Effect of viral hepatitis on type 2 diabetes:A Mendelian randomization study

BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.

Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

Evaluation of the diagnostic efficacy of noninvasive diagnosis in patients with chronic viral hepatitis B complicated with nonalcoholic fatty liver disease and significant liver fibrosis

Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combined models,and to explore their clinical features.Methods:A total of 104 inpatients with CHB diagnosed and complicated with NAFLD(hepatic steatosis suggested by liver biopsy)were retrospectively collected from January 2018 to January 2023 in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University.Liver biopsy was performed in all patients.General data,laboratory test results,liver hardness(LSM),FIB-4,APRI,GGT/PLT,AST/PLT and other results of patients were collected and grouped according to different fibrosis stages(S)to explore the clinical and pathological characteristics of patients with<S2 and S2 stages.Receiver operating characteristic curve was used to evaluate the diagnostic value of LSM,FIB-4,APRI,GGT/PLT,AST/PLT and their combined models in patients with significant liver fibrosis in CHB patients with NAFLD.Results:Among the 104 patients,there were 55 patients had S1 fibrosis,32 patients had S2 fibrosis,11 patients had S3 fibrosis and 6 patients had S4 fibrosis.Patients had<S2 fibrosis,ALT 33.75±17.15 U/L,AST 24.00(19.77,29.00)U/L,inflammation above G2 stage accounted for 92.72%,GGT/PLT 0.07(0.10,0.15),AST/PLT 0.09(0.10,0.15),LSM 8.70(6.80,10.10)kPa,FIB-41.07±0.51,APRI 0.26(0.22,0.28).In patients S2 fibrosis,ALT 42.14±21.39 U/L,AST 29.04(24.00,40.32)U/L,inflammation above G2 stage accounted for 97.95%,GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26),GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26).LSM 11.80(8.50,16.65)kPa,FIB-41.39±0.72,APRI 0.35(0.26,0.66),the difference between the two groups was statistically significant(P<0.05).The area under the receiver operator characteristic curves of the subjects of LSM,FIB-4,APRI,GGT/PLT and AST/PLT were 0.716,0.623,0.669,0.644 and 0.669(P<0.05),respectively.In the combined model,the area under the receiver operator characteristic curves of LSM combined with FIB-4,LSM combined with APRI,LSM combined with GGT/PLT and LSM combined with AST/PLT were 0.712,0.719,0.715 and 0.719,respectively(P<0.05).Conclusion:Although the currently commonly used Noninvasive diagnosis of liver fibrosis has certain diagnostic efficacy for significant liver fibrosis in CHB complicated with NAFLD,it cannot replace liver biopsy.Noninvasive Diagnosis can be used as an auxiliary method for regular clinical evaluation of liver biopsy.

Evolution of HBV Viral Load during Clinical and Biological Follow-Up of Chronic Hepatitis B Patients at the Saint Camille Hospital in Ouagadougou

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The aim of this study was to document the dynamics of HBV viral load during the follow-up of chronic hepatitis B patients at the Saint Camille Hospital in Ouagadougou (HOSCO) from 2017 to 2021. This descriptive retrospective study was carried out in the Hepato-Gastro-Enterology Department of HOSCO and focused on patients who were undergoing treatment for chronic viral hepatitis B. A total of 260 cases of chronic hepatitis B were included in the study. The most affected age group was 21 to 30 years, accounting for 48.08% of the cases. Lifestyle factors included alcohol consumption (3.08%) and tobacco use (2.69%). Major risk factors for transmission included lack of vaccination (98.46%), family history of HBV infection (68.00%) and engagement in high-risk activities (28.00%). Patients requiring treatment were prescribed Tenofovir 300 mg tablets. FibroScan® showed the presence of stage F3-F4 fibrosis (2.14%) and S3 steatosis (13.33%). After one year of follow-up, 6.92% of patients achieved an undetectable viral load with normalized transaminase levels. The majority of other patients had a detectable viral load but below 20,000 IU/mL. The prevalence of viral hepatitis B remains significant worldwide. Although effective and well-monitored treatment can lead to undetectable viremia, prevention remains the most effective strategy for successful management of this disease.

