Combination Therapy with Pegylated Interferon alpha-2b and Adefovir Dipivoxil in HBeAg-positive Chronic Hepatitis B versus Interferon Alone: A Prospective, Randomized Study

Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.

育龄期女性孕期口服富马酸替诺福韦二吡呋酯片行母婴阻断HBeAg转换率的研究

目的 观察育龄期女性孕期予富马酸替诺福韦二吡呋酯(TDF)行母婴阻断的乙型肝炎e抗原(HBeAg)转换率。方法 收集2019年1月—2022年6月赣州市第五人民医院收治的HBeAg阳性、高HBV-DNA载量的妊娠中晚期孕妇(孕24~28周)病例数据,按照纳入标准和排除标准进行筛选出60例有效病例,根据随机数字表法分为TDF组和对照组,每组30例。2组均采取常规保肝治疗与抗病毒治疗,在此基础上TDF组采用富马酸替诺福韦二吡呋酯片治疗。比较2组孕妇治疗4、8、12周后与产后4周的HBeAg转换率情况,孕妇治疗前与治疗4、8、12周后及产后4周HBV-DNA浓度、乙肝血清标志物[乙型肝炎表面抗原(HBsAg)、乙型肝炎表面抗体(HBsAb)]、肝功能指标[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)]及肌酐水平。结果 TDF组在治疗4、8、12周后与产后4周的HBeAg转换率均高于对照组(P<0.05);治疗4、8、12周后与产后4周,2组HBV-DNA浓度、HBsAg、HBsAb水平较治疗前下降,且TDF组低于对照组(P均<0.01),而2组ALT、AST及肌酐水平治疗前后比较差异均无统计学意义(P>0.05)。结论 育龄期女性孕期行母婴阻断治疗时,在常规治疗基础上,口服富马酸替诺福韦二吡呋酯片可明显提高在治疗4、8、12周后与产后4周的HBeAg转换率,对于降低HBV-DNA浓度、乙肝血清标志物HBsAg、HBsAb效果显著,而对于孕妇肝功能、肾功能影响不明显。

阿德福韦酯片的制备研究

目的:优化阿德福韦酯片的处方。方法:采用均匀设计法,以填充剂比为因素A,崩解剂为因素B,润滑剂为因素C,以溶出度相似因子作为考察指标。结果:最优化的条件为填充剂比(乳糖、预胶化淀粉比为2.6),崩解剂(5.2%交联聚维酮),润滑剂(0.5%硬脂酸钙),3批验证试验的f_(2)均大于50,与参比制剂溶出行为相似,平均累积溶出度90%以上。结论:该处方设计合理,易于操作,体外溶出度良好。

De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.

Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B

AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.

Resistant mutants induced by adefovir dipivoxil in hepatitis B virus isolates

AIM:To investigate the loci of adefovir dipivoxil(ADV)-induced resistance in hepatitis B virus(HBV)isolates and optimize the management of ADV-treated patients.METHODS:Between June 2008 and August 2010,a cross-sectional control study was conducted comprising 79 patients with chronic HBV infection-related liver disease who had been administered ADV monotherapy.Patients underwent liver imaging.Serum DNA extracts were analyzed for HBV DNA levels,genotypes,and serology markers,and deep sequencing of the HBV P gene was performed.RESULTS:ADV-resistant patients were found either with a single mutated locus,or with coexisting mutated loci.The most prevalent mutations were rt A181T,rt V214A,and rt N236T.Twenty-six patients had more than two mutated loci.The mutants were distributed among the patients without any significant affinity for gender,age,end-stage of liver disease,complications of non-alcoholic fatty liver disease,or HBV DNA levels.Patients with the rt A181T mutant were primarily infected with genotype C and e-antigen negative HBV,while patients with the rt N236T mutant were primarily infected by genotype B HBV(χ2=6.004,7.159;P=0.023,0.007).The duration of treatment with ADV was shorter in the single mutant group compared with the multi-mutant group(t=2.426,P=0.018).CONCLUSION:Drug-resistant HBV mutants are complex and diverse.Patients should receive the standard and first-line antiviral treatment,strictly comply with medication dosage,and avoid short-term withdrawal.

