In 2023, Chinese Society of Hepatology of Chinese Medical Association convened a panel of experts to update the Chinese guidelines on the management of ascites and associated complications in cirrhosis which was launched in 2017 and renamed this guidelines as \"Guidelines on the Management of Ascites in Cirrhosis.\" This comprehensive resource offers essential recommendations for the diagnosis and treatment of cirrhotic ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome.

Managing cirrhosis complications is an important measure for improving patients\' clinical outcomes. Therefore, in order to provide a complete disease assessment and comprehensive treatment, improve quality of life, and improve the prognosis for patients with cirrhosis, it is necessary to pay attention to complications such as thrombocytopenia and portal vein thrombosis in addition to common or severe complications such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. The relevant concept that an effective albumin concentration is more helpful in predicting the cirrhosis outcome is gradually being accepted; however, the detection method still needs further standardization and commercialization.
肝硬化并发症的管理是改善肝硬化患者临床结局的重要措施。除了关注腹水、食管胃静脉出血、肝性脑病、肝肾综合征等常见或危急并发症外，也需要关注血小板减少症、门静脉血栓形成等并发症，以期为肝硬化患者提供完整的病情评估和全面的治疗，提高其生活质量、改善其预后。有效白蛋白更有助于预测肝硬化结局，相关概念逐渐被接受，但其检测方法仍有待进一步标准化和商业化。.

Glycyrrhizin (GL) has immunoregulatory effects on various inflammatory diseases including hepatitis and nephritis. However, the mechanisms underlying the anti-inflammatory effect of GL on renal inflammation are not fully understood. Hepatorenal syndrome (HRS) is a functional acute renal impairment that occurs in severe liver disease, and we found that kidney injury also occurs in Con A-induced experimental hepatitis in mice. We previously found that GL can alleviate Con A-induced hepatitis by regulating the expression of IL-25 in the liver. We wanted to investigate whether GL can alleviate Con A-induced nephritis by regulating IL-25. IL-25 regulates inflammation by modulating type 2 immune responses, but the mechanism by which IL-25 affects kidney disease remains unclear. In this study, we found that the administration of GL enhanced the expression of IL-25 in renal tissues; the latter promoted the generation of type 2 macrophages (M2), which inhibited inflammation in the kidney caused by Con A challenge. IL-25 promoted the secretion of the inhibitory cytokine IL-10 by macrophages but inhibited the expression of the inflammatory cytokine IL-1β by macrophages. Moreover, IL-25 downregulated the Con A-mediated expression of Toll-like receptor (TLR) 4 on macrophages. By comparing the roles of TLR2 and TLR4, we found that TLR4 is required for the immunoregulatory effect of IL-25 on macrophages. Our data revealed that GL has anti-inflammatory effects on Con A-induced kidney injury and that the GL/IL-25/M2 axis participates in the anti-inflammatory process. This study suggested that GL is a potential therapeutic for protecting against acute kidney injury.

