Synthesis and in vitro-Anti-hepatitis B Virus Activities of Several Ethyl 5-Hydroxy-1H-indole-3-carboxylates

A series of ethyl 5-hydroxyindole-3-earboxylates 6a-10r was designed and synthesized. The structures of all the compounds were confirmed by IR, ^1H NMR, and MS and their anti-hepatitis B virus （HBV） activities were evaluated in 2.2.15 cells. Among them, compound 7g { ethyl 5-hydroxy-2- [ （ 3-methoxyphenylsulfinyl ） methyl ] -1-methyl-4- [ （4-methylpiperazin-1-yl） methyl ]-1H-indole-3-carboxylate} displays a significant anti-HBV activity, which is more potent than the positive control lamivudine.

Antiviral effects of hepatitis B virus S gene-specific anti-gene locked nucleic acid in transgenic mice

AIM To assess the antiviral effects of hepatitis B virus(HBV) S gene-specific anti-gene locked nucleic acid(LNA) in transgenic mice.METHODS Thirty HBV transgenic mice were acclimatized to laboratory conditions and positive for serum HBV surface antigen(HBs Ag) and HBV DNA, were randomly divided into 5 groups(n = 7), including negative control(blank control, unrelated sequence control), positive control(lamivudine, anti-sense-LNA), and anti-gene-LNA experimental group. LNA was injected into transgenic mice by tail vein while lamivudine was administeredby gavage. Serum HBV DNA and HBs Ag levels were determined by fluorescence-based PCR and enzymelinked immune sorbent assay, respectively. HBV S gene expression amounts were assessed by reverse transcription polymerase chain reaction. Positive rates of HBsA g in liver cells were evaluated immunohistochemistry.RESULTS Average rate reductions of HBs Ag after treatment on the 3 rd, 5 th, and 7 th days were 32.34%, 45.96%, and 59.15%, respectively. The inhibitory effect of antigene-LNA on serum HBs Ag peaked on day 7, with statistically significant differences compared with pretreatment(0.96 ± 0.18 vs 2.35 ± 0.33, P < 0.05) and control values(P < 0.05 for all). Average reduction rates of HBV DNA on the 3 rd, 5 th, and 7 th days were 38.55%, 50.95%, and 62.26%, respectively. This inhibitory effect peaked on the 7 th day after treatment with anti-gene-LNA, with statistically significant differences compared with pre-treatment(4.17 ± 1.29 vs 11.05 ± 1.25, P < 0.05) and control values(P < 0.05 for all). The mR NA levels of the HBV S gene(P < 0.05 for all) and rates of HBsA g positive liver cells(P < 0.05 for all) were significantly reduced compared with the control groups. Liver and kidney function, and histology showed no abnormalities. CONCLUSION Anti-gene-LNA targeting the S gene of HBV displays strong inhibitory effects on HBV in transgenic mice, providing theoretical and experimental bases for gene therapy in HBV.

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.

Synthesis and in vitro Anti-hepatitis B Virus Activity of Some Ethyl 5-Hydroxy-4-substituted Aminomethyl-2-sulfinylmethyl-1H-indole-3-carboxylates

A novel series of ethyl 5-hydroxy-4-substituted aminomethyl-2-sulfinylmethyl-lH-indole-3-carboxylates 8a--8j and 11e--11f was synthesized and evaluated in HepG2.2.15 cells for their anti-hepatitits B virus（HBV） activity and cytotoxicity. Among them, six compounds showed more potent inhibitory activity than lamivudine. Compound 8e exhibited the most significant anti-HBV activity with an IC50 value of 1.62 μmol/L, which was 33-times more potent than the reference drug lamivudine（IC50=54.78μmol/L）.

Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B

BACKGROUND Previous studies have suggested that the costimulatory molecule 4-1BB plays pivotal roles in regulating immunity during chronic viral infection.However,up to now,there are few studies about 4-1BB in chronic hepatitis B(CHB).AIM To clarify this issue,we report our comprehensive study results on the expression levels of 4-1BB in patients with CHB.METHODS From September 2018 to June 2019,a total of 64 patients with CHB were recruited from the Department of Hepatology,The First Hospital of Jilin University.Peripheral blood samples were collected from 52 treatment-naïve and 12 entecavir-treated patients with CHB as well as 37 healthy donors(including 24 healthy adults and 13 healthy children).The levels of soluble 4-1BB(s4-1BB)in plasma were measured by ELISA.4-1BB mRNA expression in peripheral blood mononuclear cells was detected by real-time quantitative PCR.RESULTS The s4-1BB levels in the plasma of patients with CHB were significantly higher than those in healthy adults(94.390±7.393 ng/mL vs 8.875±0.914 ng/mL,P<0.001).In addition,the s4-1BB level in plasma was significantly increased in patients with a higher viral load and a disease flare up.However,there were no significant differences between treatment-naïve and entecavir-treated patients.Interestingly,among treatment-naïve patients with CHB,the levels of s4-1BB in plasma had a significant positive correlation with hepatitis B surface antigen,hepatitis B virus DNA,hepatitis B e antigen,and triglyceride levels(r=0.748,P<0.001;r=0.406,P=0.004;r=0.356,P=0.019 and r=-0.469,P=0.007,respectively).The 4-1BB mRNA expression was higher in the peripheral blood mononuclear cells of patients with CHB than in the peripheral blood mononuclear cells of healthy adults,but the difference was not statistically significant.CONCLUSION These results suggest that the levels of s4-1BB may be associated with pathogenesis of hepatitis B virus and therefore may be a promising biomarker for disease progression.

Expression of co-stimulatory molecules B7-2 and PD-L1 on peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection

Objective： To explore the roles of the expression of the co-stimulatory molecule, B7-2, and the co-inhibitory molecule, PD-L1, on peripheral blood mononuclear cells in the mechanism of immunotolerance in chronic hepatitis B virus infection. Methods： Thirty HBV infected patients in the immunoreactive phase and 20 patients in the immunotolerant phase were enrolled in the study, while 20 healthy volunteers were used as controls. RT- PCR and real-time PCR methods were used to detect the expression levels of B7-2 and PD-L1 mRNA in peripheral blood mononuclear cells in chronic HBV infected patients. Results： The B7-2 expression in irnrnunoreactive and immunotolerant patients was significantly lower than that in the controls （P all 〈 0.01 ）; B7-2 expression in immunoreactive patients was significantly lower than in immunotolerant patients （P 〈 0.01）. PD-L1 expression in irnmunoreactive patients and immunotolerant patients was significantly higher than that in normal controls （P all 〈 0.01）. The PD-L1/BT-2 ratios in immunoreactive and immunotolerant patients were significantly higher than that of the healthy controls （P all 〈 0.01）; the PD-L1/ B7-2 ratio was significantly higher in the immunoreactive patients than in the immunotolerant patients （P 〈 0.01）. Conclusion： In chronic HBV infection, changes in the expression of co-stimulatory and co-inhibitory molecules imply a protective adjustment against the patient＇ s immune response that may result in increased immunotolerance and persistent HBV infection.

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.

Diagnostic strategy for occult hepatitis B virus infection

In 2008,the European Association for the study of the liver(EASL) defined occult hepatitis B virus infection (OBI) as the"presence of hepatitis B virus(HBV) DNA in the liver(with detectable or undetectable HBV DNA in the serum) of individuals testing hepatitis B surface antigen(HBsAg) negative by currently available assays".Several aspects of occult HBV infection are still poorly understood,including the definition itself and a standardized approach for laboratory-based detection,which is the purpose of this review.The clinical significance of OBI has not yet been established;however,in terms of public health,the clinical importance arises from the risk of HBV transmission.Consequently,it is important to detect high-risk groups for occult HBV infection to prevent transmission.The main issue is,perhaps,to identify the target population for screening OBI.Viremia is very low or undetectable in occult HBV infection,even when the most sensitive methods are used,and the detection of the viral DNA reservoir in hepatocytes would provide the best evaluation of occult HBV prevalence in a defined set of patients.However,this diagnostic approach is obviously unsuitable:blood detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection<10 IU/mL for HBV DNA and<0.1 ng/mL for HBsAg.