Development of osteomalacia in a post-liver transplant patient receiving adefovir dipivoxil

We report the case of a patient treated with living donor-related liver transplantation who suffered from osteomalacia during adefovir dipivoxil (ADV)-containing antiviral therapy for lamivudine-resistant hepatitis B virus infection. The patient had generalized bone pain,with severe hypophosphatemia after 20 mo of ADV therapy. Radiographic studies demonstrated the presence of osteomalacia. The peak plasma ADV level was 38 ng/mL after administration of ADV at 10mg/day. It was also found that ADV affected the metabolism of tacrolimus,a calcineurin-inhibitor,and caused an increase in the plasma levels of tacrolimus. The disability was reversed with the withdrawal of ADV and with mineral supplementation. ADV can cause an elevation of plasma tacrolimus levels,which may be associated with renal dysfunction. High levels of ADV and tacrolimus can cause nephrotoxicity and osteomalacia. This case highlights the importance of considering a diagnosis of osteomalacia in liver transplantation recipients treated with both ADV and tacrolimus.

Surgical treatment of HCC in a patient with lamivudine-resistant hepatitis B cirrhosis with adefovir dipivoxil

We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine.She was started on adefovir(10 mg daily)while still continuing lamivudine therapy.Four mo later her liver function improved and serum Hepatitis B virus(HBV)-DNA level became undetectable.Three years after the start of additional adefovir treatment,hepatocellular carcinoma (HCC)was detected and the patient underwent a successful hepa-tectomy.Our findings suggest tha-t the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis,but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis,allowing HCC surgery.

De novo combination therapy with lamivudine and adefovir dipivoxil in chronic hepatitis B patients

AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study.All of the patients were given 48 wk combination therapy with lamivudine(LAM) and adefovir dipivoxil(ADV) .Briefly,10 patients were given the de novo combination therapy with LAM and ADV,whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus(HBV) genetic mutation.RESULTS:Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4,12,24 and 48 wk after treatment.Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups.The serum HBV DNA level wasstill detectable in every patient in the two groups at 4 and 12 wk after combination treatment.However,in the de novo combination group,serum HBV DNA levels in 4(40%) and 9(90%) patients was decreased to below 1×10 3 copies/mL at 24 and 48 wk after the combination treatment,respectively.In parallel,serum HBV DNA levels in 2(20%) and 8(40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment,respectively.Furthermore,6(60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment,whereas only 4(20%) patients in the add-on combination group achieved seroconversion.Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment.Moreover,patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts.CONCLUSION:De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score,virus inhibition and renal function.

Relationship Between Serum DNA Replication, Clinicopathological Characteristics and Prognosis of Hepatitis B Virus-associated Glomerulonephritis with Severe Proteinuria by Lamivudine Plus Adefovir Dipivoxil Combination Therapy

Objective To explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN. Methods 102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed. Results Several findings were demonstrated with the increase of serum HBV DNA： 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly（P〈0.05）, while the plasma level of albumin decreased significantly（P〈0.05）; The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group（P〈0.01）. Conclusion With the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased.

Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B

AIM:To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and nave chronic hepatitis B,we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS:Eighty patients who had received lamivudine treatment for various periods and had a lamivudine- resistant liver function abnormality were enrolled.Forty of these patients received adefovir treatment combined with lamivudine treatment for≥2 mo,while the other 40 received adefovir alone.We assessed the levels of hepatitis B virus(HBV)DNA at 0,12 and 48 wk and serum alanine aminotransferase(ALT)levels after 0,12, 24 and 48 wk of adefovir treatment in each group. RESULTS:We found serum ALT became normalized in 72(87.5%)of the 80 patients,and HBV DNA decreased by≥2 log10 copies/mL in 60(75%)of the 80 patients at the end of a 48-wk treatment.HBV DNA levels were not significantly different between the groups.The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION:These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.

Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants

BACKGROUND: The recurrence of chronic hepatitis B after liver transplantation results in increased risk for graft failure and death of patients. Lamivudine has been shown to be effective in the treatment of chronic hepatitis B, but resistance to this agent is common after prolonged administration. METHODS: One patient with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 15 months of treatment. The resistance was confirmed by mutation in the HBV DNA polymerase gene. The patient was treated subsequently with adefovir dipivoxil for 7 months. RESULT: HBV DNA and HBsAg were tested negative, but HBeAb and HBsAb were positive. CONCLUSION: This study provides an evidence that adefovir dipivoxil can be effective in the treatment of lamivudine-resistant HBV mutants.

