Biochemical markers for non-invasive assessment of disease stage in patients with primary biliary cirrhosis

AIM： To evaluate different biochemical markers and their ratios in the assessment of primary biliary cirrhosis （PBC） stages. METHODS： This study included 112 patients with PBC who underwent a complete clinical investigation. We analyzed the correlation （Spearman＇s test） between ten biochemical markers and their ratios with different stages of PBC. The discriminative values were compared using areas under receiver operating characteristic （ROC） curves. RESULTS： The mean age of patients included in the study was 53.88 ＋ 10.59 years, including 104 females and 8 males. We found a statistically significant correlation between PBC stage and Aspartate aminotransferase （AST）, Alanine aminotransferase （ALT） to platelet ratio （APRI）, ALT/platelet count, AST/ALT, ALT/AST and ALT/Cholesterol ratios, with the values of Spearman＇s rho of 0.338, 0.476, 0.404, 0.356, 0.351 and 0.325, respectively. The best sensitivity and specificity was shown for AST/ALT, with an area under ROC of 0.660. CONCLUSION： Biochemical markers and their ratios do correlate with different sensitivity to and specificity of PBC disease stage. The use of biochemical markers and their ratios in clinical evaluation of PBC patients may reduce, but not eliminate, the need for liver biopsy.     

AST/ALT比值在慢性肝病患者中的特点和判断预后价值

目的 分析不同病因、不同病情的慢性肝病患者天冬氨酸氨基转移酶和丙氨酸氨基转移酶比值(AST/ALT)的特点,评价AST/ALT比值判断慢性肝病患者预后方面的价值.方法 对534例不同病因的肝硬化、原发性肝癌患者的住院资料进行分析,比较各类患者AST/ALT比值的特点.运用接受者运行曲线(ROC)及曲线下面积,比较AST/ALT比值与终末期肝病模型(MELD)、Child-Turcotte-Pugh(CTP)分级(CC)和评分(CS)在判断慢性肝病患者中短期预后方面的准确性;运用非参数相关分析,计算Spearman相关系数,分析三者之间的相关性.结果 在原发性肝癌患者,AST/ALT比值明显高于肝硬化患者(P＜0.05);病毒性肝病患者和非病毒性肝病患者的AST/ALT比值无明显差异(P=0.852).死亡患者的AST/ALT比值明显高于生存患者的平均值(P=0.000);随着CTP分级的升高,AST/ALT比值也逐渐升高,A、B、C三级之间的AST/ALT比值具有显著差异(P＜0.05).AST/ALT比值和MELD、CS及CC在判断慢性肝病患者生存3个月的ROC曲线下面积分别是0.88、0.92、0.69和0.59,判断生存1年时间的ROC曲线下面积分别为0.64、0.77、0.65和0.63;AST/ALT比值与MELD、CS和CC三者之间的相关系数分别是0.185、0.291和0.297(P=0.000).结论 AST/ALT比值随着肝脏病变的加重而逐渐升高.AST/ALT比值和MELD在判断慢性肝病患者短期预后方面是较好的指标.AST/ALT比值和MELD、CS、CC三者之间具有显著相关性.     

Aspartate aminotransferase : alanine aminotransferase ratio in chronic hepatitis C infection: Is it a useful predictor of cirrhosis?

BACKGROUND: The clinical usefulness of the ratio of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) has been explored in several liver disorders. It has been suggested that in patients with chronic hepatitis C virus (HCV) infection an AST:ALT > or = 1 has 100% specificity and positive predictive value in distinguishing cirrhotic from non-cirrhotic patients. Such statistical certainty attached to a simple biochemical test merits further evaluation. The present study, therefore, assessed the AST:ALT in patients with chronic HCV infection to determine the validity of the ratio in predicting cirrhosis and to correlate the ratio with the histological grade of necroinflammatory activity and fibrosis. METHODS: A retrospective analysis of 153 patients with chronic HCV infection was conducted. Serum biochemistry had been obtained within a mean of 4 weeks of liver biopsy. The histology was scored in terms of activity and fibrosis as described by Scheuer and correlated with AST:ALT. RESULTS: In 30 patients with cirrhosis, the mean AST:ALT (0.99 +/- 0.06) was higher than in 123 patients without cirrhosis (0.60 +/- 0.02; P < 0.001). A ratio > or = 1 had 95.9% specificity and 73.7% positive predictive value in distinguishing cirrhotic from non-cirrhotic patients, with a 46.7% sensitivity and 88.1% negative predictive value. The ratio also parallelled the Scheuer score with respect to fibrosis but not with respect to inflammation. CONCLUSION: Although relatively insensitive, an AST:ALT > or = 1 is highly specific but not diagnostic for the presence of cirrhosis in patients with chronic HCV infection. The ratio reflects the grade of fibrosis in these patients.     

