布地奈德与泼尼松分别联合硫唑嘌呤治疗自身免疫性肝炎

目的比较布地奈德联合硫唑嘌呤与泼尼松联合硫唑嘌呤治疗自身免疫性肝炎(AIH)的疗效。方法选择宝鸡市中心医院2015年1月至2018年1月收治的90例AIH患者,随机分为布地奈德组联合硫唑嘌呤与泼尼松组联合硫唑嘌呤,各45例。2组均连续治疗2年。比较2组临床总缓解率、治疗前后的血清ALT、AST、ALP、γ-GT水平与不良反应总发生率。结果布地奈德组临床总缓解率88.89%(40/45),显著高于泼尼松组71.11%(32/45)(P<0.05)。2组治疗2年后的血清ALT、AST、ALP、γ-GT水平均较治疗前显著下降(P<0.05)。布地奈德组治疗后的血清ALT、AST、ALP、γ-GT水平分别为(27.42±5.36)U/L、(29.97±4.52)U/L、(88.11±14.32)U/L、(49.52±7.62)U/L显著低于泼尼松组(P<0.05)。布地奈德组治疗期间不良反应总发生率15.56%(7/45),显著低于泼尼松组35.56%(16/45)(P<0.05)。结论布地奈德联合硫唑嘌呤治疗AIH可获得更高的缓解率,更明显的生物化学指标改善,且不良反应更少,效果优于泼尼松联合硫唑嘌呤。     

Failure of budesonide in a pilot study of treatment-dependent autoimmune hepatitis

BACKGROUND & AIMS: Budesonide has a high hepatic first-pass clearance and metabolites virtually devoid of glucocorticoid activity. Our goals were to assess budesonide in patients with treatment-dependent autoimmune hepatitis and to determine if efficacy and safety justified a controlled trial. METHODS: Ten patients who were dependent on continuous treatment to prevent exacerbation of their disease were treated with budesonide, 3 mg thrice daily. RESULTS: Laboratory indices did not improve significantly during 5 +/- 1 months of therapy (range, 2-12 months). Three patients entered clinical and biochemical remission; 2 of them achieved histologic remission. Seven patients either deteriorated during therapy or became drug intolerant. Withdrawal symptoms complicated conversion from prednisone to budesonide treatment, and every patient developed at least 1 side effect. Lumbar spine density decreased in 2 patients, and femur density decreased in 2 patients, including 1 with lumbar spine changes. However, mean bone densities actually increased slightly in the entire group. CONCLUSIONS: Budesonide therapy was associated with a low frequency of remission and high occurrence of treatment failure and side effects in treatment-dependent autoimmune hepatitis. Findings did not support the need for a controlled treatment trial in this select population.     

自身免疫性肝炎的临床诊治

自身免疫性肝炎(AIH)是由异常自身免疫反应介导的肝实质炎症性病变,以高丙种球蛋白血症、血清自身抗体阳性和对免疫抑制治疗应答为特点[1].在环境因素、免疫耐受失衡和遗传易感状态的共同作用下,机体出现T淋巴细胞介导的针对肝抗原的异常免疫攻击,进而导致肝内进行性炎症坏死和纤维化过程.     

Advances in the current treatment of autoimmune hepatitis

Current treatment strategies for autoimmune hepatitis are complicated by frequent relapse after drug withdrawal, medication intolerance, and refractory disease. The objective of this review is to describe advances that have improved treatment outcomes by defining the optimum objectives of initial therapy, managing relapse more effectively, identifying problematic patients early, and incorporating the new pharmacological interventions that have emerged as frontline and salvage therapies. Initial corticosteroid treatment should be continued until serum aminotransferase, γ-globulin, and immunoglobulin G levels are normal, and maintenance of this improvement for 3-8 months before liver tissue assessment. Improvement to normal liver tissue is the ideal histological result that justifies drug withdrawal, but it is achievable in only 22 % of patients. Minimum portal hepatitis, inactive cirrhosis, or minimally active cirrhosis is the most common treatment end point. Relapse after drug withdrawal warrants institution of a long-term maintenance regimen, preferably with azathioprine. Mathematical models can identify problematic adult patients early, as also can clinical phenotype (age ≤ 30 years and HLA DRB1 03), rapidity of treatment response (≤ 24 months), presence of antibodies to soluble liver antigen, and non-white ethnicity. The calcineurin inhibitors (cyclosporine and tacrolimus) can be effective in steroid-refractory disease; mycophenolate mofetil can be corticosteroid-sparing and effective for azathioprine intolerance; budesonide combined with azathioprine can be effective for treatment-na?ve, non-cirrhotic patients. Standard treatment regimens for autoimmune hepatitis can be upgraded without adjustments that require major new expertise.     

Difficult treatment decisions in autoimmune hepatitis

Treatment decisions in autoimmune hepatitis are complicated by the diversity of its clinical presentations,uncertainties about its natural history,evolving opinions regarding treatment end points,varied nature of refractory disease,and plethora of alternative immu-nosuppressive agents. The goals of this article are to review the difficult treatment decisions and to provide the bases for making sound therapeutic judgments. The English literature on the treatment problems in au-toimmune hepatitis were identif...     

Consequences of treatment withdrawal in type 1 autoimmune hepatitis.

