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Hepatic Transaminase Activity in Alcoholic Liver Disease
Abstract
Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activity were measured in precutaneous needle biopsy specimens of human liver tissue and compared with transaminase values in serum obtained on the day of biopsy. Hepatic GPT activity was significantly decreased in liver tissue of patients with alcoholic hepatitis and cirrhosis compared with the activity in individuals with normal livers (P less than 0.05) and individuals with primary biliary cirrhosis (P less than 0.05). The decreased hepatic GPT activity was not related to the presence of cirrhosis in biopsy specimens and was not increased by the addition of saturating amounts of pyridoxal phosphate to the assay mixture. Hepatic GOT was also slightly but significantly lowered in individuals with alcoholic liver disease (P less than 0.05). The GOT/GPT ratio in serum and liver tissue was increased only in individuals with alcoholic liver disease, but the increase did not reach statistical significance. The increased GOT/GPT ratio is due primarily to the low activity of GPT in liver and serum. The less than expected elevation of GPT in serum of patients with alcoholic hepatic reflects the diminished hepatic GPT activity and lesser amounts of this enzyme available to leak into serum from damaged hepatocytes.
... Previous studies have established that an AST to ALT ratio greater than 2.0 is highly suggestive of alcoholic hepatitis and cirrhosis. [9][10][11] These findings imply that serum ALT activity is consistently lower compared with serum AST activity in patients with alcohol-related diseases. This should be true throughout the entire range of transferase activity, including activities below the normal or reference range. ...
... Other investigators emphasize the consistency with which the serum AST exceeds the ALT activity in patients with alcoholic liver disease. [9][10][11] The decrease in hepatic ALT activity is specific for alcoholic liver disease and does not reflect cirrhosis or chronicity of hepatic disease. 9 Liver AST activity also is decreased in patients with alcoholic liver disease but to a lesser extent compared with hepatic ALT. 9 Data suggest that chronic pyridoxal phosphate deficiency is partially responsible for the high ratio of serum AST to ALT found in patients with alcoholic liver disease. ...
... [9][10][11] The decrease in hepatic ALT activity is specific for alcoholic liver disease and does not reflect cirrhosis or chronicity of hepatic disease. 9 Liver AST activity also is decreased in patients with alcoholic liver disease but to a lesser extent compared with hepatic ALT. 9 Data suggest that chronic pyridoxal phosphate deficiency is partially responsible for the high ratio of serum AST to ALT found in patients with alcoholic liver disease. 12,13 The low pyridoxal phosphate levels in the alcoholic population have been attributed to low dietary intake of pyridoxine, impaired synthesis of pyridoxal phosphate in the presence of severe hepatic disease or alcohol metabolites, and increased pyridoxal phosphate clearance in alcoholic subjects. ...
Two widely used and well-established enzyme tests used to detect diseases of the liver, heart, skeletal muscle, brain, and kidney are elevations in the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). We hypothesized that the frequency of low ALT would greatly exceed the frequency of low AST in a population with a high prevalence of alcoholic liver disease. During 1 year, the frequency of low AST and ALT activity (<10 U/L) was found to be 0.17% (27/16,067) and 4.1% (472/11,582), a 24-fold difference, in 26 and 261 individual patients, respectively. Patients with alcoholic liver disease and low ALT were 10 times the number of those with alcoholic liver disease and low AST, which may reflect the low hepatic and serum ALT activity seen in these patients, as well as the widespread distribution of AST in tissues.
... Serum levels depend markedly on the degree of liver damage and how recently alcohol has been consumed [9,23]. Our results show that the elevation in ALT is not as high as that of AST in ALD patients reflecting diminished hepatic activity of these enzymes, less enzyme being available to leak into the serum from damaged hepatocytes as shown by Maltoff DS et al [24] and Cohen JA et al [25].The normal activity of AST and ALT found in some of our patients with ALD could be related to depletion of vitamin B1 and B6 as suggested by studies of Borghi E et aland Diehl et al [26,27]. ...
... We found that AST/ALT ratio was >2 among ALD patients. The elevated AST/ALT ratio in ALD is due primarily to the selective and significant lowering of liver ALT by alcohol associated with increased AST levels from mitochondrial injury [24]. The ratio >1.5 strongly suggests, and a ratio >2 is almost indicative of alcohol induced liver damage [9]. ...
Aim: To assess the value of enzymes Gamma glutamyltransferase (GGT), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) as diagnostic indicators of alcoholic liver diseases. Material and Methods: Our study group comprised of 25 normal healthy controls, 50 patients with advanced alcoholic liver disease (ALD), 15 patients with acute viral hepatitis (AVH) and 10 patients with non alcoholic cirrhosis (NALD). We analysed GGT, AST, ALT, Total bilirubin, Total protein, Albumin and Prothrombin time. AST/ALT ratio and discriminant function were calculated. Results: GGT values were significantly high (6-8 times upper limit of mean of normal controls) among ALD patients in comparison with all other groups. Mean AST/ALT ratio among ALD patients was >2. 88% patients with ALD had AST/ALT ratio of ≥1.5. The ratio was<2 among all the other diseased groups with a value of 1.15 among normal healthy controls. Discriminant function score of ≥32 was found in 9 among 50 ALD patients. Conclusion: GGT and AST/ALT ratio of ≥1.5 together are good indicators of alcohol as the cause of liver disease. AST/ALT ratio >2 indicates advanced liver disease in alcoholics. Bilirubin and prothrombin time can be used to know the severity of liver disease as a part of discriminant function. A discriminant function of ≥32 have poor prognosis and also helps to select patients for steroid therapy.
... The values were then compared with the normal and standard values. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined as described [17]. Serum cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL) were determined using quantitative kit based on the previously described methods [18][19][20]. ...
Abstract Obesity results in detrimental effects on different body organs. Metformin (Met) has described to decrease the body weight of obese patient and to control the glucose level. This study aimed to evaluate the role of Met treatment for long period on the functionality of liver and kidney organs of obese rats. Forty rats were used in this study and divided into four groups as the following: group 1 (Gp1) was served as a negative control that administered orally with 200 µL of H2O. Gp2 of rats was administered with Met (200 mg/kg) daily for a month. Gp3 was obese rats, and Gp4 was obese rats administered with Met as in Gp2. All rats were sacrificed to analyze hematological, biochemical, and histopathological changes. The results showed that Met decreased the body weight of both naïve and obese rats, however, it caused hepato-renal dysfunctions in obese rats as evidenced by increased the levels of ALT, AST, urea, creatinine, and MDA and decrease in the antioxidants biomarkers (SOD, Cat and GSH). Collectively, Met causes liver and kidneys dysfunctions of obese rats and is not recommended to described for obese persons.
... ALD, alcoholic liver disease. and Baker, 10 Konttinen et al, 19 Matloff et al, 20 Moussavian et al, 21 Das and Vasudevan, 22 Maithreyi et al, 23 Mirunalini et al, 24 Jang et al, 25 Al-Jumaily, 26 Hyder et al, 27 Gayathri and Vasantha, 28 and Brandl et al. 29 However, our findings are contradictory to the study conducted by Hourigan and Bowling 30 who found normal levels of serum AST and ALT in patients with alcoholic cirrhosis. Whereas, in the study conducted by Seth et al 31 there was no significant difference in serum ALT level between the cases and controls (p = 0.21). ...
Background Alcoholic liver disease (ALD) is a major source of alcohol-related morbidity and mortality. Heavy drinkers and alcoholics may progress from fatty liver to alcoholic hepatitis to cirrhosis. The enzyme γ-glutamyltranspeptidase (GGT) is a membrane-bound glycoprotein which catalyzes the transfer of the γ-glutamyl group from γ-glutamyl peptides to other peptides, amino acids, and water. Serum GGT activity mainly attributed to hepatobiliary system and thus is an important marker of ALD. Hence the present study is conducted to estimate and correlate the levels of GGT and osteopontin (OPN) in ALD.
Aims and Objectives The objective of this study is to estimate and correlate the levels of GGT and OPN in ALD.
Materials and Methods Sixty clinically diagnosed cases of ALD and sixty age- and gender-matched healthy controls were recruited for the study. Blood samples were collected from them and serum aspartate aminotransferase, serum alanine transaminases (ALTs), serum ALP levels, and plasma OPN levels were measured. Estimation of serum aspartate transaminases (AST), ALTs, and alkaline phosphatase (ALP) was assayed by standard photometric methods in autoanalyzer ERBA-XL (EM-200) using commercially available kits. OPN was estimated by using commercial kit based on enzyme-linked immunosorbent assay.
