2. Introduction
• Chronic and excessive alcohol ingestion major causes of liver
disease
• ALD-fatty liver,alcoholic hepatitis, cirrhosis,HCC.
• In 10 yrs heavy drinkers fatty liver 90-100%, steatohepatitis
10-35% , cirrhosis 8-20%.
• Alcohol-related liver deaths up to 48% of cirrhosis-associated
deaths in USA
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3. Risk factors
Alcohol
• Amount-women >2 drinks (22–30 g)/d, men >3 drinks (33–45
g)/d
• Type- congeners/home brewd/fruit brandies
• Duration-men >60–80 g/d, women 20–40 g/d 10 yrs
• Patterns-binge drinking/continuous drinking
• Drinking outside meals
• Caffeine intake appears to protect against cirrhosis
• Early age alcohol- alcoholism later in life.
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4. Quantity of Alcohol in a Standard Drink
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BEVERAGE ALCOHOL CONTENT(%) UNITS OF ALCOHOL
Ordinary Beer 3% 2 per pint
Strong Beer 5.5% 4 per pint
Extra strong Beer 7% 5 per pint
Table wine 8-10% 7 per bottle
Fortified wines
(sherry, pot, vermouth)
13-16% 15 per bottle
Spirits(whisky, gin,
brandy, vodka)
32% 30 per bottle
5. • Women more susceptible-oestrogens synergistic impact on
oxidative stress-inflammation/lower gastric ADH / lower body
mass.
• Ethnic groups (white Hispanics>black non-Hispanics>white)-
differences genetic/amount-type of alcohol
consumed/socioeconomic status/ access to medical
• Studies in U.K suggest that south asian men are more susceptible
to alcohol related liver injury than European men
• Genetic susceptibility- due to SNPs associated with alcohol
metabolism/fibrogenesis/ fibrolysis/ inflammatory response
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6. • Obesity-risk of cirrhosis in heavy drinkers synergy between
ALD-NAFLD/fibrogenic effects of larger adipose tissue mass
(high NA, angiotensin II,leptin and low adiponectin).
• Coexistence alcohol misuse/chronic HCV infection risk of
cirrhosis 30 times greater.
• Chronic HBV/alcohol consumption increase the risk for HCC
• Iron overload (hemochromatosis) act synergistically produce
oxidative stress thus potentiate progressive liver damage.
• Medications(acetaminophen/herbal)-have increase risk of liver
injury and rapid depletion of glutathione stores .
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7. Alcohol metabolism
• Absorbed mainly-proximal portion of the small intestine.
• 2-10% ethanol excreted directly lungs/urine/ sweat
• Some part undergo first pass metabolism in gut wall
• Greater part- metabolized to acetaldehyde liver cell cytosol by
ADH/rapidly destroyed by ALDH in cytosol/mitochondria
• Second pathway-SER MEOS 10% ethanol oxidation at high
blood alcohol concentrations.
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15. Other mechanisms
• Epigenetics-ethanol affect methylation long-term reduces
hepatic levels of SAMe/DNA-histone methylation, increasing
expression of genes that regulate ER stress response/alcoholic
liver injury
• miRNA-cell growth/differentiation/apoptosis are believed to
be involved in the pathogenesis liver cancer.
• Stem Cells-oval cells (liver progenitor cells) is significantly
increased in patients with ALD/it correlates with disease
severity and might increase the risk of alcoholic liver cancer.
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16. Clinical features
Fatty liver
• Asymptomatic
• Unsuspected hepatomegaly often the only clinical finding.
• Occasionally may present with right upper quadrant
discomfort, nausea, and, rarely, jaundice.
• Differentiation of alcoholic fatty liver from nonalcoholic fatty
liver is difficult unless an accurate drinking history is
ascertained.
• Standard, validated questions accurately detect alcohol-related
problems
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17. Alcoholic hepatitis
• Clinical syndrome-recent onset of jaundice and/or ascites in a
patient with ongoing alcohol misuse. . It is an exacerbation of
an underlying chronic liver disease
• C/F AH resemble viral/toxic liver injury- anorexia, nausea and
vomiting, malaise, weight loss, abdominal distress, and
jaundice.
• Progressive jaundice is the main presenting feature of
symptomatic ASH.
• It may be associated with fever with or without infection,
weight loss and malnutrition, and a large tender liver.
• In severe cases, ASH may induce liver decompensation with
ascites, encephalopathy, and gastrointestinal bleeding.
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18. Cirrhosis
• Easy bruising
• Increasing weakness and fatigue
• Hepatocellular dysfunction and portal hypertension
• Anorexia and malnutrition lead to weight loss and a reduction
in skeletal muscle mass
• Progressive jaundice
• Bleeding from gastroesophageal varices, ascites
• Encephalopathy
• Progressive renal dysfunction often complicates the terminal
phase of the illness.
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19. Diagnosis
• Diagnosis of ALD is frequently suspected upon documentation
of excess alcohol consumption >30 g/d and the presence of
clinical and/or biological abnormalities suggestive of liver
injury.
• Several screening tools exist to establish the diagnosis of
alcoholism CAGE, AUDIT,MAST
• Signs suggestive of harmful alcohol drinking such as bilateral
parotid gland hypertrophy, muscle wasting, malnutrition,
Dupuytren’s sign, and signs of symmetric peripheral
neuropathy,gynecomastia and extensive spider angiomas.
