A Dissertation on

A study to compare the efficacy of non-invasive predictors of esophageal

varices in patients with portal hypertension

Dissertation Submitted to

THE TAMILNADU Dr.M.G.R. MEDICAL UNIVERSITY

CHENNAI - 600 032

With partial fulfillment of the regulations

for the award of the degree of

M.D. GENERAL MEDICINE

BRANCH-I

COIMBATORE MEDICAL COLLEGE,

COIMBATORE

MAY 2018

CERTIFICATE

Certified that this is the bonafide dissertation done by Dr. SRINIVASAN

KARTHIKEYAN and submitted in partial fulfillment of the requirements for

the Degree of M.D., General Medicine, Branch I of The Tamilnadu

Dr. M.G.R. Medical University, Chennai.

Date: Guide , Professor & Head

Department of Medicine

Date: Dean

Coimbatore Medical College

Coimbatore

DECLARATION

I solemnly declare that the dissertation titled “A study to compare the efficacy

of non-invasive predictors of esophageal varices in patients with portal

hypertension” was done by me from JULY 2016 to JUNE 2017 under the

guidance and supervision of Professor Dr. KUMAR NATARAJAN. M.D.,

This dissertation is submitted to The Tamilnadu Dr.M.G.R. Medical

University towards the partial fulfilment of the requirement for the award of

MD Degree in General Medicine (Branch I).

Place: Coimbatore Dr. SRINIVASAN KARTHIKEYAN

Date:

ACKNOWLEDGEMENT

I wish to express my sincere thanks to our respected former dean Dr. A.Edwin

Joe M.D., B.L. and also the present Dean Dr. B. ASHOKAN M.S.,Mch for

having allowed me to conduct this study in our hospital.

I express my heartfelt thanks and deep gratitude to the Head of the Department

of Medicine Prof. Dr.KUMAR NATARAJAN, M.D. for his generous help

and guidance in the course of the study.

I sincerely thank all professors and Asst. Professors- Dr.P.VISHNURAM

M.D., DR. N. KARUPPUSAMY M.D., Dr.A.AKILA, M.D, for their

guidance and kind help.

My sincere thanks to Dr.S.RAJA M.D, D.M, DR.V.ARULSELVAN

M.D,D.M, Assistant Professors, Department of Medical Gastroentrology and

for their help.

My sincere thanks to all my friends and post-graduate colleagues for their whole

hearted support and companionship during my studies.

I thank all my PATIENTS, who formed the backbone of this study without

whom this study would not have been possible.

Lastly, I am ever grateful to the ALMIGHTY GOD for always showering His

blessings on me and my family

DATE: Dr. SRINIVASAN KARTHIKEYAN

CERTIFICATE – II

This is to certify that this dissertation work titled A study to compare the

efficacy of non-invasive predictors of esophageal varices in patients with

portal hypertension of the candidate DR.SRINIVASAN KARTHIKEYAN

with registration Number 201511315 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 result shows 1% (One percentage)

percentage of plagiarism in the dissertation.

Guide & Supervisor sign with Seal.

