Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic ethanol ingestion leads to hepatocellular injury and alcoholic liver disease (ALD) only if multiple factors combine to favor centrilobular hepatocellular hypoxia. It is hypothesized that these factors include a shift in the redox state, the induction of the microsomal ethanol oxidizing system (MEOS), a high blood alcohol level (BAL), a high polyunsaturated fat diet and episodic decreased O2 supply to the liver. The shift in the redox state favors a low cellular pH, decreased fatty acid oxidation and increased triglyceride formation. The increased MEOS activity increases O2 consumption and portal-central O2 gradient as well as favors acetaldehyde toxic effects including retention of hepatic lipids and export proteins causing cell swelling. The resultant increase in the concentration of acetaldehyde and lactate may stimulate fibrosis as they stimulate collagen synthesis in vitro. The resultant fatty liver narrows the sinusoids slowing sinusoid blood flow. The combination of events reduces available O2 leading to decreased levels of ATP and cellular pH making the liver vulnerable to episodes of systemic hypoxia. The role of membrane changes are reviewed, i.e., 1) membrane fluidity as related to changes in the species of phospholipids, 2) mitochondrial function as related to the changes in the lipid environment of the electron transport chain, and 3) linoleic acid-prostaglandin metabolism. Acute ethanol in vitro has been shown to affect liver cell metabolism regulation by triggering and increasing protein phosphorylation through the Ca2+-phospholipase C pathway. A high fat diet enhances the liver injury caused by chronic ethanol ingestion.
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PMID:Biochemical basis for alcohol-induced liver injury. 265 Sep 22

The occurrence and intensity of staining for specific antibodies against the aminoterminal propeptide of type III procollagen (PIIIP), which is indicative of the synthesis and the degradation of that collagen type, was studied in sections from normal and alcoholic livers and compared with serum PIIIP levels, serum antipyrine clearance, fibronectin distribution and morphology as revealed by conventional stains and electronmicroscopy. Positive staining for PIIIP and fibronectin was observed in the perisinusoidal space of the normal liver and in portal tracts. In alcohol-induced fatty liver positive staining increased around the central veins, in alcoholic hepatitis increased staining reaction was seen to a limited extent in areas of cell injury. Extensive reticulin and PIIIP-positive areas were found in the periportal interstitium of the cirrhotic livers and in large fibrotic areas extending into the surrounding parenchyma in cases of active disease. The results show a distinct relationship between collagen type III metabolism, morphologically detectable hepatic injury and liver cell function tests, with tissue deposition occurring later in the disease process than biochemically detectable serum collagen levels and signs of altered liver cell function.
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PMID:Interstitial collagen in alcoholic human liver. 298 Jul 43

Collagen-, arachidonate- and ADP-stimulated platelet thromboxane B2 (TXB2) formation was studied in platelet-rich plasma (PRP) of 14 alcoholics, 7 of whom had a biopsy-verified alcoholic fatty liver. On admission for detoxication, the alcoholics showed decreased platelet count and aggregability (p less than 0.001) as compared to nonalcoholic healthy controls. Platelet TXB2 formation was decreased (p less than 0.01), if PRP was stimulated by arachidonate, but not if it was stimulated by ADP or collagen. In contrast, 9-14 days after ethanol withdrawal platelet TXB2 formation had increased to markedly higher levels than those seen in nonalcoholic controls (p less than 0.01), if PRP was stimulated by ADP, but not if it was stimulated by arachidonate or collagen. Skin bleeding time was found to be prolonged (p less than 0.05) on admission in alcoholics having fatty liver, but it normalized within 2 weeks after ethanol withdrawal. We conclude that the effect of ethanol withdrawal in alcoholics on platelet TXB2 formation is influenced by platelet count, aggregability and the agonist used to induce platelet aggregation.
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PMID:Platelet thromboxane formation capacity after ethanol withdrawal in chronic alcoholics. 314 Dec 51

Alcoholic hepatic steatosis, considered for a long time as a reversible "harmless" disease, is now re-evaluated according to the concept of cirrhosis without cell necrosis and inflammation. The study of 166 biopsies from alcoholic hepatic steatosis has demonstrated the presence of fibrotic process in 25 (15%) of the cases. Histologic and electron microscopic examination have supplied data on the distribution of this fibrosis (perivenous, perisinusoidal and extensive) as well as on the cells involved in collagen synthesis; myofibroblasts, fat storing cells (Ito cells) and the hepatocyte itself. Peritoneoscopy revealed aspects of incipient portal hypertension in some of the cases. Follow-up in time with reiteration of morphologic exploration at intervals of 2 to 3 years has shown the possible evolution toward cirrhosis in cases of steatosis with fibrosis when ethanol consumption is continued. Detection of early fibrosis, in patients with alcoholic steatosis, by means of morphologic or biochemical methods would be necessary for its therapeutic implication: possible reversibility by abstinence from alcohol and antifibrogenic therapy.
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PMID:Hepatic fibrosis in alcoholic steatosis. Morphologic aspects and evolutive tendencies. 338 76

