A new computational fluid dynamics based noninvasive assessment of portacaval pressure gradient.

Accurate assessment of portacaval pressure gradient (PCG) in patients with portal hypertension (PH) is of great significance both for diagnosis and treatment. This study aims to develop a noninvasive method for assessing PCG in PH patients and evaluate its accuracy and effectiveness. This study recruited 37 PH patients treated with transjugular intrahepatic portosystemic shunt (TIPS). computed tomography angiography was used to create three dimension (3D) models of each patient before and after TIPS. Doppler ultrasound examinations were conducted to obtain the patient's portal vein flow (or splenic vein and superior mesenteric vein). Using computational fluid dynamics (CFD) simulation, the patient's pre-TIPS and post-TIPS PCG was determined by the 3D models and ultrasound measurements. The accuracy of these noninvasive results was then compared to clinical invasive measurements. The results showed a strong linear correlation between the PCG simulated by CFD and the clinical invasive measurements both before and after TIPS (R2 = 0.998, P < 0.001 and R2 = 0.959, P < 0.001). The evaluation accuracy of this noninvasive method reached 94 %, and the influence of ultrasound result errors on the numerical accuracy was found to be marginal if the error was less than 20 %. Furthermore, the information about the hemodynamic environment in the portal system was obtained by this numerical method. Spiral flow patterns were observed in the portal vein of some patients. In a conclusion, this study proposes a noninvasive numerical method for assessing PCG in PH patients before and after TIPS. This method can assist doctors in accurately diagnosing patients and selecting appropriate treatment plans. Additionally, it can be used to further investigate potential biomechanical causes of complications related to TIPS in the future.

Clinical Impact of Spontaneous Portosystemic Shunts in Liver Transplantation: A Comprehensive Assessment Through Total Shunt Area Measurement.

BACKGROUND: The impact of spontaneous portosystemic shunts (SPSSs) on natural history of cirrhotic patients was recently evaluated through the measurement of total shunt area (TSA), a novel tool that allows a comprehensive assessment of SPSSs extension, identifying a direct correlation of higher TSA with lower patient survival. The role of SPSSs in liver transplant (LT) is still debated: we sought to investigate the clinical impact of TSA on the development of early allograft dysfunction (EAD), acute kidney injury (AKI), postoperative complications, and graft and patient survival following LT. METHODS: Preoperative imaging of 346 cirrhotic patients undergoing primary LT between 2015 and 2020 were retrospectively revised, recording the size and anatomy of each SPSS to calculate TSA. The impact of TSA and selected patient and donor characteristics on the development of EAD, AKI, and clinically relevant complications was evaluated through univariate and multivariate logistic regression, whereas their effect on graft and patient survival was investigated through Cox regression analysis. RESULTS: A TSA exceeding 78.54 mm 2 resulted as an independent risk factor for the development of EAD (odds ratio [OR]: 2.327; P = 0.003), grade 3 AKI (OR: 2.093; P = 0.041), and clinically relevant complications (OR: 1.962; P = 0.015). Moreover, higher TSA was significantly related to early graft and patient survivals, emerging as an independent risk factor for 12-mo graft loss (hazard ratio: 3.877; P = 0.007) and patient death (hazard ratio: 2.682; P = 0.018). CONCLUSIONS: Higher TSA emerged as a significant risk factor for worse postoperative outcomes following LT, supporting the need for careful hemodynamic assessment and management of patients presenting multiple/larger shunts.

Endovascular Assessment of Liver Hemodynamics in Patients with Cirrhosis Complicated by Portal Hypertension.

The hepatic venous pressure gradient (HVPG) is currently considered the gold standard to assess portal hypertension (PH) in patients with cirrhosis. A meticulous technique is important to achieve accurate and reproducible results, and values obtained during measurement are applied in risk stratification of patients with PH, allocating treatment options, monitoring follow-up, and deciding management options in surgical patients. The use of portosystemic pressure gradients in patients undergoing placement of transjugular intrahepatic portosystemic shunts has been studied extensively and has great influence on decisions on shunt diameter. The purpose of this study was to describe the recommended technique to measure HVPG and portosystemic pressure gradient and to review the existing literature describing the importance of these hemodynamic measurements in clinical practice.