LIST OF ABBREVIATIONS USED

CLD - CHRONIC LIVER DISEASE

CTP - CHILD – TURCOTTE PHUGH’S SCORE

EBL - ENDOSCOPIC VARICEAL BAND LIGATION

EST - ENDOSCOPIC SCLEROTHERAPY

EUS - ENDOSCOPIC ULTRASOUND

EV - OESOPHAGEAL VARICES

GIT - GASTROINTESTINAL TRACT

GV - GASTRIC VARICES

HVPG - HEPATIC VENOUS PRESSURE GRADIENT

HBV - HEPATITIS B VIRUS

HCV - HEPATITIS C VIRUS

LES - LOWER OESOPHAGEAL SPHINCTER

LS - LIVER STIFFNESS

LSM - LIVER STIFFNESS MEASUREMENT

MELD - MODEL FOR END STAGE LIVER DISEASE

PHT - PORTAL HYPERTENSION

PHTG/PHG - PORTAL HYPETENSIVE GASTROPATHY

PP - PORTAL PRESSURE

PV - PORTAL VEIN

PVS - PORTAL VENOUS SYSTEM

TIPS - TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT

CONTENTS

S/No Title Page No

1 INTRODUCTION 1

2 AIM OF STUDY 3

3 REVIEW OF LITERATURE 4

4 MATERIALS AND METHODS 56

5 RESULTS 60

6 DISCUSSION 84

7 SUMMARY 89

8 CONCLUSION 90

9 BIBLIOGRAPHY

10 ANNEXURES

A1 – PROFORMA

A2 – MASTER CHART

A3 – CONSENT FORM

LIST OF TABLES

S/No TABLE PAGE NO

1 HPVG AND CLINICAL PRESENTATION 9

2 AFFERENTS AND EFFERENTS OF

COLLATERALS 13

3 WESTABY CLASSIFICATION OF EV 19

4 CALE’S CLASSIFICATION OF EV 20

5 SARIN’S CLASSIFICATIO OF GV 21

6 MATHUR’S CLASSIFICATION OF GV 22

7 FEATURES IN DOPPLER FOR PHT 33

8 CHILD – TURCOTTE PHUGH’S SCORE 40

9 AGE DISTRIBUTION 60

10 SEX DISTRIBUTION 61

11 ALCOHOL INTAKE 62

12 CRYPTOGENIC CAUSES 63

13 HBV INFECTION 63

14 HCV INFECTION 64

15 COMPELETE BLOOD COUNT 65

16 PLATELET COUNT 65

17 LIVER FUNCTION TESTS 66

18 RENAL FUNCTION TESTS 67

19 SERUM ELECTROLYTES 67

20 SPLEEN DIAMETER 67

21 PLATELET COUNT / SPLEEN DIAMETER

RATIO 68

22 RIGHT LOBE DIAMETER 69

23 SERUM PROTEINS 70

24 RIGHT LOBE DIAMETER / ALBUMIN RATIO 70

25 CTP SCORE COMPARED WITH VARICES

GRADING 71

26 VARICES GRADING OF STUDY GROUP 72

27 COMPARING VARICES GRADING WITH

FIBROSCAN 73

28 COMPARING CTP SCORE GRADING WITH

FIBROSCAN 74

29 COMPARING VARICES GRADING WITH

RIGHT LOBE DIAMETER / ALBUMIN RATIO 75

30 COMPARING CTP SCORE GRADING WITH

RIGHT LOBE DIAMETER/ ALBUMIN RATIO 76

31

COMPARING VARICES GRADING WITH

PLATELET COUNT/SPLEEN DIAMETER

RATIO

77

32

COMPARING CTP SCORE GRADING WITH

PLATELET COUNT/ SPLEEN DIAMETER

RATIO

78

33 COMPARING VARICES GRADING WITH

RIGHT LOBE DIAMETER 79

34 COMPARING CTP SCORE GRADING WITH

RIGHT LOBE DIAMETER 80

35 COMPARING VARICES GRADING WITH

PLATELET COUNT 81

36 COMPARING CTP SCORE GRADING WITH

PLATELET COUNT 82

LIST OF GRAPHS

S/No DIAGRAMS PAGE NO

1 AGE DISTRIBUTION 60

2 SEX DISTRIBUTION 61

3 ALCOHOL INTAKE 62

4 CRYPTOGENIC CAUSES 63

5 HBV INFECTION 64

6 HCV INFECTION 64

7 PLATELET COUNT 66

8 SPLEEN DIAMETER 68

9 PLATELET COUNT / SPLEEN DIAMETER

RATIO 69

10 RIGHT LOBE DIAMETER 70

11 SERUM PROTEINS 71

12 RIGHT LOBE DIAMETER / ALBUMIN RATIO 72

13 CTP SCORE COMPARED WITH VARICES

GRADING 73

14 COMPARING VARICES GRADING WITH

FIBROSCAN 74

15 COMPARING CTP SCORE GRADING WITH

FIBROSCAN 75

16 COMPARING VARICES GRADING WITH

RIGHT LOBE DIAMETER / ALBUMIN RATIO 76

17 COMPARING CTP SCORE GRADING WITH

RIGHT LOBE DIAMETER/ ALBUMIN RATIO 77

18

COMPARING VARICES GRADING WITH

PLATELET COUNT/SPLEEN DIAMETER

RATIO

78

19

COMPARING CTP SCORE GRADING WITH

PLATELET COUNT/ SPLEEN DIAMETER

RATIO

79

20 COMPARING VARICES GRADING WITH

RIGHT LOBE DIAMETER 80

21 COMPARING CTP SCORE GRADING WITH

RIGHT LOBE DIAMETER 81

22 COMPARING VARICES GRADING WITH

PLATELET COUNT 82

23 COMPARING CTP SCORE GRADING WITH

PLATELET COUNT 83

LIST OF FIGURES

S/No DIAGRAMS PAGE NO

1 PORTAL VEIN FORMATION 5

2 COLLATERAL VEINS 12

3 ESOPHAGEAL VENOUS DRAINAGE

SYSTEM 15

4 CECT OF DILATED LEFT GASTRIC

VARICES 18

5 CAUSES OF PHT 23

6 LAPLACE’S LAW 26

7 ESOPHAGEAL VARICES 29

8 GASTRIC VARICES 30

9 GASTRIC ANTRAL VASCULAR ECTASIA 30

10 COLLATERALS IN EUS 32

11 PERFORATING VEINS IN EUS 32

12 MECHANISM OF TRANSIENT

ELASTOGRAPHY 35

13 LSM RANGE AND SEVERITY OF

FIBROSIS 37

14 CECT OF EV 38

15 SCLEROTHERAPY 50

16 BAND LIGATION 52

17 TIPS 54

1

INTRODUCTION

Oesophageal varices (EV) have been the troublesome

complications of PHT. The common and frequent cause of morbidity &

mortality is EV bleeding which is seen in around 25-40% of the patients.

EV can be confirmed by endoscopy.

In order to reduce the burden of endoscopy, as the prevalence of

EV bleeding has increased, studies have been done frequently to identify

modalities to identify or predict EV noninvasively.

Studies have evaluated the parameters of PHT as predictors of the

presence of EV either directly or indirectly. They are splenomegaly,

Thrombocytopenia and a poor Child phugh’s score.

In patients with CLD the presence of thrombocytopenia may be

due to several other factors like the reduced life time of platelets, low

thrombopoietin release or can also be due the myelotoxic effects of either

alcohol or the hepatitis viruses. However the splenomegaly in cirrhotic

patients is mainly due to PHT. Likewise studies have demonstrated the

platelet count/spleen diameter ratio as a parameter predicting EV by

linking thrombocytopenia to the size of spleen and Right lobe diameter /

albumin ratio has also been used in the studies to predict EV.

2

The recent noninvasive technique that has been used is transient

elastography or Fibroscan that measures the liver stiffness or hepatic

parenchymal elasticity using ultrasound elastic waves. Many studies have

proved that Fibroscan is a useful and reliable method to the assess fibrosis

of the liver parenchyma. Moreover PHT is due to liver fibrosis as proved

in many studies of the cases with fibrosis. Thus it can also be used a

method to assess PHT and can also be used to predict the EV.

EV, most of the time is asymptomatic and this can be diagnosed

easily with many noninvasive parameters .In country where there is

increased case load & higher financial constraint, there is a need for a

reliable and reproducible non-invasive predictor which can be used.

3

AIMS

To study clinical and investigative profile of patients with PHT.

To study the predictive power and compare the noninvasive investigative

parameters for detection of esophageal varices in patients with PHT as

compared to invasive parameter

4

REVIEW OF LITERATURE

HISTORY OF THE PORTAL SYSTEM

384-322 BC - Aristoteles was the first person who described about

PV(PV).

300-250 BC - Herophilos recognized the importance of PVS in acting as

the zone of discharge for all the resorbent veins from the intestine

129-199AD - Galenus described the PVS along with the intrahepatic

branches

1597-1677 - Glisson demonstrated the independent nature of portal

venous circulation from rest of the blood circulation

ANATOMY OF THE PORTAL VENOUS SYSTEM

The system of veins that transport blood from of the spleen, alimentary

tract, pancreas along with the gallbladder constitute the PVS. It is a valve-

less system that enters the liver via the porta hepatis. The formation of PV

is by the union of the superior mesenteric vein and the splenic vein

behind the pancreatic head at the L2 level.

The superior mesenteric drains the small intestine, pancreatic head and

the colon.

5

The splenic veins consists of around five to fifteen channels that begins at

the hilum of spleen and later join the pancreatic tail with short gastric to

form the main “splenic vein”. Vein later travels in a transverse direction

along the body and head of the pancreas, just below and in the front of

artery. It receives tributaries from pancreatic head and left gastro-epiploic

vein that enters near spleen. The inferior mesenteric vein brings the blood

from left part of colon and the rectum and it usually enters in the medial

third. Rarely, it enters at the junction of superior mesenteric vein and the

splenic vein3.

Fig.1- Portal vein formation

6

PORTAL BLOOD FLOW AND PRESSURE

The PV measures around 5 to 8 cm long and with a diameter of

around 1.2 cm. The portal venous pressure is around 3-7 mmHg which is

dependent on various criteria like “posture, increased intra-abdominal

pressure like in coughing, compression , respiration, Valsalva’s

manoeuvre and a number of biochemical mediators”1. Whereas the blood

flow in the portal system is around 1000–1200ml/min and it contributes

to around 72% of total supply of oxygen to the liver. The content of

oxygen in the PVS is lower than the arterial blood, but it is at the same

time significantly higher compared to that of the rest of venous system.

There is never a consistent pattern of the hepatic distribution of portal

blood.

PORTAL HYPERTENSION - DEFINITION

An elevated pressure of more than 12 mmHg in the portal venous

circulation with the PV diameter of more than 13 mm or an increased

gradient of more than 7mmHg in the portal system (difference between

pressure in the PV and to that of the pressure in the inferior vena cava) is

termed as PHT(PHT).

