Levels of hepatitis B virus replicative intermediate in serum samples of chronic hepatitis B patients

Hepatitis B virus (HBV) cccDNA levels is an absolute marker of HBV replication in the liver of HBV infected patients. This study aimed to quantify the HBV cccDNA levels in sera and liver tissue samples of treatment naïve patients with chronic hepatitis B. Eighty one chronic hepatitis B (CHB) treatment naïve patients were enrolled from January 2009 to June 2011. Total HBV DNA and HBV cccDNA levels were quantified using sensitive real time PCR assay. The mean age of recruited patients was 34 ± 11.5 years. Fifty four (66.7 %) patients were HBeAg negative. Liver tissue samples were available from 2 HBeAg positive and 21 HBeAg negative CHB patients. The amount of total intrahepatic HBV DNA ranged from 0.09 to 1508.92 copies/cell. The median intrahepatic HBV cccDNA was 0.31 and 0.20 copies/cell in HBeAg positive and HBeAg negative cases, respectively. Serum HBV cccDNA was detectable in 85.2 % HBeAg positive and 48.1 % HBeAg negative CHB patients. Median serum HBV cccDNA was 46,000 and 26,350 copies/mL in HBeAg positive and HBeAg negative subjects, respectively. There was a significant positive correlation between the levels of intrahepatic total HBV DNA and intrahepatic HBV cccDNA (r = 0.533, p = 0.009). A positive correlation was also seen between serum HBV cccDNA levels and serum HBV DNA levels (r = 0.871, p < 0.001). It was concluded that serum HBV cccDNA could be detectable in higher proportion of HBeAg positive patients compared to HBeAg negative patients. Moreover, the median level of serum HBV cccDNA was significantly higher in HBeAg positive patients in contrast to HBeAg negative subjects.     

恩替卡韦联合胸腺肽α1治疗慢性乙型肝炎疗效研究

目的：观察和比较恩替卡韦联合胸腺肽α1治疗HBeAg阳性慢性乙型肝炎的疗效。方法：选取我院58例HBeAg阳性慢性乙型肝炎患者分成联合组和对照组。联合组28例,初始同时使用恩替卡韦及胸腺肽αl24周,之后停胸腺肽αl继续用恩替卡韦至48周。对照组30例,单用恩替卡韦0．5mg／d,48周。定期检测ALT复常率,HBVDNA转阴率,HBeAg／抗HBe血清转换率,肝纤维化组合,Fibroscan评分两组在治疗结束时进行疗效评价。结果：24周时两组ALT复常率无差异显著性（P〉0．05）,联合组和对照组HBVDNA阴转率在24周、48周时均差异有显著性（P〈0．05）。联合组与单用组HBeAg血清转换率在第24周、48周时,两组比较差异均有显著性（P〈0．05）。肝纤维化组合各指标（HA,LN,PIIIP,Ⅳ型胶原）,Fibroscan评分两组治疗48周后比较差异均有显著性（P〈0．05）,且两组治疗前后差异联合组更显著。治疗过程中,未发现明显副作用。结论：恩替卡韦联合胸腺肽d1治疗HBeAg阳性慢性乙型肝炎,安全性与耐受性良好,联合组在ALT复常率,HBeAg血清转换率和HBVDNA转阴率,抗肝纤维仲韵井种P昂荽楫干蕈闱凰巷卡韦组．     

恩替卡韦治疗HBeAg 阳性乙型肝炎临床观察

目的:探讨恩替卡韦治疗HBeAg阳性乙型肝炎的疗效与安全性。方法:140例慢性乙肝患者随机分为2组:观察组予恩替卡韦0.5 mg/d,对照组予拉米夫定100 mg/d,疗程均为48周。观察两组HBV DNA阴转率、ALT复常率、HbeAg血清转换率以及不良反应发生情况。结果:在治疗12周后,观察组与对照组HBV DNA阴转率分别为47.1%、22.9%(P<0.01),ALT复常率分别为51.4%、31.4%(P<0.05),在治疗48周后,观察组与对照组HBV DNA阴转率分别为88.6%、48.6%(P<0.01),ALT复常率分别为90.0%、72.9%(P<0.01)。HbeAg血清转换率无统计学差异,两组患者未见严重不良反应。结论:恩替卡韦治疗HBeAg阳性乙肝患者,较拉米夫定起效快、作用强,且安全性好。     

