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The Treatment of Alcohol Withdrawal and Alcoholic Hepatitis Dr R J Warner SpR to Dr Summerton
 
The extent of the problem 1 <ul><li>>300,000 people in the UK have ETOH related problems </li></ul><ul><li>5% of males vs....
The extent of the problem 2 <ul><li>30-40% of A&E attendees have ETOH concentrations >legal driving limit </li></ul><ul><l...
The extent of the problem 3 <ul><li>The average GP with 2000 patients will have </li></ul><ul><li>100 heavy drinkers </li>...
Percentage of adults with excess alcohol consumption
Symptoms of withdrawal within  12 hours <ul><li>agitation </li></ul><ul><li>nausea </li></ul><ul><li>sweating </li></ul><u...
Symptoms of withdrawal within 48 hours <ul><li>Alcoholic fits ( also known as “rum fits”)  </li></ul><ul><li>common in alc...
Alcohol withdrawal after  24 hours- Delirium Tremens <ul><li>Symptoms </li></ul><ul><li>disorientation </li></ul><ul><li>a...
Differential Diagnosis for the Alcoholic Patient <ul><li>trauma </li></ul><ul><li>metabolic </li></ul><ul><li>toxicology <...
Management of alcohol withdrawal <ul><li>General alcohol withdrawal </li></ul><ul><li>Alcoholic seizures </li></ul><ul><li...
General alcohol withdrawal <ul><li>vitamins </li></ul><ul><li>chlordiazepoxide </li></ul><ul><li>fluid balance </li></ul><...
Alcoholic Seizures <ul><li>ABCDEFG </li></ul><ul><li>iv diazemuls  </li></ul><ul><li>consider phenytoin </li></ul><ul><li>...
DTs <ul><li>as for general alcohol withdrawal but more aggressive, especially electrolyte imbalance </li></ul><ul><li>cons...
Alcoholic Hepatitis <ul><li>Withdrawal of ETOH often appears to exacerbate the LFTs </li></ul><ul><li>several mechanisms i...
Mortality for alcoholic hepatitis <ul><li>Overall 30 day mortality ~ 15% </li></ul><ul><li>if severe ~ 50%  </li></ul><ul>...
Treatment of alcoholic hepatitis 1 <ul><li>Standard treatment </li></ul><ul><li>stop alcohol! </li></ul><ul><li>Vitamins -...
Treatment of alcoholic hepatitis 2 <ul><li>Treat complications </li></ul><ul><li>fits </li></ul><ul><li>withdrawal </li></...
Treatment of alcoholic hepatitis 3 <ul><li>Failed treatments </li></ul><ul><li>anabolic steroids (Mendenhall 1993) oxandro...
Treatment of alcoholic hepatitis 4 <ul><li>Successful treatments </li></ul><ul><li>transplant </li></ul><ul><li>insulin/gl...
The debate about corticosteroids 1 <ul><li>>50 studies published over 30 years </li></ul><ul><li>no benefit for mild alcoh...
The debate about corticosteroids 2 <ul><li>3 large meta-analyses favour steroids </li></ul><ul><li>1 large meta-analysis d...
Maddrey’s formula <ul><li>4.6 x (prothrombin time - control in seconds) </li></ul><ul><li>+ </li></ul><ul><li>bilirubin (m...
The debate about corticosteroids 3 <ul><li>Ramond et al 1992  </li></ul><ul><li>61 patients with severe disease  </li></ul...
Use of steroids with infliximab 1 <ul><li>Spahr et al J Hep 2002 </li></ul><ul><li>first human study (pilot)  </li></ul><u...
Maddrey’s score
Serum bilirubin
Interleukins
Conclusions from the study <ul><li>Infliximab was well tolerated  </li></ul><ul><li>significant improvement in Maddrey’s s...
The last slide! <ul><li>Without treatment prognosis for AH is poor </li></ul><ul><li>Many treatment strategies have been t...
