Hepatitis B Virus in Cirrhosis and Primary Livers Cancers

Introduction: Hepatitis B virus (HBV) infection is a public health problem in sub-Saharan Africa, due to its frequency and progression to complications such as cirrhosis and/or hepatocellular carcinoma (HCC). Objective: To help improve the management of cirrhosis and hepatocellular carcinoma. Patients and Methods: This was a 34-month cross-sectional study conducted in the Hepato-Gastroenterology Department of the CHU de l’Amitié Sino-centra-fricaine in Bangui. It included patients of both sexes aged 18 years or older with a diagnosis of HBV-related cirrhosis and/or HCC. Results: During the study period, 1344 patients were admitted to hospital, 681 of them for chronic liver disease (51%). Among patients admitted for chronic liver disease, in particular cirrhosis and/or HCC, HBV was implicated in 288 cases (42.30%), of whom 170 (24.96%) met our inclusion criteria. These included 123 men (72.35%) and 47 women (27.65%). The sex ratio was 2.61. The mean age of our patients was 40 years (±11 years) with extremes of 18 and 76 years. Cirrhosis was observed in 101 cases (59.41%), HCC on cirrhosis in 59 cases (34.70%) and HCC in 10 cases (5.89%). Cirrhosis was classified as Child-Pugh B in 62 cases and C in 20 cases. HCC on cirrhosis was classified according to BCLC stage C in 7 cases and stage D in 52 cases. Conclusion: HBV is the leading cause of cirrhosis and HCC in the Central African Republic. Chronic liver disease is diagnosed at the advanced stage of the disease. Hence the importance of early detection, prevention through vaccination at birth, and management of infected patients.

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

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

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.

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.

Lamivudine treatment of decompensated hepatitis B virus-related cirrhosis

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

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.

Metabonomic analysis of hepatitis B virus-induced liver failure:identification of potential diagnostic biomarkers by fuzzy support vector machine

Hepatitis B virus （HBV）-induced liver failure is an emergent liver disease leading to high mortality. The severity of liver failure may be reflected by the profile of some metabolites. This study assessed the potential of using metabolites as biomarkers for liver failure by identifying metabolites with good discriminative performance for its phenotype. The serum samples from 24 HBV-indueed liver failure patients and 23 healthy volunteers were collected and analyzed by gas chromatography-mass spectrometry （GC-MS） to generate metabolite profiles. The 24 patients were further grouped into two classes according to the severity of liver failure. Twenty-five eommensal peaks in all metabolite profiles were extracted, and the relative area values of these peaks were used as features for each sample. Three algorithms, F-test, k-nearest neighbor （KNN） and fuzzy support vector machine （FSVM） combined with exhaustive search （ES）, were employed to identify a subset of metabolites （biomarkers） that best predict liver failure. Based on the achieved experimental dataset, 93.62% predictive accuracy by 6 features was selected with FSVM-ES and three key metabolites, glyeerie acid, cis-aeonitie acid and citric acid, are identified as potential diagnostic biomarkers.

Adjuvant hepatic chemotherapy after resection of solitary hepatocellular carcinoma associated with hepatitis B virus cirrhosis

BACKGROUND: Although resection is the major treatment for patients with hepatocellular carcinoma ( HCC), the high intrahepatic recurrence remains a cardinal cause of death. This study was undertaken to evaluate the effect of hepatic arterial infusion chemotherapy on the survival and recurrence of HCC patients with hepatitis B virus ( HBV) cirrhosis after resection. METHODS: Twenty-eight patients who had undergone placement of a hepatic arterial pump at the time of liver wedge resection for HCC from 1998 through 2004 were reviewed retrospectively. These patients aged 23-71 years had HBV cirrhosis (Child-Pugh class A or B). They were given floxuridine(FUDR) (250 mg), doxorubicin (10 mg) and mitomycin C (4 mg) alternatively every 2 or 3 days through arterial pumps for 8 cycles each year in the first two years after resection. Meanwhile, traditional Chinese herbal medicine was prescribed to the patients. When the leucocyte count was as low as 3 x 109/L or asparate aminotransferase (AST) level was significantly increased, the regimen of chemotherapy was delayed for the normalization of leucocyte count and AST level (below 80 U/L). RESULTS: Of the 28 patients, 23 received 8 or 16 cycles of the set regimen of chemotherapy. These patients are alive with no evidence of recurrence. Among them, 5,7, and 11 patients are alive beyond 5 years, 3 years, and 1 year respectively. In the remaining 5 patients, 3 who had had a HCC 10 cm or more in diameter showed tumor recurrence within 1 year, in whom, 8 cycles of chemotherapy were not completed because of their low leucocyte count (<3 × 109/L) and poor liver function. One patient who had received 8 cycles of chemotherapy demonstrated recurrence at 16 months after resection. One patient who had received 16 cycles of chemotherapy had intrahepatic recurrence at 58 months after surgery. No recurrence was observed in 17 patients who had received 16 cycles of chemotherapy. CONCLUSION: Adjuvant hepatic arterial chemotherapy may be feasible to improve the survival of patients after resection of solitary HCC associated with HBV cirrhosis.