恩替卡韦治疗HBeAg阳性乙型肝炎临床观察

目的：探讨恩替卡韦治疗HBeAg阳性乙型肝炎的疗效与安全性。方法：140例慢性乙肝患者随机分为2组：观察组予恩替卡韦0．5mg／d,对照组予拉米夫定100mg／d,疗程均为48周。观察两组HBVDNA阴转率、ALT复常率、HbeAg血清转换率以及不良反应发生情况。结果：在治疗12周后,观察组与对照组HBVDNA阴转率分别为47．1％、22．9％（P〈0．01）,ALT复常率分别为51．4％、31．4％（P〈0．05）,在治疗48周后,观察组与对照组HBVDNA阴转率分别为88．6％、48．6％（P〈0．01）,ALT复常率分别为90．0％、72．9％（P〈0．01）。HbeAg血清转换率无统计学差异,两组患者未见严重不良反应。结论：恩替卡韦治疗HBeAg阳性乙肝患者,较拉米夫定起效快、作用强,且安全性好。     

Management of individuals with chronic hepatitis B virus infection and persistent normal or mildly elevated aminotransferase levels

No consensus exists with respect to positive hepatitis B virus (HBV) DNA results and persistent normal or mildly elevated alanine aminotransferase (ALT). The aim of this study is to investigate the appropriate management and prognosis of these populations with chronic hepatitis B (CHB). A total of 235 subjects with positive HBV DNA results and persistent normal or mildly elevated ALT were enrolled in this study. Liver biopsy and liver stiffness measurements (LSM) were performed in all participants at baseline. Antiviral therapy was initiated in patients with significant hepatic inflammation (G ≥ 2) and/or fibrosis (S ≥ 2). The patients were divided into entecavir and adefovir groups based on HBV DNA load (>2000 IU/mL vs <2000 IU/mL). The liver biopsies were repeated at 72 weeks for the patients received antiviral therapy. We found that 112 subjects were hepatitis B e antigen (HBeAg) positive, and 123 subjects were negative. The corresponding median ALTs were 46 (39.5-52.5) and 48 (41.5-57.0) U/mL, respectively. G ≥ 2 and/or S ≥ 2 diseases were present in 48.8% (82/168) of the HBeAg-positive and 51.2% (86/168) of HBeAg-negative patients, respectively. In addition, 96 HBeAg-positive and 72 HBeAg-negative patients were divided into entecavir and adefovir groups. Meanwhile, liver biopsies had greater diagnostic accuracy for determining cirrhosis than LSM (0.711 vs 1.0, P < 0.0001). At the end of the study period, undetectable HBV DNA levels and normal ALT levels were observed in CHB-infected patients. Furthermore, the patients showed histologic improvement at 72 weeks compared with baseline measurements (G, 1.72 ± 1.00 vs 0.73 ± 0.88, P = 0.0002; S, 1.484 ± 0.90 vs 0.99 ± 1.13, P < 0.0001). Collectively, liver biopsy enhanced diagnostic accuracy for CHB-infected individuals with persistent normal or mildly elevated aminotransferase levels. Moreover, antiviral therapy can improve or regress the hepatic fibrosis and cirrhosis.     