According to hemodynamic application based on the Ohm's Law ,

“ Portal pressure gradient (ΔP) is actually directly proportional to amount

of blood flowing in the PV (Q) and the resistance opposing this flow (R)

7

(ΔP = Q × R)”2. Thus the elevated PP will be considered secondary to the

increase in resistance to flow or due to the increase in blood flow, or due

to both factors.

The PHT may be

• Pre-Hepatic

• Intrahepatic

• Post-Hepatic

There are the two different modalities of PHT –

1. The congestive hypothesis has led to introduction and usage of the

surgical procedures like the “ porta-caval shunting and other operations

like the meso-caval and the spleno-renal shunts”4

2. The increased flow of blood plays the critical role for recent advanced

modern medical therapies like the usage of the splanchnic

vasoconstrictors “ eg -terlipressin, somatostatin and its derivatives”5 and

the non-selective beta-blockers for decreasing the blood flow in the portal

collaterals and thereby reducing the PP 6

In cirrhosis, the PHT occurs due to the fibrotic disruption of liver

sinusoidal architecture along with the dynamic changes of hepatic stellate

cells contractility8.

8

Bathal along with Grossmann had demonstrated the pathology of

PHT is due to a marked increase of hepatic resistance to the blood

flowing in PVS through cirrhotic liver was not always due to a

mechanical effect due to the architectural distortion of vascular anatomy

by fibrosis along with nodule formation, also along with the structural

distortion there has been a dynamic component demonstrated by the

increased “hepatic vascular tone”7.

They also found that this component of elevated resistance can also

be due to the deficit of vasodilatory substances or due to the excessive

vasoconstriction production or due to impaired “peroxisome proliferator-

activated receptors”9 . This may account for the one third of increased

resistance in cirrhotic that could be resulting in PHT.

MEASUREMENT OF THE PORTAL PRESSURE (PP)

“Hepatic venous pressure gradient (HVPG) is being used indirectly to

measure PP and also monitor PHT. HVPG is defined as the difference of

the wedged hepatic venous pressure (WHVP) and free hepatic venous

pressure (FHVP) .An HVPG value of greater than 5 mmHg is indicative

of PHT3,10,11.

9

Tab.1- HVPG and Clinical features

DEVELOPMENT OF COLLATERALS

The obstruction of PV circulation leads to the development of the

collaterals which carry blood to the systemic veins. The appearance of

collateral is also considered the most sensitive and very specific

sonographic evidence in the diagnosis of PHT. The formation of

collaterals is due to the “reopening of the collapsed embryonic vessels or

flow reversal in existing adult veins”12.

Classification of varices –

1. Oesophago-gastric varices

2. Ectopic varices-

10

“Ectopic varices actually varices those occur anywhere in

gastrointestinal system except those in the esophago-gastric region. They

are found in the duodenum predominantly, followed by sites inn small

intestine like the jejunum and ileum, large intestine along with rectum,

gallbladder, omentum, bile duct, diaphragm, uterus or vagina, and the

urinary bladder”13.

Appearance order of the varices –

The complex bowel vascular structure has

Intraepithelial channels

Superficial venous plexus

Deep submucosal veins

Adventitial veins.

The perforating veins aid in connecting those adventitial and the

deep submucosal veins.

The transmitted backpressure through tributaries of PV causes

engorgement of collaterals along the gut wall in the “para-

esophageal/para-gastric/ para-rectal/para-choledochal region”14,15,16.

Later veins in visceral wall surface dilate. Perforating veins

transmit backpressure to gut wall that leads to formation of the varices in

the submucosal region or sub-epithelial region.

11

The sub-mucous veins become the region where there is blood

logging occurs, which leads to formation of varicosities on esophagus

outer surface16.

In cases of EV the deep intrinsic venous system which is dilated

often displace all the superficial veins and later take up the sub-epithelial

position, so that they can be easily noticed on endoscopy.

They can be noted as a “red color sign on varices i.e.

telangiectasiae, cherry red spots, hemocystic spots and red wale markings

or as varices”17.

Veins on mucosal surface can lead onto gastrointestinal bleeding

and veins outside of the wall will cause extra-luminal bleeding like

pleural and peritoneal bleeding.

12

Fig.2 – Collateral veins

13

Tab.2 – Afferent & efferent of collateral veins

14

The Esophageal Venous Drainage system-

The thoracic esophagus drains into the systemic circulation via “the

azygos (AV) and the hemiazygos veins”18. Around eight or ten veins

drain into the AV caudally to the arch from right border of esophagus.

The left side of the oesophagus drains into the hemiazygos veins.

Some amount blood from the esophagus can also drain into the bronchial

or pulmonary veins.

The abdominal esophagus drains mainly into LGV- left gastric

vein, which is actually a PVS tributary and also drains partially to the

Inferior Vena Cava through both the superior and the inferior phrenic

veins.

The majority of esophageal–cardiac region and a small part of the

fundus region are drained by the LGV19. LGV has around two branches.

The cardiac area is drained by anterior branch whereas posterior branch

ends mainly in the Azygos. The paraesophageal venous system which are

present along the esophagus are connected to posterior branch.

15

Fig.3 – Esophageal venous drainage

Afferent - Left Gastric Vein.

Efferent -

1. In around 78% LGV drains into AV & SVC through the

esophageal and the para-EV.

16

2. In the rest, it drains to IVC. Rarely might anastomose with IVC

directly

3. LGV equally drains to AV and the left brachiocephalic.

4. Sometimes direct connections exist between the LGV and AV

leading to the collaterals in the para-Esophageal region without

forming the EV

EV classified into three different types:

1) Uphill

2) Downhill

3) Idiopathic

Uphill / Type I varices- The increased PP can lead to the upward through

the dilated collaterals to SVC.

Downhill Type II varices - These varices are not due to PHT, but caused

by a superior vena cava (SVC) pressure elevation leading to the downhill

cranio-caudal blood flow. Whenever obstruction of SVC or Azygous

Vein (AV) occurs, blood flows directly from head & neck region through

“inferior thyroid vein or mediastinal collateral veins to oesophageal

veins”20,21 and through “gastric veins into the PV”20,21. The causes may be

goiter in 45-60% of cases or mediastinal fibrosis or lymph nodes in 25-

35% of cases.

17

In Type IIa there is the patency of azygous vein with varices in upper

third oesophagus. The most common cause is retrosternal goiter. In Type

IIb there is azygous vein obstruction where all the blood should be

redirected to IVC. Commonly downhill EV found in upper 1/3 of

esophagus, however they also found elsewhere in any part of esophagus

according the severity and duration of the underlying condition.

They offer differential for EV. Bleeding from downhill EV is often rare

as

1. Small blood volume and lower pressure found in the SVC

2. No coagulation abnormalities

3. Mechanical tension in upper 1/3 is significantly lower.

However downhill EV have to be considered in differential pathogenic

and also the prognostic viewpoints.

18

Fig.4. – CECT of dilated Left Gastric Vein and Para-oesophageal

collaterals

Idiopathic varices have been found where there is neither SVC

obstruction nor PHT. These varices are secondary to the congenital

weakness of venous system in the esophagus.