Results The parameters of the liver function tests such as AST, ALT, and ALP were significantly increased in patients with ALD (p
... The scientific explanation on why excessive drinkers without cirrhosis do not have a high AST:ALT ratio is not clear, though it is possible that alcohol drinking might have a direct toxic effect on hepatocytes increasing in both serum AST and ALT (Nyblom et al., 2004). Once the disease progresses to a cirrhotic state, there is a significant decrease in ALT activity due to pyridoxal 5 -phosphate depletion (Matloff et al., 1980;Diehl et al., 1984) resulting in an increase in the ratio higher than 2. Taken together, the lack of sensitive non-invasive biomarkers to screen for excessive drinkers with the underlying inflammatory processes likely explains the observation that ALD is barely detected early and a majority of patients present at the late stage when the complications from portal hypertension develop (Shah et al., 2019). ...
Aims:
Alcohol-associated liver disease represents a spectrum of histopathological changes from steatosis to advanced fibrosis and cirrhosis. The major goals of this retrospective study were to characterize the histologic features in patients with excessive alcohol use who presented with an abnormal hepatic panel and/or abnormal radiographic imaging and did not meet the clinical diagnosis of alcoholic hepatitis or cirrhosis.
Methods:
We performed a retrospective study to describe hepatic histology of 62 and 83 excessive drinkers with normal and abnormal serum aspartate transaminase, respectively. The types of inflammatory cells in the liver were characterized by immunohistochemistry for CD4, CD8, CD20, CD68 and myeloperoxidase.
Results:
Among 62 patients with aspartate aminotransferase (AST) ≤ 50 U/L, 37% had histological evidence of steatosis. Of these, we found evidence of hepatocyte ballooning (21%), lobular inflammation (50%), portal inflammation (52%) and fibrosis (14%). For those with AST > 50 U/L, the presence of hepatic steatosis, lobular inflammation and portal inflammation was observed in 29, 60 and 69% of patients, respectively. Fibrosis was found in 33%, four with bridging fibrosis, and one with cirrhosis. We observed the aggregation of CD68+ macrophages, rather than normally distributed with minimal neutrophilic infiltration. Lobular and portal lymphocytic infiltrations are primarily CD8+ T cells.
Conclusion:
Abnormal hepatic histopathology occurs in excessive drinkers with normal transaminase activity. Future studies to determine the diagnostic modalities to detect such abnormalities and to better understand its clinical implications and long-term outcome are needed.
... A study carried out by Ning and collaborators in 1966 found no change in liver ALT or AST activities when homogenates of human liver were incubated with PLP [31]. However, in 1976, Horder and collaborators reported an increase in liver and serum ALT activities when patients with chronic alcoholic liver disease were given oral pyridoxine supplementation [32]. A similar observation was made by Ludwig and coresearchers (1980) who reported a marked increase in AST activity when serum from patients with acute non-cholestatic liver disease was pre-incubated with pyridoxal phosphate [33]. ...
Aim: The current study assessed the association between Pyridoxal-5'-phosphate (PLP) levels, liver and serum activities of aminotransferases (ALT and AST) and De Ritis ratio (DRR) in ten subjects with alcoholic hepatitis (test group-TG) and 10 healthy subjects without alcoholic hepatitis Original Research Article Ndeh et al.; AJRRHE, 3(1): 1-10, 2021; Article no.AJRRHE.63982 2 (control group-CG) with mean age of 41 years of both genders who were attending the University of Calabar Teaching Hospital, Calabar, Nigeria. Study Design: The current study was a randomized experimental designed work. Place and Duration of Study: The study carried out in Chemical Methodology: Appropriate samples were collected from both TG and CG after 8-10 hours fasting and treated using standard procedures. PLP was determined by techniques of Lumeng and co-workers, 1981 (reagents from New England Nuclear, Massachusetts, USA). Hepatic protein levels and aminotransferase activities were determined by spectrophotometric methods, (reagents from Sigma-Aldrich Company, USA). Liver biopsy specimens were obtained with a Klatskin needle for histology. Results: Before PLP supplementation of liver homogenates a significant decreased in PLP levels, increased liver ALT and decreased AST activities were observed in test group. After one month of pyridoxine supplementation, there was a significant increase (p<0.02) in plasma PLP level in all groups with decreased serum AST and increased serum ALT activities ,while liver ALT and AST activities increased significantly (p<0.005) resulting to a decrease serum DRR (p<0.001) in test group. Conclusion: PLP depletion may be partially responsible for the low serum DRR which is reputed to be a typical potent, non-invasive, economical and dynamic prognostic biomarker of alcoholic hepatitis.
... Based on the data obtained from other studies, the upper normal limits for ALT and AST were set at 40 U/L and 50 U/L for GGT, respectively (33)(34)(35). However, to better distinguish liver injury from other etiology, we applied the increased AST:ALT >2, and increase in GGT >50 U/L during the hospital stay (36,37). The combined elevation was used for the group allocation. ...
Short Summary: Extracellular vesicles (EVs), released during tissue/cell injury, contain a “barcode” indicating specific microRNAs (miRs) that can uncover their origin. We examined whether systemic EVs possessing hepatic miR-signatures would indicate ongoing liver injury and clinical complications in trauma patients (TP). We grouped the patients of alcoholic drinkers into “alcohol-drinkers with liver injury (LI)” (EtOH with LI) or “alcohol-drinkers without LI” (EtOH w/o LI) and we compared these groups to “non-drinkers” (no EtOH). When we examined patient blood from the EtOH with LI group we found the total number of EVs to be increased, along with an increase in miR-122 and let7f—two EV-associated miRNAs—and several inflammation-associating cytokines, such as interleukin (IL)-6 and IL-33. In contrast, all of the aforementioned readouts were found to be decreased in the EtOH w/o LI group. These novel data demonstrate that hepatocyte damage in alcohol-intoxicated trauma patients presenting with liver injury can be reflected by an increase in circulating serum EVs, their specific miR-“barcode” and the concomitant increase of systemic inflammatory markers IL-6 and IL-33. Anti-inflammatory effect of alcohol-drinking in EtOH w/o LI can be presented by a reduced number of hepato-derived EVs, no upregulation of IL-6 and IL-33, and a miR “barcode” different from patients presenting with liver injury.
Background: Alcohol abuse is associated with (neuro)protective effects related to (head) injuries, and with negative effects regarding infection rates and survival in severely injured trauma patients (TP). Extracellular vesicles (EVs), which are released during tissue and/or cell injury, can contain a “barcode” including specific microRNAs (miRs) that uncover their origin. We examined whether EVs with a hepatic miR signature can be systemically measured, and whether they can indicate ongoing liver injury in alcohol-intoxicated TP and foretell clinical complications.
Patients/Methods: We enrolled 35 TP and measured blood EVs, IL-6, TNF-alpha, IL-1beta, IL-10 and IL-33, alcohol (ethanol, EtOH) concentration (BAC), GLDH, GGT, AST, ALT, leukocytes, platelets, and bilirubin. Within circulating EVs we measured the expression levels of miR-122, let7f, miR21, miR29a, miR-155, and miR-146a. Patients of alcohol-drinkers were grouped into “alcohol drinkers with liver injury (LI)” (EtOH with LI) or “alcohol drinkers without LI” (EtOH w/o LI) and compared to “non-drinkers” (no EtOH). We assessed systemic injury characteristics and the outcome of hospitalization with regard to sepsis, septic shock, pneumonia, or mortality.
Results: EtOH with LI patients had significantly increased rates of pneumonia vs. the EtOH w/o LI group. EVs, IL-6, and IL-33 levels were significantly increased in EtOH with LI vs. EtOH w/o LI group (p < 0.05). EV number correlated positively with ALT and IL-6 (p < 0.0001). Two miRs, miR-122 and let7f, were increased only in the blood EVs from the EtOH with LI group (p < 0.05). Five miRs, miR-122, let7f, miR-21, miR-29a, and miR-146a, were reduced in the blood EVs from the EtOH w/o LI group, vs. no EtOH (p < 0.05). Notably miR-122 correlated significantly with increased bilirubin levels in the EtOH with LI group (p < 0.05).
