Acute liver failure (ALF) induces increased energy expenditure and disrupts the metabolism of essential nutrients. Hepatic encephalopathy is a complication of ALF with a poor prognosis and mainly involves the metabolic disturbance of amino acids in its pathogenesis. In this review, we discuss the nutritional management for ALF in consideration of the pathophysiology of ALF with respect to the impairment of hepatocyte function. It is known that enteral nutrition is recommended for patients with ALF, while parenteral nutrition is recommended for patients who cannot tolerate enteral nutrition. As ALF leads to a hypermetabolic state, the energy intake is recommended to cover 1.3 times the resting energy expenditure. Because of the high risk of hypoglycemia associated with disturbances in glucose metabolism, substantial glucose intake is recommended. Along with the deterioration of glucose metabolism, protein metabolism is also disrupted. As patients with ALF have increased systemic protein catabolism together with decreased protein synthesis, appropriate amounts of amino acids or protein under monitoring serum ammonia levels are recommended. In conclusion, nutritional management based on the understanding of nutritional pathophysiology is a pivotal therapeutic approach for patients with ALF. The approach should be individualized in the acute phase, the recovery phase, and the pretransplant phase.

Portal hypertension has cerebral consequences via its causes and complications, namely hepatic encephalopathy (HE), a common and devastating brain disturbance caused by liver insufficiency and portosystemic shunting. The pathogenesis involves hyperammonemia and systemic inflammation. Symptoms are disturbed personality and reduced attention. HE is minimal or grades I to IV (coma). Bouts of HE are episodic and often recurrent. Initial treatment is of events that precipitated the episode and exclusion of nonhepatic causes. Specific anti-HE treatment is lactulose. By recurrence, rifaximin is add-on. Anti-HE treatment is efficacious also for prophylaxis, but emergence of HE marks advanced liver disease and a dismal prognosis.

BACKGROUND: Dementia and hepatic encephalopathy (HE) have symptom overlap and are challenging to differentiate. The presence of undiagnosed cirrhosis may lead to missed opportunities to treat HE, which was found in a Veterans database. This needs validation in a non-Veteran cohort.
METHODS: A retrospective cohort study was conducted between 2009 and 2019 using national non-Veteran patient data from the multi-center TriNetX database. Participants included 68,807 patients with a dementia diagnosis at ≥2 visits, no prior diagnosis of cirrhosis, and with sufficient laboratory test results to calculate the Fibrosis-4 (FIB-4) index, which indicates liver disease. Prevalences of high FIB-4 scores (>2.67 and >3.25) were measured within the cohort, and associations between high FIB-4 and comorbidities/demographics were examined.
RESULTS: Within the cohort (44.7% male, 78.0% white, mean age 72.73 years (±11.09)), 7.6% (n = 5815) had a FIB-4 index >3.25 and 12.8% (n=8683) had FIB-4 >2.67. In multivariable logistic regression models, FIB-4 > 3.25 was associated with male gender (OR: 1.42 [1.33-1.51]), congestive heart failure (OR:1.73 [1.59-1.87]), viral hepatitis (OR: 2.23 [1.84-2.68]), alcohol use disorder (OR: 1.39 [1.22-1.58]), and chronic kidney disease (OR: 1.38 [1.28-1.48]), and inversely associated with white race (OR: 0.76 [0.71-0.82]) and diabetes (OR: 0.82 [0.77-0.88]). Similar findings were associated with the FIB-4 > 2.67 threshold.
CONCLUSIONS: The findings of this national cohort suggest that the FIB-4 index could be utilized to screen for potential undiagnosed cirrhosis in patients with dementia and that hepatic encephalopathy that might be misdiagnosed as dementia or cause worsening of cognitive function in patients with dementia.

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.

暂无摘要。

Type-2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis-related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long-term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin-treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p = .016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long-term HA administration was associated with better survival and a lower incidence of cirrhosis-related complications.

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.

High-protein diet is the cornerstone of supportive care for patients living with hepatic encephalopathy. Although any protein source is better than protein restriction, there is uncertainty regarding the benefits of specific protein types. Using a randomized trial, Badal et al. evaluate the effect on ammonia levels and metabolomics from 3 protein sources in burgers made from beef, vegan products, and vegetarian products. The vegan and vegetarian burgers did not raise ammonia and may result in favorable metabolomic profiles.

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.