Alcoholic Liver Disease (ALD)

Dr Kumudith Ekanayaka

26 September 2011

http://www.cmdhb.org.nz/

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 Alcohol-related, 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 Cytosol Mitochondria

Limits ethanol to portal circulation

Lower Activity in females

Inhibited by drugs - Aspirin, histamine H2

Receptor blockers

H. pylori reduces activity

Hepatic Gastric

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

Fatty Liver

Normal Liver

Perivenular Sclerosis

Alcoholic Hepatitis Cirrhosis

Hepatocellular

Carcinoma

Resolves

Resolves

Resolves Continued

Drinking

Continued

Drinking

Continued

Drinking

1-2% pa

Normal Liver Anatomy

Portal Vein

Hepatic Artery

Bile Duct

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

Telangectasia

Palmar Erythema

Clubbing

Dupytrons Contracture

Peripheral Neuropathy

Feminisation

Gynaecomastia

Hypogonadism

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

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

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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

Score CPS 1 year

survival

2 year

survival

5-6 A 100 85

7-9 B 81 57

10-15 C 45 35

Measure 1 2 3

Bilirubin 50

Albumin >35 28-35

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

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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