This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 (t = 10.58, P < 0.001), 5.59 (t = 3.37, P = 0.028) and 10.83 (t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.
Objective To study the relationship of hepatitis B virus （HBV） to spontaneous rupture of hepatocellular carcinoma （HCC-SR） and its mechanism. Method The related literatures about theory of HCC-SR were consulted and reviewed. Results The injury of small arteries was usually followed in patients with HCC-SR， which was related to vascular autoimmune injury caused by the HBV infection. The small arteries in which immune complex deposited were readily injured， as a result HCC-SR happened while vascular load increased. Conclusion The HBV infection resulted in vascular autoimmune injury maybe a important factor in the pathogenesis of HCC-SR.
目的 采用干扰素和阿德福韦酯治疗慢性乙型肝炎患者经拉米夫定治疗后出现YMDD变异，比较两种治疗策略的临床疗效。 方法 选择2002年2月-年12月经100 mg拉米夫定治疗后出现YMDD变异的慢性乙型肝炎患者76例。其中，男52例，女24例；年龄18~55岁，平均年龄33岁。服用100 mg拉米夫定52～156周发生YMDD变异，HBV DNA低于治疗前水平，丙氨酸转移酶(alanine aminotransferase，ALT)lt;2×ULN/L患者分为A组(26例)，继续用100 mg拉米夫定治疗48周；服用100 mg拉米夫定52～156周发生YMDD变异，HBV DNA定量检测高于或等于治疗前水平，ALTgt;2×ULN/L，根据患者自愿分为B组(27例)和C组(23例)。B组用100 mg拉米夫定联合10 mg阿德福韦酯治疗48周；C组用干扰素治疗48周。分别观察3组ALT复常率及HBV DNA转阴率、HBeAg阳性患者血清学转换率。 结果 治疗48周时，B、C组患者ALT复常率分别是74.1%和78.3%，明显高于A组的34.6%，差异有统计学意义(Plt;0.05)；B、C组患者HBV DNA转阴率分别是77.7%和73.9%，明显高于A组的11.5%，差异有统计学意义(Plt;0.05)；3组HBeAg阳性患者血清学转换率比较，差异均无统计学意义(Pgt;0.05)。 结论 慢性乙型肝炎患者经拉米夫定治疗后出现YMDD变异，继续用拉米夫定治疗疗效不理想，改用干扰素或联合阿德福韦酯治疗更安全有效。
Objective To evaluate the efficacy and safety of antiviral drugs for hepatitis B with YMDD motif variant. Methods We electronically searched MEDLINE (1989-April, 2004), EMBASE (1989-April, 2004), CBMdisc (expand) (1989-April, 2004), and handsearched unpublished Chinese conference proceedings. Randomized and quasi-randomized trials in patients with chronic hepatitis B with YMDD motif variant correlative to lamivudine were collected. Two reviewers extracted the data and assessed the quality of literature independently. The data were then analyzed by RevMan 4.2 software. Results Five studies involving 6 trials and 284 patients were included. According to the results of meta-analysis, antiviral therapy with adefovir plus lamivudine showed significantly better effects on the clearance of serum HBV-DNA and HBeAg and normalization of ALT than that of lamivudine alone (RR 16.61, 95%CI 2.29 to 120.71; RR 6.66, 95%CI 1.23 to 35.88 and RR 6.26, 95%CI 2.29 to 17.12 respectively); also, oxymatrine plus thymothin showed obviously better effects on the clearance of serum HBV-DNA and HBeAg (RR 2.96, 95%CI 1.26 to 6.93 and RR 2.51, 95%CI 1.05 to 5.98 respectively).But adefovir alone showed no better effects on clearance of serum HBV-DNA and HBeAg than that of lamivudine alone (RR 11.00, 95%CI 0.65 to 186.02 and RR 7.00, 95%CI 0.39 to 126.92 respectively); interferon plus lamivudine showed no better effects on the clearance of serum HBV-DNA, HBeAg and the normalization of ALT (RR 3.50, 95%CI 0.90 to 13.58; RR 4.90, 95%CI 0.70 to 35.10 and RR 2.80, 95%CI 0.91 to 8.12 respectively). Chinese herbs plus lamivudine showed no better effects on the clearance of serum HBV-DNA (RR 1.16, 95%CI 0.89 to 1.51). There were no significant side effects in the groups, except flu like symptom in the interferon group, slight kidney impairment in the adefovir group, and aggravation of rare cases in lamivudine group. Conclusions Antiviral therapy with adefovir plus lamivudine, or oxymatrine plus thymothin, shows better effects than with lamivudine alone in terms of antiviral therapy and clinical outcome improvement. However, the evidence is too weak to draw a definite conclusion in this systematic review. Larger sample size and rigorously designed randomized, double blind, placebo control trials are required for future study.
