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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. [ABSTRACT FROM AUTHOR]

Background and aims: Non-alcoholic fatty liver disease (NAFLD) has emerged as a major chronic liver disease. We explored simple and effective ways to improve NAFLD and investigate the mechanism of action. Methods: NAFLD was induced in 40 rats fed a high-fat diet (HFD). Magnetic resonance imaging was used to evaluate the progression and improvement of NAFLD. The treatment-related interventions included aerobic exercise (E) and vitamin E (VE) supplementation. Expression levels of proteins related to fat metabolism were also assessed. The activities of antioxidant enzymes in the liver and serum lipid metabolism were analyzed using biochemical methods. Results: Aerobic exercise and vitamin E effectively improved NAFLD in rats, resulting in decreased hepatic fat accumulation, reduced hepatocyte ballooning, and decreased triglyceride levels. Combination therapy achieved the best effect. Both aerobic exercise and vitamin E activate the AMPK pathway to phosphorylate acetyl-CoA carboxylase (ACC) and reduce fatty acid synthesis. The expression of sterol regulatory element-binding protein-1 (SREBP-1) was decreased significantly in the treated groups, particularly in the E + VE + HFD group. The expression of carnitine palmitoyl-transferase 1C (CPT1C) significantly increased in the treated groups, particularly in the E + VE + HFD group. Compared with the control group, reactive oxygen species (ROS) in the E + HFD group were slightly decreased, while that in the VE + HFD group were significantly decreased, with the even greater reduction observed in the E + VE + HFD group. Conclusion: Aerobic exercise and vitamin E supplementation can improve HFD-induced NAFLD in rats by regulating the AMPK pathway and reducing oxidative stress. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly significant global health burden for which there is currently no effective treatment. The present study aimed to explore the underlying mechanisms and investigate the effects of donafenib and atorvastatin in MASLD. The effects of donafenib and atorvastatin on the activity and lipid metabolism of HepG2 cells were analyzed in vitro. A rat model of MASLD was established induced by a high-fat diet in vivo. H&E and Oil red O staining were used to observe the improvement in MASLD, western blotting analysis was used to detect the expression of proteins related to fat metabolism and immunofluorescence was used to detect reactive oxygen species (ROS) levels. In vitro, donafenib and atorvastatin inhibited lipid accumulation in HepG2 cells. In vivo, donafenib and atorvastatin activated the AMP-activated protein kinase (AMPK) pathway, downregulated the expressions of proteins related to fatty acid synthesis (sterol regulatory element-binding protein-1, 3-hydroxy-3-methylglutaryl-CoA reductase and fatty acid synthase) and upregulated the expression of proteins related to fatty acid β-oxidation (carnitine palmitoyl-transferase 1C and acyl-CoA oxidase). The levels of free fatty acids, cholesterol and triglycerides in the liver and serum decreased in all three treatment groups. Additionally, donafenib and atorvastatin reduced oxidative stress in the liver tissue and decreased ROS levels. Low-dose donafenib combined with atorvastatin improved MASLD by regulating fatty acid metabolism and reducing oxidative stress through activation of the AMPK signaling pathway. [ABSTRACT FROM AUTHOR]

Aims: To investigate the impact of endovascular (EV) treatment on liver cirrhosis in Chinese patients with Budd–Chiari syndrome (BCS). Methods: From September 2011 to March 2022, 97 patients from four hospitals in China who were diagnosed with primary BCS complicated with liver cirrhosis and received EV treatment were retrospectively enrolled in this study for clinical analysis. In addition, liver tissues for basic research were acquired from 25 patients between June 2022 and March 2023, including six with benign liver tumors, 11 with BCS before EV treatment, and eight with EV‐treated BCS. Liver cirrhosis was assessed by clinical outcomes, histological studies, and the expression of related genes at the mRNA and protein levels. Results: The patients with BCS had better liver function after EV treatment, evidenced by an increased albumin level and reduced total bilirubin, ALT, and AST. The imaging findings suggested an amelioration of liver cirrhosis and portal hypertension, including increased portal vein velocity (13.52 ± 8.89 cm/s vs. 17.51 ± 6.67 cm/s, p < 0.001) and decreased liver stiffness (30.37 ± 6.39 kPa vs. 23.70 ± 7.99 kPa, p < 0.001), portal vein diameter (14.97 ± 3.42 mm vs. 13.36 ± 2.89 mm, p < 0.001), and spleen volume (870.00 ± 355.61 cm3 vs. 771.36 ± 277.45 cm3, p < 0.001). Furthermore, histological studies revealed that EV treatment resulted in a restoration of liver architecture with reduced extracellular matrix deposition. Meanwhile, hepatic angiogenesis and inflammation, which have a close relationship with cirrhosis, were also inhibited. In addition, the state of hepatocytes switches from apoptosis to proliferation after EV treatment. Conclusions: BCS‐induced liver cirrhosis could be reversed by EV treatment from macroscopic to microscopic dimensions. Our study may provide further insights into understanding BCS and treating cirrhosis. [ABSTRACT FROM AUTHOR]