High aspartate to alanine aminotransferase ratio is an indicator of cirrhosis and poor outcome in patients with primary sclerosing cholangitis.

OBJECTIVES: A liver biopsy is performed mainly to stage primary sclerosing cholangitis (PSC). In viral hepatitis, alcoholic liver disease and in primary biliary cirrhosis, the ratio of aspartate to alanine aminotransferase (AST/ALT) has been proven to be an indicator of liver cirrhosis. We wanted to test whether or not an AST/ALT ratio >/=1 is an indicator of cirrhosis also in patients with PSC. METHODS: A cohort of 154 patients diagnosed with PSC was studied retrospectively. Laboratory tests and the histological stage were scored. RESULTS: The mean AST/ALT ratio in the cirrhotic patients at the time of the first (n=117) as well as the last (n=72) histological examination was higher (1.3+/-0.5 and 1.6+/-0.7, respectively) than in the non-cirrhotic patients (0.7+/-0.4 and 1.0 +/-0.4, respectively) (P<0.0001 and P=0.0002, respectively). An AST/ALT ratio >/=1 was a strong predictor for liver-related death/orthotopic liver transplantation and liver-related death, being associated with a double and an almost fourfold higher risk, respectively. CONCLUSION: An AST/ALT ratio >/=1 is significantly associated with the presence of cirrhosis and poor outcome in PSC. It may therefore be a valuable non-invasive method for indicating cirrhosis in patients with PSC.     

Aspartate aminotransferase-linked immunoglobulin complexes in serum of a patient with primary biliary cirrhosis

A 51-year-old woman who had been treated for primary biliary cirrhosis (PBC) was admitted to our hospital for evaluation of unexplained, isolated, persistently increased aspartate aminotransferase (AST) activity. Results of laboratory tests on admission showed: AST 171 KU, alanine aminotransferase 28 KU, and anti-mitochondrial titer 1/1280. Results of hepatitis B surface antigen (HBs Ag) and hepatitis C virus antibody (HCV Ab; C100-3) assays were negative. Histology of a liver biopsy specimen was compatible with a diagnosis of PBC (stage III of Scheuer's classificiation). The molecular size of serum AST was estimated to be more than 500 000 by high-performance size-exclusion liquid chromatography. Electrophoretic analysis showed an abnormal band of AST between supernatant AST (sAST) and mitochondrial AST (mAST), which band was characteristic of AST-immunoglobulin complexes (AST-Ig). Ouchterlony double-diffusion and immunoprecipitation tests identified the immunoglobulin component as IgM. The presence of AST-Ig appeared to be responsible for the elevated serum AST.     

原发性胆汁性肝硬化发生失代偿的预测

目的建立原发性胆汁性肝硬化(PBC)发生失代偿的预测模型,验证并判断其预测价值。方法回顾性分析113例确诊时处于代偿期的PBC患者的人口统计学、实验室检查、临床表现及其他预后模型(Child-Pugh、MELD、Mayo模型)积分,研究终点为发生腹水、肝性脑病、食管胃底静脉曲张出血等失代偿。应用SPSS16.0统计软件,采用多因素(Cox回归、Kaplan-Meier(K-M)等方法建立发生失代偿的预测模型,采用接受者工作特征(ROC)曲线下面积比较所建模型与以往其他模型对PBC发生失代偿的预测价值。结果随访中位数时间31.2个月(3.37～122.43个月)期间,有21例(18.58%)患者达研究终点。所建立的PBC发生失代偿的预测模型(即D-PBC模型)指标包括AST/ALT比值、碱性磷酸酶(ALP)、胆碱酯酶(CHE)和血小板(PLT),PI=0.862×AST/ALT+0.003×ALP(U/L)-0.293×CHE(kU/L)-0.011×PLT(×10~9/L)。与其他模型相比,该预测模型的ROC曲线下面积较大,采用PI>-1.41预测PBC发生失代偿的敏感性高达0.91。结论 D-PBC模型能准确预测代偿期PBC患者临床失代偿的发生。     