苦参碱联合恩替卡韦抗乙型肝炎病毒感染的作用及其机制

目的:探讨苦参碱联合恩替卡韦治疗乙型肝炎病毒(HBV)感染的疗效并初步探讨其作用机制。方法:选择2014年9月-2016年8月我院收治的HBeAg阳性乙肝患者98例,按治疗方法分为对照组和观察组,每组49例。对照组患者给予恩替卡韦治疗,观察组患者在对照组基础上应用苦参碱联合治疗。分别在治疗后12、24、48周观察和比较两组患者的HBeAg转阴率、ALT复常率、HBV DNA转阴率、血清球蛋白水平。结果:观察组在治疗后24、48周的HBeAg转阴率、ALT复常率、HBV DNA转阴率均显著高于对照组,差异均具有统计学意义(P0.05)。观察组血清球蛋白水平明显高于对照组,差异有统计学意义(P0.05)。两组间不良反应发生情况比较差异无统计学意义(P0.05)。结论:苦参碱联合恩替卡韦对于HBV具有较好的协同治疗作用,且安全性较好,可能与苦参碱降低血清转氨酶水平,增强患者免疫功能有关。     

Pegylated-Interferon Alpha Therapy for Treatment-Experienced Chronic Hepatitis B Patients

Background

Studies are limited on pegylated interferon (Peg-IFN) therapy for chronic hepatitis B (CHB) patients who failed or relapsed on previous antiviral therapy.

Objectives

We aimed to investigate the effect of Peg-IFN therapy in treatment-experienced CHB patients.

Study Design

A total of 57 treatment-experienced CHB patients at two medical centers were enrolled. All of the patients were treated with Peg-IFN α-2a at 180 μg weekly for 24 or 48 weeks. The hepatitis B serological markers and viral loads were tested every 3 months until 1 year after stopping Peg-IFN therapy. The endpoints were HBV DNA <2000IU/mL, hepatitis B e antigen (HBeAg) seroconversion, and a hepatitis B surface antigen (HBsAg) loss at 12 months post-treatment.

Results

In HBeAg-positive patients, 25.0%, 29.2%, and 12.5% of the patients achieved HBeAg seroconversion, HBV DNA <2000 IU/mL and a combined response, respectively, at 12 months post-treatment. Prior IFN therapy, a high baseline ALT level, a low creatinine level, undetectable HBV DNA at 12 weeks and a decline in HBV DNA >2 log₁₀ IU/mL at 12 weeks of therapy were factors associated with treatment response. In HBeAg-negative patients, 9.1%, 15.2%, and 6.1% of the patients achieved undetectable HBV DNA, HBV DNA <2000 IU/mL, and an HBsAg loss, respectively, at 12 months post-treatment. No factor was significantly associated with the treatment response in the HBeAg-negative patients. The median HBsAg level declined from 3.4 to 2.6 log₁₀ IU/mL in all the patients, and the 5-year cumulative rate of the HBsAg loss was 9.8% in the HBeAg-negative patients. Overall, none of the patients prematurely discontinued the Peg-IFN therapy.

Conclusions

Peg-IFN re-treatment is effective for a proportion of HBeAg-positive treatment-experienced patients; it has limited efficacy for HBeAg-negative treatment-experienced patients. Peg-IFN might facilitate HBsAg loss in HBeAg-negative treatment-experienced patients.     

CXCL9 Associated with Sustained Virological Response in Chronic Hepatitis B Patients Receiving Peginterferon Alfa-2a Therapy: A Pilot Study

Background and Aims

There is lack of a practical biomarker to predict sustained virological response (SVR) in chronic hepatitis B (CHB) patients undergoing peginterferon alfa-2a (PEG-IFN). The aim of this pilot study was to identify immunological features associated with SVR.

Methods

Consecutive 74 CHB patients receiving 24 weeks (for hepatitis B e antigen (HBeAg)-positive) or 48 weeks (for HBeAg-negative) PEG-IFN, were prospectively enrolled. Serum HBV viral loads, hepatitis B surface antigen (HBsAg), CXCL9, IFN-γ-inducible protein 10 (IP-10), interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured at baseline and week 12. SVR was defined as HBeAg seroconversion combined with viral load <2000 IU/mL in HBeAg-positive (n=36), and viral load <2000 IU/mL in HBeAg-negative patients (n=38) at 48 weeks after the end of treatment.