Prevalence of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is characterized by the persistence of HBV DNA in the liver tissue in individuals negative for the HBV surface antigen.The prevalence of OBI is quite variable depending on the level of endemic disease in different parts of the world,the different assays utilized in the studies,and the different populations studied.Many studies have been carried out on OBI prevalence in different areas of the world and categories of individuals.The studies show that OBI prevalence seems to be higher among subjects at high risk for HBV infection and with liver disease than among individuals at low risk of infection and without liver disease.

Pathogenesis of occult chronic hepatitis B virus infection

Occult hepatitis B infection(OBI) is characterized by hepatitis B virus(HBV) DNA in serum in the absence of hepatitis B surface antigen(HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns.Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays;but more frequently it is due to a strong suppression of viral replication and gene expression.OBI is an entity with world-wide diffusion.The failure to detect HBsAg,despite the persistence of the viral DNA,is due in most cases to the strong suppression of viral replication and gene expression that characterizes this"occult"HBV infection;although the mechanisms responsible for suppression of HBV are not well understood.The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection.Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.

Occult hepatitis B virus infection among Egyptian blood donors

AIM:To identify blood donors with occult hepatitis B virus(HBV) infection(OBI) to promote safe blood donation.METHODS:Descriptive cross sectional study was conducted on 3167 blood donors negative for hepatitis B surface antigen(HBsAg),hepatitis C antibody(HCV Ab) and human immunodeficiency virus Ab.They were subjected to the detection of alanine aminotransferase(ALT) and aspartate transaminase(AST) and screening for anti-HBV core antibodies(total) by two different techniques;[Monoliza antibodies to hepatitis B core(Anti-HBc) Plus-Bio-Rad] and(ARC-HBc total-ABBOT).Positive samples were subjected to quantitative detection of antibodies to hepatitis B surface(anti-HBs)(ETI-AB-AUK-3,Dia Sorin-Italy).Serum anti-HBs titers > 10 IU/L was considered positive.Quantitative HBV DNA by real time polymerase chain reaction(PCR)(QIAGEN-Germany) with 3.8 IU/mL detection limit was estimated for blood units with negative serum anti-HBs and also for 32 whose anti-HBs serum titers were > 1000 IU/L.Also,265 recipients were included,34 of whom were followed up for 3-6 mo.Recipients were investigated for ALT and AST,HBV serological markers:HBsAg(ETI-MAK-4,Dia Sorin-Italy),anti-HBc,quantitative detection of anti-HBs and HBV-DNA.RESULTS:525/3167(16.6%) of blood units were positive for total anti-HBc,64% of those were antiHBs positive.Confirmation by ARCHITECT anti-HBc assay were carried out for 498/525 anti-HBc positive samples,where 451(90.6%) confirmed positive.Reactivity for anti-HBc was considered confirmed only if two positive results were obtained for each sample,giving an overall prevalence of 451/3167(14.2%) for total anti-HBc.HBV DNA was quantified by real time PCR in 52/303(17.2%) of anti-HBc positive blood donors(viral load range:5 to 3.5 x 105 IU/mL) with a median of 200 IU/mL(mean:1.8 x 104 ± 5.1 x 104 IU/mL).AntiHBc was the only marker in 68.6% of donors.Univariate and multivariate logistic analysis for identifying risk factors associated with anti-HBc and HBV-DNA positivity among blood donors showed that age above thirty and marriage were the most significant risk factors for prediction of anti-HBc positivity with AOR 1.8(1.4-2.4) and 1.4(1.0-1.9) respectively.Other risk factors as gender,history of blood transfusion,diabetes mellitus,frequent injections,tattooing,previous surgery,hospitalization,Bilharziasis or positive family history of HBV or HCV infections were not found to be associated with positive anti-HBc antibodies.Among anti-HBc positive blood donors,age below thirty was the most significant risk factor for prediction of HBV-DNA positivity with AOR 3.8(1.8-7.9).According to HBV-DNA concentration,positive samples were divided in two groups;group one with HBV-DNA ≥ 200 IU/mL(n = 27) and group two with HBV-DNA < 200 IU/mL(n = 26).No significant difference was detected between both groups as regards mean age,gender,liver enzymes or HBV markers.Serological profiles of all followed up blood recipients showed that,all were negative for the studied HBV markers.Also,HBV DNA was not detected among studied recipients,none developed post-transfusion hepatitis(PTH) and the clinical outcome was good.CONCLUSION:OBI is prevalent among blood donors.Nucleic acid amplification/HBV anti core screening should be considered for high risk recipients to eliminate risk of unsafe blood donation.

