Road to recompensation: Baveno VII criteria and transjugular intrahepatic portosystemic shunt in liver cirrhosis.

Liver cirrhosis has long been considered a point of no return, with limited hope for recovery. However, recent advancements, particularly the Baveno VII criteria and the utilization of transjugular intrahepatic portosystemic shunt (TIPS), have illuminated the concept of hepatic recompensation. In this editorial we comment on the article by Gao et al published in the recent issue. This editorial provides a comprehensive overview of the evolution of understanding cirrhosis, the criteria for recompensation, and the efficacy of TIPS in achieving recompensation. We discuss key findings from recent studies, including the promising outcomes observed in patients who achieved recompensation post-TIPS insertion. While further research is needed to validate these findings and elucidate the mech-anisms underlying recompensation, the insights presented here offer renewed hope for patients with decompensated cirrhosis and highlight the potential of TIPS as a therapeutic option in their management.

Comparison of specialized stent versus generic stent and bare stent combination for transjugular intrahepatic portosystemic shunt creation.

Transjugular intrahepatic portosystemic shunt (TIPS) creation using the Viatorr stent remains relatively uncommon in underdeveloped and high-burden disease regions in Asia-Pacific, and there is a lack of comparative studies regarding its prognostic effects compared with the generic stent-graft/bare stent combination. The purpose of this retrospective study is to compare the prognostic endpoints of these two treatments in patients who underwent TIPS creation. Clinical data from 145 patients were collected, including 82 in the combination group and 63 in the Viatorr group. Differences in prognostic endpoints (shunt dysfunction, death, overt hepatic encephalopathy [OHE], rebleeding) between the two groups were analyzed using Kaplan-Meier curves. The Cox proportional hazards model was used to identify independent risk factors for post-TIPS shunt dysfunction. The TIPS procedure was successful in all patients. After TIPS creation, both groups showed a significant decrease in porto-caval pressure gradient compared to that before TIPS creation. The stent patency rates at 6, 12, and 18 months were high in both the combination and Viatorr groups (93.7%, 88.5%, and 88.5% vs. 96.7%, 93.4%, and 93.4%, respectively). The stent patency rates was higher in the combination group than in the Viatorr group, although not statistically significant (HR = 2.105, 95% CI 0.640-6.922, Log-rank P = 0.259). There were no significant differences in other prognostic endpoints (death, OHE, rebleeding) between the two groups. The Cox model identified portal vein diameter (HR = 0.807, 95% CI 0.658-0.990, P = 0.040) and portal vein thrombosis (HR = 13.617, 95% CI 1.475-125.678, P = 0.021) as independent risk factors for post-TIPS shunt dysfunction. The shunt patency rates between the Viatorr stent and the generic stent-graft/bare stent combination showed no significant difference and the generic stent-graft/bare stent combination may be a viable alternative in areas where the Viatorr stent is not yet available.

Transjugular intrahepatic portosystemic shunt: A promising therapy for recompensation in cirrhotic patients.

This is a retrospective study focused on recompensation after transjugular intrahepatic portosystemic shunt (TIPS) procedure. The authors confirmed TIPS could be a treatment for recompensation of patients with cirrhosis according to Baveno VII. The paper identified age and post-TIPS portal pressure gradient as independent predictors of recompensation in patients with decompensated cirrhosis after TIPS. These results need to be validated in a larger prospective cohort.

Bayesian network-based survival prediction model for patients having undergone post-transjugular intrahepatic portosystemic shunt for portal hypertension.

BACKGROUND: Portal hypertension (PHT), primarily induced by cirrhosis, manifests severe symptoms impacting patient survival. Although transjugular intrahepatic portosystemic shunt (TIPS) is a critical intervention for managing PHT, it carries risks like hepatic encephalopathy, thus affecting patient survival prognosis. To our knowledge, existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes. Consequently, the development of an innovative modeling approach is essential to address this limitation. AIM: To develop and validate a Bayesian network (BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS. METHODS: The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed. Variables were selected using Cox and least absolute shrinkage and selection operator regression methods, and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT. RESULTS: Variable selection revealed the following as key factors impacting survival: age, ascites, hypertension, indications for TIPS, postoperative portal vein pressure (post-PVP), aspartate aminotransferase, alkaline phosphatase, total bilirubin, prealbumin, the Child-Pugh grade, and the model for end-stage liver disease (MELD) score. Based on the above-mentioned variables, a BN-based 2-year survival prognostic prediction model was constructed, which identified the following factors to be directly linked to the survival time: age, ascites, indications for TIPS, concurrent hypertension, post-PVP, the Child-Pugh grade, and the MELD score. The Bayesian information criterion was 3589.04, and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16. The model's accuracy, precision, recall, and F1 score were 0.90, 0.92, 0.97, and 0.95 respectively, with the area under the receiver operating characteristic curve being 0.72. CONCLUSION: This study successfully developed a BN-based survival prediction model with good predictive capabilities. It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.