Results

Nineteen patients (25.7%), 7 in HBeAg-positive and 12 in HBeAg-negative, achieved SVR. There were significant declines of HBV DNA, HBsAg, IP-10 and IFN-γ levels at week 12. In multivariate analysis, pre-treatment CXCL9 >80 pg/mL, HBV DNA <2.5 x 10⁷ IU/mL and on-treatment HBV viral load, HBsAg decline >10% at week 12 were predictors of SVR. The performance of CXCL9 in predicting SVR was good in patients with HBV DNA <2.5 x 10⁷ IU/mL, particularly in HBeAg-negative CHB cases (positive predictive value, PPV= 64.3%).

Conclusions

Pre-treatment CXCL9 level has the potential to select CHB patients who can respond to PEG-IFN, especially in HBeAg-negative patients with low viral loads.     

Analysis of precore/core covariances associated with viral kinetics and genotypes in hepatitis B e antigen-positive chronic hepatitis B patients

Hepatitis B virus (HBV) is one of the most common DNA viruses that can cause aggressive hepatitis, cirrhosis and hepatocellular carcinoma. Although many people are persistently infected with HBV, the kinetics in serum levels of viral loads and the host immune responses vary from person to person. HBV precore/core open reading frame (ORF) encoding proteins, hepatitis B e antigen (HBeAg) and core antigen (HBcAg), are two indicators of active viral replication. The aim of this study was to discover a variety of amino acid covariances in responses to viral kinetics, seroconversion and genotypes during the course of HBV infection. A one year follow-up study was conducted with a total number of 1,694 clones from 23 HBeAg-positive chronic hepatitis B patients. Serum alanine aminotransferase, HBV DNA and HBeAg levels were measured monthly as criteria for clustering patients into several different subgroups. Monthly derived multiple precore/core ORFs were directly sequenced and translated into amino acid sequences. For each subgroup, time-dependent covariances were identified from their time-varying sequences over the entire follow-up period. The fluctuating, wavering, HBeAg-nonseroconversion and genotype C subgroups showed greater degrees of covariances than the stationary, declining, HBeAg-seroconversion and genotype B. Referring to literature, mutation hotspots within our identified covariances were associated with the infection process. Remarkably, hotspots were predominant in genotype C. Moreover, covariances were also identified at early stage (spanning from baseline to a peak of serum HBV DNA) in order to determine the intersections with aforementioned time-dependent covariances. Preserved covariances, namely representative covariances, of each subgroup are visually presented using a tree-based structure. Our results suggested that identified covariances were strongly associated with viral kinetics, seroconversion and genotypes. Moreover, representative covariances may benefit clinicians to prescribe a suitable treatment for patients even if they have no obvious symptoms at the early stage of HBV infection.     

