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Alcoholic Liver Disease (ALD)

Dr Kumudith Ekanayaka
26 September 2011

Outline

Alcohol Overview
Alcohol and Health
Alcohol Related Liver Disease
Pathological Changes
History & Examination
Laboratory Investigations
Cases
Management of Advanced Liver Disease

Alcohol Consumption and Health


Deleterious effects of excess alcohol recognised since
early days of recorded history
Prophet Isaiah
Woe to him that is mighty to drink wine

Heberden 1699
Linked Scirrhous livers with consumption of Spirituous liquors

1916
Marked reduction in Alcohol related deaths during prohibition

Mid 1900s
Liver disease as a result of nutritional deficiency

Currently
Alcohol: Directly Hepatotoxic

Alcohol The Global Picture


Most frequently used recreational drug
Average 6.1L Alcohol / Person / Year
Northern Europe - >10L
United States - 8.4L

Changing consumption trends


Australia and Canada declining
Eastern Europe increasing

WHO: ~2.5 million deaths a year


30 years of life lost per each alcohol related death

Global Alcohol Consumption

Alcohol Consumption - New Zealand


85.2% consumed an alcoholic drink in the last 12 months
6.8% Daily alcohol consumption
16 - Median age of first drink
32% before age 14

Higher than average consumption


Maori and Pacific Islanders, Men, Lower socio-economic groups

1835% of injury-based ED presentations Alcoholrelated, rising to between 60-70% during the weekend
(Jones 2009; Humphrey 2003)
600 -1,000 die annually from alcohol-related causes
(Berl 2009)
Alcohol-related deaths
50% Injury, 25% Cancer, 25% Chronic disease (Connor 2005)
2007-2008 New Zealand Alcohol and Drug Survey

Alcohol Metabolism

Hepatic

Hepatic Cytosol

Gastric

Mitochondria

Limits ethanol to portal circulation


Lower Activity in females
Inhibited by drugs - Aspirin, histamine H2
Receptor blockers
H. pylori reduces activity

Patient Risk factors for ALD


Consumption
Continued
Quantity: 80g/d , 20g/d increased risk of cirrhosis
80g/d ~ 8 standard units

Per capita consumption and liver disease


Reduction in times of prohibition, rationing

Type of alcohol consumed seems important

Gender - Female
Reduced gastric ADH
Differences in fatty acid metabolism
Twice as sensitive: More severe disease at lower
doses and duration

Risk factors for ALD


Genetics
Certain HLA phenotypes
Polymorphisms
ADH, CYP2E1, ALDH & TNF

Up-regulation of Cytokines
CD14 and IL10

Viral Hepatitis
Hepatitis C Virus

Accelerates progression
Increases the probability of cirrhosis x8-10
Decreased survival
Related to the effect of alcohol on viral replication or on host
immune response

Risk factors for ALD


Nutrition
Micronutrient abnormality potentially aggravates LD
Low Vitamin A activates Stellate cells

Over-nutrition may be an independent RF


Related to increased TNF and insulin
Increased risk of oxidative stress and immune
hyperactivity

Concurrent exposure to other hepatotoxins


Synergistic
Paracetamol (even at therapeutic doses)

Pathogenesis
Normal Liver
Fatty Liver
Perivenular Sclerosis
Resolves

Continued
Drinking

Resolves

Continued
Drinking

Resolves

Continued
Drinking

1-2% pa

Alcoholic Hepatitis
Cirrhosis

Hepatocellular
Carcinoma

Normal Liver Anatomy

Hepatic Artery

Bile Duct

Portal Vein

Central Vein

Hepatic Steatosis
Short term consequence
Hours within binge

Direct effect of alcohol


Clinical
Asymptomatic
Mild tender hepatomegaly
Normal Bili, Mildly LFTs

Pathology
Fat droplets
Proliferation of smooth
endoplasmic reticulum
Abnormal Mitochondria
Minimal inflammation