【摘要】 目的 通过检测临床确诊为慢性乙型肝炎患者血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、甲状腺激素T3、T4及促甲状腺素（TSH）含量，进一步探讨慢性乙型肝炎患者肝损情况与甲状腺分泌功能的关系。 方法 收集2009年1-4月79例确诊为慢性乙型肝炎患者（病例组）血清标本，分别检测其ALT、AST、甲状腺激素T3、T4及TSH含量。以同期健康体检者30例作为对照组。比较两组的差异及各指标间的相关性。 结果 病例组AST为（87±113） U/L、ALT为（135±241） U/L、AST/ALT为0.97±0.57、TSH为（1.63±1.29） mU/L、T3为（1.61±0.52）ng/mL、T4为（10.7±2.9） μg/dL，对照组分别为（23±5） U/L、 （18±5） U/L、1.31±0.26、（2.13±0.90） mU/L、（1.19±0.16） ng/mL和（8.6±0.9） μg/dL，两组各指标比较均有统计学差异（Plt;0.01）。所有指标均正常的共有6例（7.6%），有73例（92.4%）存在不同程度的指标异常；在68例AST/ALT比值降低的慢性乙型肝炎患者（93.2%）中，伴有单纯T4升高的有11例（16.2%），单纯T3升高的有4例（5.9%），T3、T4同时升高的有11例（16.2%），T3、T4同时升高且TSH降低的有2例（2.9%），1例T4升高且TSH降低（1.5%），1例仅TSH升高（1.5%）；在4例AST/ALT比值正常的慢性乙型肝炎患者（5.5%）中，有1例T3、T4同时升高且TSH降低，1例T3和T4同时升高，1例单纯T4升高，1例单纯TSH降低；有1例仅AST/ALT比值升高而其他项正常。 结论 慢性乙型肝炎患者除AST/ALT比值异常外，还同时伴有不同程度的甲状腺激素指标异常，其原因可能与慢性乙型肝炎应用干扰素治疗时甲状腺功能受损有关。【Abstract】 Objective To explore the relationship between liver damage and the secretion function of thyroid by detecting the serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), T3, T4, and thyroid stimulating hormone (TSH) in patients with chronic hepatitis B. Methods The serum samples of 79 patients with chronic hepatitis B from January to April 2009 were collected, and the ALT, AST, T3, T4, and TSH concentrations were detected. Another 30 healthy subjects were selected as the control. The detected indexes were compared between the two groups. Results In the case group, the concentration of AST was (87±113)U/L, ALT was (135±241)U/L,AST/ALT was 0.97±0.57, TSH was (1.63±1.29) mU/L, T3 was (1.61±0.52) ng/mL, and T4 was (10.7±2.9) μg/dL; while in the control group, the concentrations of the items were (23±5) U/L, (18±5)U/L, 1.31±0.26, (2.13±0.90) mU/L, (1.19±0.16) ng/mL, and (8.6±0.9) μg/d L, respectively. The differences between the two groups were significant (Plt;0.01). Among the 79 case, 6 (7.6%) had a totally normal result, and 73(92.4%) had an abnormal result. There were 68 patients who had a low ratio of AST/ALT, among whom 11 (16.2%) had a simple T4 elevation, 4(5.9%) had a simple T3 elevation,11(16.2%) had an elevation of both T3 and T4, 2 (2.9%) had an elevation of both T3 and T4 and a depression of TSH, 1(1.5%) had an elevation of T4 and a depression of TSH, and 1 (1.5%) had a simple TSH elevation. There were 4 cases who had a normal ratio of AST/ALT, among whom 1 had an elevation of both T3 and T4 and a depression of TSH, 1 had an elevation of both T3 and T4, 1 had a simple T4 elevation, and 1 had a simple TSH depression. There was 1 case who had only an elevation of AST/ALT. Conclusion Most of the patients with chronic hepatitis B have an abnormal result of thyroid hormone together with the abnormal ratio of AST and ALT. The reason mainly lies in the damage of thyroid function by the usage of interferon for the therapy of chronic hepatitis B.
