The effect of chronic ethanol feeding on ornithine decarboxylase activity and liver regeneration

The effects of ethanol on liver regeneration are poorly understood. Acute and chronic exposure to ethanol have been found to exert opposite effects on the induction of ornithine decarboxylase, the rate-limiting enzyme for polyamine biosynthesis. Polyamines are necessary for DNA synthesis and liver regeneration after chemical or surgical liver injury. Short-term exposure to ethanol, which inhibits ornithine decarboxylase has been shown to inhibit DNA synthesis and liver regeneration, whereas more chronic exposure to ethanol increases ornithine decarboxylase activity and therefore could conceivably stimulate DNA synthesis and regeneration. To explore this later possibility, the effects of chronic ethanol consumption on ornithine decarboxylase activity, DNA synthesis and liver regeneration were studied in rats after sham laparotomy and partial hepatectomy. Chronic ethanol feeding failed to inhibit the induction of ornithine decarboxylase that occurred after partial hepatectomy and yet significantly inhibited posthepatectomy DNA synthesis and restitution of liver mass. These data suggest that the induction of hepatic polyamine biosynthesis is dissociated from DNA synthesis and liver regeneration after chronic consumption of ethanol.     

Disposition of Ethanol and Activity of Hepatic and Placental Alcohol Dehydrogenase and Aldehyde Dehydrogenases in the Third-Trimester Pregnant Guinea Pig for Single and Short-Term Oral Ethanol Administration

The disposition of ethanol and its metabolite, acetaldehyde, and the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenases (ALDH) were determined in the third-trimester pregnant guinea pig following single and 7-day oral administration of ethanol (0.5 g X kg maternal body weight-1 X day-1). Animals were killed at each of selected times after the single and seventh ethanol dose. For both ethanol dosage regimens, the maternal and fetal blood and brain ethanol concentrations were virtually identical during the elimination phase of the time-course study. There was initial slow transfer of ethanol into amniotic fluid, followed by significantly higher ethanol concentration in amniotic fluid relative to maternal and fetal blood during the elimination phase. Acetaldehyde was measurable in maternal blood, maternal brain, and fetal brain at concentrations that were low and variable. For both ethanol dosage regimens, ADH activity was measurable only in maternal liver. Low Km ALDH activity was measurable only in maternal liver and fetal liver. High Km ALDH was measurable in maternal liver, fetal liver, and placenta and was significantly greater in maternal liver. The data indicate that there is bidirectional placental transfer of ethanol in the maternal-fetal unit; the elimination of ethanol from the maternal and fetal compartments is regulated by maternal hepatic biotransformation involving ADH; the amniotic fluid is a reservoir for ethanol in utero; the low Km ALDH in fetal liver protects the fetus from ethanol-derived acetaldehyde in the maternal circulation; and short-term maternal administration of once-daily, low-dose ethanol does not produce major changes in ethanol disposition and the activity of the enzymes involved in ethanol biotransformation.     

Ethanol administration generates oxidative stress in the pancreas and liver,but fails to induce heat-shock proteins in rats

BACKGROUND: Heat-shock proteins (HSP) play an essential role in the sequestration and reparation of denatured cellular proteins. Because ethanol treatment can result in oxidative stress-induced protein damage, it is possible that expression of HSP is altered after ethanol consumption. Dose-response and time-course studies were performed to investigate whether acute and chronic intragastric ethanol administration can induce tissue damage, oxidative stress and expression of the heat-shock proteins HSP60 and HSP72 in the pancreas and liver of male Wistar rats. METHODS: Laboratory and morphological analysis of pancreatic and liver damage were investigated. The degree of oxidative stress was assessed by measurement of the reduced glutathione content, lipid peroxidation and protein oxidation. The levels of HSP were examined by western blot analysis. RESULTS: Ethanol administration dose- and time-dependently elevated the serum ethanol concentration and hepatic enzyme activities. Chronic ethanol treatment also resulted in morphological damage of the liver. We observed that acute and chronic ethanol consumption had markedly different effects on the oxidative parameters in the pancreas and liver. Acute ethanol administration caused oxidative stress in the liver, whereas there was no such effect in the pancreas. In contrast, chronic ethanol feeding resulted in oxidative stress in both the pancreas and the liver. Furthermore, neither acute nor chronic ethanol intake induced the synthesis of HSP, a major defense system against cellular damage in the examined organs. CONCLUSION: Ethanol administration generates oxidative stress in the pancreas and liver, but fails to induce HSP in rats.     

