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.

Bacterial infection triggers and complicates acute-on-chronic liver failure in patients with hepatitis B virus-decompensated cirrhosis: A retrospective cohort study

BACKGROUND Reports on bacterial infection(BI)in decompensated cirrhosis(DC)is mainly from alcoholic cirrhosis.The role of BI as a trigger or complication of acute-onchronic liver failure(ACLF)in patients with hepatitis B virus decompensated cirrhosis(HBV-DC)remains to be investigated.AIM To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF.METHODS This retrospective study included patients with HBV-DC admitted to two tertiary centers in China.In-hospital overall survival,90-d transplant-free survival,5-year post-discharge survival,and cumulative incidence of ACLF were evaluated.Risk factors for death were analyzed considering liver transplantation as a competing event.RESULTS A total of 1281 hospitalized HBV-DC patients were included;284 had ACLF at admission.The overall prevalence of BI was 28.1%.The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without,in both the patients admitted with and without ACLF.The presence of BI significantly increased the risk of developing ACLF[subdistribution hazard ratio(sHR)=2.52,95%CI:1.75-3.61,P<0.001]in the patients without ACLF.In the patients discharged alive,those who had an episode of BI had a significantly lower 5-year transplant-free survival.BI was an independent risk factor for death in the patients admitted without ACLF(sHR=3.28,95%CI:1.93-5.57),while in ACLF admissions,the presence of pneumonia,but not other type of BI,independently increased the risk of death(sHR=1.87,95%CI:1.24-2.82).CONCLUSION BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival.HBV-DC patients should be monitored carefully for the development of BI,especially pneumonia,to avoid an adverse outcome.

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.

Non-invasive diagnosis of hepatitis B virus-related cirrhosis

Chronic hepatitis B(CHB)infection is a major public health problem associated with significant morbidity and mortality worldwide.Twenty-three percent of patients with CHB progress naturally to liver cirrhosis,which was earlier thought to be irreversible.However,it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs.Thus,early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB.Liver biopsy is the reference standard for assessment of liver fibrosis.However,the method is invasive,and is associated with pain and complications that can be fatal.In addition,intra-and inter-observer variability compromises the accuracy of liver biopsy data.Only small tissue samples are obtained and fibrosis is heterogeneous in such samples.This confounds the two types of observer variability mentioned above.Such limitations have encouraged development of non-invasive methods for assessment of fibrosis.These include measurements of serum biomarkers of fibrosis;and assessment of liver stiffness via transient elastography,acoustic radiation force impulse imaging,real-time elastography,or magnetic resonance elastography.Although significant advances have been made,most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection.In the present review,we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice.

Benefits of nucleos(t)ide analog treatments for hepatitis B virus-related cirrhosis

Chronic hepatitis B infection induces progressive liver disease. Before nucleos(t)ide analogs(NUCs) became established as a safe and effective treatment for hepatitis B,it was difficult to suppress the activity of the hepatitis B virus(HBV). Currently,many patients withhepatitis or cirrhosis associated with HBV are treated with NUCs for an extended period of time,and the effects,benefits,and limitations of these treatments have been apparent. This article reviews HBV-related cirrhosis,its natural course and survival,histological improvement after NUC treatments,treatment effects for decompensated cirrhosis,the incidence of hepatocellular carcinoma(HCC) after NUC treatments,and the efficacy of NUC treatments before and after the treatment of patients for HBV-related HCC. Of particular interest are the histological improvements,including regression of fibrosis,that have been achieved with NUC treatments. Liver function of patients with decompensated cirrhosis has significantly improved regardless of the type of NUC applied,and treatment with NUCs has reduced the incidence of HCC in cirrhotic patients. However,cirrhosis remains the strongest risk factor for HCC occurrence following NUC treatments,and the long-term cumulative incidence of HCC after NUC treatments remains high. When recurrence does occur,it is important to reconsider the treatment modality according to the degree of improved liver function that was achieved.

