酒精性肝炎治疗方法的评价

酒精性肝病（ALD）可分为酒精性脂肪肝（AFL）、酒精性肝炎（AH）、酒精性肝硬化（ALC）三个临床类型．但三者严格上的区别仅可能是形态学的．无论AFL或ALC发展过程中。均可由于酗酒、不适当的药物应用、感染或其他因素。而进展或合并AH。在我们的181例ALD患者中有88例为AH（48．6％），其中发生于轻度AFL12例、中度AFL12例、重度AFL38例、ALC26例。可见AH在重度AFL和ALC中的发生率（72．7％）非常高。     

Advances in the treatment of severe alcoholic hepatitis

Severe alcoholic hepatitis (SAH) is a costly and worldwide public health issue with high morbidity and mortality. Specific effective treatments for SAH have yet to be established. The aim of the present article is to review the current knowledge of the pathogenesis, assessment and treatment options in patients with SAH. To date, alcohol abstinence and enteral nutrition are the recommended first-line treatments. Although corticosteroids remain the preferred therapy for certain patients with a modified Maddrey discriminant function level greater than 54, they only improve short-term survival rates. New research focuses on liver inflammation, liver regeneration, the gut–liver axis, human induced pluripotent stem cells and extracorporeal albumin dialysis. Liver transplantation is considered the last medical option for patients with SAH who are nonresponsive to other medical treatments.     

重症酒精性肝炎临床治疗进展

重症酒精性肝炎是一种由酒精导致的、潜在威胁生命的急性肝损伤,死亡率高,临床治疗面临巨大挑战。本文从营养支持治疗以及糖皮质激素、抗细胞因子应用等几个方面综述重症酒精性肝炎的临床治疗进展。     

异甘草酸镁对酒精性肝炎的疗效观察

目的 观察异甘草酸镁对于酒精性肝炎的疗效.方法 选择益阳市中心医院2006年3月至2012年3月期间收治的酒精性肝炎患者80例,完全随机分为研究组(40例)和对照组(40例),研究组给予异甘草酸镁注射液150 mg溶于10％葡萄糖溶液250 ml,1次/d静脉滴注,同时应用多烯磷脂酰胆碱10 ml溶于10％葡萄糖溶液250 ml,1次/d静脉滴注.对照组予以还原型谷胱甘肽1.8g溶于10％葡萄糖溶液250 ml,1次/d静脉滴注,同时应用多烯磷脂酰胆碱10 ml溶于10％葡萄糖溶液250ml,1次/d静脉滴注,治疗时间2～3周.结果 研究组乏力、纳差、腹胀、黄疸、肝脏肿大和压痛减轻率均高于对照组(均P＜0.05).研究组治疗后ALT、AST、γ-谷氨酰转肽酶、总胆红素的水平均低于对照组(P＜0.05).研究组治疗总有效率明显高于对照组[87.5％(35/40)比70.0％(28/40)],差异有统计学意义(P＜0.05).结论 异甘草酸镁对于控制酒精性肝炎炎症活动有显著作用,且优于还原型谷胱甘肽.     

Histopathology of the alcoholic hepatitis and mesenchymal cells]

Alcoholic hepatitis is one of the type of alcoholic liver diseases (ALD). There are definite histopathological criteria; presence of Mallory bodies and PMN leukocytes. In Japan, it has been believed that alcoholic hepatitis is very rare and alcoholic fibrosis is common type in ALD. On the other hands, some american, authorities consider that severe ballooning of hepatocytes with slight fibrosis is also inflammatory state, alcoholic hepatitis. Histological criteria is controversial. Generally, fibrosis believed to be a histological marker of chronic inflammation. However, in ALD, there is primary fibrosis, specific fibrosis produced by direct stimulation of alcohol or its metabolites on mesenchymal cells. On the fibrogenesis in hepatic lobules, the mesenchymal cells represented by Ito cells play main role. Ito cells show morphological and immunohistochemical heterogeneity depending on its physiological condition. On the other hand, Ito cells also show various degrees of transitional changes associated with fibrogenesis. Then, morphological and immunohistochemical appearance of Ito cells is very complicated. Recently, it is considered that these differences means different cell populations of the fibroblast lineage with fibrogenic potential.     

Clinical pharmacokinetics of chlordiazepoxide in patients with alcoholic hepatitis

Summary The clearance of chlordiazepoxide from the systemic circulation was studied in 20 subjects which included 15 patients with alcoholic hepatitis and 5 normal volunteers. The half-life for the appearance of the drug in the systemic circulation was found to increase exponentially with age (r=0.73, P<0.0005) and was independent of the presence of alcoholic hepatitis. The metabolic clearance of chlordiazepoxide was significantly lower in the patients than in the normal subjects (7.6 compared to 13.8 ml/kg-h, P<0.005). Linear regression analysis revealed a significant correlation between clearance and albumin (r=0.77, P<0.00005). However, the predictive value of this relationship was shown to be minimal. Multiple regression analysis produced only a slight improvement in the correlation when both albumin and lactate dehydrogenase were used as variables (r=0.83, P<0.00005). In six of the patients, a second clearance study was conducted three weeks following their initial one. All repeat subjects showed improvement both clinically and as reflected by their laboratory tests for liver injury, but there was not a significant change in their clearance of chlordiazepoxide. Multiple regression analysis of the clearance data on the initial and repeat subjects showed a significant correlation between clearance and the variables age, albumin, and lactate dehydrogenase (r=0.91, P<0.0025). This relationship suggests that over a short period of time (where age can be considered constant) changes in albumin and lactate dehydrogenase could be potentially useful in predicting clearance changes in a single individual.     

