慢性乙型肝炎患者合并肌酸激酶升高的相关因素与转归分析

目的明确临床中慢性乙型肝炎（CHB）患者合并肌酸激酶（CK）升高的相关因素及转归情况。 方法回顾性分析CHB合并CK升高患者的临床资料,明确不同抗病毒治疗方案患者在CK升高患者中所占比率。分析3/4级CK升高患者的临床转归。分析合并应用甘草酸制剂等药物对于患者CK水平的影响。分析CK水平与患者病毒学与生化学指标的相关性。 结果共纳入伴CK升高的CHB患者365例,CK升高多见于LdT单药（57.0%）或联合治疗（20.3%）患者,也见于ETV治疗患者（12.6%）等。CK 3/4级升高患者共30例,以LdT单药（66.7%）或联合治疗患者（20.0%）为主。23例定期随访的CK 3/4级升高患者转归良好。1例患者肌组织活检确诊为肌病。合并使用甘草酸制剂等未能够显著升高患者CK水平（t′ = 1.519,P > 0.05）。相关分析提示,CK水平与患者AST水平轻度正相关（rs′ = 0.246,P < 0.001）,与ALT、HBV DNA与HBsAg等无显著相关（P均> 0.05）。 结论CHB合并CK升高多见于LdT治疗患者,应用其他抗病毒治疗患者也需定期监测CK水平;CK升高患者多预后良好;合并使用甘草酸制剂与NAs等未能够显著升高患者CK水平。     

阿德福韦酯联合胸腺素治疗慢性乙型肝炎的疗效观察

阿德福韦酯是抑制HBV的核苷（酸）类似物,目前已证明能有效降低HBV DNA载量,促进ALT复常和HBeAg血清学转换,改善肝脏组织学,且与其他核苷（酸）类似物无明显交叉耐药,因此广泛应用于慢性乙型肝炎和乙型肝炎肝硬化患者[1].     

阿德福韦酯治疗HBeAg阳性慢性乙型肝炎血清学应答的预测因素分析

目的探讨基线血清TNFα、ALT、HBVDNA载量及24周HBV血清学标志物等因素对阿德福韦酯（ADV）治疗HBeAg阳性慢性乙型肝炎（CHB）48周时患者血清学应答的预测价值。方法203例HBeAg阳性CHB患者口服ADV治疗48周,10mg/d。采用ELISA测定HBV血清学标志物和基线血清TNFα水平,荧光定量PCR检测HBVDNA,Logistic回归分析影响HBeAg阳性患者血清学应答的因素。结果203例患者治疗24周时HBV DNA转阴率为31．5％（64／203）,ALT复常率为59．1％（120／203）,HBeAg转阴率为15．8％（32／203）,HBeAg转换率为8．9％（18／203）,应答率为13．3％（27／203）;治疗48周时HBV DNA转阴率为58．6％（119／203）,ALT复常率为78．3％（159／203）,HBeAg转阴率29．6％为（60／203）,HBeAg转换率为16．7％（34／203）,应答率为25．6％（52／203）。Logistic回归分析发现,48周HBeAg转阴的患者较未转阴者的24周HBV DNA转阴率、HBeAg转阴率及转换率、基线TNFα水平高（P值分别为0．017、0．001、0．029和0．040）;48周HBeAg转换的患者较未转换者的24周HBeAg转换率高,而基线HBVDNA低（P值分别为0．000和0．004）。结论24周HBVDNA转阴率、HBeAg转阴率和转换率,及基线TNFα水平可以预测48周HBeAg转阴率,而24周HBeAg转换率和基线HBV DNA载量可以预测48周HBeAg转换率。     

