This document discusses a case of alcoholic liver disease being investigated by Dr. N. Gautam. It provides background information on liver anatomy, alcohol metabolism, and the pathophysiology and clinical presentations of alcoholic liver disease. It describes the typical laboratory investigations performed for ALD including liver enzymes, bilirubin, proteins, and coagulation factors. The document then presents findings from a 45-year-old chronic alcoholic male patient presenting with abdominal pain, jaundice and altered sensorium, with laboratory results consistent with severe alcoholic hepatitis.

1. Investigating a Case of
Alcoholic Liver Disease
Presenter: Dr. N. Gautam
Moderator: Dr. T. Vivian Samuel

2.  Introduction
Liver Anatomy, Physiology, Biochemistry
Alcohol metabolism
 Pathophysiology and clinical presentations of Alocholic Liver
Disease (ALD)
 Investigations in ALD
Biochemical
Peripheral blood smear
USG & Liver biopsy
 Newer parameters of interest in ALD

3. Liver Anatomy

4. Liver Physiology

5. Liver Biochemistry

6. Alcohol Metabolism

7. Alcohol Liver Disease

8. ALD- Pathophysiology

9. ALD-Clinical features
• In early phases most of the people are asymptomatic and found
accidentally
• In late stages once cirrhosis develops patients present with the
following features
– Jaundice
– Pain abdomen
– Hepatospleenomegaly &/or Ascites
– Vomiting/hematemesis/malena
– Gynaecomastia
– Spider naevi
– Coagulation defects
– Convulsions, Altered sensorium, Coma

10. Laboratory Investigations
• Serum enzymes
– Transaminases (AST/ALT)
– Glutamate dehydrogenase
– Alkaline phosphatase
– Gamma glutamyl transferase
• Serum bilirubin
• Total proteins & A:G ratio
• Prothrombin time

11. Aminotransferases
• Most frequently used and specific indicators of hepatocellular
necrosis.
• Types :
1. Aspartate aminotransferase (AST)--- 0-35 IU/L
2. Alanine aminotransferase (ALT)--- 0-45 IU/L
• Level correlates with extent of tissue damage.

12. • AST :
 Cytosolic and mitochondrial isoenzymes.
 Found in liver, cardiac muscle, kidneys, brain, pancreas,
lungs, leucocytes and red cells.
 Less sensitive and specific for the liver.
• ALT :
A Cytosolic enzyme.
Highest concentration in liver.
More specific for liver.

13. 1. Severe (>20 times, 1000 U/L) :
– Severe viral hepatitis
– Drug or toxin induced necrosis
– Circulatory shock
2. Moderate (3-20 times) :
– Acute hepatitis
– Neonatal hepatitis
– Chronic hepatitis
– Autoimmune hepatitis
– Drug induced hepatitis
– Alcoholic hepatitis
– Acute biliary tract obstruction

14. 3. Mild (1-3 times) :
– Sepsis induced neonatal hepatitis
– Extrahepatic biliary atresia
– Cirrhosis, Fatty liver
– Non alcoholic steatohepatitis
– Drug toxicity, Myositis
– Duchenne muscular dystrophy, After vigorous exercise
4. AST:ALT ratio :
– Wilson disease, CLD, ALD : Ratio of >2
– NASH with absence of fibrosis in liver biopsy : Ratio <1
– ALT > AST: Toxic hepatitis, viral hepatitis, chronic active
hepatitis and cholestatic hepatitis

15. 5. Mitochondrial AST : Total AST ratio :
– Characteristically elevated in alcoholic liver disease and
Wilson disease.
6. False low aminotransferase levels :
– Patients on long term hemolysis.
– Uremia.

16. Glutamate Dehydrogenase
• Mitochondrial enzyme.
• Liver, heart, muscle and kidneys.
• In liver highest concentration seen in centrilobular
hepatocytes.
• Normal levels are 0-12 U/L
• Levels elevated in alcoholic hepatitis.

17. Alkaline phosphatase
– Normal range : 30-120 IU/L.
– Family of zinc metaloenzymes with a serine at active centre.
– In liver present on histochemically in the microvilli of the bile
canaliculi and on the sinusoidal surface of hepatocytes.

19. Gamma Glutamyl Transferase
• Hepatocytes and biliary epithelial cells.
• Limited due to lack of specificity.
• Large amounts are found in kidneys, pancreas, liver, intestine
and prostate.
• Values higher in neonates and infants upto 1 year and also
increase after 60 year of life.
• Normal range : <55 U/L in males
<38 U/L in females

20. If ALP raise is in parallel to GGT then the
elevation is due to ALD.

21. Serum Bilirubin
• Endogenous anion derived from hemoglobin degradation from
RBCs.
• Normal bilirubin concentration is 0.3-1 mg/dl.
• Increased bilirubin levels is seen in chronic alcoholics and
severe alcoholic liver disease due to direct toxicity effects over
RBC and splenic sequestration causing excessive RBC
damage.
• Raise in bilirubin concentration is upto 5mg/dl.

22. Serum Proteins
• Tests for proteins in liver disease include
Serum total proteins
Serum albumin
Calculation of albumin/globulin ratio
• Normal levels are
Total proteins 6 to 8 g/dl
Albumin 3.5 to 5 g/dl
A:G ratio 1.2 to 1.5:1

23. Serum Albumin
• Quantitatively most important protein in plasma synthesized by the
liver.
• Serum albumin level is not a reliable indicator of hepatic protein
synthesis in acute liver disease as half life is as long as 20 days.
• Serum levels correlates with prognosis.
• Hypoalbuminemia is not specific for liver disease and may occur.

