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.

Hepatitis B virus infection and its treatment in Eastern Ethiopia

Hepatitis B virus(HBV)infection causes acute and chronic hepatitis,compensated and decompensated cirrhosis,and hepatocellular carcinoma worldwide.The actual status of HBV infection and its treatment in certain regions of Asian and African countries,including Ethiopia,has not been well-documented thus far.Antiviral therapy for HBV infection can prevent the progression of HBV-related liver diseases and decrease the HBV-related symptoms,such as abdominal symp-toms,fatigue,systemic symptoms and others.In Eastern Ethiopia,HBV-infected patients with cirrhosis were found to be positive for the HBV e antigen and to have a higher viral load than those without cirrhosis.Notably,54.4%of patients practiced khat chewing and 18.1%consumed excessive amounts of alcohol.Teno-fovir disoproxil fumarate effectively suppressed HBV DNA in those infected with HBV.It is important to elucidate the actual status of HBV infection in Eastern Ethiopia to eliminate HBV infection worldwide by 2030.HBV vaccination and the educational programs for Health Science students that provide practical strategies could help to reduce HBV infection in Eastern Ethiopia.

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.

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.

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.

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.

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.

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.

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.

Liver stiffness in the hepatitis B virus carrier:A non-invasive marker of liver disease influenced by the pattern of transaminases

AIM： To investigate the usefulness of transient elastography by Fibroscan （FS）, a rapid non-invasive technique to evaluate liver fibrosis, in the management of chronic hepatitis B virus （HBV） carriers. METHODS： In 297 consecutive HBV carriers, we studied the correlation between liver stiffness （LS）, stage of liver disease and other factors potentially influencing FS measurements. In 87 chronic hepatitis B （CriB） patients, we monitored the FS variations according to the spontaneous or treatment-induced variations of biochemical activity during follow-up. RESULTS： FS values were 12.3 ± 3.3 kPa in acute hepatitis, 10.3 ± 8.8 kPa in chronic hepatitis, 4.3 ± 1.0 kPa in inactive carriers and 4.6 ± 1.2 kPa in blood donors. We identified the cut-offs of 7.5 and 11.8 kPa for the diagnosis of fibrosis ≥S3 and cirrhosis respectively, showing 93.9% and 86.5% sensitivity, 88.5% and 96.3% specificity, 76.7% and 86.7% positive predictive value （PPV）, 97.3% and 96.3% negative predictive value （NPV） and 90.1% and 94.2% diagnostic accuracy. At multivariate analysis in 171 untreated carriers, fibrosis stage （t = 13.187,P 〈 0.001）, active vs inactive HBV infection （t = 6.437, P 〈 0.001）, alanine aminotransferase （ALT） （t = 4.740, P 〈 0.001） and HBV-DNA levels （t = -2.046, P = 0.042） were independently associated with FS. Necroinflammation score （t = 2.158, 〉 10/18 vs ≤ 10/18, P = 0.035） and ALT levels （t = 3.566, P =0.001） were independently associated with LS in 83 untreated patients without cirrhosis and long-term biochemical remission （t = 4.662, P 〈 0.001） in 80 treated patients. During FS monitoring （mean followup 19.9 ± 7.1 mo） FS values paralleled those of ALT in patients with hepatitis exacerbation （with 1.2 to 4.4-fold increases in Crib patients） and showed a progressive decrease during antiviral therapy. CONCLUSION： FS is a non-invasive tool to monitor liver disease in chronic HBV carriers, provided that the pattern of biochemical activity is taken into account. In the inactive carrier, it identifies non-HBV-related causes of liver damage and transient reactivations. In CHB patients, it may warrant a more appropriate timing of control liver biopsies.

Non-invasive assessment of liver fibrosis in chronic hepatitis B

The goal of this review is to provide a comprehensive picture of the role,clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus(HBV)infection.During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations,mainly:invasiveness,costs,low reproducibility,poor acceptance by patients.Elastographic techniques conceived to assess liver stiffness,in particular transient elastography,and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis.Recent evidence highlights that both liver stiffness and some bio-chemical markers correlatewith survival and major clinical end-points such as liver decompensation,development of hepatocellular carcinoma and portal hypertension.Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis.Given their prognostic value,transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes.Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development.

On-treatment monitoring of liver fibrosis with serum hepatitis B core-related antigen in chronic hepatitis B

BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.

