Assessment of Liver Fibrosis in HBsAg-Negative and Anti HBc Positive Patients

Background: Surface antigen (HBsAg) is the mean marker of hepatitis B virus infection. During the course of the infection, some patients lose the HBsAg and only the presence of anti-HBc antibody indicates previous contact with the virus. Among these patients, some have detectable viral load (occult infection) but most without viral replication. There is no guideline regarding these patients. The aim of this study was to assess hepatic fibrosis in patients with only the hepatitis B virus contact marker “total anti-HBc”. Patients and methods: it was a descriptive and analytical cross-sectional study, conducted in three private hospitals from January to August 2022. Were included HBsAg-negative and HBc-positive patients, consulting in Gastroenterology departments. Noninvasive methods (APRI, FIB-4 and FIBROSCAN) were used to evaluate liver stiffness because of their easy accessibility and low-cost. The hepatic fibrosis was considered significant when the score determined by APRI, FIB-4 and FIBROSCAN® tests was respectively greater than 1.5;2.67 and 8 kPa corresponding to fibrosis level 2 (F2). Results: A total of 63 HBsAg-negative/total HBcAg-positive patients were included. The mean age was 49.9 ± 13.4 years. The male/female sex ratio was 1.78. Of the 63 patients, 19 had significant liver fibrosis (30.1%) among which 9 patients had HCC. The FIB-4 score outperformed the APRI score in assessing liver fibrosis, with a sensitivity of 84.2%, a specificity of 100% and a negative predictive value of 93.6%. In univariate analysis, there was a significant association between the occurrence of significant liver fibrosis and age over 40 years, dyslipidaemia, obesity, alcohol consumption, smoking, herbal medicine, negative anti-HBs immunological status and detectable viral load. Conclusion: Our study revealed a high prevalence of significant to severe hepatic fibrosis in anti-HBc positive patients. In most of the cases, the fibrosis was severe. Progression to HCC has also been possible. There is no consensus on the follow-up strategy for those patients. However, screening for hepatic fibrosis using noninvasive methods should be recommended for patients aged over 40 years, alcohol or herbal medicine users, patients with metabolic syndrome or occult hepatitis B. In HBsAg-negative/anti-HBc-positive patients, liver stiffness should be evaluated and if it is greater than F2, HCC screening should be started.

Durability of viral response after off-treatment in HBeAg positive chronic hepatitis B

AIM:To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS:A total of 48 HBeAg positive chronic hepatitis B patients who were administered nucleoside analogues and maintained virological response for ≥ 6 mo [hepatitis B virus (HBV) DNA < 300 copies/mL and HBeAg seroconversion] before cessation of treatment were enrolled between February 2007 and January 2010. The criteria for the cessation of the antiviral treatment were defined as follows:(1) achievement of virological response; and (2) duration of consolidation therapy (≥ 6 mo). After treatment cessation, the patients were followed up at 3-6 mo intervals. The primary endpoint was serologic and virologic recurrence rates after withdrawal of antiviral treatment. Serologic recurrence was defined as reappearance of HBeAg positivity after HBeAg seroconversion. Virologic recurrence was defined as an increase in HBV-DNA level > 104 copies/mL after HBeAg seroconversion with previously undetectable HBV-DNA level. RESULTS:During the median follow-up period of 18.2 mo (range:5.1-47.5 mo) after cessation of antiviral treatment, the cumulative serological recurrence rate was 15 % at 12 mo. The median duration between the cessation of antiviral treatment and serologic recurrence was 7.2 mo (range:1.2-10.9 mo). Of the 48 patients with HBeAg positive chronic hepatitis, 20 (41.6%) showed virological recurrence. The cumulative virologic recurrence rates at 12 mo after discontinuing the antiviral agent were 41%. The median duration between off-treatment and virologic recurrence was 7.6 mo (range:4.3-27.1 mo). The mean age of the virological recurrence group was older than that of the non-recurrence group (46.7 ± 12.1 years vs 38.8 ± 12.7 years, respectively; P = 0.022). Age (> 40 years) and the duration of consolidation treatment (≥ 15 mo) were significant predictive factors for offtreatment durability in the multivariate analysis [P = 0.049, relative risk (RR) 0.31, 95% CI (0.096-0.998) and P = 0.005, RR 11.29, 95% CI (2.054-65.12), respectively]. Patients with age (≤ 40 years) who received consolidation treatment (≥ 15 mo) significantly showed durability in HBeAg positive chronic hepatitis B patients (P = 0.014). These results suggest that additional treatment for more than 15 mo after HBeAg seroconversion in patients who are ≤ 40 years old may be beneficial in providing a sustained virological response. CONCLUSION:Our data suggest that HBeAg seroconversion is an imperfect end point in antiviral treatment. Long-term consolidation treatment (≥ 15 mo) in younger patients is important for producing better prognosis in HBeAg positive chronic hepatitis B.

