This study aimed to assess the safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy (HE) associated with large spontaneous portosystemic shunts (SPSS). Inverse probability of treatment weighting (IPTW) was employed to minimize potential bias. A total of 123 patients were included in this study (34 in the embolization group and 89 in the control group). In the unadjusted cohort, the embolization group demonstrated significantly better liver function, a larger total area of SPSS, and a higher percentage of patients with serum ammonia levels > 60 µmol/L and the presence of hepatocellular carcinoma (HCC) (all P < 0.05). In the IPTW cohort, baseline characteristics were comparable between the two groups (all P > 0.05). Patients in the embolization group exhibited significantly longer HE-free survival compared to the control group in both the unadjusted and IPTW cohorts (both P < 0.05). Subsequent subgroup analyses indicated that patients with serum ammonia level > 60 μmol/L, hepatopetal flow within the portal trunk, the presence of solitary SPSS, a baseline HE grade of II, and the absence of HCC at baseline showed statistically significant benefit from embolization treatment (all P < 0.05). No early procedural complications were observed in the embolization group. The incidence of long-term postoperative complications was comparable to that in the control group (all P > 0.05). Hence, interventional embolization appears to be a safe and effective treatment modality for cirrhotic patients with refractory HE associated with large SPSS. However, the benefits of embolization were discernible only in a specific subset of patients.

Branched-chain amino acids (BCAAs), as essential amino acids, engage in various physiological processes, such as protein synthesis, energy supply, and cellular signaling. The liver is a crucial site for BCAA metabolism, linking the changes in BCAA homeostasis with the pathogenesis of a variety of liver diseases and their complications. Peripheral circulating BCAA levels show complex trends in different liver diseases. This review delineates the alterations of BCAAs in conditions including non-alcoholic fatty liver disease, hepatocellular carcinoma, cirrhosis, hepatic encephalopathy, hepatitis C virus infection, and acute liver failure, as well as the potential mechanisms underlying these changes. A significant amount of clinical research has utilized BCAA supplements in the treatment of patients with cirrhosis and liver cancer. However, the efficacy of BCAA supplementation in clinical practice remains uncertain and controversial due to the heterogeneity of studies. This review delves into the complicated relationship between BCAAs and liver diseases and tries to untangle what role BCAAs play in the occurrence, development, and outcomes of liver diseases.

End-stage liver diseases, such as cirrhosis and liver cancer caused by hepatitis B, are often combined with hepatic encephalopathy (HE); ammonia poisoning is posited as one of its main pathogenesis mechanisms. Ammonia is closely related to autophagy, but the molecular mechanism of ammonia\'s regulatory effect on autophagy in HE remains unclear. Sialylation is an essential form of glycosylation. In the nervous system, abnormal sialylation affects various physiological processes, such as neural development and synapse formation. ST3 β‍-galactoside α2,‍3-sialyltransferase 6 (ST3GAL6) is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures. We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction, and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3 (LC3) and Beclin-1 were upregulated in ammonia-induced astrocytes. These findings suggest that ST3GAL6 is related to autophagy in HE. Therefore, we aimed to determine the regulatory relationship between ST3GAL6 and autophagy. We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II (MAL-II) and neuraminidase can inhibit autophagy. In addition, silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein β8 (HSPB8) and Bcl2-associated athanogene 3 (BAG3). Notably, the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression. Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.
肝性脑病（HE）是肝病（如乙型肝炎引起的肝硬化和肝癌）发展到终末期之后的一个常见的并发症，氨中毒被认为是其主要的发病机制之一。氨与自噬密切相关，但其对HE的自噬调节作用的分子机制尚不清楚。唾液酸化是糖基化的一种重要形式。在神经系统中，异常的唾液酸化会影响各种生理过程，例如神经发育和突触形成。ST3 β-半乳糖苷α2,3-唾液酸转移酶6（ST3GAL6）是一种重要的糖基转移酶，负责将α2,3-连接的唾液酸添加到底物并生成聚糖结构。在本研究中，我们发现经氨诱导后，HE小鼠大脑和星形胶质细胞中ST3GAL6的表达上调，并且在氨诱导的星形胶质细胞中，α2,3-唾液酸化聚糖和自噬相关蛋白微管相关蛋白轻链3（LC3）和Beclin-1的表达均上调。上述结果表明：ST3GAL6与HE中的自噬有关。因此，本研究将进一步确定ST3GAL6与自噬之间的调控关系。我们发现通过沉默ST3GAL6以及通过怀槐凝集素-II（MAL-II）和神经氨酸酶阻断或降解α2,3-唾液酸化聚糖可以抑制自噬。此外，沉默ST3GAL6的表达可以下调热休克蛋白β8（HSPB8）和Bcl2关联永生基因3（BAG3）的表达。值得注意的是，HSPB8的过表达可部分恢复因ST3GAL6表达沉默而导致的自噬水平降低。综上，我们的结果表明了ST3GAL6可通过HSPB8-BAG3复合物调节自噬。.

