS hepatic encephalopathy, opening TIPS to a larger patient population. Overall, with newer stent technology and more research in this area, the clinical utility and potential of TIPS has rapidly expanded. Going forward, a renewed focus on randomized-control trials and long-term outcomes will be a crucial element to selecting appropriate TIPS recipients and recommending emerging indications for this procedure.

3D automatic liver and spleen assessment in predicting overt hepatic encephalopathy before TIPS: a multi-center study

BackgroundOvert hepatic encephalopathy (HE) should be predicted preoperatively to identify suitable candidates for transjugular intrahepatic portosystemic shunt (TIPS) instead of first-line treatment. This study aimed to construct a 3D assessment-based model to predict post-TIPS overt HE.MethodsIn this multi-center cohort study, 487 patients who underwent TIPS were subdivided into a training dataset (390 cases from three hospitals) and an external validation dataset (97 cases from another two hospitals). Candidate factors included clinical, vascular, and 2D and 3D data. Combining the least absolute shrinkage and operator method, support vector machine, and probability calibration by isotonic regression, we constructed four predictive models: clinical, 2D, 3D, and combined models. Their discrimination and calibration were compared to identify the optimal model, with subgroup analysis performed.ResultsThe 3D model showed better discrimination than did the 2D model (training: 0.719 vs. 0.691; validation: 0.730 vs. 0.622). The model combining clinical and 3D factors outperformed the clinical and 3D models (training: 0.802 vs. 0.735 vs. 0.719; validation: 0.816 vs. 0.723 vs. 0.730; all p < 0.050). Moreover, the combined model had the best calibration. The performance of the best model was not affected by the total bilirubin level, Child–Pugh score, ammonia level, or the indication for TIPS.Conclusion3D assessment of the liver and the spleen provided additional information to predict overt HE, improving the chance of TIPS for suitable patients. 3D assessment could also be used in similar studies related to cirrhosis.Graphical abstract

The Impact of Renal Function on Hepatic Encephalopathy Following TIPS Placement for Refractory Ascites.

The impact of renal function on hepatic encephalopathy (HE) following transjugular intrahepatic portosystemic shunt (TIPS) placement for refractory ascites is poorly understood. We investigated the role of renal function on HE following TIPS placement. A retrospective study was performed for patients undergoing TIPS for refractory ascites from 2007-2019. Patients were stratified by GFR at time of TIPS placement and by whether they were on hemodialysis (HD). Chronic kidney disease (CKD) stage 3 or higher was defined as pre-TIPS GFR < 60 for at least 3 months. Logistic regression analyses were used to identify the role of GFR and CKD at time of TIPS placement on HE within 60 days post TIPS placement. Among 201 TIPS patients for refractory ascites (61% male; mean age 59.1), 78 (39%) patients were in CKD, and 16 (21%) were on HD. Mean GFR at time of TIPS placement was 62.7 ± 28.2 for all non-HD patients (n = 185). Compared with the GFR ≥ 90 group, GFR < 30 or HD (OR, 3.56; 95%CI, 1.19-10.7; p = 0.023) and CKD (OR, 2.52; 95%CI, 1.40-4.53; p = 0.002) at time of TIPS placement were significant predictors of post-TIPS placement HE within 60 days. GFRs between 30-60 and 60-90 were not significant predictors. In TIPS patients for recurrent ascites, patients with acutely impaired renal function or chronic renal dysfunction were at an increased risk for HE after TIPS.

Predicting overt hepatic encephalopathy after TIPS: Value of three minimal hepatic encephalopathy tests

Hepatic encephalopathy (HE) is a frequent and severe complication in patients after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, risk factors for post-TIPS HE remain poorly defined. Minimal HE (mHE) is a well-known risk factor for overt HE in patients with cirrhosis without TIPS. We aimed to evaluate three tools frequently used for diagnosing mHE for their dynamic changes and their predictive value for overt HE after TIPS. We prospectively recruited 84 consecutive patients before TIPS insertion and monitored them for 180 days for post-TIPS HE. Before TIPS insertion, the patients underwent the portosystemic encephalopathy (PSE) syndrome test, the animal naming test (ANT), and the critical flicker frequency (CFF). Patients were retested after TIPS insertion. The majority of patients were male (67.9%), and the predominant indication for TIPS was refractory ascites (75%). Median age was 59 years, model for end-stage liver disease score was 12, and 66.3%, 64.6%, and 28.4% patients had evidence for mHE according to the PSE syndrome test, ANT, and CFF, respectively. Overall, 25 patients developed post-TIPS HE within 180 days after TIPS insertion. Post-TIPS incidence of overt HE was 22.2, 28.6, 45.5, and 55.6% in those with no, one, two, and three pathological tests at baseline, respectively. However, none of the three tests was significantly associated with post-TIPS HE. Of note, mean performance in all tests remained stable over time after TIPS insertion. PSE syndrome test, ANT and CFF, which are frequently used for diagnosing mHE have limited value for predicting HE after TIPS insertion. We could not find evidence that TIPS insertion leads to a psychometric decline in the long term. This prospective observational study compared three diagnostic tests for mHE and showed the limited value of these tests for predicting overt HE in patients with cirrhosis undergoing TIPS insertion. In addition, the results suggest that cognitive performance generally remains stable after TIPS insertion. These results are important for physicians and researchers involved in the management of patients with cirrhosis undergoing TIPS procedures. The study's findings serve as a starting point for further investigations on the development of more effective strategies for predicting and managing post-TIPS HE. ClinicalTrials.gov NCT04801290.

