Network meta-analysis of the compensatory effect of different Chinese herbal compounds combined with Entecavir in the treatment of hepatitis B cirrhosis

Objective:To evaluate the efficacy and safety of different Chinese herbal compounds combined with Entecavir in the treatment of hepatitis B cirrhosis during the compensatory period by using mesh meta-analysis.Methods:PubMed,CNKI,Wanfang and VIP databases were searched by computer,and the retrieval time was from the establishment of each database to October 5,2022.According to inclusion and exclusion criteria,literature search was conducted independently by two researchers.RevMan5.4.1 software provided by Cochrane was used for evaluation,and Stata16.0 software was used for statistical analysis.Results:A total of 34 RCTs were included,involving 16 TCM compounds and 1543 patients.The results of network meta-analysis showed that ALT indexes of liver function were listed as Yiqi Jiedu Tongluo Method>Luoshugan Tablet>Anluo Huaxian Wan>Qishenrugan Capsule>Qingganhuaji Decoction>Ganshuang Granules>Compound Biejia Rugan Tablet>Rougan Sanjie Decoction>Shugan Jianpi Decoction>Shenqi Fuzheng Huayu Decoction>Peituhua Decoction>Shugan Jianpi Huoxu prescription>Rhubarb Zhezhan Capsule combined with Entecavir treatment respectively;The order of HA index of liver fibrosis was Heluo Shugan Tablet>Shugan Jianpi Huoxui prescription>Anluo Huaxian Wan>Compound Biejia Ruangan Tablet>Rougan Sanjie Decoction>Ganshuang Granules>Danji Huoxui Decoction>Yiqi Jiedu Tongluo Method>Rhubarb Zhezhe Capsule>Fuzheng Huayu Table>Shugan Jianpi Decoction>Rougan Huayu Decoction>Peitu Huayu Decoction>Qingganhuaji Prescription>Shenqi Fuzheng Huayu prescription combined with Entecavir respectively;In order of adverse reactions from best to worst,Shuganjianpi Decoction,Qishenrugangan Capsule,Ganshuang Granules,Peituhuazhi Decoction,compound Biejiruganpian,and He Shugan Pian combined with entecavir,respectively;The effective rate of treatment was listed as Ganshuang Granules>Compound Biejia Ruangan Tablets>uoshugan Tablets>Rougansanjie Decoction>Rhubarb Zhezhe Capsules>Yiqi Jiedu Tongluo Method>Qingganhuaji prescription>Anluo Huaxia Wan>Shugan Jianpi Decoction>Fuzheng Huayu tablets>Peituhuazhi Decoction>Shenqi Fuzheng Huayu prescription combined with Entecavir respectively.Conclusion:Entecavir combined with supplementing qi and detoxifying and dredging collages is the best method to recover ALT index of liver function during the compensation period for hepatitis B cirrhosis;Entecavir combination and Luoshugan tablet were the best treatment for HA index of hepatic fibrosis;Entecavir combined with Shuganjianpi Decoction was the best treatment for adverse reactions;The best treatment efficiency was Entecavir combined with Ganshuang granules.

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.

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.

Danshao Huaxian capsule in treatment of decompensated cirrhosis resulting from chronic hepatitis B

BACKGROUND: The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are ourweight serious sideeffects and the risk of fatal exacerbation of disease. Danshao Huaxian capsule rapidly reduces hepatitis B virus(HBV)-DNA in serum to undetectable levels. METHODS: A total of 35 patients with chronic hepatitis B and decompensated cirrhosis were treated with Danshao Huaxian 1.2g. po. tid daily. Before the treatment, HBVDNA in serum was positive in all patients. Ten patients had Child-Pugh class B and 25, class C hepatitis B. Seven patients underwent liver transplantation within 6 months of initial treatment. Of the 10 patients of class B, 5 died within 6 months, and the other 5 did not complete the treatment for some reasons; the 25 patients of class C were treated for at least 6 months (mean =19 months). RESULTS: In most of the 25 patients, liver function was improved slowly but markedly after 9 months of treatment, showing a decreased level of serum bilirubin from 67±13 to 30±4μmol/L (P<0.05, baseline vs.6 months), an increased level of serum albumin from 27±1 to 34±1 g/L(P<0.05) and a decreased level of Child-Pugh score from 10.3±0.4 to 7.5+0.5 (P<0.05). Three patients developed resistance to Danshao Huaxian because of a mutation in the YMDD motif, but liver function was not deteriorated. Inhibition of viral replication with Danshao Huaxian resulted in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term results remain uncertain. CONCLUSION: Danshao Huaxian capsule is effective in inhibiting viral DNA replication in patients with decompensated cirrhosis and making clinical improvement.