Conclusions: Liver injury in alcohol-intoxicated TP is reflected by increased EV numbers, their specific miR barcode, and the correlated increase of systemic inflammatory markers IL-6 and IL-33. Interestingly, severely injured TP without liver injury were found to have a reduced number of liver-derived EVs, no observed inflammatory infiltration and reduced specific miR “barcode.”
... In these studies K18 and cK18 levels are >1,000 U/L despite the fact that ALT levels are rarely elevated in the context of alcoholic hepatitis (3,5,6). This is likely due to endogenous suppression of the ALT enzyme by alcohol (14). Previous work from our laboratory has noted that K18 levels can increase to as much as 30,000 U/L in the absence of increases in ALT in alcoholic hepatitis (5). ...
... 21 It should be noted, though, that ALT values may be partially suppressed due to an overall reduction of ALT activity in the liver of AH cirrhotics. 22 The limited degree of cell death that occurs during AH is likely not a mitigating disease factor acutely; although, the chronic cell death that occurs during the course of ALD is still a potential driver of subsequent inflammation, fibrosis and eventual cirrhosis. ...
Alcoholic hepatitis is the most severe and acute form of alcoholic liver disease. The mortality rate associated with alcoholic hepatitis is high, largely due to the lack of suitable pharmacological interventions. While there has been substantial research in the area, generating pharmacological interventions has been plagued by the lack of a robust mouse model both for testing and for understanding the underlying pathology. A number of major notable advances have been made in this area recently, with the goal of generating a mouse model of alcoholic hepatitis. The purpose of this article is to review recent advances in modeling alcoholic liver disease both in vitro and in vivo in the mouse, and place them in the context of the greater spectrum of alcoholic liver disease, with a focus on how we can translate current advances into a high-fidelity model of alcoholic hepatitis. In addition, we will review the basic mechanisms of alcoholic hepatitis as it is currently understood, focusing on recent advancements in diagnosis, prognosis and current pathophysiology, especially as it relates to the profound immune dysfunction present during alcoholic hepatitis.
... In alcoholism, the most common disease associated with AST/ALT ratio elevation, three possible causes have been proposed: (1) deficiency of pyridoxal 5 -phosphate (the active metabolite of B6 which is required for creation of ALT, but not AST), 7 (2) mitochondrial damage leading to increased mitochondrial AST in the serum, 8 and (3) decreased production of ALT from a chronically damaged liver. 9 In addition, damage to organs that produce AST but not ALT, is possible in patients with disseminated histoplasmosis. This would include the reticuloendothelial system, including the spleen, muscle, intestine and kidneys. ...
Severe pulmonary or disseminated histoplasmosis often necessitates presumptive antifungal treatment while awaiting definitive diagnosis. Histoplasma antigen assays have improved sensitivity but results may lag up to 7 days. In order to increase diagnostic certainty, “soft clues” may be looked for in laboratory and radiologic data, such as elevated alkaline phosphatase or ferritin levels and findings of mediastinal adenopathy or hepatosplenomegaly. To determine if elevated aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio is specific to histoplasmosis or a non-specific marker for disseminated fungal infection or sepsis in general, we retrospectively examined records of all patients diagnosed with an endemic fungal infection (EFI) at Rush University Medical Center from January of 1997 to October of 2012, and a cohort of septic patients with elevated liver enzymes. We identified 90 cases of EFIs during the study period that met all inclusion criteria (Histoplasma 21, Blastomyces 56, Coccidioides 12, Paracoccidioides 1). We also evaluated 10 control patients with bacterial sepsis. The mean ratio of AST to ALT in patients with disseminated histoplasmosis was 2.69 (95% CI:1.22, 4.16) while for other EFIs, the mean ratio ranged from 0.38 to 1.14 with disseminated coccidioidomycosis and blastomycosis respectively (P < 0.0001). The ratio in patients with bacterial sepsis was 0.84. We propose the use of the AST/ALT ratio as a clinical “soft clue” suggestive of disseminated histoplasmosis in the appropriate host, and to possibly distinguish cross reactivity of the Histoplasma antigen assay with other EFIs.
... ALT levels >500 U/L exclude the diagnosis of alcoholic hepatitis [41]. Higher values should raise the suspicion of concurrence with alcohol abuse of viral, ischemic, or drug-related (e.g., by taking a relatively large amount of paracetamol) hepatitis. ...
Liver disease is responsible for more than 55% of deaths resulting from alcohol abuse, and the prevalence of alcoholic liver disease (ALD) is closely correlated with per capita alcohol consumption. ALD represents a broad range of histological changes ranging from simple steatosis to heavier forms of liver injury, including alcoholic hepatitis (AH), cirrhosis, or the parallel development of hepatocellular carcinoma (HCC). These alterations of the hepatic parenchyma are not necessary to reflect distinct stages of the liver disease progression but rather a continuum relating histological changes that may be observed simultaneously in the same patient.
The fact that only 35% of patients with substantial alcohol abuse develop advanced stages of liver disease suggests that the pathogenesis of ALD involves many other factors that include gender, obesity, drinking patterns, dietary factors, non-sex-linked genetic factors, and smoking. Also, long-term drinking can affect synergistically with hepatitis B or C or the human immunodeficiency virus, the non-alcoholic fatty liver disease, and hepatic disorders such as hemochromatosis.
The diagnosis of ALD is based on a combination of findings, including the history of significant alcohol consumption, the clinical evidence of the concomitant liver injury, and the support of the clinical case from the resultant histological, imaging, and laboratory findings.
The beneficial effect of treating AH with corticosteroids occurs in patients with encephalopathy or with poor prognosis, based on the various grading and prognostic systems of gravity, while its harmful effect is evident in patients with milder disease as they manifest an increased risk of infections compared with those not receiving corticosteroids. In patients with alcoholic hepatitis, who cannot take corticosteroids for various reasons and in those with the onset of functional renal failure (hepatorenal syndrome), the use of pentoxifylline is recommended.
... Since AST is located both in the cytosol and mitochondria, serum levels depend markedly on the degree of liver damage and also on how recently the alcohol has been consumed [8]. The determination of the Deritis ratio in alcoholic liver disease patients can be considered as a dependable marker, which has also been proved by international data [9]. ...
Background: Oxidative stress and the influence of free radicals and their metabolites decrease the serum antioxidant status. They play a very important role in the pathogenesis of liver disease. The aim of the present study is to assess the Deritis in alcoholic and nonalcoholic liver disease patients in comparison to healthy controls and to evaluate its significance as a prognostic marker of liver disease. Methods: 100 cases were studied, of which 50 were normal healthy controls, 10 were alcoholic hepatitis patients, 10 were non-alcoholic hepatitis patients, 10 were alcoholic cirrhosis patients and 20 were non-alcoholic cirrhosis patients. Serum AST and ALT levels were estimated in all subjects by using commercial kits from CPC diagnostics (Raichem USA). The readings were taken on a semiautoanalyser (STATFAX 3300). Statistical analysis was done by using the Student's 't' test. Results: The Deritis was significantly increased in patients with alcoholic hepatitis and cirrhosis as compared to non-alcoholic hepatitis and cirrhosis patients, respectively (P<0.05). Further, significantly elevated Deritis was observed in non-alcoholic hepatitis and cirrhosis patients as compared to healthy controls (P<0.001). Conclusion: The findings of the present study are consistent with previous studies, suggesting that hepatocyte damage causes leak of these enzymes into the circulation. This study concludes that Deritis is a dependable marker of alcoholic liver disease.
... However, the ratio AST/ALT seems to provide meaningful information (Reichling and Kaplan, 1988). A cut-off value of the ratio > 2 is usually assumed to reflect an alcoholic etiology of the liver disease, while most patients with non-alcoholic liver disease exhibit a ratio < 1 (Matloff et al., 1980;Niemelä, 2002;Prytz and Melin, 1993;Rosman and Lieber, 1994). ...
