恩替卡韦联合复方鳖甲软肝片对乙肝肝硬化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复方鳖甲软肝片对乙肝肝硬化患者肝功能及肝纤维化指标的影响。方法选择2017年6月～2018年6月本院收治的乙肝肝硬化患者72例,按随机数字表法分为对照组(36例)和观察组(36例),对照组给予恩替卡韦治疗,观察组在此基础上联合使用复方鳖甲软肝片治疗,两组持续用药6个月后,比较两组患者肝功能及肝纤维化指标。结果治疗后,观察组AST(22.37±7.43)U/L、ALT(26.68±9.32)U/L和TBIL(10.08±1.62)μmol/L水平均低于对照组(27.04±8.62)U/L、(36.85±10.24)U/L、(12.93±1.98)μmol/L,差异有统计学意义(P0.05);治疗后,观察组PC-Ⅲ(130.78±11.69)ng/mL、Ⅳ-C (122.47±10.69)ng/mL、HA (102.72±14.36)ng/mL和LN(121.59±13.63)ng/mL水平均低于对照组(152.48±12.13)ng/mL、(142.86±11.33)ng/mL、(149.83±15.81)ng/mL、(143.87±14.22)ng/mL,差异有统计学意义(P0.05);观察组不良反应发生率(13.89%)高于对照组的8.33%,但差异无统计学意义(P0.05)。结论乙肝肝硬化患者采用恩替卡韦联合复方鳖甲软肝片治疗,有助于抑制乙肝病毒的活性,减少肝脏纤维化的发生,从而改善肝功能,效果高于单独采用恩替卡韦治疗。     

恩替卡韦分散片治疗对高病毒载量慢性乙肝患者的T细胞亚群及血清脂联素、IFN-γ、IL-2水平的影响

目的探讨恩替卡韦分散片(ETV)治疗对高病毒载量慢性乙肝患者的T细胞亚群及血清脂联素(ADP)、干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)水平的影响。方法从本院于2018年6月至2020年6月收治慢性乙肝患者中筛选经荧光定量PCR法测定HBV-DNA>2×10⁵ IU/mL为高病毒载量86例进行研究,按随机数字表法分对照组和观察组,予以对照组常规减黄、保肝及营养支持等对症治疗,观察组在对症治疗基础上予以ETV治疗,均持续治疗6个月,比较两组T细胞亚群、病毒载量指标及Th1/Th2型与相关炎性因子水平。结果经治疗,两组CD3⁺、CD4⁺水平均见提升,CD8⁺水平有一定下降,观察组CD3⁺、CD4⁺水平较对照组更高,CD8⁺水平则更低(P<0.05);两组HBsAg、HBeAg及HBV-DNA载量水平均见相应降低,观察组低于对照组(P<0.05);两组ADP水平呈上升趋势,IFN-γ及IL-2水平均呈下降趋势,观察组ADP水平高于对照组,IFN-γ及IL-2水平均更低(P<0.05)。结论高病毒载量慢性乙肝患者应用恩替卡韦分散片治疗,有助于T细胞亚群改善,且较大程度降低了病毒载量水平,并增强了机体免疫功能。     

替诺福韦酯治疗HBeAg阳性慢性乙型肝炎患者的疗效及对肝功能指标的影响

目的探讨替诺福韦酯治疗HBeAg阳性慢性乙型肝炎患者的疗效及对肝功能指标的影响。方法选取2017年2月至2018年3月本院收治的126例HBeAg阳性慢性乙型肝炎患者,按照年龄、性别组间具有可比性原则分为对照组与观察组,各63例。对照组予以恩替卡韦治疗,观察组予以替诺福韦酯治疗,比较两组治疗前后肝功能指标及ALT复常率、HBV DNA转阴率、HBeAg转阴率。结果治疗后,两组AST、ALT、TBiI均低于治疗前,且观察组低于对照组,ALB高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05);观察组ALT复常率、HBV DNA阴转率、HBeAg转阴率均高于对照组,差异有统计学意义(P<0.05)。结论相比恩替卡韦治疗,替诺福韦酯治疗HBeAg阳性慢性乙型肝炎患者,可有效改善肝功能,提高HBV DNA阴转率及HBeAg阴转率。     