Inhibition of liver regeneration by chronic alcohol administration.

Liver regeneration is the common mechanism whereby a patient recovers form a liver injury. In the western world, ethanol is the single most important aetiological factor associated with liver disease, and it appears crucial to determine if ethanol interferes with liver regeneration. We studied the response to a 70% hepatectomy in 240 rats receiving a nutritionally adequate diet containing 36% of their calories as ethanol for three weeks and their pair-fed controls receiving a liquid diet where ethanol is isocalorically replace with carbohydrates. Criteria of liver regeneration were: incorporation of 3H-thymidine in hepatocyte DNA (cpm/10 microgram DNA) and number of hepatocyte labelled nuclei on autoradiography per 100 high power fields. Controls displayed the usual response with peak activity of liver regeneration at 24 hours. Consumption of ethanol was associated with a statistically significant reduction of liver regeneration by both criteria for up to 72 hours after a 70% hepatectomy and delayed the peak of regenerative activity by 24 hours. This inhibiting effect was not related to the presence of alcohol in blood nor to hepatic microsomal enzyme induction by ethanol nor to widespread necrosis of hepatocytes. This effect was reversible after one week of abstinence. This impairment of liver cell renewal by ethanol may be of major significance in the severity and outcome of alcohol-related liver injury.     

Pharmacokinetics of the Ethanol Bioavailability in the Regenerating Rat Liver Induced by Partial Hepatectomy

It is well known that a single ethanol administration is capable of inhibiting the two-thirds partial hepatectomy (PH)-induced liver regeneration (LR); nonetheless, it has not been elucidated how ethanol metabolism by the remnant liver is exerting the deleterious ethanol actions on LR. Indeed, pharmacokinetics analysis of ethanol elimination is lacking in rats subjected to PH, which might extend our understanding in the mechanisms that account for the ethanol-induced inhibition on LR after PH in the rat. Therefore, the present study is a pharmacokinetics analysis comparing intragastric and in-traperitoneal administrations of ethanol to rats under PH, at several times after surgery (0 to 96 hr postsurgery). Our results show that PH rats had a much lower blood ethanol peak than sham-operated, when intragastrically administered during the first 4 hr after surgery that was transient and normalized at 6 hr post-PH. The area under the curve for blood ethanol was higher in PH animals, starting after 6 hr postsurgery and extended to the all replicative period, and returned within the control values thereafter. The quantity of ethanol absorbed after its intraperitoneal injection was essentially the same as the administered dose for all of the groups tested. Hence, ethanol bioavailability diminished due to an enhanced rate of the first-pass metabolism for ethanol in PH rats at the very early times post-PH. At later times of PH, ethanol bioavailability was practically normalized, and these effects were accompanied by a drastic increase in the liver capacity to metabolize ethanol, mainly at 48 to 96 hr after surgery, as calculated as ethanol elimination per gram of liver, as well as by total body weight. The very early changes in ethanol bioavailability in PH rats were not accounted for gastric ethanol retention in these animals. In conclusion, first-pass metabolism importantly participates in the modified ethanol bioavailability at very early times after PH, an event presumably attained to gastric catabolism of ethanol. However, the very enhanced metabolism of ethanol showed by the regenerating liver, particularly after the first 24 hr postsurgery, seems to be the main factor affecting ethanol pharmacokinetics in rats subjected to PH. The underlying mechanisms in this liver enhancement of ethanol oxidation by PH rats remains to be elucidated.     