Inhibition of hepatitis B virus production by Boehmeria nivea root extract in HepG2 2.2.15 cells

AIM: To explore the anti-hepatitis B virus (HBV) effects of Boehmeria nivea (B. nivea) root extract (BNE) by using the HepG2 2.2.15 cell model system. METHODS: Hepatitis B surface antigen (HBsAg), hepatitis B virus e antigen (HBeAg), and HBV DNA were measured by using ELISA and real-time PCR, respectively. Viral DNA replication and RNA expression were determined by using Southern and Northern blot, respectively. RESULTS: In HepG2 2.2.15 cells, HBeAg (60%, P < 0.01) and particle-associated HBV DNA (> 99%, P < 0.01) secretion into supernatant were significantly inhibited by BNE at a dose of 100 mg/L, whereas the HBsAg was not inhibited. With different doses of BNE, the reduced HBeAg was correlated with the inhibition of HBV DNA. The anti-HBV effect of BNE was not caused by its cytotoxicity to cells or inhibition of viral DNA replication and RNA expression. CONCLUSION: BNE could effectively reduce the HBV production and its anti-HBV machinery might differ from the nucleoside analogues.

Exploitation of host clock gene machinery by hepatitis viruses B and C

Many aspects of cellular physiology display circadian(approximately 24-h)rhythms.Dysfunction of the circadian clock molecular circuitry is associated with human health derangements,including neurodegeneration,increased risk of cancer,cardiovascular diseases and the metabolic syndrome.Viruses triggering hepatitis depend tightly on the host cell synthesis machinery for their own replication,survival and spreading.Recent evidences support a link between the circadian clock circuitry and viruses’biological cycle within host cells.Currently,in vitro models for chronobiological studies of cells infected with viruses need to be implemented.The establishment of such in vitro models would be helpful to better understand the link between the clock gene machinery and viral replication/viral persistence in order to develop specifically targeted therapeutic regimens.Here we review the recent literature dealing with the interplay between hepatitis B and C viruses and clock genes.

Hepatitis B virus genotypes in southwest Iran: Molecular, serological and clinical outcomes

AIM: To investigate the associations of hepatitis B virus (HBV) genotype with HBeAg and anti-HBe status, alanine aminotransferase (ALT) levels and HBV-DNA detection in different groups of HBV-infected patients in southwest Iran. METHODS: A total of 89 HBsAg-positive serum samples were collected from the same number of patients. All sera were then investigated to determine HBV DNA and serological markers. For all the polymerase chain reaction (PCR)-positive samples, biochemical, histopathological assays and genotyping were also performed. RESULTS: Genotype D was the only type of HBV foundin different clinical forms of acute and chronic infections. There was a high prevalence of HBeAg-negative HBV- infected patients with chronic hepatitis (52.7%). Out of 55 patients with chronic hepatitis, seven (12.7%) were diagnosed with cirrhosis. A significant association between the presence of anti-HBe antibody and an increase in ALT level, among either HBeAg-negative (P = 0.01) or HBeAg-positive (P = 0.026) patients, was demonstrated. No significant differences were observed between the clinical outcomes of HBeAg-positive and -negative individuals (P = 0.24). CONCLUSION: Genotype D has been recognized as the only type of HBV found in different clinical forms of HBV infections, including cirrhosis, among the residents of southwest Iran. Anti-HBe possibly plays a role in disease progression in some patients with chronic hepatitis, at least for a period of disease.