Solid lipid nanoparticles loading adefovir dipivoxil for antiviral therapy

Herein,solid lipid nanoparticles(SLN)were proposed as a new drug delivery system for adefovir dipivoxil(ADV). The octadecylamine-fluorescein isothiocynate(ODA-FITC)was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15.The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system.About 15 wt%drug entrapment efficiency(EE)and 3 wt% drug loading(DL)could be reached in SLN loading ADV.Comparing with free ADV,the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg)and hepatitis B virus(HBV)DNA levels in vitro were significantly enhanced.

Observation on the effect of adefovir dipivoxil in combined with lamivudine in the treatment of hepatitis B cirrhosis

Objective:To explore the effect of adefovir dipivoxil in combined with lamivudine on the liver function in patients with hepatitis B cirrhosis and the antiviral efficacy.Methods:A total of 156 patients with hepatitis B cirrhosis who were admitted in our hospital were included in the study and randomized into the treatment group and the control group with 78 cases in each group. The patients in the treatment group were given adefovir dipivoxil in combined with lamivudine, while the patients in the control group were given entecavir. After 12-month treatment, the efficacy was evaluated. The liver function, serum virology indicators, and AFP before and after treatment in the two groups were compared. The adverse reactions during the treatment process were recorded.Results: The serum GTP, ALT, AST, and TBIL levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05);moreover, ALT and TBIL levels in the treatment group were significantly lower than those in the control group (P<0.05). HBeAg, HBV-DNA, and AFP levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05), HBeAg and AFP levels in the treatment group were significantly lower than those in the control group (P<0.05), and the comparison of HBV-DNA between the two groups was not statistically significant (P>0.05). ALT normalization rate and HBeAg negative conversion rate after treatment in the treatment group were significantly higher than those in the control group (P<0.05). The comparison of HBV-DNA negative conversion rate and HBeAg conversion rate between the two groups was not statistically significant (P>0.05). No obvious drug adverse reactions and liver function damage occurred during the treatment process in the two groups. Conclusions:Adefovir dipivoxil in combined with lamivudine can significantly improve the liver function and serum virology indicators in patients with hepatitis B cirrhosis, with antiviral efficacy significantly superior to that by entecavir.

复方甘草酸苷联合替诺福韦酯治疗HBeAg阳性慢性乙型肝炎的效果观察

目的观察复方甘草酸苷联合替诺福韦酯治疗HBeAg阳性慢性乙型肝炎的效果。方法124例HBeAg阳性慢性乙型肝炎患者随机分为两组,对照组给予替诺福韦酯治疗,观察组给予复方甘草酸苷联合替诺福韦酯治疗,比较两组的肝功能指标以及HBV DNA、HBeAg转阴率。结果治疗后,观察组的血清ALT、AST、TBIL水平均显著低于对照组,HBV DNA转阴率显著高于对照组(P<0.05);两组的HBeAg转阴率、不良反应发生率比较,差异无统计学意义(P>0.05)。结论复方甘草酸苷联合替诺福韦酯治疗HBeAg阳性慢性乙型肝炎效果显著,可有效降低血清HBV DNA水平,促进肝功能改善,且安全性较高。