基线血清外泌体miR-155-5p联合乙型肝炎病毒DNA定量实验预测聚乙二醇干扰素治疗乙型肝炎e抗原阳性慢性乙型肝炎的疗效

探讨聚乙二醇干扰素(peginterferon, Peg-IFN)治疗乙型肝炎e抗原(hepatitis B e antigen, HBeAg)阳性慢性乙型肝炎(chronic hepatitis B, CHB)患者48周后,基线血清外泌体miR-155-5p表达水平联合乙型肝炎病毒DNA定量实验在预测HBeAg血清学转换中的价值。回顾性分析2016年6月至2019年6月在本中心初次接受抗病毒治疗的HBeAg阳性CHB患者88例。根据Peg-IFN治疗48周后是否发生HBeAg血清学转换,将患者分为治疗应答组和无应答组。采用多因素logistic回归探讨预测Peg-IFN治疗应答的因子,并应用受试者工作特征(receiver operating characteristic, ROC)曲线下面积评估预测效能。结果发现基线血清外泌体miR-155-5p(OR＝2.193,95% CI 1.315～3.655,P＝0.003)和HBV DNA(OR＝0.398,95% CI 0.163～0.976,P＝0.036)是Peg-IFN治疗效果的独立预测因子。基线血清外泌体miR-155-5p和HBV DNA的截断值分别取2.3和7.2 log₁₀IU/mL时,相应的ROC曲线下面积分别为0.788(95% CI 0.682～0.893)和0.704(95% CI 0.577～0.824)。基线血清外泌体miR-155-5p表达水平≥2.3且HBV DNA定量≤7.2 log₁₀IU/mL的患者,Peg-IFN治疗48周后其HBeAg血清学转换率最高,为66.67% (10/15);而基线血清外泌体miR-155-5p表达水平<2.3且HBV DNA定量>7.2 log₁₀IU/mL的患者,Peg-IFN 治疗48周后其HBeAg血清学转换率最低,仅为3.03%(1/33)。这些结果表明,基线血清外泌体miR-155-5p表达水平联合HBV DNA定量实验可以作为Peg-IFN 治疗HBeAg阳性CHB疗效的预测因子,对于优化CHB的抗病毒治疗有积极作用。     

新疆维吾尔族与汉族乙型肝炎患者HBVDNA 及肝功能检测结果的比较

目的:探讨新疆乌鲁木齐地区伴有肝功能指标:丙氨酸氨基转移酶(ALT)浓度异常的维吾尔族(维族)及汉族HBeAg阳性乙型肝炎初次就诊患者,乙型肝炎病毒DNA复制载量及ALT浓度是否存在差异及其对患者诊断、预后的意义。方法:回顾性选取门诊伴有ALT浓度异常的汉族、维族初次就诊患者并筛选出HBeAg阳性患者汉族、维族共373例。采用实时荧光定量聚合酶链反应、生化测定及酶联免疫吸附试验法分别测定HBV DNA、ALT浓度及乙肝HBeAg。结果:(1)汉族HBV DNA组秩和8869,维族HBV DNA组秩和10359.36,经Mann-Whitney Test检验两组间尚不能肯定HBVDNA分布有统计学意义,即伴有肝功能损害的汉族、维族初次就诊HBeAg阳性患者HBV DNA复制程度没有差异。(2)汉族ALT组秩和26818.50,维族ALT组秩和22009.50,经Mann-Whitney Test检验两组间ALT分布有统计学意义,即伴有肝功能损害的初次就诊HBeAg阳性患者汉族肝功能损害程度高于维族。(3)HBVDNA低复制组(103-104copy/mL):汉族秩和3771.46,维族秩和4993.2;中复制组(104-106copy/mL):汉族秩和6412.4,维族秩和5088.2;高复制组(>106copy/mL):汉族秩和929.04,维族秩和666.96,经Mann-Whitney Test检验在低复制组两民族间ALT分布无统计学意义,在中、高复制组两民族间ALT具有统计学意义。即:伴有肝功能损害的初次就诊HBeAg阳性患者在HBV DNA低复制组两民族间肝功能损害程度无差异,但在中、高复制组汉族肝功能损害程度高于维族。结论:新疆乌鲁木齐地区伴有肝功能损害的初次就诊的HBeAg阳性的汉族与维族之间HBV DNA的病毒复制无统计学意义(P>0.05),但两民族间的ALT具有统计学意义,可能跟维族的民俗、饮食习惯及生存环境、免疫相关基因HLA基因频率分布差异等因素有关。     

Interferon-Alpha-2a and Zinc Combination Therapy in Children with Chronic Hepatitis B Infection