Factors Associated with Hepatic Steatosis in Black African Subjects with Chronic Viral Hepatitis B in Côte d’Ivoire

Context/Objectives: With the progression of the global epidemic of obesity and metabolic syndrome, the coexistence of hepatic steatosis in patients with chronic viral hepatitis B (VHB) is becoming significant. The aim of this work was to determine the factors associated with hepatic steatosis assessed by a Fibroscan with Controlled Attenuation Parameter (CAP) in patients with chronic viral hepatitis B in Côte d’Ivoire. Methods: This was a cross-sectional and analytical study. Data was collected from February 15 to July 31, 2020 in a private hospital structure in the city of Abidjan in Côte d’Ivoire. We included 83 patients with chronic viral hepatitis B. These were black patients, having performed a Fibroscan/CAP during the recruitment period and consenting to participate in the study. Patients with significant alcohol consumption, a secondary cause of hepatic steatosis, or other liver disease regardless of the etiology associated with hepatitis B were not included. Results: The frequency of hepatic steatosis in chronic VHB carriers assessed by the CAP in our study population was 48.19% including 24.10% severe steatosis. Obesity and high LDL cholesterol were statistically correlated with the presence of steatosis in our patients. Patients who had steatosis on ultrasound were 5 times more likely to have steatosis on CAP. Significant fibrosis was not significantly associated with steatosis. Conclusion: Obesity and LDL hypercholesterolemia are the main factors associated with hepatic steatosis detected by Fibroscan/CAP in patients with chronic viral hepatitis B.

Natural course of chronic hepatitis B is characterized by changing patterns of programmed death type-1 of CD8-positive T cells

AIM:To investigate if and how programmed death type-1(PD-1)expression affects the natural course of hepatitis B virus(HBV)infection. METHODS:Sixty-four patients in different natural stages of chronic HBV infection were enrolled in this study.PD-1 expression in total T cells was detected by flow cytometry.Levels of total CD8+T cell responses and proliferation in relation to PD-1 expression levels were analyzed with intracellular staining and PD-1/ PD-L1 blockage. RESULTS:The PD-1 expression in T cells was dynamically changed during the natural course of chronic HBV infection,did not significantly increase in the immune tolerance phase,and returned to normal in the inactive virus carrier stage.Blockage of the PD-1/PD-L1 pathway could not affect the T-cell response in the immune tolerance and inactive virus carrier stages of chronic HBV infection.However,it could significantly restore the T-cell response in the immune clearance stage of chronic HBV infection.Furthermore,the PD-1 expression level in T cells was associated with the alanine aminotransferase level during the immune clearance stage of chronic HBV infection. CONCLUSION:The PD-l/PD-L1 pathway plays a different role in T-cell response during the natural course of chronic HBV infection.

Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation

Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.

Serum concentration of sFas and sFasL in healthy HBsAg carriers,chronic viral hepatitis B and C patients

