Alcoholic Hepatitis

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overview of alcoholic hepatitis

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Alcoholic Hepatitis

  1. 1. Alcoholic Hepatitis Dr E M Said Gastroenterology Ward 11
  2. 2. <ul><li>Background </li></ul><ul><li>Spectrum of ALD </li></ul><ul><li>Alcoholic Hepatitis </li></ul><ul><li>Presentation </li></ul><ul><li>Investigation </li></ul><ul><li>Prognosis </li></ul><ul><li>management </li></ul>
  3. 3. background <ul><li>major cause of morbidity and mortality in the West </li></ul><ul><li>Per capita consumption has doubled between 1980-1995 </li></ul><ul><li>Even though per capita consumption has plateaued in 1990s, recent surveys suggest drinking among females and the young continues to rise </li></ul><ul><li>Alcohol consumption in the UK accounts for: </li></ul><ul><ul><li>40,000 premature deaths per year </li></ul></ul><ul><ul><li>1.3% of GP consultations </li></ul></ul><ul><ul><li>12.5% of A&E attendances </li></ul></ul><ul><ul><li>25% of ICU admissions </li></ul></ul><ul><ul><li>30% of male and 15% of female admissions to general medical and surgical wards </li></ul></ul>
  4. 4. background <ul><li>CMO's report 2001 stated a significant increase in liver cirrhosis and mortality rate in England and Wales (four- to eight-fold increase in males, three- to seven-fold increase females) </li></ul><ul><li>Alcoholic cirrhosis mortality rate: </li></ul><ul><ul><li>11/100,000 males </li></ul></ul><ul><ul><li>6/100,000 females </li></ul></ul><ul><li>Alcohol accounts for 50% of chronic liver disease </li></ul><ul><li>Economic cost: £10 billion per year </li></ul>
  5. 5. Metabolism of Alcohol <ul><li>Alcohol metabolism by the liver result in increase in the NADH/NAD ratio & change in the oxidation-reduction status with reduced intracelluar state.this lead to: </li></ul><ul><li>1-Increase hepatic fatty acid production </li></ul><ul><li>2-Impaired carbohydrate and protein metabolism </li></ul><ul><li>3-Centrilobular necrosis of the hepatic acinus </li></ul><ul><li>The exact mechanism of alcohol hepatitis and cirrhosis is unknown. </li></ul>
  6. 7. Spectrum of alcoholic liver disease <ul><li>The three most widely recognised forms of ALD are : </li></ul><ul><li>alcoholic fatty liver (steatosis). </li></ul><ul><li>acute alcoholic hepatitis. </li></ul><ul><li>alcoholic cirrhosis. </li></ul>
  7. 9. alcoholic fatty liver (steatosis ) <ul><li>appears to be the initial change and is the most common response to alcohol ingestion </li></ul><ul><li>The increased liver fat is derived from the diet, from free fatty acids mobilized from adipose tissue, and from lipid synthesized in the liver and inadequately degraded or excreted </li></ul><ul><li>may cause mild abnormalities of liver function tests, including elevated ALT </li></ul><ul><li>patients have an excellent prognosis if they abstain from alcohol. </li></ul>
  8. 11. alcoholic hepatitis <ul><li>It is characterized by necrosis of hepatocytes, and deposition of Mallory hyaline bodies. </li></ul><ul><li>A polymorphonuclear reaction develops locally in response to the Mallory-containing and necrotic liver cells. </li></ul><ul><li>typically presents with jaundice, low grade fever, and tender hepatomegaly </li></ul><ul><li>Alcoholic hepatitis is often viewed as the intermediary step between fatty liver and cirrhosis </li></ul>
  9. 12. alcoholic cirrhosis <ul><li>represents end-stage disease </li></ul><ul><li>Classically of micronodular type </li></ul><ul><li>develop in 10 to 20% of those who are chronically heavy drinkers. </li></ul><ul><li>Although irreversible, patients may live many years with few obvious effects particularly with cessation of drinking </li></ul><ul><li>Decompensation of cirrhosis triggered by sepsis, bleeding, continued excessive drinking </li></ul>