实验性脂肪肝肝纤维化组织中弹性蛋白表达的研究

目的探讨弹性蛋白表达与脂肪肝肝纤维化的关系。方法分别建立高脂饮食、低脂酒精饮食、高脂酒精饮食和四氯化碳大鼠实验性脂肪肝肝纤维化模型,用免疫组织化学方法观察造模肝组织中弹性蛋白的表达。结果低脂饮食组、高脂饮食组和低脂饮食酒精组未见弹性蛋白的表达;高脂饮食酒精组有部分表达,而四氯化碳组均见弹性蛋白的表达;窦周肝细胞表达强度明显高于肝细胞。结论在肝纤维化的发展过程中,弹性蛋白的表达见于肝纤维化后期,与肝纤维化程度相关,可反映肝纤维化的病程;窦周肝细胞（主要是肝星状细胞）在肝纤维化进程中起十分重要的作用。     

Effect of Chronic Ethanol Feeding on Hepatic and Extrahepatic Distribution of Vitamin E in Rats

The effect of chronic ethanol feeding on the status of alpha- and gamma-tocopherol in plasma, liver, lung, and testes of Sprague-Dawley rats was characterized. Rats were pair-fed liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates. After 3 weeks, ethanol ingestion resulted in a significant (p less than or equal to 0.05) increase in liver weight and induced fatty liver without affecting total body weight. Ethanol feeding did not affect the plasma concentration of alpha-tocopherol but doubled that of gamma-tocopherol. When expressed per milligram of tissue, liver alpha-tocopherol did not vary with ethanol ingestion, whereas gamma-tocopherol concentration increased 2.5 times that of control animals. However, the concentration of alpha-tocopherol expressed per milligram of total lipids was significantly (p less than or equal to 0.01) decreased in the liver with ethanol feeding. In contrast to the liver, ethanol feeding significantly increased alpha- and gamma-tocopherol levels per milligram of total lipids in the testes. The concentration of gamma-tocopherol (but not alpha-tocopherol) per milligram of lung tissue and per total lung was significantly (p less than or equal to 0.05) increased with ethanol feeding. These data indicate that chronic ethanol ingestion significantly alters the distribution of alpha-tocopherol and gamma-tocopherol in hepatic and extrahepatic tissues of the rat.     

Chronic Ethanol Administration Impairs Degradation of Formaldehyde-Treated Albumin by the Perfused Rat Liver

Nonparenchymal cells of the liver appear to be important in the pathogenesis of various liver diseases, including that caused by ethanol. It is known that chronic ethanol administration impairs the process of receptor-mediated endocytosis in hepatocytes. Liver endothelial cells are also actively endocytic cells, playing a prominent role in the clearance from the circulation of a variety of macro-molecules. In this study, we assessed the effect of ethanol administration on this "scavenger" function of liver endothelial cells by measuring the degradation of formaldehyde-treated albumin in isolated, perfused livers of ethanol-fed rats. Rats were pair-fed for 1 or 4 weeks with a liquid diet containing either ethanol as 36% of total calories or an isocaloric amount of carbohydrate. Chronic ethanol administration in this manner for 1 or 4 weeks significantly impaired the degradation of this endothelial cell iigand (by 60 ± 9% and 37 ± 9%, respectively). Liver perfusions were also performed on rats that had been administered ethanol acutely or in which ethanol was added to the perfusate. No acute effect of ethanol on the degradation of this Iigand was seen. These results demonstrate that chronic ethanol ingestion impairs receptor-mediated endocytosis of formaldehyde-treated albumin by liver endothelial cells, indicating that the adverse effects of ethanol on protein trafficking within the liver are not limited to the hepatocytes.     