Brick & Palmer were the first to classify EV as22,23 -

Intrahepatic & Extrahepatic causes of PHT

PHT without cause delineated clinically or anatomically

Due to SVC obstruction

Primary varices in upper region of oesophagus

Idiopathic varices.

19

They also graded EV using rigid oesophagoscopy with diameter as23

1. mild (<3 mm )

2. moderate (3–6 mm)

3. severe (>6 mm)

Tab.3- Westaby classification of EV

20

Tab.4 – Cales’s Classification of EV

GASTRIC VARICES

Stadelmann in the year 1913 first postulated the gastric varices formation

with PHT24. In liver cirrhosis 80% of the patients have portal

hypertensive- gastropathy25. Active acute bleeding in PHT gastropathy is

a “very rare event and the total incidence has been around less than 3% in

about three years”26.

21

Tab.5 – Sarin’s classification for GV

Tab.6. Mathur’s Classification of GV

22

LOCALIZATION AND VARIOUS FORMS

OF PHT

PHT is divided into

A. Pre-hepatic

B. Intra-hepatic

C. Post-hepatic

The intrahepatic can be further classified as

Presinusoidal

Sinusoidal

Post-sinusoidal.

23

CAUSES OF PORTAL HT

Fig.5

CLINICAL FEATURES OF EV

EV is found in around 40% cirrhosis patients and in around 60% of

persons with both cirrhosis and also ascites. “New varices develop in

cirrhotic patients in a rate of 5% per year”27. Small varices progress to

very large varices “at the rate of 10% -15% every year and it is directly

proportional to the degree of liver dysfunction”27.

24

Moreover in patients with alcoholic liver disease there is

improvement of liver function in those patients who strictly abstain and

this can also lead on to the disappearance of EV.

Around 25% of the patients who are recently diagnosed, will be

presenting with episodes of upper gastro-intestinal bleeding in two years

after the diagnosis.

Always clinically the best predictor variceal bleeding is the

variceal size. The average risk in varices with <5 mm diameter is about

7% in two years while the estimated risk is around 30% in two years , in

the patients with varices of >5 mm in diameter. Another important

predictor is HVPG as there is no risk of bleeding it is below 12 mmHg

but HVPG has not been routinely used in the clinical practice for

assessing the bleeding risk in EV. In around 90% of patients bleeding risk

can be reduced if treated early and in around 50 % of the patients the

variceal bleeding stops instantly as hypovolemia results in splanchnic

vasoconstriction thereby reducing the PP.

Active bleeding at the time of endoscopy, a very low hematocrit

value, an elevated aminotransferase levels, infections, HVPG of > 20

mm Hg and also the PV thrombosis have been associated as causes of

failure in controlling bleeding within five days. One third of the patients

who have stopped bleeding within six weeks have another episode of

bleeding. 40 % of the re-bleeding occurs within the next five days.

25

Re-bleeding predictors are

Emergency endoscopy

Gastric varices,

Hypoalbuminemia

Renal insufficiency,

HVPG >20 mm Hg.

“The death due to acute variceal bleed has been estimated to be

around 5% - 8% at first week and around 20% at sixth week”27.The

highest death risk is seen in early re-bleeders, in those whose MELD

score is more than 8, and those who has who had more than 4 units of

blood cell transfusion and also those who had renal insufficiency.

Alcohol use, high serum bilirubin, Albumin globulin reversal and hepatic

encephalopathy are associated with increased mortality rate.

Historically the principle mechanism of bleeding from the varices

was thought as a consequence of the erosion of variceal wall due to

gastroesophageal reflux and also assisted due to the trauma of swallowing

a very solid food particle. Obviously the above mentioned hypothesis had

to be abandoned as it had no supportive evidence from physiological

studies and pathological evidence from dead patients.

Later on an “explosion” theory was proposed as the varices had to

bleed due thin wall rupture that was caused as consequence of tension

on the vessel wall which was way beyond the permissible elastic limit. In

26

this circumstance the Laplace's law was used and the wall tension (Wt) of

varices was defined by the equation:

According to the equation, “Pv determines intra-variceal pressure as a

consequence of PP, Po is defined as the pressure which exists in

oesophageal lumen. r is radius of varix whereas t is the thickness of

variceal wall”28,29. Therefore whenever the variceal wall tension increases

“there is an increased PP subsequently the effect was multiplied by the

increased variceal size and also decreased variceal wall thickness”28,29.

Fig.6. Laplace’s Law

In this view, risk factors and prognostic indicators for the varices can

be identified as follows :

High PP

Child-Pugh C

Greater variceal diameter

Decreased variceal wall thickness

27

Moreover, the luminal pressure in the oesophagus is actually lower

than the intra-abdominal pressure which is during inspiration and along

without the support of external tissue of EV have greater risk of bleeding

compared to other collaterals in the body.

When the score is high the risk of bleeding as increases substantially

28

PORTAL HYPERTENSIVE VASCULOPATHY

The Portal hypertensive vasculopathy is noticed as erosions in the

endoscopic examination 30,31. These erosions are proportional to the

degree and severity of PHT. Occult bleeding in cirrhotics is due to such

intestinal erosions and which is identified in faeces.

Hyperaemic mucosa in PHG is mainly “due to the dilation of the

vessels and submucosal arteriovenous shunt formations”2. Mosaic-like

pattern is noted. Red marks -lesions pose a greater risk and bleed often.

Such changes are usually noted on the fundus.

WORKUP FOR PHT

DETECTION OF THE VARICES

UPPER GASTROINTESTINAL ENDOSCOPY-

The commonly used method to detect varices is upper

gastrointestinal endoscopy. All cirrhotic patients should undergo

screening for EV by endoscopy. In those who have normal endoscopy

initially during screening should undergo repeated endoscopy in the next

2 - 3 years and when small varices have been noted during the screening

endoscopy, it should be repeated in the next 1 - 2 years32.

The predictors of bleeding according to the endoscopy findings are

the EV sizes and also the identification of all the red wale signs like

“longitudinal dilated venules on the surface of varices”7. Grading of EV

is based on various criteria and it is always subjective.

29

Varices are noticed anywhere in the esophagus, but lower third is the

most common site and it is the site large varices are noted. The size of the

EV is estimated while withdrawing the endoscope from the lumen. Air is

aspirated from the stomach but in the esophageal lumen air is entirely

inflated.

“As a point of reference, any varix larger in diameter than an open

pinch biopsy forceps is likely to be greater than 5 mm in diameter”27.

Fig.7 - ESOPHAGEAL VARICES

30

Fig 8.-GASTRIC VARICES

Fig.9 - GASTRIC ANTRAL VASCULAR ECTASIA

31

ENDOSCOPIC ULTRASONOGRAPHY

Endoscopic ultrasonography ( EUS ) also known as the

endosonography. EUS can be either a miniaturized ultrasonography or a

Doppler enabled endoscope. EUS reveals the EV cross-section along with

the collateral veins that are found surrounding the esophagus. Perforating

veins that connect EV with collateral veins can also be used to assess and

predict the early recurrence and bleeding of EV36,37.

Higher resolution of EV can be facilitated using the miniaturized

endo-luminal high-frequency probe which can be introduced through the

biopsy channel38.

