Alcoholic Liver Disease

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Alcoholic Liver Disease

• C.P.Day
• Newcastle University
• United Kingdom

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Alcoholic Liver disease

• Epidemiology
• Susceptibility factors
• Management

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Alcoholic Liver disease

• Epidemiology
• Susceptibility factors
• Management

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ALD the burden of disease

• Commonest cause of cirrhosis in Europe/US
• In EU
• 45, 000 deaths per annum
• 65 of ALL cirrhosis deaths
• 25 of all alcohol-related deaths
• Commonest indication for OLTx in Europe/US
• Europe 1988-2000 5, 716 (17)

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The UK CMO report 2002
In England Wales (2004 versus 1999) ALD
deaths 5,824 versus 4,735 deaths In men
3,651 versus 2,872 deaths In women 2,173
versus 1,863 deaths
In the UK Cirrhosis now the 5th most common
cause of death The top 4 (IHD, CVD, COPD,
Cancer) are all falling
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The UK CMO report 2002
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UK versus Europe
Cirrhosis death rate correlates with per capita
alcohol intake You get the cirrhosis death rate
your drinking deserves
Leon et al Lancet 2006
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Alcoholic Liver disease

• Epidemiology
• Susceptibility factors
• Management

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Prevalence of disease stages in unselected heavy
drinkers
Normal (0-30)
Fatty Liver (60-100)
WHY??
Steatohepatitis (20-30)
Cirrhosis (lt10)
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Non-genetic factors

• Dose pattern of alcohol intake
• Dietary factors
• Specific nutrients
• High fat (?unsaturated) Rotily 1990
• Low carbohydrate Rotily
  1990
• ? Anti/pro-oxidants
• General excess (obesity)
• (Exercise)
• Smoking Becker 2002, Klatsky 2006
• Coffee drinking Klatsky 2006

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ALD Dose individual level
of category
Drinks per day
Bellentani et al 1997
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ALD risk and pattern of intake

• Risk of ALD increased by
• Drinking outside meal-times
• Risk? 3.41.7-6.6 Bellentani 1997
• Drinking beer/spirits rather than wine
• Risk? 2.51.7-3.3 Becker 2002
• Daily versus weekend drinking
• Risk? 2.5 1.8-4.6 Corrao 2000

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Is wine vs beer effect due to dietary factors?
Johansen, Friis, Skovenborg, Gronbaek BMJ 2006
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Diet and ALD the role of obesity

• 1604 heavy drinkers
• Overweight minimum BMIgt25 women, gt27 men in
  previous 10yr
• In multivariate analysis obesity/glucose best
  predictors of cirrhosis (Risk ? gt x 2 for
  obesity)
• Naveau et al 1997
• Raynard et al 2002

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Risk of ALD and coffee drinking

• Klatsky et al Arch Intern Med 2006
• Cohort study
• 125 580 sample 1978-1985
• 330 developed cirrhosis to 2001
• Confirmed previous risk factors
• BMI
• Smoking

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Adjusted for age, weight, smoking, gender,
ethnicity
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Gender and ALD

• Females develop ALD at lower intake
• Explanation ? blood alcohol concentration for
  dose/Kg (?body fat)
  Marshall 1983
• Estrogen sensitises liver to effects of gut
  bacteria (animal models)
  Thurman 1999

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Genetic factors non sex-linked
Concordance rates () among 15 924 twin pairs
Alcoholism genetic ALD genetic Risk
over-and-above the risk of alcoholism
Hrubec Omenn 1981
Ethnic variation in susceptibility
Caetano Clark
1998, Stinson 2001, Klatsky 2006
BUT No replicated evidence for effect of any
gene thus far
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Alcoholic Liver disease

• Epidemiology
• Susceptibility factors
• Management

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Fatty liver (steatosis)

• Inform patient they have a pre-cirrhotic
  condition
• Stop them drinking (reversible)
• ? Adjunctive therapy directed at
  steatosis/obesity
• Gradual weight loss exercise
  
• Specific metabolic treatments
• Metadoxine (ALD) Caballeria et al 1998
• Metformin (NAFLD) Marchesini 2001

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Alcoholic hepatitis a devastating illness

• Jaundice and prolonged clotting associated with
  35 28 day mortality
• Often first presentation
• Steroids improve survival IF not bleeding or
  infected
• 1 in 5 benefit

Mathurin et al 2002
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Alcoholic cirrhosis

• Standard supportive care
• No specific treatments of proven benefit
• ? SAMe worthy of further trial Mato J Hep
  1999
• ? PTU worthy of further trial
  Orrego 1987
• Transplantation for decompensation or liver
  cell cancer (HCC)

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European Liver Transplant Registry www.eltr.com
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Improves survival in selected patientsPoynard et
al 1999
C-PS 5-7
C-PS 8-10
All AFTER a period of abstinence
C-PS 11-15
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Recidivism

• ? Definition (Europe vs US)
• gt sensible limits around 15
• Lower than in non-OLTx Di Martino 2004
• Early studies showed no evidence of harm
• Compliance no worse than others
• Longer f/up shows adverse impact on outcome
• Largely unpredictable (NOT pre-op abstinence)

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Adverse effect of recidivism

• Survival no different
• But
• Drops off at 10yr
• 4/6 deaths in HD due to alcohol excess
• 3 rejections due to non-compliance
• Histology HD more fat fibrosis, 3 ASH, 1
  cirrhosis
• Needs lifelong monitoring
• Pageaux et al 2003

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Public opinion

• Assessing priorities for allocation of donor
  liver grafts survey of public and clinicians
  Neuberger 1998
• 17 of the 1000 members of the general public
• 40 of the 200 family doctors
• 33 of the gastroenterologists considered
• The patient with alcoholic liver disease was the
  least deserving candidate
• Adversely effected by recent high profile cases

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Conclusions

• ALD places a massive burden on the Health
  Services of UK Europe
• Deaths form ALD continue to rise in line with per
  capita consumption, and seem likely to rise
  further
• Susceptibility is determined by pattern as well
  as amount of alcohol consumed as well as to
  several modifiable risk factors including diet,
  exercise and coffee drinking
• Achieving abstinence is the mainstay of
  management
• Steroids for life-threatening alcoholic hepatitis
  and liver transplantation for advanced cirrhosis
  are effective in well selected patients
• Prevention is better and ?more achievable than
  cure?