“a comparative study of serum cholinesterase and...

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Dissertation on

“A COMPARATIVE STUDY OF SERUM CHOLINESTERASE

AND LIVER FUNCTION TESTS IN LIVER DISEASE”

Submitted in partial fulfilment for the Degree of

M.D GENERAL MEDICINE

BRANCH – I

INSTITUTE OF INTERNAL MEDICINE

MADRAS MEDICAL COLLEGE

THE TAMIL NADU DR. MGR MEDICAL UNIVERSITY

CHENNAI - 600003

MAY - 2019

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CERTIFICATE

This is to certify that the dissertation entitled “A COMPARATIVE

STUDY OF SERUM CHOLINESTERASE AND LIVER FUNCTION

TESTS IN LIVER DISEASE.” is a Bonafide original work done by

Dr. SHANMUKAM.V, post graduate student, Institute of Internal

Medicine, Madras Medical College, Chennai-03, under our guidance and

supervision in partial fulfilment of regulations of the Tamilnadu Dr. M.G.R

Medical University for the award of M.D. Degree Branch I (General

Medicine) during the academic period from 2016 to 2019.

PROF. Dr. P. VASANTHI, M.D. PROF. Dr. S. TITO, M.D.

Guide and Supervisor, Director (i/c) and Professor of Medicine,

Professor of Medicine, Institute of Internal Medicine,

Institute of Internal Medicine, Madras Medical College & RGGGH,

Madras Medical College & RGGGH, Chennai- 600003

Chennai – 600003

PROF.DR. S.RAGHUNANTHANAN, M.D, Dr.R.JAYANTHI,M.D.,FRCP

CO – Guide (GLAS).

Professor of Medicine – IMCU, DEAN

Madras Medical College & RGGGH, Madras Medical College & RGGGH,

Chennai – 600003. Chennai – 600003.

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DECLARATION

I hereby solemnly declare that the dissertation entitled

“A COMPARATIVE STUDY OF SERUM CHOLINESTERASE AND

LIVER FUNCTION TESTS IN LIVER DISEASE” is done by me at Institute

of Internal Medicine, Madras Medical College & Rajiv Gandhi Government

General Hospital, Chennai during August 2017 to January 2018 under the

guidance and supervision of PROF. Dr. P. VASANTHI, M.D, Institute Of

Internal Medicine, Madras Medical College, Chennai-03. This dissertation is

submitted to The Tamilnadu Dr. M.G.R Medical University, Chennai towards

the partial fulfilment of requirement for the award of M.D. Degree in General

Medicine (Branch I)

Place: Dr. SHANMUKAM.V

Date: Post Graduate Student

M.D. General Medicine,

Institute of Internal Medicine,

Madras Medical College & RGGGH,

Chennai 600003.

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ACKNOWLEDGEMENT

I would like to thank our respected Dean, Madras Medical College,

Prof. Dr. R. JAYANTHI, M.D, FRCP(GLAS), for her kind permission to use

the hospital resources for this study.

I would like to express my sincere gratitude to my bellowed Professor and

Director, Institute of Internal Medicine Prof. Dr. S. TITO M.D., for his

guidance and encouragement.

With extreme gratitude, I express my indebtedness to my respected Chief

and teacher Professor Dr. P. VASANTHI., M.D., for her motivation, advice and

valuable criticism, which enabled me to complete this work.

I would also like to thank Professor DR. S. RAGHUNANTHANAN.

M.D for his guidance and valuable criticism.

I would like to express my gratitude to my former Chief and teacher

PROF. Dr. R. SABARATNAVEL.M. D and former Director, Institute of

Internal Medicine, PROF. Dr. S. MAYILVAHANAN., M.D.

I am extremely thankful to Assistant Professor of Medicine

Dr.JACINTH PREETHI, M.D., and Dr. A. PRIYATHARICINI, M.D., for

their co-operation and guidance.

I express my heartfelt gratitude to my Postgraduate colleagues

Dr. JAINY, Dr. SABARISH, and Dr. NOKCHUR IMCHEN for their

constant support and encouragement.

I am immensely grateful to the generosity shown by the patients who

participated in this study.

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CONTENTS

S NO TITLE PAGE NO

1. INTRODUCTION 6

2. AIMS AND OBJECTIVES 9

3. REVIEW OF LITERATURE 10

4. MATERIALS AND METHODS 51

5. OBSERVATION AND RESULTS 56

6. DISCUSSION 84

7. CONCLUSION OF THE STUDY 90

8. LIMITATIONS OF THE STUDY 91

9. BIBLIOGRAPHY 93

10.

ANNEXURES

i. PROFORMA

ii. ETHICAL COMMITTEE APPROVAL

iii. PLAGIARISM SCREENSHOT

iv. PLAGIARISM CERTIFICATE

v. INFORMATION SHEET

vi. CONSENT FORM

vii. MASTER CHART

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INTRODUCTION

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INTRODUCTION

Liver being the largest vital organ, has wide range of functions. Liver disease

are one of the major causes of mortality in India and also worldwide.

Biochemical tests of assessing the liver function, includes measurements of

serum bilirubin, serum protein, serum albumin, serum aspartate transaminase,

alanine transaminase and alkaline phosphatase. These tests often show abnormal

results in patient with clinical conditions other than liver dysfunction.

Serum bilirubin can be raised because of increased erythrocyte lysis other

than failure of hepatic clearance. Serum transaminase can be raised due to

increased release from non-liver tissue sources. Albumin produced by the

hepatocyte are synthesized by polyribosomes bound to the rough endoplasmic

reticulum before secreted into plasma. Decrease in albumin reflects decreased

hepatic synthesis, although changes in plasma volume and losses, for instance in

to gut or urine, may contribute to hypoalbuminemia. Therefore, there comes a

need for a test, which should be specific as well as sensitive for liver disease

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Cholinesterases are a group of enzymes preferably splitting choline and

thiocholine esters. Serum cholinesterase is produced in liver and secreted in

plasma. There are two types of acetylcholinesterase known as RBC

cholinesterase (true cholinesterase) hanging in the cell membrane, and plasma

cholinesterase (pseudocholinesterase). Due to predominant hepatic source of

serum cholinesterase, marked decrease in its synthesis with hepatocyte

dysfunction and restoration of synthesis with hepatocyte recovery suggest that

serum cholinesterase might be a good indicator of liver dysfunction. The present

study was conducted to estimate serum cholinesterase in liver disease cases and

non-hepatic dysfunction cases, and to compare it with other liver function tests.

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AIMS & OBJECTIVE

- To estimate the level of serum cholinesterase and liver function tests in

both liver disease cases and non-liver disease cases and comparing them.

- To estimate the correlation between the serum cholinesterase level with

other liver function tests within the liver disease group.

- To assess the serum cholinesterase level in grading severity of chronic

liver disease.

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REVIEW OF LITERATURE

The very purpose of this study to evaluate the serum cholinesterase

activity as a test of liver function. The test had considerable merit, as it appeared

to be a direct test of liver function which did not depend on any abnormalities of

the protein fraction.

HISTORY:

Estimation of the level of activity of the cholinesterase found in serum

was first suggested by McArdle (1940), as a useful means for differentiating

hepatic from post – hepatic jaundice1

In 1946, Brauer and Root ² and in 1947 Ellis, sanders, Shirley and

Bodansky ³ showed that Serum cholinesterase level was lowered when rat livers

were damaged by carbon tetrachloride.

Brauer& Root⁴ also found, rise in plsma cholinesterase initially, when

administering carbon tetrachloride to dogs, and after one to four hours, it dropped

below normal.

The latter can be explained by the fact, that there is outpouring of the

enzyme, which results in rise in level.

There was no correlation between serum cholinesterase and age, sex, diet,

heart rate, blood pressure, body weight or muscle mass. This was found by Hall

& Lucas.⁵

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Croft & Richter ⁶ observed serum cholinesterase rises during muscle

exercise.,

Bauer⁷ & many others ⁸ ,⁹ ,10 ,11 ,12 ,13 ,1⁴ ,1⁵ ,1⁶ observed that serum

cholinesterase decreased in liver disease and normal in obstructive jaundice.

Any disease producing cachexia has decreased serum cholinesterase level

was observed by Schifrin, Tuchman and Antopol10‚13.

McArdle1 reported normal cholinesterase activity of serum in diabetes and

hyperthyroidism.

Faber 17‚18 noted that low serum albumin was associated with low

cholinesterase.

LIVER DISEASE:

Liver is the largest gland in humans. Liver weighs about 1500g and 5%

of body weight of a new born. The most common liver diseases are Alcoholic

liver disease, Infective hepatitis, Obstructive Jaundice, Liver abscess, Liver

metastasis etc.,

Before we see in to the pathology of the liver. Understanding of the basic

function and histology of the liver is essential.

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FUNCTION OF LIVER:

1. Carbohydrate, fat and protein metabolism

2. Bile production and secretion

3. Storage of glycogen

4. Protein synthesis

5. Production of bile pigments and Heparin

6. Erythropoiesis (in fetus)

HISTOLOGY OF LIVER:

HISTOLOGICAL STRUCTURE OF

LIVER

STROMA

RETICULAR NETWORK

CONNECTIVETISSUE CAPSULE

TRABECULAE

PARENCHYMA

BLOOD VESSELS

BILE DUCT

HEPATOCYTE

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CONCEPT OF HEPATIC LOBULES:

CLASSIC LOBULE:

Structure and functional unit of the organ is classic lobule. It is hexagonal

in shape. It has a vein at the center, which is the central vein and portal tracts in

the periphery.

PORTAL LOBULE:

Portal lobule can be defined as part of liver parenchyma that drain bile in

to hepatic ductule present at the portal triad. Portal lobule can be visualized by

drawing imaginary lines connecting the central veins of their adjacent liver

lobules with portal triad at the center.

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HEPATIC ACINUS (ACINUS OF RAPPAPORT):

Concentric region of hepatic parenchyma surrounding a distributing

artery in the center

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Hepatocyte cells are arranged in cords oriented around the central hepatic

vein. Vascular sinusoids are present between these cords. Fenestrated endothelial

cells line their sinuosity and form space of Disse.

Kupffer cells belonging to monocyte family are found in the space.

Stellate cells involved in vitamin A storage are found scattered in this space.

They are responsible for forming collagen when there is liver inflammation.

We will see some of the important cause of Liver disease and their

pathogenesis.

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ALCOHOLIC LIVER DISEASE:

INCIDENCE:

Worldwide mortality form alcoholic liver disease is estimated to be

1,50,000/year. 90-100% among heavy drinkers will develop hepatic steatosis in

10years. Only 10-30% develops steato hepatitis and 8-20% will develop cirrhosis

in the same period.

Liver cirrhosis develops in 6 – 14% of those persons who consume greater

than 60-80g alcohol, daily for man and greater than 20g, daily for women.