Collateral veins are either39

Peri-esophageal

Para-esophageal

Larger the collateral veins larger is “the risk of variceal bleeding

and recurrence” 40,41,42. EUS helps to visualize LGV whose diameter is

directly proportional to the variceal size and also the azygos vein which is

enlarged during PHT43.Perforating veins can be assessed only using EUS.

High risk of bleeding in EV is associated with higher number and greater

size of the perforating veins44.

32

Fig .10 -COLLATERAL VEIN IN EUS

Fig .11- PERFORATING VEIN IN EUS

33

NON-INVASIVE METHODS FOR IDENTIFYING VARICES

A. RADIOLOGICAL

DOPPLER ULTRASONOGRAPHY

Doppler ultrasonography of abdominal vessels has been used to assess

PHT. PHT features on ultrasonography are34

Tab.7- Features in Doppler

Ultrasound examination can also be used to detect PV thrombosis either

by non-visualization of the vein or by cavernous transformation

indicative of an extensive collateral network. Doppler ultrasonography

has been useful clinically for initial assessment of PHT.

34

TRANSIENT ELASTOGRAPHY

Transient elastography (TE) or FibroScan is the new noninvasive

technique to rapidly diagnosis and quantify the liver fibrosis. Initially it

was used to detect solid malignancies located in the soft tissues like

breast and prostate45. TE gives a reproducible measurement of liver

stiffness ( LS ) which can be an alternative for liver biopsy46. In

cirrhotics, the LS varies between 12.5 to 75.5 kPa.

Shear (secondary or S-) waves are slow waves that usually follow

the primary wave of compression. These are elastic waves that transverse

the body compared to the surface waves. Moreover these shear waves

travel transversely in contrast to the longitudinal sound waves.

Thus the affected tissue and waves are perpendicular to each other

and the shear waves propagate slowly & attenuated by the liver

parenchyma. The above mentioned effect thus based upon the elasticity

of the underlying tissue wherein the shear wave velocity is inversely

proportional compared to elasticity of the tissue.

35

Fig.12- Mechanism of TE

Measurements should be performed with patients lying on supine

posture and they should be asked to elevate their right hand with crossing

of legs. After application of gel, the probe has to be kept perpendicular to

surface of skin between the ninth to eleventh intercostal space along on

mid-axillary line adjacent to right lobe of the liver.

The TE device has a small ultra-sonographic display to identify

underlying tissue which can be identified using the probe on either A- or

M-modes. This can help because the S waves are usually affected by

medium density changes like that of vascular structures (liquid medium).

After appropriate posture the low frequency S wave can induced on skin

surface using the small piston kept on the probe. Shear wave physical

36

characteristics like “the velocity or the intensity attenuation are processed

and displayed on the screen as the liver stiffness measurement (LSM) and

controlled attenuation parameter (CAP)”47,48.

LSM is modelled on the Hook’s law that actually says if the velocity of

the shear waves is directly proportional to stiffness of the object thereby

inferring that it is inversely proportional when compared to the elasticity.

There are two types of waves that are emitted by the probe

Slow-spreading and the low-frequency (50 Hz) shear wave

Fast ultrasound waves emitted as pulse-echo fashion.

LSM values range between 1.5 and 75 kPa; lower values is more

suggestive of an elastic liver.

37

Fig.13- LSM range and severity of fibrosis

COMPUTED TOMOGRAPHY

Computed tomography can also be used to demonstrate features

suggestive of PHT like

Abnormal configuration of the liver

Ascites

Splenomegaly

Collateral vessels

Detection of the varices is emerging as an indication for CT. Multi-

detector row CT (MDCT) is as good as endoscopy in diagnosing the

fundal varices.

CT is also helpful especially for distinguishing the submucosal varices

and the peri-gastric varices in the fundus.

38

Large EV have been easily diagnosed using the single or the multi-

detector CT with a sensitivity between 84–100% and specificity between

90–100%. However there is an inter-observer variability and there is low

sensitivity in detecting small EV. Thus, the endoscopy is the preferred

screening tool and has been very cost-effective compared to the contrast-

enhanced CT followed. However at present the CT is not usually

recommended as a screening method for EV49.

Fig.14

39

MAGNETIC RESONANCE IMAGING

Magnetic resonance imaging (MRI) with gadolinium enhancement has

been used to detect EV along with measurement of blood flow in the

portal system

It gives a clarity on the vascular structures located in the liver like

detecting portal venous thrombosis. It can also be used to assess stiffness

of fatty liver accurately.

B. BLOOD INVESTIGATIONS

COMPLETE BLOOD COUNT- THROMBOCYTOPENIA

The low platelet counts are usually seen in patients with chronic liver

disease which may be due to several factors

Hypersplenism due to the increased splenic pool of platelets and

destruction.

Impaired thrombopoiesis due to the thrombopoitein deficiency as a result

of alcohol

Consumption of platelets in gastrointestinal bleeding.

40

LIVER FUNCTION TESTS –

HYPOALBUMINEMIA –

In cirrhotic patients hypoalbuminemia is always noted and it may be

caused by

Decreased liver synthesis of albumin

Sodium and water retention which causes dilution of albumin in the

extracellular space.

Increased trans-capillary transport rate

ELEVATED LIVER ENZYMES AND CHILD–TURCOTTE–PUGH

SCORE

Tab.8 – CHILD TURCOTTE PHUGH SCORE

41

RATIOS –

PLATELET SPLEEN DIAMETER RATIO-

RIGHT LOBE OF LIVER AND ALBUMIN DIAMETER RATIO-

MANAGEMENT OF EV –

CONSERVATIVE THERAPY-

Two groups of pharmacological agents have been used in treating PHT

Drugs which help to reduce splanchnic flow of blood

Drugs that help in reducing the intrahepatic vascular resistance

42

Diuretics may reduce PP by decreasing the total plasma volume however

they have not been recommended as sole agents.

Gastric pro-kinetic drugs like Metoclopramide may reduce intra-variceal

pressure with the contraction of LES however these agents have not been

used in clinical trials and not recommended.

Vasopressin and similar Analogs-

Vasopressin is a peptide hormone that is secreted endogenously and this

causes

Splanchnic vasoconstriction

Portal venous inflow reduction

PP reduction

Terlipressin, (triglycyl-lysine-vasopressin), a semisynthetic analog

of vasopressin is cleaved by the endothelial peptidases enzyme which

results in the release of lysine vasopressin. In comparison to the

vasopressin, terlipressin has a low circulatory levels and lesser systemic

side effects. When used in combination with nitrates there is a decreased

risk of systemic side effects of vasopressin and terlipressin. Terlipressin

is better compared to vasopressin as it has a better safety profile and

increased survival rate in patients with EV and bleeding.

43

Somatostatin and similar Analogs-

Somatostatin is a peptide hormone which has around five receptors

(SRTR 1 TO SRTR 5). Half-life of Somatostatin is around 1-3 minutes;

thus analogs which are long acting have been produced.

The available analogs are

Octreotide,

Lanreotide

Vapreotide.

This group of drugs decreases pressure in portal system and its

collaterals through inhibiting the glucagon release. Somatostatin also

reduces PHT by reducing the postprandial flow of blood in splanchnic

circulation.