Zinc has been reported to enhance the response to interferon (IFN) or PEG-IFN plus ribavirin therapy, improve liver function, and ameliorate hematologic side effects in patients with chronic hepatitis C. However, the role of zinc supplementation during IFN therapy in chronic hepatitis B infection (CHB) remains unclear. We therefore aimed to report the results of zinc and IFN-alpha-2a therapy in children with CHB. Twenty-two naive, HBeAg-positive children (mean age 10.4 ± 4.4 years) received IFN-α2a (9 MU/m² sc) for 6 months plus peroral zinc (7.5 mg/day for <10 years and 10 mg/day for >10 years) for 12 months. Serum zinc, alanine aminotransferase (ALT), complete blood count, hepatitis B virus DNA (HBV DNA), and serological markers were measured. Histological (HR) and sustained response (SR) were evaluated at 6 months after completion of therapy. Normalization of ALT, HBeAg seroconversion, and HBV DNA < 10,000 copies/ml were considered as SR. HR was defined as decrease in Knodell histological activity index (HAI) score by at least 2 points compared to baseline. End of therapy ALT level and log HBV DNA were significantly lower than pretherapy levels (p = 0.001 and p = 0.001, respectively), while zinc level was not different. Portal inflammation score significantly decreased after therapy (p = 0.043), however, total HAI and other HAI components were not different. SR and HR were 25% and 52.9%. In conclusion as a first study investigating the effect of zinc and IFN combination therapy in children with CHB, SR and HR rates were not better than previously reported monotherapy or combination therapies.     

Hepatitis B e Antigen Status and Hepatitis B DNA Levels in Women of Childbearing Age with Chronic Hepatitis B Infection Screening for Clinical Trials

Background

Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors including hepatitis B e antigen (HBeAg) positivity and viral load.

Aim

To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials.

Methods

Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18–69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive.

Results

Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p<0.0001), this proportion declined with increasing age. Younger women were significantly more likely to have high HBV viral load (HBV DNA>10⁸ copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p<0.0001), and this declined with increasing age. HBeAg positivity was slightly higher in Asian women, associated with a higher proportion of HBV genotypes B and C in this population. There was no obvious relationship between genotype and viral load.

Conclusions

Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load.     

Comparison of the Efficacies and Safety of Combined Therapy between Telbivudine Plus Adefovir and Lamivudine Plus Adefovir in Patients with Hepatitis B Virus Infection in Real-World Practice

MethodsThis study enrolled a total of 171 patients (110 patients received LAM+ADV and 60 patients received LdT+ADV). We analyzed the changes in renal function using the estimated glomerular filtration rate (eGFR). The DNA undetectable rate, hepatitis B e antigen (HBeAg) seroconversion rate, and alanine aminotransferase (ALT) normalization rate were analyzed. We checked the serum uric acid, phosphate and creatine kinase, and lactic acid levels to analyze safety. We observed these patients for 48 to 240 weeks and checked their serum profile every 6 months.ResultsThere was no statistically significant difference between the two groups in anti-hepatitis B virus (HBV) efficacy in terms of DNA undetectable rate, ALT normalization rate, and HBeAg seroconversion rate. Both the LAM+ADV and LdT+ADV groups had stable or improved renal function. However, a higher eGFR was found in the LdT+ADV group with continuous serum fluctuation during 3 years of combined therapy as well as a higher serum creatine kinase level.ConclusionsLong-term LdT+ADV combined therapy and LAM+ADV combined therapy were both associated with stable or improved renal function. The clinical efficacy was similar between the two groups, but the LdT group had a higher serum creatine kinase level. We need to monitor the data regularly in clinical practice.     