舒肝益脾胶囊联合恩替卡韦治疗乙型肝炎肝硬化的临床研究

目的探讨舒肝益脾胶囊联合恩替卡韦分散片治疗乙型肝炎肝硬化的临床疗效。方法选取2015年10月—2017年10月阳新县人民医院收治的100例乙型肝炎肝硬化患者为研究对象,将所有患者采用抽签方式分为对照组和治疗组,每组各50例。对照组患者口服恩替卡韦分散片,0.5 mg/次,1次/d。治疗组患者在对照组基础上口服舒肝益脾胶囊,5粒/次,3次/d。两组患者均接受治疗6个月。观察两组的临床疗效,比较两组的肝功能指标、肝纤维化指标。结果治疗后,对照组和治疗组的总有效率分别为82.00%、96.00%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转氨酶(AST)和总胆红素(TBIL)水平均显著降低,白蛋白(ALB)水平显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患者肝功能指标水平明显优于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层黏连蛋白(LN)、Ⅳ型胶原(Ⅳ-C)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组肝纤维化指标水平明显低于对照组,两组比较差异有统计学意义(P0.05)。结论舒肝益脾胶囊联合恩替卡韦分散片治疗乙型肝炎肝硬化具有较好的临床疗效,能有效改善患者肝功能和肝纤维化,安全性较好,具有一定的临床推广应用价值。     

HBsAg level and clinical course in patients with chronic hepatitis B treated with nucleoside analogue: five years of follow-up data

Background/Aims

Quantification of the hepatitis B surface antigen (HBsAg) is increasingly used to determine the treatment response in patients with chronic hepatitis B (CHB). However, there are limited data about the clinical implications of Quantification of HBsAg long-term nucleoside analogue treatment for CHB. We investigated the clinical correlation between HBsAg level and clinical course in patients with CHB who are treated long-term with nucleoside analogues.

Methods

Patients with CHB who started lamivudine or entecavir monotherapy before June 2007 were enrolled. HBsAg was quantified at baseline, at 6 months, and at 1, 2, 3, 4, and 5 years of treatment. We compared data between the groups according to the presence or absence of a virological response (VR) and resistance.

Results

Forty-eight patients were analyzed. There was no definite reduction in HBsAg level during the early period of treatment; differences in HBsAg levels between baseline and each time point were significant only at 5 years (P=0.028). In a subgroup analysis, this difference was significant only in non-resistant patients at 5 years (P=0.041).

Conclusions

There was no definite decrease in the HBsAg level during the early period of nucleoside analogue treatment, with long-term treatment being required to observe a significant reduction.     

恩替卡韦对慢性乙型肝炎患者细胞免疫功能的影响

目的 探讨慢性乙型肝炎患者接受恩替卡韦抗病毒治疗前后细胞免疫学功能的变化.方法 纳入对象为慢性乙型肝炎患者（CHB）50例,分为治疗组30例,对照组20例,治疗组接受恩替卡韦抗病毒治疗12个月,对照组未接受核苷类似物或干扰素抗病毒治疗.通过流式细胞术动态分析两组患者外周T细胞亚群和CD4＋ CD25＋ Foxp3＋调节性T细胞的表型和频率变化.结果 接受恩替卡韦治疗的患者,与治疗前比较,治疗后3个月、6个月和12个月其CD4 T细胞、CD4/CD8逐渐增高和CD4＋ CD25＋ Foxp3＋调节性T细胞比例逐渐显著性降低,差异有统计学意义（P＜0.05）;而对照组观察前后差异无统计学意义（P＞0.05）.治疗组治疗后12个月,其调节性T细胞的下降幅度与血清HBV DNA的下降水平呈显著正相关（r=0.65,P＜0.01）.结论 恩替卡韦在有效抗病毒治疗同时具有改善患者的细胞免疫功能.     