Clinical significance of hepatitis B e antigen level measurement during long-term lamivudine therapy in chronic hepatitis B patients with e antigen positive

AIM： To determine the changes of quantitative hepatitis B e antigen （HBeAg） that predicts early detection of non-response or breakthrough to long-term lamivudine （LAM） therapy. METHODS： Among HBeAg positive chronic hepatitis B patients who failed to achieve HBeAg seroconversion within 12 too, we retrospectively analyzed 220 patients who had received LAM more than 24 too. RESULTS： The mean duration of LAM therapy was 36 （range, 24-72） mo. HBeAg seroconversion after the first 12 mo of LAM therapy was achieved in 53 （24.1%） patients. Viral breakthrough was observed in 105 （47.7%） patients. To find out whether the changing patterns of HBeAg levels can predict the outcome of LAM therapy, we analyzed the reduction rates of HBeAg levels during LAM therapy. Using the decrease more than 90% of pretreatment HBeAg levels, the sensitivity and specificity of response were 96.2% and 70.1%, respectively. Patients were divided into 3 groups according to the reduction patterns of the decrease of quantitative HBeAg： decrescendo, decrescendo-crescendo, no change or fluctuating groups. The optimal time to predict non-response or breakthrough was the first 9 mo of therapy. At 9 mo of therapy, 49 （92.5%） of 53 patients who had achieved HBeAg seroconversion were included in the decrescendo group. On the contrary, in the no change or fluctuating group, only four （7.5%） had achieved HBeAg seroconversion. Among patients who did not show the continuous decrease of HBeAg levels at 9 too, 95.2% （negative predictive value） failed to achieve HBeAg seroconversion. CONCLUSION： Almost all patients who failed to show a continuous decrease of HBeAg levels at 9 mo of LAM therapy were non-response or breakthrough. Therefore, monitoring changes of HBeAg levels during LAM therapy in HBeAg positive chronic hepatitis B may be valuable for identifying patients who are at high risk of non-response or breakthrough.

Liver grafts from hepatitis B surface antigen-positive donors: A review of the literature

The scarcity of available organs and the gap between supply and demand continue to be the main limitations of liver transplantation. To relieve the organ shortage, current transplant strategies have implemented extended criteria, which include the use of liver from patients with signs of past or present hepatitis B virus(HBV) infection. While the use of liver grafts from donors with evidence of past HBV infection is quite limited, some data have been collected regarding the feasibility of transplanting a liver graft from a hepatitis B surface antigen(HBs Ag) positive donor. The aim of the present work was to review the literature regarding liver transplants from HBs Ag-positive donors. A total of 17 studies were identified by a search in Medline. To date, HBs Ag positive grafts have preferentially been allocated to HBs Ag positive recipients. The large majority of these patients continue to be HBs Ag positive despite the use of immunoglobulin, and infection prevention can only be guaranteed by using antiviral prophylaxis. Although serological persistence is evident, no significant HBV-related disease has been observed, except in patients coinfected with delta virus. Consistently less data are available for HBs Ag negative recipients, although they are mostly promising. HBs Agpositive grafts could be an additional organ source for liver transplantation, provided that the risk of reinfection/reactivation is properly prevented.

