阿德福韦酯致范可尼综合征一例

阿德福韦酯( adefovir dipivoxil,ADV)主要用于慢性乙型肝炎的治疗,临床应用中曾出现肾损害,应引起关注[1].我科近期收治1例阿德福韦酯致范可尼综合征,报道如下.     

小剂量阿德福韦酯导致低血磷性骨软化症两例并文献总结

目的 分析小剂量阿德福韦酯（ADV）导致低血磷性骨软化症的临床特点、治疗及预后。方法 结合我院诊断的两例服用阿德福韦酯后发生低血磷性骨软化症患者资料和国内外文献,对该症的临床特点、治疗、预后和早期诊断进行总结。结果 服用小剂量阿德福韦酯治疗慢性乙型肝炎导致低血磷性骨软化症患者共12例,男9例,女3例,均来自亚洲人群,年龄在（22~74）岁,服用阿德福韦酯（18~64)个月发现低血磷,血磷波动在（0.37~0.79）mmol/L,血钙正常或偏低,血钾偏低,且均有不同程度的骨质疏松,予补充钙剂、骨化三醇、欧思美等治疗预后良好。结论 小剂量阿德福韦酯所致低血磷性骨软化症临床相对少见,容易漏诊,凡服用阿德福韦酯的患者,无论剂量大小,均应定期检查血肌酐、血钙、血磷及骨密度,以监测是否发生肾损害及低血磷性骨软化症,以期早期诊断,一旦各项指标异常应立即停药,同时可换用其他抗病毒药,如干扰素、恩替卡韦等。     

拉米夫定和(或)阿德福韦酯治疗失代偿期乙型肝炎肝硬化3年疗效观察

目的 观察拉米夫定和(或)阿德福韦酯治疗失代偿期乙型肝炎肝硬化3年疗效.方法 收集乙型肝炎肝硬化失代偿期患者68例,分为抗病毒治疗组和对照组,观察入组患者的临床症状、体征、生化指标、HBV DNA和Child-Pugh分级等变化情况.结果 随访治疗中,治疗组6个月后ALT、ALB和HBV DNA水平均较对照组有明显改善,12个月后TBil和Child-Pugh评分较对照组有明显改善,差异具有统计学意义(P<0.05);治疗组和对照组36个月生存率分别为62.5%和36.1%,差异具有统计学意义(P< 0.05);36个月后治疗组和对照组肝细胞癌发生率分别为3.1%和8.3%,差异无统计学意义.结论 拉米夫定和(或)阿德福韦酯治疗失代偿期乙型肝炎肝硬化,能够改善患者肝功能,延缓疾病进展,提高生存率.     

干扰素与阿德福韦酯治疗慢性乙型肝炎疗效比较

目的比较干扰素与阿德福韦酯分别治疗慢性乙型肝炎的疗效及安全性。方法选择住院治疗的HBeAg阳性慢性乙型肝炎患者50例,随机分为干扰素组及阿德福韦酯组各25例,分别采用干扰素及阿德福韦酯治疗,比较两组患者治疗后6个月、12个月的疗效及不良反应发生情况。结果两组患者治疗后第6、12个月时,ALT复常率、HBeAg阴转率、HBeAb阳转率、HBV-DNA阴转率等比较差异均无统计学意义（P〉0.05）;两组不良反应差异有统计学意义（P〈0.05）。结论干扰素及阿德福韦酯作为作为治疗慢性乙型肝炎的常用药物疗效均比较明显,但阿德福韦酯的不良反应少,安全性更高,故值得临床推广应用。     

慢性乙型肝炎患儿拉米夫定耐药后挽救性治疗的疗效与安全性分析

拉米夫定是治疗慢性乙型肝炎的主要药物之一,但存在治疗见效停药后肝炎再次复发的问题。拉米夫定耐药后联用阿德福韦酯治疗称为“挽救性治疗”,这种方案已在成人中应用,临床上证实安全、有效,但在儿童人群中研究较少。本文通过观察30例阿德福韦酯联合拉米夫定挽救性治疗拉米夫定耐药后肝炎复发的慢性乙型肝炎患儿,探索该方案在儿童中应用的疗效与安全性。     

