Advancing hepatic recompensation:Baveno VII criteria and therapeutic innovations in liver cirrhosis management

The Baveno VII criteria redefine the management of decompensated liver cirrhosis,introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline.Central to this concept is addressing the underlying cause of cirrhosis through tailored therapies,including antivirals and lifestyle modifications.Studies on alcohol,hepatitis C virus,and hepatitis B virus-related cirrhosis demonstrate the efficacy of these interventions in improving liver function and patient outcomes.Transjugular intrahepatic portosystemic shunt(TIPS)emerges as a promising intervention,effectively resolving complications of portal hypertension and facilitating recompensation.However,optimal timing and patient selection for TIPS remain unresolved.Despite challenges,TIPS offers renewed hope for hepatic recompensation,marking a significant advancement in cirrhosis management.Further research is needed to refine its implementation and maximize its benefits.In conclusion,TIPS stands as a promising avenue for improving hepatic function and patient outcomes in decompensated liver cirrhosis within the framework of the Baveno VII criteria.

Road to recompensation:BavenoⅦcriteria 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 mechanisms 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.

Hepatic recompensation according to Baveno VII criteria via transjugular intrahepatic portosystemic shunt

Transjugular intrahepatic portosystemic shunt is a therapeutic modality done through interventional radiology.It is aimed to decrease portal pressure in special situations for patients with decompensated liver disease with portal hypertension.It represents a potential addition to the therapeutic modalities that could achieve hepatic recompensation in those patients based on Baveno VII criteria.

Chronic hepatitis B virus infection in Eastern Ethiopia:Clinical characteristics and determinants of cirrhosis

BACKGROUND Chronic hepatitis B(CHB)virus infection is a major cause of liver-associated morbidity and mortality,particularly in low-income countries.A better understanding of the epidemiological,clinical,and virological characteristics of CHB will guide appropriate treatment strategies and improve the control and management of CHB in Ethiopia.AIM To investigate the characteristics of CHB in Eastern Ethiopia and assess the efficacy and safety of antiviral treatment.METHODS This cohort study included 193 adults who were human immunodeficiency virus-negative with CHB between June 2016 and December 2019.Baseline assessments included chemistry,serologic,and viral markers.χ^(2) tests,Mann-Whitney U tests,and logistic regression analyses were used to identify the determinants of cirrhosis.Tenofovir disoproxil fumarate(TDF)was initiated using treatment criteria from the Ethiopian CHB pilot program.RESULTS A total of 132 patients(68.4%)were men,with a median age of 30 years[interquartile range(IQR):24-38].At enrollment,60(31.1%)patients had cirrhosis,of whom 35(58.3%)had decompensated cirrhosis.Khat use,hepatitis B envelope antigen positivity,and a high viral load were independently associated with cirrhosis.Additionally,66 patients(33.4%)fulfilled the treatment criteria and 59(30.6%)started TDF.Among 29 patients who completed 24 months of treatment,the median aspartate aminotransferase to platelet ratio index declined from 1.54(IQR:0.66-2.91)to 1.10(IQR:0.75-2.53)(P=0.002),and viral suppression was achieved in 80.9%and 100%of patients after 12 months and 24 months of treatment,respectively.Among the treated patients,12(20.3%)died within the first 6 months of treatment,of whom 8 had decompensated cirrhosis.CONCLUSION This study highlights the high prevalence of cirrhosis,initial mortality,and the efficacy of TDF treatment.Scaling up measures to prevent and control CHB infections in Ethiopia is crucial.