24. Calculation Of Albumin/Globulin Ratio
• Reversal of A/G ratio occurs due to low albumin and raised
gamma globulins in serum.
• Most common gamma globulins raised in alcoholic liver
disease are Ig A, G, M.
• Used in
– Cirrhosis
– Alcoholic liver disease
– Chronic active hepatitis

25. Prothrombin time
• Liver is major site for synthesis of 11 blood coagulation
proteins : Fibrinogen, prothrombin, labile factor, stable
factor, christmas factor, stuart prower factor, prekallikrein,
and high molecular weight kininogen
• The hepatic synthesis of biologically active forms of
factors II, VII, IX and X requires Vit K.
• The standard method to asses is the one stage prothrombin
time.

26. PARAMETER MILD ALD MODERATE ALD SEVERE ALD
AST
ALT
ALP
GGT
BILIRUBIN
N
ALBUMIN
PROTHROMBIN
TIME

27. Maddrey Discriminant Function
(MDF)
MDF = 4.6 X ( PT- PT Control ) + Plasma
Bilirubin (mg/dl)
• MDF >32 indicates individuals with a high mortality rate and
considered as more sensitive marker in identifying the
prognosis.

28. Model of End Stage Liver Disease Score
(MELD Score)
MELD = 3.78×ln[serum bilirubin (mg/dl)] +
11.2×ln[INR] + 9.57×ln[serum creatinine
(mg/dl)] + 6.43×aetiology
(0: cholestatic or alcoholic, 1- otherwise)
• MELD score >11 considered as more specific in identifying
the prognosis of the disease than MDF.

29. Other lab abnormalities associated
• Hypertriglyceridemia
• Hyperuricemia
• Hypokalemia
• Hypomagnesemia

30. Peripheral smear findings
• Macrocytosis
• Thrombocytopenia
• Leuckocytosis

31. USG & Liver Biopsy
• USG is useful in detecting fatty infilteration of the liver and
determining liver size.
• Demonstration of portal vein flow reversal, ascites and intra
abdominal collaterals in USG indicates serious liver injury
with less potential for complete reversal of liver disease.
• Liver biopsy mainly is used to clarify atypical cases and to
determine the severity of liver disease.

32. Newer parameters of interest

33. Carbohydrate Deficient Transferrin
• Alcohol leads to production of isoforms of transferrin with low
sialic acid content termed as hyposialyl or asialyl or carbohydrate
deficient transferrin.
• Studies proven that CDT is the only test to reliably distinguish
alcoholic hepatitis from non alcoholic fatty liver disease.
• Studies have shown that CDT along with GGT increases the
accuracy of identifying problem drinkers and their prognosis.
• Results are reported as a % of total transferrin as this reduces the
effects of gender & variations in level of transferrin.
< 1.3% - negative
1.3 to 1.6% - inconclusive
>1.7% - positive

34. Apo J or Clusterin Sialylation
(Sialic acid Index)
• It is a highly sialylated protein thought to be involved in the
exchange of lipids between different lipoproteins.
• Sialic acid index of Apo J refers to the ratio of moles of sialic
acid per mole of Apo J protein.
Immuno affinity purification of Apo J
Hydrolysis of sialic acid moieties
Spectrophotometric measurement

35. Apo J or Clusterin Sialylation
(Sialic acid Index)
• Sialic acid index of Apo J levels are reduced with chronic
alcohol intake and they then return to normal levels over a
period of 8 weeks with an approximate half life of 4-5 weeks.

36. Total Sialic acid
• Proposed as a marker for heavy alcohol consumption.
• Chronic alcohol use prevents the glycosylation of many
proteins thus sialic acid levels are found elevated in saliva &
urine.

37. Fatty acid ethyl esters
• Formed in both acute & chronic alcohol intake.
Ethyl glucoronides
• Alcohol metabolites combining with glucoronides.
• EtG in hair considered as long term marker and used in case of
doubtful diagnosis.

38. Serotonin metabolites
(5 HTOL:5 HIAA)
Serotonin
5-HTOL:5-HIAA ratio’s sensitivity & specificity is proportional
to the alcohol intake.
Aldehyde
dehydrogenase
Alcohol
dehydrogenase
Acetaldehyde
Alcohol
5-HIAA
5-HTOL

39. Cytokines
• Various inflammatory markers are studied for sensitivity &
specificity in diagnosing alcoholic liver disease.
• Among various cytokines analysed TGF-β & TNF-α which are
major factors responsible for induction of apoptosis, necrosis
and enhancement of collagen synthesis.

40. Case presentation
45 yr old male who is a chronic alcoholic presented in altered
sensorium to the emergency department.
History given by the attenders person was apparently normal 4
days back developed fever a/w chills and rigors with abdominal
pain and been restless since yesterday complaining no relief of
pain in any posture and in semiconscious state speaking
irrelevantly since evening. No episodes of vomiting/ trauma/
bleeding.
Not k/c/o DM, HTN, Epileptic & Asthmatic.
Chronic alcoholic on abstinence for a week.

41. • O/E semi conscious male moderately built & nourished
Icterus ++ Clubbing +
Vitals PR-80/min BP-102/60mm hg
• PA: soft and tenderness + around umbilicus
clinically no organomegaly detected
no evidence of free fluid
bowel sounds + and normal
• CVS/RS: Normal

42. Parameter Findings
Hb% 10.5
WBC 18,010/cc
MCV 72%
Platelet count 1,00,000/cc
PT (INR) 1.2
Parameter Findings
RBS 70mg%
Total bilirubin 26mg%
Direct 20mg%
Indirect 6mg%
Total protein 5gms%
Albumin 2gms%
Globulin 3gms%
AST/SGOT 194 IU/L
ALT/SGPT 104 IU/L
ALP 73 IU/L