Alcohol abuse is frequently associated with an increased risk of road accidents and violence, and can also lead to serious social and health problems. Therefore, the use of reliable markers to detect excessive punctual and/or chronic consumption of alcohol is necessary to prevent the harmful consequences of alcohol abuse. Ethylglucuronide (EtG) has been proposed as a marker of alcohol consumption in a variety of clinical and forensic contexts. Compared with the indirect markers (e.g. CDT, γ-GT), this minor metabolite of ethanol is very sensitive and specific, and is quantifiable in various biological matrices. It is formed by conjugation of ethanol with uridine 5'-diphosphate glucuronic acid (UDP-GA) via the action of UDP-glucuronosyltransferase (UGT) enzymes. However, the knowledge of the UGTs involved in the glucuronidation of ethanol, and the potential sources of the interindividual variability of EtG production are still not clearly established. The aims of our work were (1) to develop and validate a method for the determination of EtG in different biological matrices by gas chromatography coupled with tandem mass spectrometry, (2) to identify the human UGT isoforms involved in the glucuronidation of ethanol, and then to evaluate qualitatively and quantitatively their specific contribution in the formation of EtG, (3) to study the impact of the co-administration of drugs frequently used by ethanol consumers on the in vitro production of EtG, (4) to study the impact of functional genetic polymorphisms of two UGTs on the hepatic production of EtG, and finally (5) to study the impact of the consumption of cannabis and other drugs on the production of EtG using post-mortem samples. The main results of our study showed that (1) ethanol is primarily glucuronidated by the liver and, to a lesser extent, by kidneys, (2) UGT1A9 and 2B7 were identified as the main human UGTs involved in ethanol glucuronidation, (3) morphine, codeine, nicotine, and cotinine did not modify EtG in vitro formation rate; lorazepam and oxazepam produced a minor, but not significant, increase of EtG formation. Only cannabinol and cannabidiol significantly affected ethanol glucuronidation; cannabinol significantly increased the glucuronidation of ethanol in a concentration-dependent manner, whereas cannabidiol inhibited the glucuronoconjugaison of ethanol by a non-competitive mechanism (CI50 = 1.17 mg / L; Ki = 3.1 mg / L), (4) the SNP c.-900G>A and IVS1+399T>C affecting UGT2B7 and UGT1A9, respectively, seem to increase the in vitro production of EtG, and (5) cannabis and/or drugs consumption (mainly opioids, benzodiazepines, and paracetamol) seem to be associated with ratios of blood concentrations of EtG/ethanol significantly higher than those observed among only alcohol consumers. Taken together, these results show the existence of several factors that could potentially influence the production of EtG, and that should be taken into account when interpreting its concentration in vivo.
... High AST:ALT ratio (>2) suggests the presence of advanced alcoholic liver disease/cirrhosis. The explanation for AST:ALT>2 in alcoholic liver cirrhosis is the decreasing in ALT activity or pyridoxal 5′phosphate depletion (Diehl et al. 1984;Matloff, Selinger, and Kaplan 1980). However, the reason on why in excessive drinkers without alcoholic liver disease did not have high AST:ALT ratio is not clear, though it is possible that ongoing and excessive alcohol drinking might have direct toxic effect on both AST and ALT (Nyblom et al. 2004). ...
This current study was undertaken to carefully assess the accuracy of routinely used laboratory tests in detecting excessive/recent alcohol use. We also determined the kinetics of these markers in subjects who underwent an intensive alcohol rehabilitation program.
The study cohort consisted of 210 nonexcessive drinkers, 272 excessive drinkers, and 76 with alcoholic cirrhosis. To determine the kinetics of these markers during alcohol abstinence, we followed 45 subjects with history of excessive alcohol use for 12 weeks during the intensive alcohol treatment program.
Percentage of carbohydrate deficient transferrin (%CDT) provided the highest diagnostic performance (area under the curve [AUC] 0.77) followed by gamma-glutamyl transferase (GGT) (AUC 0.68) to detect excessive drinkers. The percentage of excessive drinkers with aspartate aminotransferase:alanine aminotransferase (AST:ALT) > 2 was only 2%, whereas 51% of subjects with alcoholic cirrhosis had AST:ALT > 2. In the multivariate analysis, the levels of GGT and %CDT were associated with the level of alcohol consumed during the past 30 days. The levels of GGT, mean corpuscular volume (MCV), and %CDT were significantly lower compared to those at baseline before alcohol rehabilitation, whereas the AST, ALT, and AST:ALT ratio were unchanged. The percent reduction was ~2.7% (for MCV), 19% (for GGT), and 43% (for %CDT) at the end of the 12-week follow-up compared to the baseline.
%CDT are useful markers to screen for excessive alcohol use and for follow-up of abstinence. Most subjects with excessive alcohol use do not have a high AST:ALT ratio. Rather, the AST:ALT > 2 is suggestive of alcoholic cirrhosis. The performance of the %CDT to screen for heavy alcohol use is still not ideal. Further research to identify the noninvasive marker(s) (i.e., using proteomic or metabolomics approach) should be considered.
Copyright © 2015 by the Research Society on Alcoholism.
... Long-term exposure to alcohol promotes mitochondrial ASAT to translocate to the cell membrane, as well as its induction by an upregulation at the transcriptional level. 57 As a result, serum mitochondrial ASAT activity is greatly increased on heavy alcohol consumption, leading to inversion of the ASAT/ALAT ratio, usually higher than 2. 58 It has been suggested that the serum mitochondrial/total ASAT activities ratio could be used to discriminate drinkers in case of hepatopathy. 59 ...
Philippe Gonzalo,1 Sylvie Radenne,2 Sylvie Gonzalo31Laboratoire de Biochimie, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France; 2Service d'Hépatologie-Gastroentérologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France; 3Laboratoire Biomnis, Lyon, FranceAbstract: Biological markers of chronic alcoholism can be divided into two groups: direct and indirect markers. Direct markers (mainly blood or serum and urine ethanol, ethylglucuronide, ethyl sulfate, and phosphatidylethanol) directly track the intake of alcohol and vary in their sensitivity and kinetics of appearance and clearance. Indirect markers (mean corpuscular volume,γ-glutamyl transferase, alanine aminotransferase and aspartate aminotransferase, and carbohydrate-deficient transferrin) are biological parameters that are influenced by a steady and significant alcohol intake. We discuss the values of these tests and the relevance of their prescriptions for the clinical evaluation of heavy drinking. We indicate, when known, the pathophysiological mechanism of their elevations. We also discuss the amount and time of alcohol consumption required to give a positive result and the duration of abstinence required for the return to normal values. The forensic use of these biomarkers will not be considered in this review.Keywords: alcoholism, biomarker, CDT, relapse, alcohol-induced liver disease
... In Leiber's [11] study elevated level of ALT were noted in 50%, 95% and 50% cases of fatty liver, hepatitis and cirrhosis respectively which differs from the findings -3]: Relationship of clinical and biochemical parameters of alcoholic liver disease with respect to duration and quantity of alcohol intake in our study. Matloff et al., [17] in their study showed ratio of AST / ALT greater than 2 is highly suggestive of alcoholic hepatitis. ALP was raised in 15% patients in our study. ...
Background:
Alcoholism is a health problem not only in developed countries but also in developing countries. Cirrhosis due to alcohol is a common cause of death among individuals abusing alcohol. A better knowledge of the spectrum of alcoholic liver diseases, its clinical, biochemical and histopathological features could result in early detection and prevention of alcoholic liver diseases before it's catastrophic and life threatening effects.
Materials and methods:
A total of 200 patients with alcoholic liver diseases were studied with respect to alcohol consumption, clinical features, biochemical and histopathological changes. The clinical features, biochemical parameters, and histopathology of liver including Ishak's modified histological activity index (HAI) were correlated with the amount and duration of alcohol consumed.
Result:
Majority of the patients were in the age group of 40-49 years and all the cases were males. Majority consumed alcohol of about 75-90 grams per day for a duration of 10-12 years. Anorexia and jaundice were the most common symptom and clinical finding respectively. Hyperbilirubinemia and hypoalbuminemia were the most common abnormalities observed in liver function tests. Advanced HAI stages with features of cirrhosis were most frequent histo-pathological finding noted in this study. Clinico-biochemical profile was significantly correlated with degree of alcohol ingestion as well as with liver histopathology.
Conclusion:
The wide prevalence of alcoholic liver disease including cirrhosis among Indian males was noted with significantly lower quantity and duration of alcohol ingestion. The severity of liver damage is directly proportional to the quantity and duration of alcohol consumed. Clinical features and biochemical changes may forecast the liver histopathology among the patients of alcoholic liver disease.