[Neurological disorders in liver transplantation].

Background and purpose: Liver transplantation is the only curative treatment in patients with end-stage liver failure. It has been associated with neurological disorders more frequently than other solid organ transplantations. We aimed to detect neurological disorders in liver transplantation patients and determine those that affect mortality. Methods: One hundred eighty-five patients, 105 with and 80 without neurological disorders, were included in this study. The follow-up was categorized into three periods: preoperative, early postoperative and late postoperative. We analyzed all medical records, including demographic, laboratory, radiological, and clinical data. Results: Neurological disorders were observed in 52 (28.1%) patients in the preoperative period, in 45 (24.3%) in the early postoperative, and in 42 (22.7%) in the late postoperative period. Hepatic encephalopathy in the preoperative and altered mental state in the post-operative period were the most common neurological disorders. Both hepatic encephalopathy (37.5%) and altered mental state (57.7%) caused high mortality (p=0.019 and 0.001) and were determined as indepen-dent risk factors for mortality. Living donor transplantation caused less frequent mental deterioration (p=0.049). The mortality rate (53.8%) was high in patients with seizures (p=0.019). While mortality was 28.6% in Wilson's disease patients with neurological disorders, no death was observed in patients without neurological disorders. Conclusion: We identified a wide variety of neurological disorders in liver transplantation patients. We also demonstrated that serious neurological disorders, including hepatic encephalopathy and seizures, are associated with high morbidity and mortality. Therefore, in order to avoid poor outcomes, hepatic encephalopathy should be considered as a prioritization criterion for liver transplantation.

Hepatic Encephalopathy: From Metabolic to Neurodegenerative.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome of both acute and chronic liver disease. As a metabolic disorder, HE is considered to be reversible and therefore is expected to resolve following the replacement of the diseased liver with a healthy liver. However, persisting neurological complications are observed in up to 47% of transplanted patients. Several retrospective studies have shown that patients with a history of HE, particularly overt-HE, had persistent neurological complications even after liver transplantation (LT). These enduring neurological conditions significantly affect patient's quality of life and continue to add to the economic burden of chronic liver disease on health care systems. This review discusses the journey of the brain through the progression of liver disease, entering the invasive surgical procedure of LT and the conditions associated with the post-transplant period. In particular, it will discuss the vulnerability of the HE brain to peri-operative factors and post-LT conditions which may explain non-resolved neurological impairment following LT. In addition, the review will provide evidence; (i) supporting overt-HE impacts on neurological complications post-LT; (ii) that overt-HE leads to permanent neuronal injury and (iii) the pathophysiological role of ammonia toxicity on astrocyte and neuronal injury/damage. Together, these findings will provide new insights on the underlying mechanisms leading to neurological complications post-LT.

Cerebellar spongiform degeneration is accompanied by metabolic, cellular, and motor disruption in male rats with portacaval anastomosis.

The episodes of cerebral dysfunction, known as encephalopathy, are usually coincident with liver failure. The primary metabolic marker of liver diseases is the increase in blood ammonium, which promotes neuronal damage. In the present project, we used an experimental model of hepatic encephalopathy in male rats by portacaval anastomosis (PCA) surgery. Sham rats had a false operation. After 13 weeks of surgery, the most distinctive finding was vacuolar/spongiform neurodegeneration exclusively in the molecular layer of the cerebellum. This cerebellar damage was further characterized by metabolic, histopathological, and behavioral approaches. The results were as follows: (a) Cellular alterations, namely loss of Purkinje cells, morphological changes, such as swelling of astrocytes and Bergmann glia, and activation of microglia; (b) Cytotoxic edema, shown by an increase in aquaporin-4 and N-acetylaspartate and a reduction in taurine and choline-derivate osmolytes; (c) Metabolic adjustments, noted by the elevation of circulating ammonium, enhanced presence of glutamine synthetase, and increase in glutamine and creatine/phosphocreatine; (d) Inflammasome activation, detected by the elevation of the marker NLRP3 and microglial activation; (e) Locomotor deficits in PCA rats as assessed by the Rotarod and open field tests. These results lead us to suggest that metabolic disturbances associated with PCA can generate the cerebellar damage that is similar to morphophysiological modifications observed in amyloidogenic disorders. In conclusion, we have characterized a distinctive cerebellar multi-disruption accompanied by high levels of ammonium and associated with spongiform neurodegeneration in a model of hepatic hypofunctioning.