22例原发性胆汁性肝硬化的临床分析

目的 研究原发性胆汁性肝硬化（PBC）的临床特点、实验室检查、治疗转归，提高对PBC的认识。方法 分析22例PBC的临床表现、实验室检查及治疗转归。结果 22例PBC中女性20例，发病平均年龄51岁，主要症状包括皮肤瘙痒、乏力、纳差、腹痛，主要体征包括黄疸、肝大、脾大、腹水，实验室检查以ALP、高GGT、高胆红素血症、高球蛋白血症、存在多种自身抗体如抗线粒体抗体（AMA）、AMA－M2及抗核抗体（ANA）等，多数患者血ALT、AST升高，所有患者血清AST高于ALT。出现症状至临床确诊时间为2月－5年，平均8个月。治疗采用以熊去氧胆酸（UCDA）为主的综合方法，治疗3个月后ALP及TBil下降达50％以上者有12例，72．7％症状改善，死亡2例。结论 PBC以中年女性多，以肝脾肿大、黄疸、瘙痒、乏力为主要临床表现，肝功能异常以胆汁淤积为主，伴有高球蛋白血症及自身抗体；UCDA能够改善患者的症状和部分肝功能异常。     

持续ALT正常乙型肝炎肝硬化的肝功能及组织病理临床分析

目的 了解ALT持续正常的乙型肝炎肝硬化的肝功能、HBeAg、HBV DNA及肝组织炎症状况,探讨其临床特点.方法 收集ALT持续12个月正常及ALT异常肝穿病理证实存在肝硬化患者肝功能、性别、HBeAg、HBV-DNA及组织病理学结果,应用秩和检验、χ2检验及Spearman相关分析进行统计分析.结果 ALT正常组与ALT异常各组比较,肝脏组织病理炎性程度无明显差异,ALT正常组HBV DNA载量较ALT异常组低,AST/ALT比值大于1与ALT异常组比较存在明显差异,血清白蛋白、性别、HBeAg及胆碱脂酶在各组之间差异无统计学意义;在ALT正常亚组中,72%的患者ALT在30～50 U/L之间,两组之间组织病理差异无统计学意义;在所有的肝硬化患者中,HBeAg定量与肝脏炎性程度无相关性,与HBV DNA载量呈正相关.结论 ALT正常乙型肝炎肝硬化患者肝脏组织存在明显炎症,AST/ALT比值大于1在肝硬化组明显升高,炎性程度各组之间无明显差异,HBeAg定量与肝脏炎性程度无相关性,而与HBV DNA载量呈正相关.     

Validity and clinical utility of the aspartate aminotransferase-alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus-related chronic liver disease