  10. 14. <ul><li>It is estimated ,that although 90-100% of heavy drinkers show evidence of fatty liver, only 10-35% develop alcoholic hepatitis and 8-20% develop cirrhosis </li></ul>
  11. 15. Mechanisms of liver injury in Alcoholic hepatitis <ul><li>Genetic factors </li></ul><ul><li>Malnutrition </li></ul><ul><li>Toxic effects on cell membranes </li></ul><ul><li>Hypermetabolic state of the hepatocyte </li></ul><ul><li>Generation of free radicals and oxidative injury </li></ul><ul><li>Formation of acetaldehyde adducts </li></ul><ul><li>Role of the immune system </li></ul><ul><li>Cytokines </li></ul><ul><li>Role of concomitant viral disease </li></ul>
  12. 16. presentation
  13. 17. INVESTIGATIONS <ul><li>Laboratory findings </li></ul><ul><li>Ultrasonography </li></ul><ul><li>Liver biopsy </li></ul>
  14. 18. laboratory findings in alcoholic hepatitis <ul><li>Liver Function tests </li></ul><ul><li>Increased AST to ALT ratio (2 to 1) (below 400IU/L) </li></ul><ul><li>ALT usually < 100 IU/L </li></ul><ul><li>Increased Gamma-GT (variable) </li></ul><ul><li>Increased alkaline phosphatase (variable) </li></ul><ul><li>Note: AST has 50% sensitivity, 82% specificity for alcohol-induced liver injury. ALT has 35% sensitivity, 86% specificity for alcohol-induced liver injury. </li></ul><ul><li>Liver synthetic function (decrease after significant liver injury) </li></ul><ul><li>INR </li></ul><ul><li>Albumin </li></ul>
  15. 19. laboratory findings in alcoholic hepatitis <ul><li>Renal function (impaired in advanced ALD) </li></ul><ul><li>Urea/ creatinine </li></ul><ul><li>Haematological </li></ul><ul><li>Mild anaemia (usually macrocytic) </li></ul><ul><li>Thrombocytopenia </li></ul><ul><li>Other abnormalities </li></ul><ul><li>Hyperuricaemia </li></ul><ul><li>Hypertriglyceridaemia </li></ul><ul><li>Raised IgA </li></ul><ul><li>Hyperglycaemia </li></ul>
  16. 20. Exclusion of other causes of liver disease: <ul><li>Alpha-1 antitrypsin genotype </li></ul><ul><li>Serum caeruloplasmin/ serum copper </li></ul><ul><li>Iron studies </li></ul><ul><li>Autoantibodies (including LKM (Liver kidney microsomal)/ AMA (anti-mitochondrial)/ ANCA (anti-nuclear)) </li></ul><ul><li>Immunoglobulins/ complement </li></ul><ul><li>Hepatitis serology (HBsAg/HbCAb/HCVAb) </li></ul>
  17. 21. Ultrasonography <ul><li>Preferred study as inexpensive ,noninvasive and widely available </li></ul><ul><li>The liver appears enlarged and diffusely hyperechoic. </li></ul><ul><li>Helpful in excluding gallstones ,bile duct obstruction and hepatic or biliary neoplasm. </li></ul>
  18. 22. Liver biopsy <ul><li>Accurate assessment of severity of liver damage </li></ul><ul><li>Consider in patients in whom diagnosis is uncertain </li></ul><ul><li>A stestosis </li></ul><ul><li>B black arrows </li></ul><ul><li>Mallory bodies </li></ul><ul><li>C pericellular fibrosis </li></ul><ul><li>D satellitosis </li></ul><ul><li>Degeneration of hepatocytes </li></ul>
  19. 23. PROGNOSIS <ul><li>Alcoholic hepatitis carries a significant mortality </li></ul><ul><li>The most established tool for predicting survival in alcoholic hepatitis is Maddrey's discriminant function (MDF) </li></ul><ul><li>An MDF ≥32 indicates a poor prognosis with a risk of mortality around 35%. </li></ul>
  20. 24. PROGNOSIS <ul><li>Others factors that correlate with poor prognosis include : </li></ul><ul><li>older age, </li></ul><ul><li>impaired renal function, </li></ul><ul><li>encephalopathy, </li></ul><ul><li>rise in the white blood cell count in the first 2 weeks of hospitalization </li></ul><ul><li>Nearly 2/3 of patients with severe alcoholic hepatitis will die in the hospital </li></ul>