Indication of Liver Transplantation in the Treatment of Newly Categorized Acute-on-Chronic Liver Failure In Japan.

AIM: This study aims to validate Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) and confirm the feasibility of performing transplantation. METHODS: We included 60 patients with acute liver injury. Demographic and clinical features were retrospectively collected, and the primary outcome was compared among 4 types: acute liver failure (ALF) with hepatic coma (n = 23), ALF without hepatic coma (n = 12), acute liver injury (n = 20), and ACLF (n = 5). Moreover, 80 transplanted patients were enrolled to compare the difficulty of transplantation between ALF (n = 8) vs non-ALF (n = 72) patients. RESULTS: Seven patients in the ALF with hepatic coma group and 1 patient in the ACLF with hepatic coma group were transplanted. Ten patients who could not be registered for transplantation died. In univariate analysis, liver failure type (P < .0001), total bilirubin level (P = .05), and prothrombin time internationalized ratio (P < .0001) were associated with patient survival. In multivariate analysis, liver failure type was associated with patient survival (P < .0001). The respective 1-, 3-, and 5-year patient survival rates were 45.9%, 45.9%, and 45.9% for ALF patients with hepatic coma; 100.0%, 100.0%, and 100.0% for ALF patients without hepatic coma and acute liver injury; and 80.0%, 80.0%, and 80.0% for ACLF patients (P < .0001). Chronic liver disease did not affect operation time (P = .46) and bleeding volume (P = .49). CONCLUSION: Patients diagnosed with ACLF via Japanese criteria presented significantly higher survival rates than ALF patients with hepatic coma.

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

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

[30 Years of Transjugular Intrahepatic Portosystemic Shunt (TIPS): casting a retrospective glance and future perspectives]. / 30 Jahre transjugulärer intrahepatischer portosystemischer Shunt (TIPS) ­ Rückblick und Perspektive.

For 30 years the transjugular intrahepatic portosystemic shunt (TIPS) is successfully used for the treatment of portal hypertension. Indication for TIPS in relation to variceal bleeding and refractory ascites is scientifically documented and defined by national and international guidelines. For rare indications such as hepatorenal syndrome, portal vein thrombosis or the neodjuvant TIPS larger evidence-based studies are missing. An important contraindication and the leading clinical complication after TIPS is the development of hepatic encephalopathy (HE). Reduction of post-TIPS HE is therefore aimed through development of further technical enhancements of the TIPS-stents.

Sigmoid Colon Varices due to Massive Thrombosis of a Noncirrhotic Extrahepatic Portosystemic Shunt.

A 33-year-old man presented with hepatic encephalopathy and was diagnosed to have a noncirrhotic extrahepatic portosystemic shunt (NCPSS). He presented with abdominal pain 16 months after the NCPSS diagnosis. Computed tomography revealed thrombosis between the intrahepatic portal vein and the left internal iliac vein, including the NCPSS, and varices of the sigmoid colon. Thrombosis was treated with danaparoid sodium and antithrombin III followed by edoxaban. After treatment, the thrombosis disappeared from the intrahepatic portal vein, but it remained in the NCPSS. The sigmoid colon varices were followed up without any treatment. Follow-up is needed in NCPSS patients in order to make an early detection of complications.

Transjugular intrahepatic portosystemic shunt and alfapump® system for refractory ascites in liver cirrhosis: Outcomes and complications.

BACKGROUND: Treatment of refractory ascites in liver cirrhosis is challenging. Transjugular intrahepatic portosystemic shunt and alfapump® have been proposed for the management, but few data comparing both exist. AIMS: The aim of this study was to evaluate the characteristics and outcomes of patients treated with transjugular intrahepatic portosystemic shunt and alfapump® for refractory ascites at our centre. METHODS: All consecutive patients were retrospectively reviewed for baseline characteristics, efficacy of treatment, complications and survival. RESULTS: In total, 19 patients with transjugular intrahepatic portosystemic shunt and 40 patients with alfapump® were included. Patients with transjugular intrahepatic portosystemic shunt had better liver function and less hepatic encephalopathy at baseline. Fifty-eight per cent of patients developed hepatic encephalopathy in the first six months after transjugular intrahepatic portosystemic shunt. In patients with alfapump®, renal function decreased and 58% developed prerenal impairment and 43% hepatorenal syndrome in the first six months. Alfapump® patients with new catheters required less reinterventions (26% versus 57% with old catheters, p = 0.049). Transplant-free survival at 1 year was 25% in alfapump® and 65% in transjugular intrahepatic portosystemic shunt. Hepatic encephalopathy predicted transplant-free survival in patients with alfapump® (hazard ratio 2.00, 95% confidence interval 0.99-4.02, p = 0.05). In a sensitivity analysis comparing patients with similar liver function, the rate of hepatorenal syndrome and prerenal impairment was higher in patients with alfapump® and these patients were hospitalised more frequently, whereas the rate of hepatic encephalopathy was similar in both treatment groups. CONCLUSIONS: Both transjugular intrahepatic portosystemic shunt and alfapump® were effective treatments for refractory ascites in cirrhosis. Patients treated with transjugular intrahepatic portosystemic shunt had a better one-year transplant-free survival but had less negative prognostic factors at baseline. Selecting patients without hepatic encephalopathy prior to implantation of an alfapump® might improve transplant-free survival.