阿德福韦酯联合鳖甲煎丸治疗慢性乙型肝炎合并肝硬化临床疗效及对患者血清炎症因子MMP-2 Ang-Ⅱ水平的影响

目的探讨阿德福韦酯联合鳖甲煎丸治疗慢性乙型肝炎合并肝硬化的临床疗效及对患者血清炎症因子、基质金属蛋白酶-2、血管紧张素-Ⅱ水平的影响。方法将72例慢性乙型肝炎合并肝硬化患者按照治疗方法不同分为研究组与对照组,各36例。两组均接受常规治疗,在此基础上对照组给予阿德福韦酯治疗,研究组给予阿德福韦酯联合鳖甲煎丸治疗,观察2个月。比较治疗前后两组肝功能(丙氨酸转移酶、白蛋白、总胆红素、凝血酶原活动度)、炎症因子(白细胞介素-1β、肿瘤坏死因子-α)、基质金属蛋白酶-2及血管紧张素-Ⅱ水平。结果(1)临床疗效:研究组总有效率为97.22%,对照组为77.78%,研究组显著高于对照组(P<0.05)。(2)肝功能:治疗后两组丙氨酸转移酶、总胆红素水平均较治疗前显著降低(P<0.01),研究组显著低于对照组(P<0.01);治疗后两组血白蛋白、凝血酶原活动度水平均较治疗前显著升高(P<0.05或0.01),研究组显著高于对照组(P<0.01)。(3)炎症因子:治疗后两组白细胞介素-1β、肿瘤坏死因子-α水平均较治疗前显著降低(P<0.01),研究组显著低于对照组(P<0.01)。(4)基质金属蛋白酶-2、血管紧张素-Ⅱ:治疗后两组基质金属蛋白酶-2、血管紧张素-Ⅱ水平均较治疗前显著降低(P<0.01),研究组显著低于对照组(P<0.01)。结论阿德福韦酯联合鳖甲煎丸治疗慢性乙型肝炎合并肝硬化临床疗效较好,优于单用阿德福韦酯治疗,其作用机制可能与降低炎症因子、基质金属蛋白酶-2、血管紧张素-Ⅱ水平有关,有利于缓解肝纤维化进程,促进患者肝功能恢复。

替诺福韦酯联合复方益肝灵片对肺结核合并HBV携带患者免疫功能及肝肾功能的影响

目的分析替诺福韦酯联合复方益肝灵片对肺结核合并乙型肝炎病毒(HBV)携带患者免疫功能及肝肾功能的影响。方法前瞻性选取2019年1月至2020年12月在秦皇岛市第二医院就诊的180例肺结核合并HBV感染患者作为研究对象,按照随机数字表法将其分为研究组和对照组,每组90例。对照组患者给予2HRZE/4HR常规化疗,同时采用葡醛内酯等进行常规保肝治疗,研究组患者在对照组治疗方案基础上加用口服富马酸替诺福韦二吡呋酯胶囊和复方益肝灵片。两组患者均连续治疗6个月,在治疗期间连续监测肝肾功能指标。对两组患者治疗6个月末时的病灶吸收和痰菌转阴比例进行比较;对两组患者治疗前和治疗6个月末时的HBV病毒载量、外周血CD4^(+)T淋巴细胞比例、CD8^(+)T淋巴细胞比例、CD4^(+)/CD8^(+)T淋巴细胞比值及血清肝功能指标[丙氨酸转移酶(ALT)、天冬氨酸转移酶(AST)、总胆红素]和肾功能指标(肌酐、尿素氮)水平进行比较;对两组患者治疗期间肝功能损害发生率及程度和肾功能损害发生率进行记录和比较。结果治疗6个月末,研究组患者病灶吸收、痰菌转阴的比例均高于对照组,差异均有统计学意义(P<0.05)。研究组患者的HBV载量较治疗前下降,对照组患者的HBV载量较治疗前上升,研究组患者治疗6个月末的HBV载量低于对照组,差异均有统计学意义(P<0.05)。研究组患者的外周血CD4^(+)T淋巴细胞比例和CD4^(+)/CD8^(+)T淋巴细胞比值均较治疗前升高,CD8^(+)T淋巴细胞比例较治疗前下降,差异均有统计学意义(P<0.05),而对照组患者外周血T淋巴细胞亚群指标与治疗前比较,差异均无统计学意义(P>0.05),研究组患者治疗6个月末的外周血CD4^(+)T淋巴细胞比例和CD4^(+)/CD8^(+)T淋巴细胞比值均高于对照组,CD8^(+)T淋巴细胞比例低于对照组,差异均有统计学意义(P<0.05)。两组患者的肝功能指标和肾功能指标均较治疗前升高,研究组患者治疗6个月末的ALT、AST、总胆红素、肌酐、尿素氮均低于对照组,差异均有统计学意义(P<0.05)。在治疗期间,研究组患者的肝功能损害和肾功能损害的发生率均低于对照组,肝功能损害程度分布低于对照组,差异均有统计学意义(P<0.05)。结论在肺结核合并HBV感染患者的治疗中,在常规抗结核化疗和保肝治疗基础上采用替诺福韦酯联合复方益肝灵片进行辅助治疗,能够显著提升化疗效果、有效降低HBV载量、调节免疫平衡、保护肝肾功能、减少化疗导致的药物性器官损害。

