Non-alcoholic steatohepatitis with normal aminotransferase values

AIM： To investigate the aspects of liver histology in patients with non-alcoholic steatohepatitis （NASH） who had normal aminotransferase levels. METHODS： Thirty-four patients diagnosed with liver steatosis by ultrasonographic examination participated in the study. We compared all non- alcoholic fatty liver disease and NASH cases, according to aminotransferase level, aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio and presence of metabolic syndrome. RESULTS： Sixteen of 25 patients with high aminotransferase levels were diagnosed with NASH and nine with simple fatty liver according to liver histology. Among the nine patients with normal aminotransferase levels, seven had NASH and two had simple fatty liver. The patients with normal and high liver enzyme levels had almost the same prevalence of NASH and metabolic syndrome. Liver histology did not reveal any difference according to aminotransferase levels and AST/ALT ratio. CONCLUSION： Aminotransferase levels and AST/AIT ratio do not seem to be reliable predictors for NASH. Despite numerous non-invasive biomarkers, all patients with fatty liver should undergo liver biopsy.     

Relationship between hepatocellular injury and transfusional iron overload prior to and during iron chelation with desferrioxamine: a study in adult patients with acquired anemias

The role of iron overload as cause of liver dysfunction has never been studied in detail in patients without concomitant hepatotropic infections who receive multiple transfusions. We therefore investigated the relationship between the extent of hepatocellular injury as reflected by serum levels of aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and several iron status indices in 39 anti-hepatitis C virus-negative (HCV(-)) nonthalassemic patients with transfusional iron overload owing to acquired anemias. In 12 patients, we monitored aminotransferase levels and indices of iron status during iron chelation treatment. Before treatment, elevated aminotransferase activity was seen only at liver iron concentrations more than 300 microM/g. During treatment all aminotransferase values were normal if the liver iron concentration returned below 350 microM/g. At the start of treatment, ALT (R(2) = 0.64, P =.006) and AST activity (R(2) = 0.57, P =.01) were closely related to urinary iron excretion, reflecting the size of the chelatable or the labile iron pool. During treatment, a comparable pattern was seen and the urinary iron excretion was also directly related to the liver iron concentration at concentrations above approximately 400 microM/g. All elevated ALT values were associated with a urinary iron excretion more than 15 mg/24 h. In conclusion, our data suggest the existence of a critical liver iron concentration range, above which hepatocellular injury is seen. The extent of the injury seems to be determined mainly by the size of the chelatable or labile iron pool, supporting the concept of the labile iron pool as the compartment directly involved in iron toxicity. Our findings may be helpful in establishing criteria for safety from complications of transfusional iron overload.     

Correlation of serum aminotransferases with HCV RNA levels and histological findings in patients with chronic hepatitis C: the role of serum aspartate transaminase in the evaluation of disease progression

OBJECTIVES: To investigate whether HCV RNA levels can be considered to be predictors of hepatocellular injury in patients with chronic hepatitis C, and whether aminotransferase levels are markers of liver damage. METHODS: We performed a retrospective study on 112 patients with chronic hepatitis C. For each patient, we considered the baseline alanine aminotransferase (ALT) and serum aspartate transaminase (AST) levels, baseline HCV RNA, HCV genotype, histological evaluation and the mean aminotransferase levels measured in the 6 months following liver biopsy. RESULTS: We found a statistically significant correlation between HCV RNA and aminotransferase levels measured during the follow-up (AST: r = 0.24, P = 0.01; ALT: r = 0.27, P = 0.004). We also observed a statistically significant correlation between HCV RNA levels and histological activity index (HAI) (r = 0.25, P = 0.008), as well as between the HAI and both baseline AST (r = 0.34, P = 0.0002) and ALT levels (r = 0.23, P = 0.01). These findings were confirmed by the mean aminotransferase values during follow-up. In the regression analysis, the fibrosis score was significantly and independently associated with baseline AST and ALT values. CONCLUSIONS: Our results demonstrate a statistically significant correlation of aminotransferase values with the histological parameters, and an even stronger correlation with the AST values. Our study therefore suggests that aminotransferase values, especially AST, may correlate with liver damage.     

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.     