BACKGROUND AND AIMS: Drug-related side effects are considered the major consequences of relapse and re-treatment in patients with autoimmune hepatitis. Our goals were to determine whether relapse is associated with disease progression and whether treatment end points can be refined. METHODS: The outcomes of 132 patients with definite type 1 autoimmune hepatitis who had been treated comparably until remission were assessed retrospectively after drug withdrawal. RESULTS: Patients who had relapsed repeatedly after initial treatment withdrawal developed cirrhosis more commonly than patients who sustained remission (18/48 vs 1/22, P=0.004), and those who relapsed once (18/48 vs 2/21, P=0.02). Hepatic death or the need for liver transplantation was also more frequent in the patients who had multiple relapses than those who sustained remission (13/64 vs 0/30, P=0.008) and those who relapsed once (13/64 vs 1/38, P=0.02). Patients who sustained their remission had a higher frequency of normal laboratory indices at drug withdrawal than patients who relapsed (88% vs 46%, P=0.003). Adverse outcomes after relapse did not distinguish patients until after 5 years of observation. CONCLUSIONS: Multiple relapses are associated with a poorer prognosis than sustained remission or single relapse episodes. Initial treatment to resolution of laboratory abnormalities may afford the greatest opportunity to prevent relapse.     

自身免疫性肝炎免疫学治疗进展

近年来自身免疫性肝炎(AIH)以其独特的临床和病理学特征,受到越来越多的关注。但目前其发病率和临床特征仍不十分清楚,尚需对其进行系统深入的研究。探讨了AIH的流行病学、病因和发病机制、临床特征及其诊断和治疗进展。指出TNFα中和性抗体、利妥昔单抗、全反式维甲酸和调节性T淋巴细胞移植在临床试验或AIH动物模型中均被证明对AIH有疗效。     

Cyclosporin in the treatment of corticosteroid resistant autoimmune chronic active hepatitis.

A 17 year old Asian patient with autoimmune chronic active hepatitis resistant to treatment with high dose corticosteroids and azathioprine was given cyclosporin at a dose of 5 mg/kg/day. Within two weeks of starting the cyclosporin treatment a favourable clinical and biochemical response was obtained and by one month serum aminotransferase activities were within normal limits. An attempted reduction in the daily dose of cyclosporin resulted in a relapse of the patient's disease. Remission was again attained by returning the dose of cyclosporin to 5 mg/kg/day. No significant side effects of the treatment have been shown. Cyclosporin seems to have a role in the treatment of corticosteroid resistant autoimmune chronic active hepatitis and its further evaluation is warranted.     

自身免疫性肝炎的诊断和治疗

自身免疫性肝炎(autoimmune hepatitis,AIH)是一种累及肝脏实质的特发性疾病.临床上,AIH以高血清转氨酶、高γ-球蛋白/Ig、高滴度自身抗体和肝组织学上以界面性肝炎(interface hepatitis)为特点,但需排除其他原因所致慢性肝病的可能.该病一般对糖皮质激素治疗应答良好.基于血清免疫学发现,AIH可分为二型:Ⅰ型AIH是最常见的疾病类型,与抗核抗体(ANA)和/或平滑肌抗体(SMA)、抗肌动蛋白抗体、非典型P-ANCA及抗可溶性肝抗原/肝胰抗体(抗SLA/LP)等有关;Ⅱ型AIH主要发生于儿童,以抗肝/肾微粒抗体1型(抗LKM -1)和抗肝细胞溶质-1抗体(抗LC-1)为主.大约有10％的患者血清自身抗体可呈阴性.按基因型可分为HLADR3( DRBI^0301)、HLA -B8和HLA - DR4CDRBI^0401,0405)等类.在存在相应的组织学改变的基础上,AIH的诊断还需结合临床和生化特点、血清自身抗体和免疫球蛋白水平.     

Diagnosis and treatment of autoimmune hepatitis

Autoimmune hepatitis (AIH) is an idiopathic hepatitis characterized by inflammation of the liver, presence of autoantibodies, and evidence of increased gamma globulins in the serum. It represents an enigmatic interaction between the immune system, autoantigens, and unknown triggering factors. This article provides a brief summary of the diagnosis of AIH, the natural history of AIH, an approach to the treatment and follow-up of AIH, and the role of liver transplantation in the treatment of AIH.     

Ornidazole-induced autoimmune hepatitis.

Ornidazole is a commonly prescribed antiparasitic drug for parasitic infestations, including amoebiasis, giardiasis and Trichomonas vaginalis. Several cases of antibiotic-induced autoimmune hepatitis (AIH) or AIH-like syndrome have been reported recently. In this report, we describe a 35-year-old woman with two relapses of AIH induced by ornidazole prescribed for diarrhoea and vaginal infection.     

自身免疫性肝炎的诊断与治疗

我国为病毒性肝炎高发区,自身免疫性肝炎(auto-immunehepatitis,AIH)相对少见,但对后者尚无系统的流行病学调查。AIH多见于女性,其临床特点为不同程度的血清转氨酶升高、高γ-球蛋白血症、血清中出现自身抗体,组织学特征为“界面性肝炎”。本病通常对糖皮质激素治疗应答良好,但严重病例如不及时治疗,6个月的病死率高达40%。因此,我们临床医生应提高对AIH的认识,熟悉其临床特点,以便及时做出诊断并给予正确治疗。1AIH的临床特点及诊断1·1临床特点本病女性多见(女∶男为4∶1),各年龄组人群均可发病,青春期和女性绝经期前后为2个高发年龄…     

自身免疫性肝炎的诊断与治疗

自身免疫性肝炎(AIH)是一种病因和发病机制尚未明确的慢性进行性肝脏炎症性疾病,以高丙种球蛋白血症、血清自身抗体阳性和对免疫抑制治疗应答良好为特点。简要介绍了AIH的流行病学概况、临床特点以及近年来在AIH的诊断及治疗方面所取得的进展,强调早期诊断并给予正确治疗有助于改善其预后。