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Alcoho1l Talk

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Alcoho1l Talk

  1. 1. The Treatment of Alcohol Withdrawal and Alcoholic Hepatitis Dr R J Warner SpR to Dr Summerton
  2. 3. The extent of the problem 1 <ul><li>>300,000 people in the UK have ETOH related problems </li></ul><ul><li>5% of males vs. 2% of females report ETOH related problems </li></ul><ul><li>mortality/morbidity is 2-3X general population </li></ul>
  3. 4. The extent of the problem 2 <ul><li>30-40% of A&E attendees have ETOH concentrations >legal driving limit </li></ul><ul><li>20% of male medical admissions are alcohol related </li></ul><ul><li>1 in 5 “healthy males” attending well-man clinics have biochemical evidence of abuse </li></ul><ul><li>average consumption has increased from 5.2litres in 1950 to 8.5litres in 1991 </li></ul>
  4. 5. The extent of the problem 3 <ul><li>The average GP with 2000 patients will have </li></ul><ul><li>100 heavy drinkers </li></ul><ul><li>40 problem drinkers </li></ul><ul><li>10 physically dependant </li></ul>
  5. 6. Percentage of adults with excess alcohol consumption
  6. 7. Symptoms of withdrawal within 12 hours <ul><li>agitation </li></ul><ul><li>nausea </li></ul><ul><li>sweating </li></ul><ul><li>misperception </li></ul><ul><li>tremor </li></ul>
  7. 8. Symptoms of withdrawal within 48 hours <ul><li>Alcoholic fits ( also known as “rum fits”) </li></ul><ul><li>common in alcoholics </li></ul><ul><li>occasionally in single binge drinkers </li></ul><ul><li>subsequent EEG in normal </li></ul>
  8. 9. Alcohol withdrawal after 24 hours- Delirium Tremens <ul><li>Symptoms </li></ul><ul><li>disorientation </li></ul><ul><li>agitation </li></ul><ul><li>tremor </li></ul><ul><li>visual hallucinations </li></ul><ul><li>Signs </li></ul><ul><li>sweating </li></ul><ul><li>tachycardia </li></ul><ul><li>tachypnoea </li></ul><ul><li>pyrexia </li></ul><ul><li>dehydration </li></ul>
  9. 10. Differential Diagnosis for the Alcoholic Patient <ul><li>trauma </li></ul><ul><li>metabolic </li></ul><ul><li>toxicology </li></ul><ul><li>infection </li></ul><ul><li>psychiatric </li></ul>
  10. 11. Management of alcohol withdrawal <ul><li>General alcohol withdrawal </li></ul><ul><li>Alcoholic seizures </li></ul><ul><li>DTs </li></ul><ul><li>Alcoholic hepatitis </li></ul>
  11. 12. General alcohol withdrawal <ul><li>vitamins </li></ul><ul><li>chlordiazepoxide </li></ul><ul><li>fluid balance </li></ul><ul><li>antibiotics if appropriate </li></ul><ul><li>nutrition </li></ul><ul><li>education </li></ul>
  12. 13. Alcoholic Seizures <ul><li>ABCDEFG </li></ul><ul><li>iv diazemuls </li></ul><ul><li>consider phenytoin </li></ul><ul><li>oral benzodiazepines </li></ul><ul><li>exclude other causes of seizures </li></ul><ul><li>without an epileptogenic focus there is no role for long term anticonvulsants </li></ul>
  13. 14. DTs <ul><li>as for general alcohol withdrawal but more aggressive, especially electrolyte imbalance </li></ul><ul><li>consider iv lorazepam </li></ul><ul><li>avoid haloperidol </li></ul><ul><li>avoid heminevrin </li></ul><ul><li>involve family </li></ul>
  14. 15. Alcoholic Hepatitis <ul><li>Withdrawal of ETOH often appears to exacerbate the LFTs </li></ul><ul><li>several mechanisms involved, but attention is now focused on the immune system </li></ul><ul><li> levels of IgA, ANA, anti ds DNA </li></ul><ul><li> IL-1, IL-6, IL-8 </li></ul><ul><li>B & T lymphocytes found in portal/periportal areas </li></ul><ul><li>TNF  can induce apoptosis of hepatocytes </li></ul>
