Antiviral therapy delays esophageal variceal bleeding in hepatitis B virus-related cirrhosis

AIM:To investigate the effect of antiviral therapy with nucleoside analogs in hepatitis B virus(HBV)-related cirrhosis and esophageal varices.METHODS:Eligible patients with HBV-related cirrhosis and esophageal varices who consulted two tertiary hospitals in Beijing,China,the Chinese Second Artillery General Hospital and Chinese PLA General Hospital,were enrolled in the study from January 2005 to December 2009. Of 117 patients,79 received treatment with different nucleoside analogs and 38 served as controls. Bleeding rate,change in variceal grade and non-bleeding duration were analyzed. Multivariate Cox proportional hazard regression was used to identify factors related to esophageal variceal bleeding.antiviral group compared to the control group(29.1%vs 65.8%,P < 0.001). Antiviral therapy was an independent factor related to esophageal bleeding in multivariate analysis(HR = 11.3,P < 0.001). The mean increase in variceal grade per year was lower in the antiviral group(1.0 ± 1.3 vs 1.7 ± 1.2,P = 0.003). Nonbleeding duration in the antiviral group was prolonged in the Kaplan-Meier model. Viral load rebound was observed in 3 cases in the lamivudine group and in 1 case in the adefovir group,all of whom experienced bleeding. Entecavir and adefovir resulted in lower bleeding rates(17.2% and 28.6%,respectively) than the control(P < 0.001 and P = 0.006,respectively),whereas lamivudine(53.3%) did not(P = 0.531).CONCLUSION:Antiviral therapy delays the progression of esophageal varices and reduces bleeding risk in HBV-related cirrhosis,however,high-resistance agents tend to be ineffective for long-term treatment.

Lamivudine treatment of decompensated hepatitis B virus-related cirrhosis

BACKGROUND: Patients with decompensated hepatitis B vires (HBV)-related cirrhosis tend to have low or undetectable HBV replication. However, some patients continue to have high levels of HBV replication and effective suppression of HBV replication with antiviral agents may potentially decrease hepatic necroinflammation and improve or stabilize liver function. This review was to under stand the efficacy and safety of lamivudine in the treatment of decompensated HBV cirrhosis. DATA SOURCES: An English-language literature search (MEDLINE January 1988-July 2005) was performed, and a total of 52 articles/abstracts relevant to the issue were selected. After review of the selected papers, the meaningful results and conclusions were extracted using scientific crite ria. The papers reviewed pertained mainly to the efficacy and safety profiles of lamivudine treatment for decompensated HBV cirrhosis. RESULTS: The ultimate treatment of decompensated HBV cirrhosis is liver transplantation, but lamivudine treatment may lead to rapid suppression of viral replication and improvement of biochemical and clinical parameters, reduced morbidity and hospitalization for complications of liver disease, increased pre-transplant survival as well as reduced need for transplantation. However, viral resistance can develop after prolonged treatment with lamivudine, and breakthrough hepatitis may be fatal in few patients. Adefovir is effective for lamivudine-resistant HBV mutants. CONCLUSIONS: Antiviral therapy with lamivudine for decompensated HBV cirrhosis can be effective. However, some patients may experience a hepatitis flare with the emergence of YMDD mutants resulting in progressive worsening of liver disease, and should be referred for 'rescue' therapy with other nucleoside/nucleotide analogues such as adefovir dipivoxil.

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.

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.

Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside(acid)analogs therapy:A retrospective cross-sectional study