Differential hepatic features presenting in Wilson disease-associated cirrhosis and hepatitis B-associated cirrhosis

BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses,alcoholism, and metabolic disorders, such as Wilson disease(WD). There are no clear markers or clinical features that define cirrhosis originating from these disparate origins. We hypothesized that cirrhosis is not one disease and cirrhosis of different etiology may have differential clinical hepatic features.AIM To delineate the liver features between WD-associated cirrhosis and hepatitis Bassociated cirrhosis in the Chinese population.METHODS In this observational study, we reviewed the medical data of consecutive inpatients who had WD-associated cirrhosis or hepatitis B-associated cirrhosis from January 2010 to August 2018, and excluded patients who had carcinoma,severe heart or pulmonary diseases, or other liver diseases. According to the etiology of cirrhosis, patients were divided into two groups: WD-associated cirrhosis group(60 patients) and hepatitis B-associated cirrhosis group(56 patients). The liver fibrosis degree, liver function indices, and portal hypertension features of these patients were compared between the two groups.RESULTS No inter-group differences were observed in the diagnostic liver fibrosis markers,however, clinical features clearly defined the origin of cirrhosis. WD-associated cirrhosis patients(16-29 years) had lower levels of alanine transaminase,aspartate transaminase, and bilirubin, lower prothrombin time, lower incidence of hepatic encephalopathy, and lower portal vein diameter(P < 0.05), compared to cirrhosis resulting from hepatitis B in older patients(45-62 years). Importantly,they had decreased risks of progression from Child-Pugh grade A to B(odds ratio = 0.046, 95% confidence interval: 0.006-0.387, P = 0.005) and of ascites(odds ratio = 0.08, 95% confidence interval: 0.01-0.48, P = 0.005). Conversely, WDassociated cirrhosis patients had a higher risk of splenomegaly(odds ratio = 4.15,95% confidence interval: 1.38-12.45, P = 0.011).CONCLUSION WD-associated cirrhosis presents a higher risk of splenomegaly associated with leukopenia and thrombocytopenia, although revealing milder liver dysfunction and portal hypertension symptoms, which recommends WD patients to be monitored for associated complications.

Risk factors for hepatic decompensation in patients with primary biliary cirrhosis

AIM:To examine the clinical features and analyze prognostic factors in a prospective study of primary biliary cirrhosis(PBC) patients.METHODS:From 1995 to 2010,PBC patients without hepatic decompensation seen at the Peking Union Medical College Hospital were enrolled.Clinical signs and manifestations(pruritus,persistent fatigue,jaundice and pain in the right hypochondrium),laboratory parameters(auto-antibodies for autoimmune hepatic disease,biliary and hepatic enzymes,immunoglobulin,bilirubin,and albumin) and imaging findings were recorded at entry and at specific time points during follow-up.Cox regression and Kaplan-Meier analyses,respectively,assessed the risk factors for hepatic decompensation and survival.RESULTS:Two hundred and sixty-two PBC patients were enrolled with a median follow-up of 75.2 mo(range,21-201 mo).The 240 patients were aged 51.5 ± 10.2 years at diagnosis and 91.6% were female.Two hundred and forty-five(93.5%) were seropositive for anti-mitochondrial antibodies.At presentation,170 patients(64.9%) were symptomatic,while 96 patients(36.6%) had extra-hepatic autoimmune disease.During the follow-up period,62(23.7%) patients developed hepatic decompensation of whom four underwent liver transplantation and 17 died.The cumulative survival rate and median survival time were 83.9% and 181.7 mo,respectively.Cox regression analysis revealed that an incomplete ursodeoxycholic acid(UDCA) response or inconsistent treatment [P < 0.001;hazard risk(HR) 95%CI = 2.423-7.541],anti-centromere antibodies(ACA) positivity(P < 0.001;HR 95%CI = 2.516-7.137),alanine aminotransferase ratio(AAR) elevations(P < 0.001;HR 95%CI = 1.357-2.678),and histological advanced liver disease(P = 0.006;HR 95%CI = 1.481-10.847) were predictors of hepatic decompensation.The clinical features and survival of PBC in China are consistent with those described in Western countries.CONCLUSION:Incomplete UDCA response or inconsistent treatment,ACA positivity,AAR elevations,and advanced histological stage are predictors of decompensation.