Low level of hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in compensated cirrhotic patients

BACKGROUND Whether patients with compensated cirrhosis and low-level viremia(LLV)of hepatitis B should receive antiviral therapy(AVT)is still controversial,and published results are inconsistent.AIM To investigate the link between LLV in compensated cirrhosis and prognosis concerning hepatocellular carcinoma(HCC),decompensation,and liver-related events.METHODS The PubMed,EMBASE,and Cochrane Library databases were searched up to March 5,2023.Outcomes of interest were assessed by pooled hazard ratios(HRs).The study was registered with PROSPERO(CRD42023405345).RESULTS Six cohort studies representing 3155 patients were included.Compared with patients with undetectable HBV DNA,patients with LLV was associated with increased risk of HCC(HR:2.06,95%CI:1.36-3.13;Q-statistic-P=0.07,I^(2)=51%)regardless of receiving AVT or not(AVT group:HR:3.14;95%CI:1.73-5.69;Qstatistic-P=0.60,I2=0%;un-AVT group:HR:1.73,95%CI:1.09-2.76;Q-statistic-P=0.11,I2=50%).The pooled results showed no statistical association between LLV and decompensation of cirrhosis(HR:2.06,95%CI:0.89-4.76;Q-statistic-P=0.04,I2=69%),and liver-related events(HR:1.84,95%CI:0.92-3.67;Q-statistic-P=0.03,I2=72%),respectively.Grading of Recommendations Assessment,Development and Evaluation assessment indicated moderate certainty for HCC,very low certainty for decompensation of cirrhosis and liver-related clinical events.CONCLUSION LLV in compensated cirrhotic patients is associated with increased risk of HCC,higher tendency for hepatic decompensation and liver-related events.Closer screening of HCC should be conducted in this population.

Effect of Qianggan Pills combined with antiviral treatment on the fibrosis indexes, immune and inflammatory response in patients with compensated hepatitis b cirrhosis

Objective:To study the effect of Qianggan Pills combined with antiviral treatment on the fibrosis indexes, immune and inflammatory response in patients with compensated hepatitis b cirrhosis.Methods:A total of 88 patients with compensated hepatitis b cirrhosis treated in our hospital between April 2013 and March 2016 were collected and divided into observation group and control group according to single blind randomized control. Observation group of patients accepted Qianggan Pills combined with antiviral treatment and control group of patients received antiviral treatment alone. After 6 months of treatment, chemiluminescence method was used to detect serum fibrosis indexes, flow cytometer was used to detect peripheral blood T lymphocyte subset levels, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of inflammatory factors.Results: Before treatment, differences in fibrosis indexes, immune and inflammatory response indexes were not statistically significant between two groups of patients;after 6 months of treatment, serum LN, HA andⅣ-C levels of observation group were lower than those of control group, peripheral blood CD3+ and CD4+T lymphocyte levels as well as CD4+/CD8+ ratio were higher than those of control group, and CD8+ T lymphocyte level was lower than that of control group;serum PCT and CRP levels were lower than those of control group while IL-10 and IL-13 levels were higher than those of control group.Conclusion:Qianggan Pills combined with antiviral treatment can inhibit the fibrosis process, strengthen the body's immune function and also relieve systemic inflammatory response in patients with compensated hepatitis b cirrhosis.

Virus-related liver cirrhosis: Molecular basis and therapeutic options

Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8+ T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.

Progress in hepatitis B virus-related acute-on-chronic liver failure treatment in China:A large,multicenter,retrospective cohort study using a propensity score matching analysis

Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.

Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China

BACKGROUND Noninvasive,practical,and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed.AIM To develop a precise noninvasive test to stage liver fibrosis and cirrhosis.METHODS With liver biopsy as the gold standard,we established a new index,[alkaline phosphatase(U/L)+gamma-glutamyl transpeptidase(U/L)/platelet(109/L)(AGPR)],to predict liver fibrosis and cirrhosis.In addition,we compared the area under the receiver operating characteristic curve(AUROC)of AGPR,gammaglutamyl transpeptidase to platelet ratio,aspartate transaminase to platelet ratio index,and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis.RESULTS Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage(P<0.001).In the training cohort,the AUROC of AGPR was 0.83(95%CI:0.78-0.87)for predicting fibrosis(≥F2),0.84(95%CI:0.79-0.88)for predicting extensive fibrosis(≥F3),and 0.87(95%CI:0.83-0.91)for predicting cirrhosis(F4).In the validation cohort,the AUROCs of AGPR to predict≥F2,≥F3 and F4 were 0.83(95%CI:0.77-0.88),0.83(95%CI:0.77-0.89),and 0.84(95%CI:0.78-0.89),respectively.CONCLUSION The AGPR index should become a new,simple,accurate,and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.

Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis

AIM: To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis.

Computed tomography perfusion in liver and spleen for hepatitis B virus-related portal hypertension:A correlation study with hepatic venous pressure gradient

BACKGROUND Hepatic venous pressure gradient(HVPG)is the gold standard for diagnosis of portal hypertension(PH).However,its use can be limited because it is an invasive procedure.Therefore,it is necessary to explore a non-invasive method to assess PH.AIM To investigate the correlation of computed tomography(CT)perfusion of the liver with HVPG and Child-Pugh score in hepatitis B virus(HBV)-related PH.METHODS Twenty-eight patients(4 female,24 male)with gastroesophageal variceal bleeding induced by HBV-related PH were recruited in our study.All patients received CT perfusion of the liver before transjugular intrahepatic portosystemic stent-shunt(TIPS)therapy.Quantitative parameters of CT perfusion of the liver,including liver blood flow(LBF),liver blood volume(LBV),hepatic artery fraction,splenic blood flow and splenic blood volume were measured.HVPG was recorded during TIPS therapy.Correlation of liver perfusion with Child-Pugh score and HVPG were analyzed,and the receiver operating characteristic curve was analyzed.Based on HVPG(>12 mmHg vs≤12 mmHg),patients were divided into moderate and severe groups,and all parameters were compared.RESULTS Based on HVPG,18 patients were classified into the moderate group and 10 patients were classified into the severe group.The Child-Pugh score,HVPG,LBF and LBV were significantly higher in the moderate group compared to the severe group(all P<0.05).LBF and LBV were negatively associated with HVPG(r=-0.473,P<0.05 and r=-0.503,P<0.01,respectively),whereas splenic blood flow was positively associated with hepatic artery fraction(r=0.434,P<0.05).LBV was negatively correlated with Child-Pugh score.Child-Pugh score was not related to HVPG.Using a cutoff value of 17.85 mL/min/100 g for LBV,the sensitivity and specificity of HVPG≥12 mmHg for diagnosis were 80%and 89%,respectively.CONCLUSION LBV and LBF were negatively correlated with HVPG and Child-Pugh scores.CT perfusion imaging is a potential non-invasive quantitative predictor for PH in HBV-related liver cirrhosis.

Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

EXPRESSION OF INSULIN-LIKE GROWTH FACTOR Ⅱ(IGF-Ⅱ)IN HUMAN HEPATOCELLULAR CARCINOMA AND LIVER CIRRHOSIS:ITS RELATIONSHIP WITH HEPATITIS B VIRUS X PROTEIN EXPRESSION

Sixty cases of hepatocellular carcinoma (HCC) and 47 cases of liver cirrhosis (LC) were examined with immunocytochemistry method using antibodies against IGF-II and HBxAg on formalin-fixed, paraffin-embedded tissue sections. 32 HCC and 37 LC were found to be positive to HBxAg, in which the positive rates of IGF-II were 100% (32/32) and 94.6% (35/37) respectively. 28 HCC and 10 LC were found to be HBxAg negative, IGF-II was positive in 23 HCC (83.1%) and 6 LC (60%). The positive expression rates of IGF-II in HBxAg positive tissues were significantly higher than those in HBxAg negative tissues (P<0.05). There were three types of distribution of IGF-II expression in HCC and LC: (1) perinucleus; (2) diffuse in cytoplasm; (3) inside nucleus. IGF-II was highly expressed in most of hyperplastic and neoplastic nodules hepatocytes and some of regeneration nodules. Small polygonal liver cells (SPLCs) were found in the liver tissues surrounding the tumor and cirrhosis and they were positive to both IGF-II and HBxAg. The positive rates of IGF-II in SPLC were 86.4% (38/44) in the HBxAg-positive tissues and 40.5%, (15/37) in the HBxAg-negative tissues. The above findings suggest that IGF-II plays an important role in abnormal proliferation of HCC and SPLC. The relation between IGF-II andHBxAg and the nature of SPLCs are also discussed.