阿德福韦酯致低血磷性骨软化症2例分析

目的探讨长期服用小剂量阿德福韦酯导致低血磷性骨软化症的临床特点。方法对大连大学附属中山医院2015年2月至6月收治的2例长期口服阿德福韦酯(10 mg/d)导致低血磷性骨软化症患者的临床资料进行回顾性病例分析。结果2例患者分别为75岁男性和79岁女性,均因全身骨痛、肌肉无力和行走困难2年就诊,既往均有慢性乙型肝炎病史,分别口服阿德福韦酯(10 mg/d)8年和4年;化验提示低磷血症(男患为0.44 mmol/L,女患为0.47 mmol/L),低钾血症(男患为3.0mmol/L,女患为3.1 mmol/L),血碱性磷酸酶升高(男患为227 IU/L,女患为566 IU/L),25(OH)D降低(男患为18.16 ng/ml,女患为3 ng/ml),尿常规检测提示尿蛋白及尿糖为阳性,骨密度均提示骨质疏松,影像学显示多发性骨折。停服阿德福韦酯,补充钙剂、骨化三醇、氯化钾和中性磷溶液等治疗,患者生化指标逐渐恢复正常,骨痛及肌肉无力减轻,行走较正常。结论长期服用小剂量阿德福韦酯可以导致低血磷性骨软化症,应定期监测血电解质、肾脏功能、尿常规及骨密度,一旦出现阿德福韦酯相关的肾损伤,应停用阿德福韦酯,并纠正电解质紊乱,以避免引起低血磷性骨软化症。     

阿德福韦酯治疗乙型肝炎肝硬化的研究进展

阿德福韦酯（ADV）是抑制HBV的有效药物,现已广泛应用慢性乙型肝炎（CHB）的抗病毒治疗,因与其他核苷（酸）类似物无明显交叉耐药,且安全性良好,也是治疗乙型肝炎肝硬化较理想的抗病毒药物,现就ADV治疗乙型肝炎肝硬化的研究进展作一概述。     

阿德福韦酯治疗HBeAg阳性慢性乙型肝炎近期疗效分析

目的评价阿德福韦酯治疗HBeAg阳性的慢性乙型肝炎（CHB）患者的疗效。方法58例核苷（酸）类似物初治的HBeAg阳性的慢性乙型肝炎患者,随机分为阿德福韦酯组（10mg／d）36例和安慰剂组22例,分别接受12周治疗后,所有患者均进入为期36周的开放用药（阿德福韦酯10ms／d）阶段。观察患者血清HBVDNA水平、HBeAg和肝脏生物化学功能的变化。结果经过12周的治疗,阿德福韦酯组患者的血清HBVDNA平均下降3．17 log10拷贝／ml,降幅显著高于服用安慰剂组的0．79 log10拷贝／ml（P〈0．05）。第12周和48周时,两组患者的ALT复常率、HBeAg阴转率和HBeAb血清转换率均无明显差异。在治疗结束时,有5例患者出现了HBVDNA反弹,其中1例患者发生了与阿德福韦酯耐药相关的变异。结论（1）阿德福韦酯（10mg／d）治疗HBeAg阳性的慢性乙型肝炎患者具有良好的抗病毒和临床疗效;（2）在48周疗程中,5例（8．8％）患者出现HBVDNA反弹,其中1例为耐药突变,其余4例未检测到相关耐药突变;（3）阿德福韦酯治疗48周,相关耐药突变的发生率为1．7％。     