BACKGROUND: The aspartate aminotransferase-alanine aminotransferase ratio (AST/ALT ratio) has been used to noninvasively assess the severity of disease in patients with chronic liver disease (CLD). We previously demonstrated that progressive liver functional impairment is associated with an increase in the AST/ALT ratio. OBJECTIVES: To evaluate the reproducibility and transportability of the AST/ALT ratio in a large cohort of patients with different degrees of hepatitis C virus (HCV)-related CLD, to confirm the correlation between progressive impairment of liver function and increase in the AST/ALT ratio, to evaluate whether diagnostic accuracy of the ALT/AST ratio can be improved by using it with other biochemical variables, and to assess the 1-year prognostic capability of the AST/ALT ratio in patients with liver cirrhosis. PATIENTS AND METHODS: We retrospectively evaluated 252 patients with HCV-related CLD. The AST/ALT ratio was correlated with the degree of liver fibrosis in patients with chronic hepatitis and with the Child-Pugh score in patients with cirrhosis. All patients had undergone monoethylglycinexylidide (MEGX) testing to evaluate liver function. We assessed the prognostic ability of the AST/ALT ratio in a subset of 63 cirrhotic patients who were followed up for at least 1 year. RESULTS: The AST/ALT ratio was more frequently 1 or higher in cirrhotic patients (P<.001). There was a significant correlation between MEGX values and the AST/ALT ratio (r(s) = -0.621, P<.001). Multivariate stepwise logistic analysis showed that AST/ALT ratio, platelet count (PLT), MEGX values, and prothrombin activity were independently associated with the presence of cirrhosis. Combined assessment of the AST/ALT ratio and/or PLT obtained 97.0% positive predictive value and 97.9% negative predictive value for the diagnosis of cirrhosis. The AST/ALT ratio had 81.3% sensitivity and 55.3% specificity in identifying cirrhotic patients who died within 1-year of follow-up. CONCLUSIONS: The AST/ALT ratio is both reproducible and transportable in patients with HCV-related CLD. The AST/ALT ratio is correlated with both histologic stage and clinical evaluation. Progressive liver functional impairment is reflected by an increase in the AST/ALT ratio. Noninvasive evaluation by means of the combined AST/ALT ratio and PLT assessment misclassifies only a few cirrhotic patients. In cirrhotic patients, the AST/ALT ratio provides medium-term prognostic information that is no different from that provided by established prognostic scores.     

Aspartate aminotransferase-immunoglobulin complexes in patients with chronic liver disease

AIM: To determine the complex of AST and immunoglobulin and to investigate its clinical significance in patients with liver disease. METHODS: The complex of AST and immunoglobulin was determined by encounter immunoelectrophoresis and its clinical significance was investigated in 128 patients with liver disease. RESULTS: AST was bound to immunoglobulin of anti-immunoglobulin A (IgA) class, but any binding to anti-immunoglobulin G and anti-immunoglobulin M classes was not observed. Although the incidence of AST-immunoglobulin complex was 41.8% in chronic hepatitis (CH), the incidences in liver cirrhosis and hepatocellular carcinoma were 62.2 and 90.0%, respectively. In alcoholic liver disease with high level of serum IgA, the incidence of the complex was 66.7%, which was higher than that in CH. The ratio of binding to lambda-chain of IgA was higher than that to kappa-chain of IgA. The serum level of IgA and the ratio of AST/alanine aminotransferase (ALT) were significantly higher in patients with AST-IgA complex than in those without complex. CONCLUSION: These results suggest that AST-IgA complex in patients with progressive liver diseases and alcoholic liver injury can lead to elevation of the ratio of AST/ALT.     

70例原发性胆汁性肝硬化患者的临床特点分析

目的 探讨原发性胆汁性肝硬化（PBC）患者的临床特点.方法 回顾性分析2008年1月至2013年3月诊断为PBC的住院患者70例,记录患者的首诊症状、肝功能情况、AMA 亚型抗体（M2、M4、M9）以及3例病理结果,并对ALT、AST、ALP、GGT增高的程度进行秩和检验,采用Wilcoxon法.结果 84.3%为女性患者,平均年龄（59.2±8.7）岁.主要的临床表现为乏力25.7%,皮肤瘙痒24.3%,右胁不适18.6%,腹胀18.6%.生化学异常以GGT[（324.5±250.4）U/L]、ALP[（381.1±259.0）U/L]增高最明显.GGT增高5倍以上的患者较多,与ALT、AST、ALP相比差异有统计学意义（u值分别为-5.861、-4.036、-4.445,P均为0 000）,AST、ALP增高2倍以上的患者亦较ALT多（u值分别为-4.405、-3.625,P均为0.000）.87.1%的患者AM2A阳性; AM4A阳性占31.4%,AM9A阳性占11.4%.结论 PBC是女性多见的以GGT、ALP增高为明显的慢性肝功能损害,AMA抗体亚型（M2、M4、M9）的阳性是诊断该病的重要依据.     