After the variceal bleeding, blood in GIT behaves similar to a meal so

that it can lead on to an increased flow in portal circulation and also an

elevated PP. Thus this can be ameliorated by somatostatin.

Octreotide has half-life of around 80 -120 minutes. Randomized

controlled trials have established that somatostatin and it analogs are

equally efficacious when compared with the sclerotherapy or

administration of terlipressin for management of acute variceal bleeding.

44

Vapreotide administration has been associated with a greater control of

variceal bleeding and a there is no reduction in the mortality.

Somatostatin and its analogs have been used along with endoscopy for

the treatment of variceal bleeding in the clinical practice.

β-Adrenergic Blocking Agents-

For preventing the variceal bleeding nonselective β- blockers are used

extensively. Preferred nonselective beta blockers are

Propranolol

Nadolol

Mechanism of action – Blockage of β1- receptors decreases the

cardiac output by acting on the heart whereas the blockage of β2-

receptors causes vasodilation of the vessels in the mesenteric circulation

and along with this there is an unopposed α1-adrenergic receptor which

causes reduced flow in the portal circulation. All these effects decrease

PHT.

Propranolol reduces the PP by 50%. Dosage has to be adjusted based

on the heart rate like to around 25% lesser to that of initial heart rate.

However it should not be below 55/min. Propranolol is also helpful in the

prophylaxis of erosive gastropathy.

45

Nadolol is preferred over propranolol because it has mainly excreted

through the kidneys and it also because of it is lower lipid solubility. It

has reduced CNS side effects. Dose is adjusted by modifying the dosage

to around 1 mg per day twice daily.

Nitrates -

Nitrates cause vasodilatation by decreasing the intracellular calcium

levels by acting on the smooth muscle cells in the vascular system.

Nitrates predominantly cause veno-dilatation, which results in the

reduced blood flow in PVS. Nitrates can be

Short-acting –nitroglycerin

Long-acting -isosorbide mononitrate

Nitroglycerin has been used along with vasopressin in controlling

variceal bleeding previously. The infusion rate is around 50 to 400 μg per

minute and the systolic BP has to be maintained above 90 mm Hg.

For primary prophylaxis nitrates are not recommended. For secondary

prophylaxis, isosorbide mononitrate can be used as an additional drug

with beta blockers.

Drugs That Decrease Intrahepatic Vascular Resistance

α1-adrenergic blockers like prazosin can be used to reduce the PHT.

However the long term use can result in sodium and water retention

46

leading on to ascites. They can be administered at a dosage of 2 to 4 mg

per day.

ARB ( Angiotensin II receptor Blockers ) like Losartan can also be used.

They can reduce the PP without any systemic effects. However they

resulted in decreased in renal function

INVASIVE THERAPY

ENDOSCOPY –

Endoscopic assessment of varices and the bleeding is the method

preferred usually. They amount of bleeding is usually risk stratified by

various methods. The most common method is the Rockall Scoring

System.

Score > 8 has poor prognosis

Score < 3 has good prognosis

47

The two commonly used for treating EV are

Endoscopic sclerotherapy or EST

Endoscopic band ligation or EBL.

Endoscopic therapy is actually the local therapy which does not influence

pathological process that influence PHT or variceal bleeding. But there

has been reports that there can be a spontaneous reduction of HVPG in

about 30% of all patients who have been treated by EST or EBL50.

Endoscopic sclerotherapy-

EST is the method of injecting of the sclerosing agent with a flexible

catheter in and around the variceal lumen thereby causing thrombosis of

dilated vessel and also causing inflammation in surrounding tissues51,52.

The commonly used sclerosing agents53-

Ethanolamine oleate

Polidocanol

Sodium morrhuate

In active bleeding, EST causes hemostasis by producing variceal

thrombosis and tissue edema. On repeated use there can be inflammation

which can lead on to fibrosis around the vascular wall which results in

obliteration of EV54.

48

The sclerosants are injected by two techniques

Intra-variceal

Para-variceal.

Paravariceal injection – In this technique large volume of sclerosing

agents is injected adjacent to the bleeding vessel. This causes fibrosis

around the varices. This technique is difficult because of ongoing

bleeding , so it used in elective sclerotherapy.

Intravariceal injection – This technique directly causes variceal

thrombosis. Initially 1-3 mL of the agent is injected below the site of

bleeding. Later 2-3 mL is injected adjacent to bleeding varix. Totally

around 10 to 15 mL of the sclerosant can be used in a single session55.

Advantages

Cheap and very easy technique

Rapidly assembled

Quick thrombosis.

Minor complications occurring in the initial 24 to 48 hours which do not

need any treatment51

Low grade fever

Retrosternal chest pain

Temporary dysphagia

49

Asymptomatic minimal pleural effusions

Nonspecific transient changes in the chest radiography

Local complications56:

Esophageal ulcers

esophageal stricture

Complications with cardiovascular and respiratory system:

Pleural effusion

Adult respiratory distress syndrome

Pericarditis

Systemic complications:

Fever due to bacteremia

Spontaneous bacterial peritonitis

Distant embolism or abscess

Mortality is 2% and it mainly due to perforation, recurrent bleeding,

sepsis, and ARDS57

50

Fig.15. - Sclerotherapy

Endoscopic band ligation

EVL is the technique by which the rubber rings are placed on the variceal

columns. The EV are initially aspirated into a hollow plastic cylinder

which is attached to endoscope tip58.

Ligation Devices have around 4 to 10 preloaded bands. After performing

initial diagnostic endoscopy, identification of the bleeding is done. Later

the distance between the varix and mouth is measured. Then scope is

withdrawn and the device is loaded55. After loading the scope with

ligating device in neutral mode the endoscope is advanced with slightly

neck flexion and gentle advancement of the endoscope. The device is the

kept ‘‘forward only’’ mode and advanced. Finally after identifying the

bleeding varix, “the tip is pointed toward it and continuous suction

51

applied so it can fill the cap”55 and the red out sign appears. At this

juncture the band is fired and they are all applied as helical fashion so as

to prevent the circumferential placement of band. Bands are applied

progressively within 6 to 8 cm of the palisade and the perforating zones.

The bands usually fall off after few days. Following which esophageal

ulcers develop at the ligated sites and later EV become smaller.

Eradication of EV needs around 2-4 sessions. Varices are said to be

eradicated if they have disappeared or if they could not be grasped or

banded. In 90% of patients EV can be eradicated , however recurrences

are common.The problematic disadvantage of EVL is greater chance of

recurrent varices59.

Complications60

Esophageal laceration or perforation

Transient dysphagia and Retrosternal pain

Esophageal stricture and Ulcer bleeding

Transient accentuation of PHG

Bacteremia

52

Fig.16.- Band ligation

Other methods-

Argon plasma-coagulation with EVL

Endoscopic clipping injecting tissue adhesives [n-butyl-2-cyanoacrylate

or isobutyl-2-cyanoacrylate]

Applying detachable nylon mini-loops

53

54

TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC STENT

SHUNT (TIPS)-

TIPS is a technique by which the raised PP is reduced by a shunt between

the hepatic vein and the intrahepatic branch of the PV. Percutaneously the

balloon-expanded stents are placed61,62,63

Indications-

The stent must be monitored as in around 50% of the patients, shunts are

thrombosed in a period of 6 to 24 months.