Review article: the diagnosis and management of alcoholic hepatitis

Background  Alcoholic hepatitis is a severe, cholestatic liver disease occurring in patients with alcohol abuse. Mortality is substantial; however, therapies may improve clinical outcomes.
Aim  To provide an updated review of the epidemiology, diagnosis, staging and treatment of alcoholic hepatitis.
Methods  A MEDLINE literature search was performed to identify pertinent articles. Relevant clinical abstracts were also reviewed.
Results  Severe alcoholic hepatitis occurs in a small fraction of patients who abuse alcohol. The 28-day mortality ranges from 30% to 50% in most series. Diagnosis is generally based on clinical features, with a limited role for liver biopsy. Beneficial treatment options include alcohol abstinence and nutritional therapy. Despite variable results in clinical trials, corticosteroids and pentoxifylline appear to provide moderate survival benefit. Anti-tumour necrosis factor agents and antioxidants have not proven beneficial, and should be limited to clinical trials. Liver transplant is not a frequent option given the active or recent alcohol use.
Conclusions  Severe alcoholic hepatitis is a clinically-diagnosed condition associated with significant mortality. Alcohol abstinence and nutritional therapy have been associated with improved clinical parameters and should be considered in all patients. Corticosteroid therapy and pentoxifylline therapy appear to show moderate survival benefit and should be considered as first-line therapeutic agents.     

复方甘草酸苷治疗酒精性肝炎临床疗效观察

目的 观察复方甘草酸苷治疗酒精性肝炎的临床疗效.方法 对照组30例,戒酒,运动,调整饮食.治疗组35例,在对照组基础上加用复方甘草酸苷片.4周为1个疗程,共3个疗程.治疗前后分别测定肝功能及肝脏B型超声波检查.结果 治疗组临床症状明显减轻,血清ALT、AST、GGT水平降低,治疗组明显优于对照组(P＜0.05).肝脏B超显示脂肪肝影像明显改善或消失.结论 复方甘草酸苷治疗酒精性肝炎可以明显改善患者的临床症状和肝功能.     

五酯片治疗酒精性肝炎的疗效观察

目的观察五酯片治疗酒精性肝炎的疗效。方法将符合纳入标准的110名患者随机分成试验组和对照组。试验组使用五酯片;对照组使用甘草酸二铵肠溶胶囊。观察两组治疗前后临床疗效及谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）、γ-谷氨酰转肽酶（γ-GT）的差别。结果①试验组总有效率（92．86％）显著高于对照组（77．78％）,差异有统计学意义（P〈0．05）;②两组治疗后ALT、AST、TBIL、γ-GT较治疗前均显著下降,差异均有统计学意义（P〈0．01）;③治疗后,试验组ALT、AST、TBIL、γ-GT显著低于对照组,差异均有统计学意义（P〈0．01）。结论五酯片可提高酒精性肝炎临床疗效．改善肝功能。     

Pharmacokinetics of diclofenac sodium in chronic active hepatitis and alcoholic cirrhosis

The objective of this study was to assess the pharmacokinetics of diclofenac sodium and its five metabolites following administration of a 150 mg oral dose to healthy subjects and patients with either chronic active hepatitis of varying morphology or alcoholic cirrhosis. Six healthy subjects, 6 chronic active hepatitis patients, and 6 alcoholic cirrhosis patients were enrolled in this prospective, open-label, parallel study. Blood samples were drawn at 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 312, and 480 hours, and urine samples were collected for 144 hours after administration of a single oral dose of diclofenac sodium. The mean area under the serum concentration-time curve extrapolated to infinity, oral clearance, half-life, maximal concentration, and time to peak concentration for diclofenac and its metabolites were determined and compared using analysis of variance. Cirrhotics had a mean +/- SD diclofenac AUC value (19,114 +/- 6806 ng.h/ml) significantly different (p < 0.02) from hepatitis patients (6071 +/- 1867 ng.h/ml) and healthy subjects (7008 +/- 2006 ng.h/ml), whereas healthy subjects and hepatitis patients had similar values. Comparable results were found for 4'-hydroxydiclofenac. The AUC values for 3'-hydroxydiclofenac and 3'-hydroxy-4'methoxydiclofeanc were significantly different when healthy subjects were compared to cirrhotics. However, hepatitis subjects were not significantly different from either group. The results indicate that hepatitis does not alter the pharmacokinetics of diclofenac. Alcoholic cirrhosis increased the mean diclofenac AUC approximately three times compared to normal subjects, indicating that one-third of the usual dose in cirrhotics would produce equivalent AUC values in normal subjects and subjects with alcoholic cirrhosis. However, since pharmacodynamic measurements were not made and no increase in untoward or side effects was noted in the alcoholic cirrhosis patients after a single dose, maintenance doses should be titrated to patients response.     

