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  Alcoholic Liver Disease (ALD) Dr Kumudith Ekanayaka 26 September 2011

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Alkohol Liver Disease

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  • 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

    http://www.google.co.nz/imgres?imgurl=http://www.meddean.luc.edu/lumen/meded/mech/cases/case10/Scan27.jpg&imgrefurl=http://www.meddean.luc.edu/lumen/meded/mech/cases/case10/image_f.htm&usg=__XdAWihv8r6P26rRyEPq07hp9CWk=&h=540&w=389&sz=45&hl=en&start=9&zoom=1&tbnid=OZdv84mI1VQLuM:&tbnh=132&tbnw=95&ei=ooJ_TsfqDOGPiAeilIjFDg&prev=/search%3Fq%3Dparotid%2Benlargement%26um%3D1%26hl%3Den%26sa%3DN%26tbm%3Disch&um=1&itbs=1

  • 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

    http://www.google.co.nz/imgres?imgurl=http://www.gastrointestinalatlas.com/Varixstds7.jpg&imgrefurl=http://www.gastrointestinalatlas.com/English/Esophagus/Variceal_Banding_III/variceal_banding_iii.html&usg=__GJfG3tdfDxdgtbb6RMPyPQiTXQc=&h=255&w=400&sz=13&hl=en&start=7&zoom=1&tbnid=3KJbDikKswUcoM:&tbnh=79&tbnw=124&ei=sId_TvzKHomziQfTpeXLDA&prev=/search%3Fq%3Dbleeding%2Boesophageal%2Bvarices%26um%3D1%26hl%3Den%26sa%3DN%26tbm%3Disch&um=1&itbs=1

  • 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