Despite cessation of alcohol use, only 10% will have normalization of

liver histology and liver function tests

PROGRESSION IN ALCOHOLIC LIVER DISEASE

Normal liver 90 to 100 percent Fatty liver

10 to 35 percent 80 to 20 percent

Alcoholic hepatitis cirrhosis

? 40 percent

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BEVERAGES AND THEIR ALCOHOL CONTEST

1. 12 g of alcohol present in 12oz of Beer

2. 12 g of alcohol present in 50oz of Wine

3. 12 g of alcohol present in 1.5oz of HARD LIQUOR

4. One drink is equal to 8g in UK and 19.75g in Japan

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PATHOGENESIS:

Pathophysiology of Alcohol induced liver injury

Alteration in membrane fluidity

Fatty acid ethylesterss, phosphatidylethanol

Alcohol

Lipid peroxidation

Toll like receptor heat shock protein

Decreased

Induces CYP2E1 Hydroxy

ethylradicals

Aldehyde

Iron overload

Perivenular hypoxic

Endotoxemic

SAM synthesis

vitA & VitE

Antioxidant

defense

Mitochondria

GSH

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CENTRILOBULAR HYPOXIA:

Chronic alcohol ingestion have demonstrated susceptibility of the hepatic

pericentral area to hypoxemic due to parallel competitive O2 consumption by

ethanol metabolism.

NEUTROPHIL INFILTRATION AND ACTIVATION:

The characteristic pathologic hallmarks of alcohol hepatitis infiltration of

neutrophils

Both IL-8 and arachidonic acid metabolite acts as a neutrophil

chemoattractant

Kupffer cell secreting inflammatory mediators also have a role in ethanol

induced hepatic injury.

ANTIGENIC ADDUCT FORMATION:

Acetaldehyde and hydroxy ethyl radicals bind covalently to protein

present in the hepatocytes, thereby forming adducts that are antigenic

ACTION OF INJURIOUS CYTOKINES:

Many studies have demonstrated increased levels of the proinflammatory

cytokines, TNFα and IL - 6

In one important study, mice lacking TNF-1alpha receptor gene were

protected from the occurrence of liver disease following ethanol injection.

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COFACTORS THAT POTENTIATE THE DEVELOPMENT OF

ALCOHOL LIVER DISEASE.

AGE:

Early age alcohol consumption is more likely associated with

alcoholism later in life.

GENDER:

Overall prevalence is higher among men than women.

Women are more prone to alcohol related injury and fibrosis then men,

for the same amount of the alcohol consumption.

HEPATITIS C INFCETION:

14 % to 36% individual with Alcohol liver disease also have chronic

infection with hepatitis C.

Increases the risk of HCC.

HBV INFECTION:

Datas suggest that chronic HBV infection and alcohol consumption

increases the risk for HCC.

MEDICATIONS:

Multiple doses of acetaminophens have increased risk of liver injury, due

to rapid depletion of glutathione stores.

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EXCESS IRON:

Iron and alcohol generate reactive O2 species that promote lipid

peroxidation of cell membrane and further damage to cellular integrity occurs.

INFECTIVE HEPATITIS:

HEPATITIS A:

It is usually a self-limited illness that does not become chronic disease.

Fulminant hepatic failure occurs in less than 1 percent of cases.

HAV is a member of the genus Hepato virus in the family picornoviridae.

It is usually transmitted by the faeco oral route.

PATHOGENESIS:

Hepatic injury occurs because of the host immune response to HAV. Viral

replication occurs in the hepatocyte cytoplasm. Hepatocyte damage and

destruction of infected hepatocytes is mediated by human leukocyte antigen –

restricted, HAV- specific CD8+ T lymphocytes and natural killer cells.

Interferon- gamma appears to have a central role in promoting clearance of

infected hepatocytes.

HEPATITIS B:

Hepatitis B virus is a double- stranded DNA virus belonging to the family

of hepadna viruses. It is estimated that there are more than 250 million HBV

carrier in the world, of whom approximately 6,00,000 dies annually from HBV

related liver disease .

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PATHOGENESIS:

The pathogenesis of HBV related liver disease is largely due to immune

mediated mechanism. It can also case direct cytotoxic liver injury.

IMMUNE MEDIATED LIVER INJURY:

HBV related liver disease is generally thought to be related to cytotoxic T

cell mediated lysis of infected hepatocytes.

Patient with chronic hepatitis B, who clear HBeAg have more vigorous

cytotoxic T lymphocyte response to HBV antigen than those who remain HBe

Ag positive.

Fulminant hepatitis B is believed to be due to massive immune mediated

lysis of infected hepatocytes.

DIRECT CYTOTOXIC LIVER INJURY:

There is no correlation between viral load and the severity of liver disease.

Direct cytopathic liver injury can occur when the viral load is very high as in

fibrosing cholestatic hepatitis.

HEPATITIS C:

An estimated amount of 130-170 million people is affected by Hepatitis C

infection worldwide.

Around 75-85% will develop chronic infection.

Around 60 – 70 percent of people develop chronic liver disease.

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Around 5 – 20 percent people develops cirrhosis over the course of CLD

1 – 5percent will develop hepatocellular carcinoma.

HCV is a single stranded RNA virus, which belongs to Genus Hepa – C

virus and family. Flavi – viridae.

It has high spontaneous mutation rate.

There are 11 geno types with 90 sub types.

PATHOGENESIS:

DIRECT CELL INJURY DUE TO VIRAL REPLICATION

Geno type 1 – high viral application

Geno type 1 b – more progressive liver disease

IMMUNE MEDICATED CELL INJURY:

CD8+T lymphocyte found in portal, periportal and lobular areas in

patients with hepatitis C infection.

FACTORS PROMOTING CIRRHOSIS IN HCV INFECTION:

Male sex

Age over 40years at the time of infection

Alcohol use

Coinfection with HIV and/or HBV.

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OBSTRUCTIVE JAUNDICE

BENJAMIN CLASSIFICATION 1983

Type 1: complete obstruction

It has classical symptoms with biochemical changes.

Tumors: Ca head of pancreas

ligation of the common Bile duet

cholangio carcinoma

parenchymal liver disease

Type 2: Intermittent obstruction

Symptoms and biochemical parameters changes but jaundice may or may

not be present.

Choledocholithiasis

Periampullary tumor

Duodenal diverticula

Choledochal cyst

Papillomas of the bile buct

Intrabiliary parasites

Hemobilia

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Type 3: chronic incomplete obstruction:

Pathological changes are present in bile duct and liver with or without

classical symptoms

Strictures of the CBD

Congenital

Traumatic

Sclerosis cholangitis

Post radio therapy

Stenosed biliary enteric anastomosis

Cystic fibrosis

Chronic pancreatitis

Stenosis of the sphincter of oddi

Type 4: segmental obstruction

One or more segment of intra hepatic biliary tract should be obstructed

Traumatic

Sclerosing cholangitis

Intra hepatic stones

Cholangio carcinoma

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HEPATIC FIBROSIS AND CIRRHOSIS:

Hepatic fibrosis can be defined as a reversible wound healing response

characterized by the accumulation of extra cellular matrix or ‘scar’, it follows

chronic liver disease but not self-limited.

Hepatic stellate cells activation is a main central event in hepatic fibrosis.

‘Not only is hepatic fibrosis reversible, but it is also increasingly clear that

cirrhosis may be reversible as well. The exact stage at which fibrosis / cirrhosis

becomes truly irreversible and its biologic determinants, are not known19

20 types of collagens are identified in the liver. Type 1, 3, 5, 11 are largely

present in the capsule, blood vessels and in the portal triad.

Type 4 collagens are present in the space of Disse as delicate strands.

In fibrosis, deposition of type1 and 3 collages results in septae formation.

Blood shunting occurs due to vascular channels formation in these septae.

Irrespective of etiology, cirrhosis is initiated by hepato cellular necrosis followed

by collagen gets deposited in the space of Disse

Fenestrations in the Sinusoidal cells are obliterated

No exchange of solutes between plasma and hepatocytes

Secretory function of liver gets affected.

(chronic inflammation cause activation of Kupffer cells which cause

cytotoxic secretion activation of stellate cells (central event) formation

ECM deposition).

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Perisinusoidal cells and stellate cells acquire myofibrils which cause

increased vascular resistance in the liver.

Hepatocytes which remain, regenerate to form spherical nodules

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CAUSE OF FIBROSIS AND CIRRHOSIS

PRESINUSOIDAL FIBROSIS

I. Idiopathic portal fibrosis

II. Schistosomiasis

PARENCHYMAL FIBROSIS

DRUGS AND TOXIC

Alcohol

Methotrexate

Vitamin A

Isoniazid

Aminodarone

Perhexiline maleate

α methyldopa

INFECTIONS

chronic hepatitis B and C

brucellosis

echinococcosis

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AUTO IMMUNE DISEASE:

Auto immune hepatitis

METABOLIC GENETIC DISEASE

Wilson disease

Genetic hemochromatosis

α,1 anti trypsin deficiency

carbohydrate metabolism disorder

lipid metabolism disorder

urea cycle defects

amino acid metabolism

porphyria

bile acid disorder

BILIARY OBSTRUCTION:

primary biliary cirrhosis

secondary biliary cirrhosis

cystic fibrosis

biliary atresia

neonatal hepatitis

congenital biliary cyst

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IDIOPATHIC/ MISCELLENOUS:

Non alcoholic steato hepatitis

Indian childhood cirrhosis

Granulomatous liver disease

Polycystic liver disease

POST SINUSOIDAL FIBRONS

Sinusoidal obstruction syndromes (venoocculusive disease)

CLINICAL FEATURE OF CIRRHOSIS

Anorexia, wasting, and easy fatiguability

Jaundice

Hyper dynamic circulation

Spider neavi

Palmar erythema

White nails

Hypogonadism

Gynecomastia

Enlargement of alcoholic (alcoholic)

Ascites, peripheral edema

Bleeding from GIT

Hepatic flaps

Splenomegaly

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COMPLICATION OF CIRRHOSIS

1. PORTAL HYPERTENSION

Portal hypertensive gastropathy

Gastroesophageal varices

Splenomegaly

Hypersplenism

Ascites

Spontaneous bacterial peritonitis

Hepatorenal syndrome type1, 2

Hepatic encephalopathy

Portopulmonary hypertension

Hepatopulmonary syndrome

Malnutrition

COAGULOPATHY

Factor deficiency

Fibrinolysis

Thrombocytopenia

BONE DISEASE

Osteopenia

Osteoporosis

Osteomalacia

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HEMATOLOGIC ABNORMALITIES

Hemolysis

Anemia

Thrombocytopenia

Neutropenia

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LIVER FUNCTION TEST

Routine liver function test includes

1. Serum albumin

Albumin is the major constituent of plasma protein with

concentration of 3.5 – 5.0 g/dl

Liver synthesis around 12g albumin per day, around 25% of total

hepatic protein synthesis

FUNCTIONS

1. Colloidal osmotic pressure

2. Transport function

3. Nutritive function

4. Buffering function

Hypoalbuminemia occur when there is damage to

hepatocytes and decreased ability to synthesize albumin

However other causes of Hypoalbuminemia

- Enteropathy

- Malnutrition

- Kidney disease

- Hormonal disturbances

Half life of albumin – 20 days, and hence not useful in assessing

hepatic synthesis in acute liver disease.

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Serum albumin can be used for assessing the prognosis in chronic liver

disease Pre albumin, which is also synthesized by liver, has shorter half

life

PROTHROMBIN TIME:

Prothrombin Time is a measure the rate of formation of thrombin

from prothrombin.

This is dependent on factor II, VII, IX, &X, and other factors along

the extrinsic pathway. Thus, prothrombin time is a measure of hepatocyte

synthetic function.