【摘要】 目的 分析慢性乙肝患者血清生化、血常规、血清病毒载量及乙型肝炎标志物与肝组织炎症分级、纤维化分期的相关性,以找到有较好相关性的临床指标；通过肝活检证实临床诊断与病理诊断的符合情况,探讨肝活检的重要性及价值。方法 对2007年6月—2009年8月在传染科行肝穿刺活检的359例慢性乙型肝炎患者的血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、总胆红素(TB)、白蛋白(ALB)、球蛋白(GLB)等指标,白细胞(WBC)、血小板(PLT)等指标,凝血酶原时间(PT),血清HBV DNA定量及乙肝标志物的不同状态与肝穿病理分级、分期的相关性进行分析；统计慢性乙肝患者临床诊断与病理诊断的符合情况。结果 肝组织炎症分级及纤维化分期之间有一定相关性(Plt;0.05)；血清ALT、AST、ALB、GLB、PT有助于判断肝组织炎症程度(Plt;0.05)；ALB、GLB、WBC、PLT、PT对肝组织纤维化程度的评估有意义(Plt;0.05)；HBV DNA复制水平与肝组织炎症及纤维化无关(Pgt;0.05),但存在负相关的趋势；纤维化程度高的患者HBeAg阴性组较HBeAg阳性组更多(Plt;0.05)。慢性乙型肝炎患者临床与病理诊断总符合率为56.3％。结论 动态监测慢性乙肝患者肝功能、血常规、凝血常规在一定程度上有助于判断疾病的程度,但要确诊肝组织炎症分级及纤维化分期,肝组织病理活检是必需的。
ObjectiveAntiviral treatments could benefit chronic hepatitis B (CHB) patients with the regression or improvement of liver fibrosis. However, the degree of dynamic change of liver fibrosis for patients who had not received antiviral treatment remained to be studied. The current study aimed to observe the long-term variation of liver stiffness measurement (LSM), virological and biochemical response on patients without standard antiviral therapy.MethodsA total of 220 patients who were diagnosed with chronic HBV infection, who had not reached the standard of antiviral therapy, and completed a follow-up date of over 2 years in the First Affiliated Hospital of Xi’an Jiaotong University from 2012 to 2018 were retrospectively enrolled. According to the changes of LSM in baseline and follow-up period, the patients were divided into regression group, non-progressive group, and progressive group. The virological and biochemical characteristics of each group were analyzed.ResultsAmong the 220 patients, 153 patients (69.5%) had no progress in LSM degree. Alanine aminotransferase (ALT), HBV DNA, and HBsAg in a few patients increased or slightly decreased, while the vast majority remained in a relatively stable state. 89.5% (137/153) of the non-progressive patients were in grade F0. In addition, 58 patients showed spontaneous improvement with a decreasing rate of 0.460 kPa per year. Patients with ALT of 1-2 ULN had a statistically significant decrease in LSM improvement compared to patients with normal ALT. 82.8% of the LSM-improving patients showed baseline LSM of F1-F3. Only 9 patients showed LSM deterioration, however, which could not be explained by virus replication or necroinflammatory activity. ConclusionsFor patients unsatisfying standard antiviral therapy, most patients with baseline LSM of F0 grade fail to progress, and patients with baseline LSM of F1-F3 show a decrease during follow-up, LSM progression occurs in 4.1% of patients.