Alcoholic Hepatitis

Clinical and pathologic criteria


Clinical
Fever
Hepatomegaly
Jaundice

LFTs
Hyperbilirubinaemia
Elevated ALP, GGT

Pathology

Liver cell necrosis


Mallory bodies
Neutrophil infiltration
Perivenular distribution of
inflammation

Alcoholic Fibrosis & Cirrhosis


Proliferation of ECM
Insoluble scar
Similar in all forms of disease

Fibrosis
Potentially reversible

Cirrhosis
Irreversible

Pathology
Fibrosis initially - pericentral
zone, then progresses to
panlobular fibrosis
Presence of regenerative
nodules

Patient History

Quantity and duration


Social and psychosocial consequences
Other consequences of Alcohol intake
Trauma Falls, injuries
Social situation
Alcohol Questionnaire
Other Liver Disease
Complications Portal Hypertension
Other organs
Cardiac, Pancreatic, Neurological

Examination Findings

Asterixis

Examination Findings

Dupytrons Contracture

Examination Findings

Palmar Erythema

Examination Findings

Gynaecomastia

Examination Findings

Spider Naevi

Examination Findings

Encephalopathy
Portal Hypertension
Ascites
Splenomegaly
Venous Hum

Hepatic Injury

No single sign or
constellation of signs
is 100% specific or
sensitive for ALD

Telangectasia
Palmar Erythema
Clubbing
Dupytrons Contracture
Peripheral Neuropathy

Feminisation
Gynaecomastia
Hypogonadism

Significant Liver
Disease
Ascites
Poor Nutrition
Telengectasia

Examination Other Complications


of Excess Alcohol Consumption

Nasopharyngeal Carcinoma
Parotid Disease
Skeletal Muscle Wasting
Cardiomyopathy
Pancreatic dysfunction
Pancreatitis
Pancreatic Insufficiency

Neurotoxicity
Wernickes-Korsakoff
Cerebellar Disease

Investigations

Full Blood Count


Urea, Electrolytes & Liver Function
Amylase
ECG
Liver Screen
Viral: HAV, HBV, HCV, CMV, EBV
Autoimmune: ANA, IG, AI Screen (SMA, LKM)
Metabolic: Cu, Caeruloplasmin, Iron Studies, Ferritin

Ultrasound Scan
Rule out other pathology
Assess for Portal Hypertension

Nutritional Assessment
Albumin, B12, Folate and Micronutrients

ALD - Laboratory Findings


Liver Function Tests
AST>ALT (Ratio usually >2)
AST>500 or ALT>200 consider other Diagnosis
Elevated GGT - Low sensitivity & specificity

Full Blood Count


Macrocytosis

Carbohydrate-deficient Transferrin
Elevated - Good sensitivity & specificity

Non Specific
Uric Acid, Lactate, TG, IgA & IgG, Ferritin
Mg2+, Glucose, PO43-, K+

Case 1 - AG
43
Routine Check-up
PMHx
Overweight
T2DM
Hypercholesterolaemia

EtOH 30u/wk 15 years


Examination: Mild Hepatomegaly

Case 1 - AG
Bloods
FBC, U&E Normal
LFTs: Bil 6, GGT 80(), ALP 140(), ALT 75()
HbA1C: 9

Other Investigations:

Liver Screen: Negative


INR 1.1, Albumin 39
Chol 3.8
Ultrasound Scan
Increased echogenicity (Fatty Liver), no PHT

Case 1 - AG
Diagnosis
Fatty Liver Disease
No evidence of Advanced Liver Disease
RF: T2DM, increased EtOH intake, BMI

Management
Risk Factor Modification
Weight loss
Reduction in EtOH intake
Control T2DM

6 Monthly Review with LFTs

Case 2 - FL

52
Presentation: Anorexia, Lethargy
PMHx: Pancreatitis, Previous IVDU
EtOH: 30u/wk 25 years
Examination

Tattooed
Muscle wasting
Yellow Sclera
Abdominal Distension

Case 2 - FL
Bloods:
FBC: Hb 99(), MCV 99(), Plate 78(), WC 4
LFTs: Bil 124, ALP 200, GGT 250, ALT 85 ()

