Comparisons between groups were made with the Kruskal—Wallis test and Tamhane's T2 post hoc test. Correlations were calculated using Spearman's rank correlation. Table 1 summarizes the values of the various biomarkers of liver status in the groups of heavy drinkers, moderate drinkers and abstainers. When the study population was further divided into subgroups according to gender, the alcoholic men showed significantly higher values than both moderate drinkers and abstainers in all of the study variables Table 1.
In women, the heavy drinkers also showed the highest values, whereas in comparisons between moderate drinkers and abstainers, no significant differences were noted Table 1. Liver enzyme and protein levels in heavy drinkers, moderate drinkers and abstainers. For abbreviations, see Table 1. In order to explore the interpretation of these variables as possible biomarkers of alcohol abuse, we also determined their upper normal limits based on the present population of abstainers or moderate drinkers Table 3.
Notable differences in the cutoffs based either on the use of the database obtained from moderate drinkers or abstainers were found for serum GGT, AST, ALT and ferritin. The incidences of observations, which exceeded the abstainer-based upper normal limits among heavy drinkers and moderate drinkers, are summarized in Figure 1. Upper normal limits for the study parameters, as based either on the data from abstainers or moderate drinkers.
The percentages in parentheses indicate the relative change in the upper normal limits in moderate drinkers as compared to abstainers, calculated upper normal limits calculated as The present study in a large population of subjects with a wide range of alcohol consumption indicates that excessive drinking even in individuals without apparent liver disease induces the activities of several liver-derived enzymes and elevates the concentrations of hepatic proteins, which have recently been linked with defence mechanisms towards oxidative stress Whitfield, ; Lee and Jacobs Jr, ; Faure et al.
Moderate drinkers also show higher enzyme activities than abstainers underscoring an early occurrence of the biochemical responses in response to ethanol intake. While GGT and transaminase enzymes are also known to specifically increase as a result of obesity Lawlor et al. Obviously, overweight when occurring together with alcohol drinking could, however, aggravate the metabolic burden and hepatic enzyme responses, as recently observed for both GGT Puukka et al.
Current BMIs Although the relatively small number of observations in the heavy drinker group here does not provide enough statistical power for assessing independent effects of ethanol drinking and overweight on hepatic enzymes and proteins within this subgroup, it should be noted that obesity has been previously found to be a risk factor for cirrhosis in the alcoholics Naveau et al.
When compared to abstainers, the group of moderate drinkers also showed elevated levels of serum ferritin, a marker of stored body iron. Thus, ethanol-related biochemical consequences in iron homeostasis may also be expected to occur at rather low levels of ethanol consumption. Previously, heavy drinking has been shown to increase ferritin levels, and secondary hepatic iron overload is a typical characteristic of alcoholic patients Fletcher, ; Whitfield et al.
Deposition of excess iron in hepatic tissue is in turn an important secondary risk factor for the development of alcoholic liver disease.
In experimental animals, iron and alcohol have been shown to act in a synergistic manner to enhance lipid peroxidation and liver injury Bacon and Britton, ; Tsukamoto et al. Alcohol consumption also increases the risk of liver injury in human patients with iron overload Fletcher et al. It has recently been hypothesized that serum ferritin may be produced in order to sequester catalytically active free iron and increases in serum ferritin could actually reflect a defence mechanism, which occurs in response to ethanol-induced oxidative stress Lee and Jacobs Jr, Increased ferritin levels could thereby protect from oxidative stress and consequent pathology due to free iron.
In a similar manner, the responses in serum GGT, which is responsible for extracellular metabolism of glutathione, the main antioxidant in mammalian cells, could be linked to protection from reactive oxygen species Whitfield, ; Puukka et al.
Since the ferritin concentration is also under tight genetic control, it is also possible that its concentration may be affected in a similar way rather than through the cellular iron concentration. The present data also show increased levels of serum albumin among heavy drinkers suggesting increased rates of albumin protein synthesis in response to regular ethanol intake prior to the development of liver dysfunction, whereas in patients with advanced liver disease the rates of hepatic protein synthesis are obviously decreased.
