慢性乙型肝炎抗病毒药物治疗的评价

本文对慢性乙型肝炎抗病毒芗治疗的应答反应作一评价。单一治疗：干扰素－α：治疗前血清ALT水平升高者，30％－40％患者对治疗呈完全应答反应，HBV携带者或免疫耐受者对治疗无效；拉米夫定：能明显抑制BV复制，但HBeAg转阴者少，停药后HBV－DNA迅速反跳，延长治疗时间可引起YMDD变异；治疗前血清ALT水平在正常上限5倍以上者，60％患者呈完全应答反应；法昔洛维：抑制HBV复制作用弱，且较短暂，长期用药可引起基因突变，发生耐药性。联合治疗：拉米夫定－干扰素、拉米夫定－法昔洛维／阿地洛维、强的松－拉米夫定／干扰素等联合应用。联合治疗可降低HBV负荷，改善CD4＋－T细胞功能及减少耐药性。     

阿德福韦酯治疗e抗原阳性慢性乙型肝炎的疗效预测指标探讨

目的 评价HBeAg阳性慢性乙型肝炎患者治疗前ALT、HBeAg、HBV DNA水平以及治疗12周时HBV抑制程度对阿德福韦酯(ADV)治疗52周患者疗效的预测价值.方法 98例HBeAg阳性成年慢性乙型肝炎患者进入研究.筛选时血浆HBV DNA定量≥1×106拷贝/ml,血清ALT水平1.5～10倍正常值上限(ULN).患者接受ADV 10mg/d,共52周治疗.定期随访,检测血清HBV标志物及HBV DNA.比较不同基线ALT、HBeAg、HBV DNA水平以及治疗12周时不同血清HBV DNA水平患者治疗52周时的疗效差异. 结果 ADV治疗52周时,血清HBV DNA＜103拷贝/ml的患者,基线ALT＞5 × ULN者(72.7%)高于ALT＜2×ULN者(38.0%),P＜0.05;基线HBeAg≤350 s/co者(66.7%)高于HBeAg＞350 s/co者(30.2%),P＜0.01;基线HBV DNA≤108拷贝/ml者(53.0%)高于血清HBV DNA＞108拷贝/ml者(34.4%),P＜0.05.52周HBeAg血清学转换率在基线HBeAg水平≤350 s/co者和HBeAg＞350 s/co者分别为42.2%和7.5%(P＜0.01).治疗12周时血清HBV DNA＜103拷贝/ml、103～105拷贝/ml和＞105拷贝/ml组患者,52周时血清HBV DNA＜103拷贝/ml的比例分别为82.6%、57.1%和17.5%,组间差异均有统计学意义(P值均＜0.05);3组患者HBeAg血清学转换率分别为52.2%、25.7%和5.0%,组间差异均有统计学意义(P值均＜0.05);3组患者52周ALT复常率分别为100%、83%和75%,血清HBV DNA＜103拷贝/ml组高于＞105拷贝/ml组(P＜0.05).相关分析显示,治疗52周时的血清HBV DNA水平及HBeAg血清转换与治疗12周时血清HBV DNA水平中度相关(P＜0.01).结论 HBeAg阳性慢性乙型肝炎患者ADV治疗12周时血清HBV DNA水平对治疗52周的疗效的预测价值优于基线指标,治疗12周时血清HBV DNA＜103拷贝/ml者,52周时能达到更佳的疗效.     