Normal value: 10.9 – 12.5seconds

Prothrombin time can also be increased by

i. Use of anticoagulants

ii. Deficiency of vit K

iii. DIC

iv. Clotting factor deficiencies

INR (international normalized ratio) has been used to standardize

anticoagulation therapy monitoring and is used in CHILD PUGH scoring system

and MELD scoring system

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TESTS FOR HEPATO CELLULAR DAMAGE AND EXCRETORY

FUNCTION OF LIVER

I. AST (SGOT) – Aspartate aminotransferase

II. ALT (SGPT) – alanine aminotransferase

ALT enzyme found in the hepatocyte cytoplasm

But, AST found in organs like skeletal muscle, brain, kidney,

myocardium, RBC, pancreas, in the cytoplasm and mitochondria

NORMAL VALUES:

ALT – 10-55 U/L

AST- 10-40 U/L

In patients with elevated AST levels disproportionate to ALT levels,

extrahepatic origin of this enzyme must be excluded. Both enzymes are high in

severe rhabdomyolysis.

In initial phase of hepatocellular damage, enzymes elevate, but correlates

poorly with severity of liver injury.

So, it becomes not a good predictor of the outcome in liver disease.

Ureamia can cause a falsely low serum levels of AST

AST/ALT ratio:

1. Alcoholic hepatitis - ≥ 2

2. Cirrhosis - > 1

3. Nonalcoholic steatohepatitis - ≤ 1

4. Wilson’s disease- may have ratio even greater than 4 in severe cases.

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MARKERS OF CHOLESTASIS:

ALKALINE PHOSPHATASE(ALP):

It is a hydrolase enzyme responsible for removing phosphate groups, from many

types of molecule including nucleotides, alkaloids and proteins.

It is present in all tissue, particularly concentrated in liver, bile duct, kidney

bones, placenta, and intestinal mucosa.

Three Isoenzymes of ALP:

1. ALP-I- present in Intestine

2. ALP-L- tissue, nonspecific (Liver , bone, kidney)

3. ALP-p-Specific in placenta

Half life- 5 – 7 days

Normal level-35 – 130U/L

CONDITIONS WITH RAISED LEVELS:

1. Biliary obstruction

2. Osteoblastic bone tumor

3. Hepatitis

4. Osteomalacia

5. Leukemia

6. Lymphoma

7. Paget’s disease

8. Sarcoidosis

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9. Hyperthyroidism

10. Hyperparathyroidism

11. Myocardial infarction

12. Pregnancy

Wilson’s disease can be associated with very low undetectable levels of

alkaline phosphatase.

“BY STANDER PHENOMENON”: Values are raised as a result of

nonspecific hepatitis in Hodgkin disease and malignancies of kidney, but

without direct liver involvement.

“REGAN ISOENZYME”: ALP levels are raised in patients with

malignancy but without bone/liver involvement

GAMMA GLUTAMYL TRANSPEPTIDASE (GGTP):

It is microsomal enzyme, formed in hepatocyte, biliary epithelium,

kidney, pancreas, heart, lung, brain, and spleen.

Normal: 0-30 U/L

Values are raised in cholestasis GGT/ALP > 2.5 suggest alcoholism

5’ NUCLEOTIDASE:

It is formed in liver, pancreas, blood vessels, brain and myocardium.

It is found primarily in canalicular, and sinusoidal plasma membrane in liver.

Normal value- 0-11U/L

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Although, it is elevated in cholestasis but lags behind elevations of GGT and

ALP.

BILIRUBIN:

Synthesis of bilirubin

Hemoglobin

Heme

Biliverdin

Biliverdin reductase

Bilirubin

(RED YELLOW)

(GREEN)

NADPH+ H+

NADP+

H2O2

CO

Globlin Amino acid pool

( Ring Open)

Heme- oxygenase system

(NADPH,Cytohromic C&O2)

O2

Iron liberated – Iron reutilized

(fe 2+)

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[

Normal value < 1.1 g/dl]

Bilirubin is fractionated in to direct and indirect bilirubin

DIRECT BILIRUBIN:

1. Also called conjugated bilirubin

2. Water soluble

3. Make up less than 10%

4. Excreted in urine

INDIRECT BILIRUBIN:

1. Also called as Unconjugated bilirubin

2. Lipid soluble

3. Make up more than 90% of total bilirubin

4. Excreted by the biliary system

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CAUSES OF INCREASED INDIRECT BILIRUBIN

1. Hemolysis

2. Ineffective erythropoiesis

3. Hematoma resolution

4. Rhabdomyolysis

CAUSES OF INCREASED DIRECT BILIRUBIN:

1. Hepatitis

2. Obstructive jaundice

3. Cirrhosis of liver

4. Metastatic liver disease

Conjugated hyperbilirubinemia cannot differentiate hepatocellular liver

injury from biliary obstruction.

Since, serum bilirubin indicates prognosis in liver cirrhosis, acute liver

failure, alcoholic hepatitis, and primary biliary cirrhosis, It is incorporated

in CHILD PUGH and MELD scoring system

PROGNOSTIC SCORING USED IN LIVER CIRRHOSIS

I. Child Turcotte Pugh classification (CTP)

II. Model for end stage liver disease (MELD)

1. CHILD TURCOTTE PUGH SCORE (CTP)

It is initially designed to predict prognose of patients, about to

undergo Portosystemic shunt surgery due to liver disease.

42

It also gives information almost the frequency of complication

occurring post operatively like, encephalopathy, intractable ascites,

gastro intestine bleeding and worsening of liver function.

43

CHILD PUGH CLASSES AND THEIR SURGICAL OUTCOMES:

Class A- well compensated cirrhosis

There is only moderate increase in surgical risk

Class B and C

There is substantial increase in surgical risk

In child class C surgery should be done only in life threatening conditions

example incarcerated hernia

Extreme care is essential in patients undergoing surgery.

Complication should be treated before elective surgery

MODEL FOR ENDSTAGE LIVER DISEASE (MELD)

MELD scoring system is based on serum bilirubin, serum creatinine and INR

value

Ranges between 6 and 40

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ADVANTAGES OF MELD SCORING SYSTEM OVER CTP

Variables in CTP lack reproductivity and consistency

Patients are classified only into three categories in CTP

Patients with severe decompensation are not quantified

CTP prone to subjective variations

Although MELD score is advantageous over CTP scoring system, CTP scoring

is used in our study to grade the severity of chronic liver disease.

CHOLINESTERASES:

Cholinesterase are a group of enzymes preferable splitting choline and

thiocholinester

There are two types of cholinesterase

Acetyl cholinesterase Serum or butyrl cholinesterase

Or

True cholinesterase

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ACETYLCHOLINESTERASE (AchE):

If not for cholinesterase, which are a family of enzymes known to

catalyze the hydrolysis of acetylcholine to choline and acetic acid, thereby

impeding the neurotransmitter ability to signal contraction – skeletal muscle

would to incapable of relaxation²⁰ (Pohanka, 2011).

AchE is structurally determined to have much narrower substrate

specificity than BchE (Butyrl cholinesterase), as they specifically bind to Ach.

The existence of large aromatic residue from the volume of the AchE

aromatic gorge creates a narrow pathway, allowing for higher selectivity of the

enzyme at its active site21 (Sussman et al, 1991).

This enzyme would require more positive charged substrate or inhibitor

than BchE

SITES:

RBC, CNS, PNS and in MUSCLES

MAJOR PROPERTIES:

High turnover

High affinity for acetylcholine

Low affinity for non-cholinester

gets inhibited when concentration of acetylcholine is high

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SERUM CHOLINESTERASE (PSEUDO (OR) BUTYRL

CHOLINESTERASE):

BChE (Butyrl cholinesterase) more commonly found in the liver and

serum of the organisms²².

BChE is known to improve the hydrolysis rate of cocaine, protect the

mice from cocaine’s toxic effects, and protect the human body from OPC

compounds, suggestive of detoxification role in the body²³,²⁴ ‚²⁵ .

BChE has a wider active site than AchE, it has lesser aromatic residues

lining the catalytic gorge and therefore is more voluminous and easily

accomodative for various substrate, specifically for butyrlcholine (Nicolet et

al,2003²⁶ .

HALF LIFE 12 days

SERUM CHOLINESTERSE IN VARIOUS PHYSIOLOGICAL AND

PATHOLOGICAL CONDITIONS:

Many investigators 18,27,28,29 have studied serum cholinesterase in healthy

people and have stated the wide range of variation in enzyme concentration from

person to person

Difference in enzyme activity did not correlate with age, sex, weight,

height or surface area.

Level of cholineterase constant for each healthy, well fed individual, from

month to month.

47

LOW SERUM CHOLINESTERASE

1. LIVER DISEASE AND DISEASE OF THE BILIARY SYSTEM:

when hepatic parenchyma deceased, the serum cholinesterase decrease,

almost invariably. This finding was observed by Antopol et al27

Depression is more marked in patient with CLD, such as cirrhosis than

in patients with acute condition such as viral hepatitis, ascending

cholangitis etc.

Serial studies of serum cholineterase in both acute and chronic disease

have shown that, changes in its concentration closely reflect changes in

the hepatocellular function.

When compared with other liver function tests (serum albumin, serum

bilirubin, SGPT, SGOT, total protein), none appeared to mirror the

changing status of the hepatic parenchyma as sensitively as did the serum

cholinesterase.

Normal levels of serum cholinesterase activity were found in patients

suffering with obstructive jaundice, unless complicated by considerable

hepatic parenchymal involvement.

2. MALNUTRITION AND CHRONIC DEBILITATING DISEASE:

Low levels have been formed in blood from patients, who were mal

nourished, as a result of starvation, anorexia or any chronic inflammatory

disease.

MILHORAT³º observed, that when patients with debilitating disease are

treated and rehabilitated, then rise in their serum cholinesterase activity noted.

48

3. ANEMIA

Many authors have commented upon low level of serum

cholinesterase in various type of anemia’s such as, pernicious anemia,

anemia due to celiac sprue, cooley’s anemia, anemia due to blood loss,

and anemia of chronic infection.

4. OPC poisoning and drugs acting through enzyme inhibition.

5. Drugs such as caffeine, theophylline, aresenochlonline, morphine,

desomorphine, codeine, phenothiazine derivatives, procaine

hydrochloride, etc., are known to decrease cholinesterase activities in

serum 31,6,32,33,34. The mechanism is not known.

6. European studies shows that there is a prevalence of about 3- 4% of

congenital serum cholinesterase deficiency 35

7. Serum cholinesterase is found to be decreased in some community people

in southern India (e.g Arya vysya chettiar)44

Disease state in which serum cholinesterase is normal to high

Myasthenia gravis36

Bronchial asthma³⁷ ‚³⁸

Epilepsy 28,30

Hyperthyroiudism38,29,30

Diabetes milletus 28,30

49

Conditions in which serum cholinesterase activity is high

1. Nephrosis38,18:

Elevated level of cholinesterase in the serum of patients with

nephrotic syndrome have been found by several investigators. One of

the speculation is that the high level of serum cholinesterase in

nephrosis reflects on increased and maximal effect of liver to synthesis

new proteins.

Since the size of cholinesterase molecule is over twice the size

of the albumin molecule, it does not pass through the glomerular

membrane and not dissipated in the urine.

2. Exercise

Croft and Richter6 reported, the vigorous muscular exercise of

short duration cause a transient increase in serum cholinesterase, which

returned to normal after rest.