Short Term Efficacy of Entecavir in the Treatment of Decompensated Chronic Hepatitis B Cirrhosis

Objective:To explore the effect of entecavir on patients with decompensated chronic hepatitis B cirrhosis.Methods:From October 2007 to December 2019,100 patients with decompensated chronic hepatitis B cirrhosis who were treated in our hospital were selected to carry out this study.The clinical data of the patients were analyzed.According to whether entecavir treatment was carried out,100 patients were divided into two groups,50 cases in the control group and 50 cases in the observation group.The control group was treated with conventional drugs,and the observation group was treated with entecavir.Liver function indexes,liver fibrosis indexes,HBV-DNA negative conversion rate and incidence of adverse reactions were compared between the two groups.Results:Compared with the control group,the liver function indexes of the observation group were lower,P<0.05;Compared with the control group,the observation group was better,P<0.05;The negative rate of HBV-DNA in the observation group was lower than that in the control group(P<0.05);There was no difference in the incidence of adverse reactions between the two groups,P>0.05.Conclusion:Entecavir can not only improve the liver function,but also enhance the shortterm treatment effect,without increasing adverse reactions,and has high safety,which is worthy of recommendation.

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 Dahuang Zhechong pill combined with antiviral therapy on serum virus replication indexes as well as immunity and inflammation indexes in patients with chronic hepatitis B cirrhosis

Objective:To study the effect of Dahuang Zhechong pill combined with antiviral therapy on serum virus replication indexes as well as immunity and inflammation indexes in patients with chronic hepatitis B cirrhosis.Methods: A total of 104 patients with chronic hepatitis B cirrhosis who were treated in our hospital between May 2013 and April 2016 were selected and randomly divided into combined treatment group and western medicine treatment group who accepted Dahuang Zhechong pill combined with entecavir treatment and entecavir monotherapy respectively. Before and after treatment, the HBV-DNA loads, liver fibrosis index and immune cell levels as well as inflammatory cytokine levels were determined.Results:HBV-DNA loads of both groups of patients at 48 weeks after treatment were significantly lower than those before treatment, and the HBV-DNA loads were not significantly different between the two groups after treatment;serum HA, LN, PC-III, IV-C, IL-15, IL-16 and TGF-β1 levels as well as peripheral blood Treg cell levels of both groups at 24 weeks and 48 weeks after treatment were significantly lower than those before treatment while peripheral blood NK cell levels were higher than those before treatment, and serum HA, LN, PC-III, IV-C, IL-15, IL-16 and TGF-β1 levels as well as peripheral blood Treg cell levels of combined treatment group were significantly lower than those of western medicine treatment group while peripheral blood NK cell levels were higher than those of western medicine treatment group. Conclusion:Dahuang Zhechong pill combined with antiviral treatment of chronic hepatitis B cirrhosis can regulate the immune response and inflammatory reaction without affecting the inhibiting effect of antiviral drugs on viral replication.

Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease

BACKGROUND Although many studies have investigated the impact of chronic hepatitis B virus(HBV)infection and nonalcoholic fatty liver disease(NAFLD)on liver disease,few have investigated the relationship between nonalcoholic steatohepatitis(NASH)defined by liver pathology and the prognosis of chronic HBV infection.Most patients were followed up for a short time.This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection.AIM To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events[cirrhosis,hepatocellular carcinoma(HCC),and death]in patients with chronic hepatitis B(CHB)virus infection.METHODS We enrolled patients with chronic hepatitis B virus(HBV)infection who underwent liver biopsy at the Third People’s Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020.Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected.Propensity score matching(PSM)was used to balance baseline parameters,Kaplan-Meier(K-M)survival analysis was used to evaluate the risk of clinical events,and Cox regression was used to analyze the risk factors of events.RESULTS Overall,456 patients with chronic HBV infection were included in the study,of whom 152(33.3%)had histologically confirmed NAFLD.The median follow-up time of the entire cohort was 70.5 mo.Thirty-four patients developed cirrhosis,which was diagnosed using ultrasound during the follow-up period.K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis(log-rank test,P>0.05).Patients with CHB with fibrosis at baseline were more prone to cirrhosis(log-rank test,P=0.046).After PSM,multivariate analysis showed that diabetes mellitus,ballooning deformation(BD),and platelet(PLT)were independent risk factors for cirrhosis diagnosed using ultrasound(P<0.05).A total of 10 patients(2.2%)developed HCC,and six of these patients were in the combined NAFLD group.K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher(log-rank test,P<0.05).Hepatocyte ballooning,and severe liver fibrosis were also associated with an increased risk of HCC(log-rank test,all P<0.05).Cox multivariate analysis revealed that hepatocyte ballooning,liver fibrosis,and diabetes mellitus were independent risk factors for HCC.CONCLUSION There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD.Diabetes mellitus,BD,and PLT were independent risk factors for liver cirrhosis.Patients with chronic HBV infection and NASH have an increased risk of HCC.BD,liver fibrosis,and diabetes mellitus are independent risk factors for HCC.

Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection

BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.

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.

Risk for hepatocellular carcinoma in the course of chronic hepatitis B virus infection and the protective effect of therapy with nucleos(t)ide analogues

Hepatocellular carcinoma(HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus(HBV) infection(CHB) is the most important etiologic factor of this tumor, accounting for the development of more than50% of the cases in the world. Primary prevention ofHCC is possible by hepatitis B vaccination conferring protection from HBV infection. However, according to the World Health Organization Hepatitis B Fact sheet N° 204(update of July 2014) globally there exists a large pool of > 240 million people chronically infected with HBV who are at risk for development of HCC. These individuals represent a target population for secondary prevention both of cirrhosis and of HCC. Since ongoing HBV replication in CHB is linked with the progression of the underlying liver disease to cirrhosis as well as with the development of HCC, effective antiviral treatment in CHB has also been evaluated in terms of secondary prevention of HCC. Currently, most patients with active CHB are subjected to long term treatment with the first line nucleos(t)ide analogues entecavir and tenofovir. These compounds are of high antiviral potency and have a high barrier to HBV resistance compared to lamivudine, adefovir dipivoxil and even telbivudine. Many studies have shown that patients under antiviral treatment, especially those in virological remission, develop less frequently HCC compared to the untreated ones. However, the risk for development of HCC cannot be eliminated. Therefore, surveillance for the development of HCC of patients with chronic hepatitis B must be lifelong or until a time in the future when new treatments will be able to completely eradicate HBV from the liver particularly in the early stages of CHB infection. In this context, the aim of this review is to outline the magnitude of the risk for development of HCC among patients with CHB, in the various phases of the infection and in relation to virus, host and environmental factors as evaluated in the world literature. Moreover, the benefits of antiviral treatment of CHB with nucleos/tide analogs, which have changed the natural history of the disease and have reduced but not eliminated the risk of HCC are also reviewed.

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.

Natural regression of fibrosis in chronic hepatitis B

The fibrosis of liver cirrhosis was considered to be irreversible before the anti-viral drugs showed that it is reversible when they lead to continuous suppression of viral replication and inflammation. However, several reports previously showed that fibrosis of type B liver cirrhosis was almost completely absorbed after the natural remission of chronic inflammation. This phenomenon might not be limited to exceptional patients, but rather occur commonly, considering the dynamic clinical features of chronic hepatitis B(CHB), where inactive carrier stage normally follows aggravation of hepatitis and progression of fibrosis at the time of HBe Ag seroconversion. Thus, fibrosis levels of CHB as a hepatocellular carcinoma(HCC)-surveillance marker, particularly those of the inactive stage, could be underestimated, because some of them might have been(pre)cirrhotic in the past and recovered with the natural regression of fibrosis. We argue that cirrhosisinduced HCC mechanisms, rather than direct action of viral genome, may be more common than generally considered in CHB patients. This may have some impact on reconsidering the surveillance rationale for HCC in CHB, from where advanced HCCs tended to be missed. In addition, a molecular marker to assess the cancer-prone characteristics of the liver will definitely be needed to resolve the issue.