Adjuvant hepatic chemotherapy after resection of solitary hepatocellular carcinoma associated with hepatitis B virus cirrhosis

BACKGROUND: Although resection is the major treatment for patients with hepatocellular carcinoma ( HCC), the high intrahepatic recurrence remains a cardinal cause of death. This study was undertaken to evaluate the effect of hepatic arterial infusion chemotherapy on the survival and recurrence of HCC patients with hepatitis B virus ( HBV) cirrhosis after resection. METHODS: Twenty-eight patients who had undergone placement of a hepatic arterial pump at the time of liver wedge resection for HCC from 1998 through 2004 were reviewed retrospectively. These patients aged 23-71 years had HBV cirrhosis (Child-Pugh class A or B). They were given floxuridine(FUDR) (250 mg), doxorubicin (10 mg) and mitomycin C (4 mg) alternatively every 2 or 3 days through arterial pumps for 8 cycles each year in the first two years after resection. Meanwhile, traditional Chinese herbal medicine was prescribed to the patients. When the leucocyte count was as low as 3 x 109/L or asparate aminotransferase (AST) level was significantly increased, the regimen of chemotherapy was delayed for the normalization of leucocyte count and AST level (below 80 U/L). RESULTS: Of the 28 patients, 23 received 8 or 16 cycles of the set regimen of chemotherapy. These patients are alive with no evidence of recurrence. Among them, 5,7, and 11 patients are alive beyond 5 years, 3 years, and 1 year respectively. In the remaining 5 patients, 3 who had had a HCC 10 cm or more in diameter showed tumor recurrence within 1 year, in whom, 8 cycles of chemotherapy were not completed because of their low leucocyte count (<3 × 109/L) and poor liver function. One patient who had received 8 cycles of chemotherapy demonstrated recurrence at 16 months after resection. One patient who had received 16 cycles of chemotherapy had intrahepatic recurrence at 58 months after surgery. No recurrence was observed in 17 patients who had received 16 cycles of chemotherapy. CONCLUSION: Adjuvant hepatic arterial chemotherapy may be feasible to improve the survival of patients after resection of solitary HCC associated with HBV cirrhosis.

C–C motif chemokine ligand 16 inhibits the progression of liver cirrhosis via inactivating hepatic stellate cells

Background:Liver cirrhosis results from many forms of chronic damage,characterized by accumulation of extracellular matrix.The present study aimed to explore a potential non-invasive biomarker and its mechanism in the progression of liver cirrhosis.Methods:Gene Expression Omnibus(GEO)dataset(GSE15654,n=216)was analyzed to screen genes associated with progression of liver cirrhosis.A total of 181 plasma samples,including healthy control(HC,n=20),chronic hepatitis B(CHB,n=77)and HBV-related liver cirrhosis(LC,n=84),were enrolled for validation.In vitro and in vivo experiments were employed for the mechanistic investigation.Results:GEO dataset analysis showed that relatively low mRNA-expression of C–C motif chemokine ligand 16(CCL16)was associated with elevated Child-Pugh score(P=0.034)and worse prognosis(P=0.025).Plasma CCL16 level decreased in a stepwise pattern,with a median concentration of 10.29,6.57 and 4.47 ng/mL in the HC,CHB and LC groups,respectively(P<0.001).Low plasma CCL16 was significantly related to hepatic dysfunction both in the CHB and LC groups(P<0.05).Combination of CCL16 and ALT showed improved distinguishing capability for LC compared to either alone.In vitro,CCL16 expression was downregulated by lipopolysaccharide and hypoxia.Overexpression of CCL16 from human normal liver cell line(LO2)reduced the extracellular matrix associated proteins(Col1 and Col4)in human hepatic stellate cell line(LX-2).In vivo,the pathological feature of cirrhosis was alleviated by the hepatocytespecific expression of CCL16.Conclusions:CCL16 could be a feasible plasma marker to predict the occurrence and progression of liver cirrhosis.CCL16 might impact liver cirrhosis through inactivating hepatic stellate cells.