50

MATERIALS

AND

METHODS

51

MATERIALS AND METHODS:

SOURCE OF DATA:

Patients who were admitted in the Institute of Internal Medicine, Madras

Medical College and Rajiv Gandhi Government General Hospital, Chennai-

600003

SAMPLE SIZE - 150

Group I : Liver disease patients- 75

Group II: Non Liver disease patients – 75

STUDY DESIGN:

Hospital based cross sectional study

STUDY DURATION: 6 months(Aug 2017 – Jan 2018)

INCLUSION CRITERIA:

Patients with any liver disease like infective Hepatitis, Liver cirrhosis,

Obstructive Jaundice, Liver metastasis, Liver abscess were included.

EXCLUSION CRITERIA FOR BOTH GROUPS:

A. Patients with age <20 or > 70 years

B. Acute abdominal disease

C. Chronic Infection

D. Protein energy malnutrition

E. Post operative subjects

52

F. Organophosphorus poisoning

G. Exposure to Succinylcholine, Cocaine, codeine and morphine

H. Acute myocardial infarction.

DATA COLLECTION AND METHODS:

After selection, patients were subjected to thorough history taking and

clinical examination. Following Investigations were performed

1. Serum cholinesterase – DGKC method

2. Total and direct bilirubin – DMSO method45

3. Alanine aminotransferase- NADH, Kinetic UV, method IFCC45

4. Aspartate aminotransferase- NADH, kinetic UV method, IFCC45

5. Total protein – Biuret method45

6. Alkaline phosphatase-p- Nitrophenylphosphate, kinetic method DGKC 45

7. Serum albumin- Bromocresol Green method45

8. Prothrombin time and INR

9. Ultrasonography of abdomen

SERUM CHOLINESTERASE ANALYSIS:

METHOD: Kinetic test, optimized method according to the recommendation of

the german society of clinical chemistry (DGKC)

53

PRINCIPLE:

Cholinesterase hydrolyses butyrlthiocholine under release of butyric

acid and thiocholine. Thiocholine reduces yellow potassium hexacyanoferrate(

III) to colorless potassium hexacyanoferrate(II). The decrease of absorbance is

measured at 405nm

Butyrlthiocholine + H2o Thiocholine + butyrate

2 Thiocholine+ 2[ fe( CN)6]3- + H2o choline+ 2[fe(CN)6]4-+ H2o

REAGENTS:

Components and concentration

R1: Pyrophosphate pH 7.6 95mmol/L

Potassium hexacyanoferrate(III) 2.5mmol/L

R2: Butyrlcholine 75mmol/L

Fresh and non hemolyzed serum was used for assay

About 20 microlitres of the sample was used with 1ml of the reagent and

absorbance was first read at 15 seconds and then at 45 seconds and results were

calculated by the formula

Activity in U/L = Absorbance/ 30 seconds * factor

Factor = [ TV* 1000*2] ÷ [ 14.64 * SV*P]

TV – Total reaction volume in ml

SV- sample volume in ml

Cholinesterase

54

14.64 = millimoles absorption

Coefficient of 5 thio- 2 nitro benzoic acid at 405nm

P- Cuvette pathlength in cm

2= conversion from absorbance per second to absorbance per minute

Reference Range at 37 degree

Men – [ 4620-11500 U/L]

Women- [ 3930-10800 U/L]

STATISTICAL METHODS USED:

The data was analyzed using SPSS software. Pearson correlation

coefficient and P value were calculated to find the correlation and the statistical

significance respectively.

P< 0.05 – Significant

P> 0.05 – not significant

P < 0.0001 – highly significant

55

OBSERVATIONS

AND

RESULTS

56

OBSERVATIONS AND RESULTS:

Liver disease patients: Total no.of cases- 75

1 Chronic liver disease 50

2 Infective Hepatitis 10

3 Obstructive Jaundice 10

4 Liver metastasis 5

Table 1 showing distribution of Patients of liver diseases

Non liver disease patients – Total No.of cases- 75

1 Acute respiratory infection 17

2 CAD 8

3 Cellulitis 6

4 Chronic kidney disease 5

5 COPD 16

6 Dermatitis 9

7 Anasarca 9

8 Bone disease 5

Table 2 showing distribution of patients of non-liver disease

57

Table 3 : ETIOLOGY OF CHRONIC LIVER DISEASE

ETIOLOGY FREQUENCY PERCENTAGE

Alcohol 38 76

Alcohol + HbSAg positive 6 12

Alcohol + HCV 1 2

HbSAg positive 2 4

HCV 1 2

Others 2 4

Total 50 100

58

Table 4 :

AGE DISTRIBUTION:

age group Frequency Percent

20-30 Years 20 13.3

31-40 Years 31 20.7

41-50 Years 42 28.0

51-60 Years 33 22.0

Above 60 Years 24 16.0

Total 150 100.0

INTERPRETATION:

The above table depicts the percentage of the age group of the patients and

the maximum percentage is in 41-50 years (28%)

13%

20%

28%

22%

16%

0%

5%

10%

15%

20%

25%

30%

20-30 Years 31-40 Years 41-50 Years 51-60 Years Above 60 Years

AGE GROUP

20-30 Years 31-40 Years 41-50 Years 51-60 Years Above 60 Years

59

Table 5:

SEX DISTRIBUTION:

Gender Frequency Percent

Male 93 62.0

Female 57 38.0

Total 150 100.0

INTERPRETATION:

The above table depicts the percentage of gender .The maximum percentage is

male(62%).

62%

38%

0%

10%

20%

30%

40%

50%

60%

70%

Male Female

GENDER

Male Female

60

Table 6 : DISTRIBUTION OF ALCOHOLICS

Group

Total (chronic

liver disease)

( Infective

hepatitis)

(obstructive

jaundice)

(Liver

metastasis)

Non

Liver

disease

DRINKING

ALCOHOL

No

Count 5 8 7 3 58 81

% within

group

10.0% 80.0% 70.0% 60.0% 77.3% 54.0%

Yes

Count 45 2 3 2 17 69

% within

group

90.0% 20.0% 30.0% 40.0% 22.7% 46.0%

Total

Count 50 10 10 5 75 150

% within

group

100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

61

Table 7: COMPARISON OF MEANS OF LABORATORY

PARAMETERS IN BOTH GROUPS

Variables N Mean Std. Deviation

Std. Error Mean

I value p value

Serum cholinesterase U/L

Non liver disease

75 6494.21 1269.16 146.55

12.197 p<0.0001 Liver disease patients

75 3816.53 1415.51 163.45

Total bilirubin mgdl_

Non liver disease

75 0.79 0.47 0.05

-6.406 p<0.0001 Liver disease patients

75 7.84 9.51 1.10

Direct bilirubin mg/dl

Non liver disease

75 0.39 0.29 0.03


75 4.58 5.45 0.63

Indirect bilirubin mg/dl

Non liver disease

75 0.41 0.27 0.03


75 3.18 4.48 0.52

SGPT IU/L

Non liver disease

75 35.40 30.93 3.57


75 181.03 354.44 40.93

SGOT IU/L Non liver disease

75 32.40 19.26 2.22 -4.862 p<0.0001

92%

8%

50% 50%50% 50%60%

40%45%55%

0%

20%

40%

60%

80%

100%

MALE FEMALE

CASES(CHRONIC LIVER DISEASE) CASES(INFECTIVE HEPATITIS)

CASES(OBSTRUCTIVE JAUNDICE) CASES(LIVER METASTASIS)

NON LIVER DISEASE

62

Liver disease patients

75 189.39 278.99 32.21

ALP IU/L

Non liver disease

75 94.96 43.17 4.98


75 170.19 115.33 13.32

TOTAL PROTEIN g/dl

Non liver disease

75 6.87 0.66 0.08


75 6.15 0.61 0.07

Serum albumin g/dl

Non liver disease

75 3.78 0.49 0.06


75 2.99 0.52 0.06

P<0.0001 – Highly significant

63

CHOLINESTERASE

U/L

NO.OF LIVER

DISEASE

PATIENTS

NO. OF NON

LIVER DISEASE

PATIENTS

TOTAL

< 4500

>4500

50

25

2

73

52

98

TOTAL 75 75 50

Above table shows that cholinesterase level decrease in 66.7% patient of Liver

disease patients, and only 2.7% of non liver disease patients

SENSITIVITY TO DIAGNOSE LIVER DISEASE – 88.9%

SPECIFICITY TO DIAGNOSE LIVER DISEASE – 97.33%

3492.644488.5 4595.4 4153.8

6494.21

01000200030004000500060007000

Sr cholinesterase



NON LIVER DISEASE

64

Table 8:

TOTAL

BILIRUBIN mg/dl

NO.OF LIVER

DISEASE

PATIENTS

NO.OF NON

LIVER DISEASE

PATIENTS

TOTAL

>1.1

<1.1

70

5

20

55

90

60

TOTAL 75 75 150

Above table shows that Total bilirubin raised in 93.3% of liver disease patients,

and in 26.7% of non liver disease patients.

SENSITIVITY TO DIAGNOSE LIVER PATIENTS – 93.33%

SPECIFICITY TO DIAGNOSE LIVER PATIETNS – 73.33%

9.1

4.95

7.22

2.3

0.79

0

1

2

3

4

5

6

7

8

9

10

CASES(CHRONICLIVER DISEASE)

CASES(INFECTIVEHEPATITIS)

CASES(OBSTRUCTIVEJAUNDICE)

CASES(LIVERMETASTASIS)

NON LIVER DISEASE

Total bilirubin mg/dl



NON LIVER DISEASE

65

Table 9

DIRECT

BILIRUBIN mg/dl

NO.OF LIVER

DISEASE

PATIENTS

NO.OF NON LIVER

DISEASE

PATIENTS

TOTAL

>0.3

<0.3

73

2

37

38

110

40

TOTAL 75 75 150

Above table shows that Direct Bilirubin raised in 97.3% cases of liver disease,

but it is also raised in 49.3% non-liver disease patients.

SENSITIVITY TO DIAGNOSE LIVER DISEASE PATIENTS- 97.3%

SPECIFICITY TO DIAGNOSE LIVER DISEASE PATIENTS – 50.7%

5.11

3.06

5

1.48

0.39

0

1

2

3

4

5

6


66

Table 10

INDIRECT

BILIRUBIN mg/dl

NO.OF LIVER

DISEASE

PATIENTS

NO. OF NON

LIVER DISEASE

PATIENTS

TOTAL

>0.8

<0.8

49

26

5

70

54

96

TOTAL 75 75 150

Above table shows the indirect bilirubin is raised in 65.3% of liver disease patient

and also 6.7% in non liver disease patients.



3.88

1.832.22

0.840.41

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

Indirect bilirubin mgdl

67

Table 11

SGPT IU/L NO.OF LIVER

DISEASE

PATIENTS

NO.OF NON

LIVER

DISEASE

PATIENTS

TOTAL

>40

<40

45

30

13

62

58

92

TOTAL 75 75 150

Above table shows that SGPT is raised in 60% of liver disease and 17.3% of non

liver disease patients.