AIM: To estimate the amount of apoptosis among healthy HBsAg carriers, patients with chronic HBV infection treated with lamivudine and patients with chronic HCV infedJon treated with interferon alpha and ribavirin. Activity of apoptosis was evaluated by serum sFas/sFasL concentration measurement.Moreover dependence between apoptosis and HBV-DNA or HCV-RNA levels was studied.METHODS: Eighty-six persons were included into study: 34 healthy HBsAg carriers, 33 patients with chronic HBV infection and 19 patients with chronic HCV infection. Serum levels of sFas/sFasL were measured by ELISA assay. HBV-DNA and HCV-RNA were measured by RT-PCR assay. Levels of sFas/sFasL were determined before and 2 and 12 wk after therapy in patients with chronic hepatitis B and C infection.HBV-DNA or HCV-RNA was detected before treatment and 6 mo after treatment.RFSULTS: Twenty-four (71%) healthy HBsAg carriers showed HBV-DNA over 10^5/mL, which was comparable to the patients with chronic hepatitis B. Independently from HBV-DNA levels,the concentration of sFas among healthy HBsAg carriers was comparable to healthy persons. Among patients with chronic hepatitis B and C, the concentration of sFas was significantly higher in comparison to healthy HBsAg carriers and healthy persons. In chronic hepatitis B patients the concentration of sFas was decreased during lamivudine treatment. Among chronic hepatitis C patients the concentration of sFas was increased during IFN alpha and ribavirin treatment, sFasL was not detected in control group. Furthermore sFasL oo:urred more frequently in chronic hepatitis C patients in comparison to chronic hepatitis B patients.CONCLUSION: There are no correlations between apoptosis and HBV-DNA levels. However ther is an association between apoptosis and activity of inflammation in patients with chronic HBV infection. Apoptosis can be increased in patients with chronic hepatitis C by effective treatment which may be a result of apoptosis stimulation by IFN-α.

Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B

Several clinical trials have demonstrated the potent antiviral efficacy of entecavir(ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B(CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions(ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immunemediated responses(i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic(type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-yearold woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had selfdiscontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type Ⅳb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.

Hepatitis B virus genotypes in chronic liver disease patients from New Delhi,India

AIM: To study the Hepatitis B virus (HBV) genotypes and their effect on the progression and outcome in patients with chronic liver diseases from New Delhi, India. METHODS: Sera from 100 HBV-related chronic liver disease (CLDB) cases were tested for HBV genotype using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Type-specific primers-based PCR (TSP-PCR) targeting to the surface (S) gene encoding hepatitis B surface antigen. RESULTS: Only genotypes A and D were present and genotype D was dominant. Genotype D was present in all CLDB patient categories. The genotype distribution for the 100 patients with CLDB was as follows: genotype A, 16/100 (16%) (7/40- 17% chronic hepatitis B (CHB); 8/47, 17%, HBV-related cirrhosis (CRB); 1/13, 7.6%, HBV-related hepatocellular carcinoma (HCCB); genotype D- 84/100 (84%) (32/40- 80% CHB; 38/47- 81%, CRB; 11/13, 85%, HCCB); genotype A + D, 3/100 (3%) (1/40- 3% CHB; 1/47- 2%, CRB; 1/13, 7.6%, HCCB); C, 0; B, 0; E, 0; F, 0; G 0, H 0; (P < 0.01, genotype D vs A). CONCLUSION: Only HBV genotypes A and D were present in patients with CLDB from New Delhi, India. Compared with genotype D, genotype A patients had no significant clinical or biochemical differences (P > 0.05). Mixed infection with genotype A and D were seen in 3% of the cases. Genotype D was the dominant genotype prevalent in all patient categories.

Chronic hepatitis B in pregnant women: Current trends and approaches

Chronic hepatitis B(CHB)is a significant public health problem worldwide.The aim of the present review is to summarize the actual trends in the management of CHB in pregnant women.The prevalence of hepatitis B virus(HBV)infection in pregnant women is usually comparable to that in the general population in the corresponding geographic area.All women have to be screened for hepatitis B surface antigen(HBsAg)during pregnancy.Additional examinations of pregnant women with CHB may include maternal hepatitis B e antigen,HBV viral load,alanine aminotransferase level,and HBsAg level.The management of pregnancy depends on the phase of the HBV infection,which has to be determined before pregnancy.In women of childbearing age with CHB,antiviral therapy can pursue two main goals:Treatment of active CHB,and vertical transmission prevention.During pregnancy,tenofovir is the drug of choice in both cases.A combination of hepatitis B immunoglobulin and vaccine against hepatitis B should be administered within the first 12 h to all infants born to mothers with CHB.In such cases,there are no contraindications to breastfeeding.