Spleen Stiffness Performance in the Noninvasive Assessment of Gastroesophageal Varices after Transjugular Intrahepatic Portosystemic Shunts.

OBJECTIVES: To investigate the performance of spleen stiffness (SS) by using two-dimensional shear-wave elastography (2D-SWE) for assessing the severity of gastroesophageal varices (GEVs) after transjugular intrahepatic portosystemic shunt (TIPS). METHODS: 102 eligible patients were categorized as in the post-TIPS short-term (n = 69) and long-term (n = 38) follow-up groups. The performance of SS by using 2D-SWE for evaluating the severity of GEVs was compared with liver stiffness (LS), spleen stiffness-to-liver stiffness ratio (SS/LS), liver stiffness spleen-diameter-to-platelet-ratio score (LSPS), portal hypertension (PH) risk score, platelet count-to-spleen diameter ratio (PSR), and varices risk score by using receiver operating characteristic (ROC) curve and DeLong test. RESULTS: In the post-TIPS short-term follow-up group, area under the receiver operating characteristic curves (AUCs) of SS were 0.585 for mild (cutoff value = 30.3 kPa), 0.655 for moderate (cutoff value = 30.6 kPa), and 0.739 for severe (cutoff value = 31.9 kPa) GEVs, which were higher than other parameters for severe GEVs. AUCs of SS were lower than other parameters for mild and moderate GEVs, but no difference was found (p > 0.05). In the post-TIPS long-term follow-up group, AUCs of SS were 0.778 for mild (cutoff value = 28.9 kPa), 0.82 for moderate (cutoff value = 29.9 kPa), and 0.824 for severe (cutoff value = 37.7 kPa) GEVs, which were higher than other parameters except for severe GEVs. AUC of SS was lower than other parameters for severe GEVs, but no significant difference was found (p > 0.05). CONCLUSION: SS is an effective noninvasive tool to predict GEV severity during the post-TIPS follow-up.

Long-term survival prediction for transjugular intrahepatic portosystemic shunt in severe cirrhotic ascites: assessment of ten prognostic models.

OBJECTIVES: Patients with severe cirrhotic ascites have poor prognosis, yet individual patient survival varies greatly. Therefore, suitable prognostic models can be helpful in clinical decision making. The aim of this study was to evaluate and compare the performance of 10 scores in predicting transplant-free survival (TFS) after transjugular intrahepatic portosystemic shunt (TIPS) in severe cirrhotic ascites. METHODS: Two hundred eighty consecutive cirrhotic patients with severe ascites undergoing TIPS between March 2006 and December 2017 were retrospectively screened and included from nine tertiary Chinese centers, consisting of 123 patients with refractory ascites and 157 with recurrent ascites. Discriminatory ability of these models was further assessed in the whole cohort and subgroups. RESULTS: TFS rates of all 280 patients were 75.4, 65.7, and 53.6% at 6-month, 1-year, and 2-year follow-up, respectively. Compared with other prognostic systems, the integrated model for end-stage liver disease (iMELD, incorporating serum sodium and age) showed optimal performance in predicting 6-month, 1-year, and 2-year TFS. Cutoffs were determined according to c-index and were used to stratify patients into three strata presenting significantly different TFS for short-term and long-term: iMELD < 32, ≥32 but <38 and ≥38 (log-rank P < 0.001). CONCLUSIONS: The iMELD score proved to be the best prognostic model in predicting TFS in patients with severe cirrhotic ascites receiving TIPS. Meanwhile, the model could stratify patients in three strata to help guiding clinical practice.