Inhibition of hepatitis B virus surface antigen expression by small hairpin RNA in vitro

AIM: To explore the anti-hepatitis B virus effect of RNA interference (RNAi) using small hairpin RNA (shRNA)expression vector.METHODS: Hepatitis B virus surface antigen green fluorescent protein (HBs-GFP) fusion vector and shRNA expression vectors were constructed and cotransfected transiently into HepG2 cells. mRNAs extracted from HepG2 cells were detected by real-time PCR. Fluorescence of HBs-GFP protein was detected by fluorescence-activated cell sorting (FACS). The effective shRNA expression vector was transfected into HepG2.2.15 cells. HBsAg and HBeAg in HepG2.2.15 cells were analyzed by radioimmunoassay (RIA) method.RESULTS: FACS revealed that shRNA targeting at HBsAg reduced the GFP signal by 56% compared to the control.Real-time PCR showed that HBs-GFP mRNA extracted from HepG2 cells cotransfected with pAVU6+27 and HBs-GFP expression plasmids decreased by 90% compared to the empty vector control. The expressions of HBsAg and HBeAg were also inhibited by 43% and 64%, respectively.CONCLUSION: RNAi using shRNA expression vector can inhibit the expression of HBsAg, providing a fresh approach to screening the efficient small interfering RNAs (siRNAs).

Combination of small interfering RNAs mediates greater suppression on hepatitis B virus cccDNA in HepG2.2.15 cells

AIM： To observe the inhibition of hepatitis B virus （HBV） replication and expression in HepG2.2.15 cells by combination of small interfering RNAs （siRNAs）. METHODS： Recombinant plasmid psiI-HBV was constructed and transfected into HepG2.2.15 cells. At 48 h, 72 h and 96 h after transfection, culture media were collected and cells were harvested for HBV replication assay. HBsAg and HBeAg in the cell culture medium were detected by enzyme-linked immunoadsorbent assay （ELISA）. Intracellular viral DNA and covalently closed circular DNA （cccDNA） were quantified by real-time polymerase chain reaction （PCR）. HBV viral mRNA was reverse transcribed and quantified by reverse-transcript PCR （RT-PCR）. RESULTS： siRNAs showed marked anti-HBV effects. siRNAs could specifically inhibit the expression of HBsAg and the replication of HBV DNA in a dosedependent manner. Furthermore, combination of siRNAs, compared with individual use of each siRNA, exerted a stronger inhibition on antigen expression and viral replication. More importantlycombination of siRNAs significantly suppressed HBV cccDNA amplification. CONCLUSION： Combination of siRNAs mediates a stronger inhibition on viral replication and antigenexpression in HepG2.2.15 cells, especially on cccDNA amplification.

Positive Rate of Different Hepatitis B Virus Serological Markers in Peking Union Medical College Hospital,a General Tertiary Hospital in Beijing

Objectives To investigate the positive rate of different hepatitis B virus （HBV） serological markers, and the demographic factors related to HBV infection. Methods We enrolled all patients tested for HBV serological markers, such as HBV surface antigen （HBsAg）, HBV surface antibody （HBsAb）, hepatitis B e antigen （HBeAg）, hepatitis B e antibody （HBeAb）, HBV core antibody （HBcAb）, and HBV-DNA from July 2008 to July 2009 in Peking Union Medical College Hospital. The positive rate of each HBV serological marker was calculated according to gender, age, and department, respectively. The positive rates of HBV-DNA among patients with positive HBsAg were also analyzed. Results Among 27 409 samples included, 2681 （9.8%） were HBsAg positive. When patients were divided into 9 age groups, the age-specific positive rate of HBsAg was 1.2%, 9.6%, 12.3%, 10.9%, 10.3%, 9.7%, 8.0%, 5.8%, and 4.3%, respectively. The positive rate of HBsAg in non-surgical department, surgical department, and health examination center was 16.2%, 5.8%, and 4.7%, respectively. The positive rate of HBsAg of males （13.3%） was higher than that of females （7.3%, P=0.000）. Among the 2681 HBsAg （＋） patients, 1230 （45.9%） had HBV-DNA test, of whom 564 （45.9%） were positive. Patients with HBsAg （＋）, HBeAg （＋）, and HBcAg （＋） result usually had high positive rate of HBV-DNA results （71.8%, P=0.000）. Conclusions Among this group of patients in our hospital, the positive rate of HBsAg was relatively high. Age group of 20-29, males, and patients in non-surgical departments were factors associated with high positive rate of HBsAg.

Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy

AIM To detect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene therapy.METHODS The study included 27 chronic hepatitis B treatmentnaive patients in various clinical stages(from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeA g-negative and HBeA g-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/m L, the HBX 5' end region [nucleotide(nt) 1255-1611] was PCRamplified and submitted to next-generation sequencing(NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences(haplotypes) obtained by NGS. Conservation at the HBx protein amino acid(aa) level was also analyzed.RESULTS NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample(2487-9279, IQR 2817). In 14/27 patients(51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region(nt 1255-1286) and the other in the 5' end coding region(nt 1519-1603). This last region coded for a conserved amino acid region(aa 63-76) that partially overlaps a Kunitz-like domain.CONCLUSION Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype.

Applicability and efficacy of a model for prevention of perinatal transmission of hepatitis B virus infection:Single center study in Egypt

AIM: To identify possible maternal risk factors for hepatitis B virus (HBV) acquisition and assess the efficacy of immunoprophylaxis given to infants born to hepatitis B virus surface antigen (HBsAg) positive mothers.

Efficacy compared between entecavir and adefovir dipivoxil on HBeAg-positive nucleos(t)ide-naive patients with chronic hepatitis B at week 12 and week 48

Objective:To evaluate the efficacy of entecavir and adefovir dipivoxil on HBeAg-positive nucleos(t)ide-naive patients with chronic hepatitis B with the method of Meta analysis.Methods:We searched PUBMED,EMBASE,CNKI (China National Knowledge Infrastructure),the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews with reference to all data documented before May 2010.The dosage of entecavir and adefovir dipivoxil was 0.5 mg/d and 10 mg/d,respectively.Heterogeneity was examined by Chi-square test,the relative risk calculated and forest plot drawn.Rates of undetected serum HBV DNA,serum alanine aminotransferase (ALT) normalization,HBeAg clearance,HBeAg seroconversion and adverse effect occurrence were analyzed.Results:Six articles were included,which fit well in with this study.Meta analysis showed that the rate of undetected serum HBV DNA(P=0.000 2 at week 12,P=0.002 at week 48)and that of serum ALT normalization(P=0.04 at week 12,P=0.008 at week 48)in the entecavir group were higher than those in the adefovir dipivoxil group.However,no statistic significance existed between the two groups in the rate of HBeAg clearance (P=0.17),the rate of HBeAg seroconversion(P=0.53)or the rate of adverse effect occurrence(P=0.92)at week 48.Conclusion:Entecavir was superior to adefovir dipivoxil in decreasing serum HBV DNA and normalizing serum ALT in the HBeAg-positive nucleos(t)ide-naive patients with chronic hepatitis B.

Conservation and variability of hepatitis B core at different chronic hepatitis stages

BACKGROUND Since it is currently not possible to eradicate hepatitis B virus(HBV)infection with existing treatments,research continues to uncover new therapeutic strategies.HBV core protein,encoded by the HBV core gene(HBC),intervenes in both structural and functional processes,and is a key protein in the HBV life cycle.For this reason,both the protein and the gene could be valuable targets for new therapeutic and diagnostic strategies.Moreover,alterations in the protein sequence could serve as potential markers of disease progression.AIM To detect,by next-generation sequencing,HBC hyper-conserved regions that could potentially be prognostic factors and targets for new therapies.METHODS Thirty-eight of 45 patients with chronic HBV initially selected were included and grouped according to liver disease stage[chronic hepatitis B infection without liver damage(CHB,n=16),liver cirrhosis(LC,n=5),and hepatocellular carcinoma(HCC,n=17)].HBV DNA was extracted from patients’plasma.A region between nucleotide(nt)1863 and 2483,which includes HBC,was amplified and analyzed by next-generation sequencing(Illumina Mi Seq platform).Sequences were genotyped by distance-based discriminant analysis.General and intergroup nt and amino acid(aa)conservation was determined by sliding window analysis.The presence of nt insertion and deletions and/or aa substitutions in the different groups was determined by aligning the sequences with genotype-specific consensus sequences.RESULTS Three nt(nt 1900-1929,2249-2284,2364-2398)and 2 aa(aa 117-120,159-167)hyper-conserved regions were shared by all the clinical groups.All groups showed a similar pattern of conservation,except for five nt regions(nt 1946-1992,2060-2095,2145-2175,2230-2250,2270-2293)and one aa region(aa 140-160),where CHB and LC,respectively,were less conserved(P<0.05).Some group-specific conserved regions were also observed at both nt(2306-2334 in CHB and 1935-1976 and 2402-2435 in LC)and aa(between aa 98-103 in CHB and 28-30 and 51-54 in LC)levels.No differences in insertion and deletions frequencies were observed.An aa substitution(P79 Q)was observed in the HCC group with a median(interquartile range)frequency of 15.82(0-78.88)vs 0(0-0)in the other groups(P<0.05 vs CHB group).CONCLUSION The differentially conserved HBC and HBV core protein regions and the P79 Q substitution could be involved in disease progression.The hyper-conserved regions detected could be targets for future therapeutic and diagnostic strategies.