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.

Noninvasive assessment of liver damage in chronic hepatitis B

AIM:To evaluate the efficacy of the aspartate aminotransferase/platelet ratio index(APRI)and neutrophillymphocyte(N/L)ratio to predict liver damage in chronic hepatitis B(CHB).METHODS:We analyzed 89 patients diagnosed with CHB by percutaneous liver biopsy and 43 healthy subjects.Liver biopsy materials were stained with hematoxylin-eosin and Masson’s trichrome.Patients’fibrosis scores and histological activity index(HAI)were calculated according to the Ishak scoring system.Fibrosis score was recognized as follows:F0-1 No/early-stage fibrosis,F2-6 significant fibrosis,F0-4 non-cirrhotic and F5-6 cirrhotic.Significant liver fibrosis was defined as an Ishak score of≥2.APRI and N/L ratio calculation was made by blood test results.RESULTS:The hepatitis B and control group showed no difference in N/L ratios while there was a significant difference in terms of APRI scores(P<0.001).Multiple logistic regression analysis revealed that the only independent predictive factor for liver fibrosis in CHB was platelet count.APRI score was significantly higher in cirrhotic patients than in non-cirrhotic patients.However,this significance was not confirmed by multiple logistic regression analysis.The optimum APRI score cut-off point to identify patients with cirrhosis was 1.01with sensitivity,specificity,positive predictive value and negative predictive value of 62%(36%-86%),74%(62%-83%),29%(13%-49%)and 92%(82%-97%),respectively.In addition,correlation analyses revealed that N/L ratio has a negative and significant relationship with HAI(r=-0.218,P=0.041).CONCLUSION:N/L ratio was negatively correlated with HAI.APRI score may be useful to exclude cirrhosis in CHB patients.

Liver fibrosis index-based nomograms for identifying esophageal varices in patients with chronic hepatitis B related cirrhosis

BACKGROUND Esophageal varices(EV)are the most fatal complication of chronic hepatitis B(CHB)related cirrhosis.The prognosis is poor,especially after the first upper gastrointestinal hemorrhage.AIM To construct nomograms to predict the risk and severity of EV in patients with CHB related cirrhosis.METHODS Between 2016 and 2018,the patients with CHB related cirrhosis were recruited and divided into a training or validation cohort at The First Affiliated Hospital of Wenzhou Medical University.Clinical and ultrasonic parameters that were closely related to EV risk and severity were screened out by univariate and multivariate logistic regression analyses,and integrated into two nomograms,respectively.Both nomograms were internally and externally validated by calibration,concordance index(C-index),receiver operating characteristic curve,and decision curve analyses(DCA).RESULTS A total of 307 patients with CHB related cirrhosis were recruited.The independent risk factors for EV included Child-Pugh class[odds ratio(OR)=7.705,95%confidence interval(CI)=2.169-27.370,P=0.002],platelet count(OR=0.992,95%CI=0.984-1.000,P=0.044),splenic portal index(SPI)(OR=3.895,95%CI=1.630-9.308,P=0.002),and liver fibrosis index(LFI)(OR=3.603,95%CI=1.336-9.719,P=0.011);those of EV severity included Child-Pugh class(OR=5.436,95%CI=2.112-13.990,P<0.001),mean portal vein velocity(OR=1.479,95%CI=1.043-2.098,P=0.028),portal vein diameter(OR=1.397,95%CI=1.021-1.912,P=0.037),SPI(OR=1.463,95%CI=1.030-2.079,P=0.034),and LFI(OR=3.089,95%CI=1.442-6.617,P=0.004).Two nomograms(predicting EV risk and severity,respectively)were well-calibrated and had a favorable discriminative ability,with C-indexes of 0.916 and 0.846 in the training cohort,respectively,higher than those of other predictive indexes,like LFI(C-indexes=0.781 and 0.738),SPI(C-indexes=0.805 and 0.714),ratio of platelet count to spleen diameter(PSR)(C-indexes=0.822 and 0.726),King’s score(C-indexes=0.694 and 0.609),and Lok index(C-indexes=0.788 and 0.700).The areas under the curves(AUCs)of the two nomograms were 0.916 and 0.846 in the training cohort,respectively,higher than those of LFI(AUCs=0.781 and 0.738),SPI(AUCs=0.805 and 0.714),PSR(AUCs=0.822 and 0.726),King’s score(AUCs=0.694 and 0.609),and Lok index(AUCs=0.788 and 0.700).Better net benefits were shown in the DCA.The results were validated in the validation cohort.CONCLUSION Nomograms incorporating clinical and ultrasonic variables are efficient in noninvasively predicting the risk and severity of EV.

Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B

AIM: To investigate the effect of human leukocyte antigen(HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B.METHODS: Patient records at a single institution's hepatology clinic were reviewed. Demographic data, laboratory results, endoscopy results, virological parameters, biopsy scores and treatment statuses were recorded. In total, 355 patients were eligible for thestudy, of whom 226(63.7%) were male. Overall, 82(23.1%) were hepatitis B early antigen(HBeAg) positive, 87(24.5%) had cirrhosis, and 66(18.6%) had inactive disease. The presence of DQB1 and DRB1 alleles was determined by polymerase chain reaction with sequence-specific primers. The distribution of the genotyped alleles among patients with cirrhosis and patients with chronic active hepatitis was analyzed.RESULTS: The most frequent HLA DQB1 allele was DQB1*03:01(48.2%), and the most frequent HLA DRB1 allele was DRB1*13/14(51.8%). DQB1*05:01 was more frequent in patients with active disease than in inactive patients(27% vs 9.1%; P = 0.002, Pc = 0.026). DRB1*07 was rare in patients with cirrhosis compared with non-cirrhotics(3.4% vs 16%; P = 0.002, Pc = 0.022). Older age(P < 0.001) and male gender(P = 0.008) were the other factors that affected the presence of cirrhosis. In a multivariate logistic regression analysis, DRB1*07 remained a significant negative predictor of cirrhosis(P = 0.015). A bioinformatics analysis revealed that a polymorphic amino acid sequence in DRB1*07 may alter interaction with the T-cell recognition site.CONCLUSION: This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients.

Clinical features of acute hepatitis E super-infections on chronic hepatitis B

AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B(CHB) superimposed with hepatitis E virus(HEV).METHODS This retrospective cohort study included 228 patients with acute HEV infection(showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB(confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus(HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases(defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes.RESULTS The symptoms caused by superimposed acute hepatitis E(AHE) were much more severe in cirrhotic patients(n = 94) than in non-cirrhotic patients(n = 134), as evidenced by significantly higher liver complications(77.7% vs 28.4%, P < 0.001) and mortality rate(21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients(n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels(OR: 5.1, P = 0.012), alcohol consumption(OR: 6.4, P = 0.020), and underlying diabetes(OR: 7.5, P = 0.003) and kidney diseases(OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome.

Study on the Correlation of Plasma NO, ET-1 and ALT in the Patients with Chronic Hepatitis and Cirrhosis

The levels of plasma nitric oxide (NO), endothelin 1 (ET 1) and ALT in the patients with chronic hepatitis B and active cirrhosis and the correlation among them were observed and analyzed. NO 3 ˉ was restored by using cadmium column assay and NO 2 ˉ measured by heavy nitrogen assay. The primitive NO 3 ˉ and total restored NO 2 ˉ(NO 3 ˉ/ NO 2 ˉ) in plasma of the patients with chronic hepatitis and cirrhosis. Plasma ET 1 and ALT levels were determined by using radioimmunological assay and Lai's assay, respectively. Compared with normal control group, the plasma levels of NO 2 ˉ/NO 3 ˉ and ET 1 in the patients with chronic active hepatitis and active cirrhosis were significantly increased ( P <0.05-0.01). There was a positive correlation between NO and ALT, and ET 1 and ALT in the patients with chronic active hepatitis and active cirrhosis respectively. It was suggested that elevation of both NO and ET 1 levels were closely related with injury severity of liver function.