拉米夫定和泛昔洛韦联合治疗慢性乙型肝炎

背景现有的抗病毒药物单用均难以完全清除乙型肝炎病毒(HBV)感染。体外研究证明,拉米夫定(LMD)和Penciclovir[泛昔洛韦(FCV)的活性代谢物]联合应用对HBV复制具有相加或协同抑制作用。目的研究LMD和FCV联合疗法对慢性乙型肝炎感染的疗效。方法21例慢性乙型肝炎患者在联合治疗前曾接受6个月以上的LMD治疗,但均未取得改善。所有患者均为血清乙型肝炎表面抗原(HBsAg)阳性,具有高水平HBVDNA和丙氨酸转氨酶(ALT),17例乙型肝炎e抗原(HBeAg)阳性。12例HBeAg阳性患者的诊断得到组织学证实。联合用药方案为治疗期LMD100mgqd+FCV500mgtid口服4个月;随访期(5～10个月)单用LMD,剂量同前。结果21例患者的血清HBVDNA水平在治疗前为1×10819±0.58copies/ml,治疗期末为1×104.55±1.18copies/ml,随访期为1×105.25±1.82copies/ml(P＜0.01);ALT水平从联合治疗前的225U/L±110U/L降至治疗期末的79U/L±50U/L和随访期的81U/L±48U/L(P＜0.01)。17例HBeAg阳性患者中,8例(47.1％)发生HBeAg/抗HBe血清转换;与此同时,血清ALT均正常化,HBVDNA降至1×104copies/ml以下(P＜0.01)。4例HBeAg阴性患者中,3例HBVDNA降至1×104copies/ml以下,ALT同时降至正常或明显降低。共有2例患者在随访期复发,其中1例HBeAg再次转为阳性,但HBVDNA和ALT均低于治疗前水平。10例接受肝活检复查的患者中,分别有8例(80％)和4例(40％)肝脏炎症活动度和纤维化程度得到改善(P＜0.05),无一例病变加重。结论LMD和FCV有协同或相加性抗HBV作用,可作为慢性乙型肝炎可供选择的治疗方法。     

拉米夫定治疗HBeAg阳性慢性乙型肝炎患者7年结果总结

目的 评估拉米夫定治疗乙型肝炎5年的长期疗效和安全性,以及对病毒变异发生率的影响.方法 429例HBsAg,HBeAg阳性的慢性乙型肝炎患者,先按3:1随机双盲分成拉米夫定组和安慰剂组,治疗共12周,以后所有患者均服拉米夫定100 mg/d,共5年.结果 服药治疗5年后,血清HBV DNA仍持续降低,在YMDD变异患者中则增高,中位值为107.5 Meq/nd.HBeAg阴转率和HBeAg/抗Hbe血清转换率分别为28.6%和27.5%.与治疗前ALT水平有显著关系.治疗前ALT基础值＞2×ULN(正常值上限)和＞5×ULN者,5年时HBeAg阴转率和血清转换率均为50%和67%.治疗前ALT增高的患者,5年治疗后,ALT的复常率为58%,治疗前ALT正常的患者,67.0%仍正常.1,2,3,4和5年的YMDD变异率分别为12.1%,49.7%,70.5%,67.0%和70.8%.发生变异后,HBV DNA大多仍可有一定程度抑制,在基线以下少部分可回升.在YMDD变异患者,继续有HBeAg阴转和血清转换,分别为18.4%和17.8%,低于非变异组患者.疗程中ALT增高＞5×ULN有22例,其中变异者16例,非变异者6例,经处理后均缓解.在5年治疗期间,不良反应24.8%.结论 长期应用拉米夫定可持久抑制HBV复制和促进血清转换,耐受性和安全性好,选择适合的患者,可取得最佳疗效.     

替比夫定治疗新疆慢性乙型肝炎患者疗效、安全性及影响因素分析

目的观察替比夫定(Telbivudine)治疗慢性乙型肝炎的疗效并评价安全性,探讨影响替比夫定治疗效果的因素。方法采用替比夫定治疗118例慢性乙型肝炎患者,分别于治疗前行基因型检测及治疗前后24、52、96周进行病毒学、血清学及生化学指标及乙肝病毒基因耐药的检测,探讨24周HBV DNA水平与52周、96周抗病毒疗效的关系、影响替比夫定治疗效果的因素及替比夫定治疗的安全性。结果 118例患者应用替比夫定治疗96周时,HBV DNA不可测率、ALT复常率、HBeAg转阴率、HBeAg血清转换率和耐药率分别为81.4%、79.7%、49.2%、37.3%、1.7%;HBV DNA300 copies/ml的患者HBV DNA不可测率、ALT复常率、HBeAg转阴率、HBeAg转换率显著高于HBV DNA≥300 copies/ml的患者,差异有统计学意义(P0.05);基线ALT水平≥5倍ULN组患者HBV DNA不可测率、ALT复常率、HBeAg转阴率、HBeAg转换率均高于2-5倍ULN组的患者(P0.05);基线HBV DNA中低载量组的HBV DNA不可测率、ALT复常率、HBeAg转换率显著高于高载量组的患者(P0.05);D基因型的HBeAg转阴率与HBeAb阳转率均高于B、C基因型,但三组之间无统计学差异(P0.05),HBeAg阴性组ALT复常率、HBeAg转阴率、HBeAg转换率高于HBeAg阳性患者(P0.05)。观察期间仅有2例患者出现耐药,曾有27例检测血清肌酸激酶升高,无严重不良事件导致停药发生。结论替比夫定可迅速有效抑制HBV DNA复制,使ALT复常、HBeAg转阴、HBeAg血清转换且耐药发生率低,安全性良好,是一种安全有效的抗病毒药物。治疗24周HBV DNA下降幅度能较好预测治疗第52周、96周的疗效,高ALT水平、中低载量HBV DNA、HBeAg阴性、D基因型患者疗效可能更好,建议大样本、多中心临床研究。     