Portocaval shunts'role in gut microbiota and hepatic encephalopathy:The gut-to-brain pathway

I read the study by Zhao et al with great interest.Although the study design was quite complicated,it was successful in raising awareness of science and relevant researchers.Thirty patients with liver cirrhosis and portal hypertension secondary to chronic hepatitis B were included in the study.They were treated for variceal bleeding and underwent trans-jugular intrahepatic portosystemic shunt to prevent the recurrence of variceal bleeding and to reduce portal pressure.The authors evaluated the effects of changes in gut microbiota(GM)on hepatic encephalopathy secondary to portocaval bypass.The GM is greatly affected by local and general factors,including herbal and medical drugs,a person's dietary characteristics(carnivorous,vegan,vegetarian),supplementary foods,drinking water sources,and living in a city center or town.Therefore,I congratulate Zhao et al for their concise and comprehensive study on a multifactorial subject.

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis

BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been determined.AIM To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC patients.METHODS This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020.Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only.Fecal samples were collected at the onset and conclusion of the 12-wk intervention period.The structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were assessed.RESULTS Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria.Additionally,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.

Impact of Nursing Interventions Based on Self- Efficacy Theory on HAMA and HAMD Scores in Patients with Hepatitis B Cirrhosis

Objective:To explore the effect of nursing interventions based on self-efficacy theory guidance on psychological stress indicators in patients with hepatitis B cirrhosis.Methods:70 patients with hepatitis B cirrhosis from October 2023 to May 2024 were selected and grouped by random number table.The observation group received nursing intervention based on self-efficacy theory,while the control group received routine nursing.The differences in psychological stress indicators,self-efficacy indicators,and nursing satisfaction were compared between the two groups.Results:Hamilton Anxiety Rating Scale(HAMA)and Hamilton Depression Rating Scale(HAMD)scores of the observation group were significantly lower than those of the control group(P<0.05);Chronic Disease Self-Efficacy Scale(CDSES)scores of the observation group were significantly higher than those of the control group(P<0.05);and nursing satisfaction scores of the observation group were significantly higher than those of the control group(P<0.05).Conclusion:Hepatitis B cirrhosis patients receiving nursing care based on self-efficacy theory can stimulate patients'self-efficacy,calm their emotions,and their overall satisfaction is high.

Expression of HBxAg in human chronic hepatitis,cirrhosis and primary hepatic carcinoma and its significance

The specimens of this study were obtained from 110 cases of chronic hepatitis,108cirrhosis and 110 primary hepatic carcinoma(PHC).Formalin-fixed and paraffin-embedded seetions were stained by ABC method forHBxAg,and by PAP method for HRsAg and HBcAgOf the 110 cases of chronic hepatitis,72(65.5％)were positive HBxAg in the liver cells,66(60％)were postitive in HBsAg and 35(31.8％)in HBcAg.Among the 108 eases of drrhosis,84(77.8％)revealed to be HBxAg positive in the liver cells,73(67.6％)were demonstrated to beHBsAg-positive and 18(16.7％)were shown to be HBcAg-positive.Among the 110 eases of pri-mary hepatic carcinoma,64(58.2％)showed HBxAg-positive reaction in cancerous tissues.Therates of positive HRsAg and HBcAg in tumor tissues were 15.5％ and 10.9％,respectively.Six-ty-three(78.8％)of 80 cases of the non-cancerous hepatic tissues displayed HBxAg positivenessand the rates of positive HRsAg and HBcAg in the non-tumor tissues were 47(58.8％)and 21(2.6.3％),respectively.The above-mentioned results sugared that the detection rote of HBxAg inchronic hepatitis,cirrhosis and PHC was higher than that of HBsAg and HBcAg.This studydemonstrates a dose relationship between chronic hepatitis,cirrhosis,PHC and chronic persistentinfection of hepatitis B virus(HBV).Persistent chronic HBV infection plays an important role inthe pathogenesis of chronic hepatitis, cirrhosis and PHC.It is possible that the detection ofHBxAg with anti-HBx could be an additional new diagnostic marker for HBV infection.Howev-er,the role of HBxAg in the pathogenesis of chronic liver diseases needs to be furtherinvestigated.