Clinical and pathological differences between alcoholic hepatitis and non-alcoholic steatohepatitis.

To determine the difference between alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH) in Japan, six patients with Ah and four patients with NASH, recently treated at our institute, were clinically and pathologically evaluated. Clinical features of the diseases differed: in NASH patients, mean age was higher, mean body mass index much higher, and the prevalence of diabetes mellitus was higher than in AH patients. The patients with NASH presented with unremarkable symptoms and signs. Abnormalities in liver function tests including prothrombin time and choline esterase were mild in NASH patients, except for the indocyanine green test. They had ALT-dominant hypertransaminasemia. AST, ALT and gamma GTP did not normalize as promptly as in AH patients after admission. However, there was no significant difference in the histological grade of fibrosis, inflammation or hepatocytic metamorphosis between NASH and AH patients. Stellate-form fibrosis was characteristic of AH, whereas pericellular and perivenular types were common in NASH patients. Focal cell necrosis was rather intense, and fatty deposits prominent, in NASH patients. However, it was difficult to histopathologically discriminate between NASH and AH patients. If AH is histologically suspected in non-alcoholic patients, the possibility of NASH should always be considered. Furthermore, even in patients with suspected simple fatty liver, a liver biopsy should be performed, especially in cases with prolonged abnormal liver function findings.     

还原型谷胱甘肽对酒精性肝炎患者肝纤维化指标的影响

目的：观察酒精性肝炎患者使用还原型谷胱甘肽治疗后肝纤维化指标的改善情况及临床症状、体征、肝功能的变化。方法：将72例酒精性肝炎患者分成治疗组（37例）和对照组（35例）,对照组给予甘利欣、门冬氨酸钾镁注射液、多种维生素等综合治疗,治疗组在综合治疗的基础上加用还原型谷胱甘肽（1．5g,一日一次）,疗程均为8周。观察治疗前后两组的血清纤维化指标[透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型前胶原N端肽（PⅢ-P）、Ⅳ型胶原（C-Ⅳ）]及生化指标[总胆红素（TBIL）、ALT、AST、γ-谷氨酰转肽酶（GGT）]的变化。结果：治疗组在症状、体征、肝功能、血清纤维化的改善方面明显优于对照组,治疗组血清肝纤维化指标与治疗前相比均有明显下降（P〈0．01）,而对照组下降不明显,两组相比有统计学差异（P〈0．01）。结论：还原型谷胱甘肽对酒精性肝炎患者有明显的抗纤维化作用和保肝护肝作用。     

88例酒精性肝炎临床特征及疗效分析

目的探讨酒精性肝炎(AH)的发病情况、临床特点、治疗和预后。方法对88例AH患者的一般情况、饮酒史、饮酒年限、临床表现、实验室检查等进行回顾性分析;除一般治疗外,有47.7%(42/88)单独或联合应用多烯磷脂酰胆碱(易善复),有66.7%(10/15)高度黄疸患者合用S-腺苷蛋氨酸(思美泰),有53.3%(8/15)高度黄疸患者应用激素冲击治疗(包括9例DF≥32患者中的5例);激素应用的指征为总胆红素(Tbil)>171μmol/L,D/T>50%,甲强龙120 mg,1次/d,静脉滴注,第3天TBil下降10%以上或第7天下降30%以上作为对激素有反应的指标,然后根据TBil的水平改为口服强的松30～60mg,对高度黄疸而对激素不敏感者,主要应用思美泰。结果⑴88例患者中合并酒精性脂肪肝(AFL)62例(轻度12例、中度12例、重度38例),酒精性肝硬化(ALC)26例;⑵AH的平均年龄为47.2±9.6岁;患者均有短期内大量饮酒史(最短3d),最长持续40年,最短2年,平均持续饮酒时间19.3±7.6年,饮酒种类中以白酒居多92.0%(81/88),平均日饮酒量114.0±72.8g;⑶临床上以腹胀、黄疸、腹痛、纳差为多见;⑷实验室检查中除ALT或/和AST不同程度升高外,主要是GGT、TBil和PT升高或延长为主,无论AFL和ALC外周血小板均有减低的趋势,合并黄疸38例,高度黄疸15例,均表现为肝内淤胆型黄疸;⑸住院最长时间为36d,最短为8d,平均3w,有82例出院时临床症状改善、酶学恢复正常、TBil降到40μmol/L以下、急性并发症得到控制,死亡1例(DF≥32的患者),无变化退院5例,8例激素冲击治疗的患者中,有7例对激素敏感。结论无论AFL或ALC均可合并AH;黄疸以肝内淤胆为主;DF与PT延长程度相关、高度黄疸多见。易善复和思美泰对改善肝脏功能和降低胆红素有非常好的疗效,在高度黄疸的AH中糖皮质激素仍然是主要的治疗药物。