替比夫定治疗HBeAg阳性慢性乙型肝炎的疗效及相关预测因子的Logistic回归分析

目的观察替比夫定（LdT）治疗HBeAg阳性慢性乙型肝炎（CHB）患者3年的疗效,应用Logistic回归探讨HBeAg血清学转换的预测因子。方法收集58例采用LdT治疗的HBeAg阳性CHB患者,分析其性别、年龄、基线ALT水平、基线HBV DNA载量、基线HBeAg和HBsAg滴度与治疗3年时ALT复常率、HBV DNA阴转率、HBeAg阴转率和HBeAg血清转换率的相关性;采用Logistic回归分析HBeAg血清转换的相关因素。结果治疗3年时ALT复常率为84.48%,HBV DNA阴转率为70.69%,HBeAg阴转率为50.00%,HBeAg血清转换率为43.10%。与ALT≤2倍正常值上限（2×ULN）相比,基线ALT〉5×ULN的患者HBeAg转换率显著增高（P〈0.05）;与HBeAg≤100（S/CO）组相比,基线HBeAg〉200 S/CO的患者HBeAg的阴转率和血清转换率均显著下降（P〈0.05）;与HBV DNA≤6 log拷贝/ml组相比,HBV DNA〉7 log拷贝/ml的患者HBV DNA转阴率、HBeAg转阴率和HBeAg转换率下降显著（P〈0.05）;患者性别、年龄及基线HBsAg滴度对以上疗效指标无影响（P〉0.05）。多因素Logistic回归分析发现仅基线HBeAg滴度低的患者更易出现HBeAg血清学转换。结论 LdT能有效恢复肝功能,抑制HBV复制和提高HBeAg血清转换;基线HBeAg滴度可预测LdT治疗HBeAg阳性CHB患者的HBeAg血清转换率。     

拉米夫定治疗慢性乙型肝炎的临床观察

目的研究拉米夫定治疗慢性乙型肝炎的疗效。方法慢性乙型肝炎患者以治疗前ALT水平分为A、B两组。A组32例,HBsAg、HBeAg和HBV DNA阳性,ALT在6-20×ULN(正常值上限)和B组32例,HBsAg、HBeAg和HBVDNA阳性,ALT在2-5×ULN。两组患者均单用拉米夫定,观察用药后第3天、7天、10天1、5天3、0天、60天、90天、52周患者血清和HBV DNA定量变化。结果治疗90天后A、B两组的HBV DNA累计阴转率分别为90.6%(29/32)和71.9%(23/32)。治疗52周后,A、B两组的HBeAg阴转率分别为65.6%(21/32)4、0.6%(13/32),P<0.05。HBeAg/抗-HBe转换率分别为34.4%(11/32)、15.6%(5/32),P<0.05。在治疗后30天内A、B两组均存在不同程度的ALT反跳,A组ALT反跳的幅度高于B组。B组ALT出现反跳的峰值迟于A组。结论拉米夫定能强烈抑制HBV DNA的复制。治疗前ALT的水平和治疗后ALT的反跳幅度及峰值出现的迟缓极大可能反映机体对拉米夫定治疗后诱发的免疫应答强度,并与持久疗效有关。     