Effect of the reduced glutathione antioxidation combined with conventional antiviral drugs on hepatic fibrosis in patient with hepatitis b cirrhosis

Objective: To study the effect of the reduced glutathione antioxidation combined with conventional antiviral drugs on hepatic fibrosis in patient with liver cirrhosis. Methods: A total of 300 patients with hepatitis b cirrhosis who were treated in Shangluo Central Hospital between August 2012 and August 2016 were collected and divided into the control group (n=159) who received conventional antiviral therapy and the observation group (n=141) who received reduced glutathione antioxidation combined with conventional antiviral drug therapy. The differences in serum levels of fibrosis indicators, inflammatory factors and oxidative stress indexes were compared between the two groups of patients before and after treatment. Results: Before treatment, differences in serum levels of fibrosis indexes, inflammatory factors and oxidative stress indexes were not statistically significant between two groups of patients. After treatment, serum HA, Ⅳ-C, LN, PCⅢ, PCT, IL-6, IL-22, IL-31, TNF-α and MDA levels of both groups of patients were lower than those before treatment while GSH-Px and T-SOD levels were higher than those before treatment, and serum HA, Ⅳ-C, LN, PCⅢ, PCT, IL-6, IL-22, IL-31, TNF-α and MDA levels of observation group after treatment were lower than those of control group while GSH-Px and T-SOD levels were higher than those of control group. Conclusion: Reduced glutathione antioxidation combined with conventional antiviral drugs can effectively inhibit the fibrosis process in patients with hepatitis b cirrhosis, which is because that it reduces the degree of inflammation and oxidative stress reaction.

Effects of adjuvant therapy with anluohuaxian capsule on serum inflammatory factors, hepatic fibrosis indexes and immune function in patients with hepatitis B cirrhosis

Objective: To investigate the effect of adjuvant therapy with anluohuaxian capsule on the treatment of hepatitis B cirrhosis, and its influence on serum inflammatory factors, liver fibrosis indexes and immune function. Methods: A total of 112 cases of hepatitis B cirrhosis patients were divided into the control group (n=55) and observation group (n=57) according to the random data table, patients in the two groups were given routine treatment, on this basis, the control group received the treatment of Adefovir Dipivoxil Tablets, and the observation group was treated with Adefovir Dipivoxil Tablets combined with Anluo Huaxian pill treatment, two groups were treated for 48 weeks. The levels of serum inflammatory factors, liver fibrosis indexes and immune function indexes of the two groups were compared before and after treatment. Results: Before treatment, There was no significant difference between the two groups of TNF-α, IL-6, hs-CRP, IVC, HA, PIIIP, LN, CD3+, CD4+, CD8+and CD4+/CD8+ levels. After treatment, TNF-α, IL-6, hs-CRP, IVC, HA, PIIIP, LN, CD3+, CD4+, CD8+and CD4+/CD8+ levels in the observation group and control group were significantly lower than those before treatment in the same group, and levels in the observation group after treatment were significantly lower than the control group;Compared with the group before treatment, the levels of CD3+, CD4+ and CD4+/CD8+ of two groups after treatment were significantly increased, and the observation group was significantly higher than the control group. Conclusion: Adjuvant therapy with anluohuaxian capsule on the treatment of hepatitis B cirrhosis, can effectively reduce the inflammatory stress reaction, reduce the level of serum liver fibrosis index and improve the immune function, and has important clinical value.