Hepatitis B virus pre-S/S variants in liver diseases

Chronic hepatitis B is a global health problem. The clinical outcomes of chronic hepatitis B infection include asymptomatic carrier state, chronic hepatitis(CH), liver cirrhosis(LC), and hepatocellular carcinoma(HCC). Because of the spontaneous error rate inherent to viral reverse transcriptase, the hepatitis B virus(HBV) genome evolves during the course of infection under the antiviral pressure of host immunity. The clinical significance of pre-S/S variants has become increasingly recognized in patients with chronic HBV infection. Pre-S/S variants are often identified in hepatitis B carriers with CH, LC, and HCC, which suggests that these naturally occurring pre-S/S variants may contribute to the development of progressive liver damage and hepatocarcinogenesis. This paper reviews the function of the pre-S/S region along with recent findings related to the role of pre-S/S variants in liver diseases. According to the mutation type, five pre-S/S variants have been identified: pre-S deletion, pre-S point mutation, pre-S1 splice variant, C-terminus S point mutation, and pre-S/S nonsense mutation. Their associations with HBV genotype and the possible pathogenesis of pre-S/S variants are discussed. Different pre-S/S variants cause liver diseases through different mechanisms. Most cause the intracellular retention of HBV envelope proteins and induction of endoplasmic reticulum stress, which results in liver diseases. Pre-S/S variants should be routinely determined in HBV carriers to help identify individuals who may be at a high risk of less favorable liver disease progression. Additional investigations are required to explore the molecular mechanisms of the pre-S/S variants involved in the pathogenesis of each stage of liver disease.

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.

Lamivudine prophylaxis of liver allograft HBV reinfection in HBV related cirrhotic patients after liver transplantation

BACKGROUND: Liver allograft hepatitis B virus (HBV) reinfection and hepatitis B (HB) recurrence jeopardize the long-term survival of recipient and liver allograft. Lamivu- dine has been referred as a novel antiviral agent against HBV in HBV cirrhotic patients even in liver transplantation setting. We assessed the prophylatic effect of lamivudine on liver allograft HBV reinfection and clarified the dynamic changes of HBV markers in HBV related decompensated liver cirrhosis after liver transplantation. METHODS: Twenty-five recipients were divided into three groups: HBV active replication group (15 recipients), HBV inactive replication group (7), and control group (3). 100 mg/d lamivudine was administered preoperatively except in the control group. The HBV markers of serial sera and liver biopsy samples of the 25 recipients were evaluated re- gularly with enzyme-linked radioimmunoassay, HBV DNA fluorecent quantitative assay, immunohistochemical stain- ing , labelled streptavidin biotin ( LSAB) and digoxin la- belled HBV DNA hybridization in situ. The dynamic alter- nation of HBV markers under lamivudine prophylaxis was observed. RESULTS: In the HBV active replication group who had received lamivudine 2 weeks before liver transplantation, serum HBV DNA positive converted to negative by 80%. HBsAg of all recipients disappeared after liver transplanta- tion , but corresponding antibodies of HBV appeared within one week after the operation. HBsAb 9/15, HBcAb 13/15 and HBeAb 11/15 appeared and subsided gradually within 24 weeks. HBV DNA in sera was kept negative; HBsAg, HBcAg and HBV DNA hybridization in situ of liver biopsy samples remained negative after use of lamivudine. Ten of the 15 recipients showed clearance of HBV, and per se HBV markers were undetectable both in serum and liver bi- opsy samples between 12 to 44 weeks (24 weeks on ave- rage). The 1-, 2-year survival rates were 83% in this group. Two of the 15 recipients developed HBV allograft reinfection or recurrence of hepatitis 2 years after lamivudi- ne monoprophylaxis (2/15, 13.3%). In the HBV inactive replication group, the outcome was similar to that of the HBV active group. The HBV antibody frequency was HBs- Ab 4/7, HBcAb 6/7, and HBeAb 2/7. Three of 7 recipients showed HBV clearance both in sera and liver biopsy sam- ples , whereas in the control group all 3 recipients developed HBV allograft reinfection and recurrent hepatitis 8, 10, 12 months postoperatively; one of them died of fibrosing cho- lestatic hepatitis, and the remaining 2 recovered after addi- tional lamivudine therapy. The overall allograft reinfection rate was 9.1% (2/22) and the overall 1-, 2-year survival rates were 87%) in the lamivudine prophylaxis group. CONCLUSIONS: Lamivudine prophylaxis can prevent ef- fectively liver allograft from HBV reinfection in patients with HBV-related decompensated liver cirrhosis even in HBV active replication recipient after liver transplantation. Its long-term outcome remains to be studied.

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.

Hepatitis B and liver transplantation: Molecular and clinical features that influence recurrence and outcome

Hepatitis B virus (HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin (HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV (entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of &#x0201c;hepatitis B virus AND liver transplantation&#x0201d;. We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.