抗甲状腺药物所致肝损伤的诊断与治疗原则

药物治疗是甲状腺功能亢进的主要治疗方法。抗甲状腺药物可引起肝损伤,药物性肝损伤的诊断多采用排他性诊断,诊断基于病史采集、临床症状、血清生化、影像学及组织学等。药物性肝损伤可依据肝损伤严重程度分为轻度、中度、重度和致命四种等级,轻者常不必停药,但需定期监测肝功能,重者可发生肝衰竭,病死率高,若能尽早发现、及时停药,辅以合理药物治疗,可避免致命后果。抗甲状腺药物性肝损伤的治疗原则是促进肝损伤恢复、防止肝损伤重症化、慢性化和降低死亡风险。规范用药、及时监测、早期发现和早期治疗是防治抗甲状腺药物肝损伤的重要举措。     

高剂量普萘洛尔联合丙硫氧嘧啶治疗甲状腺功能亢进合并房颤患者的临床效果

目的分析高剂量普萘洛尔联合丙硫氧嘧啶治疗甲状腺功能亢进(甲亢)合并房颤患者的临床效果。方法选取2018年2月至2019年6月我院72例甲亢合并房颤患者,按随机数字表法分两组,各36例,小剂量组予以小剂量普萘洛尔联合丙硫氧嘧啶,高剂量组予以高剂量普萘洛尔联合丙硫氧嘧啶。对比两组疗效、窦性心律转复率、不良反应发生率及治疗前后心率(HR)、左心室射血分数(LVEF)、血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)。结果高剂量组总有效率91.67%(33/36)较小剂量组72.22%(26/36)高(P<0.05);治疗后,高剂量组HR较小剂量组低,LVEF较小剂量组高(P<0.05);治疗后,高剂量组血清FT3、FT4水平较小剂量组低,血清TSH水平较小剂量组高(P<0.05);高剂量组窦性心律转复率52.78%(19/36)较小剂量组27.78%(10/36)高(P<0.05);高剂量组不良反应发生率8.33%(3/36)与小剂量组5.56%(2/36)相比无显著差异(P>0.05)。结论高剂量普萘洛尔联合丙硫氧嘧啶治疗甲亢合并房颤患者效果显著,可有效改善患者心功能,并能促使甲状腺功能恢复正常,可提高窦性心律转复率,且未明显增加不良反应,具有安全性,值得临床推广应用。     

病毒性肝炎合并甲状腺功能亢进症11例临床分析

目的分析病毒性肝炎合并甲亢时的病情，探讨有效治疗方案。方法选择病毒性肝炎合并甲状腺功能亢进症11例，仅予护肝支持对症治疗9例，护肝和^131碘治疗2例。结果病毒性肝炎合并甲亢大多肝功损害明显，病情较重，其中重型肝炎5例，慢性肝炎重度4例，慢性肝炎中度2例。9例不抗甲亢治疗效果差，2例^131碘治疗病情好转。结论病毒性肝炎合并甲亢易造成肝损害及甲亢加重，不抗甲亢治疗预后差。     

甲巯咪唑与丙硫氧嘧啶治疗Graves甲状腺机能亢进症疗效比较

目的探讨甲巯咪唑与丙硫氧嘧啶治疗Graves甲状腺机能亢进症（简称甲亢）的临床疗效差异,为Graves甲亢的临床用药提供理论依据。方法选择100例Graves甲亢初诊患者随机分成两组各50例,分别采用剂量相当的甲巯咪唑与丙硫氧嘧啶治疗。于治疗前、治疗第45天、第90天采血检测血清促甲状腺素（TSH）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺素受体抗体（TRAb）、甲状腺过氧化物酶抗体（TPOAb）,比较两组各时间点TSH、FT3、FT4、TRAb、TPOAb水平的差异。结果治疗前两组TSH、FT3、FT4、TRAb、TPOAb水平无统计学差异（P均〉0.05）。治疗后与治疗前比较,两组TSH、FT3、FT4、TRAb、TPOAb水平均降低（P均〈0.05）。治疗第45天、第90天后丙硫氧嘧啶组FT3、FT4水平均高于甲巯咪唑组（P均〈0.01）。治疗后TRAb、TPOAb水平两组间差异无统计学意义（P均〉0.05）。结论甲巯咪唑治疗Graves甲亢疗效显著性优于丙硫氧嘧啶。     

