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alcoholoc liver disease


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alcoholoc liver disease

  2. 2. India : alcohol The prevalence of use of alcohol Ranges from a low of 7% in Gujarat, to 75% in Arunachal Pradesh. The per capita consumption is 4 lit/adult/year It accounts for 50% of CLD ALD cause of mortality M: 11/100000 F:6/100000 Alcohol induced liver diseases 2
  3. 3. Alcohol induced liver diseases 3  Symptoms of Alcoholic Liver Disease may not appear until the condition is relatively advanced. They vary with the severity of the disease and worsen after a bout of heavy drinking.  Alcoholics are at an increased risk for gastrointestinal disorders, heart diseases and high blood pressure. Excessive alcohol use can also cause peptic ulcers, aggression, anxiety and depression.  A number of cancers can be developed as a result of alcoholism. Cancer of mouth, throat, oesophagus, stomach and liver are the few commonly- occurring ones.
  4. 4. Common symptoms: Dry mouth Fatigue/nausea /loss of appetite Swollen abdomen due to an enlarged liver Pain in the abdomen Jaundice/ fever/Pallor Weight loss Fluid build-up in legs (oedema) and abdomen in case of cirrhosis Pain/numbness in hands and legs Hypo /hyper pigmentation on the skin Small spider like blood vessels on skin Red colouration on hands /feet Yellow colouration of skin /eyes in case of jaundice Bloody faeces Bleeding nose /gums Vomiting blood Changing moods /confusion/hallucinations/decreased alertness Impaired memory /poor judgment Alcohol induced liver diseases 4
  5. 5. Serious complications of alcohol consumption:  It include advanced diseases such as brain damage (Alcoholic Encephalopathy) and hypertension (high blood pressure within the liver).  The disease usually affects those who are older than 30 years. Alcohol induced liver diseases 5
  6. 6. Liver  Liver is the Largest solid organ,  Largest Gland,  Main Metabolic organ of the Body  The liver is located in the upper right-hand portion of the abdominal cavity, beneath the diaphragm, and on top of the stomach, right kidney, and intestines. Shaped like a cone, the liver is a dark reddish- brown organ that weighs about 3 pounds. Liver is Made up of different cell types however 4 important cell types are discussing here  Hepatocytes,  Endothelial cells  Kupffer cell  Stellate cell Alcohol induced liver diseases 6
  7. 7. Alcohol induced liver diseases 7
  8. 8. Hepatocytes: They are rich in Organelle such as ER, Golgi complex, Mitochondria. Function:  Participate in Protein, Carbohydrate & Lipid Metabolism.  Produce serum protein such Albumin, Coagulation factor, Trasferrin. Endothelial cells:  Sinusoidal endothelial cell lines the walls of hepatic sinusoid. Function:  Filtration due to presence of Fenestration. Alcohol induced liver diseases 8
  9. 9. Kupffer cell: They are located within sinusoidal cell. Upon activation they secrete Inflammatory mediator: Cytokine Function: Phagocytosis Stellate cell: Play central role in storage of Vitamin A(Retinol). Overall functions of Liver:  As a Detoxifying Organ  As a Metabolic Organ  As an Immunological Organ,  As an Emulsifying agent(Bile salts) Producing Organ. Alcohol induced liver diseases 9
  10. 10. ALCOHOL  Ethanol: is a small two carbon alcohol that, due to its small size and alcoholic hydroxyl group is soluble in both aqueous and lipid environments.  This allows ethanol to freely pass from bodily fluids into cells.  Since the portal circulation from the gut passes first through the liver, the bulk of ingested alcohol is metabolized in the liver.  The process of ethanol oxidation involves at least three distinct enzymatic pathways. Alcohol induced liver diseases 10
  11. 11. Alcohol induced liver diseases 11 Alcohol dehydrogenase Microsomal ethanol oxidizing system (MEOS) which involves the cytochrome P450 enzyme CYP2E1 and requires NADPH instead of NAD+ as for ADH. The MEOS pathway is induced in individuals who chronically consume alcohol. Fatty acid ethyl ester (FAEE) synthase. This latter pathway results in the formation of fatty acid ethyl esters and takes place primarily in the liver and pancreas, both of which are highly susceptible to the toxic effects of alcohol.