Ethanol consumption decreases alanine uptake by rat basolateral liver plasma membrane vesicles

Alterations of amino acid metabolism may play an important role in the pathogenesis of ethanol-induced liver disease. Previous studies indicate that ethanol added in vitro inhibits amino acid uptake by cultured hepatocytes and liver plasma membrane vesicles; however, the effect of chronic ethanol consumption on amino acid uptake by the liver remains unknown. Therefore, the present studies were performed to determine if chronic ethanol consumption impairs alanine uptake by rat basolateral liver plasma membrane vesicles. Male Sprague-Dawley rats were pair-fed for 6 weeks a diet containing 36% of calories as ethanol or a control diet in which ethanol was isocalorically replaced with carbohydrate. Chronic ethanol consumption reduced basolateral liver plasma membrane sodium-dependent alanine transport activity by 36.3% +/- 15.9% (p less than 0.01). This reduction was caused primarily by impaired activity of amino acid transport system A. The response of system A to glucagon was reduced in the ethanol-fed rats, suggesting that impaired hormonal regulation is at least partially responsible for the lower system-A activity. Kinetic analysis shows that ethanol consumption reduces the Vmax of sodium-dependent alanine transport without affecting the Km. These studies indicate that chronic ethanol consumption reduces alanine uptake by the rat liver. They further show that the reduced uptake is at least partially caused by an intrinsic defect in membrane-transport processes rather than another regulatory mechanism.     

Chronic ethanol consumption and aging: changes in lipid composition of liver microsomes

Both aging and chronic ethanol consumption have been found to produce changes in lipid composition. Severity of intoxication, withdrawal and release of gamma-aminobutyric acid following chronic ethanol consumption have been shown to be associated with age. It was predicted in this study that aged mice would differ in response to ethanol-induced changes in lipid composition of liver microsomes as compared to younger mice. Two different age groups of C57BL/6NNIA male mice (6 and 28 months) were administered an ethanol or control liquid diet for 24 days. Liver microsomes were prepared on Day 25. Age and ethanol consumption significantly affected liver weight and the ratio of liver weight to body weight. PC significantly decreased and PE significantly increased in both the young and old ethanol groups. Cholesterol and total phospholipid content were not affected by age or chronic ethanol consumption. Aged animals were able to adapt to the effects of chronic ethanol administration to the same extent as younger animals. These findings differ from studies that have examined effects of chronic ethanol consumption on behavior and neurotransmitter release among different age groups of mice. While the results are specific for liver microsomes, it appears that chronic ethanol consumption has less of an effect on liver function as compared to brain function in aged mice.     

Ethanol metabolism in the generation of new antigenic determinants on liver cells.

Antibodies directed against ethanol altered liver cell components have been detected in the serum of nearly 50% of patients with alcoholic liver disease although the pathogenetic mechanisms are unclear. The importance of ethanol metabolism in the generation of new antigenic determinants on liver cells was investigated by in vivo inhibition of alcohol or acetaldehyde dehydrogenase and an induced cytotoxicity assay. There was a significant reduction in cytotoxicity to hepatocytes isolated from rabbits treated with ethanol 1 g/kg when the metabolism of ethanol to acetaldehyde by alcohol dehydrogenase was inhibited. In contrast when the oxidation of acetaldehyde was inhibited by disulfiram cytotoxicity was significantly enhanced. These results show that ethanol metabolism is integral to the expression of the ethanol related determinant and suggest that an impaired ability to metabolism acetaldehyde could lead to the development of immunological reactions to alcohol altered liver membrane antigens.     

Morphological and Biochemical Effects of a Low Ethanol Dose on Rat Liver Regeneration Role of Route and Timing of Administration

We have demonstrated that in rats subjected topartial hepatectomy (PH), the regenerating liver had anenhanced metabolism of ethanol, which largely dependedon the route and timing of ethanol administration. Therefore, the influence of the administrationroute and timing for ethanol-induced deleterious effectson the regenerating rat liver was evaluated in animalssubjected to 70% PH. Remnant liver showed moderate fatty infiltration, extended distortion ofhepatocellular structure, and high mitotic index.Intragastric ethanol administration (1.5 g/kg bodyweight) considerably reduced the PH-induced changes inliver structures. Ethanol treatment also decreasedliver thymidine kinase activity, serum albumin, andglucose levels. Intraperitoneal administration of thesame ethanol dose to PH rats promoted lesser alterations on liver regeneration. Independently of itsadministration route, ethanol abruptly shortened aPH-induced selective increase in serum enzymeactivities. These data suggest that the inhibitoryeffect of a low dose of ethanol on PH-induced liverregeneration is dependent on the timing and route ofadministration.     

