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Alcoho1l Talk

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