SENSITIVITY TO DIAGNOSE LIVER PATIENTS: 60%

SPECIFICITY TO DIAGNOSE LIVER PATIENTS: 82.7%

65.96

890.6

94.2 86.235.4

0100200300400500600700800900

1000

SGPT IU/L

68

Table 12

SGOT U/L NO.OF LIVER

DISEASE

PATIENTS

NO.OF NON

LIVER DISEASE

PATIENTS

TOTAL

>38

<38

65

10

21

54

86

64

TOTAL 75 75 150

Above table shows that SGOT is raised in 86.7% of patients with liver disease

and 13.3% of patient with non liver disease

SENSITIVITY TO DIAGNOSE LIVER DISEASE: 86.7%

SPECIFICITY TO DIAGNOSE LIVER DISEASE: 72.0%

108.3

729.6

114.270.2 32.4

0100200300400500600700800

SGOT IU/L

69

Table 13

ALP IU/L NO.OF LIVER

DISEASE

PATIENTS

NO.OF NON

LIVER DISEASE

PATIENTS

TOTAL

>130

<130

40

35

11

64

51

99

TOTAL 75 75 150

Above table shows that ALP is raised in 53,33% patient of liver disease and in

14.7% patients of non liver disease patients



120.16

217.6

405.5

105 94

0

50

100

150

200

250

300

350

400

450

ALP IU/L

70

Table 14

TOTAL PROTEIN

g/dl

NO.OF LIVER

DISEASE

PATIENTS

NO. OF NON

LIVER DISEASE

PATIENTS

TOTAL

<6.5

>6.5

57

18

9

66

66

84

TOTAL 75 75 150

Above table shows that Total protein is decreased in 76% of patients with Liver

disease and 13.63% of patients with non liver diseases

SENSITIVITY TO DIAGNOSE LIVER DISEASE – 76%

SPECIFICITY TO DIAGNOSE LIVER DISEASE – 88%

6.116.22 6.21 6.24

6.87

5.6

5.8

6

6.2

6.4

6.6

6.8

7

Total Protein g/dl

71

Table 15

SERUM

ALBUMIN g/dl

NO. OF LIVER

DISEASE

PATIENTS

NO. OF NON

LIVER DISEASE

PATIENTS

TOTAL

<3.5

>3.5

63

12

16

59

79

71

TOTAL 75 75 150

Above table shows that Serum albumin is decreased in 84% of liver disease

patients and 21.33% of patients with non liver disease patients

SENSITIVITY TO DIAGNOSE LIVER DISEASE PATIENT- 84%

SPECIFICITY TO DIAGNOSE LIVER DISEASE PATIENT – 78.7%

2.893.27 3.18 3.08

3.78

0

0.5

1

1.5

2

2.5

3

3.5

4

Sr albumin g/dl

72

Table 16: COMPARISON OF MEANS OF LABORATORY

PARAMETERS IN CHRONIC LIVER DISEASE GROUP:

(Patients are grouped according to CTP scoring system)

N Mean Std. Deviation

Std. Error

95% Confidence Interval for Mean

Minimum

Maximum

Lower Bound

Upper Bound

f value p value

Sr cholinesterase UL

A 10 5490.60

628.68

198.81

5040.87

5940.33

4823.00

6780.00

105.936 0.000

B 16 4111.56

587.82

146.95

3798.34

4424.79

3367.00

5797.00

C 24 2247.54

650.36

132.75

1972.92

2522.17

1342.00

3394.00

Total

50 3492.64

1440.82

203.76

3083.16

3902.12

1342.00

6780.00


A 10 1.74 0.57 0.18 1.34 2.14 .90 2.30

11.068** p<00.001

B 16 3.91 4.10 1.03 1.73 6.10 .60 12.00

C 24 15.62 13.14 2.68 10.07 21.17 1.20 38.80

Total

50 9.10 11.27 1.59 5.89 12.30 .60 38.80


A 10 1.15 0.46 0.14 0.82 1.48 .40 1.60

12.304** p<00.001 B 16 1.78 1.92 0.48 0.75 2.80 .10 7.00

C 24 8.98 7.42 1.51 5.84 12.11 .50 23.70

Total

50 5.11 6.42 0.91 3.28 6.93 .10 23.70


A 10 0.59 0.17 0.05 0.47 0.71 .30 .80

8.222** p<00.001 B 16 1.80 2.17 0.54 0.65 2.95 .20 7.30

C 24 6.64 6.46 1.32 3.91 9.37 .60 19.40

Total

50 3.88 5.33 0.75 2.37 5.40 .20 19.40

SGPT IU/L

A 10 48.80 47.87 15.14 14.55 83.05 17.00 146.00

.473 .626

B 16 67.19 69.79 17.45 30.00 104.37 13.00 250.00

C 24 72.29 66.51 13.58 44.21 100.37 20.00 250.00

Total

50 65.96 63.78 9.02 47.83 84.09 13.00 250.00

SGOT IU/L

A 10 77.00 43.66 13.81 45.77 108.23 27.00 172.00

.746 .480

B 16 116.06

66.43 16.61 80.67 151.46 32.00 261.00

C 24 116.17

114.70

23.41 67.73 164.60 10.00 496.00

Total

50 108.30

90.15 12.75 82.68 133.92 10.00 496.00

ALP IU/L

A 10 101.00

34.41 10.88 76.39 125.61 62.00 164.00

1.121 0.335

B 16 132.50

43.94 10.98 109.09 155.91 79.00 256.00

C 24 119.92

62.01 12.66 93.73 146.10 36.00 309.00

Total

50 120.16

52.33 7.40 105.29 135.03 36.00 309.00

A 10 6.49 0.43 0.14 6.18 6.80 5.50 7.00 3.266* 0.047

73

TOTAL PROTEIN g/dl

B 16 6.21 0.59 0.15 5.90 6.53 5.10 7.30

C 24 5.89 0.75 0.15 5.57 6.21 4.00 7.10

Total

50 6.11 0.68 0.10 5.92 6.31 4.00 7.30

Sr albumin g/dl

A 10 3.62 0.32 0.10 3.39 3.85 3.30 4.30

38.750** p<00.001

B 16 3.09 0.40 0.10 2.87 3.30 2.20 3.70

C 24 2.46 0.36 0.07 2.31 2.61 1.70 3.00

Total

50 2.89 0.58 0.08 2.73 3.06 1.70 4.30

Since, SGPT, SGOT, ALP don’t show statistical significance, they are not taken

in to Bonferroni Multiple Comparisons

74

MULTIPLE COMPARISONS

Bonferroni

Dependent

Variable

(I)

CTPscore

(J)

CTPscore

Mean

Difference (I-

J)

Std. Error Sig. 95% Confidence Interval

Lower

Bound

Upper Bound

Sr

cholinesterase

U/L

A B 1379.03750* 252.69237 .000 751.6795 2006.3955

C 3243.05833* 235.93876 .000 2657.2945 3828.8222

B A

-

1379.03750* 252.69237 .000

-

2006.3955 -751.6795

C 1864.02083* 202.31582 .000 1361.7325 2366.3092

C

A -

3243.05833* 235.93876 .000

-

3828.8222 -2657.2945

B -

1864.02083* 202.31582 .000

-

2366.3092 -1361.7325

Total bilirubin

mg/dl

A B -2.17250 3.82360 1.000 -11.6653 7.3203

C -13.87667* 3.57010 .001 -22.7401 -5.0132

B A 2.17250 3.82360 1.000 -7.3203 11.6653

C -11.70417* 3.06133 .001 -19.3045 -4.1038

C A 13.87667* 3.57010 .001 5.0132 22.7401

B 11.70417* 3.06133 .001 4.1038 19.3045

Direct bilirubin

mg/dl

A B -.62500 2.13966 1.000 -5.9371 4.6871

C -7.82500* 1.99780 .001 -12.7849 -2.8651

B A .62500 2.13966 1.000 -4.6871 5.9371

C -7.20000* 1.71310 .000 -11.4531 -2.9469

C A 7.82500* 1.99780 .001 2.8651 12.7849

B 7.20000* 1.71310 .000 2.9469 11.4531

Indirect bilirubin

mg/dl

A B -1.21000 1.88746 1.000 -5.8960 3.4760

C -6.05167* 1.76232 .004 -10.4270 -1.6764

B A 1.21000 1.88746 1.000 -3.4760 5.8960

C -4.84167* 1.51118 .007 -8.5935 -1.0899

C A 6.05167* 1.76232 .004 1.6764 10.4270

B 4.84167* 1.51118 .007 1.0899 8.5935

TOTAL

PROTEIN g/dl

A B .27750 .26181 .884 -.3725 .9275

C .59833 .24445 .055 -.0086 1.2052

B A -.27750 .26181 .884 -.9275 .3725

C .32083 .20961 .398 -.1996 .8412

C A -.59833 .24445 .055 -1.2052 .0086

B -.32083 .20961 .398 -.8412 .1996

Sr albumin g/dl

A B .53250* .14723 .002 .1670 .8980

C 1.15750* .13747 .000 .8162 1.4988

B A -.53250* .14723 .002 -.8980 -.1670

C .62500* .11788 .000 .3323 .9177

C A -1.15750* .13747 .000 -1.4988 -.8162

B -.62500* .11788 .000 -.9177 -.3323

*. The mean difference is significant at the 0.05 level.

75

Interpretation:

The above table depicts the CTP group’s percentage .The group C has

maximum (48%) percentage comparing to group A,B .

26%

32%

48%

0%

10%

20%

30%

40%

50%

60%

A B C

CTP SCORE

A B C

76

CORRELATION BETWEEN SERUM CHOLINESTERASE AND

PARAMETERS OF LFT:

CASES(CHRONIC LIVER DISEASE)


N Minimum Maximum Mean Standard

Deviation r


>0.3 48 1342.00 6780.00 3467.10 1462.94

.473**

<0.3 2 3687.00 4524.00 4105.50 591.85

Indirect bilirubin

mg/dl

>0.8 29 1342.00 5797.00 2810.90 1064.74

.396**

<0.8 21 1377.00 6780.00 4434.10 1376.

38

SGPT IU/L

>40 21 1342.00 5797.00 3283.38 1284.48

-.156

<40 29 1377.00 6780.00 3644.17 1548.49

SGOT IU/L

>38 40 1342.00 6780.00 3563.75 1495.61

-.129

<38 10 1450.00 5387.00 3208.20 1223.55

ALP IU/L <130 30 6780.00 1377.00 3501.00 1617.00 0,04

>130 20 5797.00 1342.00 3472.15 1166.23

Serum albumin g/dl

>3.5 5 3510.00 6780.00 5279.80 1232.84

.704** 3.0-3.5 20 1617.00 6124.00 4252.30 1107.62

<3.0 25 1342.00 4588.00 2527.48 947.22


>1.1 45 1342.00 6124.00 3306.24 1354.62

-.452**

<1.1 5 3687.00 6780.00 5170.20 1156.24

**P<0.001

Serum cholinesterase showed moderate negative correlation with serum bilirubin

Strong positive Correlation with albumin at p value <0.001

Correlation with Total bilirubin, Direct bilirubin, Indirect bilirubin is negative at p value

<0.001

Correlation with serum transaminases are statistically not significant

77

Scatter diagram showing strong Positive correlation between serum cholinesterase and

serum albumin in chronic liver disease group.

Scatter diagram showing moderate negative correlation between serum cholinesterase

and Total bilirubin in Chronic liver disease group.