Although the mechanisms underlying this observation remain unclear, it should be noted that previous studies in cell cultures have shown elevated hepatic protein synthesis rates as a result of chronic ethanol administration Potter et al. Recently, Tyulina and co-workers found elevated plasma albumin levels in alcoholics, which correlated with elevated protein carbonyls, suggesting that covalent modifications of proteins by acetaldehyde could also be associated with albumin protein expression among heavy drinkers.
Serum albumin is also an important antioxidant agent, whereas any structural modification of albumin induced by ethanol metabolites, glucose or free radicals has been suggested to impair its antioxidant properties Faure et al.
The ethanol-induced biochemical changes in hepatic tissue appear to occur in a gender-dependent manner. It remains to be established whether such findings would also correlate with the differences in the individual susceptibility to tissue damage, which is known to be not equal between men and women Schenker, It should also be noted that previous studies have indicated effects of smoking Whitehead et al.
Unfortunately, in this study, the possible confounding effects of smoking or coffee consumption could not be addressed. Since people who drink heavily usually also smoke a lot, we cannot rule out the possibility of additional increasing effects of smoking on hepatic enzymes among the heavy drinkers. However, in comparisons between the present population of moderate drinkers and abstainers, the enzyme activities or protein levels were not found to be significantly different between smokers and non-smokers data not shown.
In light of recent evidence indicating that coffee drinking could protect against liver injury and lead to reduced activities of liver enzymes Nakanishi et al. Our data also emphasize the view that due to the possible effects of even rather low ethanol doses on hepatic enzymes and proteins, the clinical interpretations of any ethanol-sensitive biomarkers as diagnostic tests in health care need further attention.
Current surveys indicate a trend towards permanent increases in GGT activities at the population level Hietala et al.
On the other hand, serum activities of hepatic enzymes have recently been suggested to be useful as general indicators of health and disease and long-term survival Kazemi-Shirazi et al. Moreover, the possible roles of a wide variety of biochemical markers as players in defence mechanisms towards oxidative stress warrant further studies.
Google Scholar. Unfortunately, among those who develop ALD, symptoms often present only after severe, life-threatening liver disease has developed. There are three main types of alcohol-related liver disease: alcoholic fatty liver disease, alcoholic hepatitis, and alcoholic cirrhosis.
The last is the most serious form of the liver diseases. Many heavy drinkers will progress from fatty liver disease to alcoholic hepatitis to alcoholic cirrhosis over time. However, some heavy drinkers may develop cirrhosis without first acquiring alcoholic hepatitis. Since susceptibility to the toxic effects of alcohol may vary by many factors including age, gender, genetics, and coexistent medical conditions, individuals should discuss alcohol use with their physician.
Complications from alcohol-related liver disease usually occur after years of heavy drinking, and overconsumption of alcohol is the major cause of liver disease in Western countries.
Although steatosis fatty liver will develop in any individual who consumes a large quantity of alcoholic beverages over a long period of time, this process is transient and reversible. In this article, we briefly review signs and symptoms, pathophysiology, diagnosis, and treatment of this serious medical problem.
The signs and symptoms of ALD differ depending on the stage of liver damage and the severity of the disease. People with alcoholic fatty liver disease are typically asymptomatic. ALD is a major cause of chronic liver disease worldwide. Research on ALD has been rapidly growing since it was reported that alcohol is a true hepatotoxin that causes hepatocellular damage.
Alcoholic fatty liver disease results from the deposit of fat mainly triglycerides, phospholipids, and cholesterol esters in liver cells, and it is the earliest stage of ALD. There are usually no symptoms. If symptoms do occur, they may include fatigue, weakness, and discomfort in the upper-right abdomen. Liver enzymes may be elevated, but tests of liver function are often normal.