  12. 12. Acute Effects of Ethanol Metabolism  The metabolism of ethanol via the CYP2E1 pathway results in increased ROS production, including superoxide, hydrogen peroxide (H2O2), and hydroxyl radicals.  ROS production is associated with cancer development, atherosclerosis, diabetes, inflammation, aging, and other harmful processes.  The cell regulates ROS levels via numerous defense systems involving a variety of different antioxidant compounds (e.g. glutathione, GSH).  During ethanol oxidation ROS production increases dramatically due to induction of CYP2E1 and by activation of Kupffer cells in the liver. Both acute and chronic alcohol consumption can increase ROS production and lead to oxidative stress. Alcohol induced liver diseases 12
  13. 13. Alcohol induced liver diseases 13
  14. 14. Chronic Effects of Ethanol Metabolism  In addition to the negative effects of the altered NADH/NAD+ ratio on hepatic gluconeogenesis, fatty acid oxidation is also reduced as this process requires NAD+ as a cofactor.  Concomitant with reduced fatty acid oxidation is enhanced fatty acid synthesis and increased triacylglyceride production by the liver.  In the mitochondria, the production of acetate from acetaldehyde leads to increased levels of acetyl-CoA. Since the increased generation of NADH also reduces the activity of the TCA cycle, the acetyl-CoA is diverted to fatty acid synthesis. Alcohol induced liver diseases 14
  15. 15. Alcohol induced liver diseases 15  The reduction in cytosolic NAD+ leads to reduced activity of glycerol-3-phosphate dehydrogenase (in the glycerol 3-phosphate to DHAP direction) resulting in increased levels of glycerol 3- phosphate which is the backbone for the synthesis of the triglycerides.  Both of these two events lead to fatty acid deposition in the liver leading to fatty liver syndrome and excessive levels of lipids in the blood, referred to as hyperlipidemia.  Because ethanol metabolism by ADH and ALDH occurs essentially only in the liver, any of the adverse effects described above that are associated with ethanol metabolism by these enzymes, and the associated ROS production, primarily affect that organ.
  16. 16.  In contrast, CYP2E1 is found in many tissues in addition to the liver, including the brain, heart, lungs, neutrophils, and macrophages.  Accordingly, metabolic consequences of CYP2E1-mediated ethanol oxidation will affect numerous tissues. The harmful effects associated with CYP2E1-mediated ethanol metabolism are primarily related to the production of ROS, mainly superoxide and hydroxyl radicals.  In the liver, the oxidative stress resulting from CYP2E1- mediated ethanol metabolism plays an important role in alcohol-related development of liver cancer. Alcohol induced liver diseases 16
  17. 17. Alcohol induced liver diseases 17  Chronic ethanol consumption and alcohol metabolism also negatively affects several other metabolic pathways, thereby contributing to the spectrum of metabolic disorders frequently found in alcoholics.  These disorders include fatty liver syndromes such as NAFLD and NASH, hyperlipidemia, lactic acidosis, ketoacidosis, and hyperuricemia.  The first stage of liver damage following chronic alcohol consumption is the appearance of fatty liver, which is followed by inflammation, apoptosis, fibrosis, and finally cirrhosis. .
  18. 18. Alcohol induced liver diseases 18
  19. 19. Methanol
  20. 20. Alcohol induced liver diseases 20  In the home, methanol is most frequently found in the form of "canned heat" or in windshield-washing products. Poisonings occur from accidental ingestion of methanol- containing products or when it is misguidedly ingested as an ethanol substitute.  Methanol poisoning causes visual disturbance, frequently described as "like being in a snowstorm.  Methanol (methyl alcohol, wood alcohol) is widely used in the industrial production of synthetic organic compounds and as a constituent of many commercial solvents.
  21. 21. Alcohol induced liver diseases 21 BEVERAGES Beverage Alcohol(%) Beer(12 oz) 5% Wine(4 oz) 12% Hard liquor (1.5 oz) 40% (Brandy,Whisky,Rum) Local brew Arrack 40-50 Toddy 5-10
  22. 22. Alcohol induced liver diseases 22 Risk for the development of ALD. Time to develop ALD = to amount of alcohol consumed Men: 60-80 gm/day for 10 years Women:20-40 gm/day for 10 years Alcoholic cirrhosis, Develops ONLY in 10 to 20% of those who are chronically heavy drinkers.