78

CORRELATION OF SERUM CHOLINESTERASE AND PARAMETERS OF

LFT IN INFECTIOUS HEPATITIS GROUP:

Cases ( Infective hepatitis)

Serum cholinesterase UL

N Minimum Maximum Mean

Standard

Deviation

Direct bilirubin mg/dl >0.3 10 3100.00 6454.00 4488.50 1092.14 -.840**

<0.3 0

Indirect bilirubin mg/dl >0.8 9 3100.00 6454.00 4381.33 1101.20 -.920**

<0.8 1 5453.00 5453.00 5453.00

SGPT IU/L >40 10 3100.00 6454.00 4488.50 1092.14 .587

<40 0

SGOT IU/L >38 10 3100.00 6454.00 4488.50 1092.14 .667*

<38 0

ALP IU/L <130 0 0.648

>130 10 6454.00 3100.00 4488.50 1092.14

Serum albumin g/dl >3.5 1 5600.00 5600.00 5600.00

.680*

3.0-3.5 9 3100.00 6454.00 4365.00 1081.79

<3.0 0

Total bilirubin mg/dl >1.1 10 3100.00 6454.00 4488.50 1092.14 -.928**

<1.1 0

**p<0.001

*p<0.05

Serum cholinesterase has moderate to strong positive correlation with serum

albumin and SGOT at p value <0.05

Serum cholinesterase has strong negative correlation with Total bilirubin, Direct

bilirubin, Indirect bilirubin at p value <0.001

correlation with SGPT and ALP are statistically not significant

79

Scatter diagram

showing Positive

correlation

between serum

albumin and serum

cholinesterase in

Infective hepatitis

group

Scatter diagram showing

Negative correlation between

Total bilirubin and serum

cholinesterase in Infective

hepatitis group

80

CORRELATION OF SERUM CHOLINESTRASE WITH

PARAMETERS OF LFT IN OBSTRUCTIVE JAUNDICE GROUP:

Cases ( obstructive jaundice)


N Minimum Maximum Mean Standard

Deviation

Direct bilirubin

mg/dl

>0.3 10 2879.00 6232.00 4595.40 1241.04 -.820**

<0.3 0

Indirect bilirubin

mg/dl

>0.8 10 2879.00 6232.00 4595.40 1241.04 -.550

<0.8 0

SGPT IU/L >40 10 2879.00 6232.00 4595.40 1241.04

.194

<40 0

SGOT IU/L >38 10 2879.00 6232.00 4595.40 1241.04

-.130

<38 0

ALP IU/L <130 0 -0.408

>130 10 6232.00 2879.00 4595.00 1241.04

Serum albumin g/dl

>3.5 0

.963** 3.0-3.5 8 3620.00 6232.00 4983.00 1055.41

<3.0 2 2879.00 3211.00 3045.00 234.76

Total bilirubin mg/dl >1.1 10 2879.00 6232.00 4595.40 1241.04

-.850** <1.1 0

**p<0.001

Serum cholinesterase has strong positive correlation with serum albumin at p

value <0.001 Serum cholinesterase has strong negative correlation with Total and

Direct bilirubin at p value <0.001. Correlation with other variables are statistically not

significant.

81

CORRELATION OF SERUM CHOLINESTERASE WITH PARAMETERS OF

LFT IN LIVER METASTASIS:

Cases(Liver metastasis) Serum cholinesterase U/L

N Minimum Maximum Mean Standard Deviation

Directbilirubin mg/dl

>0.3 5 2324.00 5349.00 4153.80 1178.73 -.762

<0.3 0


>0.8 1 2324.00 2324.00 2324.00 -.869

<0.8 4 3732.00 5349.00 4611.25 676.35

SGPT IU/L >40 4 2324.00 4832.00 3855.00 1121.30 -.708

<40 1 5349.00 5349.00 5349.00

SGOT IU/L >38 5 2324.00 5349.00 4153.80 1178.73 -.861

<38 0

ALP IU/L <130 5 5349.00 2324.00 4153.00 1178.73 -0.31

>130 0

Serum albumin g/dl >3.5 0 .994**

3.0-3.5

3 4532.00 5349.00 4904.33 413.28

<3.0 2 2324.00 3732.00 3028.00 995.61

Total bilirubin mg/dl >1.1 4 2324.00 5349.00 3984.25 1288.75 -.821 <1.1 1 4832.00 4832.00 4832.00

**p value<0.001


value<0.001 Correlation with other variables are significantly not significant

82

CORRELATION OF SERUM CHOLINESTERASE WITH SEVERITY OF

CHRONIC LIVER DISEASE ACCORDING TO CHILD TURCOTTE PUGH

SCORING:

+


Count Minimum Maximum Mean

Standard

Deviation

r VALUE

CTP

SCORE

A 10 4823.00 6780.00 5490.60 628.68

-0.857** B 16 3367.00 5797.00 4111.56 587.82

C 24 1342.00 3394.00 2247.54 650.36

**p value<0.001

Serum cholinesterase has strong negative correlation with CTP score and it is

statistically significant. (i.e severity of chronic liver disease increase with decrease in

serum cholinesterase.

Mean Serum cholinesterase CTP score

5490.60±628.68 A

4111.56±587.82 B

2247.54±650.36 C

83

DISCUSSIONS

84

DISSCUSSION:

Our study was conducted to estimate the level of serum cholinesterase and

other liver function test( i.e serum albumin, Total protein, SGPT, SGOT, ALP,

Total bilirubin, Indirect bilirubin, Direct bilirubin) to 150 cases ( fulfilling the

inclusion and exclusion criteria) admitted during period of August 2017 to

January 2018.

The patients were divided into two groups:

a. GROUP I – Liver disease patients

b. GROUP II- Non liver disease patients

Analysis was done to study the comparison of serum cholinesterase and

other liver function tests between Hepatic and non-hepatic cases.

Analysis was also done to study the correlation between levels of serum

cholinesterase and levels of serum albumin, serum bilirubin, and severity of

cirrhosis of liver ( CTP scoring system) using pearson’s correlation coefficient

Following Observations were made from our study:

i. AGE DISTRIBUTION:

Out of 150 patient, majority were in the 41-50 years age group

(28%)

ii. SEX DISTRIBUTION:

Out of 150 patients, 93 patients were made (62%) and

remaining 57 patients (38%) were females.

85

COMPARISON OF MEANS OF LABORATORY PARAMETRS IN

BOTH GROUPS:

In the study, the level of serum cholinesterase was significantly lower in

liver disease patients comparing non-liver patients. Mean of non - liver patients

being 6494.21± 1269.16U/L and mean of liver disease patients being 3816.53±

1414.51 U/L, which is highly significant, p value<0.001. Similarly, Total

bilirubin, direct bilirubin, Indirect bilirubin, SGPT and SGOT, ALP was

significantly higher in liver disease when comparing to non-liver disease patient.

Cholinesterase levels decrease in 66.7% of liver disease patients and in

only 2.7% of non-liver disease patients. Total protein levels were lowered in both

groups of patients,76% in liver disease patients while in non-liver disease

patients it was 88%.

Serum albumin was not only low in liver disease patients (84%), but also in non-

liver disease patients (21.33%). Sensitivity – 84%, specificity – 78.7%, at

3.5g/dl.

In our study, it is clearly showed that assay of cholinesterase level has

sensitivity of 89.9% and specificity of 97.33%, at 4500 U/L

SERUM CHOLINESTERASE IN VARIOUS CHILD PUGH SCORE

GROUPS

In chronic liver disease group, patient is classified according to CTP scoring

system. The result shows that cholinesterase tends to decrease in three grades

Mean Serum cholinesterase CTP score

5490.60±628.68 A

4111.56±587.82 B

86

2247.54±650.36 C

The result is in agree with findings of Gu and Zhong 39. Their data

demonstrated that cholinesterase in the three grades were :

(Child A – 5978 ± 535 u/l)

(Child B – 3957 ± 454 U/l)

(Child C – 2267 ± 332 u/l)

and also agrees with FANPING MENG,XIAOJUAN YIN48,where their sample size is

866 cirrhotic patients and the results are

(child A- 5368±1657.32 U/L)

(child B-2943.06±1212.84U/L)

(child C-1832.51±710.68 U/L)

The child pugh score employs five clinical measures of liver disease, among which

ascites and hepatic encephalopathy are subjective measures. Compared with the Child

Pugh score, cholinesterase is easier and more objective in evaluating the liver reserve

function of cirrhotic patients.

In our study in cirrhotic patients, cholinesterase was positively correlated with

albumin and negatively correlated with total bilirubin, confirming that those substances

were synthesized in the liver and reduced in liver dysfunction due to reduced synthesis.

r value(pearson coefficient) for correlation between serum choilnesterase and serum

albumin is 0.702, r value(pearson coefficient) for correlation between serum

cholinesterase and CTP scoring system is - 0.857 . This shows that serum cholinesterase

has strong correlation with CTP scoring system comparing serum albumin. Correlation

87

with albumin is positive. Correlation with CTP score system is negative. i.e serum

cholinesterase decreases with increasing severity of chronic liver disease.

In their study Gu and Zhong, demonstrated that three cirrhotic patients (two child B

and one child A score patient) suffered hepatic encephalopathy following portal

azygous disconnection operation, with cholinesterase levels of <2,000 u/l. Thus, author

suggested that cirrhotic patients with cholinesterase of <2,000 u/l may have higher risk

of failure.

Data from study conducted by khan40 pointed that 100% patients with cirrhosis

had lower serum cholinesterase level and he also showed that there was close

relationship between the severity of cirrhosis and level of serum cholinesterase .

William burnett found serum cholinesterase is useful both as a liver function

test and in diagnosis of jaundice.

Ramachandran et al found median serum ChE in chronic liver disease patients

was 1590 IU/L (110-8143) compared to non-liver disease patients 7886IU/L

(2022-21673), p<0.001. Serum ChE levels below 3506 had a 98.7% sensitivity

and 80.3% specificity in predicting cirrhosis found serum ChE is an excellent

biom arker of cirrhosis with good sensitivity and specificity42

The finding of present study correlate well with finding of previous studies of

. Ruchi Gokani et al46 (2014), Vihan C et al47 (2014), S Venkata Rao et

al43(2011) etc.

88

INFECTIVE HEPATITIS GROUP:

Serum cholinesterase has moderate to strong positive correlation with

serum albumin and SGOT at p value <0.05. Serum cholinesterase has strong

negative correlation with Total bilirubin, Direct bilirubin, Indirect bilirubin at p

value <0.001. Correlation with SGPT and ALP are statistically not significant.

SGPT and SGOT are raised significantly when comparing to other groups (i.e. Chronic

liver disease ,obstructive jaundice and liver metastasis)

OBSTRUCTIVE JAUNDICE:


value <0.001Serum cholinesterase has strong negative correlation with Total and Direct

bilirubin at p value <0.001. Correlation with other variables are statistically not

significant. ALP is raised significantly when comparing to other groups (Chronic liver

disease, infective hepatitis and liver metastasis)

LIVER METASTASIS:

Serum cholinesterase shows positive correlation with serum albumin. There

is no significant correlation between serum cholinesterase and any other lab

parameters of liver function test.

89

CONCLUSION

90

CONCLUSION:

From our study, the following results were concluded:

The most commonly observed etiology for chronic liver diseases is

alcohol.

In our study, serum cholinesterase were decreased in liver disease

patients (mean value of chronic liver disease – 3492.64±1440.82 U/L,

Infective hepatitis – 4488.5±1092.14 U/L, Obstructive jaundice –

4595.4 ± 1241.04 U/L, Liver metastasis- 4153.8 ± 1178.73 U/L, Non

liver disease patients – 6494.21 ± 1269.16 U/L).

Serum cholinesterase below 4500u/l has good specificity comparing

to serum albumin in diagnosing liver disease patients.

There was significant positive correlation between serum albumin and

serum cholinesterase level in all cases of liver disease patients.