阿德福韦酯联合拉米夫定治疗乙型肝炎肝硬化失代偿期的临床体会

目的对阿德福韦酯联合拉米夫定治疗乙型肝炎肝硬化失代偿期的临床疗效和药物安全性进行观察和探讨。方法将102例乙型肝炎肝硬化失代偿期患者随机分成两组：每组各51例。对两组都进行常规护肝及抗纤维化对症治疗,观察组在常规的基础上对其进行阿德福韦酯10mg/d和拉米夫定100mg/d的联合治疗,对照组在常规的基础上对其进行阿德福韦酯10mg/d的治疗,并对两组患者治疗后的各项疗效指标进行比较和观察。结果治疗48周时观察组的各项指标在改善程度上都比对照组组高,两组数据差异具有统计学意义（P〈0.05）。结论阿德福韦酯联合拉米夫定治疗乙型肝炎肝硬化失代偿期疗效显著,是理想的抗乙肝病毒药物,两种药物的联合使用可以增加抗毒效果,对患者预后能明显改善。     

不同治疗方案应用于IgA肾病患者中的效果分析

目的研究不同西医方案治疗IgA肾病患者的临床疗效以及安全性。方法以2016年1月至2018年6月于高州市人民医院接受治疗的72例IgA肾病患者作为研究对象。将其按照随机数字表法均分成环磷酰胺组、霉酚酸酯组以及对照组,每组各24例。对照组予以单纯糖皮质激素治疗,环磷酰胺组予以糖皮质激素联合环磷酰胺治疗,霉酚酸酯组则采用糖皮质激素联合霉酚酸酯治疗。3组患者均治疗6个月,比较3组临床疗效、治疗前后各项生化指标水平以及不良反应发生情况。结果环磷酰胺组、霉酚酸酯组、对照组不同Haas分型患者的临床治疗总有效率之间无显著差异(均P0.05)。治疗后环磷酰胺组、霉酚酸酯组患者24 h尿蛋白定量、血肌酐、血清尿素、血尿酸均显著低于对照组(均P0.05);而环磷酰胺组、霉酚酸酯组上述指标水平对比无明显差异(均P0.05)。霉酚酸酯组不良反应发生率为0.00%(0/24),相比环磷酰胺组16.67%(4/24)以及对照组25.00%(6/24)均较低(均P0.05)。结论糖皮质激素联合环磷酰胺以及糖皮质激素联合霉酚酸酯治疗IgA肾病患者的临床疗效相当,但后者不良反应发生率较低,具有更好的安全性,值得临床推广应用。     

Treatment with adefovir dipivoxil in a renal transplant patient with renal insufficiency and lamivudine-resistant hepatitis B infection

Lamivudine is a safe, effective treatment for hepatitis B virus (HBV) reactivation after renal transplantation. However, prolonged lamivudine therapy can produce resistance to the drug. Adefovir dipivoxil (ADV) has demonstrated efficacy in patients with lamivudine resistance, but there is limited clinical experience in patients with either renal transplants or severe renal insufficiency. A 47-year-old man with asymptomatic HBV infection underwent renal transplantation in November 1995. In September 2000 lamivudine therapy was initiated to treat HBV reactivation. The outcome was good, with negative HBV DNA levels. Two years later, significant viral replication developed again. At that time the patient already had advanced renal insufficiency due to chronic graft nephropathy. The transaminase levels were increased, and the HBV DNA reached greater than 200,000 copies/mL by polymerase chain reaction, with development of ascites and cirrhosis. The patient was started on ADV 10 mg every 72 hours (dose adjusted to renal function). There was rapid normalization of hepatic enzymes and progressive decline of the viral load. HBV DNA became negative after 6 months of ADV treatment. The renal function has since remained stable. This case suggests that ADV can be safe and effective in the treatment of renal transplant patients with lamivudine-resistant hepatitis B, even in the presence of advanced renal insufficiency.     

阿德福韦酯治疗慢性乙型肝炎致低磷性骨软化症8例

目的：进一步探讨阿德福韦酯（ADV）所致低磷性骨软化症的临床特点。方法回顾性分析2010至2012年共收治的8例慢性乙型肝炎患者经ADV治疗所致低磷性骨软化症的临床表现、治疗和转归。结果8例患者均在服用ADV后出现低磷血症及骨质疏松，其主要临床表现为乏力、多发骨痛，进行加重至行走障碍；低血磷、低尿酸和高碱性磷酸酶血症、骨密度检查提示骨质疏松。经停用ADV、对症补钙、补磷治疗后患者的血磷恢复正常，疼痛缓解，骨质疏松改善。结论 ADV可引起低磷性骨软化症；补充磷、维生素D3及钙剂治疗可恢复。     

