扶正化瘀胶囊联合阿德福韦酯治疗乙型肝炎肝硬化的临床观察

目的观察扶正化瘀胶囊联合阿德福韦酯治疗乙肝病毒引起肝炎肝硬化的临床疗效。方法选择100例乙型肝炎肝硬化患者随机分为治疗组和对照组,治疗组口服扶正化瘀胶囊联合阿德福韦酯,对照组单用阿德福韦酯,疗程均6个月,观察治疗前后患者的临床表现、肝功能、乙肝病毒基因定量(HBV-DNA)、肝纤维化指标。结果治疗组在改善临床症状,恢复肝功能优于对照组(P<0.05),HBV-DNA阴转无明显差异(P>0.05),肝纤维化指标明显改善(P<0.05)。结论扶正化瘀胶囊联合阿德福韦酯治疗乙型肝炎肝硬化能有效地改善临床症状,恢复肝功能,使患者HBV-DNA阴转,提高生存率。     

阿德福韦酯联合拉米夫定治疗HBV-YMDD变异的研究

目的比较阿德福韦酯联合拉米夫定和单用阿德福韦酯治疗YMDD变异的慢性乙型肝炎的疗效和安全性。方法将112例在拉米夫定治疗过程中出现YMDD变异的慢性乙型肝炎患者随机分为两组(各56例),治疗组:继续接受拉米夫定100mg·d-1治疗,全程联合阿德福韦酯10 mg·d-1;对照组:拉米夫定100 mg·d-1和阿德福韦酯10 mg·d-1联合治疗12周后单用阿德福韦酯10 mg·d-1,疗程96周。结果两组患者治疗后ALT、AST水平均较治疗前显著改善(P0.05);治疗组治疗48周,96周时肝功能ALT、AST改善优于对照组(P0.05);HBV DNA转阴率显著高于对照组(P0.05)。结论阿德福韦酯对YMDD变异的慢性乙型肝炎患者有良好的疗效和安全性,联合拉米夫定临床疗效更显著。     

In vitro anti-hepatitis B and SARS virus activities of a titanium-substituted-heteropolytungstate

A structural determined heteropolytungstate, [K₄(H₂O)₈Cl][K₄(H₂O)₄PTi₂W₁₀O₄₀]·NH₂OH 1, has been synthesized and evaluated for in vitro antiviral activities against hepatitis B (HBV) and SARS virus. The identity and high purity of compound 1 were confirmed by elemental analysis, NMR, IR analysis and single-crystal X-ray diffraction. The compound 1, evaluated in HepG 2.2.15 cells expressing permanently HBV, significantly reduced the levels of HBV antigens and HBV DNA in a dose-dependent and time-dependent manner. EC₅₀ values were determined to be 54 μM for HBeAg, 61 μM for HBsAg and 2.66 μM for supernatant HBV DNA, as compared to 1671, 1570, 169 μM, respectively, for the commercially-available hepatitis B drug adefovir dipivoxil (ADV). Intracellular cccDNA, pgRNA and HBcAg were also found to be decreased by compound 1 in a concentration-dependent manner. Cytotoxicity results showed that compound 1 has low toxicity in HepG 2 cells with CC₅₀ value of 515.20 μM. The results indicate that compound 1 can efficiently inhibit HBV replication in HepG 2.2.15 cells line in vitro. Additionally, compound 1 also shows high anti-SARS activity at an EC₅₀ of 7.08 μM and toxicity with a CC₅₀ of 118.6 μM against MDCK cells.     

New paradigms for the treatment of chronic hepatitis B

The main goals of chronic hepatitis B treatment should be the long-term suppression of viral replication to minimize disease progression and the risk for the development of hepatocellular carcinoma. Treatment end-points, depending on surrogate markers alone, in particular hepatitis B e-antigen seroconversion, may not be ideal for patients who acquire the disease early in life.
Currently-available drugs include interferons and oral nucleoside/nucleotide analogs. Although interferon therapy provides a finite treatment period, a significant proportion of patients may not respond, and long-term outcome is inconclusive. Long-term efficacy has been demonstrated for both lamivudine and adefovir. However, prolonged nucleoside/nucleotide analog therapy is associated with the emergence of drug-resistant mutations. Therefore, nucleoside/nucleotide analogs with a high genetic barrier and potent antiviral activity, such as entecavir, should be used to reduce the chance of developing drug-resistant mutations. Drugs with a low genetic barrier, including lamivudine and telbivudine, should be used in conjunction with early testing for antiviral response. This can predict favorable outcomes in the long term. The early detection of drug-resistant mutations should prompt clinicians to either add or switch to another agent with a different drug-resistance profile. There are currently no treatment models in the use of combination or sequential therapy in treatment-naïve patients.
To date, long-term treatment appears to be the most effective option. Despite recent advances made with better understanding on the natural history of chronic hepatitis B infection and with newer antiviral drugs available, challenges remain with respect to treatment criteria, treatment end-points, and duration of treatment.     

