ALCOHOLIC LIVER DISEASE

DR ALEX MOGERE.
CONSULTANT PHYSICIAN
Spectrum of alcoholic liver disease
1) Fatty liver/steatosis >90%

2) Alcoholic hepatitis 10-15%

3) Cirrhosis 10-20%
↓
4) Hepatocellular carcinoma
 Risk factors in development of Alcoholic
liver disease.
Quantity & duration of alcohol use
Genetics:
 Sex: Females more susceptible >males in
progression of liver disease
 Non gender linked genetic factors
 Metabolic traits
Diet & Obesity
 Risk factors :Quantity & Duration
 Risk of development of ALD starts at 30gms/day of
ethanol
 But for most individuals the dose that confers
significant risk is >80gms/day
 Studies show that males consuming >160gms/day
for>8yrs developed cirrhosis
 Wine drinkers have lower risk >beer & spirit
drinkers
 Daily drinking worse effect >intermittent as the
latter gives liver opportunity to recover
 Alcohol abuse vs dependence
• Alcohol abusers- drink despite recurrent
interpersonal, social or legal problems
• Dependence: presence of 3 or > of the following:
• Tolerance
• Withdrawal symptoms
• Loss of control over drinking
• Strong desire to drink
• Drinking despite harm
 Detection of alcohol abuse
• CAGE(cut down, annoyed by criticism,Guilty
about drinking,Eye opener in the morning)
• AUDIT(alcohol use disorders identification
tests)-a 10 item questionnare
 Alcohol metabolism

 Alcohol absorption occurs in duodenum &

jejunum
 Absorption rapid with empty stomach &
delayed with food
 Has 3 mjr pathways: alcohol dehydrogenases,
cytochrome P450 2E1, catalase
 Alcohol metabolism
 80-85% of ethanol oxidation is by initial
conversion to acetaldehyde catabolised by
alcohol dehydrogenase(ADH)
 Acetaldehyde is further oxidized by
acetaldehyde dehydrogenase
 Both oxidation lead to ↑ ration of
NADH/NAD & this plays a major role in the
initial pathogenesis of alcohol induced fatty
liver
 Pathogenesis
• Genetic factors(ADH2,ALDH2)
• Toxic metabolites of ALDH(adducts)
• Free radicals and oxidative stress
• Role of immune system
• Hypermetabolic state of hepatocyte
• Cytokines(TNF, TGF)
• malnutrition
 Clinical features
 History of heavy alcohol consumption

 Vague abdominal complaints e.g RUQ discomfort

 Physical exam:
Hepatomegally +/-tender
Vascular spider +/-
Features of CLD +/-
 Clinical features/Syndrome
Fatty liver:
Usually asymptomatic
+/-Tender smooth ,firm palpable liver

LFTs may be normal or have

↑GGT +
slightly ↑transaminase
 Clinical features/Syndrome
Acute alcoholic hepatitis
Is a distinct clinical presentation characterized by
jaundice & liver failure in a patient with
prolonged & excessive alcohol consumption
Recent jaundice helps to distinguish with
decompensated cirrhosis
Encephalopathy,RF,Coagulopathy (based on PT) &
serum levels of bilirubin are independent
prognostic markers in AH
Alcoholic Hepatitis:
Diagnosis is based on history of alcohol abuse +
lab results + exclusion of other causes of Acute
liver Injury

Labs: Serum Bilirubin >85µmol/L,

AST>ALT, AST usually <400IU/ml
WBC >10,000/mm3 with an ↑PMN
Alcoholic hepatitis: some clinical manifestations
 Fatigue,anorexia,jaundice,RUQ pain
 Tender hepatomegally , +/-arterial bruit over liver
 +/-fever
 Florid vascular spider
 +/- Associated malnutrition/vit def.
 +/- associated liver failure e.g
ascites,encephalopathy,bleeding diathesis
 Clinical features/Syndrome
Alcoholic liver cirrhosis
 H/O alcohol use
 Hepatomegally –nodular
 Extrahepatic features e.g. Dupuytrens
contracture(feature of alcohol rather than
cirrhosis),features of liver failure
 Splenomegally in portal hypertension
 Evaluation
Liver biochemistry:
↑ AST>ALT
↑ GGT
↑ ALP : particularly those with cholestasis & alcohol related
hepatitis
↓ Albumin: Particularly in cirrhosis

Serum IgA +/-↑

Elevated levels of CDT(carbohydrate deficient Transferin)- is an
alcohol biomarker test
CDT can be used to test whether one is a binge drinker or a daily
heavy drinker.cane even check alcoholic relapse
 Evaluation
Haematology
 ↑MCV

 Macrocytosis is presumed to be due to a direct

effect of alcohol on bone marrow.
Def of folate & vit. B12.can contribute in the
malnourished

 The combination of ↑MCV & ↑GGT will identify

90% of alcoholic dependent pts.
 Evaluation
Imaging
 Abdominal ultrasound
Check for fatty change ,fibrosis, cirrhosis
 CT scan / MRI Scan: Shows fatty liver, cirrhosis

Liver biopsy:
 Rarely required to exclude other causes;
 Differentiates steatosis from steatohepatitis & alcoholic
hepatitis from cirrhosis
 Treatment of ALD
General/universal issues:

 Stop alcohol: Watch for withdrawal symptoms

& treat.- vitamins, diazepam /
chlordiazepoxide
 Identify & treat psychological & physical issues
Treatment of ALD: Acute alcoholic hepatitis.

1) Corticosteroids:
 suppresses hepatic inflammatory response & most effective therapy
 However C/I in active sepsis & bleeding: If present treat then start
steroid
 Failure of drop of bilirubin level by day 7 is indicative of steroid non
responsive: these patients have poor prognosis.
 Increase albumin prdn
 Antifibrotic
 Improves caloric intake by increasing appetite
 32 mg p.o x 4/52 then taper
 Prednisolone preferred over prednisone
 Ct .prednisolone
Ideal patient has:
• MDF > 32 with spont encephalopathy.

C/I:
• Active G/I bleeds,
• HRS
• Sepsis
• AVH
 Pentoxyfilline
• Attenuates TNF a release and action
• Decreases blood viscousity
• Lower portal htn
• Antifibrogenic
• Improves organ microcirculation
• Tissue oxygenation
• 400mg tid x 4 weeks
Treatment of ALD: Acute alcoholic hepatitis

2) Pentoxifyillin:
Give in those in whom steroid is C/I
Improves survival in severe disease by 40%

3) Correct protein & calorie malnutrition

 Treatment of ALD: Cirrhosis
 Give vitamins

 Treat complications

 Liver transplantation: Alcohol related liver

disease account for 20-30% of all indications
of liver transplantation in USA/UK
 PROGNOSTIC SCORES FOR ALCOHOLIC
HEPATITIS
• Maddrey Discriminant Fxn (Modified DF):
4.6x(prolongation of PT)+bilirubin; <32 1
month mortality is 10%;> 32 1 month
mortality is 35%;
• Glasgow alcoholic hepatitis score (score > 9
poor prognosis)
• MELD
• CTP-child- Turcotte- pugh
END