SLC34 A1和 RGS14单核苷酸多态性与阿德福韦酯治疗的慢性乙型肝炎患者血磷浓度的相关性

目的：探讨SLC34A1（rs6420094）和RGS14（rs4074995）单核苷酸多态性与长期服用阿德福韦酯治疗的慢性HBV感染者血磷浓度的相关性。方法选取2012年10月至2013年8月河北医科大学第三医院连续服用阿德福韦酯（10 mg／d）单药或联合治疗至少2年的慢性HBV感染者91例,其中低磷血症患者31例,血磷正常患者60例。应用聚合酶链反应-限制性片段长度多态性分析法测定两位点的基因型,应用χ^2检验分析两位点等位基因分布频率与血磷浓度的关系。结果低磷血症组中,rs6420094基因A／A、A／G和G／G型的例数分别为13,13和5例,而血磷正常组上述基因型的例数分别为35,24和1例。此位点的等位基因A在血磷正常组出现的频率高于低磷血症组（78．3％∶62．9％）,两组比较差异有统计学意义（χ^2＝4．947,P＜0．05）。低磷血症组中,rs4074995基因A／A、A／G和G／G型的例数分别为2,11和18例,而血磷正常组上述基因型的例数分别为1,21和38例,等位基因分布频率在两组间差异无统计学意义（χ^2＝0．625,P＞0．05）。结论 rs6420094多态性可能会影响长期服用阿德福韦酯治疗的慢性HBV感染者的血磷浓度。     

阿德福韦酯耐药慢性乙型肝炎患者HBsAg变异分析

目的探讨阿德福韦酯耐药慢性乙型肝炎患者相关S抗原变异、疫苗逃逸相关变异以及部分已知特异性T细胞表位变异情况。 方法收集2007年12月至2011年9月于首都医科大学附属北京地坛医院收治的阿德福韦酯治疗失败的慢性乙型肝炎患者70例,并随机选择ADV治疗非耐药患者70例作为对照。采用PCR产物直接测序法获得患者HBV反转录酶区与S抗原序列。应用PCR产物直接测序法与焦磷酸测序法明确阿德福韦酯耐药情况。比较阿德福韦酯耐药患者与无阿德福韦酯耐药患者耐药相关S抗原变异、疫苗逃逸相关变异以及HBV特异性T细胞表位变异情况。 结果ADV耐药组与对照组患者人口学等指标差异无统计学意义。本组患者中42例rtA181T耐药变异关联的HBsAg变异均为sW172^*。在rtA181T/ sW172^*变异患者体内,该变异株在病毒准种中所占平均比率为（42.6 ± 22.1）%（12.2%~100%）。与非ADV耐药组患者相比,ADV耐药组患者发生HBsAg疫苗逃逸变异（χ² = 12.8736、P = 0.0003）以及T细胞抗原表位变异（χ² = 4.8344、P = 0.0279）几率显著升高。 结论我国ADV耐药患者rtA181T变异关联的HBsAg变异主要为sW172^*变异,HBsAg抗原疫苗逃逸变异以及T细胞抗原表位变异与ADV耐药相互影响,相关机制尚待进一步研究。     

干扰素α联合阿德福韦酯对干扰素治疗无应答HBeAg阳性慢性乙型肝炎疗效观察

目的 评估干扰素α (IFNα)联合阿德福韦酯(ADV)对IFNα单药治疗24周无应答慢性乙型肝炎(CHB)的疗效和安全性.方法 选择2009至2012年在厦门大学附属第一医院门诊及住院接受IFNα抗病毒治疗24周无应答的CHB患者60例.采用数字表法将病例随机分为3组,每组20例:实验组采用IFNα联合ADV治疗,对照组1继续使用IFNα治疗,对照组2停用IFNα改用ADV序贯治疗.比较三组患者的病毒学、血清学和生化学应答情况,并观察不良反应.应用SPSS 19.0统计软件进行数据分析.结果 治疗24周时,分别比较各组病例的HBV DNA载量、ALT水平、HBeAg滴度和HBsAg滴度,差异均无统计学意义(F=0.985,0.717,1.850和0.233,P＞0.05),且无病例发生HBeAg血清学转换.治疗48周时,实验组比对照组1有更高的HBV DNA转阴率、ALT复常率和HBeAg血清学转换率(x2=10.00,3.956和4.800,P＜0.05),但HBeAg转阴率比较差异无统计学意义(x2=0.693,P＞0.05);实验组在HBV DNA转阴率、ALT复常率和HBeAg转阴率方面与对照组2比较差异无统计学意义(x2=1.026,1.905和0.156,P＞0.05),但HBeAg血清学转换率显著高于对照组2 (x2=4.800,P＜0.05);所有病例均未发生HBsAg血清学转阴或转换,三组间HBsAg滴度差异无统计学意义(F=1.935,P＞0.05).未发现严重不良反应.结论 IFNα单药治疗24周无应答者联合ADV可获得较高的ALT复常率、HBeAg血清学转换率和HBV DNA阴转率,从总体上提高了CHB抗病毒的疗效.     