2型糖尿病患者血清肝酶谱与甲状腺激素和中国人内脏脂肪指数的关系

目的探讨2型糖尿病患者血清肝酶谱与甲状腺激素和中国人内脏脂肪指数(Chinese visceral adipose index,CVAI)的关系,分析影响肝酶的因素。方法选取700例于本院内分泌科住院的2型糖尿病患者,根据肝酶是否升高分为肝酶升高组和肝酶正常组,再将丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、谷氨酰胺转肽酶(GGT)分别进行三等分分组。比较2组间及ALT、AST、GGT三等分分组间甲状腺激素和CVAI的差异,分析ALT、AST、GGT与甲状腺激素和CVAI的相关性。结果肝酶升高组较肝酶正常组T4、CVAI升高(P<0.05)。随着ALT、AST的升高,FT3、T3、T4逐渐升高(P<0.05);随着ALT、GGT的升高,CVAI也逐渐升高(P<0.05)。相关性分析显示,ALT、AST与FT3、T3、T4呈正相关;ALT、GGT与CVAI呈正相关;CVAI与FT3、T3呈正相关;HbA1C与FT3、T3和T4呈负相关。回归分析显示,FT3、CVAI和HbA1C是ALT的影响因素,T4是AST的影响因素,T3和HbA1C是GGT的影响因素。结论2型糖尿病患者中甲状腺激素和CVAI与肝酶水平均有一定相关性。     

Hyper-CK-emia in pediatric celiac disease: prevalence and clinical importance

Hyper-transaminasemia (HT) is a well-known laboratory sign of celiac disease (CD); however, hyper-creatine phosphokinase (CK)-emia (HCK) is not so familiar. As there are reported cases of myopathy associated CD in the literature, we aimed to investigate serum CK levels of children with CD. Newly diagnosed 126 children were included. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and CK levels were determined. Mean age was 8.7+/-4.4 years (11 mo to 18 y). Of patients, 77 (61.1%) had classic form, 49 (38.9%) had atypical form. Elevated levels of AST, ALT, and CK, respectively, were found in 65 (51.6%), 45 (35.7%), and 50 (39.7%) patients. Isolated HCK was detected in 9 (7.1%) patients. AST, ALT, and CK were all elevated in 29 (23.0%) children. Mean serum AST, ALT, and CK levels were found as 56.1+/-53.7 U/L (11 to 403), 44.7+/-44.0 U/L (7 to 290), and 258.0+/-686.5 U/L (36 to 5956), respectively. In 95 (75.4%) children, AST/ALT value was greater than 1, and in 19 (15.1%) it was greater than 2. We found positive correlations with the level of CK and AST, and ALT (P=0.01). CK level was inversely correlated with hemoglobin and cholesterol levels (P=0.013 and 0.007). In conclusion, this is the first study, which determined elevated serum levels of CK in CD and demonstrated that HCK is as common as HT in children with CD. We emphasize that HT seen in CD is not necessarily a sign of liver injury, but may also be due to myopathy.     

Hepatocellular injury with distinctive mitochondrial changes induced by lergotrile mesylate: a dopaminergic ergot derivative.

Increased serum activities of the enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) occurred in 12 out of 19 patients with idiopathic parkinsonism when they were treated with the ergot derivative lergotrile at an oral dose varying from 50 to 150 mg daily. Hepatocellular injury was confirmed by microscopic examination of liver biopsies obtained from 3 of these patients when the serum activities of ALT and AST were appreciably elevated. Light microscopy revealed features of mild acute hepatocellular injury, and electron microscopy showed proliferation of the smooth endoplasmic reticulum and apparently unique mitochondrial changes in hepatocytes. This is the first report of pathological changes in the liver associated with the therapeutic use of an ergot derivative. The presence of a potentially reactive cyanide group in the lergotrile molecule could be causally related to the observed hepatocellular injury. It is suggested that serum ALT and AST activities should be monitored carefully when the therapeutic potential of any new ergot derivative is assessed.     

Serum markers for necroinflammatory activity in patients with chronic viral hepatitis and normal or mildly elevated aminotransferase levels