... In alcoholism, the most common disease associated with AST/ALT ratio elevation, three possible causes have been proposed: (1) deficiency of pyridoxal 5 -phosphate (the active metabolite of B6 which is required for creation of ALT, but not AST), 7 (2) mitochondrial damage leading to increased mitochondrial AST in the serum, 8 and (3) decreased production of ALT from a chronically damaged liver. 9 In addition, damage to organs that produce AST but not ALT, is possible in patients with disseminated histoplasmosis. This would include the reticuloendothelial system, including the spleen, muscle, intestine and kidneys. ...
Background: Histoplasma capsulatum is one of the most common causes of fungal infection in the United States. Severe pulmonary or disseminated infection necessitates presumptive treatment while awaiting definitive tissue diagnosis. Histoplasma antigenemia/antigenuria assays have improved earlier detection but results may be delayed. In order to increase diagnostic certainty, “soft clues” may be looked for in laboratory data, such as elevated alkaline phosphatase or ferritin levels. At our institution, we observed an elevated AST/ALT ratio in patients with disseminated histoplasmosis. We sought to determine whether this finding is unique to histoplasmosis or a non-specific marker for disseminated fungal infection or sepsis in general.
Methods: We retrospectively examined electronic and microbiology records of all patients with tissue cultures positive for endemic fungi. We identified 90 cases of endemic fungal infections (EFIs) at our institution from 1997-2012 (Histoplasma 21, Blastomyces 56, Coccidioides 12, Paracoccidioides 1). We also evaluated 9 patients that met 3 to 4 SIRS (systemic inflammatory response syndrome) criteria and had proven bacterial infection. We analyzed data based on type of fungal infection, underlying host immune status, and extent of disease. The data was analyzed using one way and two way ANOVAs.
Results: The mean AST/ALT ratio in patients with disseminated histoplasmosis was 2.53 (range 0.85-5.7). For other EFIs, the mean ratio was 0.99 (range 0.11-1.63). The AST/ALT ratio was significantly higher in patients with disseminated histoplasmosis (p<0.0001). Although not as high as in disseminated histoplasmosis, patients with musculoskeletal blastomycosis had a higher AST/ALT ratio than other groups, likely from skeletal muscle inflammation.
Conclusion: We propose use of the AST/ALT ratio as a clinical “soft clue” suggestive of the diagnosis of disseminated histoplasmosis in the appropriate host.
... Decreased levels of tissue marker enzyme in myocardially infarcted rats can be attributed to the damaged structural integrity of the liver [9] because these are cytoplasmic in location and are released into circulation after cellular damage. [10] Measurements of aminotransferases and LDH assess hepatocyte integrity. Even mild changes in their levels may be due to the presence of potentially significant liver disease. ...
Myocardial infarction produces significant abnormal liver functioning. In the present study the effect of Tribulus terrestris Fruit aqueous Extract (TTFAEt) in myocardial Infarcted rats was investigated. The oral administration of TTFAEt to rats for 40 days afforded good protection against isoproterenol-induced alterations in tissue marker enzymes of liver injury like alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase. The protective effect of TTFAEt was further supported by the reversal of isoproterenol-induced histological changes in the liver. The results suggest that TTFAEt, which can protect the heart and circulatory system, can also be hepotoprotective and maintain the near healthy architecture of liver tissue. ©2012 Universal Research Publications. All rights reserved Key words; -Tribulus terrestris Fruit aqueous Extract, liver marker enzymes, plasma proteins, histopathology. Introduction Myocardial infarction is a clinical syndrome arising from sudden and persistent curtailment of myocardial blood supply which results in the necrosis of the myocardium (Anversa and Sonnerblick, 1990).Cardiovascular diseases (CVD) remain the principal cause of death in both developed and developing countries, accounting for roughly 20% of all annual deaths worldwide. Myocardial infarction (MI) is the rapid development of myocardial necrosis caused by critical imbalance between oxygen supply and the demand of the myocardium. Oxidative stress resulting from increased production of free radicals associated with decreased levels of antioxidants in the myocardium plays a major role in CVD such as ischemic heart disease, atherosclerosis, congestive heart failure, cardiomyopathy and arrhythmias [1]. Damage to the myocardial cells occurs due to the generation of toxic reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide and hydroxyl radical [2]. Isoproterenol (ISO) is a potent synthetic catecholamine which causes the development of infarct-like lesions when injected into animals. These lesions are morphologically similar to those of coagulative myocytolysis or myofibrillar degeneration, which is one of the signs of acute myocardial infarction in man (Milei et al., 1978). Isoproterenol (ISO), a synthetic catecholamine and _-adrenoceptor agonist, has been found to cause severe stress in the myocardium resulting in infarct-like necrosis [3]. Therefore, isoproterenol-induced myocardial injury serves as a well standardized model to study the beneficial effects of many drugs (Harada et al., 1993).The consumption of diets rich in plant foods is associated with reduced risk of CVD, and this has been observed in numerous epidemiological studies [4]. T. terrestris has the action of dilating coronary artery and improving coronary circulation. (Wang et al., 1990). The present work seeks to investigate the protective effect of the aqueous extract of Tribulus terrestris against isoproterenol-induced myocardial infarction in albino rats. Materials and methods Tribulus terrestris was received as a gift from Chemiloids manufacturers and exporters of chemicals, alkaloids and herbal extracts, based in Vijayawada, Andhra Pradesh, India. Animals and Experimental protocol Adult male rats of wistar strain, weighing 120-150g, were procured from the National Centre for Animal Science, National Institute of Nutrition, Hyderabad, India. The study was approved by Animal Ethics Committee of S. K University, Anantapur (Reg. no.470/01/a/CPCSEA). The rats were fed with commercial pellet rat chow (M/s. Sai Durga Feeds and Foods, Bangalore., India) and water ad libitum and maintained under standard laboratory conditions with 12 :12 h light : dark cycle. The rats were divided into four groups of six animals each. Group I rats
... The investigative significance of a high AST/ALT ratio for alcohol-related hepatic disease was reported [24]. The high AST/ALT ratio in alcoholic liver disease: 1) a decrease hepatic ALT activity [25]; 2) pyridoxal 5phosphate diminution in the livers of alcoholics [26]; and 3) damage of mitochondrial in patients with high alcohol consumption may increase activity of mitochondrial aspartate in serum [27]. In early report high AST/ALT ratio with increased serum aminotransferase activity has also been correlated with the growth of cirrhosis in Nonalcoholic Steatohepatitis patients [28]. ...
Background: This study was designed to inves-tigate the BMI and alcohol consumption effects on hepatic enzymes. The degree of alteration among moderate drinkers is still unclear. Objec-tive: To determine causes of liver failure due to alcohol and obesity. We observed the associa-tion between moderate alcohol consumption, body mass index (BMI; in kg/m 2) and transami-nase, cholestatic enzymes. Design: Serum ala-nine aminotransferase (ALT), alkaline phosphate (ALP), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were exam-ined in 995 healthy persons. In this study 400 persons were reported as abstainers and 595 participants involved as a moderate drinkers. The study population was further split into ac-cording to BMI as follows: <19 (underweight), ≥19 and <25 (normal weight), ≥25 and <30 (over-weight), and ≥30 (obese). Results: Serum ALT (P < 0.002), GGT (P < 0.001) and ALP (P < 0.001) but not AST (P < 0.883) activities in moderate drink-ers were higher than those in abstainers. Mean ALT activity is higher in obese and over weight in alcohol consumers and abstainers as com-pared to mean AST activity in the same groups. ALP activity was increased with BMI in moderate drinkers. In abstainers activity of ALP shows weak relation in order to BMI. Conclusion: The result of moderate alcohol use raises activity of hepatic enzymes with increasing BMI. Most par-ticipants with alcohol consumption have an AST/ALT ratio above 1.
... [62] Serum activities are generally within the reference interval or only slightly increased in alcoholic liver disease. [63] Serum alkaline phosphatase Serum alkaline phosphatase is produced by many tissues especially bone, liver, intestine, placenta and is excreted in the bile. Serum alkaline phosphatase increases to some extent in most types of liver injury. ...