Risks of Viral Hepatitis B Transmission in Mother-to-Infant of Pregnant Women Carriers of Chronic Viral Hepatitis B in Cote d’Ivoire

The aim of this study was to identify the risk factors of mother-to-child transmission of HBV in positive Ag Hbs pregnant women in Cote d’Ivoire. Methods: This was a transversal prospective study that took place over a period of 7 months (from February 2016 to August 2016) in 2 university hospital and 2 private clinics. We consecutively recruited 91 pregnant women who were positive for HBs Ag in prenatal consultations. For each pregnant woman record included in the study, we provided Socio-demographic (Age, marital status, education level, social rank, gravidity, parity) and biological data (HBs Ag, Anti-HBc Total Ac, Hbe Ag, Ac anti-Hbe Ac, DNA-VHB, Ac anti-HCV Ac, retroviral serology, transaminases). All of these data were collected using a survey sheet developed for the study. Results: The age of our pregnant women HBs positive ranged from 18 years to 44 years with a mean age of 30.10 years. The age group from 20 to 39 years was the most represented with a frequency of 92.31%. Almost of all positive HBs Ag pregnant women was HBe Ag negative, only 3.3% was HBe Ag positive. The viral load above 2000 IU/ml was found in 21 (23.03%) patients. There were 4 co-infected patients, which 3 HBV-HIV and 1 HBV-HCV. Only 19 (20.88%) pregnant HBs Ag positive women were able to bring back the supplementary virological assessment within a period less than one month. Conclusion: According to our work the virologic profile of positive HBs Ag in pregnant women in Cote d’Ivoire is characterized by an important viral replication objectified by a high viral load in about 23% pregnant women, a negativity of HBe antigen in 96.6% of them.

Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat

AIM: To present the characteristics and the course of a series of anti- hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after immunosuppression. METHODS: We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DNA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). RESULTS: Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. CONCLUSION: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving.

小细胞外囊泡(sEVs)介导HBV感染及相关机制的研究进展

小细胞外囊泡(sEVs)是由大多数细胞分泌的具有脂质双分子层的纳米级别的膜性囊泡,因其是物质交换和信号传递的重要媒介,而被研究者广泛关注。治愈乙型肝炎的基础在于充分掌握HBV复制调控分子机制,HBV主要通过与膜表面受体结合进行复制传代,但其并不是唯一传染途径,除受体途径外,sEVs可将游离的HBV传播给未感染的肝细胞。但sEVs介导HBV感染的机制并不十分明确,因此,本文主要对HBV感染后肝细胞分泌的sEVs与HBV病毒传递的关系和感染机制进行探讨,为临床上治疗HBV感染疾病提供科学的理论指导。