Minimal Hepatic Encephalopathy: Effect of H. pylori infection and small intestinal bacterial overgrowth treatment on clinical outcomes.

The effect Helicobacter pylori (Hp) infection and small intestinal bacterial over growth (SIBO) in minimal hepatic encephalopathy (MHE) is not well understood. The aim of the study was to determine the effect of eradication of Hp infection and SIBO treatment on MHE in patients with cirrhosis. Patients with cirrhosis were enrolled and MHE was determined by psychometric tests and critical flicker frequency analysis. Hp infection and SIBO were assessed by urea breath and Hydrogen breath tests respectively in patients with cirrhosis and in healthy volunteers. Patients with Hp infection and SIBO were given appropriate treatment. At six weeks follow-up, presence of Hp infection, SIBO and MHE status was reassessed. Ninety patients with cirrhosis and equal number of healthy controls were included. 55 (61.1%) patients in the cirrhotic group were diagnosed to have underlying MHE. Among cirrhotic group, Hp infection was present in 28 with MHE (50.9%) vs. in 15 without MHE (42.8%) (p = 0.45). Similarly, SIBO was present in 17 (30.9%) vs. 11 (31.4%) (p = 0.95) in patients with and without MHE respectively. In comparison with healthy controls, patients with cirrhosis were more frequently harboring Hp and SIBO (47.7% vs. 17.7% (p < 0.001) and 31.1% vs. 4.4% (p < 0.001) respectively. On follow-up, all patients showed evidence of eradication of Hp and SIBO infection. Treatment of SIBO significantly improved the state of MHE in cirrhotics, however eradication of Hp infection did not improve MHE significantly. Additionally, patients with low Model for End-Stage Liver Disease (MELD) score and belonging to Child class B had significantly better improvement in MHE. A large number of patients with cirrhosis had either active Hp infection or SIBO with or without MHE, compared to healthy controls. Treatment of SIBO significantly improved MHE in patients with cirrhosis, whereas eradication of Hp did not affect the outcome of MHE in these patients.

Successful Surgical Intervention for Recurring Severe Hepatic Encephalopathy Caused by Portosystemic Collaterals After Living-Donor Liver Transplantation: A Case Report.

INTRODUCTION: Portosystemic collaterals (PsC) are a common finding in patients with cirrhosis who need liver transplantation (LT), and PsCs may cause several problems before and after LT. We report a case of successful surgical treatment of severe hepatic encephalopathy (HE) caused by PsC after living-donor LT (LDLT). CASE: A 71-year-old woman with hepatocellular carcinoma underwent LDLT for chronic hepatitis C virus infection at 64 years of age. The splenocaval collateral vein was ligated during LDLT to prevent portal flow steal. A recurrent episode of coma due to HE was triggered 7 years after LDLT and gradually became refractory to any drug treatments. Contrast-enhanced computed tomography revealed the development of the right gastroepiploic vein (RGEV), which flowed to the inferior vena cava via the inferior mesenteric vein (IMV). Owing to the chronic kidney disease (estimated glomerular filtration rate, 11-31 mL/min), interventional radiology (IVR) was not indicated, so surgical treatment was selected to treat the symptom. PsC was resected at the point of the RGEV and IMV, just before flowing into the IVC with vascular staplers. Antegrade portal blood flow was obtained by ultrasonography 2 days after surgery, and the patient was discharged from the hospital 26 days after the operation. After discharge, she has had no recurrent episode of HE. CONCLUSION: Surgical resection of the PsC was effective for treatment of HE caused by shunt flow after LDLT.

The cerebellar form of acquired hepatocerebral degeneration: The hepatic ataxia.

This article reports a patient with acquired hepatocerebral degeneration that presented with progressive cerebellar ataxia, cerebellar atrophy, and middle cerebellar peduncle lesions. He had a marked improvement after liver transplantation. We reinforce that hepatic failure should be investigated in patients with pure cerebellar syndrome, resembling neurodegenerative diseases.