几种不同治疗方法对肝炎合并甲状腺功能亢进患者的疗效研究

目的:探究几种不同治疗方法尤其是甲巯咪唑(赛治),对于肝炎合并甲亢的治疗效果;同时观察血浆置换对于该类患者肝功能恢复的临床效果。方法:将43例肝炎合并甲状腺功能亢进(甲亢)的患者按治疗方法分成不同的组,观察赛治等各种治疗方法治疗前后ALT、AST、TBil、DBil等肝功能指标的变化情况;对用赛治治疗与不进行抗甲状腺治疗的两组患者的转归进行统计学分析。结果:用赛治治疗组的患者治疗前后ALT、AST、TBil、DBil显著降低;不进行甲亢治疗与用赛治治疗甲亢者比较转归差异无显著性意义;血浆置换的患者在治疗前TBil,DBil显著高于未作血浆置换者,治疗后各项肝功能指标比较差异无显著性意义。血浆置换前后,TBil,DBil有显著变化,而不用血浆置换者ALT,AST变化显著。结论:对于肝炎合并甲亢的患者可以选用赛治治疗,对改善患者肝功能,及控制甲状腺毒症有很好的效果;对于严重患者及时进行血浆置换治疗,有利于患者肝功能的恢复。     

甲状腺功能亢进症的药物治疗

抗甲状腺药物(ATD)治疗的最佳方案要从药物的选择、具体剂量、给药方式、服药疗程、是否合用左旋甲状腺素(L-T4)、免疫抑制剂及其他影响患者缓解率的因素等多方面综合考虑.除妊娠期妇女外,目前大多数学者将甲硫咪唑(MMI)列为治疗甲状腺功能亢进症(甲亢)的首选药物.药物具体起始剂量可根据患者甲状腺的大小、甲亢病情的严重程...     

小剂量甲巯咪唑治疗亚临床甲状腺功能亢进症合并阵发性房颤的临床观察

应用小剂量甲巯咪唑+比索洛尔治疗27例亚临床甲状腺功能亢进症合并阵发性房颤患者,治疗前后均接受多普勒超声心动仪、24 h动态心电图检查,放射免疫法测定血清FT3、FT4及TSH,观察期3个月,结果显示治疗后患者左室舒张功能明显改善(P<0.01),窦性心律维持率高,甲减发生率低,提示小剂量甲巯咪唑治疗亚临床甲状腺功能亢进症合并阵发性房颤安全有效.

Abstract：

Twenty-seven patients with subclinical hyperthyroidism(SH)complicated by paroxysmal atrial fibrillation(PAF)were treated with methimazole plus bisoprolol.All patients were examined by Doppler echocardiogram and 24 h ambulatory electrocardiograms before and 3 months after treatment.Serum FT3,FT4,and TSH levels were measured with RIA.The results showed that low-dose methimazole therapy could improve the left ventricular diastolic function(P < 0.01)and help maintain sinus rhythm.The incidence of subclinical hypothyroidism was low.Low-dose methimazole was effective and safe in patients with SH complicated by PAF.     

抗甲状腺药物对131Ⅰ治疗甲状腺功能亢进症疗效的影响

^131Ⅰ是治疗甲状腺功能亢进症（甲亢）的主要药物之一，治疗前应用硫氧嘧啶类药物如丙硫氧嘧啶可能会降低^131Ⅰ治疗甲亢的治愈率，咪唑类药物如甲巯咪唑则不会影响其疗效。^131Ⅰ治疗甲亢后应用丙硫氧嘧啶或甲巯咪唑对^131Ⅰ疗效的影响尚有争议之处。抗甲状腺药物影响^131Ⅰ疗效的机理可能在于改变了^131Ⅰ的有效半衰期和（或）甲状腺对^131Ⅰ的摄取率。     

血浆置换治疗甲状腺功能亢进合并戊型病毒性肝炎三例临床分析

甲状腺功能亢进症(简称甲亢)患者较多合并肝损害,包括甲亢性肝损害、病毒性肝损害、药物性肝损害及非酒精性脂肪性肝炎等,症状多较严重,治疗棘手.在其合并病毒性肝损害中,以合并戊型病毒性肝炎(简称戊肝)多见.当甲亢合并严重肝损害时,抗甲状腺药物、手术及131I治疗均有一定的局限性,而血液净化已在治疗中显示一定的价值[1].现对我院2000～2011年收治的12例甲亢合并戊型肝炎患者的临床资料进行回顾性分析,总结其中2例合并重型肝炎及1例胆汁淤积严重患者采用血浆置换治疗的临床疗效.     