Clinical significance of"anti-HBc alone"in human immunodeficiency virus-positive patients

AIM:To determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection("anti-HBc alone")among human immunodeficiency virus(HIV) type-1 infected patients.Occult hepatitis B infection frequency was also evaluated. METHODS:Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed.Patients with serological markers of hepatitis B virus(HBV)infection were classified into three groups:past hepatitis,"anti-HBc alone"and chronic hepatitis.Determination of DNA from HBV,and RNA and genotype from hepatitis C virus(HCV)were performed on"anti-HBc alone"patients. RESULTS:One hundred and eighty seven(53.7%) HIV-positive patients had markers of HBV infection: 118 past infection(63.1%),14 chronic hepatitis (7.5%)and 55"anti-HBc alone"(29.4%).Younger age[2.3-fold higher per every 10 years younger;95% confidence intervals(CI)1.33-4.00]and antibodies to HCV infection[odds ratio(OR)2.87;95%CI 1.10-7.48]were factors independently associated with the"anti-HBc alone"pattern.No differences in liver disease frequency were detected between both groups. Serum levels of anti-HBs were not associated with HCV infection(nor viral replication or HCV genotype),or with HIV replication or CD4 level.No"anti-HBc alone" patient tested positive for HBV DNA. CONCLUSION:"Anti-HBc alone"prevalence in HIVpositive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection.In clinical practice,HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury.

Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs

Hepatitis B virus(HBV) reactivation in rheumatoid arthritis(RA) patients undergoing biological therapy is not infrequent. This condition can occur in patients with chronic hepatitis B as well as in patients with resolved HBV infection. Current recommendations are mainlyfocused on prevention and management strategies of viral reactivation under tumor necrosis factor-α inhibitors or chimeric monoclonal antibody rituximab. In recent years, growing data concerning HBV reactivation in RA patients treated with newer biological drugs like tocilizumab and abatacept have cumulated. In this review, epidemiology, pathogenesis and natural history of HBV infection have been revised first, mainly focusing on the role that specific therapeutic targets of current biotechnological drugs play in HBV pathobiology; finally we have summarized current evidences from scientific literature, including either observational studies and case reports as well, concerning HBV reactivation under different classes of biological drugs in RA patients. Taking all these evidences into account, some practical guidelines for screening, vaccination, prophylaxis and treatment of HBV reactivation have been proposed.

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.

Studies on Mutual Relationship between Anti-HBx and sFas, IL-10 or IL-12 in Sera of Cases with Chronic Hepatitis B Infection

Objective To study the mutual relationship between anti-HBx and IL-10, IL-12 or soluble Fas(s Fas) in sera of patients with chronic HBV infection and to explore the importance of anti-HBx detection as well as its role in the development of chronic HBV infection.Methods Total of 90 cases with chronic HBV infection were randomly selected, including 10 of asymptomatic carriers(ASC), 28 of chronic hepatitis B(CHB), 26 of liver cirrhosis(LC) and 26 patients of hepatocellular carcinoma(HCC). Their clinical data and blood samples were collected, and serum was prepared and stored at-73℃. Anti-HBx was detected with an indirect ELISA established in our earlier research, and levels of IL-10, IL-12 and Fas were determined with commercial double-antibody sandwich ELISA kits. The mutual relationship between anti-HBx and IL-10, IL-12 or s Fas in serum were analyzed with the software SPSS 20.0. Results All levels of IL-10, IL-12 and s Fas in peripheral blood showed a rising trend with development of chronic HBV infection. The levels of IL-10 in ASC, CHB, LC and HCC groups were 13.93 ± 14.40 ng/L, 39.38 ± 20.77 ng/L, 69.06 ± 46.37 ng/L and 62.82 ± 23.42 ng/L, respectively, levels of IL-12 in the 4 groups were 15.64 ± 23.04 ng/L, 68.50 ± 23.14 ng/L, 76.83 ± 12.82 ng/L and 83.74 ± 24.88 ng/L, respectively, and levels of s Fas were 58.17 ± 77.42 ng/L, 179.88 ± 104.36 ng/L, 249.22 ± 107.80 ng/L and 252.98 ± 87.65 ng/L, respectively. Twenty-seven out of 90 patients showed a positive result for anti-HBx detection, including 1 in ASC, 4 in CHB, 12 in LC and 10 in HCC group. The levels of IL-10, IL-12 and sF as were higher in anti-HBx positive group than in negative group. Statistical analysis demonstrated significant differences of IL-10 and IL-12 between the two groups(P < 0.05), but the differences of s Fas had no statistical significance(P = 0.094). Conclusions Anti-HBx antibody is not protective, and is closely related to IL-10, IL-12 and s Fas. It may be an important serum indicator for aggravation from chronic hepatitis B to liver cirrhosis or hepatocellular carcinoma in patients with chronic HBV infection.