Objective: To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF). Methods: 220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi\'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ(2) test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results: There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group (P < 0.05). Among the 220 ACLF cases, 158 (71.82%) were infected with the hepatitis B virus (HBV). The incidence rate of infection during hospitalization was 69.09% (152/220). The common sites of infection were intraabdominal (57.07%) and pulmonary infection (29.29%). Pearson correlation analysis showed that PNI and MELD-Na were negatively correlated (r = -0.150, P < 0.05). Multivariate logistic analysis results showed that low PNI score (OR=0.916, 95%CI: 0.865~0.970), ascites (OR=4.243, 95%CI: 2.237~8.047), and hepatorenal syndrome (OR=4.082, 95%CI : 1.106~15.067) were risk factors for ACLF co-infection (P < 0.05). The ROC results showed that the PNI curve area (0.648) was higher than the MELD-Na score curve area (0.610, P < 0.05). The effectiveness of predicting infection risk when PNI was combined with ascites and hepatorenal syndrome complications was raised. Patients with co-infections had a good predictive effect when PNI ≤ 40.625. The sensitivity and specificity were 84.2% and 41.2%, respectively. Conclusion: Low PNI score and ACLF co-infection have a close correlation. Therefore, PNI has a certain appraisal value for ACLF co-infection.
目的： 探讨预后营养指数（PNI）对慢加急性肝衰竭（ACLF）患者并发感染的预测价值。 方法： 选取2011年1月至2016年12月西安交通大学第一附属医院诊治的220例ACLF患者，根据病程中是否合并感染分为感染组和非感染组，比较两组患者临床资料的差异。用二元logistic回归分析，筛选出与合并感染有关的影响因素。再应用受试者操作特征曲线法（ROC）评估PNI对于ACLF合并感染的预测价值。计量资料组间数据比较采用独立样本t检验、Mann-Whitney U秩和检验；计数资料采用Fisher精确概率法检验或Pearson χ(2)检验进行分析；Pearson法进行相关性分析；用logistic多因素分析肝衰竭合并感染的独立危险因素。 结果： 感染组与非感染组患者腹水、肝肾综合征、PNI评分、白蛋白等差异有统计学意义（P值均< 0.05）。220例ACLF患者病因中乙型肝炎病毒（HBV）感染的有158例（71.82%），住院期间感染发生率为69.09%（152/220)；常见感染部位为腹腔感染（57.07%）和肺部感染（29.29%）。Pearson相关性分析显示PNI与终末期肝病模型联合血清钠（MELD-Na）呈负相关（r = -0.150, P < 0.05）。Logistic多因素分析结果显示低PNI评分（OR = 0.916, 95%CI: 0.865～0.970）、腹水（OR = 4.243, 95%CI: 2.237～8.047）、肝肾综合征（OR = 4.082, 95%CI: 1.106～15.067）是ACLF合并感染的危险因素（P值均< 0.05）。ROC结果显示PNI曲线下面积（0.648）高于MELD-Na评分的曲线下面积（0.610，P < 0.05)；PNI联合腹水、肝肾综合征合并症时，预测感染风险效能升高。当PNI≤40.625时，对患者合并感染有较好的预测作用，灵敏度和特异度分别为84.2%和41.2%。 结论： 低PNI评分与ACLF合并感染有密切关系，PNI对ACLF合并感染有一定的评估价值。.

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The sympathetic nervous system(SNS)plays a pivotal role in maintaining organ homeostasis and the pathogenesis of various ailments.Studies have unveiled a profound interconnection between sympathetic nerves and the development of liver cirrhosis,cirrhotic cardiomyopathy,and hepatorenal syndrome.Therefore,researchers have proposed SNS as a candidate therapeutic target for liver-related disorders.This article reviewed the research progress of sympathetic nerves in liver cirrhosis,cirrhotic cardiomyopathy,and hepatorenal syndrome,aiming to enrich the knowledge about the roles of sympathetic nerves in cirrhosis and its complications and provide new ideas for the treatment of liver cirrhosis and its complications.
交感神经系统(SNS)在维持器官正常功能和疾病发生发展中起着重要作用。目前研究发现交感神经与肝硬化、肝硬化心肌病和肝肾综合征(HRS)的发生发展密切相关,SNS也许可作为肝脏相关疾病的治疗靶点。为了深入理解交感神经在肝硬化及其并发症的作用,本文综述了交感神经在肝硬化、肝硬化心肌病和HRS中的作用研究进展,以此为治疗肝硬化及其并发症提供新思路。.