Fig.17-TIPS

55

SURGICAL THERAPY

Surgical treatment for PHT can be

Non-shunt procedures

Portosystemic shunt procedures

Liver transplantation.

56

MATERIALS AND METHODS

SOURCE OF STUDY-

Data was collected from the patients who are admitted in the Government

Coimbatore Medical College and Hospital with symptoms and signs

suggestive of PHT.

DESIGN OF STUDY:

Cross Sectional Study.

PERIOD OF STUDY:

One year.

SAMPLE SIZE: 50 patients

INCLUSION CRITERIA:

Patients of both sex who were diagnosed as case of PHT at Coimbatore

Medical College Hospital clinically, biochemically, radiologically and

endoscopically were included.

Age above 18 yrs.

EXCLUSION CRITERIA:

HIV

Hepatocellular carcinoma

Liver Metastasis

57

H/O treatment taken for PHT in form of surgery or EVL or EST

Pregnancy and lactating mothers

Patients not capable of giving consent (psychiatric patients).

Patients not willing to participate in the study (who refused to consent).

METHODOLOGY

The study is will be undertaken on the patients attending

outpatient department and as well as getting admitted in the Coimbatore

Medical College and Hospital, Coimbatore during the study period .A

total of 50 patients will be enrolled in the study.

The list of the patients enrolled in the study is appended along with

the dissertation. The study excludes minors, pregnant women, mentally-

ill and non-volunteering patients, Presence of HIV, Hepatocellular

carcinoma, Metastasis to the liver and patients who have undergone

treatments like banding and sclerotherapy.

The study is proposed to be conducted after obtaining informed

signed consent from the patients. The duration of the study is one year.

After obtaining informed signed consent from the patients to participate

in the study, collects their baseline characteristic details, medical history

details and physical examination details.

58

All patient will be subjected to complete blood count ,activated

partial thromboplastin time ,prothrombin time and INR, Liver function

tests[serum bilirubin, alkaline phosphate (ALP), alanine transaminase

(ALT),aspartate transaminase (AST)], total serum proteins, albumin and

globulin levels, coagulation profile [APTT ,PT,INR] serum electrolytes

and blood urea, serum creatinine, random blood sugar, HbsAg, anti HCV

and abdominal ultrasonography to assess the spleen longitudinal diameter

and portal vein diameter and upper gastrointestinal endoscopic

examination. Fibro-elastography was determined using FibroScan.

Patients will be assessed with Child – Pugh’s score and the EV will

graded using Westaby’s Classification.

59

STATISTICAL ANALYSIS-

All the dates were entered in a data collection sheet in an Excel format and

analysed using SPSS Software. Numerical values were reported using mean

and standard deviation or median. Categorical values are reported using

number and percentages. Probability value (p) value less than 0.05 was

considered a statistically significant

60

RESULTS

TAB.9-AGE DISTRIBUTION

AGE (IN YRS) NO OF PATIENTS PERCENTAGE

< 40 2 4%

41-50 18 36%

51-60 22 44%

>60 8 16%

In the study predominant population was between the age group 51 to 60

years (44%) followed by the age group 41 to 50 years (36%), very few

were below the age of 40 years (4%).

2

18

22

8

< 40 41-50 51-60 > 60

GRAPH.1-AGE DISTRIBUTION

61

TAB.10 -SEX DISTRIBUTION

SEX NO OF PATIENTS PERCENTAGE

MALE 41 82%

FEMALE 9 18%

In the study 82 % of patients were males. This is mainly because

predominant of the study population were alcoholics and they were

predominantly males.

82%

18%

GRAPH.2-SEX DISTRIBUTION

MALE

FEMALE

62

TAB.11.ALCOHOL INTAKE

ALCOHOL INTAKE NO OF PATIENTS PERCENTAGE

PRESENT 38 76%

ABSENT 12 24%

Most of the patients were alcoholics – 76% and among the rest

cryptogenic cause was around 15 %. Viral infection was also noticed in

patients. There were around 6% of patients with HBV and 4 % of patients

had HCV.

38

12

0 5 10 15 20 25 30 35 40

PRESENT

ABSENT

GRAPH.3-ALCOHOL INTAKE

63

TAB.12. CRYTOGENIC CASES

CRYPTOGENIC NO OF PATIENTS PERCENTAGE

YES 8 15%

NO 42 84%

TAB.13- HBV INFECTION

HBV NO OF PATIENTS PERCENTAGE

PRESERT 3 6%

ABSENT 47 94%

16%

84%

GRAPH.4-CRYPTOGENIC

YES

NO

64

TAB.14- HCV INFECTION

HCV NO FO PATIENTS PERCENTAGE

PRESENT 2 4%

ABSENT 48 96%

6%

94%

GRAPH.5-HBV

PRESERT

ABSENT

2

48

GRAPH.6-HCV

PRESENT ABSENT

65

TAB.15.COMPLETE BLOOD COUNT

PARAMETER MEAN SD

HEMOGLOBIN% 10.11 2.19

TOTAL COUNT 7040 3348

PLATELET COUNT 35061 31671

Predominantly the patients had thrombocytopenia and the mean was

around 35,061 and the mean hemoglobin was 10.11g/dL.

TAB.16-PLATELET COUNT

PLATELET COUNT NO OF PATIENTS PERCENTAGE

< 20000 24 48%

20000 – 50000 16 32%

50000 – 100000 7 14%

> 100000 3 6%

Majority of the patients (48%) had very low platelet count of less than

20,000 followed by 32% of patients in the group between 20,000-50,000.

Only 6% of the patients had platelet count over 100,000.

66

TAB.17-LIVER FUNCTION TESTS

LIVER FUNCTION TEST

PARAMETER MEAN SD

TOTAL BILIRUBIN 6.86 5.75

DIRECT 3.66 3.07

INDIRECT 3.19 2.78

SGOT 131.96 86.28

SGPT 97.57 66.29

ALP 72.2 29.33

PT 19.21 7.7

The mean bilirubin among the study population is around 6.86 mg/dL.

Most of the patients had elevated levels of SGOT and SGPT since the

mean was 131.96 IU/L and 97.57 IU/L respectively.

24

16

7

3

0

5

10

15

20

25

30

< 20000 20000 - 50000 50000 - 100000 > 100000

GRAPH.7-PLATELET COUNT

67

TAB.18 – RENAL FUNCTION TESTS

RENAL FUNCTION TEST

PARAMETER MEAN SD

UREA 62.88 35.15

CREATININE 1.6 2.44

TAB.19.SERUM ELECTROLYTES

ELECTROLYTES

PARAMETERS MEAN SD

SODIUM 137.24 5.39

POTASSIUM 4.35 0.77

Renal parameters were predominantly slightly elevated with mean urea

level being 137.24 mg/d L and the mean creatinine level being 1.6 mg/ d

L. Electrolytes were normal mostly in the study population.

TAB.20-SPLEEN DIAMETER

SIZE IN MM NO OF PATIENTS PERCENTAGE

< 130 28 56%

> 130 22 44%

68

Around 56% of the patients had splenomegaly of more than 130 mm.