乙肝肝硬化失代偿期并发肝功能衰竭患者血清Autotaxin、Copeptin、LBP与预后的关系研究

目的探讨乙肝肝硬化失代偿期(HBV-DC)并发肝功能衰竭(LF)患者血清自分泌运动因子(Autotaxin)、和肽素(Copeptin)、内毒素结合蛋白(LBP)与预后的关系。方法选取2018年2月至2023年8月我院收治的143例HBV-DC并发LF患者为研究对象,随访90 d,根据预后情况分组为死亡组(55例)与存活组(88例),比较两组血清Autotaxin、Copeptin、LBP水平。收集HBV-DC并发LF患者的临床资料,采用单因素和多因素Logistic回归模型分析HBV-DC并发LF患者预后的影响因素。采用受试者工作特征(ROC)曲线分析血清Autotaxin、Copeptin、LBP单独或联合预测HBV-DC并发LF患者预后的临床价值。结果143例HBV-DC并发LF患者随访90 d时,有55例死亡,88例存活,死亡率38.46%。与存活组比较,死亡组血清Autotaxin、Copeptin、LBP水平明显增加(P<0.05)。与存活组比较,死亡组住院时间≥14 d比例、并发腹水比例、并发肝性脑病比例、谷丙转氨酶、总胆红素、终末期肝病模型(MELD)评分显著升高(P<0.05),白蛋白显著降低(P<0.05),年龄、性别、合并糖尿病、合并高血压、血肌酐、血小板计数、纤维蛋白原无显著性差异(P>0.05)。总胆红素升高、并发肝性脑病、MELD评分升高以及血清Autotaxin、Copeptin、LBP水平升高均为HBV-DC并发LF患者预后不良的危险因素(P<0.05)。ROC曲线结果显示,血清Autotaxin、LBP、Copeptin标联合检测预测HBV-DC并发LF患者预后不良的曲线下面积(AUC)、灵敏度、特异度分别为0.930、85.45%、88.64%,显著优于单项指标检测预测的效能。结论血清Autotaxin、Copeptin、LBP高表达与HBV-DC并发LF患者短期死亡发生风险有关,且联合检测对HBV-DC并发LF患者短期死亡的发生具有较高的临床预测价值。

慢性HBV感染者外周血可诱导共刺激分子在CD8+ T淋巴细胞的表达及其临床意义

目的 探讨慢性乙型肝炎病毒(HBV)感染者外周血可诱导共刺激分子(ICOS)在CD8+T淋巴细胞的表达特点及临床意义。方法 选取2017年5月—2018年10月就诊的慢性乙型肝炎(CHB)100例、HBV-肝硬化(LC)25例和HBV-慢加急(或亚急)性肝衰竭(ACLF)26例分别纳入CHB组、HBV-LC组和HBV-ACLF组,健康对照(NC)组35例来自同期门诊体检健康者。采用流式细胞仪检测各组ICOS在CD8+T淋巴细胞的表达情况;分析CD8+T淋巴细胞ICOS表达水平与慢性HBV感染者疾病严重程度、HBV-ACLF预后及并发症的相关性;动态观察HBV-ACLF患者治疗过程中CD8+T淋巴细胞ICOS表达变化。结果 HBV-ACLF组外周血CD8+T淋巴细胞ICOS表达比率及平均荧光强度(MFI)均高于CHB组、HBV-LC组和NC组(P<0.05)。慢性HBV感染者ICOS的MFI与白蛋白、胆碱酯酶、总胆固醇、血红蛋白呈负相关(r=-0.263、-0.269、-0.273、-0.302,P=0.003、0.003、0.011、0.004);与直接胆红素、天冬氨酸转氨酶、凝血酶原时间、国际标准化比值呈正相关(r=0.248、0.208、0.331、0.315,P=0.005、0.020、0.003、0.009);与HBV-DNA、腹水及感染无明显相关性(P>0.05)。治疗过程中,HBV-ACLF患者ICOS的MFI无明显改变。但生存组ICOS的MFI在治疗第1周时较治疗前上升(P<0.05)。结论 HBV-ACLF患者外周血CD8+T淋巴细胞ICOS的表达水平明显升高,并与肝脏合成功能、炎症程度及预后相关,治疗早期ICOS水平变化有助于预测慢性HBV感染者的预后。