AST/ALT Ratio Predicts Cirrhosis in Patients With Chronic Hepatitis C Virus Infection

Objective: A liver biopsy is necessary to grade and stage chronic hepatitis C virus (HCV) infection. In a previous study of patients with nonalcoholic liver disease, an aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio > 1 suggested cirrhosis. We sought to examine the value of the AST/ALT ratio in distinguishing cirrhotic patients with chronic HCV infection from noncirrhotic patients and to correlate the ratio with the grade and stage of hepatitis and other biochemical indices.
Methods: We retrospectively studied 139 patients with chronic HCV infection. Routine biochemical indices were determined, and the histological grade of necroinflammatory activity and the stage of fibrosis of the liver biopsy specimens were scored.
Results: The mean AST/ALT ratio in the cirrhotic patients (  n = 47  ) was higher than in the noncirrhotic patients (  n = 92  ) (  1.06 ± 0.06 vs 0.60 ± 0.09  ;   p < 0.001  ). A ratio ≥1 had 100% specificity and positive predictive value in distinguishing cirrhotic from noncirrhotic patients, with a 53.2% sensitivity and 80.7% negative predictive value. The ratio correlated positively with the stage of fibrosis but not with the grade of activity or other biochemical indices. Of the cirrhotic patients, 17% had no clinical or biochemical features suggestive of chronic liver disease except for an AST/ALT ratio ≥1.
Conclusion: The AST/ALT ratio is a dependable marker of fibrosis stage and cirrhosis in patients with chronic HCV infection.     

The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease

OBJECTIVE: The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is often greater than 2:1 in alcoholic hepatitis. The purpose of this study was to determine whether this ratio may be used to distinguish nonalcoholic steatohepatitis (NASH) from alcoholic liver disease. METHODS: Patients with NASH were matched with controls with alcoholic liver disease based on age, gender, and date of diagnosis. The diagnosis of alcoholic liver disease was based on exclusion of other causes and a significant history of alcohol consumption. The diagnosis of nonalcoholic steatohepatitis was based on exclusion of other causes of liver disease and a liver biopsy showing > 10% steatosis and inflammation. The two sided Student t test was used for statistical analysis. RESULTS: From 1990 to 1996, 70 patients with NASH were matched with 70 subjects with alcoholic liver disease. Patients with NASH had a mean AST to ALT ratio of 0.9 (range 0.3-2.8, median 0.7) and subjects with alcoholic liver disease a mean ratio of 2.6 (range 1.1-11.2, median 2.0). The mean AST levels were 66 U/L and 152 U/L, and the mean ALT levels 91 U/L and 70 U/L, in the nonalcoholic steatohepatitis and alcoholic liver disease groups, respectively. Although the absolute aminotransferase levels were significantly different in the two groups (p < 0.05), the greatest difference was observed in the AST to ALT ratio (p < 0.000001). Subset analysis of patients with NASH revealed mean AST to ALT ratios of 0.7, 0.9, and 1.4 for subjects with no fibrosis, mild fibrosis, or cirrhosis, respectively. The differences among these ratios were statistically significant (p < 0.05). CONCLUSIONS: The AST to ALT ratio appears to be a useful index for distinguishing nonalcoholic steatohepatitis from alcoholic liver disease. Although values < 1 suggest NASH, a ratio of > or = 2 is strongly suggestive of alcoholic liver disease.     

A novel liver stiffness measurement‐based prediction model for cirrhosis in hepatitis B patients