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

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

GCN5 Acetyltransferase Inhibits PGC1α-induced Hepatitis B Virus Biosynthesis

Hepatitis B virus （HBV） biosynthesis is primarily restricted to hepatocytes due to the governing of liver-enriched nuclear receptors （NRs） on viral RNA synthesis. The liver-enriched NR hepatocyte nuclear factor 4α （HNF4α, the key regulator of genes implicated in hepatic glucose metabolism, is also a primary determinant of HBV pregenomic RNA synthesis and HBV replication. Peroxisome proliferator-activated receptor-r coactivator la （PGCla） coactivates and further enhances the effect of HNF4α on HBV biosynthesis. Here, we showed that the acetyltransferase General Control Non-repressed Protein 5 （GCN5） acetylated PGC 1 α, leading to alteration of PGC 1 α from a transcriptionally active state into an inactive state. As a result, the coactivation activity of PGCla on HBV transcription and replication was suppressed. Apparently, an acetylation site mutant of PGC 1 α （PGC 1 αR13） still had coactivation activity as GCN5 could not suppress the coactivation activity of the mutant. Moreover, a catalytically inactive acetyltransferase mutant GCN5m, due to the loss of acetylation activity, failed to inhibit the coactivation function of PGClα in HBV biosynthesis. Our results demonstrate that GCN5, through its acetyltransferase activity, inhibits PGCla-induced enhancement of HBV transcription and replication both in vitro and in vivo.

Antiviral Effect of Interferon-Induced Guanylate Binding Protein-1 against Coxsackie Virus and Hepatitis B Virus B3 in Vitro

Guanylate binding protein-1(GBP-1)is an interferon-induced protein.To observe its antiviral effect against Hepatitis B virus(HBV)and Coxsackie virus B3(CVB3),we constructed an eukaryotic expression vector of human GBP-1(hGBP-1).Full-length encoding sequence of hGBP-1 was amplified by long chain RT-PCR and inserted into a pCR2.1 vector,then subcloned into a pCDNA3.1(-)vector.Recombinant hGBP-1 plasmids and pHBV1.3 carrying 1.3-fold genome of HBV were contransfected into HepG2 cells,and inhibition effect of hGBP-1 against HBV replication was observed.Hela cells transfected with recombinant hGBP-1 plasmids were challenged with CVB3,and viral yield in cultures were detected.The results indicated that recombinant eukaryotic expression plasmid of hGBP-1 was constructed successfully and the hGBP-1 gene carried in this plasmid could be efficiently expressed in HepG2 cells and Hela cells.hGBP-1 inhibit CVB3 but not HBV replication in vitro.These results demonstrate that hGBP-1 mediates an antiviral effect against CVB3 but not HBV and perhaps plays an important role in the interferon-mediated antiviral response against CVB3.

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.

Is positivity for hepatitis C virus antibody predictive of lower risk of death in COVID-19 patients with cirrhosis?

Liver injury has been reported in coronavirus disease 2019(COVID-19)cases but the impact of pre-existing liver damage and related etiology have not been completely elucidated.Our research interests include the potential reciprocal influence of COVID-19 and pre-existing liver damage related to hepatitis C virus(HCV)infection,in particular.To this end,we have evaluated three cohorts of patients admitted at three Italian hospitals during the coronavirus pandemic;these included 332 patients with COVID-19 and 1527 patients with HCV who were from established real-world antiviral treatment study cohorts(sofosbuvir/velpatasvir),with either liver disease(various severities;n=1319)or cirrhosis(n=208).Among the COVID-19 patients,10 had cirrhosis(3%),including 7 of metabolic origin and 3 of viral origin.Mortality among the COVID-19 patients was 27.1%,with 70%of those with cirrhosis of metabolic etiology having died.Cirrhosis,older age,low white blood cell count and lymphocyte count being identified as risk predictors of death[odds ratio(OR)=13.7,95%confidence interval(CI):2.59-83.01,P=0.006;OR=1.05,95%CI:1.03-1.08,P=0.0001;OR=1.09,95%CI:1.36-1.16,P=0.001;OR=0.61,95%CI:0.39-0.93,P=0.023,respectively].In the two cohorts of HCV patients,COVID-19 diagnosis was made in 0.07%of those with liver disease and 1%of those with cirrhosis.Thus,the prevalence of HCV antibodies among COVID-19-infected patients was comparable to that currently reported for the general population in Italy.Amongst the COVID-19 patients,pre-existing metabolic cirrhosis appears to be associated with higher mortality,while HCV antibodies may be suggestive of“protection”against COVID-19.