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.

Hepatic encephalopathy (HE) is a clinical manifestation of neurological and psychiatric abnormalities that are caused by complications of liver dysfunction including hyperammonemia, hyperuricemia, and portal hypertension. Accumulating evidence suggests that HE could be reversed through therapeutic modifications of gut microbiota. Multiple preclinical and clinical studies have indicated that gut microbiome affects the physiological function of the liver, such as the regulation of metabolism, secretion, and immunity, through the gut-liver crosstalk. In addition, gut microbiota also influences the brain through the gut-brain crosstalk, altering its physiological functions including the regulation of the immune, neuroendocrine, and vagal pathways. Thus, key molecules that are involved in the microbiota-gut-liver-brain axis might be able to serve as clinical biomarkers for early diagnosis of HE, and could be effective therapeutic targets for clinical interventions. In this review, we summarize the pathophysiology of HE and further propose approaches modulating the microbiota-gut-liver-brain axis in order to provide a comprehensive understanding of the prevention and potential clinical treatment for HE with a microbiota-targeted therapy.

End-stage liver diseases, such as cirrhosis and liver cancer caused by hepatitis B, are often combined with hepatic encephalopathy (HE); ammonia poisoning is posited as one of its main pathogenesis mechanisms. Ammonia is closely related to autophagy, but the molecular mechanism of ammonia\'s regulatory effect on autophagy in HE remains unclear. Sialylation is an essential form of glycosylation. In the nervous system, abnormal sialylation affects various physiological processes, such as neural development and synapse formation. ST3 β‍-galactoside α2,‍3-sialyltransferase 6 (ST3GAL6) is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures. We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction, and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3 (LC3) and Beclin-1 were upregulated in ammonia-induced astrocytes. These findings suggest that ST3GAL6 is related to autophagy in HE. Therefore, we aimed to determine the regulatory relationship between ST3GAL6 and autophagy. We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II (MAL-II) and neuraminidase can inhibit autophagy. In addition, silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein β8 (HSPB8) and Bcl2-associated athanogene 3 (BAG3). Notably, the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression. Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.
肝性脑病（HE）是肝病（如乙型肝炎引起的肝硬化和肝癌）发展到终末期之后的一个常见的并发症，氨中毒被认为是其主要的发病机制之一。氨与自噬密切相关，但其对HE的自噬调节作用的分子机制尚不清楚。唾液酸化是糖基化的一种重要形式。在神经系统中，异常的唾液酸化会影响各种生理过程，例如神经发育和突触形成。ST3 β-半乳糖苷α2,3-唾液酸转移酶6（ST3GAL6）是一种重要的糖基转移酶，负责将α2,3-连接的唾液酸添加到底物并生成聚糖结构。在本研究中，我们发现经氨诱导后，HE小鼠大脑和星形胶质细胞中ST3GAL6的表达上调，并且在氨诱导的星形胶质细胞中，α2,3-唾液酸化聚糖和自噬相关蛋白微管相关蛋白轻链3（LC3）和Beclin-1的表达均上调。上述结果表明：ST3GAL6与HE中的自噬有关。因此，本研究将进一步确定ST3GAL6与自噬之间的调控关系。我们发现通过沉默ST3GAL6以及通过怀槐凝集素-II（MAL-II）和神经氨酸酶阻断或降解α2,3-唾液酸化聚糖可以抑制自噬。此外，沉默ST3GAL6的表达可以下调热休克蛋白β8（HSPB8）和Bcl2关联永生基因3（BAG3）的表达。值得注意的是，HSPB8的过表达可部分恢复因ST3GAL6表达沉默而导致的自噬水平降低。综上，我们的结果表明了ST3GAL6可通过HSPB8-BAG3复合物调节自噬。.

OBJECTIVE: The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs.
METHODS: This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at 7 medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality.
RESULTS: A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% vs 13.6%; P = .005) and OHE (31.0% vs 39.4%; P = .02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% vs 9.7%; P = .42). In patients with GOV2 and IGV1, TIPS plus variceal embolization reduced both rebleeding (GOV2: 7.8% vs 25.1%; P = .01; IGV1: 5.6% vs 30.8%; P = .03) and OHE (GOV2: 31.8% vs 51.5%; P = .008; IGV1: 11.6% vs 38.5%; P = .04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% vs 8.7%; P = .37) or OHE (33.1% vs 35.3%; P = .60).
CONCLUSIONS: Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.

BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF).
METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed.
RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes.
CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.

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.

暂无摘要。