BACKGROUND Antiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma(HCC).Furthermore,there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog(NA)therapy.AIM The study aim was to clarify risk factors and the diagnostic value of alphafetoprotein(AFP)for HCC progression in NA-treated hepatitis B virus(HBV)-related cirrhosis patients.METHODS In this retrospective cross-sectional study,we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital.The patients were divided into two groups,145 who did not progress to HCC(No-HCC group),and 121 who progressed to HCC during NA treatment(HCC group).The logistic regression analysis was used to analyze the risk factors of HCC progression.The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed that age≥60 years(P=0.001),hepatitis B and alcoholic etiology(P=0.007),smoking history(P<0.001),family history of HBV-related HCC(P=0.002),lamivudine resistance(P=0.011),HBV DNA negative(P=0.023),aspartate aminotransferase>80 U/L(P=0.002),gamma-glutamyl transpeptidase>120 U/L(P=0.001),alkaline phosphatase>250 U/L(P=0.001),fasting blood glucose(FBG)≥6.16(mmol/L)(P=0.001)and Child-Pugh class C(P=0.005)were correlated with HCC progression.In multivariate analysis,age≥60 years[hazard ratio(HR)=3.089,95%confidence interval(CI):1.437-6.631,P=0.004],smoking history(HR=4.001,95%CI:1.836-8.716,P<0.01),family history of HBV-related HCC(HR=6.763,95%CI:1.253-36.499,P<0.05),lamivudine resistance(HR=2.949,95%CI:1.207-7.208,P=0.018),HBV DNA negative(HR=0.026,95%CI:0.007-0.139,P<0.01),FBG≥6.16 mmol/L(HR=7.219,95%CI:3.716-14.024,P<0.01)were independent risk factors of HCC progression.ROC of AFP for diagnosis of HCC was 0.746(95%CI:0.674-0.818).A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609,and specificity of 0.818 for diagnosing HCC.CONCLUSION Age≥60 years,smoking history,family history of HCC,lamivudine resistance,HBV DNA negative,FBG≥6.16 mmol/L were risk factors of HCC progression.Serum AFP had limited diagnostic value for HCC.

Prognosis of 153 patients with decompensated hepatitis B virus-related cirrhosis is improved after 3-year continuous lamivudine treatment

Background The long-term effectiveness and safety of lamivudine in patients with decompensated hepatitis B virus-related cirrhosis are still not clear. The present study attempted to describe the clinical outcomes of lamivudine therapy in these special patients over three years. Methods This study was a retrospective, controlled cohort study which involved 153 patients with decompensated hepatitis B virus-related cJrrhosJs. Of these, 86 patients received lamJvudJne 100 mg daily accompanied with general internal treatment, and the other 67 were given general internal treatment only. Significant clinical responses were recorded after years of antiviral treatment. Results The patients in both groups were matched in terms of age, sex and laboratory results at baseline. After years of therapy, the Child-Pugh-Turcotte scores and laboratory values of the patients receiving lamivudine were remarkably improved compared to the patients in the control group. The mortality rate and the incidence of cirrhosis-related complications were much lower in the lamivudine group than in the control group. Genotypic resistance tyrosine, methionine, aspartate, aspartate mutations developed in 26.7 percent of the patients during 3-year lamivudine treatment, and cirrhosis-related death and the hepatocellular carcinoma were more likely to occur in patients with these mutations than in the other patients who were treated with lamivudine. Conclusions Continuous long-term lamivudine treatment in patients with decompensated hepatitis B virus-related cirrhosis delays clinical progression, and significantly improves hepatic function and prognosis. However, the use of a retrospective control cohort precludes drawin（~ definitive conclusions.

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.

Antiviral therapy of decompensated hepatitis B virus-related cirrhosis

Objective To review the development,mechanism,necessity and limitation of antiviral therapy in decompensated hepatitis B virus-related cirrhosis.Data sources Most information was pulled from a literature search （Pubmed 2000 to 2011） using the keywords of antiviral and decompensated hepatitis B virus-related cirrhosis.Relevant book chapters were also reviewed.Study selection Well-controlled,prospective landmark studies and review articles on antiviral therapy in decompesated hepatitis B virus-related cirrhosis were selected.Results Specific antiviral agents not only control viral replication,which permits liver transplantation,but also improve liver function so significantly that patients could be removed from the transplant waiting list.However,the emergence of drug-resistant mutants can result in treatment failure.Combination therapy is a save-strategy in drug-resistant.Conclusions Although the treatment of end-stage liver disease is still a challenge worldwide,antiviral therapy has altered the natural history of hepatitis B patients with decompensated cirrhosis.The approval of the new generation of antivirals is opening new perspectives for finding the optimal antiviral treatment for patients with decompensated cirrhosis and preventing antiviral resistance.A combination of antivirals may be one of the future strategies for fulfilling these goals.

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.

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.