黄芪甲苷对人外周血单个核细胞内HBV表达的影响

目的:探索黄芪甲苷对乙肝后肝硬化患者外周血单个核细胞(PBMC)内HBV表达的影响。方法:选取2019年2月—2022年2月于江西省人民医院就诊的20例乙肝后肝硬化患者,分离并培养外周血单个核细胞,依据培养液所含药物类型分为对照组、拉米夫定组、黄芪甲苷组。拉米夫定组和黄芪甲苷组又根据药物终浓度各分为低、中、高浓度3个亚组。培养1周后,分别检测各组HBsAg、HBeAg、HBV-DNA、HBV-cccDNA表达。结果:与对照组相比,黄芪甲苷各浓度组HBsAg表达量均显著降低,差异具有统计学意义(P<0.05);黄芪甲苷各浓度组HBeAg表达量无统计学差异(P>0.05),黄芪甲苷低浓度组HBV-DNA表达量无统计学差异(P>0.05),黄芪甲苷中、高浓度组HBV-DNA表达量显著降低,差异具有统计学意义(P<0.05),黄芪甲苷各浓度组HBV-cccDNA表达量无统计学差异(P>0.05)。与对照组相比,拉米夫定各浓度组HBsAg、HBeAg、HBV-DNA表达量均显著降低,差异具有统计学意义(P<0.05);拉米夫定低浓度组HBV-cccDNA表达量无统计学差异(P>0.05),拉米夫定中、高浓度组HBV-cccDNA表达量显著降低,差异具有统计学意义(P<0.05)。Spearman检验分析提示黄芪甲苷浓度与HBsAg、HBeAg、HBV-DNA、HBV-cccDNA表达量呈线性负相关,其中与HBsAg、HBV-DNA的负相关性有统计学意义(P<0.05)。结论:黄芪甲苷能够在一定程度上抑制乙肝后肝硬化患者PBMC中HBV的复制,能为解决肝移植术后HBV复发提供新的治疗思路。

De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.

Long-term antiviral efficacy of entecavir and liver histology improvement in Chinese patients with hepatitis B virus-related cirrhosis

AIM: To evaluate the clinical outcomes of 240-wk treatment with entecavir(0.5 mg) in Chinese nucleosidenaive patients with cirrhosis.METHODS: A total of 204 nucleoside-naive patients with compensated(n = 96) or decompensated(n = 108) hepatitis B virus(HBV)-induced cirrhosis at the Department of Gastroenterology of the China-Japan Union Hospital(Jilin University, Changchun, China) who were treated with entecavir(0.5 mg) for 240 wk were enrolled in this study. Liver biopsy samples obtained from 38 patients prior to treatment(baseline) and at week 240 were evaluated by different independent histopathologists. Efficacy assessments included the proportions of patients who achieved an HBV DNA level < 500 copies/m L, the association of interleukin-28 B genetic variation with antivirus therapy, clinical outcomes, and histologic improvement. Changes in liver disease severity were analyzed, and liver histologic evaluation was performed in 38 patients with paired biopsies. Student t tests were used to compare the means of continuous variables between the groups, and the proportions of patients who achieved the endpoints were compared using the χ2 test.RESULTS: At week 240, 87.5% of the patients with compensated cirrhosis and 92.6% of the patients with decompensated cirrhosis achieved a HBV DNA level < 500 copies/m L. Three patients had genotypic entecavir resistance within the 240-wk period. No significant association was observed between virologic response and interleukin-28 genotype(CT, 88.2% vs CC, 90.6%). The proportion of patients with Child-Pughclass A disease was significantly increased at week 240(68%) from the baseline(47%; P < 0.01). The proportion of patients with Child-Pugh class B disease was significantly decreased at week 240(25%) from the baseline(39%; P = 0.02). In the patients with paired liver biopsies, the mean reduction in the Knodell necroinflammatory score from the baseline was 3.58 ± 1.03 points(7.11 ± 1.80 vs 3.53 ± 1.35, P < 0.01). The mean reduction in Ishak fibrosis score from the baseline was 1.26 ± 0.64 points(5.58 ± 0.50 vs 4.32 ± 0.81, P < 0.01).CONCLUSION: Entecavir is an effective treatment option for patients with HBV-related compensated or decompensated cirrhosis that can result in sustained virologic suppression and histologic improvement.