Nutritional status in hepatic encephalopathy and transjugular intrahepatic portosystemic shunt - TIPS, and strategies to improve the outcomes.

Hepatic encephalopathy (HE) is one of the most severe complications following transjugular intrahepatic portosystemic shunt (TIPS). The identification and treatment of risk factors associated with the development of this complication may reduce the incidence and severity of post-TIPS HE. Several studies have demonstrated that the nutritional status plays a major role in the outcome of the cirrhotic population, particularly those who are decompensated. Although scarce, there are also studies highlighting an association between poor nutritional status, sarcopenia, fragile status, and post-TIPS HE. If these data are confirmed, nutritional support could become a means for decreasing this complication, thereby enhancing the use of TIPs in the treatment of refractory ascites or variceal bleeding. In this review, we will discuss the pathogenesis of HE, the data that supports an association with sarcopenia, nutritional status and frailty and the implications that these conditions have on the use of TIPS in clinical practice.

Safety and Efficacy of Transjugular Intrahepatic Portosystemic Shunt for Non-tumoral Cirrhotic Portal Vein Thrombosis Not Responding to Anticoagulation Therapy.

To evaluate the feasibility, safety, and efficacy of add-on transjugular-intrahepatic-portosystemic shunt (TIPS) for portal vein recanalization (PVR) in cirrhotic patients with non-tumoral chronic portal vein thrombosis (PVT) after 6months of monitored anticoagulation therapy (ACT). We conducted a retrospective search of the hospital database for patients who underwent TIPS for persistent PVT despite 6months of ACT (January 2011 to August 2021). These patients were compared to control group (ACT group; no TIPS but continued on ACT). Post-TIPS periodic assessment was done to look for clinical outcome, PVR (using contrast-enhanced CT scan), and complications. A total of 90 patients were analyzed. Thirty-six patients in TIPS group and 54 patients in ACT group. TIPS was successfully performed in all patients. TIPS group showed complete recanalization of portal vein in 77.8%, partial recanalization in 16.7%, and stable thrombus in 5.5% of the patients. TIPS thrombosis was seen in 3 patients, all underwent successful endovascular thrombolysis. Seven patients developed post-TIPS hepatic encephalopathy and were managed conservatively. In contrast, no patient in ACT group achieved PVR on 12-month follow-up. After propensity score matching, patients in TIPS group showed significantly lower incidence of variceal re-bleeding (22.2% vs. 77.8%, p = 0.03) and refractory ascites (11.1% vs. 51.9%, p < 0.01) with significantly better 12-month survival as compared to ACT group (88.9% vs. 69.4%, p = 0.04). TIPS in cirrhotic patients with PVT result in superior recanalization rates, better control of ascites, and variceal re-bleeding resulting in better survival. TIPS may be considered a preferred therapy after anticoagulation failure. TIPS is associated with good technical and clinical success in patients of cirrhosis with PVT and should be considered in patients not responding to ACT.

The influence of shunting left/right portal vein branch on post-TIPS hepatic encephalopathy: a study protocol for multicenter randomized blinded controlled trial