Giant Hepatic Regenerative Nodule in a Patient With Hepatitis B Virus-related Cirrhosis

Hepatic regenerative nodules are reactive hepatocellular proliferations that develop in response to liver injury.Giant hepatic regenerative nodules of 10 cm or more are extremely rare and have only been reported in patients with biliary atresia or Alagille syndrome.A 50-year-old man presented with a pathologically confirmed giant 11.3×9.4×11.2 cm hepatic regenerative nodule and hepatitis B virus-related cirrhosis.Imaging of intrahepatic nodule included mild hyperenhancement in the portal phase of contrast-enhanced CT and the hepatobiliary phase in the gadoxetic acid-enhanced MRI scan,as well as the portal vein crossing through sign in the setting of liver cirrhosis.This case highlights the imaging characteristics of giant hepatic regenerative nodules in hepatitis cirrhosis.

Clinical characteristics and risk factors of hepatitis B virus-related cirrhosis/hepatocellular carcinoma:A single-center retrospective study

Background and aims:Hepatitis B virus(HBV)infection is a major global health problem which progresses to liver cirrhosis(LC)and hepatocellular carcinoma(HCC).Early prediction of disease changes and intervention are essential to slow disease progression and protect liver function.This study aimed to analyze the clinical characteristics of patients with HBV-related LC and HCC at different serum alanine aminotransferase(ALT)levels and explore the risk factors of HBV infection progressing to LC/HCC.Methods:A total of 379 patients with HBV infection treated in The Third People's Hospital of Shenzhen between January 2014 and December 2016 without any antiviral drug therapy were enrolled.Patients were divided into the LC/HCC and non-LC/HCC groups based on clinical diagnosis,which was determined through imaging and expressions of pathological and laboratory test markers,and patients with LC/HCC were further divided into three groups according to the serum ALT levels.Differences in general information,clinical symptoms,and expression levels of serological indices of the above groups were compared and analyzed,logistic regression was used to analyze the risk factors for LC/HCC development,and the clinical diagnostic efficacy of indicators was judged by the receiver operator characteristic(ROC).Results:LC/HCC mainly occurred in the ALT normal and mildly elevated groups,with 70.83% of patients with HCC having an LC background.In the comparison of different ALT level groups,the moderately eseverely elevated group had the highest proportion of patients with skin jaundice,abdominal varices,rebound tenderness,higher white blood cell and neutrophil(NEUT)counts;and higher levels of aspartate aminotransferase,glutamyl transpeptidase,total bilirubin,and direct bilirubin.The LC/HCC group was older and had significantly higher proportions of male patients,alcohol consumption,and combined hypertension than the non-LC/HCC group(all P<0.05).Logistic regression analysis showed that age,combined hypertension,abdominal varicose veins,subcostal palpation,and NEUT count were risk factors for LC/HCC development;and the area under the curve for this model on the ROC analysis was 0.935(95%confidence interval 0.899e0.972)with specificity and sensitivity of 97.4%and 70.7%,respectively.

Detection of carboxyhemoglobin in patients with hepatic encephalopathy due to hepatitis B virus-related cirrhosis

Background The heme oxygenase/carbon monoxide （HO/CO） system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin （COHb） level. The aims of this study were to reveal the significance of COHb in patients with hepatitis B virus-related cirrhosis （HBC） complicated by hepatic encephalopathy （HE）, and to further investigate the influence of the HO/CO pathway on the end-stage cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC. Methods According to the diagnostic criteria, 63 HBC inpatients with HE were enrolled in group H. Patients regaining awareness with current therapies were categorized into group P-H. Comparisons were made with a control group （group N） consisting of 20 health volunteers. The levels of COHb, partial pressure of oxygen （PaO2） and oxygen saturation （SaO2） were determined by arterial blood gas analysis method. The incidences of hepatorenal syndrome （HRS）, upper gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial peritonitis （SBP） in group H were recorded. COHb levels in different groups were compared, and the correlations of COHb levels with HE grades （I, II, III, and IV）, PaO2, SaO2 and hypoxemia were analyzed. Results The COHb level in group P-H （（1.672＋0.761）%） was significantly higher than that in group N （（0.983±0.231）%） （P 〈0.01 ）, and the level in group H （（2.102±1.021）%） was significantly higher than groups P-H and N （P 〈0.01 ）. A positive correlation was observed between the COHb concentration and the grade of HE （rs=0.357, P=-0.004）. There were no significant differences of COHb levels between HE patients with and without complications such as esophagogastric varices （（2.302±1.072）% vs. （1.802±1.041）%, P 〉0.05） or the occurrence of SBP （（2.960±0.561）% vs. （2.030±1.021）%, P 〉0.05）. Compared with HE patients with HRS, the level of COHb was significantly higher in HE patients without HRS （（2.502±1.073）% vs. （1.981＋1.020）%, P=0.029）. The COHb level had a negative correlation with PaO2 （r=-0.335, P=0.007） while no statistically significant relationship was found with SaO2 （r=-0.071, P 〉0.05）. However, when the above two parameters met the diagnostic criteria of hypoxemia, the COHb concentration increased （（2.621±0.880）% vs. （1.910±0.931）%, P=0.011 ）. Conclusions COHb is a potential candidate to estimate the severity and therapeutic effect of HE. The levels of COHb may be tissue-specific in cirrhotic patients with different complications.