Background: Reports on the usefulness of serum markers for predicting liver necroinflammation are limited. The aim of this study was to determine the serum markers that predict significant inflammation in patients with chronic hepatitis B (CHB) and C (CHC) and normal or mildly elevated serum aminotransferase levels. Methods: Two hundred twenty‐seven patients with CHB or CHC with normal or mildly elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (≤60 IU/L) were enrolled in this study. Significant inflammation was defined as inflammatory grade ≥3 activities using the Batt–Ludwig scoring system. The correlation between liver histology and serum markers of liver inflammation was analysed. Results: Forty‐eight (21.1%) and eight patients (3.5%) had grade 3 and 4 inflammation respectively. Univariate analysis revealed that age, platelet coun, and AST, ALT, γ‐glutamyl transpeptidase, alkaline phosphatase, hyaluronic acid, haptoglobin, apolipoprotein A1 and procollagen III N‐terminal peptide levels were significantly different between the patients with and without significant inflammation. There were no significant differences in the cytokeratin‐18 fragment levels between the two groups. On the basis of multivariate analysis, the AST and apolipoprotein A1 levels and stage of fibrosis were highly predictive of significant inflammation. Using AST and apolipoprotein cut‐off values ≥44 IU/L and ≤100 ng/ml, respectively, the presence of significant inflammation was predicted with high specificity (96.5%) and with a negative predictive value of 76.3%. Conclusion: The AST and apolipoprotein A1 levels were shown to be independent predictors of significant inflammatory activities in patients with CHB and CHC and normal or mildly elevated aminotransferase levels.     

Evidence for liver injury in the setting of obstructive sleep apnea

Introduction. Obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) are both strongly associated with obesity. Whether OSA is an independent risk factor for liver injury is uncertain.Objective. To assess the hypothesis that OSA is associated with liver injury independent of obesity.Materials and methods. We reviewed the histories of 73 consecutive patients referred to a hospital-based sleep lab because of suspected OSA. OSA was determined to be present if the apnea-hypopnea index was > 10. Obesity was defined as a BMI ≥ 30 kg/m². Patients were included for analysis if they had aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels obtained within 60 days of sleep study. Patients with evidence of viral hepatitis, autoimmune-, metabolic-or established alcoholic-liver disease were excluded. Patients who reported alcohol intake equivalent to a dose ≥ 20 g/day were also excluded. 53 of 73 patients met study criteria. Patients were subdivided for analysis into groups meeting or not meeting OSA and obesity criteria, and having or not having elevated aminotransferase levels.Results. 35/53 patients (66%) had OSA. 31/53 (58%) patients were obese. 15 (28%) and 12 (23%) patients had elevated AST and ALT, respectively. Mean age, gender distribution, mean BMI and percentage with either diabetes or hyperlipi-demia were not significantly different in those with or without OSA. Elevated ALT was found in 11/35 (31%) patients with OSA, compared to 1/18 patients without OSA (p = 0.041). Frequency of elevated AST [obese 11/31 (35%); non-obese 4/22 (18%)] or ALT [obese 10/31 (32%); non-obese 2/22 (9%)] was not significantly different in the obese and non-obese cohorts.Conclusions. OSA may be a risk factor for liver injury independent of obesity. The prevalence and nature of liver disease in the setting of OSA should be determined with larger, prospective studies. The impact of OSA treatment, if any, on liver injury should be similarly evaluated.     

Sequential changes of serum aminotransferase levels in patients with severe acute respiratory syndrome

Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease. To describe the hepatic injury caused by this disease, we report the sequential changes of serum transaminase in probable SARS patients during a hospital outbreak in southern Taiwan. From April to June, 2003, 52 probable SARS patients were hospitalized. Serial serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were retrospectively analyzed and hepatitis B surface antigen (HBsAg) was also evaluated to correlate with the progression of this disease. Fifty-three percent of the patients had abnormal liver function during hospitalization. More than 70% of abnormal transaminase levels were mildly elevated. Most elevated levels were noted during the second week after onset of fever. Neither transaminase elevation nor HBsAg was related to the prognosis of SARS, and only advanced age was an independent predictor of poor outcome. Our study suggested that coronavirus causing SARS might induce liver damage.     

Abnormal liver chemistries as a predictor of COVID-19 severity and clinical outcomes in hospitalized patients