In vitro incubation of cytokine-induced killer cells from patients with and without hepatitis B virus and a cell subset analysis

Objective The aim of the study was to explore the difference between immune cell subsets during the incubation of cytokine-induced kill cells （CIKs） from patients with and without hepatitis B virus （HBV）. Methods Peripheral blood samples were extracted from 50 tumor patients, and were divided into two groups according to the presence or absence of HBV. The proliferation rate and activity of CIK cells were examined based on counts on days 1, 5, 7, 9, 11, 13, and 15 of culture. Additionally, the CD3＋, CD4＋, CD8＋, CD3＋CD8＋, C＋）3＋CD4＋, and CD3＋CD56＋ T cell populations were analyzed by flow cytometry on days 5, 7, 10, 13, and 15 of culture. Results Proliferation over a 15-day period was higher in the HBV-positive group than in the negative group （280-fold vs. 180-fold increase, respectively）, but there was no significant difference between the two groups at each time point. The frequencies of CD3＋, CD8＋ T, CD3＋CD8＋, and CD3＋CD56＋T cells increased over time, while those of CD4＋ and CD3＋CD4＋ T cells decreased over time, and these changes were greater in the positive group than in the negative group. The differences in CD8＋ T cells and CD3＋CD4＋ T cells between the two groups were significant （P 〈 0.05）. Conclusion The proliferative capacity of CIK cells was higher for patients in the HBV-positive group than those in the HBV-negative group, and immune cell subsets were more favorable in the HBV-positive group than the neaative arouD.

Community-Based Hepatitis B Campaign in Asian Americans

Chronic hepatitis B (CHB) disproportionately affects minority groups in the US, particularly Asian Americans, with numerous factors contributing to this disparity. Of the 2.4 million people living with chronic HBV in the US, 60% are Asian American. Many are unaware of their status and lack access to proper clinical care, with less than ten percent receiving necessary antiviral treatment. Barriers to screening and care include lack of disease awareness, language and cultural barriers, and financial constraints. Additionally, healthcare providers and systems in the US often overlook the importance of CHB, leading to inadequate care. In response, the Center for Viral Hepatitis (CVH) has implemented a community-based outreach program over the past sixteen years, employing a multifaceted approach involving all sectors of society and various organizations to combat health disparities in CHB. This grassroots campaign has proven highly effective, leveraging CVH’s leadership in spearheading numerous collaborative activities with community members, healthcare professionals, and policymakers. We have summarized the key points of CVH's efforts and their significance in combating CHB-related health disparities. The CHB Screening and Awareness Campaign, tailored to the Asian American community, serves as a successful model for increasing CHB screening, linkage-to-care, and addressing socio-cultural barriers and health literacy. Insights from these outreach programs have guided the development of culturally relevant resources and education initiatives. These findings suggest that such community-driven approaches are essential for addressing health disparities. The strategies and outcomes of CVH’s efforts can inform future health initiatives for other minority communities in the US and globally.

Novel Evidence Suggests Hepatitis B Virus Surface Proteins Participate in Regulation of HBV Genome Replication

Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV) usually result in altered hepatitis B surface antigen(HBsAg) secretion efficiency.In the present study,we reported two conserved residues,M75 and M103 with respect to HBsAg,mutations of which not only attenuated HBsAg secretion(M75 only),but also suppressed HBV genome replication without compromising the overlapping p-gene product.We also found M75 and M103 can initiate truncated surface protein(TSPs) synthesis upon over-expression of full-length surface proteins,which may possibly contribute to HBV genome replication.However,attempts to rescue replicationdefective HBV mutant by co-expression of TSPs initiated from M75 or M103 were unsuccessful,which indicated surface proteins rather than the putative TSPs were involved in regulation of HBV genome replication.