Non-selective β blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output. This study aimed to systematically investigate their association.
PubMed, EMBASE, and Cochrane library databases were searched to identify all relevant studies evaluating the association of NSBBs with renal dysfunction in cirrhotic patients. Unadjusted and adjusted data were separately extracted. Odds ratios (ORs) and hazard ratios (HRs) were pooled. Subgroup meta-analyses were performed according to the proportions of ascites and Child-Pugh class B/C and the mean model for end-stage liver disease (MELD) score. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.
Fourteen studies were finally included. Based on unadjusted data, NSBBs significantly increased the risk of developing renal dysfunction (OR = 1.49; p = 0.03), and this association remained significant in subgroup analyses of studies where the proportions of ascites was >70% and Child-Pugh class B/C was 100%. Based on adjusted data with propensity score matching (adjusted OR = 0.61; p = 0.08) and multivariable regression modelling (adjusted HR = 0.86; p = 0.713), NSBBs did not increase the risk of developing renal dysfunction, and this association remained not significant in subgroup analyses of studies where the proportions of ascites was >70% and <70%, the proportion of Child-Pugh class B/C was <100%, and the mean MELD score was <15. The quality of evidence was very low for all meta-analyses.
NSBBs may not be associated with the development of renal dysfunction in liver cirrhosis. However, more evidence is required to clarify their association in specific populations.
Non-selective β blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output in liver cirrhosis.Our meta-analysis failed to support the association of NSBBs with an increased risk of developing renal dysfunction after covariate adjustment.

Systemic therapies have improved the management of hepatocellular carcinoma, but there is still a need to further enhance overall survival in first-line advanced stages. This study aimed to evaluate the addition of pembrolizumab to lenvatinib versus lenvatinib plus placebo in the first-line setting for unresectable hepatocellular carcinoma.
In this global, randomised, double-blind, phase 3 study (LEAP-002), patients aged 18 years or older with unresectable hepatocellular carcinoma, Child Pugh class A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no previous systemic treatment were enrolled at 172 global sites. Patients were randomly assigned (1:1) with a central interactive voice-response system (block size of 4) to receive lenvatinib (bodyweight <60 kg, 8 mg/day; bodyweight ≥60 kg, 12 mg/day) plus pembrolizumab (200 mg every 3 weeks) or lenvatinib plus placebo. Randomisation was stratified by geographical region, macrovascular portal vein invasion or extrahepatic spread or both, α-fetoprotein concentration, and Eastern Cooperative Oncology Group performance status. Dual primary endpoints were overall survival (superiority threshold at final overall survival analysis, one-sided p=0·019; final analysis to occur after 532 events) and progression-free survival (superiority threshold one-sided p=0·002; final analysis to occur after 571 events) in the intention-to-treat population. Results from the final analysis are reported. This study is registered with ClinicalTrials.gov, NCT03713593, and is active but not recruiting.
Between Jan 17, 2019, and April 28, 2020, of 1309 patients assessed, 794 were randomly assigned to lenvatinib plus pembrolizumab (n=395) or lenvatinib plus placebo (n=399). Median age was 66·0 years (IQR 57·0-72·0), 644 (81%) of 794 were male, 150 (19%) were female, 345 (43%) were Asian, 345 (43%) were White, 22 (3%) were multiple races, 21 (3%) were American Indian or Alaska Native, 21 (3%) were Native Hawaiian or other Pacific Islander, 13 (2%) were Black or African American, and 46 (6%) did not have available race data. Median follow up as of data cutoff for the final analysis (June 21, 2022) was 32·1 months (IQR 29·4-35·3). Median overall survival was 21·2 months (95% CI 19·0-23·6; 252 [64%] of 395 died) with lenvatinib plus pembrolizumab versus 19·0 months (17·2-21·7; 282 [71%] of 399 died) with lenvatinib plus placebo (hazard ratio [HR] 0·84; 95% CI 0·71-1·00; stratified log-rank p=0·023). As of data cutoff for the progression-free survival final analysis (April 5, 2021), median progression-free survival was 8·2 months (95% CI 6·4-8·4; 270 events occurred [42 deaths; 228 progressions]) with lenvatinib plus pembrolizumab versus 8·0 months (6·3-8·2; 301 events occurred [36 deaths; 265 progressions]) with lenvatinib plus placebo (HR 0·87; 95% CI 0·73-1·02; stratified log-rank p=0·047). The most common treatment-related grade 3-4 adverse events were hypertension (69 [17%] of 395 patients in the lenvatinib plus pembrolizumab group vs 68 [17%] of 395 patients) in the lenvatinib plus placebo group), increased aspartate aminotransferase (27 [7%] vs 17 [4%]), and diarrhoea (25 [6%] vs 15 [4%]). Treatment-related deaths occurred in four (1%) patients in the lenvatinib plus pembrolizumab group (due to gastrointestinal haemorrhage and hepatorenal syndrome [n=1 each] and hepatic encephalopathy [n=2]) and in three (1%) patients in the lenvatinib plus placebo group (due to gastrointestinal haemorrhage, hepatorenal syndrome, and cerebrovascular accident [n=1 each]).
In earlier studies, the addition of pembrolizumab to lenvatinib as first-line therapy for advanced hepatocellular carcinoma has shown promising clinical activity; however, lenvatinib plus pembrolizumab did not meet prespecified significance for improved overall survival and progression-free survival versus lenvatinib plus placebo. Our findings do not support a change in clinical practice.
Eisai US, and Merck Sharp & Dohme, a subsidiary of Merck.