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20. Laboratory diagnosis of alcoholic fatty liver and
alcoholic hepatitis
• AST- Increased 2-7 fold, <400 U/L, AST> ALT
• ALT- Increased 2-7 fold, <400 U/L; AST/ALT- >1;
• Bilirubin- may be markedly increased in alcoholic hepatitis
despite modest elevation in alkaline phosphatase;
• PMN- If >5500/L predicts severe alcoholic hepatitis when
discriminant function > 32.
• MCV, GGT, glutamic oxaloacetic transaminase, glutamic
pyruvic transaminase can indicate early ALD
• Decreased albumin,prolonged PT, increased bilirubin level,
thrombocytopenia advanced ALD is suspected
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21. • Carbohydrate deficient transferrin and GGT are the most
frequently used markers to detect previous alcohol
consumption
• Sensitivity-specificity for detection of daily >50g/day ethanol
consumption -CDT -69% /92% & GGT-73%/75%,
• Non-invasive tests to estimate liver fibrosis
-Serum markers (APRI,FibrometerA , Hepascore, Fibro-Test)
and Transient elastography(Fibroscan/Liver stiffness
measurement)
• Ultrasound, CT scan, and MRI can be used to diagnose fatty
change/cirrhosis/complications /neoplastic diseases.
• Liver biopsy-cofactors suspected/clinical studies/ severe
steatohepatitis requiring specific therapies
• Other tests-CXR,KFT,ECG,Urine R/E,UGIE,viral markers
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23. Indices of prognosis
• Maddrey's DF = (4.6 x [PT - control PT]) + (serum
bilirubin) ,Used for estimation of disease severity and
mortality risk .
• Value >32 high short-term mortality/need corticosteroids in
patients with severe alcoholic hepatitis .
• DF > 32 spontaneous survival 50-65 % & < 32 -90 % .
• One-month mortality 45 % in patients DF >32 with
encephalopathy who did not receive corticosteroids
• Other indices-MELD score,Glasgow alcoholic hepatitis
score,Lille model, Child-Pugh score, ABIC score
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24. Treatment
Fatty liver
• Alcoholic fatty liver regarded as entirely benign.
• Cessation of drinking results in normalization fat content
within the liver
• Nutritional support
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25. Alcoholic steatohepatitis
General measures
• Abstinence-leads to reversal of liver disease and improvement
in survival
• Nutrition-B-complex vitamins,liposoluble vitamins,daily
protein intake of 1.5 g/kg bw,volume expansion
• Radiocontrast avoidance-risk of HRS
• Infections-to be treated
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26. • Screening -psychiatric disorders/substance abuse- specialist
consultation
• Early management of alcohol abuse/ dependence is warranted
in all patients with ASH
• Management of AWS- benzodiazepines long-acting
seizures,delirium/ short-intermediate acting elderly
pts/hepatic dysfunction.Medical therapy of alcohol
dependence in patients with ALD
• Alcohol-dependent pts without advanced ALD disulfiram,
naltrexone,acamprosate, combined with counseling, reduce
alcohol consumption and prevent relapse.
• Topiramate and baclofen promising for AWS treatment/
prevent relapse.
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27. Corticosteroids
• The most recent cochrane meta-analysis
– corticosteroid reduced mortality with DF 32 or HE.
– Higher 28 day survival.
• Most studies
– Only severe forms of ASH benefit from steroids
– Poor responders – switch to pentoxyfylline, but do not
modify the outcome
– Early liver transplantation.
• Limitation of steroid treatment-
– Sepsis, GI bleed, HRS
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28. Pentoxifylline
• In sepsis – steroid C/I , therefore pentoxyfylline can be
considered as first line therapy.
• Anti-oxidant & anti-TNF properties.
• Compared to placebo in severe AH (DF>32), has higher 6 mth
survival.
• Survival benefit related to marked reduction in HRS & not
related to improvement in LFT.
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29. • N-acetylcysteine-antioxidant/replenishes glutathione stores in
hepatocytesrates
• HRS/infectionlower/better 1-month survivalin patients treated
with corticosteroids and N-acetylcysteine.
• SAM-antioxidant/methyl donor- maintain mitochondrial
function/decreasing TNF levels/producing glutathione.
• A multicenter clinical study-SAM 1200 mg/d significantly
reduced mortality rate/decreased need for liver transplantation
in Child's A/B alcoholic cirrhosis pts
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30. • Anabolic steroids, propylthiouracil, antioxidants, colchicine,
and penicillamine - no clear-cut benefits/not recommended.
• Anti-TNF agents-no clear-cut improvement in survival/higher
probability of severe infections/death
• Silmyrin-used for 2000 yrs in Europe for treatment of liver
disease enhance liver regeneration/protect hapetocytes from
toxicity but clinical trails have yet to demonstrate a clear
benefit.
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32. Cirrhosis
• No specific pharmacological therapy available
• Abstinence from alcohol reduces the risks of complications
and mortality
• Identification and management of cofactors, obesity/insulin
resistance/malnutrition/ cigarette smoking/iron overload/viral
hepatitis
• Screening andmanagement of complications of cirrhosis
• Liver transplantation confers a survival benefit in patients with
Child-Pugh C and/or MELD ≥15
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33. Liver Transplantation
• Liver transplantation-definitive therapy .
• Alcoholic hepatitis- contraindication to liver transplantation .
• 6-month abstinence before listing-obviates unnecessary LT in
pts who will spontaneously improve
• Regular screening for cardiovascular disease/neoplasms is of
particular importance before and after LT
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