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。     

干扰素α治疗HBeAg阳性慢性乙型肝炎应答不佳的优化疗效研究

目的 观察干扰素α（IFNα）联合阿德福韦酯（ADV）和替比夫定（LdT）序贯治疗对IFNα治疗应答不佳的HBeAg阳性慢性乙型肝炎（CHB）的临床疗效.方法 选择2010年2月至2013年4月浙江省绍兴市第六人民医院收治的接受IFNα治疗24周后应答不佳的HBeAg阳性CHB患者86例.根据患者意愿分为继续单用IFNα治疗组21例,IFNα联合ADV治疗组30例,改用LdT序贯治疗组35例.采用x2检验比较三组患者治疗48周时的ALT复常率、HBV DNA低于检测值下限（500拷贝/mL）的比例、HBeAg及HBsAg血清学转换率.结果 治疗48周时,继续单用IFNα治疗组的ALT复常率为52.6％ （10/19）,低于IFNα联合ADV治疗组（86.7％,26/30）和LdT序贯治疗组（84.8％,28/33）,差异有统计学意义（x2=6.913和6.361,P＜0.05）;继续单用IFNα治疗组的HBV DNA低于检测值下限（500拷贝/mL）的比例为26.3％（5/19）,低于IFNα联合ADV治疗组（60.0％,18/30）和LdT序贯治疗组（54.5％,18/33）,差异有统计学意义（x2=11.33和3.895,P＜0.05）;继续单用IFNα治疗组没有HBeAg转阴或血清学转换,而IFNα联合ADV组和LdT序贯治疗组分别有6例（20.0％,6/30）和7例（21.2％,7/33）发生HBeAg转阴或血清学转换（x2=4.330和4.657,P ＜0.05）.三组患者均未发生HBsAg转阴或血清学转换.IFNα联合ADV治疗组与LdT序贯治疗组之间的ALT复常率、HBV DNA低于检测值下限率和HBeAg转阴或血清学转换率比较差异无统计学意义（x2=0.042,0.019和0.064,P ＞0.05）.结论 对于IFNα治疗应答不佳的HBeAg阳性CHB患者,IFNα联合ADV治疗或LdT序贯治疗可明显改善患者的肝功能和病毒学应答,两种治疗方案疗效相近.     

阿德福韦酯联合拉米夫定治疗拉米夫定耐药慢性乙型肝炎患者随机对照试验的Meta分析

目的评价阿德福韦酯（ADV）联合拉米夫定（LAM）治疗对拉米夫定耐药的慢性乙型肝炎患者的疗效及安全性。方法纳入阿德福韦酯联合拉米夫定治疗拉米夫定耐药的慢性乙型肝炎患者的随机对照试验（RCT）研究结果,对照组均为ADV单药治疗。由两名评价员独立筛查文献,进行质量评价和资料提取。使用Cochrance协作网提供的RevMan5.0软件进行Meta分析。结果 Meta分析结果显示,经过48周或48个月治疗,治疗组丙氨酸氨基转移酶（ALT）复常率均优于对照组,其OR（95%CI,P）分别为1.84（1.12～3.00,0.02）和80.29（4.18～1541.64,0.004）;治疗组HBVDNA低于检测下限的比率优于对照组,RR（95%CI,P）分别为1.22（1.06～1.39,0.004）或1.90（1.10～3.30,0.02）;两组HBeAg转阴率无显著性差异,OR（95%CI,P）为1.02（0.40～2.58,0.97）;HBeAg血清学转换率无统计学差异,RR（95%CI,P）为1.30（0.63～2.68,0.47）。ADV相关耐药发生率,治疗组显著低于对照组,OR（95%CI,P）分别为0.13（0.03～0.58,0.008）和0.07（0.01～0.40,0.003）。结论与ADV单用治疗方案相比,ADV联合LAM治疗LAM耐药的慢性乙型肝炎患者,能显著提高ALT复常率、HBVDNA低于检测下限的比率,降低ADV相关耐药发生率;HBeAg阴转率或HBeAg血清学转换率相似。ADV10mg/d长期治疗慢性乙型肝炎未出现严重不良事件,相对较为安全。     