抗甲状腺药物与哺乳

长久以来国内外的医生们一直建议在服用抗甲状腺药物 (ATDs)治疗甲状腺功能亢进症 (甲亢 )期间最好不要哺乳 ,如果一定需要哺乳 ,应选用丙基硫氧嘧啶 (PTU) ,而不要选用甲巯咪唑 (MMI)。新近的研究结果显示 ,无论是在服用PTU还是在服用MMI治疗期间哺乳 ,无论是在服用小剂量ATDs还是服用大剂量ATDs期间哺乳 ,对喂养婴幼儿的甲状腺功能和智力发育都未产生不良影响。但报道仅局限在几个研究中心 ,还需要大样本、多中心、跨地域的协作研究 ,以进一步证实目前的研究结果。     

抗甲状腺药物不良反应的再认识

抗甲状腺药物(ATD)是治疗甲状腺功能亢进症主要手段,其不良反应备受学者们关注.ATD常用药物为丙基硫氧嘧啶(PTU)和甲巯咪唑(MMI).总的来说,ATD治疗是安全且有效的,但其临床不良反应亦较常见,如对肝脏、血液系统的毒性作用、抗中性粒细胞胞浆抗体相关性肺小血管炎、低血糖、变态反应、肌肉损伤等,一般程度较轻,如能及时停用ATD则能够自行恢复,但亦可出现少见、严重的副作用,可能存在潜在致命的危险,故需引起临床医生的重视.MMI与PTU比较,其不良反应显著低于PTU,且前者大多具有剂量依赖性,后者与药物的剂量无显著相关.此外,PTU的肝毒性强于MMI,甚至可能发生致命性肝损伤和肝衰竭,在儿童甲亢治疗中推荐首选MMI.

Abstract：

Antithyroid drugs(ATD)is the main treatment for hyperthyroidism and its adverse reactions have been much concerned by physicians. Methimazole(MMI)and propylthiouracil(PTU)are the two common antitithyroid drugs used currently. Generally, the ATD are safe and effective, though their clinical adverse reactions are also relatively common. The toxic effects include liver damage and leukocytopenia, antineutrophil cytoplasmic antibody-associated pulmonary small-vessel vasculitis, hypoglycemia, allergic reactions, muscle impairment,and so on. They are usually reversible and disappear spontaneously when the drug is discontinued. However,the serious rare side effects can also occur and there may have potentially deadly threatening effects which need to be cautious for the clinicians. MMI is usually preferred over PTU because it has significantly fewer side effects. And unlike the dose-dependent side effects of MMI, there has no significant correlation between adverse reaction and drug dosage in using PTU. Moreover, PTU has more severe hepatotoxity than MMI, even fatal liver impairment and liver failure. The risk of liver damage from PTU is an important concern, particularly in children. For this reason, MMI is the first choice for treating children with hyperthyroidism.     

Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs: A long‐term followup study

Objective

To test whether antineutrophil cytoplasmic antibodies (ANCA) and ANCA‐associated vasculitis (AAV) are not only induced during treatment with antithyroid drugs, but can also become evident when medication has been ceased, possibly after years.

Methods

Patients who visited our hospital for the treatment of hyperthyroidism were included (n = 207). Treatment consisted of antithyroid medications, radioactive iodide, thyroidectomy, or a combination of these treatment options. Patients were retested 3–6 years later to evaluate long‐term effects of antithyroid drugs. Patients were tested for the presence of ANCA and, if positive, evaluated for the presence of AAV.

Results

Of 209 patients with hyperthyroidism, 12 patients (6%) were positive for myeloperoxidase‐ (MPO‐), proteinase 3‐, or human leukocyte elastase‐ANCA. Seventy‐seven of 209 patients were retested; 1 patient who had not been treated with antithyroid drugs had developed MPO‐ANCA. In 3 of 6 patients previously positive, ANCA could still be detected. The presence of ANCA was highly associated with treatment with antithyroid drugs (odds ratio 11.8 [95% confidence interval 1.5–93.3]). Of 13 patients with a positive ANCA result on enzyme‐linked immunosorbent assay, AAV with glomerulonephritis was diagnosed in 4 (31%).

Conclusion

The presence of ANCA with or without vasculitis is associated with previous treatment with antithyroid drugs, possibly after years.