Adaptation of Lipogenesis and Lipolysis to Dietary Ethanol

The effect of dietary ethanol on metabolic fates of glucose and ethanol, and activities of lipoprotein lipase and hormone-sensitive lipase in several tissues of miniature pigs were determined in vitro. Ethanol and glucose were used at similar rates for fatty acid synthesis in liver and brain and CO2 production in liver. Ethanol was preferred over glucose for fatty acid and CO2 production in ileal mucosal cells. Glucose was the preferred substrate for lipogenesis and oxidation to CO2 in adipose tissue and skeletal muscle, and for oxidation to CO2 in brain. Dietary ethanol decreased glucose and ethanol conversion to fatty acids in ileal mucosa and brain, respectively. Dietary ethanol had no effect on the capacity of liver, adipose tissue, and skeletal muscle to convert either glucose or ethanol to long-chain fatty acids. The capacity to oxidize ethanol, but not glucose, to CO2 in liver was increased by dietary ethanol. No dietary ethanol effect was observed in other tissues. The capacity for removal of plasma triglycerides (based on lipoprotein lipase activity) tended to increase in adipose tissue and skeletal muscle of pigs fed ethanol. Mobilization of long-chain fatty acids from adipose tissue (based on hormone-sensitive lipase activity), triglyceride concentration in plasma, and percentage of lipid in liver remained unchanged when ethanol was fed. Livers of ethanol-fed pigs, however, were larger than livers of control pigs. Our results indicate that feeding miniature pigs 21-37% of total caloric intake as ethanol causes significant metabolic adaptations of lipid metabolism in liver and ileal mucosa, but not in adipose tissue, skeletal muscle, and brain. The ethanol feeding, however, did not cause fatty livers or hyperlipidemia.     

Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: correlation with radical formation in vitro.

Rats fed a high-fat ethanol-containing diet for 2 weeks were found to generate free radicals in liver and heart in vivo. The radicals are believed to be carbon-centered radicals, were detected by administering spin-trapping agents to the rats, and were characterized by electron paramagnetic resonance spectroscopy. The radicals in the liver were demonstrated to be localized in the endoplasmic reticulum. Rats fed ethanol in a low-fat diet showed significantly less free radical generation. Control animals given isocaloric diets without ethanol showed no evidence of free radicals in liver and heart. When liver microsomes prepared from rats fed the high-fat ethanol diet were incubated in a system containing ethanol, NADPH, and a spin-trapping agent, the generation of 1-hydroxyethyl radicals was observed. The latter was verified by using 13C-substituted ethanol. Microsomes from animals fed the high-fat ethanol-containing diet had higher levels of cytochrome P-450 than microsomes from rats fed the low-fat ethanol-containing diet. The results suggest that the consumption of ethanol results in the production of free radicals in rat liver and heart in vivo that appear to initiate lipid peroxidation.     

Comparison of Effects of Long-Term Ethanol Consumption on the Heart and Liver of the Rat

Alterations in heart and liver metabolism were determined periodically in Sprague-Dawley rats pair-fed a liquid diet (ethanol, 36% of calories) for times as long as 1 year. In liver mitochondria the rate of ATP synthesis was lowered significantly after ethanol administration for 1 month and longer feeding periods. In liver microsomes from ethanol-fed animals, ethanol oxidation and aniline hydroxylation increased 1.5- and 3.5-fold, respectively, after 1 month and remained elevated at the longer feeding intervals. Electron microscopic analyses of heart left ventricles revealed no alterations from ethanol consumption for 1 month. Alterations including disrupted mitochondrial cristae, dilatation of sarcoplasmic reticulum, and widening of the intercalated discs were observed after 6.5-month feeding periods. Myocardial concentrations of creatine, creatine phosphate, ATP, ADP, and Pi remained constant even after ethanol consumption for 9 months. After a 12-month feeding period slight changes in cardiac mitochondrial energy-linked properties were observed which were not as pronounced as those occurring in liver mitochondria. The activity and oligomycin sensitivity of the ATPase were not altered in cardiac mitochondria, whereas in liver preparations significant alterations in these properties of the ATPase were apparent after ethanol consumption for 1 month and the longer feeding periods. These observations suggest that the liver responds more quickly and dramatically to chronic ethanol consumption than does the heart.     