Many heavy drinkers have fatty liver disease. Alcoholic fatty liver disease may be reversible with abstinence from alcohol. Alcoholic hepatitis AH is a syndrome characterized by inflammation of the liver due to hepatocellular injury and is characterized by fat deposition in liver cells, inflammation, and mild scarring of the liver. AH develops in patients with steatosis and is usually associated with progressive fibrosis.
Symptoms may include loss of appetite, nausea, vomiting, abdominal pain, fever, and jaundice. Liver enzymes are typically elevated, and tests of liver function may be abnormal. AH can be mild or severe. Mild AH may be reversed with abstinence. Severe AH may occur suddenly and lead to serious complications, including liver failure and death. Alcoholic cirrhosis, the most advanced type of alcohol-induced liver injury, is characterized by severe scarring and disruption of the normal structure of the liver in which hard scar tissue replaces soft, healthy tissue.
Symptoms of cirrhosis may be similar to those of severe AH. Patients who develop cirrhosis may report jaundice, weakness, peripheral edema, abdominal distention, or symptoms of GI bleeding such as hematemesis or melena. Cirrhosis is the most advanced type of alcohol-related liver disease and is not reversible with abstinence. However, abstinence may improve the symptoms of liver disease and prevent further damage. Ethanol metabolism—associated oxidative stress, glutathione depletion, abnormal methionine metabolism, malnutrition, and ethanol-mediated induction of gut endotoxins have important roles in the pathogenesis of ALD.
Alcohol intake has also been shown to augment the supply of lipids to the liver from the small intestine, increasing mobilization of fatty acids from adipose tissue and uptake of fatty acids by the liver. This will subsequently prime and sensitize hepatocytes to injury. In hepatocytes, ethanol is primarily metabolized into acetaldehyde a carcinogen with mutagenic properties by alcohol dehydrogenase in the cytosol, cytochrome P in microsomes, and catalase in peroxisomes.
Acetaldehyde is rapidly metabolized into acetate by aldehyde dehydrogenase in the mitochondria. While acetaldehyde is highly toxic to hepatocytes, acetate has no direct hepatotoxicity, but it is believed to regulate the inflammatory response in patients with AH via the up-regulation of proinflammatory cytokines in macrophages.
It is reported that the phenomenon of autophagy a normal physiological process in the body that deals with destruction of cells in the body has an important role in removing lipid droplets in hepatocytes. Long-term alcohol consumption inhibits autophagy, while short-term alcohol exposure activates autophagy by generating reactive-oxygen species during the early stages of alcohol liver injury.
The inside guide Evidence-based tools to empower you to live a healthier, longer life. Mocktails anyone? Found primarily in your liver cells, ALT is an enzyme that plays a role in converting stored glucose into usable energy. When liver cells are damaged, ALT can leak out into your bloodstream. What causes elevated ALT? Many lifestyle factors can influence your ALT levels, including: Alcohol intake Body weight Triglyceride levels Smoking Muscle damage One of the more frequent causes of high ALT levels is a condition commonly referred to as a fatty liver , which is a reversible condition that occurs when large amounts of triglycerides the type of fat typically found in food accumulate in liver cells.
How can I decrease my elevated ALT? The good news is that many people can lower their elevated ALT with changes in their lifestyle and exercise: Limit alcohol consumption Lose weight Quit smoking Get regular exercise Consider taking probiotic supplements to improve your digestive health Eat a healthy diet InsideTracker will recommend personalized lifestyle changes to help you decrease your ALT. What types of foods will help to lower elevated ALT?
What you eat also has an effect on ALT. Limiting high-fat foods, especially ones that are derived from animal sources, may help decrease elevated ALT levels. High-fat foods increase fat levels in your blood, which may end up being deposited in the liver. Helpful changes can include: Choosing lean proteins, such as chicken breast, fish, or beans, and low-fat dairy products.
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