恩替卡韦联合水飞蓟宾对慢性乙型病毒性肝炎患者肝功能及肝纤维化指标的影响

目的探讨恩替卡韦联合水飞蓟宾对慢性乙型病毒性肝炎患者肝功能及肝纤维化的影响。方法 200例慢性乙型病毒性肝炎患者依据治疗方式的不同分为两组各100例,观察组使用恩替卡韦联合水飞蓟宾治疗,对照组使用恩替卡韦治疗,比较两组的肝功能和肝纤维化指标。结果治疗6个月后,两组的ALT、 TBil、 AST、 HA、 IVC、 LN水平均显著低于治疗前,且观察组显著低于对照组(P <0.05)。结论恩替卡韦联合水飞蓟宾治疗慢性乙型病毒性肝炎患者能够有效缓解肝纤维化损伤,改善肝功能。     

恩替卡韦治疗乙型肝炎患者血清铁蛋白的检测与临床意义

目的:检测慢性乙型肝炎患者血清铁蛋白(SF)的水平及恩替卡韦抗病毒治疗前后的变化。方法:采用化学发光法检测102例慢性乙型肝炎患者SF水平,并检测ALT、HBV DNA、基因型等指标。结果:轻度、中度至重度患者SF水平依次递增,均高于健康对照组,SF与ALT水平呈正相关,不同基因型之间SF水平差异无统计学意义(P>0.05)。抗病毒治疗48周后,ALT复常组及HBV DNA阴性组患者SF水平均明显下降。结论:检测SF水平可以在一定程度上反映肝脏炎性反应程度。定期监测SF的变化,对判断恩替卡韦抗病毒疗效及疾病预后有一定意义。     

Asociación Mexicana de Hepatología A.C. Guía Clínica de Hepatitis B

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.     

肝达康胶囊联合恩替卡韦治疗慢性乙型肝炎的临床研究

目的 探讨肝达康胶囊联合恩替卡韦治疗慢性乙型肝炎的临床疗效。方法 选取2018年1月-2019年6月于新乡医学院第一附属医院感染科就诊的124例慢性乙型肝炎患者,随机分为对照组和治疗组,每组各62例。对照组口服马来酸恩替卡韦片,1片/次,1次/d。治疗组在对照组治疗的基础上口服肝达康胶囊,8粒/次,3次/d。两组均连续治疗3个月。观察两组的临床疗效,比较两组治疗前后肝功能指标、肝纤维化指标、Th1和Th2细胞百分比和细胞因子水平的变化情况。结果 治疗后,治疗组和对照组的总有效率分别是95.16%、82.26%（P<0.05）。治疗后,两组患者血清丙氨酸氨基转氨酶（ALT）和天门冬氨酸氨基转移酶（AST）同各组治疗前相比均显著降低（P<0.05）;与对照组相比,治疗后治疗组患者血清ALT和AST水平降低更加明显（P<0.05）。治疗后两组患者血清层黏连蛋白（LN）、透明质酸（HA）、Ⅲ型前胶原N端肽（PCIII）、Ⅳ型胶原（IV-C）水平均明显下降（P<0.05）;且治疗后治疗组上述指标同对照组相比降低更加明显（P<0.05）。治疗后,两组Th1、Th1/Th2显著降低,而Th2显著升高（P<0.05）;与对照组相比,治疗后治疗组Th1、Th1/Th2显著更低,而Th2显著更高（P<0.05）。治疗后,两组患者γ干扰素（IFN-γ）、肿瘤坏死因子α（TNF-α）水平均显著下降,而白细胞介素4（IL-4）、白细胞介素6（IL-6）水平均显著升高（P<0.05）;治疗后,治疗组患者IFN-γ、TNF-α水平低于对照组,而IL-4、IL-6水平高于对照组（P<0.05）。结论 肝达康胶囊联合恩替卡韦治疗慢性乙型肝炎具有较好的临床疗效,能显著改善患者肝脏损伤情况,可能与改善Th1/Th2细胞失衡有关,具有一定的临床推广应用价值。     

聚乙二醇干扰素alpha-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎的临床研究

目的 观察聚乙二醇干扰素alpha-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎的疗效及安全性.方法 60例HBeAg阳性患者随机分成三组:聚乙二醇干扰素α-2a组20例(A组),恩替卡韦组20例(B组),聚乙二醇干扰素联合恩替卡韦组20例(C组)(联合治疗12周后单用聚乙二醇干扰素治疗).观察三组患者治疗4、12及24周时丙氨酸氨基转移酶(ALT)复常率、HBV DNA阴转率、HBsAg和HBeAg血清转换情况,并观察其不良反应.结果 分别在治疗第4、12、24周时比较三组,A组、B组的HBV DNA阴转率均明显低于C组(分别为:Z=-4.6,P＜0.0001;Z=-2.53,P=0.0114);A组ALT复常率明显低于C组(Z=-2.63,P=0.0086),B组与C组的ALT复常率差异无统计学意义;C组的HBsAg、HBeAg下降幅度大于A组和B组.结论 聚乙二醇干扰素alpha-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎患者,6个月疗程中HBV DNA阴转率、ALT复常率均优于聚乙二醇干扰素单药治疗,且安全性良好.     