Effects of entecavir and lamivudine for hepatitis B decompensated cirrhosis: Meta-analysis

AIM:To compare the effects of entecavir(ETV)and lamivudine(LAM)for the treatment of hepatitis B decompensated cirrhosis using a meta-analysis.METHODS:We conducted a literature search for all eligible studies published prior to May 30,2013 using PUBMED,MEDLINE,EMBASE,the China National Knowledge Infrastructure(CNKI),the VIP database,the Wanfang database and the Cochrane Controlled Trial Register.Randomized controlled trials(RCTs)comparing ETV with LAM for the treatment of hepatitis B decompensated cirrhosis were included.The data were analyzed with Review Manager Software 5.0.2.We used RR as an effect measure,and reported its95%CI.The meta-analysis was performed using either a fixed-effect or random-effect model,based on the absence or presence of significant heterogeneity.Two reviewers assessed the risk of bias and extracted data independently and in duplicate.The analysis was executed using the main outcome parameters including hepatitis B virus(HBV)DNA undetectability,HBV DNA level,hepatitis B e antigen(HBeAg)seroconversion,alanine aminotransferase(ALT)level,albumin level,total bilirubin(TBIL)level,prothrombin time activity(PTA)level,Child-Turcotte-Pugh(CTP)score,mortality,drugresistance,and adverse reactions.Meta-analysis of the included trials and subgroup analyses were conducted to examine the association between pre-specified characteristics and the therapeutic effects of the two agents.RESULTS:Thirteen eligible trials(873 patients in total)were included and evaluated for methodological quality and heterogeneity.Of these studies,all had baseline comparability,12 of them reported baseline values of the two treatment groups in detail.Following various treatment durations(12,24,36,48 and>48 wk),both ETV and LAM significantly reduced HBV DNA level,however,reductions were greater in the ETV group(MD=-0.66,95%CI:-0.83-0.50,P<0.00001),(MD=-0.93,95%CI:-1.36-0.51,P<0.0001),(MD=-1.4,95%CI:-1.78-1.01,P<0.00001),(MD=-1.18,95%CI:-1.90-0.46,P=0.001),(MD=-0.14,95%CI:-0.17-0.11,P<0.00001,respectively).At 12,24 and48 wk of treatment,ETV had a significant effect on the rate of HBV DNA undetectability(RR=1.55,95%CI:1.22-1.99,P=0.0004),(RR=1.25,95%CI:1.13-1.38,P<0.0001),(RR=1.2,95%CI:1.10-1.32,P<0.0001,respectively).Although HBeAg seroconversion in the ETV group was more pronounced than that in the LAM group at 24 wk(27.90%vs 26.19%)and 48 wk(31.52%vs 25.00%)of treatment,there was no statistically significant difference between them(RR=1.49,95%CI:0.98-2.28,P=0.07),(RR=1.27,95%CI:0.98-1.65,P=0.07,respectively).Following various treatment durations,both the ETV group and the LAM group showed significantly improved liver function(ALT,AIB,TBIL,PTA and CTP levels)and reduced mortality(ETV 6.37%,LAM 7.89%).The effects in the ETV group(0.33%)were statistically lower than those in the LAM group(14.33%)regarding the rate of drug-resistance(RR=0.1,95%CI:0.04-0.24,P≤0.00001).In addition,no severe adverse reactions were observed in the two treatment groups.CONCLUSION:ETV and LAM significantly improved liver function and reduced mortality.Both drugs produced similar serological responses,and were safe and well tolerated.However,ETV resulted in a better virological response and lower drug-resistance,but is more expensive.