阿德福韦酯联合苦参素胶囊治疗乙型肝炎肝硬化疗效观察

目的 观察阿德福韦酯联合苦参素胶囊治疗乙型肝炎肝硬化疗效以及对患者HBV DNA载量的影响.方法 260例乙型肝炎肝硬化患者随机分为治疗组和对照组.治疗组140例给予阿德福韦酯10 mg/次,1次/d,苦参素胶囊每次0.3 g,3次/d口服;对照组120例给予苦参素胶囊每次0.3 g,3次/d 口服.两组疗程均为48周.每12周检测1次患者肝功能、乙型肝炎病毒血清学标志物及HBV DNA载量.结果 治疗组用药48周后HBV DNA低于检测下限的比率及ALT复常率显著优于对照组.结论 阿德福韦酯联合苦参素胶囊治疗乙型肝炎肝硬化疗效较好,建议长期服用.     

阿德福韦酯致乙型肝炎肝硬化患者引发横纹肌溶解症一例

患者男,30岁,因乏力、双下肢肌痛10d,于2012年2月17日就诊,5年前曾因纳差、腹胀人院。查体：面色晦暗,肝掌、蜘蛛痣（＋）,巩膜无黄染,肝脾肋缘下未及,腹部移动性浊音（＋＋）,双下肢轻度水肿。血液生化学检查：总胆红素（TBil）10．1μmol／L,AIJT63U／L,AST83U／L,     

Asymptomatic elevation of creatine kinase in patients with hyponatremia

Elevated creatine kinase (hyper-CKemia) has been observed in small number of patients with hyponatremia. This study evaluated the features and outcomes of patients admitted with hyponatremia complicated by hyper-CKemia. Patients admitted with hyponatremia and concurrently found to have elevated creatine kinase (CK) of above 375?IU/L (male) or 225?IU/L (female), over a 5-year period were retrospectively reviewed. Those with myocardial injury (elevated CK-MB isoenzyme [CK-MB/CK percentage of >2.5%] or Troponin T [>0.02?μg/L]), traumatic or ischemic muscle damage, primary myopathic disorder, seizures prior to CK measurement or those taking medications which can cause myopathy, were excluded. Thirty-two patients with hyponatremia and hyper-CKemia were identified. All patients had no muscular symptoms or weakness. The commonest cause of hyponatremia in this cohort was related to diuretics (50%). The mean sodium level on presentation was 116.0?±?6.9?mmol/L and the median peak CK was 895.5 (interquartile range: 610.8–1691.8) IU/L. Six (18%) patients developed acute kidney injury (AKI). The length of hospital admission of the entire cohort was 8.0?±?5.8 days. Patients with hyper-CKemia in the setting of diuretic-associated hyponatremia were older and had longer hospital length of stay compared with primary-polydipsia-associated. Asymptomatic hyper-CKemia is an uncommon association with hyponatremia of various etiologies. Hyponatremia-associated hyper-CKemia can be complicated by AKI.     

Successful management of a patient with rhabdomyolysis and marked elevation of serum creatine kinase level

We experienced successful management of a patient with severe rhabdomyolysis by conservative treatment. A 41-year-old man developed Stanford-A-type acute aortic dissection and underwent an emergent replacement of the aortic root and arch. After the weaning from cardiopulmonary bypass, his left femoral artery was found non-pulsatile, probably due to extension of the aortic dissection, and femoro-femoral artery bypass surgery was added. Estimated ischemia time of the lower extremities was 7 hours. On admission to the intensive care unit (ICU), his left lower extremity showed signs of reperfusion injury accompanied with marked elevation of serum creatine kinase (12,397 IU x l(-1)) and myoglobin (19,980 ng x ml(-1)), and impaired oxygenation (a ratio of PaO2 to FIO2, 130 mmHg). We performed (1) moderately aggressive infusion treatment, (2) maintenance of hyperdynamic states using catecholamine, (3) diuresis therapy using atrial natriuretic peptide and furosemide, and (4) lung protective strategy. Although serum creatinine increased to 2.0 mg x dl(-1) on postoperative day (POD) 1, diuresis was maintained and the level of creatinine returned to normal on POD 6. He was extubated on POD 6 and discharged on POD 7. The early start of these combined therapies seems to have prevented acute renal failure without blood purification.     