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.

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.

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.

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.

Long term outcome of antiviral therapy in patients with hepatitis B associated decompensated cirrhosis

AIM To investigate survival rate and incidence of hepatocellular carcinoma(HCC) in patients with decompensated cirrhosis in the antiviral era.METHODS We used the Korean Health Insurance Review and Assessment. Korea's health insurance system is a public single-payer system. The study population consisted of 286871 patients who were prescribed hepatitis B antiviral therapy for the first time between 2007 and 2014 in accordance with the insurance guidelines.Overall, 48365 antiviral treatment-na?ve patients treated between 2008 and 2009 were included, and each had a follow-up period ≥ 5 years. Data were analyzed for the 1 st decompensated chronic hepatitis B(CHB) and treatment-na?ve patients(n = 7166). RESULTS The mean patient age was 43.5 years. The annual mortality rates were 2.4%-19.1%, and 5-year cumulative mortality rate was 32.6% in 1^(st) decompensated CHB treatment-na?ve subjects. But the annual mortality rates sharply decreased to 3.4%(2.4%-4.9%, 2-5 year) after one year of antiviral treatment. Incidence of HCC at first year was 14.3%, the annual incidence of HCC decreased to 2.5%(1.8%-3.7%, 2-5 year) after one year. 5-year cumulative incidence of HCC was 24.1%. Recurrence rate of decompensated event was 46.9% at first year, but the annual incidence of second decompensation events in decompensated CHB treatment-na?ve patients was 3.4%(2.1%-5.4%, 2-5 year) after one year antiviral treatment. 5-year cumulative recurrence rate of decompensated events was 60.6%. Meanwhile, 5-year cumulative mortality rate was 3.1%, and 5-year cumulative incidence of HCC was 11.5% in compensated CHB treatment-na?ve patients.CONCLUSION Long term outcome of decompensated cirrhosis treated with antiviral agent improved much, and incidence of hepatocellular carcinoma and mortality sharply decreased after one year treatment.

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.

Serum and ascites levels of macrophage migration inhibitory factor, TNF-α and IL-6 in patients with chronic virus hepatitis B and hepatitis cirrhosis

Objective: To study the potential role of macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the development of chronic virus hepatitis B (CH) and hepatitis cirrhosis (HC). Methods: The serum concentrations of MIF, TNF-α and IL-6 in 18 patients with chronic virus hepatitis B and in 14 patients with hepatitis cirrhosis without as- citic fluid, and the serum and ascites cytokine con- centrations in 22 HC patients with ascitic fluid were detected by enzyme linked immunity sorbed assay. Results: The cytokine concentrations of the patients were significantly higher than those of the controls. The serum levels of MIF, TNF-α and IL-6 of the 22 patients with ascitic fluid were higer than those of 14 HC patients without ascites. In the 18 patients with CH, the serum cytokine concentrations were the low- est. The serum cytokine concentrations of the 22 HC patients with ascites were significantly higher than those of the 14 HC patients without ascites (P< 0. 01). Their serum cytokine concentrations were sig- nificantly higher than those in the 18 patients with CH (P<0. 01). The concentration of IL-6 in ascites was the highest among all the groups. The serum le- vels of MIF, TNF-α and IL-6 are correlated with al- anine aminotransferase (ALT) in the patients with CH, but not in those with HC with or without asci- tes. Conclusions: These results indicated that MIF, TNF- α and IL-6 may participate in the pathological process of CH and cirrhosis, that IL-6 seems to play an important role in ascites formation, and that se- rum levels of MIF, TNF-α and IL-6 appear to reflect the severity of tissue injury in HBV disease.