Metabolic aspects of alcoholic liver damage: 1984/5 update. 1. Epidemiology and alcohol metabolism

In western industrialized countries ethanol is an important etiologic factor in the development of cirrhosis of the liver. Metabolic, immunologic and physico-chemical alterations of the hepatocyte due to ethanol are involved in the pathogenesis of alcoholic liver disease. However, the mechanisms by which ethanol damages the liver are far from clear. During the last two decades, the effect of ethanol on multiple biochemical pathways of the hepatocyte has been investigated intensively. The present paper is focusing on the metabolic aspects of alcoholic liver disease. In the first part of the review, special emphasis has been led on the metabolites of ethanol oxidation, while in the second part microsomal enzyme induction due to alcohol has been discussed. More than 90% of ethanol metabolism takes place in the liver via cytoplasmic alcoholdehydrogenase (ADH) and via a microsomal ethanol oxidizing system (MEOS). The products of these reactions are reduced nicotinadenine dinucleotide phosphate (NADH), acetaldehyde and acetate. NADH alters the redox state of the liver cell favouring all reductive processes. This shift in metabolic pathways results in hyperlactacidaemia, lactacidosis, ketosis and hyperuricaemia. Disturbances of the carbohydrate metabolism may lead either to hypo- or hyperglycaemia. The altered redox state also influences the metabolic pathways of lipid metabolism leading to lipid accumulation within the hepatocyte which can be morphologically observed as alcoholic fatty liver. In addition, porphyrin and collagen metabolism is also affected by the increased NADH/NAD+ ratio. On the other hand, acetaldehyde damages the microtubular system and the mitochondria. Acetaldehyde may also be responsible for the increased lipidperoxidation after chronic ethanol ingestion.     

Pathogenesis of alcoholic liver disease: interactions between parenchymal and non-parenchymal cells

The development of alcoholic liver disease (ALD) is a complex process involving both the parenchymal and non-parenchymal cells in the liver. The impact of ethanol on hepatocytes can be characterized as a condition of organelle stress with multifactorial changes in hepatocellular function accumulating during ethanol exposure. These changes include oxidative stress, mitochondrial dysfunction, decreased methylation capacity, endoplasmic reticulum stress, impaired vesicular trafficking and altered proteasome function. Injury to hepatocytes is attributed, in part, to ethanol metabolism by the hepatocytes. Changes in the structural integrity of hepatic sinusoidal endothelial cells, as well as enhanced inflammation in the liver during ethanol exposure are also important contributors to injury. Activation of hepatic stellate cells initiates the deposition of extracellular matrix proteins characteristic of fibrosis. Kupffer cells, the resident macrophages in the liver, are particularly critical to the onset of ethanol-induced liver injury. Chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharides via toll-like receptor 4. This sensitization enhances the production of inflammatory mediators, such as tumor necrosis factor-α and reactive oxygen species that contribute to hepatocyte dysfunction, necrosis and apoptosis of hepatocytes and the generation of extracellular matrix proteins leading to fibrosis. In this review we provide an overview of the complex interactions between parenchymal and non-parenchymal cells in the liver during the progression of ethanol-induced liver injury.     