  15. 16. Mortality for alcoholic hepatitis <ul><li>Overall 30 day mortality ~ 15% </li></ul><ul><li>if severe ~ 50% </li></ul><ul><li>if mild ~ < 5% </li></ul><ul><li>1 year mortality ~ 40% </li></ul>
  16. 17. Treatment of alcoholic hepatitis 1 <ul><li>Standard treatment </li></ul><ul><li>stop alcohol! </li></ul><ul><li>Vitamins - pabrinex & thiamine </li></ul><ul><li>? Vitamin K </li></ul>
  17. 18. Treatment of alcoholic hepatitis 2 <ul><li>Treat complications </li></ul><ul><li>fits </li></ul><ul><li>withdrawal </li></ul><ul><li>DTs </li></ul><ul><li>GI bleeding </li></ul><ul><li>encephalopathy </li></ul>
  18. 19. Treatment of alcoholic hepatitis 3 <ul><li>Failed treatments </li></ul><ul><li>anabolic steroids (Mendenhall 1993) oxandrolone had no benefit </li></ul><ul><li>propylthiouracil  basal metabolic rate of liver - no benefit in 2 large randomised studies </li></ul><ul><li>parvolex/vitamin E/amlodipine all tried with no benefit </li></ul>
  19. 20. Treatment of alcoholic hepatitis 4 <ul><li>Successful treatments </li></ul><ul><li>transplant </li></ul><ul><li>insulin/glucagon </li></ul><ul><li>nutrition </li></ul><ul><li>corticosteroids </li></ul><ul><li>infliximab </li></ul>
  20. 21. The debate about corticosteroids 1 <ul><li>>50 studies published over 30 years </li></ul><ul><li>no benefit for mild alcoholic hepatitis </li></ul><ul><li>suppress inflammatory & immune mediated hepatic destruction </li></ul><ul><li>anti-anabolic effects suppress regeneration & may slow healing </li></ul><ul><li> risk of complications </li></ul>
  21. 22. The debate about corticosteroids 2 <ul><li>3 large meta-analyses favour steroids </li></ul><ul><li>1 large meta-analysis does not </li></ul><ul><li>overall benefit is for severe disease +/- encephalopathy </li></ul><ul><li>severe alcoholic hepatitis defined by Maddrey’s discriminate factor (DF) >32 (Maddrey et al 1978) </li></ul>
  22. 23. Maddrey’s formula <ul><li>4.6 x (prothrombin time - control in seconds) </li></ul><ul><li>+ </li></ul><ul><li>bilirubin (micromols/litre) /17 </li></ul>
  23. 24. The debate about corticosteroids 3 <ul><li>Ramond et al 1992 </li></ul><ul><li>61 patients with severe disease </li></ul><ul><li>32 had 40mg prednisolone for 28/7 </li></ul><ul><li>29 had placebo </li></ul><ul><li>16/29 died by 2 months </li></ul><ul><li>4/32 died by 2 months </li></ul>
  24. 25. Use of steroids with infliximab 1 <ul><li>Spahr et al J Hep 2002 </li></ul><ul><li>first human study (pilot) </li></ul><ul><li>20 patients with severe AH </li></ul><ul><li>11 received prednisolone 40mg & infliximab 5mg/kg iv </li></ul><ul><li>9 received prednisolone 40mg & placebo </li></ul><ul><li>histology, IL-6 & IL-8 were measured @ days 0 & 10 </li></ul>
  25. 26. Maddrey’s score
  26. 27. Serum bilirubin
  27. 28. Interleukins
  28. 29. Conclusions from the study <ul><li>Infliximab was well tolerated </li></ul><ul><li>significant improvement in Maddrey’s score </li></ul><ul><li>favourable changes in IL levels </li></ul><ul><li>hopefully larger studies will now take place </li></ul>
  29. 30. The last slide! <ul><li>Without treatment prognosis for AH is poor </li></ul><ul><li>Many treatment strategies have been tried </li></ul><ul><li>Prednisolone & nutrition are indicated </li></ul><ul><li>Infliximab may have a role </li></ul>

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