Purpose: To assess and compare the value of psoas muscle thickness at the level of the third lumbar (L3) vertebra (TPML) or umbilicus (TPMU) and skeletal muscle index (SMI) for diagnosing sarcopenia and predicting mortality in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). Materials and Methods: Two hundred forty-nine patients undergoing TIPS were included in this retrospective study. The cut-offs of L3-SMI for sarcopenia were 42.0 cm2/m2 in men and 38.0 cm2/m2 in women. The cut-offs for TPML/height and TPMU/height to predict mortality was established using a receiver-operating characteristic analysis. The Kaplan–Meier and Cox regression were used for survival analyses. Results: Compared with TPMU/height, TPML/height was more consistent with L3-SM for the diagnosis of sarcopenia (Kappa coefficient: 0.63 vs. 0.36 in men; 0.61 vs. 0.45 in women). The Cox analysis showed that both TPML/height and TPMU/height were independent risk factors for mortality. The optimal cut-off values of TPML/height and TPMU/height for mortality in men and women were 11.2 mm/m, 9.4 mm/m, 18.4 mm/m, 15.1 mm/m, respectively. There were 119 (47.8%), 87 (34.9%), and 82 (32.9%) patients diagnosed with sarcopenia in the TPMU/height, TPML/height, and L3-SMI models, respectively. Kaplan–Meier analysis showed that the overall survival was significantly lower in the sarcopenia group in all three models. Conclusion: TPMU/height and TPML/height have a similar survival prognostic value as L3-SMI. TPML/height has better consistency with L3-SMI in diagnosing sarcopenia and is a more stable alternative to L3-SMI for diagnosing sarcopenia in patients undergoing TIPS. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is the most frequent haematologic disorder in patients with cirrhosis, and it is perceived as a contributory factor for bleeding events. Cirrhosis patients with portal hypertension (PHT) is often accompanied with mild to moderate thrombocytopenia when they treated with transjugular intrahepatic portosystemic shunt (TIPS). To address whether the risk of variceal hemorrhage after TIPS varies with different platelet count in patients with normal platelet count and thrombocytopenia, we conducted the retrospective controlled study to evaluate the association of platelet count with the risk of variceal bleeding after TIPS. 304 patients were selected to the study. Propensity score matching was performed to adjust for potential selection bias. 63 patients from each group could be paired. Cox proportional hazards models were used to evaluate the association between platelet and variceal bleeding after TIPS. Platelet counts of two groups are 185.0 ± 98.7 × 109/L (normal platelet count) and 70.6 ± 39.3 × 109/L (thrombocytopenia) respectively. The bleeding rates of two groups in overall cohort are 10.9% (normal platelet count) and 12.9% (thrombocytopenia). After matched, the bleeding rates of two groups are 11.1% (normal platelet count) and 14.3% (thrombocytopenia) There was no statistically significant difference in bleeding rates between the two groups, either in the whole cohort (P = 0.671) or in the matched cohort (P = 0.593). Platelet count was not associated with bleeding events after TIPS (hazard ratio (HR) 95% confidence interval: 0.986–1.005, P = 0.397 in normal platelet count and 95% confidence interval: 0.968–1.020, P = 0.648 in thrombocytopenia). Thrombocytopenia in patients with cirrhosis was not associated with the risk of variceal bleeding episodes post-TIPS. Thrombocytopenia should not be viewed as an absolute contraindication for TIPS. [ABSTRACT FROM AUTHOR]

Background: Targeted puncture of an appropriate portal venous branch during transjugular intrahepatic portosystemic shunt (TIPS) procedure may reduce the risk of postprocedural overt hepatic encephalopathy (HE). This study aimed to describe blood distribution under portography and combined it with puncture site to determine portal flow diversion, and to evaluate its prognostic value in predicting post-TIPS overt HE.Methods: In this retrospective analysis of patients with cirrhosis undergoing TIPS, we included 252 patients to describe blood distribution under portography and 243 patients to assess the association between portal flow diversion and post-TIPS overt HE.Results: At the first stage, 51 (20.2%) patients were identified as type A (unilateral type with the right portal branch receives blood from splenic vein [SV]), 16 (6.4%) as type B (unilateral type with the right branch receives blood from superior mesenteric vein [SMV]) and 185 (73.4%) as type C (fully mixed type). At the second stage, 40 patients were divided into the SV group, 25 into the SMV group and 178 into the mixed group. Compared with the mixed group, the risk of post-TIPS overt HE was significantly higher in the SMV group (adjusted HR 3.70 [95% CI 2.01-6.80]; p < 0.001), whereas the SV group showed a non-significantly decreased risk (adjusted HR 0.57 [95% CI 0.22-1.48]; p = 0.25). Additionally, the SMV group showed a substantial increase in ammonia level at 3 days and 1 month after procedure.Conclusions: Our results support the clinical use of portal flow diversion for risk stratification and decision-making in the management of post-TIPS overt HE. [ABSTRACT FROM AUTHOR]