Backgrounds/aims: While liver stiffness measurement (LSM) predicts histological cirrhosis accurately, complementary methods are needed for better performance. Furthermore, alanine aminotransferase (ALT) influences LSM, making it necessary to modify its use in patients with high ALT levels. We developed a new LSM‐based prediction model for cirrhosis and estimated the thresholds for different ALT levels. Methods: From 2008 to 2009, we prospectively enrolled 330 consecutive patients who were diagnosed with chronic hepatitis B (CHB) and underwent a liver biopsy and LSM on the same day. For detection of cirrhosis, we performed univariate and multivariate analyses, using the χ²‐test/t‐test and logistic regression respectively. Thereafter, a prediction model was derived from multivariate predictors. Results: In multivariate analyses of patients with and without cirrhosis, we found significant differences in the LSM, spleen diameter and platelet count. Then, we developed an LSM–spleen diameter to platelet ratio index (LSPI): (LSM × spleen diameter/platelet count) × 100. The area under the receiver operating curve was 0.956, significantly higher than LSM alone (0.919, P=0.032). We suggested different thresholds in patients with ALT≤upper limit of normal (ULN) (normal‐ALT group, 164 patients) and ALT>ULN (high‐ALT group, 166 patients). In the normal‐ALT group, LSPI thresholds of 38 and 62 provided 95.7% negative predictive value (NPV) and a 95.5% PPV (positive predictive value), while in the high‐ALT group, thresholds of 42 and 94 yielded 95.1% NPV and 96.4% PPV respectively. Therefore, liver biopsy could be avoided in 76.7% of the subjects. Conclusions: LSPI is a useful, non‐invasive tool that can replace liver biopsy in the assessment of liver fibrosis in the majority of CHB patients.     

Serum enzyme pattern in acute liver disease: Relation to type of cell death

To examine the hypothesis that different histological forms of liver cell death result in a characteristic serum enzyme pattern, the serum concentration of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase (LD) enzymes were measured in three aetiologically distinct groups of patients with acute hepatocellular injury. Thirty patients had serologically confirmed acute viral hepatitis B, twenty had histologically proven ischaemic hepatitis and five had paracetamol hepatotoxicity. Serum AST and ALT levels were similar in the patients with viral and ischaemic hepatitis, but the serum LD was significantly higher (P < 0.001) in the ischaemic hepatitis group. The pattern of enzyme elevation in the patients with paracetamol hepatotoxicity was similar to that found in ischaemic hepatitis. AST/LD and ALT/LD ratios, which were greater than 2 and 3 respectively, usually distinguished the patients with viral hepatitis from those with ischaemic hepatitis or paracetamol hepatotoxicity. Because of differences in the clearance of these enzymes from the serum it is likely that the AST/LD ratio will prove of greater discriminatory value and that this will be most evident early in the patient's clinical course and become progressively less with time.     