  21. 25. management <ul><li>General measures: </li></ul><ul><li>Stop drinking </li></ul><ul><li>Treat withdrawal symptoms </li></ul><ul><li>Thiamine/multivitamins </li></ul><ul><li>Bed rest </li></ul><ul><li>High protein diet </li></ul><ul><li>Treat decompansaton </li></ul>
  22. 26. THERAPY <ul><li>Evidence </li></ul><ul><li>support use of: </li></ul><ul><li>1-corticosteroids </li></ul><ul><li>2-pentoxifylline </li></ul><ul><li>3-nutritional support </li></ul><ul><li>Insufficient </li></ul><ul><li>evidence: </li></ul><ul><li>1-Anabolic steroids </li></ul><ul><li>2-Malotilate </li></ul><ul><li>3-Etanercept </li></ul><ul><li>4-Infliximab </li></ul><ul><li>Therapeutic agents for alcoholic hepatitis: </li></ul>Evidence not supporting use: 1-Propylthiouracil 2-Insulin and glucagon 3-Colchicine
  23. 27. Corticosteroids <ul><li>Steroid effects are mediated through a decrease in immune mediated injury, inhibition of cytokine production and activation, as well as suppression of extracellular matrix protein expression. </li></ul><ul><li>should not be started until a sepsis screen has excluded infection </li></ul><ul><li>Meta-analysis of three randomised trials showed an improvement in 28 day survival, but benefit was not seen at later time points </li></ul><ul><li>The side effects of corticosteroids are justified only in patients with severe alcoholic hepatitis (MDF >32). </li></ul>
  24. 28. <ul><li>Randomized, controlled trials using prednisolone 40 mg/d (or an equivalent) for 28 days have shown an increase in both short-term (30 and 60 day) and long-term (1 year) survival in a subgroup of patients with severe alcoholic hepatitis </li></ul>
  25. 29. Pentoxifylline <ul><li>Pentoxifylline inhibits tumor necrosis factor (TNF)- production. </li></ul><ul><li>showed promise in one randomised controlled trial of patients with an MDF ≥32 who were not treated by steroids </li></ul><ul><li>associated with a marked reduction in the incidence of hepatorenal syndrome and improved 28 day mortality with no significant side effects </li></ul><ul><li>No trial has assessed combination therapy with steroids and pentoxifylline </li></ul>
  26. 30. <ul><li>A recent randomized, controlled study in severe alcoholic hepatitis used pentoxifylline 400mg thrice daily (mean duration, 21 days), to show a short-term survival benefit of 22% (absolute risk reduction) </li></ul>
  27. 31. Nutritional support <ul><li>Energy expenditure increased up to 60% in AH </li></ul><ul><li>Severe negative nitrogen balance occurs in AH </li></ul><ul><li>Nutritional status correlates with survival in moderate and severe AH </li></ul><ul><li>1-1.5g/Kg/day protein is required to achieve neutral balance in cirrhotics. This requirement increases significantly in AH </li></ul><ul><li>Total enteral nutrition is recommended in patients admitted with AH. Studies have shown a decreased mortality rate in patients receiving enteral feeding. </li></ul><ul><li>Oral supplementation is ineffective due to anorexia and poor compliance due to encephalopathy and insufficient protein-calorie content to meet metabolic demands </li></ul>
  28. 32. In summary… <ul><li>Common condition, high mortality </li></ul><ul><li>Diagnosis :history of alcohol intake, physical finings,imaging,lab results and exclusion of other conditions </li></ul><ul><li>Treatment:steroids,after exclusion of sepsis,pentoxifylline and nutrition support. </li></ul>
  29. 34. Thank you <ul><li>Questions? </li></ul>

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