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
2
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.
3
4. Quantity of Alcohol in a Standard Drink
4
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
5
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 .
6
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.
7
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.
15
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
16
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.
17
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.
18
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.
19
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
20
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
21
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
23
24. Treatment
Fatty liver
• Alcoholic fatty liver regarded as entirely benign.
• Cessation of drinking results in normalization fat content
within the liver
• Nutritional support
24
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
25
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.
26
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
27
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.
28
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
29
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.
30
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
32
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
33