Reactivation of Hepatitis B after Administration of Anti-TNF<i>α</i>in a Patient with Psoriasis

In patients with severe psoriasis that at the same time have multiple comorbidities and chronic infections, is difficult to establish safer and more effective therapy. There are contradictions between the indications of the international protocols of systemic treatments, and the most recent publications which show that anti-TNFα agents could be safe therapeutic options in patients with chronic hepatitis. In the case of chronic viral infections, specifically hepatitis B, there are several conflicts in reference to the biological treatments that can block tumoral necrosis factor-α (TNFα) because there is evidence of a risk of reactivation of hepatitis. Most viral reactivations with the administration of an anti-TNFα agent have been reported in patients with inflammatory diseases. However, there are a few cases described in psoriasis. We’ll present the first case reported in literature of hepatisis B viral (HBV) reactivation in a patient with severe psoriasis secondary to the administration of adalimumab.

抗病毒联合抗结核治疗HBV-DNA阳性初治肺结核的疗效及肝功能、IFN-γ、SSS评分相关性分析

目的 分析抗病毒联合抗结核治疗乙肝病毒的脱氧核糖核酸(HBV-DNA)阳性初治肺结核的疗效并分析患者干扰素-γ(IFN-γ)、半定量积分系统(SSS)评分与肝功能的相关性。方法 选择2022年3月—2023年3月南通大学附属如皋医院收治的120例HBV-DNA阳性初治肺结核患者作为研究对象,按随机数字表法分为2组,各60例。对照组采取常规抗结核治疗,观察组在对照组基础上联合抗病毒治疗。患者均治疗6个月,比较2组临床疗效(病灶吸收、痰菌转阴、HBV-DNA转阴情况);治疗前、治疗后肝功能、炎症因子水平;比较2组不同时点(治疗前、治疗1、3、6个月)IFN-γ、HBV-DNA、SSS评分水平;采用双变量相关性Pearson分析肝功能、IFN-γ、SSS评分的相关性。结果 观察组病灶吸收、痰菌转阴、HBV-DNA转阴患者占比高于对照组(P<0.05);治疗后,2组谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)水平高于治疗前,白细胞介素-2(IL-2)、IL-6、IL-8、肿瘤坏死因子-α(TNF-α)水平低于治疗前,观察组低于对照组(P<0.05);治疗1、3、6个月时IFN-γ水平高于治疗前,观察组低于对照组,2组时点、组间比较差异具有统计学意义(P<0.05);治疗1、3、6个月时观察组HBV-DNA水平相较于治疗前逐步降低,而对照组HBV-DNA水平相较于治疗前升高,观察组低于对照组,2组时点、组间比较差异具有统计学意义(P<0.05);治疗1、3、6个月时SSS评分高于治疗前,但观察组低于对照组,2组时点、组间比较差异具有统计学意义(P<0.05);双变量相关性Pearson分析结果显示,IFN-γ水平与HBV-DNA阳性初治肺结核患者ALT、AST、TBiL、SSS评分呈正相关(r>0,P<0.05);2组不良反应发生率比较差异无统计学意义(P>0.05)。结论 HBV-DNA阳性初治肺结核经抗病毒联合抗结核治疗能够有效提升临床治疗效果,降低机体炎症及HBV-DNA水平,避免肝脏损伤,稳定肝功能,且不会增加患者发生不良反应的风险。