Cost-Effectiveness of Transjugular Intrahepatic Portosystemic Shunt versus Large-Volume Paracentesis in Refractory Ascites: Results of a Markov Model Incorporating Individual Patient-Level Meta-Analysis and Nationally Representative Cost Data.

PURPOSE: To compare relative cost-effectiveness of serial large-volume paracentesis (LVP) and transjugular intrahepatic portosystemic shunt (TIPS) creation for treatment of refractory ascites. MATERIALS AND METHODS: A decisional Markov model was developed to estimate payer cost and quality-adjusted life-ears (QALYs) associated with LVP and TIPS treatment strategies for cirrhotic patients with refractory ascites. Survival estimates were derived from an individual patient-level meta-analysis of prospective randomized clinical trials. Health utilities for potential health states were derived from a prospective study of patients with cirrhosis. Cost data were derived from national representative claims databases (MarketScan and Medicare) and included reimbursement amounts for relevant procedures, hospitalizations, and outpatient pharmaceutical costs. One-way and probabilistic sensitivity analyses were performed. RESULTS: LVP resulted in 1.72 QALYs gained at a cost of $41,391, whereas TIPS resulted in 2.76 QALYs gained at a cost of $100,538. Incremental cost-effectiveness ratio of TIPS versus LVP was $57,003/QALY. At a willingness-to-pay ratio of $100,000/QALY, TIPS has a 62% probability of being acceptable compared with LVP. CONCLUSIONS: This study suggests that TIPS should be considered cost-effective in a country that places a relatively high value on health improvements but less so in countries with lower levels of health care resources.

Transjugular intrahepatic portosystemic shunt versus open splenectomy and esophagogastric devascularization for portal hypertension with recurrent variceal bleeding.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) and open splenectomy and esophagogastric devascularization (OSED) are widely used to treat patients with portal hypertension and recurrent variceal bleeding (PHRVB). This study aimed to compare the effectiveness between TIPS and OSED for the treatment of PHRVB. METHODS: The data were retrospectively retrieved from 479 cirrhotic patients (Child-Pugh A or B class) with PHRVB, who had undergone TIPS (TIPS group) or OSED (OSED group) between January 1, 2010 and October 31, 2014. RESULTS: A total of 196 patients received TIPS, whereas 283 underwent OSED. Within one month after TIPS and OSED, the rebleeding rates were 6.1% and 3.2%, respectively (P=0.122). Significantly lower incidence of pleural effusion, splenic vein thrombosis, and pulmonary infection, as well as higher hepatic encephalopathy rate, shorter postoperative length of hospital stay, and higher hospital costs were observed in the TIPS group than those in the OSED group. During the follow-up periods (29 months), significantly higher incidences of rebleeding (15.3% vs 4.6%, P=0.001) and hepatic encephalopathy (17.3% vs 3.9%, P=0.001) were observed in the TIPS group than in the OSED group. The incidence of in-stent stenosis was 18.9%. The survival rates were 91.3% in the TIPS group and 95.1% in the OSED group. The long-term liver function did not worsen after either TIPS or OSED. CONCLUSION: For the patients with liver function in the Child-Pugh A or B class, TIPS is not superior over OSED in terms of PHRVB treatment and rebleeding prevention.

Direct acting inhibitors of ammoniagenesis: a role in post-TIPS encephalopathy?

A limited number of medications are typically considered for the management of hepatic encephalopathy occurring as a complication of transjugular intrahepatic portosystemic shunt (TIPS) placement. Multiple alternative compounds aimed at disrupting ammoniagenesis are or will soon be available, though their use tends to be limited by a lack of large data sets and of clinical awareness. In this review, we provide a targeted overview of the mechanisms and availability of five anti-ammoniagenic compounds (sodium phenylbutyrate, glycerol phenylbutyrate, sodium benzoate, L-ornithine L-aspartate, and ornithine phenylacetate) identified as possibly useful alternative therapeutic agents for cirrhotic encephalopathy. Three of these medications have been FDA approved for use in congenital urea cycle disorders only, while two are under active investigation for use in cirrhotic patients. In spite of limitations posed by cost and comorbidities, familiarity with these options may prove beneficial in cases refractory to conventional management.