Liver is a primary organ involved in metabolism of food and drugs. Liver disorders are mainly caused by toxic chemicals, such as antibiotics, chemotherapeutic agents, peroxidised oil, aflatoxin, carbon tetrachloride, chlorinated hydrocarbons etc. Toxic liver injury produced by drugs and chemicals may virtually mimic any form of naturally occurring liver disease. In view of multiplicity and complexity of the liver functions, it is obvious that no single test can establish the disturbances in liver function. Thus, a battery of liver function tests is employed for accurate diagnosis, to assess the severity of damage, to judge prognosis and to evaluate therapy. To study hepatoprotective potential of any herbal product, isolated phytochemical or synthetically developed moiety induction of experimental liver damage is prerequisite. The selection of toxicant depends on type and nature of liver damage required as every toxicant has its unique mode of action producing specific type of destruction. The hepatoprotective mechanism of any drug under study can be explained based on its protective behavior against different toxicants. This review is precise compilation of experimental liver pharmacology taking concern dose, route, and schedule of different liver toxicants along with evaluation biochemical, histological and functional ability parameters. The literature compilation will definitely help researcher in design and assessment of studies involving liver function.
... A higher AST/ALT ratio has been described in alcoholism (qv) which may be influenced by low B6 levels. 33,34 However others have shown that correction of B6 deficiency does not significantly alter the high AST/ALT ratio often seen in alcoholic hepatitis. 35 Patients being treated for malignancy may also have low B6 levels and underestimated transaminase levels, so using supplemented assays in these patients has been suggested. ...
De Ritis described the ratio between the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) almost 50 years ago. While initially described as a characteristic of acute viral hepatitis where ALT was usually higher than AST, other authors have subsequently found it useful in alcoholic hepatitis, where AST is usually higher than ALT. These interpretations are far too simplistic however as acute viral hepatitis can have AST greater than ALT, and this can be a sign of fulminant disease, while alcoholic hepatitis can have ALT greater than AST when several days have elapsed since alcohol exposure. The ratio therefore represents the time course and aggressiveness of disease that would be predicted from the relatively short half-life of AST (18 h) compared to ALT (36 h). In chronic viral illnesses such as chronic viral hepatitis and chronic alcoholism as well as non-alcoholic fatty liver disease, an elevated AST/ALT ratio is predictive of long terms complications including fibrosis and cirrhosis. There are methodological issues, particularly whether or not pyridoxal phosphate is used in the transaminase assays, and although this can have specific effects when patient samples are deficient in this vitamin, these method differences generally have mild effects on the usefulness of the assays or the ratio. Ideally laboratories should be using pyridoxal phosphate supplemented assays in alcoholic, elderly and cancer patients who may be pyridoxine deplete. Ideally all laboratories reporting abnormal ALT should also report AST and calculate the De Ritis ratio because it provides useful diagnostic and prognostic information.
There are studies that present metabolic disorders in alcohol drinkers are associated with thiamine deficiency. Therefore, in the present study, it was aimed to investigate the effectiveness of thiamine in rats with binge drinking model. For this purpose, total 21 spraque dawley rats were divided into three equal groups as control, alcohol and thiamine+alcohol groups. The thiamine+ethanol group was given thiamine at a daily dose of 100 mg/kg by oral gavage, starting 2 days before the ethanol administration. Alcohol and thiamine+alcohol groups were given 3.45g/kg/day ethanol as 20%. At the end of the study, while serum total bile acid, total bilirubin and insulin levels increased in rats in the alcohol group compared to the rats in the control group; total protein and albumin levels decreased (P<0.05). In the thiamine + alcohol group, LDL-cholesterol, total cholesterol, bile acid levels and AST enzyme activity increased, while ALT enzyme activity and total protein levels decreased compared to the control group (P<0.05). There was no statistically significant result in the values in the thiamine+alcohol group compared to the alcohol group. It has been concluded that acutely administered thiamine supplementation had no effect on alcohol-induced biochemical parameter changes in binge-drinking animals. In this sense, studies with longer-term thiamine use are needed.
Aim
Accurate detection of the hepatic fibrosis stage is essential to estimate the outcome of patients with non-alcoholic fatty liver disease (NAFLD). Many formulas, biomarkers, and imaging tests are being developed to predict advanced liver fibrosis without performing a liver biopsy. However, these tests do not have high efficiency in detecting early-stage hepatic fibrosis. Therefore, we aimed to detect the presence of hepatic fibrosis (≥F1) merely by using only standard clinical markers. Methods: A total of 436 patients with NAFLD who underwent liver biopsy were retrospectively enrolled as the discovery cohort (316 patients) and the validation cohort (120 patients). Liver biopsy and laboratory data were matched to extract simple parameters for identifying ≥F1. Results: We developed a novel simplified ≥F1 detecting system, designated as 2-Step PLT16-AST44 method, where 1) PLT of 16 ×10⁴/μL or less, or 2) PLT greater than 16 ×10⁴/μL and AST greater than 44 U/L is determined as having ≥F1 fibrosis. The 2-Step PLT16-AST44 method had a sensitivity of 68%, a specificity of 90%, a positive predictive value (PPV) of 97%, a negative predictive value (NPV) of 40%, and an accuracy of 72% to detect ≥F1 fibrosis in the discovery cohort. Validation studies further supported these results. Despite its simplicity, the 2-Step PLT16-AST44 method’s power to detect ≥F1 fibrosis in total NAFLD patients was comparable to hyaluronic acid, type 4 collagen 7S, FIB-4, and APRI. Conclusions: We propose the 2-Step PLT16-AST44 method as a simple and beneficial early-stage hepatic fibrosis detection system.
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We examined 74 patients with acute decompensation of alcoholic liver cirrhosis: 34 (45.9%) with bacterial infection (group 1) and 40 (54.1%) without bacterial infection (group 2). The degree and index of acute-on-chronic liver failure (ACLF) were determined using an on-line CLIF-C ACLF Calculator and the levels of cytokeratin-18 fragments, TNFα, IL-1β, IL-4, IL-6, and IL-8. In group 1, AST, cytokeratin-18, TNFα, IL-1β, IL-6, degree and score of ACLF were significantly higher than in group 2. ACLF developed in 18 (52.9%) patients in group 1 and in 11 (27.5%) (p<0.05) patients in group 2. Within 1 month, 10 (29.4%) patients of group 1 and 2 (5%) patients of group 2 died (p<0.05). Patients with bacterial infection showed a more severe course of alcoholic liver cirrhosis and ACLF than those without bacterial infection.
Liver disease associated with long-term drinking is one of the leading causes of death. There is an urgent need for more effective drugs to reduce alcoholic liver damage. Yin Chen Hao, a traditional Chinese herbal medicine, is widely used for liver diseases. Here, we aimed to explore the protective effect of β-sitosterol (the active ingredient of Artemisia spp.) on alcoholic liver injuries. We treated the rats with alcohol and different dosages of β-sitosterol to detect the expression levels of liver function indicators in serum. The functions of β-sitosterol were evaluated based on variations in histology, liver function indicators and DNA oxidative damages. The underlying mechanism was investigated by measuring lipid peroxidation, the antioxidant, the expression of cytochrome P450 2E1 and the expression of apoptosis related genes. The results showed that β-sitosterol could improve liver histology and suppress biochemical indicators caused by alcohol in serum. In addition, β-sitosterol alleviates alcohol-induced oxidative stress, such as restoring erythrocyte membrane fluidity, reducing glutathione depletion, restoring antioxidant enzyme activity and reducing malondialdehyde overproduction. Furthermore, β-sitosterol downregulated the expression of apoptosis-related genes through the PI3K/Akt pathway. In conclusion, β-sitosterol has a protective effect on chronic alcoholism and has broad clinical application prospects in the treatment of alcohol-induced liver damage.
This study was conducted to determine the effect of alcohol dduct on some of blood parameters and biochemical activities. there for fourty blood samples from anormal and alcohol addicted healthy males Then they were compared with (20) blood samples collected from anon-alcohclic healthy persons as a contral group. Results show a significent increase in the concentration of Hb and PCV in all (3) groups as compared with control group. There were a significent decrease in the concentration of total protein in (3) groups acompared with the a control group, while the blood urea increased significantly as compared with the control group and the results revealed also significent increase in the enzyme of transaminases (Alanine amino transferase ALT and aspartate aminotransferase AST) as compared with the control group.