HBeAg/HBeAb双阳性慢性乙型肝炎患者血清HBV RNA的变化及临床转归分析

目的探讨HBeAg/HBeAb双阳性慢性乙型肝炎(CHB)患者血清HBV RNA的变化及临床转归分析。方法选取2020年6月至2022年8月诊治的102例HBeAg/HBeAb双阳性CHB患者作为研究对象,设立为双阳组,同期选取51例HBeAg阳性、HBeAb阴性的CHB患者和52例HBeAg阴性、HBeAb阳性的CHB患者设立为对照1组和对照2组,对比血清HBV RNA变化。根据治疗方法不同将双阳组分为干扰素组(予以干扰素治疗,n=52)和恩替卡韦组(予以恩替卡韦治疗,n=50),对比HBeAg、HBeAb浓度及HBeAg转阴,HBeAb仍阳性、HBeAg和HBeAb同时转阴、HBeAg未转阴,HBeAb仍阳性占比。结果双阳组的HBV RNA水平均高于对照1、2组(P<0.05)。治疗前,干扰素组和恩替卡韦组的HBeAg、HBeAb、HBV RNA比较,差异无统计学意义(P>0.05),治疗后,干扰素组的HBeAg、HBeAb、HBV RNA低于恩替卡韦组(P<0.05)。干扰素组的HBeAg转阴,HBeAb仍阳性占比高于恩替卡韦组,而HBeAg未转阴,HBeAb仍阳性占比低于恩替卡韦组(P<0.05)。2组HBeAg和HBeAb同时转阴占比比较,差异无统计学意义(P>0.05)。ROC曲线分析显示,HBV RNA预测CHB患者HBeAg/HBeAb双阳性和临床转归不良的AUC值分别为(0.936、0.954,P<0.05);敏感度分别为100.00%、93.10%;特异度分别为88.70%、76.70%。结论HBV RNA在HBeAg/HBeAb双阳性CHB患者中呈高表达趋势,观察其水平变化有助于为预测临床转归提供指导。

聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗HBeAg阳性慢性乙肝的临床效果

目的观察聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗乙肝e抗原(HBeAg)阳性慢性乙肝的临床效果。方法选取2019年1月—2023年1月厦门市第三医院收治的HBeAg阳性慢性乙肝患者80例,按随机数字表法分为联合组(n=40)和单药组(n=40)。单药组予替诺福韦二吡呋酯治疗,联合组在单药组基础上予聚乙二醇干扰素α-2b治疗,2组均持续治疗6个月。比较2组HBeAg及乙肝病毒脱氧核糖核酸(HBV-DNA)转阴率,治疗前后肝功能指标[天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆红素(TBil)]、血清炎性因子[肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、IL-10]、肝纤维化指标[透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)]及不良反应。结果与单药组比较,联合组HBeAg及HBV-DNA转阴率均更高(χ^(2)=10.208,P=0.001;χ^(2)=4.507,P=0.034);与治疗前比较,治疗6个月后,2组AST、ALT、TBil、TNF-α、IL-6、IL-10、HA、PCⅢ、LN水平均降低,且联合组低于单药组(P<0.01)。联合组与单药组不良反应总发生率比较差异不明显(12.50%vs.7.50%,χ^(2)=0.139,P=0.709)。结论HBeAg阳性慢性乙肝患者应用聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗效果确切,有助于提高HBeAg、HBV-DNA转阴率,改善肝功能,减轻炎性反应及肝纤维化程度,且安全性较高。

宁夏地区孕产妇HBV检测及感染状况调查研究

目的 了解2015—2021年宁夏地区孕产妇乙型肝炎病毒(HBV)检测及感染情况。方法 收集2015—2021年宁夏各助产机构发现并上报的感染HBV的孕产妇信息,通过预防艾滋病、梅毒和乙型肝炎母婴传播信息管理系统收集相关数据,并分析宁夏地区孕产妇HBV检测率、检测时期和HBV表面抗原(HBsAg)阳性率及其分布特征。结果 2015—2021年宁夏孕产妇HBV检测率99.95%,孕期检测率从69.11%上升至98.13%。累计648 360例孕产妇接受了HBV检测,报告HBsAg阳性孕产妇24 600例,HBsAg阳性率3.79%。24 600例HBsAg阳性孕产妇中,4 847例(19.70%)为仅产时接受检测。孕产妇孕期HBsAg阳性率呈逐年上升趋势,仅产时HBsAg阳性率呈逐年下降趋势,且2015—2019年孕产妇仅产时HBsAg阳性率均高于同期孕产妇孕期HBsAg阳性率。此外,2021年报告2 435例HBV感染孕产妇感染模式,14~<25岁组以模式1感染为主,25~<35岁组、35~<47岁组均以模式2感染为主。结论 2015—2021年宁夏地区孕产妇HBV检测率保持较高水平,孕期检测率显著上升,但仍存在一定比例的产时检测,需进一步采取措施促进孕产妇孕期尽早接受HBV检测,同时加强HBV感染孕产妇疾病监测管理。