恩替卡韦治疗高ALT水平HBeAg阳性慢性乙型肝炎疗效观察

目的观察恩替卡韦治疗高ALT水平HBeAg阳性慢性乙型肝炎（CHB）患者的疗效。方法 60例HBeAg阳性的CHB患者以ALT为依据分为低ALT组（ALT在2倍ULN与10倍之间）和高ALT组（ALT在10倍ULN与20倍之间）,给予恩替卡韦0.5mg/d,观者治疗48周时的应答情况（HBV DNA阴转率,HBeAg/抗-HBe血清转换率,HBsAg/抗-HBs血清转换率和ALT复常率）。结果治疗48周时,高ALT组HBV DNA阴转率为95.0%,低ALT组为75.0%,差异有统计学意义（P=0.0225）;低ALT组HBeAg阴转率、HBeAg血清学转换率、HBsAg阴转率、HBsAg血清学转换率依次为25.0%、25.0%、0.0%、0.0%,均明显低于高ALT组的55.0%、45.0%、15.0%、15.0%,差异有统计学意义（P=0.0184,0.0302,0.0015,0.0012）;高ALT组中有3例出现HBsAg阴转,3例出现了HBsAb;低ALT组中没有出现HBsAg阴转及血清学转换。48周时两组患者ALT复常率、病毒学反弹、对恩替卡韦耐药及药物不良反应水平相似。结论高水平ALT是恩替卡韦治疗应答较好的预测因子。     

阿德福韦酯联合聚乙二醇干扰素α-2a治疗高病毒载量慢性乙肝的疗效观察

目的观察阿德福韦酯(ADV)联合聚乙二醇干扰素α-2a(Peg-IFNα-2a)治疗高病毒载量HBeAg阳性慢性乙型肝炎(CHB)的疗效。方法 73例HBV DNA≥1×107copies/ml的HBeAg阳性慢性乙型肝炎患者分为3组:联合治疗组25例,ADV治疗组24例和Peg-IFNα-2a治疗组24例,疗程为48周。对比分析在治疗48周时的HBsAg血清转换率、HBeAg血清转换率、ALT复常率和HBV DNA转阴率。结果联合治疗组HBeAg血清转换率明显高于ADV治疗组和Peg-IFNα-2a治疗组(P<0.05),联合治疗组ALT复常率明显高于Peg-IFNα-2a治疗组(P<0.05),联合治疗组HBV DNA转阴率显著高于Peg-IFNα-2a治疗组(P<0.05)。结论阿德福韦酯联合Peg-IFNα-2a治疗高病毒载量HBeAg阳性慢性乙型肝炎疗效优于单药治疗。     

慢性乙肝患者拉米夫定治疗前后肝脏病理变化

拉米夫定(LMD)是新一代的核苷类抗病毒药物，临床实验证明每日口服100mg治疗慢性乙型肝炎具有明显抑制乙型肝炎病毒(HBV)复制的作用，患者血清内HBV水平显著降低，丙氨酸转氨酶(ALT)恢复正常伴有肝组织学坏死、炎症的减轻，部分患者HBeAg转阴和出现HBeAg／抗-HBeAb血清转换。但是，LMD是否可以有效减轻慢性乙型肝炎患者的肝组织损伤，还鲜有报道。2000年3月至2002年12月，我们应用LMD对30例慢性乙型肝炎患者进行治疗，观察其肝组织变化。     

Therapy with budesonide in patients with refractory sprue

INTRODUCTION: Refractory sprue (RS) is a rare malabsorption syndrome, which often requires long-term corticosteroid treatment. Locally acting budesonide could replace systemic corticosteroid therapy and reduce toxicity in patients with RS. Aims: To evaluate the efficacy and toxicity of budesonide in patients with RS. PATIENTS AND METHODS: Clinical and histological data from patients with RS who received budesonide were analyzed. RS was defined as villous atrophy and malabsorption in spite of a strict gluten-free diet persisting for >6 months or requiring earlier therapeutic intervention. RESULTS: We identified 9 patients (1 with autoimmune enteropathy, 4 with RS type I without and 3 with RS type II with signs of early T cell lymphoma and 1 with CD4-positive sprue-like intestinal T cell lymphoma), who received 9 mg/day of budesonide (range 6-12) for 24 months (1-60), and 7 of whom had an initial treatment with 40 mg/day of prednisolone (30-60) for 4 months (1-144). The initial body mass index was 18 (13.1-22.8) and increased similarly under prednisolone [21.5 (14.9-26.7), p < 0.05] and budesonide therapy [21 (18-27.2), p < 0.05]. The stool frequency per day also decreased similarly from 6 (2-8) to 2 (1-3) and 2 (1-5), each p < 0.05, under prednisolone and budesonide therapy, respectively. Two patients with RS type II did not respond and 7, including all 4 with RS type I, were clinically stable with budesonide therapy. Skin fragility in 1 patient was the only adverse effect of budesonide therapy. CONCLUSIONS: Budesonide may be an effective treatment option in patients with RS type I, which can stabilize the clinical condition similar to prednisolone.     