Hepatitis B virus genotypes:Global distribution and clinical importance

At least 600000 individuals worldwide annually die of hepatitis B virus(HBV)-related diseases,such as chronic hepatitis B(CHB),liver cirrhosis(LC),and hepatocellular carcinoma(HCC).Many viral factors,such as viral load,genotype,and specific viral mutations,are known to affect disease progression.HBV reverse transcriptase does not have a proofreading function,therefore,many HBV genotypes,sub-genotypes,mutants,and recombinants emerge.Differences between genotypes in response to antiviral treatment have been determined.To date,10 HBV genotypes,scattered across different geographical regions,have been identified.For example,genotype A has a tendency for chronicity,whereas viral mutations are frequently encountered in genotype C.Both chronicity and mutation frequency are common in genotype D.LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes.Pathogenic differences between HBV genotypes explain disease intensity,progression to LC,and HCC.In conclusion,genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment.

Similar efficacy and safety of tenofovir in Asians and non-Asians with chronic hepatitis B

AIM:To compare the efficacy and safety of tenofovir disoproxil fumarate(TDF)in Asian and non-Asian chronic hepatitis B(CHB)patients.METHODS:The efficacy and safety of the initial 48wk of treatment with TDF was compared in a posthoc analysis of combined data from 217 Asians and299 non-Asians included in Studies 102 and 103and a post-approval,open-label trial(Study 123).Patient groups were compared according to baseline hepatitis B e antigen(HBe Ag)status and viral load.The main outcome measures included the proportion of patients who achieved a hepatitis B virus(HBV)DNA level<400 copies/m L at Week 48 of treatment.Secondary measures included:HBV DNA and alanine aminotransaminase(ALT)levels over time;proportion of patients with normal ALT levels;proportion of patients with HBe Ag loss/seroconversion and proportion of patients with hepatitis B surface antigen loss/seroconversion;changes in liver histology.Safety and tolerability were evaluated by the occurrence of adverse events(AEs),serious AEs,laboratory abnormalities,discontinuation of the study drug due to AEs,or death.The primary efficacy and safety analysis set included all patients who were randomly assigned to treatment and received at least one dose of study drug.RESULTS:At week 48,similar proportions of Asians and non-Asians reached HBV DNA<400 copies/m L(96%of Asian and 97%of non-Asian patients with HBe Ag-negative CHB and 83%of Asian and 79%of non-Asian patients with HBe Ag-positive CHB had HBV DNA)and normal ALT(78%of Asian and 81%of nonAsian patients with HBe Ag-negative CHB and 71%of Asian and 74%of non-Asian patients with HBe Agpositive CHB had normal ALT).On-treatment HBV DNA decline rates were similar between Asians and nonAsians regardless of baseline HBe Ag status and viralload.HBV DNA decline during the first four weeks was2.9 log10 copies/m L in HBe Ag-negative Asians and nonAsians,and in HBe Ag-positive non-Asians,and 3.1log10 copies/m L in HBe Ag-positive Asians.HBe Ag loss and seroconversion was achieved in 14%of Asians vs 26%and 24%,respectively,in non-Asians.Liver histology improved in 77.2%of Asians and 71.5%of non-Asians.No resistance to TDF developed.No renal safety signals were observed.CONCLUSION:TDF demonstrated similar viral suppression,normalization of ALT,improvements in liver fibrosis,and no detectable resistance in Asian and non-Asian patients regardless of baseline HBe Ag status.