  23. 23. Alcohol induced liver diseases 23 SIMPLE CONVERSION BEER: ml/25 WINE: ml/10 Gms of alcohol HARD LIQOUR : ml/3
  24. 24. Alcohol induced liver diseases 24
  25. 25. Alcohol induced liver diseases 25 ALCOHOL ABUSE VS. ALCOHOL DEPENDENCE ALCOHOL abuses as those who drink despite recurrent social, interpersonal, and legal problems Dependence- presence of 3 or more symptoms a) Tolerance b) Withdrawal symptoms c) Loss of control over drinking d) Strong desire to drink e) Drinking despite harm
  26. 26. Alcohol induced liver diseases 26 DETECTION OF ALCOHOL ABUSE CAGE(Cut down,annoyed by criticism, guity about drinking, Eye-opener in the morning) AUDIT (Alcohol use Disorders Identification Test) 10- item questionnaire
  27. 27. Alcohol induced liver diseases 27 CLINICAL FEATURES SYMPTOMS PHYSICAL EXAMINATION Jaundice stigma of CLD Fatigue Tender hepatomegaly Anorexia Hepatic Weight loss decompensation Fever Ascities, Pain in RHC Eso.varies Encephalopathy.
  28. 28. Alcohol induced liver diseases 28 LAB Both AST and ALT are INC., <300IU/ml AST>ALT of 2 (80%) Inc in GGT Macocytosis with anemia Thrombocytopenia Leukocytosis –correlates with degree of injury. Increasing Bilrubin and PT correlate with severity of liver disease
  29. 29. Alcohol induced liver diseases 29 OTHERS…. •High CDT •High gamma globulin (IGA) •High uric acid •High serum lactate •Low albumin •High triglycerides
  30. 30. Alcohol induced liver diseases 30 Life style Medication EtoH intake : 80% survival rate in those who abstain Smoking: Cigarette smoking is an independent risk factore for cirrhosis in ALD Obesity
  31. 31. Alcohol induced liver diseases 31 NATURITION THERAPY Nutritional supplement improves hepatic function, and out come in AH, •Patients consuming > 3000kcal/d had virtually no mortality, •Whereas those consuming <1000 kcal/d had > 80% 6-month mortality
  32. 32. Alcohol induced liver diseases 32 DRUGS
  33. 33. Alcohol induced liver diseases 33
  34. 34. Alcohol induced liver diseases 34 Corticosteroids Decrease the immune response Anti inflammatory Antifibritic Increase production of albumin Improve ascites Improve caloric intake by improving appetite
  35. 35. Alcohol induced liver diseases 35 Prednisolone: 32 mg Po for 4 week followed by taper Active form prednisolone, rather than the in active precursor prednisone, is preferred No long term survival benefits
  36. 36. Alcohol induced liver diseases 36 Pentoxifylline It attenuates TNF-a release and action Exertes an antifibrinogenic action Lower portal hypertention Decrease blood viscosity Improve organ microcirculation Tissue Oxygenation
  37. 37. Alcohol induced liver diseases 37 Side-effects: Epigastric pain, vomiting, and dyspepsia Dose: 400 mg TID Improvement in short-term (4-week) Survival Decrease in the rate of development of hepatorenal syndrome
  38. 38. Alcohol induced liver diseases 38 Antioxidants: s-adenosylmethionine: Benefits of SAM in ALD include roles as an Antioxidant Critical methyl donor Decreasing TNF levels, and Glutathionine
  39. 39. Alcohol induced liver diseases 39 Propylthiouracil: No siginificant effects of PTU vs Placebo on mortality, complications of liver disease Colchicine: No beneficial effect on overall mortality
  40. 40. Alcohol induced liver diseases 40 Newer Approaches  Polyenylphosphatidylcholine N-Acetyl cysteine Combinational therapy Liver transplantation: OLT for alcoholic hepatitis is not currently recommended.
  41. 41. Alcohol induced liver diseases 41
  42. 42. Alcohol induced liver diseases 42 CONCLUSION  All Alcoholic patients should be screened for alcoholic liver disease. The diagnosis of alcoholic liver disease requires a detailed patient history, with supportive laboratory and imaging studies.  Liver biopsy may be useful to confirm the diagnosis, rule out other diseases, and prognosticate. All patients with alcohol-related liver disease should abstain from alcohol.  For those with severe disease and no contraindications to their use, steroids should be considered. Liver transplantation remains an option for select patients with end-stage liver disease due to alcohol.
  43. 43. Alcohol induced liver diseases 43 Thank you