Hepatitis B cirrhosis combined with Budd-Chiari syndrome treated by liver transplantation:Case report and literature review

Objective:To summarize and analyze the clinical treatment experience of hepatitis B cirrhosis combined with Budd-Chiari syndrome.Methods:Data was obtained from a patient who were diagnosed with hepatitis B cirrhosis combined with Budd-Chiari syndrome.We retrospectively analyzed the clinical character of the patient.Results:The patient was diagnosed with Budd-Chiari syndrome incidentally during operation.so the patient underwent orthotopic liver transplanation,in which the liver and retrohepatic vena cava were resected,and recovered uneventfully.Conclusion:Orthotopic liver transplantation is not only an ideal treatment but also improves the prognosis of patients for hepatitis B cirrhosis combined with Budd-Chiari syndrome.

Influence of antiviral drugs combined with antioxidant therapy on liver injury and fibrosis process in patients with chronic hepatitis B cirrhosis

Objective:To study the influence of antiviral drugs combined with antioxidant therapy on liver injury and fibrosis process in patients with chronic hepatitis B cirrhosis.Methods: A total of118 patients with chronic hepatitis B cirrhosis who were treated in Dongying Hospital for Infectious Diseases between May 2013 and February 2016 were retrospectively analyzed and divided into the control group (n=60) who underwent routine antiviral therapy and the observation group (n=58) who underwent antiviral drugs combined with antioxidant therapy. Serum levels of oxidative stress indexes, liver function indexes and liver fibrosis indexes were compared between two groups of patients before and after treatment.Results:Before treatment, there were no significant differences in serum oxidative stress indexes, liver function indexes and liver fibrosis indexes between two groups of patients. 3 months after treatment, serum oxidative stress index SOD level in observation group was higher than that in control group while AOPPs level was lower than that in control group;serum liver function indexes AST, ALT and TBIL levels in observation group were lower than those in control group while ALB level was higher than that in control group;serum liver fibrosis indexes HA,Ⅳ-C, PCIII and LN levels in observation group were lower than those in control group.Conclusion:Antiviral drugs combined with antioxidant therapy can significantly reduce oxidative stress injury in patients with chronic hepatitis B cirrhosis so as to protect the liver function and inhibit the liver fibrosis process.

Effect of Thymosin Injection combined with entecavir therapy on the viral load, liver fibrosis and immune response of patients with compensated liver cirrhosis

Objective: To study the effect of Thymosin Injection combined with entecavir therapy on the viral load, liver fibrosis and immune response of patients with compensated liver cirrhosis. Methods: Patients who were diagnosed with chronic hepatitis b complicated by compensated liver cirrhosis in our hospital between March 2015 and January 2017 were selected and randomly divided into two groups, observation group received Thymosin Injection combined with entecavir therapy, and control group received entecavir therapy. The viral load, liver function injury indexes, liver fibrosis indexes, immune cytokines and immune cell apoptosis molecules were measured 24 weeks after treatment. Results: 24 weeks after treatment, HBV-DNA copy number in peripheral blood as well as ALT, AST, TBIL, HA, PC-III, LN, C-IV, IL-4, IL-10, TGF-β1, IL-17 and IL-22 levels in serum of observation group was significantly lower than those of control group, and peripheral blood FAS, CYCS, CASP8, CASP9 and CASP3 mRNA expression were significantly lower than those of control group. Conclusion:Thymosin Injection combined with entecavir therapy can reduce viral load, improve liver function, inhibit liver fibrosis and regulate immune function in patients with compensated liver cirrhosis.

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.

Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications:Molecular mechanisms and therapeutic inventions

Hepatitis B virus(HBV)has posed a threat to public health,mainly resulting in liver damage.With long-term accumulation of extracellular matrix,patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma.The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality.With deeper understanding of the bidirectional interaction between the liver and the gut(gut-liver axis),there is a growing consensus that the human health closely relates to the gut microbiota.Supported by animal and human studies,the gut microbiota alters as the HBV-related liver fibrosis initials and progresses,characterized as the decrease of the ratio between“good”and“potentially pathogenic”microbes.When the primary disease is controlled via antiviral treatment,the gut microbiota dysfunction tends to be improved.Conversely,the recovery of gut microbiota can promote the regression of liver fibrosis.Therapeutic strategies targeted on gut microbiota(rifaximin,probiotics,engineered probiotics and fecal microbiota transplantation)have been applied to animal models and patients,obtaining satisfactory results.

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.