IntroductionGastroesophageal varices (GOV) bleeding is a common and serious complication of advanced liver cirrhosis with a median survival of less than 2 years. Multiple guidelines have pointed out that transjugular intrahepatic portosystemic shunt (TIPS) is the rescue treatment of acute variceal hemorrhage (AVB) after failure of standard therapy and an effective second-line treatment for preventing patients with high risks from rebleeding of GOV. The safety and stability of TIPS have been greatly improved due to the improvements of related technologies and the emergence of various novel devices, but the incidence of hepatic encephalopathy (HE) after shunting (10–50%) hindered the widespread use of TIPS. The target portal vein branch might affect the incidence of HE after TIPS. The aim of this study is to compare the rate of HE in patients with hepatitis B virus (HBV) related cirrhosis receiving TIPS either the left or right branch of the portal vein with 8mm Viatorr stent for preventing rebleeding from GOV.Methods and analysisThis study is a multicenter randomized controlled trial comparing the influence of shunting left or right portal vein branch on post-TIPS hepatic encephalopathy for preventing rebleeding from GOV in patients with HBV-related cirrhosis. A total of 130 patients will be recruited over a period of 24 months across 5 centers in China. Eligible patients will be stratified 1:1 to constructing either a left or right portal vein shunt with an 8-mm Viatorr stent. The primary objective was to compare the incidence of post-TIPS hepatic encephalopathy between the two groups. The secondary objectives were to compare the grade and duration of hepatic encephalopathy, the rate of shunt dysfunction, the rate of variceal rebleeding, the HE-free survival, the cumulative patency rate of the stent, and the overall survival at 12 months and 24 months between two groups.Ethics and disseminationThis study was approved by the ethics committee of Zhongshan Hospital of Fudan University (No. B2018-292R) and was registered at ClinicalTrials.gov (NCT03825848). All participants give written informed consent.Trial registrationClinicalTrials.gov NCT03825848. Registered on January 31, 2019Trial statusThe first patient was recruited into our study on June 19, 2019. A total of 55 patients were recruited till May 27, 2021 (27 and 28 patients assigned to shunting the left (L Group) and right (R Group) branches of the portal vein, respectively).

Comparative Efficacy of Treatment Options for Prevention of Post-TIPS Hepatic Encephalopathy:

Please view the PDF to see the formatted meeting abstract.

Individualized portal pressure gradient threshold based on liver function categories in preventing rebleeding after TIPS

BackgroundThe evidence in Portal pressure gradient (PPG) < 12 mmHg after transjugular intrahepatic portosystemic shunt (TIPS) for preventing rebleeding mostly comes from observations in uncovered stents era. Moreover, association between Child–Pugh classes and post-TIPS hepatic encephalopathy (HE) has indicated that tolerance of PPG reduction depends on liver function. This study aimed to investigate the optimal PPG for covered TIPS and explore the optimal threshold tailored to the Child–Pugh classes to find individualized PPG to balance rebleeding and overt HE.MethodsThis multicenter retrospective study analyzed rebleeding, OHE, and mortality of patients associated with post-TIPS PPGs (8, 10, 12, and 14 mmHg) in the entire cohort and among different Child–Pugh classes. Propensity score matching (PSM) and competing risk analyses were performed for sensitivity analyses.ResultsWe included 2100 consecutively screened patients undergoing TIPS. In all patients, PPG < 12 mmHg reduced rebleeding after TIPS (p = 0.022). In Child–Pugh class A, none of the PPG thresholds were discriminative of clinical outcomes. In Child–Pugh class B, 12 mmHg (p = 0.022) and 14 mmHg (p = 0.037) discriminated rebleeding, but 12 mmHg showed a higher net benefit. In Child–Pugh class C, PPG < 14 mmHg had a lower rebleeding incidence (p = 0.017), and exhibited more net benefit than 12 mmHg.ConclusionDifferent PPG standards may be required for patients with different liver function categories. A PPG threshold < 12 mmHg might be suitable for patients in Child–Pugh class B, while < 14 mmHg might be optimal for patients in Child–Pugh class C.Graphical

Low adipose tissue index as an indicator of hepatic encephalopathy in cirrhotic patients following transjugular intrahepatic portosystemic shunt.

We aimed to investigate the predictive value of body compositions measured by CT, including skeletal muscle and adipose tissue, for hepatic encephalopathy (HE) in cirrhotic patients following transjugular intrahepatic portosystemic shunt (TIPS). Patients who underwent TIPS between November 2015 and April 2021 were included in this retrospective study. CT images taken at L3 were quantified for three body composition indexes (cm2/m2), visceral fat area index (VFAI), subcutaneous fat area index (SFAI), and skeletal muscle index (SMI) at baseline. Multivariable logistic regression models were conducted to assess associations between post-TIPS HE and body compositions. Nomograms based on the multivariable logistic regression models were developed and were evaluated from Calibration curves. Male patients had greater SMI, whereas SFAI and VFAI were higher in females (p < 0.001 for each). In sex stratified multivariate analyses after adjustment for other confounding variables, VFAI in males (p = 0.033) and SFAI in females (p = 0.003) were significant predictors of post-TIPS HE. Male patients with low VFAI (< 53.52cm2/m2) (OR 6.44; 95% CI 1.72-23.59; p = 0.006) and female patients with low SFAI (< 70.05cm2/m2) (OR 10.55; 95% CI 2.36-46.23; p = 0.002) had a higher risk of post-TIPS HE. Risk factors in the nomogram contributing to the male model included age, height, Child-Pugh score, and low VFAI; pre-albumin and low SFAI were contributed to female model. Body compositions could not only be noninvasively used for nutritional assessment, but also be utilized to predict HE risk of cirrhotic patients after TIPS.

Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Creation.

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.

Diagnosis and management of hepatic encephalopathy: The French recommendations.

Hepatic encephalopathy (HE) is a frequent and severe complication of liver disease with poor patient outcomes. However, it is a poorly understood complication, with no consensus for diagnosis. Therefore, HE is often underdiagnosed. Differential diagnosis may be cumbersome because of non-specific symptoms, such as confusion, cognitive disorders, the aetiological factors of cirrhosis and comorbidities, which are often observed in cirrhotic patients. Therefore, an overt or covert form of HE should be systematically investigated. Advice is provided to drive patient work-up. Effective treatments are available to prevent or treat HE bouts, but the issue of single or combination therapy has not been resolved. Transjugular intrahepatic portosystemic shunt (TIPS) placement largely improved the prognosis of cirrhotic patients, but HE occurrence of HE is often a fear, even when post-TIPS HE can be avoided by a careful selection of patients and preventive treatment. HE is an indication of liver transplantation. However, its reversibility post-transplantation and the consequences of transplantation in patients with other causes of neurological disorders remain controversial, which supports the performance of an extensive work-up in expert centres for this subset of patients. The present guidelines assist clinicians in the diagnosis of the overt or covert form of HE to implement curative and preventive treatments and clarify which patients require referral to expert centres for consideration for liver transplantation. These guidelines are very clinically oriented and address different frequent clinical issues to help physicians make bedside decisions.

Reply.

We appreciate the interest of Lo in our recent study published in Hepatology.1 First, the indication of TIPS in our trial was gastroesophageal variceal bleeding occurring within the past 6 to 42 days despite the endoscopic plus nonselective beta blockers for secondary prophylaxis, which is in agreement with current practice guidelines.2 Second, we agree with Lo that the prior history of HE (hepatic encephalopathy) could increase the risk of HE after TIPS. Thus, we conducted a sensitivity analysis excluding patients with previous HE (Figure 3B in the original study).1 Nevertheless, the conclusion that concurrent embolization of large spontaneous portosystemic shunt reduced the incidence, severity and frequency of post-TIPS overt HE is not changed. Third, the survival was not significantly different in our trial. However, it should be noted that the sample size was calculated based on the primary endpoint (overt HE) and our study is not powerful enough to detect the differences of survival.1 Finally, showed that rifaximin reduced the risk of HE after TIPS when administered 15 days before the procedure and maintained 6 months after,3 while an earlier trial showed that lactulose had no such protective effect.4 In our opinion, the impact of lactulose on the post-TIPS HE merits more investigation.

Transjugular Intrahepatic Portosystemic Shunt Outcomes in the Elderly Population: A Systematic Review and Meta-Analysis.

Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure typically utilized to treat refractory ascites and variceal bleeding. However, TIPS can lead to significant complications, most commonly hepatic encephalopathy (HE). Advanced age has been described as a risk factor for HE, as the elderly population tends to have decreased cognitive reserve and increased sarcopenia. We conducted a systematic review and meta-analysis of the available literature to summarize the association between advanced age and risk of adverse events after undergoing TIPS. A comprehensive search strategy to identify reports of specific outcomes (HE, 30-day and 90-day mortality, and 30-day readmission due to HE) in elderly patients after undergoing TIPS was developed in Embase (Embase.com, Elsevier). We compared outcomes and performed separate data analyses for patients aged < 70 vs. > 70 years and patients aged < 65 vs. > 65 years. Six studies with a total of 1,591 patients met our inclusion criteria and were included in the final meta-analysis. Three studies divided patients by age < 65 vs. > 65 years, with a total of 816 patients who were 54% male. The remaining three studies divided patients by age < 70 vs. > 70 years, with a total of 775 patients who were 63% male. Results demonstrated a significantly lower risk of post-TIPS HE (risk ratio (RR): 0.42, confidence interval (CI): 0.185 - 0.953, P = 0.03, I2 = 49%), 30-day mortality (RR: 0.37, CI: 0.188 - 0.74, P = 0.005, I2 = 0%), and 90-day mortality (RR: 0.35, CI: 0.24 - 0.49, P = 0.001, I2 = 0%) in patients aged > 70 vs. < 70 years, as well as a trend towards lower risk of 30-day readmission due to HE. There was no significant difference in post-TIPS HE, 30-day or 90-day mortality, or 30-day readmission due to HE between patients aged < 65 vs. > 65 years. Age > 70 years is associated with significantly higher rates of HE and 30-day and 90-day mortality rates in patients after undergoing TIPS, as well as a trend towards higher 30-day readmission due to HE.