Prognostic capability of different liver disease scoring systems for prediction of early mortality after transjugular intrahepatic portosystemic shunt creation.

PURPOSE: To compare the performance of various liver disease scoring systems in predicting early mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: In this single-institution retrospective study, eight scoring systems were used to grade liver disease in 211 patients (male-to-female ratio = 131:80; mean age, 54 y) before TIPS creation from 1999-2011. Scoring systems included bilirubin level, Child-Pugh (CP) score, Model for End-Stage Liver Disease (MELD) and Model for End-Stage Liver Disease sodium (MELD-Na) score, Emory score, prognostic index (PI), Acute Physiology and Chronic Health Evaluation (APACHE) 2 score, and Bonn TIPS early mortality (BOTEM) score. Medical record review was used to identify 30-day and 90-day clinical outcomes. The relationship of scoring parameters with mortality outcomes was assessed with multivariate analysis, and the relative ability of systems to predict mortality after TIPS creation was evaluated by comparing area under receiver operating characteristic (AUROC) curves. RESULTS: TIPS were successfully created for variceal hemorrhage (n = 121), ascites (n = 72), hepatic hydrothorax (n = 15), and portal vein thrombosis (n = 3). All scoring systems had a significant association with 30-day and 90-day mortality (P<.050 in each case) on multivariate analysis. Based on 30-day and 90-day AUROC, MELD (0.878, 0.816) and MELD-Na (0.863, 0.823) scores had the best capability to predict early mortality compared with bilirubin (0.786, 0.749), CP (0.822, 0.771), Emory (0.786, 0.681), PI (0.854, 0.760), APACHE 2 (0.836, 0.735), and BOTEM (0.798, 0.698), with statistical superiority over bilirubin, Emory, and BOTEM scores. CONCLUSIONS: Several liver disease scoring systems have prognostic value for early mortality after TIPS creation. MELD and MELD-Na scores most effectively predict survival after TIPS creation.

Outcomes of transjugular intrahepatic portosystemic shunt through the left branch vs. the right branch of the portal vein in advanced cirrhosis: a randomized trial.

BACKGROUND/AIMS: The transjugular intrahepatic portosystemic shunt (TIPS) is technically divided into TIPS through the left branch of the portal vein (TIPS-LBPV) and TIPS through the right branch of the portal vein (TIPS-RBPV). In order to compare their advantages and disadvantages, this randomized, controlled trial was designed to investigate their outcomes in advanced cirrhotic patients. METHODS: Seventy-two patients were randomly placed into TIPS-LBPV (36 patients) and TIPS-RBPV (36 patients, with four failures) groups, and they were prospectively followed for 2 years after TIPS implantation. RESULTS: Patients who underwent the two different kinds of TIPS were balanced during recruitment for this study. The incidences of overall encephalopathy and de novo encephalopathy in the TIPS-LBPV group were significantly lower than that of the TIPS-RBPV group during follow-up (P=0.036 and 0.012 respectively). The incidences of rebleeding or re-intervention and improvement of ascites were similar between groups (P>0.05). Patients undergoing TIPS-RBPV required more rehospitalization and incurred more costs than those who underwent TIPS-LBPV (P=0.030 and 0.039 respectively). There was no significant difference between the two groups in survival based on a survival curve constructed according to the Kaplan-Meier method (P>0.05). CONCLUSION: Patients undergoing TIPS-LBPV had a lower incidence of encephalopathy, less rehospitalization and lower costs after TIPS implantation compared with patients undergoing TIPS-RBPV.

TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: a randomized controlled trial.