Socioeconomic development has led to a progressive increase of alcohol consumption in Taiwan, with an accompanying increase in alcohol‐related psychiatric problems, traffic accidents, and liver disease. The prevalent rates of alcohol dependence for Han Chinese and Fomosan aborigines were 0.1% and 1%, respectively in 1950. The rate of alcohol dependence increased to 23% for aborigines in 1995. The number of cases of death and serious injuries due to alcohol‐related traffic accident has decreased, and the number of fatalities resulting from these accidents has decreased from third to eighth since the inception of a program of random traffic stops with alcohol breath test in 1997. Alcohol liver disease (ALD) was defined as daily alcohol consumption of 60 g, for a duration of longer than 5 years. We classified ALD patients into two groups: (1) those whose average daily consumption of alcohol exceeded 120 g for a duration longer than 15 years (group A); and (2) all other patients (group B). The case records of 33 cases of biopsy‐confirmed ALD were obtained for study. The average of daily alcohol consumption in these cases was 160 g. All but one of these patients were male, age ranged from 26 to 69 years, with an average of 43.1. Clinically, ill‐defined gastrointestinal symptoms were the most common presentation (61%), and hepatomegaly was the main physical sign (73%). The average mean corpuscular volume values of ALD and non‐ALD patients were 102.3 ± 10.94 and 94.5 ± 8.1, respectively (p < 0.01). The mean corpuscular volume values of group A and group B were 102.9 ± 9.7 vs. 96.5 ± 9.11 (p < 0.05). Result from serum SGOT/SGPT and γ‐glutamyltransferase/alkaline phosphatase for ALD and non‐ALD revealed statistically significant differences between these groups. Using the avidin‐biotin complex technique, tissue IgA deposition for ALD patients was found to be different from that of non‐ALD patients. Ten of 13 ALD patients vs. 2 of 13 non‐ALD patients had continuous‐form IgA deposition. Histologically, 45.5% of ALD patients had alcoholic cirrhosis, whereas alcoholic hepatitis was present in only 9.1% of patients. Overall, 88% of cases showed various severity of fatty metamorphosis.
The aminotransferases are a group of enzymes that catalyze the
reversible transfer of the amino group from an a-amino-acid to an oxo
acid. There are over 50 such enzymes characterized. Two of these,
aspartate aminotransferase (AST, EC 2.6.1.1, formerly known as glutamate-oxalacetate transaminase or GOT) and alanine aminotransferase (ALT, EC 2.6.1.2, formerly known as glutamate-pyruvate transaminase or GPT), entered the repertoire of the diagnostic laboratory in the mid-1950s and have remained mainstays of diagnostic enzymology for the subsequent three decades.
Detection of clinicaHy silent liver disease and determination of the causes of acute and chronic liver disease often require a panoply of blood tests and, occasionally, liver biopsy. Knowing when to order tests and which tests to order not only facilitates diagnosis but also leads to earlier intervention with appropriate therapy. This article reviews the most common blood tests for detecting liver disease, including viral hepatitis.
We do not know when and where drink able grape juice was originally pressed from wild vines, nor when and where wine was produced and enjoyed for the first time following fermentation and purification. • The oldest find is probably a grape squeezer containing grape seeds found in the region south of Damascus, dating back to the time around 6000 bc. • Wine consumption and drunkenness are described in the Epic of Gilgamesh, which goes back to 4000–3000 bc. God told Noah, who is called Utnapishtim in the epic, to grow grapevines following the Flood (around 4000 bc). This he did: “And he drank of the wine, and was drunken” (Genesis, 9.21). • About 2700 bc, Chinese writings mention the benefits as well as the dangers of consuming wine. • Many descriptions pertaining to the consumption of wine (and also beer) as well as to drunkenness can be found in the rock tombs at El Kab in Upper Egypt (around 2500 bc), in the Eber’s Papyrus (around 1550 bc) and in various other discoveries. A Babylonian clay tablet from the year 2230 BC shows a prescription written by a Sumerian physician regarding the use ofwine formedical purposes.
Hepatitis alcohólica (HA) es una entidad que forma parte de un conjunto de lesiones hepáticas producidas por la ingestión crónica de alcohol. Dichas lesiones son hígado graso, cirrosis, degeneración espumosa alcohólica (1), colestasis (2) (3), hepatitiscrónica (6), fibrosis y esclerosis perivenicular (4) (5), que en conjunto, configuran la llamada enfermedad hepática alcohólica (EHA).
Alcohol abuse is associated with an increased risk of cancer and birth defects, two disease processes that at some stage involve alterations in gene expression and cell development. The biochemical, molecular, and physiological mechanisms through which alcohol consumption produces these pathological effects are not thoroughly understood and seem to be multifactorial in nature. This chapter focuses largely on the experimental systems that have provided insights into potential mechanisms underlying the carcinogenic and teratogenic effects of alcohol abuse. The epidemiologic studies that established the association between alcohol abuse and cancer and birth defects have recently been reviewed (Garro and Lieber, 1990; Abel and Sokol, 1989) and are not discussed in detail here.
A biological marker of ethanol consumption would be a valuable tool in the diagnosis and treatment of alcohol-ism. There are several areas of potential clinical applica-tion. First, a biological marker would be useful for the early detection of alcoholism, as many patients do not seek medical attention at an early stage (Clark, 1981). Previous studies have demonstrated the medical and social advantages of early intervention in the treatment of alcoholism (Reiff, 1985; Paredes, 1985). In addition, a biological marker would improve the monitoring of sobriety in alcoholics undergoing treatment. Furthermore, many patients who are suffering from a disease in which alcoholism is the suspected etiological agent (e.g., chronic pancreatitis, cirrhosis) fail to give an accurate history of their alcohol consumption. These patients are then subjected to an exhaustive diagnostic workup to rule out other etiological factors. A reliable biological marker of alcoholism would expedite the diagnostic workup and perhaps avoid invasive procedures (e.g., endoscopic retrograde pancreatography, liver biopsy). Finally, selected patients with alcohol-induced liver disease may become candidates for liver transplantation if there is a proven record of abstinence (Maddrey and Van Thiel, 1988); a reliable biological marker would provide objective verification of absti-nence and thus improve the selection process.
Liver diseases are common disorders encountered in clinical practice. Investigations in Liver diseases are used to detect hepatic abnormality, to measure its severity, to define its structural effect on the liver to look for specific causes of Liver diseases to assess prognosis and to evaluate therapy. Aims and Objectives: To study and compare the altered serum levels of Alkaline phosphatase, Bilirubin and Derits ratio in Liver disease and also to assess their usefulness in differential diagnosis of liver disease. Method: The patients admitted to Chigateri General Hospital and Bapuji Hospital Davangere were selected for the present study. Total number of 124 subjects were chosen which include 50 controls and the cases of Liver diseases. The liver diseases were further grouped into Acute Hepatitis, chronic hepatitis and cirrhosis of liver. Abbreviations: ALP-Alkaline phosphatase; Bil-Bilrubin; AST/ALT- Deritis ratio AST-Aspartate transaminase; ALT-Alanine Transaminase. Results: The mean levels of Alkaline phosphatase was statistically significant in all liver diseases as compared to controls, the P value is highly significant P<0.001. There is no statistical significance observed in non alcoholic and alcoholic cirrhosis and duration wise comparison in cirrhosis of liver. The mean levels of total Bilirubin was increased in all groups of liver diseases studied when compared to controls. Derits ratio (AST/ALT ratio) It is statistically significant in chronic hepatitis, non alcoholic cirrhosis of liver, and alcoholic cirrhosis when compared to controls. It is statistically not significant in acute hepatitis when compared to controls. Conclusion: The liver function test can be of value prognostically and screening for liver disease in response to treatment.
Alcoholic hepatitis is a clinical syndrome of jaundice and liver failure that generally occurs after decades of heavy alcohol use. The typical age of presentation is between 40 and 60 years, and female sex is an independent risk factor. Alcoholic hepatitis is a treatable form of alcoholic liver disease. Since up to 40% of patients with severe alcoholic hepatitis die within 6 months after the onset of the clinical syndrome, appropriate diagnosis and treatment are essential. Liver biopsy is a valuable diagnostic aid when it is possible for it to be performed. A variety of scoring systems: Maddrey index, Glasgow score, model for end stage liver disease (MELD), Lille score, have been used to assess the severity of alcoholic hepatitis and to guide treatment. Treatment of alcoholic hepatitis includes the general measures for patients with decompensated liver disease and specific measures directed at the underlying liver injury. Immediate and lifetime abstinence from alcohol use is the cornerstone of recovery, and in addition it is essential to prevent the progression to liver failure and death. Malnourished subjects should be given adequate caloric and protein support. The use of corticosteroids is controversial. Pentoxifylline may be of benefit, by preventing development of the hepatorenal syndrome. This review focuses on the most recent developments in diagnosis and treatment of alcoholic hepatitis.