Early hepatitis B viral DNA clearance predicts treatment response at week 96

AIM To investigate whether hepatitis viral DNA load at 24 wk of treatment predicts response at 96 wk in patients with chronic hepatitis B.METHODS A total of 172 hepatitis B envelope antigen(HBe Ag)-positive chronic hepatitis B patients who received initial treatment at 16 tertiary hospitals in Hunan Province, China were enrolled in this study. All patients received conventional doses of lamivudine and adefovir dipivoxil, telbivudine, entecavir dispersible tablets, or entecavir tablets for 96 wk. Patients who used other antiviral drugs or antitumor and immune regulation therapy were excluded. Patients were stratified into three groups according to their viral DNA load at 24 wk: < 10 IU/m L(group 1), 10-103 IU/m L(group 2), and > 103 IU/m L(group 3). Correlations of 24-wk DNA load with HBe Ag negative status and HBe Ag seroconversion at 96 wk were analyzed. Receiver operating characteristic curve analysis was used to test the predictive value of the HBV DNA load at 24 wk for long-term response.RESULTS The rates of conversion to HBe Ag negative status and HBe Ag seroconversion rates were 53.7% and 51.9%, respectively, in group 1; 35.21% and 32.39% in group 2; and 6.38% and 6.38% in group 3. The receiver operating characteristic curves for the three subgroups revealed that the lowest DNA load(< 10 IU/m L) was better correlated with response at 96 wk than a higher DNA load(10-103 IU/m L). Nested PCR was used for amplifying and sequencing viral DNA in patients with a viral DNA load > 200 IU/m L at 96 wk; resistance mutations involving different loci were present in 26 patients, and three of these patients had a viral DNA load 10-103 IU/m L at 96 wk. CONCLUSION Hepatitis B viral DNA load at 24 wk of antiviral treatment in patients with chronic hepatitis B is a predictor of the viral load and response rate at 96 wk.

CHB肝硬化患者aMAP评分与HEV之间的相关性分析

目的探讨慢性乙型肝炎肝硬化患者aMAP评分与高危食管静脉曲张(HEV)发生风险之间的关联性。方法选取2017年1月1日至2023年1月1日于安徽医科大学第一附属医院确诊为慢性乙型肝炎肝硬化的患者为研究对象。收集所有研究对象的一般资料,同时收集入院24小时内的实验室检查指标并计算aMAP评分。所有研究对象均完成胃镜检查以评估食管静脉曲张(EV)程度。采用多元Logistic回归评估aMAP评分与HEV风险之间的相关性,采用趋势性检验(P for trend)评估两者之间的相关性是否存在剂量反应关系,最后采用平滑曲线拟合和阈值效应分析明确两者之间是否存在非线性关系。结果最终共纳入患者207例,其中HEV患者104例。与非HEV患者相比,HEV患者aMAP评分更高(P=0.002)。在多个模型中,aMAP评分与HEV之间存在明显的正向相关关系,全调整模型的结果为(OR=1.16,95%CI∶1.03-1.30)。随着aMAP评分的增加,HEV的发生风险也随之增加,趋势性检验具有显著的统计学差异(P for trend<0.01),平滑曲线拟合分析和阈值效应分析提示两者之间为直线效应关系。受试者工作特征曲线(ROC)下面积(AUC)为0.73(0.64-0.78),aMAP评分对HEV诊断的最佳截断值为63.57。结论在慢性乙型肝炎肝硬化患者中,aMAP评分与HEV发病风险之间存在直线性的正性相关关系,并且随着aMAP评分的升高这种正性相关关系更加明显。aMAP评分对HEV具有较好的诊断价值,最佳截断值为63.57。

Lower baseline ALT cut-off values and HBV DNA levels better differentiate HBeAg(-) chronic hepatitis B patients from inactive chronic carriers