基线HBsAg和ALT水平是替比夫定治疗HBeAg阳性慢性乙型肝炎患者e抗原血清学转换的重要预测因素

目的评价初治、单药使用替比夫定治疗HBeAg阳性的慢性乙型肝炎（CHB）患者48周的e抗原血清学转换的基线预测因素。方法97例HBeAg阳性CHB患者分别以基线HBsAg、ALT和HBVDNA水平高低分组,对比两组治疗48周时生化学、病毒学和血清学应答情况。结果基线HBsAg-101500IU／mL组e抗原阴转率和血清学转换率均为42．3％,基线HBsAg〉1500IU／mL组分别为20％和17．8％,两组比较差异均有统计学意义（P〈0．05）;基线ALT〉5ULN组e抗原阴转率和血清学转换率均为45．1％,基线ALT05ULN组分别17．4％和15．2％,两组比较差异均有统计学意义（P〈0．01）;基线HBVDNA〈8．0log-10copies／mL组和基线HBVDNA≥8．0log-10copies／mL组e抗原阴转率和血清学转换率相比,差异无统计学意义（P〉0．05）;基线水平HBsAg≤1500IU／mL且ALT〉5ULN的CHB患者共40例作为观察组,其余57例患者作为对照组,治疗48周时观察组e抗原阴转率和血清学转换率均为45％,对照组分别为22．8％和21．1％,两组比较差异均有统计学意义（P〈0．05）。结论基线HBsAg水平≤1500IU／mL和ALT水平〉5ULN的HBeAg阳性慢性乙型肝炎患者,在接受替比夫定治疗48周时,有较高的e抗原转阴率和血清学转换率;基线HBsAg和ALT水平是替比夫定治疗e抗原血清学转换的重要预测因素。     

乙肝免疫标志物与乙肝病毒核酸含量与肝功能的关系研究

目的:研究乙肝免疫标记物(HBV-M)与乙肝病毒脱氧核苷酸(HBV-DNA)载量与肝功能的关系。方法:检测104例乙肝患者HBs Ag、HBe Ag、HBc Ab、HBs Ab、HBe Ab5种HBV-M;用PCR法检测HBV-DNA含量;同时检测天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、胆碱酯酶(CHE)等肝功能指标,对三者关系采用Spearman相关性分析。结果:HBs Ag、HBc Ab、HBe Ag阳性组HBV-DNA阳性率及载量均大于其余组(P0.05);HBe Ag含量、ALT浓度与HBV-DNA载量均呈正相关(r=0.48,P0.05)、(r=0.36,P0.05);AST、CHE与HBV-DNA含量无明显相关性,但在无病毒载量与有病毒载量组之间AST比较有统计学意义(P0.05)。结论:HBV-M、HBV-DNA与肝功能之间有一定的相关性,但HBe Ag阴转不代表病毒复制停止,HBV-DNA也不能完全反应肝损害程度,临床应加大重视。     

High Hepatitis B Surface Antigen Levels Predict Insignificant Fibrosis in Hepatitis B e Antigen Positive Chronic Hepatitis B

Introduction

There is no data on the relationship between hepatitis B surface antigen (HBsAg) levels and liver fibrosis in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B (CHB).

Methods

Serum HBsAg and HBV DNA levels in HBeAg-positive CHB patients with liver biopsies were analyzed. The upper limit of normal (ULN) of alanine aminotransferase (ALT) was 30 and 19 U/L for men and women respectively. Histologic assessment was based on Ishak fibrosis staging for fibrosis and Knodell histologic activity index (HAI) for necroinflammation.

Results

140 patients (65% male, median age 32.7 years) were recruited. 56 (40%) had ALT ≤2×ULN. 72 (51.4%) and 42 (30%) had fibrosis score ≤1 and necroinflammation grading ≤4 respectively. Patients with fibrosis score ≤1, when compared to patients with fibrosis score >1, had significantly higher median HBsAg levels (50,320 and 7,820 IU/mL respectively, p<0.001). Among patients with ALT ≤2×ULN, serum HBsAg levels achieved an area under receiver operating characteristic curve of 0.869 in predicting fibrosis score ≤1. HBsAg levels did not accurately predict necroinflammation score. HBsAg ≥25,000 IU/mL was independently associated with fibrosis score ≤1 (p = 0.025, odds ratio 9.042).Using this cut-off HBsAg level in patients with ALT ≤2×ULN, positive and negative predictive values for predicting fibrosis score ≤1 were 92.7% and 60.0% respectively. HBV DNA levels had no association with liver histology.

Conclusion

Among HBeAg-positive patients with ALT ≤2×ULN, high serum HBsAg levels can accurately predict fibrosis score ≤1, and could potentially influence decisions concerning treatment commencement and reduce the need for liver biopsy.