Efficacy of Entecavir Treatment for up to 5 Years in Nucleos(t)ide-Na?ve Chronic Hepatitis B Patients in Real Life

Objective: To analyze the efficacy and safety of entecavir (ETV) treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B patients in real life.Methods: We retrospectively analyzed 230 nucleos(t)ide naïve chronic hepatitis B patients who received ETV 0.5 mg/day monotherapy for at least 3 months, of whom 113 were HBeAg positive and 117 were HBeAg negative. The primary endpoints was cumulative probability of achieving a virological response (undetectable serum HBV DNA, <100IU/mL). Secondary endpoints were rates of ALT normalization (ALT < upper limit of normal), HBeAg seroconversion, resistance, and safety.Results: The median follow-up duration was 27.5 months (3-73 months) and mean age was 42 years. With 230, 214, 180, 142, 88, 42 and 11 patients followed-up for at least 3 months,6 months, 1, 2, 3, 4 and 5 years, respectively. In all, Incremental increases were observed in the rates of undetectable HBV DNA. 67.0%, 85.0%, 89.4%, 94.4%, 95.5%, 97.6%, 100% had undetectable HBV DNA at month 3, month 6, 1 year, 2 years, 3 years, 4 years and 5 years. Proportions of patients achieving normal ALT were 73.9%, 85.5%, 82.8%, 89.4%, 80.7%, 85.7%, 100%, respectively. The rate of HBeAg seroconversion reached 21.4% and 15.4% at year2, 3, respectively. One patient achieved HBsAg seroclearance after 1 year, and achieved anti-HBs seroconversion at year 3. Of 180 patients, HBV DNA was detectable (partial virological response, PVR) in 19 patients at year 1 of follow-up, twelve of 14 (85.7%) patients with PVR need more than 1 year of continuous ETV therapy to achieved VR. At baseline, no ETV-resistance was detected in 25 ETV-naïve patients. One patient developed ETV-resistance mutations due to noncompliance. No serious adverse event was reported.Conclusion: Long-term ETV treatment of nucleos(t)ide-naïve was effective and safe in real life. Adjustment of ETV monotherapy in nucleos(t)ide-naïve patients with a partial virological response at 1 year may be unnecessary.     

Entecavir up-regulates dendritic cell function in patients with chronic hepatitis B

AIM： To investigate the in vitro effect of entecavir （ETV on the function of dendritic cells （DCs） derived from chronic hepatitis B （CHB） patients. METHODS： Mononuclear cells were isolated from peripheral blood of patients with CHB. DCs wer incubated with RPMI-1640 medium supplemented wit fetal bovine serum, IL-4, granulocyte-macrophag colony-stimulating factor （GM-CSF）. DCs were treate with or without ETV on the fourth day. Cell surfac molecules, including CD1a, CD80, CD83 and HLA-DR were assessed by flow cytometry. Concentrations of IL- and IL-12 in the supernatant were assayed by enzyme linked immunosorbent assay （ELISA）. The ability of th generated DCs to stimulate lymphocyte proliferation wa observed. RESULTS： Compared with CHB control group, th expression levels of CD1a （29.07 ± 3.20 vs 26.85 ± 2.80 CD83 （25.66 ± 3.19 vs 23.21 ± 3.10）, CD80 （28.00 ± 2.7 vs 25.75 ± 2.51） and HLA-DR （41.96 ± 3.81 vs 32.20 ± 3.04） in ETV-treated group were higher （P 〈 0.05）. ETV treated group secreted significantly more IL-12 （157.6 ± 26.85 pg/mL vs 132.60 ± 22.00 pg/mL （P 〈 0.05） an had a lower level of IL-6 in the culture supernatant （83.0 ± 13.88 pg/mL vs 93.60 ± 13.61 pg/mL, P 〈 0.05） tha CHB control group. The ability of DCs to stimulate th proliferation of allogeneic lymphocytes was increase in ETV-treated group compared with CHB control grou （1.53 ± 0.09 vs 1.42 ± 0.08, P 〈 0.05）.CONCLUSION： Entecavir can enhance the biological activity of DCs derived from CHB patients.