Prevention of variceal rebleeding is mandatory in cirrhotic patients. We compared the efficacy, safety, and cost of transjugular intrahepatic portosystemic shunt (TIPS) versus pharmacologic therapy in preventing variceal rebleeding in patients with advanced cirrhosis. A total of 91 Child-Pugh class B/C cirrhotic patients surviving their first episode of variceal bleeding were randomized to receive TIPS (n = 47) or drug therapy (propranolol + isosorbide-5-mononitrate) (n = 44) to prevent variceal rebleeding. Mean follow-up was 15 months. Rebleeding occurred in 6 (13%) TIPS-treated patients versus 17 (39%) drug-treated patients (P =.007). The 2-year rebleeding probability was 13% versus 49% (P =.01). A similar number of reinterventions were required in the 2 groups; these were mainly angioplasty +/- restenting in the TIPS group (90 of 98) and endoscopic therapy for rebleeding in the medical group (45 of 62) (not significant). Encephalopathy was more frequent in TIPS than in drug-treated patients (38% vs. 14%, P =.007). Child-Pugh class improved more frequently in drug-treated than in TIPS-treated patients (72% vs. 45%; P =.04). The 2-year survival probability was identical (72%). The identified cost of therapy was double for TIPS-treated patients. In summary, medical therapy was less effective than TIPS in preventing rebleeding. However, it caused less encephalopathy, identical survival, and more frequent improvement in Child-Pugh class with lower costs than TIPS in high-risk cirrhotic patients. This suggests that TIPS should not be used as a first-line treatment, but as a rescue for failures of medical/endoscopic treatments (first-option therapies).

A randomized trial comparing transjugular intrahepatic portosystemic stent-shunt with variceal band ligation in the prevention of rebleeding from esophageal varices.

The aim of this study was to compare transjugular intrahepatic portosystemic stent-shunt (TIPSS) with variceal band ligation (VBL) in the secondary prophylaxis of esophageal variceal hemorrhage in patients with cirrhosis. Fifty-eight patients with cirrhosis who presented with the first episode of esophageal variceal hemorrhage were randomized to TIPSS (31) or VBL (27), 24 hours after control of bleeding. Shunt function was assessed after 1 month and then at 6 monthly intervals thereafter. VBL was performed weekly until variceal eradication, and then at 3 months, 6 months, and yearly thereafter. Mean follow-up in the TIPSS group was 15.7 (+/-10.2) months; in the VBL group, it was 16.8 (+/-10.9) months. Results for rebleeding and mortality were analyzed on an intention-to-treat basis and using the Kaplan-Meier method. The frequency and the severity of variceal rebleeding was significantly lower in the TIPSS group (9.8%), compared with the VBL group (51.9%) (P < .0006). Although mortality rates were not significantly different, 8 of the patients who rebled in the VBL group required TIPSS therapy for uncontrolled bleeding. No significant differences were found in the frequency of other complications such as encephalopathy and sepsis. Patients in the VBL group required significantly greater time in the intensive care unit during the period of this study (<0.03). The total direct cost of treatment incurred was pound sterling 1,373 ($2,200) per patient, the cost being less in the patients treated with TIPSS compared with VBL. The results of this study show that TIPSS is superior to VBL for the secondary prophylaxis of variceal hemorrhage in patients with cirrhosis.

Transjugular intrahepatic portosystemic shunts: assessment with helical CT angiography.

To evaluate diagnostic computed tomographic (CT) angiograms of transjugular intrahepatic portosystemic shunts (TIPS), helical CT angiography was performed in 10 patients with (n = 7) or without (n = 3) shunt dysfunction. CT angiography was performed with 3-mm-thick sections, pitch of 1, 120 kV, and 180-220 mA, after injection of 150 mL nonionic contrast material at 5 mL/sec, with a 50-second scanning delay after initiation of injection. All patients underwent transjugular portography within 1 week after CT angiography. In all cases, CT angiography correctly showed the presence or absence of the abnormality. These preliminary data suggest that CT angiography can provide diagnostic images of normal and abnormal TIPS.