Treatment of lamivudine-resistant hepatitis B infection in post-renal transplant patients with adefovir dipivoxil: preliminary results

We report the treatment outcome in six post-renal transplant patients with lamivudine-resistant hepatitis B virus (LR-HBV) infection using adefovir dipivoxil and followed for 6 to 18 months. Posttransplant immunosuppressive therapy was not altered. Adefovir dipivoxil effectively suppressed hepatitis B virus DNA and improved alanine transferase, although DNA suppression seemed dependent on continued therapy. Nephrotoxicity led to withdrawal of the drug in three patients. This may limit therapeutic usefulness in a significant proportion of post-renal transplant patients with LR-HBV infection.     

Prevention of de novo hepatitis B with adefovir dipivoxil in recipients of liver grafts from hepatitis B core antibody-positive donors

Lamivudine has been shown to prevent de novo hepatitis B virus (HBV) infections in liver transplantation (LT) patients receiving hepatitis B core antibody-positive (HBcAb(+)) grafts, but it may produce long-term resistance. Adefovir dipivoxil (ADV) might be effective in preventing de novo hepatitis and resistance. A single-center, prospective trial was conducted with 16 adults (10 men and 6 women, mean age = 54 ± 11 years) who underwent LT with HBcAb(+) grafts between September 2007 and October 2009. After LT, patients were given ADV [10 mg daily (adjusted for renal function)]. No hepatitis B immune globulin was administered. At LT, all graft recipients were hepatitis B surface antigen-negative (HBsAg(-)), 38% were surface antibody-positive (HBsAb(+)), and 50% were HBcAb(+). The median follow-up after LT was 1.8 years (range = 1.0-2.6 years). All recipients had undetectable HBV DNA (<40 IU/mL) after LT until the end of follow-up. One recipient (6%) who was HBsAb(-) and HBcAb(-) before LT became HBsAg(+) after 52 weeks. One recipient was switched from ADV to entecavir for chronic renal insufficiency, and 19% of the patients had renal dose adjustments. There was a nonsignificant trend of increasing creatinine levels over time (1.2 mg/dL at LT, 1.3 mg/dL 1 year after LT, and 2.0 mg/dL 2 years after LT, P = 0.27). A comparison with a control cohort of LT recipients with hepatitis C virus who did not receive ADV showed no difference in the creatinine levels at LT or 1 year after LT. In conclusion, ADV prophylaxis prevents HBV replication in recipients of HBcAb(+) livers but does not fully protect recipients from de novo HBV. Long-term follow-up is needed to better determine the risk of de novo infection.     

Efficacy of adefovir dipivoxil combined with a corticosteroid in 38 cases of nephrotic syndrome induced by hepatitis B virus-associated glomerulonephritis

Objective: To investigate the treatment efficacy of adefovir dipivoxil combined with a corticosteroid on hepatitis B virus-associated glomerulonephritis (HBV-GN). Methods: A total of 38 patients with nephrotic syndrome induced by HBV-GN were treated for 36 weeks between 2010 and 2012. Results: The efficacy analysis showed that 11 patients achieved complete remission and 17 patients achieved partial remission, and the effective remission rate was 73.7%. In addition, 10 patients achieved no remission. Conclusions: Adefovir dipivoxil combined with corticosteroids has a certain efficacy on the HBV-GN and displays few adverse reactions. A large sample, randomized double-blind controlled study and long-term follow-up are needed to verify the efficacy of adefovir dipivoxil combined with corticosteroids.     