替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎的对比研究

目的:观察替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者的临床疗效及安全性。方法:将140例慢性乙型肝炎患者随机分为替比夫定治疗组75例,恩替卡韦组治疗组65例,疗程均为72周。观察两组治疗8、12、24、52、72周时ALT复常率、HBVDNA低于检测下限值率、HBeAg血清学转换率及药物的安全性。结果:治疗8、12、24、52、72周时ALT复常率、HBVDNA低于检测下限值率两组比较差异均无统计学意义(均P>0.05);治疗8、12、24周时HBeAg血清学转换率两组比较差异均无统计学意义(均P>0.05);治疗52周及72周时两组HBeAg血清学转换率分别为30.7%和16.9%(P<0.05),36.0%和23.1%(P<0.05)。两组均未发现明显不良反应。结论:替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎均具有快速强效抗病毒作用,近期ALT复常率、HBVDNA低于检测下限值率、HBeAg血清学转换率均无明显差异,但治疗52、72周时替比夫定组HBeAg血清学转换率高于恩替卡韦组。两药治疗的安全性和耐受性良好。

tRNA^(val)-shRNA表达框在筛选HBV C基因小干扰RNA靶位中的应用

目的:以tRNAval-shRNA表达框技术筛选高效的HBV C基因siRNA靶位。方法:针对HBV C基因序列设定5个siRNA靶位,以一步重叠延伸PCR技术生成含tRNAval启动子的shRNA表达框(SEC),分别与HBV C基因与EGFP融合表达质粒(pC-EGFP)共转染AD 293细胞,转染后48 h,流式细胞术检测融合基因荧光表达情况,半定量RT-PCR法检测HBV-C基因mRNA表达水平。以筛选的shRNA表达框转染hepG 2.2.15细胞,72 h后放免法检测细胞培养上清HbsA g、HbeA g水平,RT-PCR检测细胞HBV pgRNA水平。结果:共转染shRNA表达框能有效抑制融合表达质粒(pC-GFP)荧光强度和HBV C mRNA表达,其中SEC-492 i抑制效率最佳,而SEC-282 i相对较差。选定的492 i表达框(SEC-492 i)及282 ishRNA表达框(SEC-282 i),均呈剂量依赖性抑制hepG 2.2.15细胞HbeA g分泌和HBV pgRNA水平,其中SEC-492 i抑制HbeA g和HBV pgRNA水平明显优于SEC-282 i。结论:在选定的5个siRNA靶位中,以492 i靶位RNA i效率最高。tRNAval-shRNA表达框技术可用于抗HBV高效siRNA靶位的筛选,有进一步推广应用价值。

替比夫定治疗HBeAg阳性慢乙肝患者的HBeAg血清转换预测因素探讨

目的:观察替比夫定治疗HBeAg阳性慢性乙型肝炎52周的临床疗效并探讨HBeAg血清转换预测因素。方法:100例入组患者,口服替比夫定600 mg,每天1次,治疗52周进行疗效评估。以52周出现HBeAg血清转换有无为应变量,以年龄、性别、基线ALT、基线HBeAg、基线HBV DNA、治疗期间HBV DNA变化模式(12、24、36周HBV DNA低于检测下限)、治疗期间HBeAg变化模式(12、24、36周HBeAg下降>1 log及12、24、36周HBeAg下降>2 log)14个因素作为自变量进行多因素Lo-gistic回归分析。结果:替比夫定治疗52周完全病毒学应答率81%,HBeAg血清转换率31%,病毒学突破率4%。治疗52周时HBeAg血清转换与基线HBeAg值相关(P<0.01),而与基线ALT值和基线HBV DNA无相关性。其中基线HBeAg≤500 PEIU/ml与HBeAg>500 PEIU/ml的患者52周时HBeAg血清转换率有统计学差异(P<0.01)。多因素Logistic回归分析显示3个因素进入Logistic回归方程,按其作用强弱依次为:24周时HBeAg下降>2 log PEIU/ml;12周时HBeAg下降>1 log PEIU/ml;基线HBeAg值,HBV DNA未能进入。结论:替比夫定治疗HBeAg阳性慢性乙型肝炎,52周HBeAg血清转换的预测因素以24周HBeAg下降>2 log PEIU/ml的预测效果最强。