Failure of adefovir 20 mg to improve suboptimal response in lamivudine‐resistant hepatitis B patients treated with adefovir 10 mg and lamivudine

Summary. Nine patients with lamivudine‐resistant chronic hepatitis B infection who had been treated with adefovir 10 mg/day and had had a suboptimal response but did not have genotypic resistance to adefovir were treated with high‐dose adefovir (20 mg/day). The response to the increased dose of adefovir was compared with the response in 15 patients with a suboptimal response who did not receive an increase in the dose of adefovir. The increase in the dose of adefovir did not lead to a significant reduction in hepatitis B DNA when compared with patients maintained on the standard dose. These data suggest that increasing the dose of adefovir in patients with a suboptimal response does not lead to an improved response.     

手术切除联合阿德福韦酯应用对原发性肝癌复发和生存期的影响

目的探讨肝癌根治术联合阿德福韦酯应用对减少原发性肝癌根治术后的复发转移和延长生存期的效果。方法对100例行肝癌根治术治疗的原发性肝癌患者随机分治疗组和观察组各50例,治疗组在肝癌根治术的基础上,加口服阿德福韦酯10mg至发现复发表现。对照组不用阿德福韦酯治疗。肝癌根治术后第1个月及以后每3个月复查CT/MRI,对病灶复发转移情况进行评价,同时作生存分析。结果治疗组与对照组平均复发或转移时间分别为160d（95%可信区间80～280d）和90d（95%可信区间40～221d）,两组差异有统计学意义（P〈0.05）。中位生存期分别为21个月（95%可信区间13～28月）和13个月（95%可信区间11～17月）,两组差异有统计学意义（P〈0.05）。治疗组6个月、12个月、18个月、24个月生存率分别为：治疗组：95.5%、80.5%、57.O%、42.O%;对照组：83.O%、52.O%、40.O%、23.5%。采用x2检验,结果P值分别为：O.101、0.02、0.015、0.008。结论肝癌根治术联合阿德福韦酯,能延长原发性肝癌患者术后复发转移发生时间,并能适当延长中位生存期。     

复方鳖甲软肝片联合阿德福韦酯片治疗乙型肝炎肝硬化疗效观察

目的：观察复方鳖甲软肝片联合阿德福韦酯片治疗乙型肝炎肝硬化的临床疗效。方法：将50例乙型肝炎肝硬化代偿期（chind—pugh积分≤7分）患者随机分为治疗组与对照组。治疗组25例给予复方鳖甲软肝片联合阿德福韦酯片治疗。对照组25例仅给予口服阿德福韦酯片治疗。48周后观察临床疗效。结果：在改善症状、肝功能及肝纤维化指标方面,治疗组均优于对照组,差异有统计学意义（P〈0．05）。HBV—DNA阴转率比较两组差异无统计学意义（P〉0．05）。结论：复方鳖甲软肝片联合阿德福韦酯片治疗乙型肝炎肝硬化疗效确切,且能很好地改善肝功能,缓解临床症状,阻止肝硬化进展。     

阿德福韦酯治疗HBeAg阳性的慢性乙型肝炎38例

目的观察阿德福韦酯对HBeAg阳性的慢性乙型肝炎患者的临床疗效及耐药情况。方法将70例患者随机分为两组,治疗组38例给予阿德福韦酯片10mg,对照组32例给予拉米夫定片0．1g,两组均为1次／d,服用48周。治疗24周和48周后观察丙氨酸氨基转移酶（ALT）复常率、HBeAg的阴转率及血清学转换率、HBV—DNA定量、HBV—YMDD变异株。结果两组临床疗效无显著差异（P〉0．05）。治疗组在治疗过程中未发现肝功能再次异常,无耐药情况发生;对照组在治疗24周后肝功能轻度反弹,且出现病毒变异株。结论阿德福韦酯治疗HBeAg阳性的慢性乙型肝炎耐药率低,疗效较好。