The effect of fibrosis on drug metabolism in alcoholic liver disease was evaluated in a comparison of the concentrations of serum aminoterminal propeptide of type III procollagen and basement membrane (BM; 7S domain of type IV collagen and laminin) antigens with in vitro (cytochrome P-450) and in vivo (antipyrine) drug metabolism in 67 alcoholics classified by liver histology. Alcoholics with intact or fatty liver had rapid or normal drug metabolism and normal collagen metabolism. Alcoholics with a fatty liver plus fibrosis or active cirrhosis had reduced drug metabolism and elevated levels of serum markers for collagen and BM metabolism. Alcoholics with inactive cirrhosis who had received therapy with enzyme inducers had a tendency toward normal drug and collagen metabolism parameters. Antipyrine metabolism, but not P-450 content, was related to the levels of serum type III collagen and BM markers. The fibrotic process, especially BM formation, creates a mechanical barrier that may prevent contact between blood and hepatocytes, thus delaying substrate availability.
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PMID:Fibrotic process and drug metabolism in alcoholic liver disease. 372 Jan 78

Liver biopsy specimens (178 percutaneous and 39 transjugular) were assessed from 217 consecutive patients with alcoholic liver disease, 77 noncirrhotics and 140 cirrhotics, whose cases were followed for 5 yr. Cirrhotic patients were categorized into two groups, with and without "hepatitis" using a criteria to define "hepatitis" that included only degrees of inflammation, necrosis, and Mallory bodies that had a prognostic weight in terms of mortality in 1 yr. This classification resulted in a sharp separation between a group of 42 patients with cirrhosis without "hepatitis" and with low mortality, both at 1 yr (7.1% +/- 4.0%) and at 5 yr (31% +/- 7%), and another group of 98 patients with cirrhosis and "hepatitis" and a high mortality both at 1 yr (26.5% +/- 4.5%, p less than 0.01), and at 5 yr (47% +/- 5%, p less than 0.02). Importantly, the 1-yr mortality in patients with cirrhosis and no "hepatitis" was not statistically different from that of patients with no cirrhosis or "hepatitis" (most of whom had only fatty liver) both at 1 yr (6.9% +/- 3.3%) and at 5 yr (24% +/- 6%). There were marked differences in several variables between cirrhosis with and without "hepatitis" [combined clinical and laboratory index: no "hepatitis": 4.9 +/- 0.7, with "hepatitis": 7.8 +/- 0.5, p less than 0.01; score of collagen in space of Disse: no "hepatitis": 2.1 +/- 0.4, with "hepatitis": 3.7 +/- 0.3, p less than 0.01; hepatocyte cross-sectional surface area: no "hepatitis": 682 +/- 51 micron 2, with "hepatitis": 841 +/- 31 micron 2, p less than 0.01]. These findings were more severe in the transjugular group than in the percutaneous group. Collagen in the space of Disse and hepatocyte surface area were not statistically different when cirrhosis without "hepatitis" was compared with a similar no "hepatitis" group of patients having noncirrhotic alcoholic liver disease. In this patient sample the presence of parenchymal nodules and fibrous septa, per se, did not result in an increase in mortality with respect to alcoholic patients without cirrhosis and with no "hepatitis."
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PMID:Prognosis of alcoholic cirrhosis in the presence and absence of alcoholic hepatitis. 378 Nov 89

Reye's syndrome (RS) is generally considered a childhood disease. We report our experience with RS in adults in the metropolitan Milwaukee area. Reye's syndrome was diagnosed in seven 18- to 46-year-old adults. The diagnostic criteria were as follows: viral prodrome followed by vomiting and encephalopathy without focal neurological signs, normal cerebrospinal fluid values, increased levels of serum aminotransferases (transaminase), prolonged prothrombin time, elevated blood ammonia levels, and characteristic microvesicular fatty liver and mitochondrial changes. None of the patients was hypoglycemic. The diagnosis of RS was entertained in 22 but confirmed in only seven patients. In cases of non-Reye's encephalopathy, drug ingestion presented as one of the most difficult differential diagnostic problems, which also included alcohol abuse, collagen vascular disease, and hepatitis B surface antigenemia. Clinical jaundice, distinctly uncommon in RS, was present in only one patient who presented to us in stage V coma. In adults, RS is more difficult to diagnose and should be suspected more frequently in patients with unexplained altered behavior following a viral illness and vomiting. Liver biopsy can be performed safely and is usually mandatory in adults. Patients with RS diagnosed during stage I or II coma and treated experienced an uneventful recovery.
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PMID:Reye's syndrome in adults. Diagnostic considerations. 380 May 31