AIM:To determine whether new cut-off values for alanine aminotransferase(ALT)and baseline hepatitis B virus(HBV)DNA levels better differentiate HBeAg(-) chronic hepatitis B(CHB)patients from inactive chronic carriers. METHODS:Ninety-one patients[32 HBeAg(+)CHB, 19 inactive carriers and 40 HBeAg(-)CHB]were followed up for 2 years and were tested for HBV DNA levels by a PCR-based assay.ALT was tested twice during the last 6 mo using new cut-off values:ULN(upper limit of normal)30 IU/L for males,19 IU/L for females. Diagnostic accuracy,sensitivity,specificity,positive and negative predictive values were calculated by discriminant analysis. RESULTS:When using the revised ALT cut-off values, the lowest optimal HBV DNA level that differentiated HBeAg(-)CHB patients from inactive carriers was 50000 copies/mL.The diagnostic accuracy of HBV DNA to determine inactive carriers with a cut-off of 50000 copies/mL was similar to the previously recommended cut-off of 100 000 copies/mL(91%).HBV DNA levels were lower than the cut-off value in 95%of inactive carriers and in 28%of HBeAg(-)CHB patients.With ALT<30 IU/L in men and<19 IU/L in women and HBV DNA levels<100 000 copies/mL,the risk of CHB is 5%.On the other hand,if ALT values were>30 IU in men and>19 IU in women and baseline HBV DNA levels were>100000 copies/mL,the risk is 86%. CONCLUSION:New cut-off values for ALT together with HBV DNA levels proposed by AASLD(American Association for the Study of Liver Diseases)and NIH (National Institute of Health)consensus seem appropriate to characterize inactive carriers.

The natural history of chronic hepatitis B:a retrospective study

OBJECTIVE: To clarify the natural history, of chronic hepatitis B so as to evaluate its long-term therapeutic outcome of the patients and the efficacy of antiviral drugs. METHODS: A cohort of 183 biopsy-proven chronic hepatitis B patients (mean age of 31.75±8.03 years, male/female ratio: 152:31) and 247 controls were followed up retrospectively for 11.81±4.08 years. This study was focused on long-term clinical outcome including the rates of liver cirrhosis, hepatocellular carcinoma and death, apart from the long-term effect of antiviral drugs and prognostic factors. RESULTS: In the 183 chronic hepatitis B patients, 22 (12.02%) developed liver cirrhosis, 12 (6.56%) developed hepatocellular carcinoma, and 20 (10.93%) died. The 5-, 10- and 15-year survival rates were 97. 27%, 91.62%, and 84.47%, respectively. The 5-, 10- and 15-year incidence rates of HCC were O, 3.19%, and 11.56%, respectively. In the 247 controls, 6 (2.43%) died; none of them developed cirrhosis or HCC. The rates of death, liver cirrhosis, and HCC in the hepatitis B patients were markedly different (P<0. 005) compared with the controls. The overall mortality of hepatitis B patients was 4.5-fold higher than the general population. Cox multiple regression analysis showed that old age, severe histological injury, and positive HBeAg were closely related to liver cirrhosis; old age, severe histological injury, and male were major factors leading to death. The independent variable of predicted HCC was not found. CONCLUSION: The long-term outcome of hepatitis B patients is poor and the efficacy of antiviral drugs needs further study.

Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy

The spread of hepatitis B virus(HBV)infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B,from 10/100000 inhabitants in1984 to 0.85/100000 in 2012,and by the reduced prevalence of hepatitis B surface antigen(HBsAg)-positive cases among chronic hepatitis patients with different etiologies,from 60%in 1975 to about 10%in 2001.The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3%in the 1980s to 1%in 2010.Linked to HBV by its characteristics of defective virus,the hepatitis delta virus(HDV)has shown a similar epidemiological impact on the Italian population over time.The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from24%in 1990 to 8.5%in 2006.Before the beneficial effects of HBV mass vaccination introduced in 1991,the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations,the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size.A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.

Two-year Observation of the Clinical Efficacy in Treating Chronic Hepatitis B Patients with Ganxian Recipe (肝纤方) and Lamivudine