Other Investigations
Liver Screen
HCV Reactive, Elevated IgA, Ferritin 400()

INR 2.4(), Alb 24()


Ultrasound Scan Poor views
Coarse liver outline, Splenomegaly, Acites
Portal Vein patent

Case 2 - FL
Diagnosis
Alcoholic Liver Disease with Cirrhosis
Childs Pugh Score: 11 - C

Management
Immediate Abstinence with Counselling
Watch for withdrawal

Low Na diet, Fluid restrict (1.5L), Spironolactone 50mg


Bowel Cares
FP
Improve Nutrition
Hepatitis C: Viral PCR and Genotype
Specialist Referral
Endoscopy ? Varices
Consider Rx HCV

Management
Abstinence

Improved histology and survival


portal pressure and progression to cirrhosis
Support groups
Naltrexone

Optimise Nutrition Many studies


Benefits: Improved histology, LFTs & survival
Detrimental effect of BMI

Identify those at highest risk


Females, concurrent HCV, Family History

Recognising Advanced liver disease

Recognising Advanced Liver Disease


Why Important?

Alcoholic Cirrhosis has worse prognosis than others


Hepatoma 1-2% per annum
Variceal Bleeding
Decompensation Risk of Liver Failure

Suggested By
Bloods
Platelets, Albumin, INR, Bilirubin

Clinical Examination
Liver Specific / Other Organ injury

Imaging: USS / CT
Irregular contour, PV size, Splenomegaly, Varices

Endoscopy
Varices, Portal Hypertensive Gastropathy (PHG)

Indices of prognosis
Alcoholic hepatitis
Maddrey Discriminant Function &
Glasgow Alcoholic Hepatitis score (GAHS)

Alcoholic Cirrhosis
MELD score & Child Pugh Score
Measure

Bilirubin

<34

35-50

>50

Albumin

>35

28-35

INR

<1.7

Ascites
Enceph

Score

CPS

1 year
survival

2 year
survival

<28

5-6

100

85

1.7-2.2

>2.2

7-9

81

57

Nil

Mild

Severe

10-15

45

35

Nil

Controlled

Grade 3-4

Management - Advanced Liver Disease


Recognising Advanced Liver Disease
Specialist Referral
Complications
Encephalopathy
Ascites
Oesophageal Varices
Hepatoma
Transplant Assessment

Management - Encephalopathy
Reversible impairment of neuropsychiatric
function associated with impaired hepatic function
Limited understanding of pathogenesis
Increase in NH3 concentration implicated

Treatment

Treat precipitant (If any)


Lactulose and enemas
No evidence to support dietary protein restriction
Others: Neomycin, Metronidazole, LOLA, Rifaximin

Management - Ascites
80% secondary to liver cirrhosis
Complication of PHT
Spontaneous Bacterial Peritonitis
PMN >250 cells/mm3
Increased risk with higher MELD

Treatment

Fluid Restriction
Low Na+ Intake
Diuretics Spironolactone / Frusemide
Paracentesis
Antibiotic Prophylaxis

Management - Varices
Risk of bleeding
Size, Appearance and Child-Pugh class

15-20% mortality - Severe liver dysfunction


Surveillance Gastroscopy
Bi-annually: Compensated
Annually: Decompensation

Treatment
Non Selective - Blocker: Nadolol, Propranolol
Oesophageal Variceal Ligation

Management - Endoscopic Findings


Normal

Normal

Management - Hepatoma
Worldwide cancer
5th Diagnosis, 2nd Death
7th Diagnosis 6th death

1-2% per annum risk in Cirrhosis


Surveillance
6 monthly USS and FP

Treatment
Transplant If within criteria
Transarterial Chemoembolisation (TACE),
Radiofrequency Ablation (RFA)

Management - Transplant
Consideration
Childs Pugh C
Hepatoma
Other complications
Encephalopathy, Ascites

Six months of abstinence usually required


Alcohol counseling
Risk of recidivism considered

Co-morbid disease
Pancreatitis and cardiomyopathy

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