Background and Aim: An increasing number of patients with autoimmune hepatitis (AIH)-induced cirrhosis and variceal bleeding are currently referred for transjugular intrahepatic portosystemic shunt (TIPS). The aim of this study was to evaluate the safety and efficacy of TIPS in such patients, and to compare these results with data from patients with hepatitis B virus (HBV)-induced cirrhosis. Materials and Methods: This retrospective study consisted of 211 patients between August 2016 and May 2021, and patients were allocated to AIH (n = 35) and HBV (n = 176) groups according to the etiology of the cirrhosis. The primary endpoint was mortality after TIPS use; the secondary endpoints were recurrent bleeding, overt hepatic encephalopathy (OHE), shunt dysfunction, and dynamic changes in liver function over time. Results: During a median follow-up period of 27 months, 23 (10.9%) patients died, 22 (10.4%) experienced recurrent bleeding, 50 (23.7%) experienced OHE, and 25 (11.8%) developed shunt dysfunction. Compared with the HBV group, the AIH group exhibited a similar mortality risk (adjusted hazard ratio, HR 1.199; 95% confidence interval, CI 0.367–3.917; p = 0.764), OHE (adjusted HR 1.023, 95% CI 0.483–2.167, p = 0.954), and shunt dysfunction (adjusted HR 0.862, 95% CI 0.285–2.610, p = 0.792); but a higher risk of recurrent bleeding (adjusted HR 2.731, 95% CI 1.112–6.708, p = 0.028). The dynamic changes in liver function manifested an initial trend toward deterioration, and then subsequent recovery in both the AIH and HBV groups. Conclusions: TIPS is a safe and effective treatment, and should be considered for those patients with AIH-induced cirrhosis and variceal bleeding. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it.Methods: In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS.Results: A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8-30.5 months) and the median PFS was 15.7 months (95% CI: 14.7-16.6 months). The ORR was 58.8% (95% CI: 47.2-69.6) and DCR reached 81.2% (95% CI: 71.0-89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060-0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184-0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed.Conclusion: TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination. [ABSTRACT FROM AUTHOR]

Endoscopic stent placement is a palliative therapy for malignant digestive tract obstruction. However, its use for malignant afferent loop obstruction (mALO) has not been adequately investigated. From March 2009 to December 2020, 137 patients with mALO who underwent endoscopic stent placement at three tertiary care centers were retrospectively enrolled. The primary aim of this study was to compare stent dysfunction (SD) between the covered self-expandable metal stent (CSEMS) and uncovered self-expandable metal stent (UCSEMS) groups, with subgroup analysis among patients with extrinsic and intrinsic tumors separately. Twenty-three patients developed SD in the CSEMS group and 29 patients in the UCSEMS group (log-rank p =.974). The primary contributors to SD included a higher risk of stent migration in the CSEMS group and stent ingrowth in the UCSEMS group (p =.003; p <.001). Among patients with extrinsic tumors, the CSEMS group showed a significantly higher probability of overall SD (p =.008) and stent migration (p =.001) with a shorter time to SD (log-rank p =.006) than the UCSEMS group. Among patients with intrinsic tumors, the CSEMS group showed a significantly lower incidence of overall SD (p <.001) and stent ingrowth (p <.001) with a longer time to SD (log-rank p =.011) than the UCSEMS group. Our results showed no significant difference in SD between the CSEMS and UCSEMS groups for palliation of mALO. Furthermore, subgroup analysis suggested using CSEMSs for patients with intrinsic tumors, and UCSEMSs for those with extrinsic tumors. [ABSTRACT FROM AUTHOR]

Liver fibrosis plays a crucial role in promoting tumor immune escape and tumor aggressiveness for liver cancer. However, an interesting phenomenon is that the tumor size of liver cancer patients with liver fibrosis is smaller than that of patients without liver fibrosis. In this study, 16 SD rats were used to establish orthotopic liver tumor transplantation models with Walker-256 cell lines, respectively on the fibrotic liver (n = 8, LF group) and normal liver (n = 8, control group). MRI (magnetic resonance imaging) was used to monitor the size of the tumors. All rats were executed at the third week after modeling, and the immunohistochemical staining was used to reflect the changes in the tumor microenvironment. The results showed that, compared to the control group, the PD-L1 (programmed cell death protein receptor-L1) expression was higher, and the neutrophil infiltration increased while the effector (CD8+) T cell infiltration decreased in the LF group. Additionally, the expression of MMP-9 (matrix metalloproteinase-9) of tumor tissue in the LF group increased. Three weeks after modeling, the size of tumors in the LF group was significantly smaller than that in the control group (382.47 ± 195.06 mm3 vs. 1736.21 ± 657.25 mm3, P < 0.001). Taken together, we concluded that liver fibrosis facilitated tumor immunity escape but limited the expansion of tumor size. [ABSTRACT FROM AUTHOR]