There was significant negative correlation between serum bilirubin

and serum cholinesterase level in all liver disease patients except liver

metastasis in our study.

Significant correlation was found between serum cholinesterase and

CTP scoring in chronic liver disease patients. Levels were lower

among patients in CHILD PUGH class C.

Thus, there was significant correlation between levels of serum

cholinesterase and severity of liver cirrhosis.

91

LIMITATIONS

1. It is a single centered study. We need multicentric study involving

patients of different geographical areas to have a better analysis.

2. Sample sizes of sub-groups of liver disease patients (CLD(n50), infective

hepatitis(n10), obstructive jaundice(n10) and liver metastasis(n5)) were

small

3. congenitally cholinesterase deficient community people (e.g. arya vysya

chettiar in southern India) were not included in exclusion criteria.

4. Liver biopsy/elastography was not done to confirm the diagnosis of

cirrhosis.

92

BIBLIOGRAPHY

93

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99

ANNEXURES

100

PROFORMA

PATIENT DETAILS:

Name: Age: Sex:

IP No.:

ON ADMISSION:

Main Complaints:

H/o jaundice

H/o abdominal distension

H/o pedal oedema

H/o reduced urine output

H/o breathlessness

H/o orthopnoea/PND

H/o haemetemesis

H/o melena

H/o seizures

H/o altered sensorium

H/o altered sleep pattern

H/o chest pain

H/o abdominal pain

H/o fever

H/o constipation

H/o intake of any drugs

Co – Morbid Illness :

Significant Past History :

CLINICAL EXAMINATION:

Pulse BP :

RR : Temp :

Pallor : Icterus :

101

CVS : RS :

P/A :

CNS :

INVESTIGATIONS :

Hemogram :

Renal Function Test :

BT/CT/PT/INR :

Blood Grouping :

Serum cholinesterase :

ECG :

CXR :

USG Abdomen :

LFT :

102

ETHICAL COMMITTEE APPROVAL CERTIFICATE

103

PLAGIARISM SCREENSHOT

104

PLAGIARISM CERTIFICATE

This is to certify that this dissertation work entitled

“A COMPARATIVE STUDY OF SERUM CHOLINESTERASE AND

LIVER FUNCTION TESTS IN LIVER DISEASE” of the candidate Dr.

V. SHANMUKAM with registration number 201611022 for the award of

M.D. in the Branch of General Medicine. I personally verified the

urkund.com website for the purpose of plagiarism check. I found that the

uploaded thesis file contains from introduction to conclusion pages and the

result shows 6% of plagiarism in the dissertation.

Guide & supervisor sign with seal

105

INFORMATION SHEET

We are conducting a study on “A COMPARITIVE STUDY OF

SERUM CHOLINESTERASE AND LIVER FUNTION TEST IN LIVER

DISEASE” among patients attending Rajiv Gandhi Government General

Hospital, Chennai and for that your specimen may be valuable to us.

The purpose of the study is

1. To estimate the level of serum Cholinesterase in both liver disease

and non liver disease patients

2. To compare its level with other tests of liver function like bilirubin,

SGPT, SGOT, ALT, total protein and serum albumin.

3. To assess the serum cholinesterase level with severity of chronic

liver disease.

We are selecting certain cases and if you are found eligible, we

may be using your information which in any way do not affect your final

report or management.

The privacy of the patients in the research will be maintained

throughout the study. In the event of any publication or presentation resulting

from the research, no personally identifiable information will be shared.

Taking part in this study is voluntary. You are free to decide whether to

participate in this study or to withdraw at any time; your decision will not

result in any loss of benefits to which you are otherwise entitled.

The results of the special study may be intimated to you at the end

of the study period or during the study if anything is found abnormal which

may aid in the management or treatment.

Signature of Investigator Signature of Participant

Date:

Place:

108

MASTER CHART

S.NO NAME AGE/SEXMARTIAL

STATUSSMOKING

DRINKING/ALCO

HOLIC

Sr. Cholinesterace

level U/L

Total bilirubin

mg/dl Direct bilirubin mg/dl

Indirect bilirubin

mg/dl

SGPT

IU/L

SGOT

IU/L

ALP

IU/L

Total protein

g/dl

Sr.albumin

g/dl

1 Mani 34/m Married 5105 1.2 0.6 0.6 41 39 129 6.5 3.8

2 Muniyammmal 66/f Married 6994 0.8 0.5 0.3 32 16 124 7.2 4.3

3 Adhilakshmi 42/f Married 6622 0.6 0.4 0.2 16 14 124 7.5 4.9

4 Gopi 50/m Married 6774 0.6 0.3 0.3 16 14 117 6.3 3.6

5 Chandra 50/f Married 5701 0.9 0.4 0.5 32 36 164 8.9 4.4

6 Rani 65/f Married 9990 0.8 0.6 0.2 20 14 102 7.4 3.2

7 Chandra 56/f Married 5643 0.5 0.2 0.3 21 15 69 8 4.6

8 Lakshmi 55/f Married 7156 0.7 0.5 0.2 16 28 82 7.6 3.8

9 Mary 65/f Married 6125 1.2 0.8 0.4 24 18 133 4.8 3.1

10 Parvathy 56/f Married 6626 1.2 0.8 0.4 22 16 78 6.5 3.9

11 Kalaivani 45/f Married 5801 0.7 0.5 0.2 22 18 134 6.9 4.1

12 Fowgiya begum 55/f Married 5335 1.2 0.6 0.6 42 30 123 6.8 4.1

13 Munusamy 55/m Married 6413 0.8 0.3 0.5 37 48 55 6.6 3.7

14 Penicillah 66/m Married Yes Yes 7470 0.7 0.4 0.3 25 42 63 6.5 3.6

15 Hemalatha 38/f Married 7308 0.2 0.1 0.1 23 31 123 7.5 3.6

16 Syed 56/m Married Yes 7986 0.7 0.3 0.4 17 19 53 8.4 4.8

17 Saroja 60/f Married 5847 0.3 0.2 0.1 12 21 77 7.1 4.2

18 Pushpa 55/f Married 7669 0.3 0.1 0.2 14 22 129 6.5 3.7

19 Nirmala 42/f Married 5040 0.2 0.1 0.1 16 23 67 7.2 4.1

20 Jaya 65/f Married 5140 0.3 0.1 0.2 35 22 99 6.7 3.9

21 Malliga 35/f Married 6013 1.2 0.2 1 40 26 102 7.8 3.7

22 Gopal 60/m Married Yes 5700 1.7 1.3 0.4 30 34 105 6.5 2.8

23 Raji 55/f Married Yes 8648 0.3 0.1 0.2 27 58 88 6.3 2.5

24 Viswanathan 48/m Married 8195 0.2 0.1 0.1 19 23 24 6.6 3.7

25 Kuppammal 64/f Married 4870 0.6 0.2 0.4 41 68 119 6.8 3.7

26 Saroja 60/f Married 4913 0.5 0.1 0.4 112 63 71 5.4 3.4

27 Ganesh sharma 52/m Married 5750 0.7 0.2 0.5 63 72 226 7.3 3.9

28 Kathiresan 24/m Unmarried 5376 2.9 1.7 1.2 35 48 83 6.3 3.1

29 Ponnusamy 50/m Married Yes Yes 6477 0.5 0.1 0.4 112 63 71 5.4 3.4

30 Kamala 65/f Married 7396 0.7 0.2 0.5 13 17 105 6.3 3

31 Maheswari 30/f Married 5042 0.9 0.8 0.1 13 11 50 7.1 4.1

32 Vanitha 21/f Unmarried 6622 0.5 0.1 0.4 23 21 72 7.1 3.3

33 Dhatchayani 27/f Unmarried 6993 0.4 0.1 0.3 182 52 189 6.1 3.4

34 Pandu 59/m Married Yes Yes 7207 0.3 0.1 0.2 27 31 163 6.8 3

35 Aravindhkumar 46/m Married Yes Yes 6308 1.2 0.7 0.5 24 19 80 6 3.8

36 Arumugam 44/m Married Yes 6140 1.2 0.7 0.5 22 26 18 6.6 3.7

37 Chandramoorthy 69/m Married Yes Yes 6140 1.2 0.7 0.5 26 22 98 6.6 3.7

38 Kamala 25/m Married 5140 1.2 0.6 0.6 31 25 110 6.5 3.7

39 Jothi 45/m Married 6182 0.2 0.1 0.1 16 21 79 7.5 4.2

40 Venkatachalam 65/m Married 5243 0.4 0.1 0.3 18 24 116 6.7 3.2

41 Ramachandran 56/m Married Yes 6258 0.3 0.1 0.2 32 35 122 6.9 3.8

42 Chinna 20/m Unmarried 5183 1.5 0.3 1.2 35 15 114 7.3 4.1

43 Robert 45/m Married Yes 6428 0.5 0.3 0.2 54 61 102 6.8 3.9

44 Karunakaran 52/m Married 6842 1.6 0.9 0.7 39 32 100 6.5 3.1

45 Baby 49/f Married 4367 0.3 0.1 0.2 76 55 64 6.8 3.2

46 Palani 40/m Married Yes Yes 8488 0.8 0.5 0.3 34 26 65 6.9 4

47 Priyadharshini 22/f Unmarried 4873 1.3 0.8 0.5 37 55 48 6.8 3.9

48 Chandra 70/f Married 5055 0.6 0.3 0.3 21 26 76 6.7 3.8

49 Parimala 30/f Married 6413 0.8 0.5 0.3 37 48 55 6.6 3.7

50 Murugesan 52/f Married Yes Yes 7209 1.2 0.4 0.8 63 116 149 6.9 3.8

51 Padmavathy 78/f Married 6070 0.7 0.3 0.4 18 24 88 6.8 3.7

52 Fathima 56/f Married 7922 1.1 0.5 0.6 68 37 223 6.8 3.1

53 Krishna 65/m Married Yes 7415 0.9 0.4 0.5 27 42 72 6.3 3.5

54 Mariyammal 62/f Married 6086 0.5 0.2 0.3 69 52 25.9 6.5 3.4

55 Datchayani 30/f Married 7748 0.2 0.1 0.1 29 82 152 7.1 4

56 Shanthi 49/f Married 9999 1.2 0.5 0.7 22 20 101 7.4 4.5

57

58 Malliga 55/f Married 9340 0.3 0.1 0.2 30 60 76 6.8 3.7

59 Renuga 43/f Married 8154 0.3 0.1 0.2 27 21 154 7.5 4.1

60 Kanaga 70/f Married 7594 1.8 0.6 1.2 25 39 107 6.9 3.7

61 Sathish kumar 22/m Unmarried 6600 1.7 0.4 1.3 15 18 72 7.9 4.6

62 Kumar 52/m Married 4997 0.6 0.2 0.4 37 35 37 6.5 4.5

63 Dhatchnamoorthy 70/m Married 5915 0.6 0.3 0.3 30 13 37 6.5 4.4

64 Madhivanan 60/m Married 6253 0.5 0.3 0.2 16 18 67 6.3 4.5

65 Ravikumar 52/m Married 8162 1 0.3 0.7 13 14 113 7.9 3.9

66 Subramani 36/m Married Yes 4435 0.4 0.2 0.2 27 18 117 6.7 4.1

67 Suganthi 28/f Unmarried 4532 0.7 0.4 0.3 22 15 34 6.8 3.4

68 Priya 30/f Married 5676 0.6 0.4 0.2 34 20 56 7.8 3.2

69 Kumar 40/m Married Yes Yes 6787 0.8 0.4 0.4 20 21 67 6.6 3.4

70 Selvam 35/m Married 7654 1.2 0.8 0.4 32 32 89 7.7 3.8

71 Mohan 45/m Married Yes Yes 4532 0.9 0.6 0.3 22 31 77 8 4.2

72 Sudha 50/f Married 5676 0.7 0.4 0.3 24 11 56 6.5 4.4

73 Durai 45/m Married Yes 6766 0.9 0.5 0.4 24 34 111 6.7 4.7

74 Felix 44/m Married Yes 7888 1.2 0.4 0.8 35 23 36 7.6 3.4

75 Jamuna 56/f Married 7656 0.8 0.4 0.4 22 19 56 6.5 4.2

S.NO NAME AGE/SEX MARITAL STATUS SMOKING

DRINKING/ALCOH

OLIC

Viral

markers

Sr.choilnestera

se U/L

Total

bilirubin

mg/dl Direct bilirubin mg/dl

Indirect

bilirubin

mg/dl SGPT IU/L SGOT IU/L ALP IU/L

TOTAL PROTEIN

g/dl

Sr.albumi

n g/dl CTP

CASES(CHRONIC

LIVER DISEASE)