阿德福韦酯治疗拉米夫定耐药慢性乙肝患者的临床效果分析

目的探讨阿德福韦酯治疗拉米夫定耐药慢性乙肝患者的临床效果。方法回顾性选取2016年8月—2020年6月期间在厦门市第三医院传染科接受治疗的拉米夫定耐药慢性乙肝患者103例的临床资料,以随机数表法分组。对照组50例患者接受阿德福韦酯治疗,观察组53例患者接受阿德福韦酯+拉米夫定治疗。对比治疗后患者治疗效果、不同时间点乙肝病毒脱氧核糖核酸(HBV-DNA)水平及转阴率、谷丙转氨酶(ALT)水平、复常率以及用药期间不良反应发生情况。结果治疗后,观察组有效率为96.23%,高于对照组的70.00%,差异有统计学意义(χ^(2)=12.841,P<0.05)。治疗3个月、6个月、9个月、1年后,观察组HBV-DNA水平更低于对照组,差异有统计学意义(P<0.05)。治疗3个月、6个月、1年后,观察组HBV-DNA转阴率更高于对照组,差异有统计学意义(P<0.05)。治疗3个月、6个月、9个月、1年后,观察组ALT水平更低于对照组,差异有统计学意义(P<0.05)。治疗1年后,两组ALT复常率对比,观察组更高,差异有统计学意义(P<0.05)。两组不良反应发生率对比,差异无统计学意义(P>0.05)。结论耐药慢性乙肝患者接受阿德福韦酯治疗取得了显著治疗效果,患者的HBV-DNA水平降低,ALT水平也显著降低,转阴率增高,ALT复常率显著增高,且联合用药并未增加治疗期间不良反应发生率。

拉米夫定联合阿德福韦酯对慢性乙型肝炎患者HBV DNA载量和Treg水平的影响

目的探究拉米夫定联合阿德福韦酯对慢性乙型肝炎患者乙型肝炎病毒载量(HBV DNA)和外周血调节性T细胞(Treg)水平的影响。方法选取2021年1月—2022年1月本院收治的126例慢性乙型肝炎患者作为研究对象,依据治疗方式的不同将其分为对照组与联合组,每组63例。对照组患者予以阿德福韦酯单药治疗,联合组患者予以拉米夫定联合阿德福韦酯治疗。比较2组患者丙氨酸转氨酶(ALT)复常率、HBV DNA转阴率、乙肝表面抗原(HBsAg)血清学转换率、Treg、辅助性T细胞(Th17)、Treg/Th17、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)水平以及不良反应发生情况。结果治疗12周、24周时,2组患者ALT复常率、HBV DNA转阴率、HBsAg血清学转换率的差异均无统计学意义(P>0.05)。治疗36周时,联合组患者ALT复常率、HBV DNA转阴率显著高于对照组(P<0.05)。治疗前,2组患者Treg、Th17与Treg/Th17比较,差异均无统计学意义(P>0.05)。治疗后,2组患者Treg、Th17与Treg/Th17显著降低,且联合组低于对照组,差异均有统计学意义(P<0.05)。治疗前,2组患者CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)比较,差异均无统计学意义(P>0.05)。治疗后,2组患者CD4^(+)及CD4^(+)/CD8^(+)显著升高,且联合组高于对照组,差异均有统计学意义(P<0.05);2组患者CD8^(+)显著降低,且联合组低于对照组,差异均有统计学意义(P<0.05)。治疗期间,对照组患者不良反应发生率为1.59%,联合组患者不良反应发生率为6.35%,2组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论拉米夫定联合阿德福韦酯治疗慢性乙型肝炎可改善机体病理性免疫反应,调节细胞免疫功能,增强抗病毒效果,提高疗效。