BACKGROUND Abnormal liver chemistries are common findings in patients with Coronavirus Disease 2019(COVID-19).However,the association of these abnormalities with the severity of COVID-19 and clinical outcomes is poorly understood AIM We aimed to assess the prevalence of elevated liver chemistries in hospitalized patients with COVID-19 and compare the serum liver chemistries to predict the severity and in-hospital mortality.METHODS This retrospective,observational study included 3380 patients with COVID-19 who were hospitalized in the Johns Hopkins Health System(Baltimore,MD,United States).Demographic data,clinical characteristics,laboratory findings,treatment measures,and outcome data were collected.Cox regression modeling was used to explore variables associated with abnormal liver chemistries on admission with disease severity and prognosis RESULTS A total of 2698(70.4%)had abnormal alanine aminotransferase(ALT)at the time of admission.Other more prevalent abnormal liver chemistries were aspartate aminotransferase(AST)(44.4%),alkaline phosphatase(ALP)(16.1%),and total bilirubin(T-Bil)(5.9%).Factors associated with liver injury were older age,Asian ethnicity,other race,being overweight,and obesity.Higher ALT,AST,T-Bil,and ALP levels were more commonly associated with disease severity.Multivariable adjusted Cox regression analysis revealed that abnormal AST and T-Bil were associated with the highest mortality risk than other liver injury indicators during hospitalization.Abnormal AST,T-Bil,and ALP were associated with a need for vasopressor drugs,whereas higher levels of AST,T-Bil,and a decreased albumin levels were associated with mechanical ventilation CONCLUSION Abnormal liver chemistries are common at the time of hospital admission in COVID-19 patients and can be closely related to the patient’s severity and prognosis.Elevated liver chemistries,specifically ALT,AST,ALP,and T-Bil levels,can be used to stratify risk and predict the need for advanced therapies in these patients.     

The relative expression of hepatocellular and cholestatic liver enzymes in adult patients with liver disease

Introduction and objectivesHepatocellular liver injury is characterized by elevations in serum alanine (ALT) and aspartate (AST) aminotransferases while cholestasis is associated with elevated serum alkaline phosphatase (ALP) levels. When both sets of enzymes are elevated, distinguishing between the two patterns of liver disease can be difficult. The aim of this study was to document the predicted ranges of serum ALP values in patients with hepatocellular liver injury and ALT or AST values in patients with cholestasis.Materials and methodsLiver enzyme levels were documented in adult patients with various types and degrees of hepatocellular (non-alcoholic fatty liver disease, hepatitis B and C, alcohol and autoimmune hepatitis) and cholestatic (primary biliary cholangitis and primary sclerosing cholangitis) disease.ResultsIn 5167 hepatocellular disease patients with ALT (or AST) values that were normal, 1–5×, 5–10× or >10× elevated, median (95% CI) serum ALP levels were 0.64 (0.62–0.66), 0.72 (0.71–0.73), 0.80 (0.77–0.82) and 1.15 (1.0–1.22) fold elevated respectively. In 252 cholestatic patients with ALP values that were normal, 1–5× or >5× elevated, serum ALT (or AST) values were 1.13 (0.93–1.63), 2.47 (2.13–2.70) and 4.57 (3.27–5.63) fold elevated respectively. In 56 patients with concurrent diseases, ALP levels were beyond predicted values for their hepatitis in 38 (68%) and ALT (or AST) values beyond predicted values for their cholestatic disorder in 24 (43%).ConclusionsThese data provide health care providers with predicted ranges of liver enzymes in patients with hepatocellular or cholestatic liver disease and may thereby help to identify patients with concurrent forms of liver disease.     

The AST/ALT ratio as an indicator of cirrhosis in patients with PBC.

OBJECTIVES: A non-invasive, simple and non-expensive test to predict cirrhosis would be highly desirable. The aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio has been proven to be such an indicator of cirrhosis in alcoholic liver disease, hepatitis C. AIM: To test whether the AST/ALT ratio is a marker of cirrhosis also in patients with primary biliary cirrhosis (PBC). METHODS: The study consisted of 160 patients. In 126 patients, we had clinical and laboratory data at the time of diagnosis and follow-up with outcome: liver-related death, liver transplantation and survival. In 121 patients, we had laboratory data and liver histology. RESULTS: We found that the AST/ALT ratio was significantly higher in cirrhotic patients than in non-cirrhotic patients. A high AST/ALT ratio was significantly associated with esophageal varices and ascites. In a multivariate analysis, bilirubin and ALP were predictors of poor prognosis. CONCLUSION: The AST/ALT ratio seems to be of clinical value as a hint to the diagnosis of cirrhosis in patients with PBC but not as a prognostic factor.     

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.     

Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians

A recent genome-wide study revealed an association between variation in the PNPLA3 gene and liver fat content. In addition, the PNPLA3 single-nucleotide polymorphism rs738409 (M148I) was reported to be associated with advanced alcoholic liver disease in alcohol-dependent individuals of Mestizo descent. We therefore evaluated the impact of rs738409 on the manifestation of alcoholic liver disease in two independent German cohorts. Genotype and allele frequencies of rs738409 (M148I) were determined in 1,043 alcoholic patients with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort. Relative to alcoholic patients without liver damage (n = 439), rs738409 genotype GG was strongly overrepresented in patients with alcoholic liver cirrhosis (n = 210; OR 2.79; P(genotype) = 1.2 × 10(-5) ; P(allelic) = 1.6 × 10(-6) ) and in alcoholic patients without cirrhosis but with elevated alanine aminotransferase levels (n = 219; OR 2.33; P(genotype) = 0.0085; P(allelic) = 0.0042). The latter, biochemically defined association was confirmed in an independent population-based cohort of at-risk drinkers with a median alcohol intake of 300 g/week (OR 4.75; P(genotype) = 0.040; P(allelic) = 0.022), and for aspartate aminotransferase (AST) levels. Frequencies of allele PNPLA3 rs738409(G) in individuals with steatosis and normal alanine aminotransferase (ALT) and AST levels were lower than in alcoholics without steatosis and normal ALT/AST (P(combined) = 0.03). The population attributable risk of cirrhosis in alcoholic carriers of allele PNPLA3 rs738409(G) was estimated at 26.6%. CONCLUSION: Genotype PNPLA3 rs738409(GG) is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians.     

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.     

Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population.

BACKGROUND & AIMS: Both alcohol and obesity are associated with hepatic steatosis. However, little is known about whether the toxicity of alcohol to the liver is influenced by adiposity. We examined the relationship of alcohol drinking and binge drinking with abnormal serum aminotransferase activity in normal weight, overweight, and obese persons in a national, population-based study. METHODS: Data were analyzed from 13,580 adult participants in the third US National Health and Nutrition Examination Survey, 1988-1994, after excluding participants with hepatitis B or C or iron overload. Abnormal aminotransferase levels were defined by using sex-specific cutoffs for ALT and AST. Analyses were adjusted for other liver injury risk factors. RESULTS: The prevalence of abnormal aminotransferase activity was elevated with consumption of >2 drinks per day or with overweight and obesity. In multivariate analysis, there was no association of alcohol intake with a higher prevalence of elevated aminotransferase levels among normal weight persons. In contrast, among overweight persons, consumption of >2 drinks per day increased the risk of elevated aminotransferase levels, and among the obese, > or = 1 drink per day was associated with a higher risk. Results were similar with elevated ALT alone as the outcome. With elevated AST alone as the outcome, intake of >2 drinks per day increased the risk, even among normal weight persons. Binge drinking was associated with aminotransferase elevation among obese consumers of 1-2 drinks per day. CONCLUSIONS: In this large, national, population-based study, overweight and obesity increased the risk of alcohol-related abnormal aminotransferase activity.     

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.     

临床诊断的肝细胞型急性药物性肝损伤患者血清ALT/ALP比值变化特点与组织病理学特征分析

目的 探讨药物性肝损伤(DILI)患者临床分型的变化及其组织病理学特征。方法 2018年8月～2019年8月入院临床诊断为肝细胞型DILI患者43例,在入院治疗2周后行肝穿活检,在病理学检查当日再次根据临床指标确定临床分型,观察组织病理学特征。结果 43例临床诊断的肝细胞型DILI患者在肝穿时血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血清总胆红素(TBIL)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)和总胆汁酸(TBA)水平已显著降低,其R值较入院时也显著下降(19.6±13.6对3.29±3.26),差异具有统计学意义(P<0.05);组织病理学检查诊断急性炎症型21例,炎症淤胆型22例;在入院时,急性炎症型与炎症淤胆型患者血清ALT、AST、TBIL、ALP和GGT水平无显著性差异(P>0.05),仅急性炎症型患者R值显著小于炎症淤胆型(13.8±6.2对25.5±16.5,P=0.004),血清TBA水平显著低于炎症淤胆型(61.0±60.8 μmol/L对115.3±80.9μmol/L,P=0.017);入院时诊断为肝细胞型DILI的43例患者在肝穿时仅9例符合肝细胞型临床分型;经ROC曲线分析,以R值等于14.9为截断点,其曲线下面积(AUC)为0.708,具有一定的诊断意义。结论 药物性肝损伤的临床分型会随着病情的变化而呈动态变化,入院时以较高的R值诊断胆汁淤积具有一定的指导意义,值得进一步观察。     

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.