恩替卡韦治疗慢性乙型肝炎初治患者3年疗效观察

目的 观察恩替卡韦治疗慢性乙型肝炎初治患者3年的疗效.方法 82例慢性乙型肝炎初治患者,口服恩替卡韦0.5 mg,每日1次,观察治疗前后血清ALT和HBV DNA水平及治疗1、2、3年ALT复常率、HBV DNA阴转率、HBeAg消失率、HBeAg血清学转换率.结果 82例患者治疗1、2、3年时ALT复常率分别为79.3％ （65/82）、84.2％ （69/82）、92.7％ （76/82）;血清HBV DNA载量分别为（3.108＆#177;1.394）、（2.637＆#177;0.571）、（2.670＆#177;0.982） log10拷贝/ml;HBV DNA阴转率分别为65.9％ （54/82）、81.7％ （67/82）、89.0％（73/82）.其中60例HBeAg阳性患者治疗1、2、3年时HBeAg消失率分别为18.3％ （11/60）、43.3％（26/60）、41.7％ （25/60）;血清学转换率分别为16.7％（10/60）、28.3％ （17/60）、31.7％ （19/60）.结论 恩替卡韦初始治疗慢性乙型肝炎患者,能有效抑制HBV DNA复制,促进ALT复常,促使HBeAg血清学转换.延长疗程,可增加HBV DNA阴转、HBeAg消失和血清学转换.     

恩替卡韦联合熊去氧胆酸治疗活动性乙肝失代偿期的临床观察

目的：研究恩替卡韦联合熊去氧胆酸治疗活动性乙肝失代偿期的临床疗效。方法：选取我院2008年至2012年间就诊的68例乙肝失代偿患者,随机分为恩替卡韦＋熊去氧胆酸联合治疗组（n=40）和对照组（n=28）,给予对照组基本治疗,联合治疗组在此基础上给予恩替卡韦联合熊去氧胆酸,疗程为48w。观察患者治疗前后临床表现,肝功能指标,HBv—DNA拷贝数,Child—Plugh评分变化。结果：两组患者治疗前后丙氨酸转氨酶（ALT）、门冬氨酸转移酶（AST）、谷氨酰转肽酶（GGT）、碱性磷酸酶（ALP）有明显改善;总胆红素（TBIL）、总胆汁酸（TBA）、血清球蛋白（Glo）、总胆固醇（TCho）、Child-Pugh等指标用药组有显著改善,对照组无显著改善;治疗组中HBV-DNA拷贝数小于1000·ml-1的例数显著提高,而对照组中几乎没有明显变化。结论：恩替卡韦联合熊去氧胆酸对治疗活动性乙肝失代偿期有突出的退黄降酶、抑制病毒复制作用．并且无明显不良反应和药物相互作用,值得临床进一步研究和推广。     

High efficacy of adefovir and entecavir combination therapy in patients with nucleoside-refractory hepatitis B

Background/Aims

Newly developed and potent antiviral agents suffer from the problem of drug resistance. Multidrug resistance is a major impediment in the treatment of patients with chronic hepatitis B (CHB). In line with American Association for the Study of Liver Diseases guidelines, adefovir dipivoxil (ADV) add-on therapy is recommended in the case of lamivudine resistance, while tenofovir disoproxil fumarate (TDF) is recommended for ADV or entecavir (ETV) resistance. TDF is currently not available in Korea. ADV+ETV combination therapy may be a viable alternative to TDF in patients with either ADV or ETV resistance. However, the efficacy of ADV+ETV combination therapy in patients with CHB and multidrug resistance is unclear. This study investigated the efficacy of ADV+ETV combination therapy in patients with multidrug resistance.

Methods

Twenty-five patients were enrolled and were administered ADV+ETV combination therapy for at least 6 months. Blood was drawn at baseline and at 3, 6, 9, and 12 months after commencing treatment, and the following blood parameters were analyzed: alanine transaminase, hepatitis B e-antigen (HBeAg), anti-hepatitis B e-antigen, and hepatitis B virus (HBV) DNA levels. The initial virological response (IVR) was defined as an HBV DNA level of <4 log₁₀ copies/mL after 6 months of combination therapy.

Results

The IVR rate was 76%. The proportion of patients with a high viral load (≥5.0 log) dropped from 76% at baseline to only 5% after 6 months of treatment. The biochemical response rate during the first 6 months was 71%. HBeAg was lost in 2 patients (10%).

Conclusions

ADV+ETV combination therapy induced a good IVR in CHB patients who were refractory to more than 2 antiviral agents. This regimen may be a good alternative to TDF in Korea, where that drug is not available.