1 Hari 45/m Married No Yes HbSAg + 1501 2.8 1 1.8 23 10 106 5.2 2.6 11(c)

2 Ramesh 36/m Married Yes Yes 3016 23.6 12.6 11 140 37 60 5.6 2.3 11(c)

3 Gajendran 27/m Unmarried No Yes 3261 24.3 15.4 8.9 113 23 79 6 2.3 11(c)

4 Mathivanan 58/m Married No Yes 2342 35.5 19.7 15.8 146 66 106 6.4 2.5 11(c)

5 Kuppan 60/m Married No Yes 2702 8.6 4.5 4.1 45 257 195 5.8 2.7 12(c)

6 Ravi 50/m Married No Yes 3253 2.8 1.5 1.3 37 47 139 7.1 2.9 11(c)

7 Gopu 42/m Married Yes Yes HbSAg + 1412 26.2 14.5 11.7 35 144 60 5.8 1.9 14(c)

8 Suresh kumar 35/m Married Yes Yes 1617 2.3 1.4 0.9 24 79 82 6.6 3 10(c)

9 Nagaraj 33/m Married No Yes 2406 25.8 13.8 12 63 18 151 4 2 12(c)

10 Sasi Kumar 42/m Married No Yes 2373 37 17.9 19.1 194 106 134 4.9 2.1 12(c)

11 Krishnan 70/m Married No Yes 1450 1.6 0.8 0.8 26 15 62 6.3 2.8 12(c)

12 Manikandan 33/m Married Yes Yes 1997 11.5 10.5 1 59 221 90 5.6 1.7 12(c)

13 Kuppan 40/m Married Yes Yes 2849 5.5 4.9 0.6 38 211 182 5.7 2.6 10(c)

14 Narayanan 36/m Married No Yes 1993 25.5 20.8 4.7 54 145 127 6.2 2.6 12(c)

15 Ramalingam 51/m Married No Yes HbSAg + 1998 5.3 2.2 3.1 25 76 73 7.1 2.4 10(c)

16 Vinothraja 34/m Married No Yes 2874 2.5 1 1.5 28 61 198 6.9 2.5 10(c)

17 Manivannan 54/m Married No Yes 3394 11.9 9.3 2.6 22 32 309 5.5 2.5 11(c)

18 Gunasundari 56/f Married No No 1841 2.3 1 1.3 21 54 151 6.3 2.7 11(c)

19 Rajendran 56/m Married No Yes 1672 13.1 8.7 4.4 52 123 38 5.7 2.8 11(c)

20 Nagammal 40/f Married No No 1342 38.8 23.7 15.1 250 170 160 5.2 2.4 10(c)

21 Anil 31/m Unmarried No Yes 2372 34.4 15 19.4 22 44 100 6 3 11(c)

22 Thirunavukarasu 42/m Married Yes Yes 2699 26.7 11.7 15 100 301 36 6.7 2.4 10(C)

23 Pushparaj 38/m Married Yes Yes HbSAg + 1377 1.2 0.5 0.7 20 52 91 4.8 1.8 10(C)

24 Chinnathambi 70/m Married No Yes 2200 5.6 3 2.6 198 496 149 6 2.6 11(C)

25 Arokiya 34/m Married Yes Yes 4269 12 0.6 6 28 124 141 7.3 3.3 9(B)

26 Arumugam 70/m Married No Yes 3687 0.6 0.1 0.5 14 98 98 6 3.2 8(B)

27 Murugan 43/m Married Yes Yes 4199 5.9 4.6 1.3 32 56 115 6.4 3.1 9(B)

28 Vasugi 37/m Married No No HbSAg + 3923 1.9 1 0.9 25 84 111 6.4 3.4 8(B)

29 Selvam 38/m Married No Yes 3367 1.4 0.8 0.6 185 189 134 6.3 3.4 7(B)

30 Subramaniam 70/m Married Yes Yes 4524 0.7 0.2 0.5 13 34 102 5.8 2.2 8(B)

31 Murugan 43/m Married No Yes 5797 11.9 4.6 7.3 48 168 134 7.3 3.3 8(B)

32 Muralidhar 30/m Married Yes Yes 4199 2.5 2 0.5 102 176 142 5.8 3 9(B)

33 Kannan 48/m Married Yes Yes HbSAg + 4588 1.9 1.2 0.7 146 187 172 5.6 2.8 8(B)

34 Balaji 47/m Married Yes Yes 4329 1.7 0.9 0.8 86 74 256 5.9 3 9(B)

35 Martin 50/m Married Yes Yes 3717 1.7 1.2 0.5 250 261 186 5.7 3.1 9(B)

36 Selvi 45/f Married No No Anti-HCV+ 4123 1.2 1 0.2 35 121 120 5.1 2.2 9(B)

37 Ramamoorthy 42/m Married No Yes 3510 3.1 0.9 2.2 27 32 79 6.4 3.7 8(B)

38 Shanmugam 40/m Married No Yes 4344 11.5 7 4.5 32 134 140 6.4 3.3 8(B)

39 Gangadaran 62/m Married No Yes 3576 1.6 0.7 0.9 24 84 108 6.2 3.2 8(B)

40 Gunasekaran 38/m Married No Yes 3633 3 1.6 1.4 28 35 82 6.8 3.2 9(B)

41 Selvam 42/m Married No Yes 4916 1.9 1.3 0.6 146 172 164 6.6 4.3 6(A)

42 Lalitha 62/f Married No Yes 5387 0.9 0.4 0.5 22 27 62 5.5 3.3 6(A)

43 Rajendraprasad 56/m Married No No HbSAg + 5170 2.2 1.4 0.8 17 44 96 7 3.9 6(A)

44 Meganathan 42/m Married No Yes 6780 1.1 0.6 0.5 35 60 79 6.8 3.9 6(A)

45 Mani 45/m Married No Yes 5473 0.9 0.5 0.4 25 63 82 6.2 3.3 6(A)

46 Rajeevam 50/m Married No Yes 4998 2 1.4 0.6 18 45 86 6.6 3.5 5(A)

47 Selvaraj 30/m Unmarried No Yes 4823 1.7 1.4 0.3 130 126 163 6.3 3.5 5(A)

48 Muniraj 41/m Married Yes Yes 5212 2.3 1.6 0.7 45 98 96 6.4 3.5 6(A)

49 Jayabal 43/m Married No Yes 6023 2.3 1.5 0.8 24 65 90 6.6 3.6 5(A)

50 Ranganathan 60/m Married No Yes HbSAg + 6124 2.1 1.4 0.7 26 70 92 6.9 3.4 5(A)

S.no NAME AGE/SEX MARITAL STATUS SMOKING

DRINKING/ALCOH

OLIC

TOTAL

BILIRUBIN

mg/dl

DIRECT

BILIRUBIN

mg/dl INDIRECT BILIRUBIN mg/dl SGPT IU/L SGOT IU/L ACP IU/L

TOTAL

PROTEIN g/dl Sr.albumin g/dl

1 Prashanth 40/m Married Yes 4.6 3.4 1.2 785 545 320 6.5 3.3

2 Ramasamy 35/m Married 1.4 0.5 0.9 795 745 324 7.1 3.6

3 Marimuthu 30/m Married Yes 5.6 3.3 2.3 461 398 165 5.5 3

4 Munusamy 65/m Married 3 1.6 1.4 1974 1497 142 6.4 3.4

5 Ramasamy 60/m Married Yes 3.3 2.6 0.7 1934 1541 169 6.4 3.5

6 Roja 50/f Married 1.4 0.5 0.9 1122 1044 320 6.1 3.3

7 Rasathi 45/f Married 8.1 5.8 2.3 461 398 195 5.9 3

8 Thamarai 34/f Married 7.5 4.2 2.7 488 395 184 6 3.1

9 Kanimozhi 43/f Married 7.4 4.3 3.1 454 382 182 6.1 3.2

10 Selvi 28/f Unmarried 7.2 4.4 2.8 432 351 175 6.2 3.3


DRINKING

ALCOHOL

Total bilirubin

mg/dl

Direct

bilirubin

mg/dl Indirect bilirubin mg/dl SGPT IU/L SGOT IU/L ALP IU/L

Total protein

g/dl Sr.albumin g/dl

1 Ravi 34/m Married Yes Yes 13.2 10.2 3 61 145 552 5.2 2.9

2 Sathish 39/m Married Yes 5.3 3.1 2.2 103 128 423 6.1 3.4

3 Durai 40/m Married 4.5 3.2 1.3 123 87 398 6.3 3.5

4 Dinesh 45/m Married Yes 3.2 2.1 1.1 97 118 353 6.4 3.3

5 Joesph 27/m Unmarried Yes 5.2 2.9 2.3 113 89 453 5.9 3.1

6 Divya 38/f Married 10.7 8.7 2 130 138 523 6.2 2.9

7 Rajathi 45/f Married 5.9 3.4 2.5 85 142 318 6 3.4

8 Elavarasi 50/f Married 8.5 4.9 3.6 95 102 232 7.4 3.1

9 Sumaiya 32/f Married 7.2 5.3 1.9 73 95 419 6.3 3.2

10 Sruthi 23/f Unmarried 8.5 6.2 2.3 62 98 384 6.3 3


DRINKING/ALCHO

LIC

Total bilirubin

mg/dl

Direct

bilirubin

mg/dl Indirect bilirubin mg/dl SGPT IU/L SGOT IU/L ALP IU/L

Total protein

g/dl Sr.albumin g/dl

1 Raja 69/m Married 1.6 1.1 0.5 116 51 99 5.8 2.9

2 Manjula 52/f Married 0.6 0.4 0.2 107 46 120 6.5 3.4

3 Murugan 59/m Married Yes 5.4 3.1 2.3 120 137 111 6.2 2.3

4 Selvi 63/f Married 2 1.5 0.5 40 52 88 6.3 3.5

5 Uma Maheswaran 40/m Married Yes Yes 1.9 1.3 0.7 48 65 107 6.4 3.3

Cases ( Infective hepatitis)

Cases( obstructive

Cases(Liver metastasis)

“a comparative study of serum cholinesterase and...

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