Aim of study: The aim of our study was to find out the definite diagnosis of hepatomegaly and the prevalence of variopus causes of hepatomegaly in Balochistan. Study Design: Experimental and Observational study. Place and Duration of Study: This study was conducted in the Medical Unit-III, Bolan Medical College, Quetta from April 2009 to December 2010. Patients and Methods: 105 patients were admitted in our medical unit III with the clinical presentation of hepatomegaly .Patients were the age group 10 years to 85 years,73 patients were males and 23 patients were females. Patients with congestive hepatomegaly were excluded from this study and methods used in this study were history, clinical examination, LFTs and liver biopsy. Results: The incidence of various common causes of hepatomegaly in Balochistann are ameobic liver abscess 12% hydatid disease of liver 13% hepatocelluar carcinoma 15%, hepatitis 17%,obstructive jaundice 9% & normal 9%. Conclusion: The most common causes of Hepatomegaly in Balochistan are ameobic liver abscess , hydatid disease of liver, hepatocelluar carcinoma ,viral hepatitis ,obstructive jaundice. This study has shown that percentage of hydatid disease of liver, fatty liver and lymphoma, as compare to Durban study was higher. This study will help in managing and under standing various causes of hepatomegaly in field of Therapeutics and Research, especially in Balochistan.
The present study investigates the protective effects of Tribulus terrestris Fruit aqueous Extract (TTFAEt) in myocardially infarcted rats. The oral administration of TTFAEt to rats for 40 days afforded good protection against isoproterenol-induced alterations, like Hyperlipidemia: the disorders of lipid metabolism have been ranked as one of the greatest risk factors contributing to the prevalence and severity of atherosclerosis, stroke and coronary heart diseases. Cardiac levels of lipid peroxidation (LPO) as well as the activities of antioxidant enzymes like Superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GPx), Glutathione-S-transferase (GST). Antioxidants can prevent reactive oxygen species-mediated damage and thus may have potential application in the prevention and cure of such diseases. Myocardial infarction produces a significant abnormal liver functioning. Liver tissue marker enzymes like alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). The protective effect of TTFAEt was further supported by the reversal of isoproterenol-induced histological changes in the liver. The results suggest that TTFAEt protect the heart and circulatory system and also hepatoprotective and thereby maintain the near normal architecture of liver tissue.
Acute myocardial infarction is a wearisome risk inherent in all major surgeries. Preoperative evaluation has been directed mainly to assess its risk because it carries with it a very high mortality. Living donor liver transplantation has been subject to inquiry not only because of the morbidity risk but also because of the mortality risk it carries to the live donor. The present study investigates the protective effects of Tribulus terrestris Fruit aqueous Extract (TTFAEt) in myocardially infarcted rats. The oral administration of TTFAEt to rats for 40 days afforded good protection against isoproterenol-induced alterations in cardiac levels of lipid peroxidation (LPO) as well as the activities of antioxidant enzymes like Superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GPx), Glutathione-S-transferase (GST). Antioxidants can prevent reactive oxygen species-mediated damage and thus may have potential application in the prevention and cure of chronic diseases. Myocardial infarction produces a significant abnormal liver functioning. Liver tissue marker enzymes injury like alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). The protective effect of TTFAEt was further supported by the reversal of isoproterenol-induced histological changes in the liver. The results suggest that TTFAEt protect the heart and circulatory system and also hepatoprotective and thereby maintain the near normal architecture of liver tissues.
Laboratory investigations reflecting liver disease are commonly termed as liver function tests. Although this term is misnomer, it has been traditionally continued to use by clinicians. Meanwhile, some terms such as liver panels, liver biochemistries or hepatic profiles have been used. An alternative term is routine tests of the liver. This article reviews routine tests for liver disease including serum aminotransferases, alkaline phosphatase, gamma glutamyl transferase, bilirubin, albumin and prothrombin time.
各種肝疾患における生化学検査の意義は, 診断, 経過観察, 治癒あるいは予後の判定にあると考えられる. しかし, 肝疾患はそれぞれにおいて異なる病態をとることから, 選択されるべき生化学検査も異なってくる. すなはち, 急性肝炎では経過観察と治癒判定が重要であり, それにはトランスアミナーゼの測定が有用である. さらに劇症肝炎の早期診断には凝固因子の測定が, 慢性肝炎の炎症所見の把握にはトランスアミナーゼとγ-グロブリンの測定が, 肝硬変の予後の判定にはICG検査が有用であり, 広く行われている. 本稿では生化学検査を肝細胞からの逸脱酵素, 肝で生成される蛋白質, γ-グロブリン, 胆道系酵素, 色素排泄試験の5グループに分け, 各肝疾患におけるこれら生化学検査の特徴およびその発現機序を述べ, その意義について略述した.
Combined data suggest a bimodal association of alanine aminotransferase (ALT) with mortality in the general population. Little is known about the association of ALT with mortality in patients with type 2 diabetes. We therefore investigated the association of ALT with all-cause, cardiovascular, and non-cardiovascular mortality in patients with type 2 diabetes.
A prospective study was performed in patients with type 2 diabetes, treated in primary care, participating in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study. Cox regression analyses were performed to determine associations of log2 -transformed baseline ALT with all-cause, cardiovascular, and non-cardiovascular mortality.
In 1,187 patients with type 2 diabetes (67±12 years, 45% female), ALT levels were 11 (8-16) U/l. During median follow-up for 11.1 (6.1-14.0) years, 553 (47%) patients died, with 238 (20%) attributable to cardiovascular causes. Overall, ALT was inversely associated with all-cause mortality (Hazard Ratio [HR] 0.81; 95% Confidence Interval [CI] 0.72-0.92), independently of potential confounders. This was less attributable to cardiovascular mortality (HR 0.87; 95% CI 0.72-1.05), than to non-cardiovascular mortality (HR 0.77; 95% CI 0.65-0.90). Despite the overall inverse association of ALT with mortality, it appeared that a bimodal association with all-cause mortality was present with increasing risk for levels of ALT above normal (P=0.003).
In patients with type 2 diabetes, low levels of ALT are associated with an increased risk of all-cause mortality, in particular non-cardiovascular mortality, compared to normal levels of ALT, while risk again starts to increase when levels are above normal. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
The acute and sub-chronic toxicities of Venestin Cleansers® (VC)-a polyherbal supplement in female Wistar Albino Rats Was Evaluated. Acute toxicity of VC in rats was determined. Twenty four weight-matched animals divided into 3 groups of eight rats each were given feed and water only (control), feed + water + 500 mg/kg and feed + water + 1000 mg/kg VC for 28-days. Feed and fluid intakes were measured daily and body weight was taken weekly. Blood was collected by cardiac puncture and necropsy was done after 28 days. Liver and ovary were harvested and histopathological analysis was done. Liver and renal functions tests were carried out. Administration of 2000 mg/kg of VC showed no mortality in the rats after 14 days. Fluid , feed intakes and body weight were increased by 500 and 1000mg/kg VC. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activities increased significantly (p≤0.05) after VC administration. There was significant (p≤0.05) increase in conjugated bilirubin and total protein levels following administration of 500 and 1000mg/kg VC. Liver histology of the 500 and 1000 mg/kg of VC treated groups showed widespread ballooning, degeneration of the hepatocytes, periportal infiltration by chronic inflammatory cells with loss of radial arrangement of hepatocytes around the central veins. Histological examination of the ovaries showed areas of luteinized stromal cells, normal follicles, normal fallopian tubes. Chronic exposure of VC may have public health importance in man.
It is widely acknowledged that alcohol consumption increases the risk of liver disease. More than two centuries ago, autopsy pathologists noted an increased prevalence of cirrhosis in alcoholic subjects. 28 Later, population-based studies identified a correlation between liver disease mortality and per capita consumption of alcoholic beverages. 12 More recently, carefully-controlled studies in well-nourished animal models have clearly demonstrated that both the prevalence and the severity of liver disease increase with chronic consumption of alcohol. 31 Current efforts focus on explaining interindividual variability in susceptibility to alcohol-mediated liver injury. Success in the latter endeavor will require a more detailed understanding of the mechanisms involved in the pathogenesis of alcoholic liver disease (ALD). Such knowledge should, in turn, suggest strategies to prevent and treat ALD. This article reviews the histologic and clinical features of alcoholic liver disease, integrates recent insights into the molecular pathogenesis of ALD and suggests treatment opportunities when possible.
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