抗线粒体抗体与原发性胆汁性胆管炎临床血清学和肝硬化指标的相关性

目的探究首次就诊的抗线粒体抗体(AMA)阳性原发性胆汁性胆管炎(PBC)患者的AMA水平及其与临床指标的相关性。方法通过北京大学人民医院信息系统,收集2013年1月至2016年12月首次检测AMA和(或)M2型抗线粒体抗体(AMA-M2)阳性的1323例患者的临床资料,其中采用间接免疫荧光法183例、免疫印迹法431例、ELISA法709例;分为未诊断PBC组(973例)和新诊断PBC组(350例,其中非肝硬化者268例,肝硬化者82例)。709例采用ELISA法的患者中,未诊断PBC组567例,新诊断PBC组142例(PBC非肝硬化组115例,PBC肝硬化组27例)。183例采用间接免疫荧光法的患者中,未诊断PBC组118例,新诊断PBC组65例;其中AMA滴度为低滴度(1∶40~1∶80)者69例(未诊断PBC组53例,新诊断PBC组16例)、中滴度(1∶160~1∶320)者95例(未诊断PBC组59例,新诊断PBC组36例)、高滴度(≥1∶640)者19例(未诊断PBC组6例,新诊断PBC组13例)。比较各组患者的AMA水平,分析其与PBC临床指标免疫球蛋白(Ig)G、IgM、血小板计数、ALT、AST、GGT、ALP、血清总蛋白、TBil、总胆固醇,以及肝硬化指标天冬氨酸转氨酶与血小板比率指数(APRI)、基于四因子的纤维化指数(Fib-4)的相关性。统计学方法采用Mann-Whitney U检验、Kruskal-Wallis检验和线性回归分析。结果采用ELISA法检测的709例患者的AMA-M2滴度中位值为53 RU/mL,新诊断PBC组的血清AMA和AMA-M2中位水平均高于未诊断PBC组(1∶320比1∶80和180 RU/mL比47 RU/mL),差异均有统计学意义(χ^2=14.111,Z=-7.531,P均<0.01)。未诊断PBC组的AMA-M2值与年龄、IgG、IgM、AST、GGT、ALP、血清总蛋白、总胆固醇水平均呈正相关,均有统计学意义(Rho值=0.114、0.108、0.337、0.089、0.197、0.086、0.121、0.073,P均<0.05);新诊断PBC组的AMA-M2值与年龄、IgM、血清总蛋白、总胆固醇水平均呈正相关,与血小板计数呈负相关,均有统计学意义(Rho值=0.218、0.483、0.230、0.161、-0.183,P均<0.05);PBC非肝硬化组的血清AMA和AMA-M2中位水平均有低于PBC肝硬化组的趋势(1∶160比1∶320和174 RU/mL比495 RU/mL),但差异均无统计学意义(P均>0.05);PBC肝硬化组者组患者的AMA-M2值与IgM水平呈正相关(r=0.38,P=0.039),但与APRI、Fib-4均无明确相关性(P均>0.05)。采用间接免疫荧光法检测的183例患者的AMA滴度中位值为1∶160;未诊断PBC组中AMA低滴度、中滴度和高滴度者的IgM中位水平逐渐升高(分别为1.2、1.7和1.8 g/L),新诊断PBC组中AMA低滴度、中滴度和高滴度者的IgM、GGT、ALP的水平均逐渐升高(中位水平分别为1.5、3.7和4.1 g/L,144、182和317 U/L,137、168和221 U/L),差异均有统计学意义(χ^2=6.260、7.081、8.030、15.226,P均<0.05)。总体中未诊断PBC组男性的血清AMA-M2中位水平低于女性(41 RU/mL比50 RU/mL),差异有统计学意义(Z=-2.945,P=0.003);新诊断PBC组男性的血清AMA-M2中位水平有低于女性的趋势(113 RU/mL比206 RU/mL),但差异无统计学意义(P=0.257)。结论血清AMA水平与诸多临床指标有一定的相关性,并可能与PBC患者的疾病严重程度相关。     

Prediction of coronary atherosclerotic disease with liver transaminase level.

BACKGROUND/AIMS: Recent studies have shown that liver transaminases are associated with components of the metabolic syndrome including central obesity, type 2 diabetes, dyslipidaemia and high blood pressure, but their direct influence on coronary atherosclerosis has not been investigated before. We conducted this study to evaluate the predictive value of liver transaminases for angiography-documented coronary atherosclerosis in patients with coronary heart disease. METHODS: Six hundred and thirty consecutive patients with suspicious coronary artery disease (CAD) who were candidates for coronary angiography were enrolled. In addition to coronary angiography, measurements of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, C-reactive protein (CRP) level and assessment of the traits of the metabolic syndrome were performed in all patients. RESULTS: ALT and ALT/AST ratios were significantly correlated with angiographic atherosclerosis score in women (r=0.17 and 0.24 respectively). Logistic regression analysis showed that the ALT/AST ratio in women could predict severe CAD [odds ratio (OR) 3.93, 95% confidence interval (CI) 1.76-8.76]. After adjustment for components of the metabolic syndrome and CRP concentration, the OR remained significant (4.00 [1.76-9.14]). Although significant in univariate analysis, neither ALT (OR 0.98, 95% CI 0.77-1.15) nor AST (OR 0.99, 95% CI 0.72-1.22) could predict severe CAD in men. CONCLUSION: An elevated ALT/AST ratio in women predicts coronary atherosclerosis independently of the metabolic syndrome and serum CRP concentration, and should warrant further diagnostic and therapeutic interventions.     