Objective: To evaluate the clinical efficacy of Ganxian recipe (肝纤方, GXR) and lamivudine (LVD) in a two-year treatment of chronic hepatitis B (CHB). Methods: One hundred and twenty patients with CHB were randomly divided into the combinedly treated group (combined group) of 40 CHB patients who were treated with GXR combined with LVD. Another 40 CHB patients were treated with LVD alone (WM group), and still another 40 CHB patients were treated with GXR alone (TCM group). All these cases were randomly controlled and observed for two years. Results: Comprehensive efficacy: Total effective rate of the combined group (complete response and partial response) was 92.5%, while that of the WM group was 67.5% and TCM group 57.5%, respectively, with the difference between them was significant ( P <0.01); after treatment, the hepatic functions (AST, ALT, SB) of the three groups were all reduced, and the reduction in the combined group was particularly significant in comparison with the WM group or TCM group, P <0.05 or P < 0.01 respectively, suggesting that the effect in the combined group was better than that in the other two groups; the rate of tyrosine-methionine-aspartate-aspartate (YMDD) virus mutation: it was 7.5% in the combined group, 40.0% in the WM group, and 5.0% in the TCM group; liver fibrosis improvement parameter: after treatment, the results in the combined group got better than those in the other two groups. Conclusion: GXR could inhibit the appearance of YMDD after long-term application of LVD, and combined use has marked synergism.

Hepatitis B Surface Antigen Serum Level Is Correlated with Fibrosis Severity in Treatment-Naïve, Chronic Hepatitis B Patients in Côte d’Ivoire (West Africa)?

HBsAg serum level (quantification) may be useful for managing hepatitis B virus (HBV) infection patients. However few studies especially in Africa have evaluated the association between HBsAg serum level and liver fibrosis severity. The objective of this study was to estimate the correlation between HBsAg serum level and liver fibrosis severity with treatment naive chronic hepatitis B patients in Cote d’Ivoire. Methodology: It is a prospective study covering from February 1st, 2014 to April 30st, 2015 at Centre Hospitalier et Universitaire de Yopougon and a private medical office in Abidjan, Cote d’Ivoire. Inclusion criteria for patients were: HBsAg positive, known HBeAg status, serum HBsAg levels, serum HBV DNA levels, complex serum markers and absence of HCV, HDV, or HIV co-infection, drinking more than 30 g/day for men and 20 g/day in women over 10 years, metabolic disease and/or hepatic overload. Pearson’s Chi-square test (r2), Anova, Spearman, T-Student, Pearson’s (r) correlations and Mann Withney’s Test were carried out as appropriate. A p value < 0.05 was taken as significant. Results: We recruited, 105 patients (77 men) of whom the medium age was 39.01 ± 9.72 years. Predominant hepatitis B viral genotype was E (93%). Less than 10% patients had an inactive HBV in HBeAg-negative. Patients had an average high HBsAg serum level (mean 12111.2 ± 10617.4 IU/ml) as well as the one viral load (mean 4.4 e7 ± 7.5 e7). Serum ALAT levels averaged at the upper limit of normal value. The average liver fibrosis score was 0.34 ± 0.22 and the degree of viral activity was 0.19 ± 0.20. Half of our patients had no fibrosis (35.24%) or had mild fibrosis (20.95%). No significant association was observed between HBsAg serum level and patient age (p = 0.3994), genre (p = 0.8075) or serum ALT levels (p = 0, 0787). In multivariate analysis, there’s a significant correlation (r = 0.239, p = 0.014) between HBV DNA levels and HBsAg serum level. There’s a significant correlation (r = 0.923, p < 0.0001) between HBsAg serum level and the dosage of alpha-fetoprotein. HBsAg serum level was not associated with the fibrosis stage (p = 0.281). HBsAg levels average with patients without fibrosis or carry a slight fibrosis (F0, F1) was higher than patients with moderate to severe fibrosis (F2, F3, F4): 13679.2 UI/ml ± 1956.48 versus 10610.52 UI/ml ± 8998.99 (p = 0.29). There’s a negative correlation between HBsAg level and the liver fibrosis score was negative (r = -0.069, p = 0.48). No significant association between HBsAg level and the liver fibrosis patients that were normal (p = 0.7965) or elevated (p = 0.5845). HBV DNA level was significantly associated with fibrosis score (r = 0.30, p = 0.0018). Conclusion: This study shows that there’s a negative correlation between HBsAg serum level and liver fibrosis severity treatment naive with African chronic hepatitis B viral HBeAg-negative patients.