     

重型病毒性肝炎并发低血糖临床分析

目的 探讨重型病毒性肝炎患者血糖低于正常值的临床特点及防治对策。方法 回顾性分析2002年6月至2004年4月住院重型病毒性肝炎患者空腹血糖,对其在治疗过程中的变化做动态分析。结果 92例重型病毒性肝炎患者,空腹血糖低于正常67例(72．8％),其中死亡56例(68．7％),与其他并发症并存的发生率较高。动态分析空腹血糖降低患者治疗过程中血糖变化有三种形式,空腹血糖持续多次减低患者死亡率亦较高。空腹血糖减低患者中,仅部分呈典型低血糖症表现,死亡率最高。结论 重型病毒性肝炎常并发空腹血糖减低者的死亡率高。在积极综合治疗后,持续多次空腹血糖减低患者死亡率较高。呈低血糖症患者死亡率最高。血糖减低的治疗需要采取综合措施,个体化原则。     

Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus （HBV）/ hepatitis C virus （HCV） infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an ＂automatic pilot＂ for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients.     

Update on the management and treatment of viral hepatitis

This review aims to summarize the current evidence on the treatment of viral hepatitis, focusing on its clinical management. Also, future treatment options and areas of potential research interest are detailed. PubMed and Scopus databases were searched for primary studies published within the last ten years. Keywords included hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus, hepatitis D virus (HDV), hepatitis E virus, and treatment. Outcomes reported in the studies were summarized, tabulated, and synthesized. Significant advances in viral hepatitis treatment were accomplished, such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A, hepatitis B, and hepatitis E vaccination. Drugs that cure hepatitis B, going beyond viral suppression, are so far unavailable; however, targeted antiviral drugs against HBV (immunomodulatory therapies and gene silencing technologies) are promising approaches to eradicating the virus. Ultimately, high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems. The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B, albeit further investigation is required. Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.     

病毒性肝炎患者血中一氧化碳的测定及临床意义

目的了解不同程度病毒性肝炎患者静脉血中碳氧血红蛋白(COHb)的变化并分析其临床意义,探讨一氧化碳(CO)在肝脏疾病中的作用。方法采用双波长分光光度法测量不同程度病毒性肝炎患者血中COHb的浓度,并与正常对照组进行比较,对各组间COHb水平进行统计学分析。结果病毒性肝炎患者组血中COHb水平较正常对照组有显著性差异,病毒性肝炎重度组COHb水平与血中丙氨酸氨基转移酶(ALT)统计分析显示具有正相关性。结论不同程度病毒性肝炎患者血中COHb水平的改变提示CO在肝脏炎性疾病中发挥一定的作用。     

Hepatitis B and hepatitis C viral infections in patients with chronic lymphocytic leukemia

BACKGROUND:

Whether chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections contribute to the pathogenesis and/or course of chronic lymphocytic leukemia is unclear.

OBJECTIVE:

To document the prevalences of HBV and HCV infections in chronic lymphocytic leukemia patients, and to determine whether infected patients experience more aggressive disease than those without infection.

METHODS:

Patient sera were screened for antibodies to HBV core antigen and HCV (anti-HCV) using ELISA; both sera and peripheral blood lymphocytes were further tested (regardless of antibody results) for HBV-DNA and HCV-RNA using real-time polymerase chain reaction. Prognostic markers for chronic lymphocytic leukemia included Rai stage, IgV_H mutational status, β₂-microglobulin levels, Zap-70 and CD38 status.

RESULTS:

Fourteen of 222 (6.3%) chronic lymphocytic leukemia patients and two of 72 (2.8%) healthy controls tested positive for previous or ongoing HBV infection (OR 2.4 [95% CI 0.5 to 7.7]; P=0.25) while four of 222 (1.8%) chronic lymphocytic leukemia patients and one of 72 (1.4%) controls tested positive for HCV markers (OR 1.3 [95% CI 0.2 to 6.4]; P=0.81). The levels and distribution of the various indicators of aggressive chronic lymphocytic leukemia disease were similar among HBV- and HCV-infected and uninfected patients. Survival times were also similar. Occult HBV and HCV infection (HBV-DNA or HCV-RNA positive in the absence of diagnostic serological markers) were uncommon in chronic lymphocytic leukemia patients (0.5% and 1.8%, respectively).

CONCLUSIONS:

The results of the present study do not support the hypothesis that HBV or HCV infections play an important role in the pathogenesis or course of chronic lymphocytic leukemia.