Predicting clinical outcomes using baseline and follow-up laboratory data from the hepatitis C long-term treatment against cirrhosis trial

Predicting clinical outcomes in patients with chronic hepatitis C is challenging. We used the hepatitis C long-term treatment against cirrhosis (HALT-C) trial database to develop two models, using baseline values of routinely available laboratory tests together with changes in these values during follow-up to predict clinical decompensation and liver-related death/liver transplant in patients with advanced hepatitis C. Patients randomized to no treatment and who had ≥ 2-year follow-up without a clinical outcome were included in the analysis. Four variables (platelet count, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] ratio, total bilirubin, and albumin) with three categories of change (stable, mild, or severe) over 2 years were analyzed. Cumulative incidence of clinical outcome was determined by Kaplan-Meier analysis and Cox regression was used to evaluate predictors of clinical outcome. In all, 470 patients with 60 events were used to develop models to predict clinical decompensation. Baseline values of all four variables were predictive of decompensation. There was a general trend of increasing outcomes with more marked worsening of laboratory values over 2 years, particularly for patients with abnormal baseline values. A model that included baseline platelet count, AST/ALT ratio, bilirubin, and severe worsening of platelet count, bilirubin, and albumin was the best predictor of clinical decompensation. A total of 483 patients with 79 events were used to evaluate predictors of liver-related death or liver transplant. A model that included baseline platelet count and albumin as well as severe worsening of AST/ALT ratio and albumin was the best predictor of liver-related outcomes. CONCLUSION: Both the baseline value and the rapidity in change of the value of routine laboratory variables were shown to be important in predicting clinical outcomes in patients with advanced chronic hepatitis C.     

加味茵陈蒿汤联合熊去氧胆酸治疗原发性胆汁性肝硬化的临床研究

目的:观察加味茵陈蒿汤联合熊去氧胆酸治疗30例原发性胆汁性肝硬化临床分期为早中期患者的临床疗效。方法:60例患者随机分为对照组和治疗组各30例。两组均给予基础治疗,对照组患者同时口服熊去氧胆酸胶囊15～20mg.kg-1.d-1;治疗组患者在对照组基础上加服加味茵陈蒿汤,1剂/d,疗程均为24周。观察治疗前后两组患者的临床疗效、肝功能(γ-GT、ALP、ALT、AST、TBil)、免疫指标(IgM、IgG及IgA)的变化。结果:治疗结束时,治疗组26例(86.7%)患者得到完全反应,与对照组19例(63.3%)比较差异有显著性意义(P<0.05);两组患者治疗后肝功能(γ-GT、ALP、ALT、AST、TBil)均较治疗前明显下降(P<0.05),治疗组治疗后肝功能下降明显优于对照组(P<0.05或P<0.01);治疗后两组患者免疫指标IgM、IgG、IgA均较前有所下降,经比较差异无统计学意义(P>0.05)。结论:加味茵陈蒿汤联合熊去氧胆酸治疗原发性胆汁性肝硬化,较单用熊去氧胆酸疗效更好,并能明显改善患者的肝功能。     

Progressive Liver Functional Impairment Is Associated with an Increase in AST/ALT Ratio

The ratio of serum aspartate aminotransferase toalanine aminotransferase (AST/ALT ratio) has beenproposed as a noninvasive method of assessing liverfibrosis and cirrhosis. Our aims were to confirm the usefulness of the AST/ALT ratio in diagnosingcirrhosis noninvasively as well as to verify theexistence of a relationship between the ratio and liverfunctional impairment. In all, 348 patients (177 with chronic hepatitis, 171 with cirrhosis) wereretrospectively evaluated and the AST/ALT ratio wasrelated to monoethyl glycine xylidide (MEGX) formation.Moreover, in a subgroup of 54 patients we analyzed the relationships among the AST/ALT ratio andindocyanine green clearance and half-life. The AST/ALTratio was able to separate patients with mild fibrosisfrom those with severe fibrosis and cirrhosis. The AST/ALT ratio, MEGX, prothrombin activity,and platelet count were selected by multivariateanalysis as variables associated with cirrhosis. TheAST/ALT ratio showed significant correlations both with MEGX formation and with indocyanine greenclearance and half-life. The alterations of indocyaninegreen kinetics, which depend upon liver blood flow anduptake, were likely due to progressive fibrosis. These findings might partially explain theincrease in the AST/ALT ratio as diseaseprogresses.