4-hydroxynonenal levels are enhanced in fetal liver mitochondria by in utero ethanol exposure

Lipid peroxidation has been implicated in ethanol-induced liver injury and observed in fetal liver and brain after maternal ethanol consumption with mitochondria being the target organelles. This process generates a highly reactive and toxic product, 4-hydroxynonenal (HNE). In the present study, HNE levels and metabolism were assessed in mitochondria of fetal and maternal liver after in vivo ethanol exposure. Female Sprague-Dawley rats received five doses of ethanol (4 g/kg orally at 12-hour intervals) and were killed on day 19 of gestation. The results showed that HNE levels were enhanced in hepatic mitochondria of fetal rats exposed to ethanol, far in excess of that in adult liver mitochondria. Measurement of HNE metabolism showed that fetal mitochondria had a lower capacity for HNE catabolism than adult mitochondria. In adult mitochondria, HNE could be metabolized by nicotine adenine dinucleotide-dependent oxidation, reduced glutathione conjugation, and reduced nicotine adenine dinucleotide-dependent reduction, whereas in fetal liver only the former two pathways were active, but to a lesser degree than in adult mitochondria. On the other hand, mitochondria from fetal liver showed a higher production of HNE when oxidative stress was induced with t-butyl hydroperoxide. Prior in vivo ethanol exposure further potentiated HNE formation in t-butyl hydroperoxide-stimulated fetal liver mitochondria, but not in adult mitochondria. These findings indicate that increased levels of HNE in fetal liver mitochondria after maternal ethanol consumption reflect a higher susceptibility to HNE formation in addition to a lesser capacity to metabolize it. The enhanced accumulation of this toxic aldehyde may contribute to oxidative damage observed in fetal tissues after in utero ethanol exposure.(Hepatology 1997 Jan;25(1):142-7)     

Serum ethanol estimations in the control of alcohol abstinence in patients with liver disease

Eighty-eight patients with a non-alcoholic and 105 patients with an alcoholic liver disease were warned against alcohol consumption. On three consecutive ambulatory visits, serum ethanol was measured and compared with patients' admission of alcohol intake. None in the non-alcoholic group had a positive serum ethanol test, whereas 60 samples from 40 patients with alcoholic liver disease were positive. The serum ethanol values were higher in women than in men. Continuation of drinking was unrelated to sex, age, or type of alcoholic liver disease. Twenty-seven of the 40 patients with ethanol in serum denied alcohol consumption. The reliability of the patients was unrelated to sex, age, or type of alcoholic liver disease. Serum ethanol was more valuable than aspartate aminotransferase, alkaline phosphatase, bilirubin, and coagulation factors in pointing out the patients who continued drinking.     

Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis

OBJECTIVES: Similarities between histological features of alcoholic hepatitis and obesity-related liver disease suggest a common pathogenic mechanism. Because intestinal bacteria can produce ethanol, it is conceivable that intestinally derived alcohol may contribute to fatty liver disease. An indirect way of measuring endogenous ethanol is to measure the breath ethanol concentration. In a previous study in ob/ob mice, breath ethanol decreased with a course of non-absorbable antibiotics, suggesting that the ethanol is derived from intestinal bacterial flora. The aims of this study were 1) to determine whether alcohol can be detected in the breath of human subjects, and 2) to assess whether there is any correlation between ethanol and obesity in patients with nonalcoholic steatohepatits (NASH) and control subjects without known liver disease. METHODS: Breath ethanol concentration was determined in 21 patients with biopsy-proven NASH and in 10 control subjects by gas chromatography. An abnormal breath ethanol level was defined as two standard deviations above the mean value of the breath ethanol of lean controls. RESULTS: Minute quantities of ethanol were detected in the breath of human subjects who had not consumed alcohol in the recent past. Patients who were obese were more likely to have higher breath ethanol concentrations. Women also had higher breath alcohol than men. However, there was no difference between patients with NASH and controls. Severity of liver disease, as evidenced by cirrhosis, did not influence the breath ethanol concentration. CONCLUSIONS: Higher breath ethanol concentrations are observed in obese subjects than in leaner ones. It is possible that intestinally derived ethanol may contribute to the pathogenesis of NASH.