高龄脊柱后凸患者胰十二指肠切除术一例

1 临床资料 患者男,83岁.因无痛性进行性黄疸3周于2012年3月14日入院.体格检查:皮肤及巩膜黄染,有散在抓痕,未触及淋巴结肿大.脊柱严重后凸畸形,Cobb法测量其角度为60°.桶状胸,心肺听诊无异常.腹上区触压不适,无反跳痛及肌紧张,肝脾肋下未触及,肝肾区无叩击痛.实验室检查:CEA11.1 μg/L,CA19-9 162.7 U/ml,TP 68.5 g/L,Alb 34.0 g/L,Ibil 122.8 μmol/L,Tbil 162.5μmol/L,GGT 470.8 U/L,ALT109.2 U/L,Hb 105.0 g/L.上腹部增强CT及MRCP检查提示肝内外胆管明显扩张,考虑壶腹部或十二指肠乳头肿瘤.十二指肠镜检查示十二指肠乳头部3 cm×3 cm菜花样占位性病变,合并溃疡,活组织病理检查提示为十二指肠乳头腺癌.胸部X线片检查:脊柱后凸畸形,右侧多发性陈旧性骨折,主动脉硬化.心电图检查未见明显异常.心脏超声检查提示主动脉瓣钙化伴轻度反流.肺功能检查提示轻度通气功能障碍.入院诊断:十二指肠乳头腺癌、梗阻性黄疸、脊柱后凸畸形.给予保肝、改善心、肺功能及营养状态等术前准备.     

Pyoderma gangrenosum at multiple sites in a post‐colostomy ulcerative colitis patient with chronic hepatitis B virus: A case report

Pyoderma gangrenosum is an uncommon ulcerative cutaneous lesion manifesting as rapidly progressing single or multiple skin ulcers. Permanent stoma in inflammatory bowel disease patients remains an independent risk of pyoderma gangrenosum. In the current report, we describe a case of pyoderma gangrenosum in a post‐colostomy ulcerative colitis patient with chronic hepatitis B. Pyoderma gangrenosum began seemingly as peristomal dermatitis that rapidly developed into painful ulcerations with subsequent appearance of sterile pustules and ulcerations in the left lower leg. The patient significantly improved after active management with prednisolone, antiviral therapy with entecavir, and wound dressings. Our case suggests that physicians and surgeons should have a high index of suspicion of pyoderma gangrenosum in post‐colostomy ulcerative colitis patients who develop peristomal dermatitis.     

Diagnostic value of creatine kinase and creatine kinase MB isoenzyme in chronic hemodialysis patients: a longitudinal study

Serial measurements of total creatine kinase (CK) and the MB isoenzyme of CK (CK-MB) were performed on 18 stable hemodialysis patients over a 36 month interval in a longitudinal study designed to examine CK and CK-MB variability. Total CK was measured by the DuPont ACA pack procedure. CK-MB was quantitated by the ACA CK-MB ion exchange pack procedure, and by electrophoresis. The mean CK level was 242 +/- 179 IU/l (+/- SD). The mean CK-MB level was approximately 8% of the total CK. Seventy-two percent of the patients had at least one elevated CK level during the course of this study. Depending upon the method of analysis, 88 to 100% of the patients had at least one elevated CK-MB level. Marked and sporadic variations in both total CK and CK-MB levels were apparent, but were not related to the assay. Patients receiving long-term intramuscular androgens had higher CK, but not CK-MB, than did hemodialysis patients not receiving these agents. Discontinuation of the intramuscular androgens for four weeks led to a fall in CK in only one of four patients. Therefore there appears to be a biological effect of exogenous androgens which may play a role in elevating CK in hemodialysis patients.     

Bilateral renal aneurysms in a chronic hepatitis B patient.

We describe a 41-year-old female with a medical history of chronichepatitis B. She was not hypertensive. Following right lowerback pain, the patient consulted at a