Baseline HBV Load Increases the Risk of Anti-tuberculous Drug-induced Hepatitis Flares in Patients with Tuberculosis

Hepatitis associated anti-tuberculous treatment（HATT） has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus（HBV）. Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Increases in serum transaminase levels of 〉3, 5, and 10 times the upper limit of normal（ULN） were used to define liver damage as mild, moderate, and severe, respectively. Patients with elevated total bilirubin（TBil） levels that were more than 10 times the ULN（〉171 μmol/L） with or without decreased（〈40%） prothrombin activity（PTA） were diagnosed with liver failure. A cohort of 87 patients was analyzed. The incidence of liver damage and liver failure was 59.8%（n=52） and 25.3%（n=22）, respectively. The following variables were correlated with the severity of hepatotoxicity： albumin（ALB） levels, PTA, platelet counts（PLT）, and the use of antiretroviral therapies（P〈0.05）. Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure, and high viral loads were a significant risk factor with an odds ratio（OR） of 2.066. Judicious follow-up of clinical conditions, liver function tests, and coagulation function, especially in patients with high HBV loads and hypoalbuminemia is recommended. It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.

Inhibition of Hepatitis B Virus Replication by Rheum palmatum L. Ethanol Extract in a Stable HBV-producing Cell Line

肝炎 B 病毒(HBV ) 感染是在世界上的一个严重健康问题。然而，仍然为 HBV 感染没有令人满意的治疗学的策略。到为有更高的功效和更少的副作用的新 anti-HBV 代理人的搜索，繁体中文药感冒 palmatum L 的禁止的活动。对 HBV 复制的乙醇摘录(RPE ) 在这研究被调查。量的即时聚合酶链反应(PCR ) 被采用在稳定的生产 HBV 房间线 HepAD38 对 HBV-DNA 复制分析 RPE 的禁止的活动；HBV 表面抗原(HBsAg ) 和 e 抗原(HBeAg ) 的表示层次被酶也决定在 RPE 处理以后的连接 immunosorbent 试金(ELISA ) 。RPE 能 dose-dependently 禁止 HBV-DNA 和 HBsAg 的生产。50% 抑制(IC50 ) 的集中在 209.63 点被计算， 252.53 渭 g /mL， respectivel y。然而，它对 HBeAg 表示的禁止的活动甚至在高集中是细微的。RPE 在 HepAD38 房间上有弱细胞毒素的效果(CC50 = 1 640 渭 g /mL ) 并且选择索引(SI ) 在 7.82 点被计算。与二 anthraquinone 衍生物 emodin 和 rhein 相比， RPE 显示出 anti-HBV 和更弱的 cytotoxicity 的更高的能力。那么感冒 palmatum L。可能拥有能有效地禁止 HBV-DNA 复制和 HBsAg 表示的另外的功能的代理人。他们改进功效并且减少的结构的活跃代理人，鉴定和修正的进一步的纯化 cytotoxicity 被要求。关键词肝炎 B 病毒(HBV )- 抗病毒 - 感冒 palmatum L.ethanol 摘录(RPE )- HepAD38 房间 CLC 数字 R373 同等地相应的作者。

Tea Polyphenols Exerts Anti-hepatitis B Virus Effects in a Stably HBV-transfected Cell Line

In this study, the anti-HBV effects of tea polyphenols （TP） were examined. After cells were exposed to TP for 3, 6, 9 days, amounts of HBsAg, HBeAg and HBV-DNA released into the supernatant of the cultured HepG2 2.2.15 cells were detected. TP, to some extent, inhibited the secretion of HBsAg and strongly suppressed the secretion of HBeAg in a dose-dependent （P〈0.01） and time-dependent manner, with 50% maximal inhibitory concentration （IC50） value being 7.34μg/mL on the 9th day, but the time-dependence was not significant （P=0.051）. Expression of HBV-DNA in the supernatant of the cell culture also was significantly decreased in a dose-dependent fashion （P〈0.01）. The ICS0 of TP in inhibiting HBV DNA was 2.54 pg/mL. It concluded that TP possessed potential anti-HBV effects and may be used as a treatment alternative for HBV infection.

Studies of Hepatitis B Virus-Specific Transfer Factor reparation

制备一种乙型肝炎病毒特异性转移因子制剂 (HBV STF) ,为临床应用提供有价值的实验依据。从人HBsAg阳性胎盘中制备了HBV STF ,并对其理化性质、免疫学活性进行了检测和初步的临床试用。每批样品经无菌试验、热原质检查、动物安全性试验等均符合药典要求。本品最大紫外吸收光谱在 2 5 6± 2nm处 ,E2 60nm/E2 80nm比值大于 2 7。其水解氨基酸含 17种。对人T淋巴细胞E受体的激活试验结果显示 ,HBV STF的Ea RFc平均增高率在 83 47%～ 10 3 48%之间 ,抗原特异性皮肤试验表明HBV STF能刺激小鼠体内T淋巴细胞增殖 ,诱导小鼠跖趾部皮肤的迟发性变态反应。对HBV STF的初步临床试用也取得明显效果 ,显示HBV STF是一种可用于治疗乙肝的安全。