The high levels of bile acids are a critical factor in hepatorenal syndrome. Organic solute transporter α/β (Ostα/β) participate in bile acids reabsorption in the kidney. Fucoidan has the great potential in protecting against liver and kidney injury. However, whether Ostα/β increase bile acids reabsorption in bile duct ligature (BDL)-induced hepatorenal syndrome and the blockade of fucoidan are still not clear. Male mice that received BDL were given to fucoidan (at 12.5, 25 and 50 ​mg/kg) through intraperitoneal injection once daily for three weeks. The serum, liver and kidney samples of these experimental mice were collected to carry out biochemical, pathological and Western blot analysis. In this study, fucoidan significantly lowered serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), decreased serum levels of uric acid, creatinine and uric nitrogen, restored the deregulation of the renal urate transporter 1 (URAT1), organic anion transporter 1 (OAT1), and organic cation/carnitine transporter 1/2 (OCTN1/2), consistence with alleviation BDL-induced liver and kidney dysfunction, inflammation and fibrosis in mice. Furthermore, fucoidan significantly hampered Ostα/β and reduced bile acids reabsorption in BDL-induced mice, protected against AML12 and HK-2 ​cells injury in vitro. These results demonstrate that fucoidan alleviates BDL-induced hepatorenal syndrome through inhibition Ostα/β to reduce bile acids reabsorption in mice. Therefore, suppression of Ostα/β by fucoidan may be a novel strategy for attenuating hepatorenal syndrome.

Spontaneous portosystemic shunt (SPSS) other than esophago-gastric varices is one of the consequences of cirrhosis-induced portal hypertension (PHT), but its role is not fully understood. Therefore, we conducted a systematic review and meta-analysis to determine the prevalence and clinical characteristics of SPSS (excluding esophago-gastric varices) and its impact on mortality in patients with cirrhosis.
Eligible studies were identified from MedLine, PubMed, Embase, Web of Science, and Cochrane Library between Jan 1, 1980 and Sep 30, 2022. Outcome indicators were SPSS prevalence, liver function, decompensated events, and overall survival (OS).
Totally, 2015 studies were reviewed, of which 19 studies recruiting 6884 patients were included. On pooled analysis, the prevalence of SPSS was 34.2% (26.6%∼42.1%). SPSS patients had significantly higher Child-Pugh scores and grades and Model for End-stage Liver Disease scores (all P<0.05). Moreover, SPSS patients experienced a higher incidence of decompensated events, including hepatic encephalopathy, portal vein thrombosis, and hepatorenal syndrome (all P<0.05). Additionally, SPSS patients had significantly shorter OS than the non-SPSS group (P<0.05).
In patients with cirrhosis, SPSS outside the esophago-gastric region is common, characterized by severe impairment of liver function, high rates of decompensated events, including HE, PVT, and hepatorenal syndrome, as well as a high mortality rate.