The two major constituents of basement membranes are type IV collagen and laminin. Specific radioimmunoassays are described here for two structural domains of these proteins (7-S collagen and the fragment P1, respectively) that allow the related antigens to be quantified in human serum. The serum 7-S collagen antigen was uniform in size, whereas the laminin P1 antigenicity was heterogeneous. These proteins were measured in sera from sixty-three alcoholics, divided on the basis of liver histology into four groups: normal light microscopy, fatty liver, alcoholic cirrhosis with hepatitis and inactive cirrhosis. The group with cirrhosis and hepatitis had clearly elevated values in both assays, differing significantly from the others. A few pathological results were also seen in the other groups. The increases noted in 7-S collagen concentration were larger than those in laminin P1. During follow-up of a patient with cirrhosis and hepatitis the 7-S collagen level in particular seemed to reflect the course of the disease. The elevated basement membrane protein concentrations in serum may be associated with the formation of real basement membranes in the perisinusoidal space, a process known as capillarization of the sinusoids which is found during the development of liver cirrhosis.
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PMID:Type IV collagen and laminin-related antigens in human serum in alcoholic liver disease. 392 6

To determine how choline supplementation affects the liver and whether it can protect against ethanol-induced liver injury, baboons were fed either normal or choline-supplemented diets, each with or without ethanol. Eighteen baboons were pair-fed for 3 to 4 years liquid diets with 50% of total energy as ethanol or isocaloric carbohydrate; ten animals were given our regular diets, whereas in eight the choline content was increased 5-fold. Six additional animals were fed individually with the control diets (with or without additional choline). With both ethanol-containing diets, ethanol intake was comparable and resulted in hepatic steatosis and striking mitochondrial lesions, with increases in serum bilirubin and SGOT, SGPT and glutamate dehydrogenase activities. In addition, of the five animals fed alcohol with the regular diet, one progressed to incomplete cirrhosis and two others developed perivenular and associated perisinusoidal fibrosis. Similarly, in the four baboons fed alcohol with choline supplementation, incomplete cirrhosis developed in one and perivenular fibrosis in two. Collagen deposition was demonstrated by immunoperoxidase with a specific antibody against procollagen Type III. These animals also displayed proliferation of myofibroblasts in the perivenular area and transformation of fat-storing cells to transitional cells in the perisinusoidal space, with associated enhanced collagen fiber deposition. Thus, in baboons, choline supplementation failed to prevent alcohol-induced steatosis and fibrosis. All parameters remained normal in the eight baboons fed the regular control diet. However, in the choline-supplemented controls, serum bilirubin, SGOT and glutamate dehydrogenase activities increased moderately and serum albumin decreased. Occasional fat droplets appeared in hepatocytes with mitochondrial changes (enlargement and alterations of the cristae) and an abundance of "myelin" figures in the cytoplasm, indicating that choline supplementation exerts moderate hepatotoxicity.
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PMID:Choline fails to prevent liver fibrosis in ethanol-fed baboons but causes toxicity. 401 29

To determine if alterations in collagen degradation may contribute to the pathogenesis of fibrosis and cirrhosis, we studied the hepatic collagenase activity of 20 baboons given alcohol containing diets or control diets under carefully controlled experimental conditions. We also studied 28 patients whose livers were biopsied for diagnostic purposes. Hepatic collagenase activity was significantly increased in baboons with fatty liver compared to levels in normal, control fed animals [(1.98 +/- 0.19 vs 1.20 +/- 0.08 units (microgram collagen digested/hour/mg liver protein) +/- S.E.M., p less than 0.001)]. The increase in hepatic collagenase activity persisted at the stage of fibrosis when compared to the activity in control baboons (2.16 +/- 0.07 vs 1.20 +/- 0.08 units +/- S.E.M., p less than 0.001). A single cirrhotic baboon available for study had an hepatic collagenase activity of 1.58 units. Patients with hepatic fibrosis had significantly higher hepatic collagenase activity than those with fatty livers [(9.12 +/- 0.94 (n =14) vs 4.52 +/- 0.54 (n = 7) units +/- S.E.M., p less than 0.001)]. However, in the group with cirrhosis, hepatic collagenase was lower [(3.92 +/- 0.61 (n = 7) units +/- S.E.M., p less than 0.001)] than in the group with fibrosis. Our findings suggest that the development of cirrhosis is coincident with, or favored by a failure of hepatic collagen degradative enzymes to keep pace with hepatic collagen synthesis.
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PMID:Mammalian collagenase increases in early alcoholic liver disease and decreases with cirrhosis. 628 91


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