Use of adefovir in the treatment of the chronic hepatitis B virus infection with resistance to lamivudine

Current therapies for the treatment of chronic hepatitis B virus (HBV) infection do not eliminate viral replication once therapy is stopped, resulting in a rapid rebound of viremia in a majority of patients. Prolonged therapy results in emergence of resistant virus, which is a major clinical concern. The appearance of resistant HBV is associated with decreased seroconversion rates as well as worse liver histology. Adefovir dipivoxil, a nucleotide analogue with potent antiviral activity against HBV and human immunodeficiency virus (HIV), has shown in vivo and in vitro to have activity against lamivudine-resistant HBV. We present a series of 6 patients with chronic HBV infection and lamivudine-resistant HBV treated with adefovir dipivoxil. The viremia decreased in all patients; in 4 of them, serum HBV DNA was negative by chain reaction (PCR) in a mean period of 10 months from beginning of treatment. Resistance to adefovir after 12 months of treatment has not been detected. Alanine aminotransferase (ALT) levels decreased in all patients and, at this moment, 5 of 6 patients present normal levels. There were no toxic side effects due to adefovir treatment. The data confirm that adefovir treatment has efficacy against HBV lamivudine-resistant forms.     

乙型肝炎肝硬化并脾亢脾部分栓塞术后阿德福韦酯疗效分析

目的观察乙型肝炎肝硬化并脾功能亢进患者行脾部分栓塞术后阿德福韦酯疗效。方法41例乙型肝炎肝硬化并脾功能亢进患者行脾部分栓塞术治疗后,21例口服阿德福韦酯10mg／d,疗程1年,对照组20例常规护肝、降酶等对症治疗。观察两组患者肝功能、血清肝纤维化指标、HBVDNA、HBeAg／抗．HBe血清学变化、Child-Pugh分级比较和不良反应。结果治疗组ALT、AST、TBil、ALB各项指标优于对照组,血清肝纤维化HA、PC-Ⅲ、Ⅳ—C各项优于对照组,治疗组HBVDNA转阴11例,对照组转阴1例,差异有统计学意义（Χ^2=8．5,P〈0．05）。治疗组发生HBeAg／抗．HBe血清转换者4例,对照组1例,差异有统计学意义（Χ^2=3．2,P〈0．05）。治疗组Child．Pugh分级为A级者9例,B级10例,C级2例;对照组A级6例,B级7例,C级7例,差异有统计学意义（Χ^2=5．9,P〈0．05）。阿德福韦酯治疗组未发现相关的肾功能损害和其他不良反应。结论乙型肝炎肝硬化并脾功能亢进患者行脾部分栓塞术治疗,脾功能亢进可获得明显改善,但不能阻止乙型肝炎肝硬化病情进展,脾栓塞术后采用阿德福韦酯是较理想的长期抗病毒药物。     

阿德福韦酯对慢性乙型肝炎患者血清cccDNA的影响

目的探讨阿德福韦酯对慢性乙型肝炎患者血清HBVCCCDNA的影响。方法40例慢性乙型肝炎患者，按1：1随机分配接受阿德福韦酯或安慰剂治疗，所有患者均治疗52周并在停药后随访52周；应用实时荧光定量聚合酶链反应技术检测慢性乙型肝炎患者0周、26周、52周、78周、104周血清HBVCCCDNA及HBVDNA含量。结果治疗组20例患者治疗前（0周）血清HBVCCCDNA中位数水平为8．29×10^6拷贝／ml（与对照组相比P〉0．05）；接受阿德福韦酯治疗半年（26周）及1年（52周）血清HBVCCCDNA中位数水平分别为2．61×10^4拷贝／ml、7．78×10^3拷贝／ml（与治疗前相比两者P〈0．05），停药半年（78周）及1年（104周）血清HBVCCCDNA中位数水平分别为3．38×10^4拷贝／ml、3．60×10^4拷贝／ml（与治疗前相比两者P〈0．05）；接受阿德福韦酯治疗半年及1年血清HBVCCCDNA分别下降2．502log10、3．028log10（与对照组相比两者P〈0．05），停药半年及1年血清HBVCCCDNA较停药时上升0．638log10、0．665log10（与对照组相比两者P〈0．05）。结论阿德福韦酯对血清HBVCCCDNA有明显抑制作用；血清HBVCCCDNA可作为阿德福韦酯抗病毒治疗的重要监测指标。