Gammagraphy with sucralfate labelled with technetium in esophagitis

In previous studies it has been reported that, after being labeled with technetium, sucralfate, an useful drug in peptic diseases, can be used to detect peptic lesions of the digestive tract. In this work we report our experience with this technique in the diagnosis of esophagitis. 25 studies (11 controls and 14 patients) were undertaken. Sucralfate scintigraphy was normal in the 11 control studies, and abnormal in 10 out of 14 patients. Scintigraphy was abnormal in peptic as well as caustic lesions.     

Mental disorders in patients with obesity in comparison with healthy probands

OBJECTIVE: Findings concerning the association of obesity and mental disorders are inconsistent. The present epidemiological study investigates adjusted 4-week, 12-month, and lifetime prevalence rates of mental disorders in obese individuals compared with physically healthy probands and overweight individuals. Correlates of the associations are examined. METHODS: Prevalence rates were calculated from two large epidemiological surveys from both the general population of Germany and inpatient centers. The surveys investigated subjects with obesity (n=910) and overweight (n=1550), as well as physically healthy probands (n=495). The prevalence rates were based on the Munich-composite international diagnostic interview, a standardized interview for the assessment of mental disorders. Correlates of mental disorders in obese individuals were assessed using self-report questionnaires and medical examinations. RESULTS: The adjusted odds ratios (OR) of obese inpatients and obese patients from the general population were significantly elevated in comparison with healthy probands for the 4-week (OR: 2.2; 2.3), 12-month (OR: 1.8; 2.7) and lifetime (OR: 1.4; 2.0) periods. Prevalence rates of overweight individuals were below those of obese individuals. Mood, anxiety and somatoform disorders were most frequent. In particular, sex, marital status and comorbid musculoskeletal diseases proved to be correlates of an increased risk for mental disorders in obese individuals. The presence of comorbid mental disorders was associated with significantly increased health care use and lower quality of life. CONCLUSIONS: There is a strong relationship between obesity and mental disorders. A future task is to improve care of mental disorders in patients with obesity.     

Changes in coagulation parameters with exercise in patients with classic hemophilia

Vigorous exercise is known to increase VIII:C and VIIIR:Ag levels transiently in normal individuals. Although exercise programs are frequently advocated in the management of hemophilia, the effects of exercise on coagulation parameters in these patients have not been well studied. Eleven hemophiliacs were exercised on a bicycle ergometer to maximum voluntary effort as evidenced by an increase in pulse, blood pressure, and plasma catecholamine (norepinephrine and epinephrine) levels. The effects of this exercise on coagulation parameters, including functional and antigenic components of the factor VIII molecule, were determined. The entire group demonstrated a decrease in mean prothrombin time (11.7 to 11.2 sec). Four mild hemophiliacs demonstrated an increase in mean VIII:C (14.5% to 17.3%), and VIII:CAg (12% to 17.8%). Changes in VIII:C and VIII:CAg were not noted in the seven severe hemophiliacs. Both severe and mild patients demonstrated significant changes in fibrinogen, factor II, and factor VII after exercise. This study indicates that submaximal exercise modifies coagulation parameters in patients with hemophilia.     

Metabolic remission with octreotide in patients with insulinoma

Abstract. Objectives . The efficacy of octreotide was studied in a group of patients with biochemical evidence of insulinoma. Design . A phase-II study Setting . A university department of internal medicine. Subjects . Seven patients with biochemical evidence of insulinoma and without metastatic lesions. Intervention . Daily treatment with octreotide, a somatostatin analogue, mainly within the dosage of 100–300 μg day^-1. The treatment was continued in patients with biochemical evidence of response or until surgery was undertaken. Main outcome . Five patients avoided hypoglycaemic symptoms and had normalization of blood glucose values for a median of 15+ months (range 0.2–54 months). Two did not improve metabolically. The treatment was well tolerated and had no deleterious effects on blood glucose regulation. Conclusion . Octreotide seems to be a promising treatment for many of the patients with insulinoma who are not suitable for surgery.     

Polymyositis-like syndrome with rhabdomyolysis in association with brucellosis

Diffuse myositis with progression to rhabdomyolysis has been reported in association with wide range of viral infections. We report a case of polymyositis-like syndrome complicated by rhabdomyolysis secondary to brucellosis. This case report thus contributes yet another atypical presentation to a disease already infamous for its protean manifestations.