TAB.21-PLATELET COUNT /SPLEEN DIAMETER RATIO

RATIO NO OF PATIENTS PERCENTAGE

< 100 17 34%

100-300 17 34%

300-500 9 18%

>500 7 14%

< 130, 28

> 130, 22

GRAPH.8-SPLEEN DIAMETER

69

Platelet and spleen diameter ratio was calculated and equal number of

patients were found in the group <100 and 100-300.

TAB.22-RIGHT LOBE LIVER DIAMETER

RT LOBE DIAMETER IN MM NO OF PATIENTS PERCENTAGE

<140 15 30%

>140 35 70%

Right lobe diameter was measured and most of the patients (around -

70%) had a diameter of more than 140mm

17 17

9

7

0

2

4

6

8

10

12

14

16

18

< 100 100-300 300-500 >500

GRAPH.9-PLATELET SPLEEN RATIO

70

TAB.23.- SERUM PROTEINS

MEAN SD

ALBUMIN in Gram / liter 23.08 6.01

GLOBULIN in Gram / liter 27.31 5.68

The mean albumin levels in the study population is around 23.08g/L and

globulin was 27.31g/L suggestive of albumin reversal in the patients.

TAB.24- RIGHT LOBE DIAMETER/ALBUMIN RATIO

RT LOBE/ALB RATIO NO OF PATIENTS PERCENTAGE

2 TO 4 3 6%

4 TO 6 17 34%

6 TO 10 23 46%

> 10 7 14%

30%

70%

GRAPH.10-RIGHT LOBE DIAMETER

<140

>140

71

Majority of the patients about 46% had a right lobe diameter albumin

ratio between 6 -10 followed by 4-6 , very few found (6%) in the

group 2-4 .

TAB.25-CTP SCORE

CTP SCORE NO OF PATIENTS PERCENTAGE

A 3 6%

B 13 26%

C 34 68%

3

17

23

7

0

5

10

15

20

25

2 TO 4 4 TO 6 6 TO 10 > 10

GRAPH.11-RT LOBE/ALBUMIN RATIO

72

Majority of the patients had a CTP score of C , around 68 % , very few

had a score of A

TAB.26-VARICES AND GARDING

VARICES GRADE NO OF PATIENTS PERCENTAGE

ZERO 2 4%

ONE 13 26%

TWO 17 34%

THREE 18 36%

3

13

34

A B C

GRAPH.12-CTP SCORE

73

36 % of the study group had grade III EV, followed by 34% of patients

with grade II. Only 2 patients did not have EV.

Tab.27- Comparing varices grading with Fibroscan FIBROSCAN

VARICES GRADE MEAN SD

ZERO 25.45 1.34

ONE 38.34 3.7

TWO 44.77 7

THREE 62.43 6.95

P VALUE - 0.001

SIGNIFICANT

ANOVA

Patients with grade III varices had mean Fibroscan score of 62.43 and

grade II varices had a mean score of 44.77. The mean score of grade I

varices is around 38.34.

2

13

1718

0

2

4

6

8

10

12

14

16

18

20

ZERO ONE TWO THREE

GRAPH.13-VARICES GRADE

74

The relationship with Fibroscan and EV was significant as the p value is

around 0.001.

Tab.28- Comparing CTP score with Fibroscan FIBROSCAN

CTP SCORE MEAN SD

A 30.2 8.28

B 43.58 10.21

C 51.96 11.93

P VALUE - 0.003

SIGNIFICANT

ANOVA

25.45

38.3444.77

62.43

0

10

20

30

40

50

60

70

ZERO ONE TWO THREE

VARICES GRADE

GRAPH.14-Comparing varices grading with Fibroscan

75

When Fibroscan was compared with CTP score the p value was

significant 0.003. The mean score for CTP – C is 51.96, CTP –B is 43.58

and CTP – 30.2

Tab.29- Comparing varices grading

with Right lobe/albumin ratio RT LOBE/ALBUMIN RATIO

VARICES GRADE MEAN SD

ZERO 3.8 0.15

ONE 6.03 2.2

TWO 7.4 1.7

THREE 7.61 2.2

P VALUE - 0.05

SIGNIFICANT

ANOVA

0

10

20

30

40

50

60

A B C

30.2

43.5851.96

CTP GRADE

GRAPH.15-Comparing CTP score with Fibroscan

76

Patients with grade III varices had mean Right lobe / albumin ratio of

7.61 and grade II varices had a mean ratio of 7.4. The mean score of

grade I varices is around 6.03.The relationship with Right lobe/ albumin

ratio and EV was significant as the p value is around 0.05.

Tab.30- Comparing CTP score with Right lobe/albumin ratio

RT LOBE ALBUMIN/RATIO

CTP SCORE MEAN SD

A 4.56 1.27

B 5.64 0.98

C 7.49 2.19

P VALUE - 0.003

SIGNIFICANT

ANOVA

3.8

6.03

7.4 7.61

Z E R O O N E T W O T H R E E

VARICES GRADE

GRAPH.16-Comparing varices grading with r ight lobe/albumin ratio

77

When Right lobe / albumin ratio was compared with CTP score the p

value was significant 0.003. The mean score for CTP – C is 7.49, CTP –B

is 5.64 and CTP – 4.56.

Tab.31- Comparing varices grading with

platelet /spleen ratio

PLATELET/SPLEEN

RATIO

VARICES GRADE MEAN SD

ZERO 858 189

ONE 289 249

TWO 253 250

THREE 190 143

P VALUE - 0.002

SIGNIFICANT

ANOVA

4.56

5.64

7.49

0

1

2

3

4

5

6

7

8

A B C

GRAPH.17-Comparing CTP score with Right lobe/albumin ratio

78

Patients with grade III varices had mean Platelet / spleen ratio of 190 and

grade II varices had a mean ratio of 253. The mean score of grade I

varices is around 289.The relationship with platelet / spleen ratio and EV

was significant as the p value is around 0.002.

Tab.32- Comparing CTP score with

platelet /spleen ratio

PLATELET/SPLEEN

RATIO

CTP SCORE MEAN SD

A 649.2 386.3

B 421.8 255.5

C 169.3 156.9

P VALUE - 0.001

SIGNIFICANT

ANOVA

0

200

400

600

800

1000

ZERO ONE TWO THREE

858

289 253 190

VARICES GRADE

GRAPH.18-Comparing varices grading with platelet /spleen ratio

79

When platelet / spleen ratio was compared with CTP score the p value

was significant 0.001. The mean ratio for CTP – C is 169.3, CTP –B is

421.8 and CTP – 649.2.

Tab.33- Comparing varices grading with Right

lobe diameter

RT LOBE

DIAMETER

VARICES GRADE MEAN SD

ZERO 134 0

ONE 144.3 11.74

TWO 148.1 9.09

THREE 145.2 8.7

P VALUE - 0.245

NON SIGNIFICANT

ANOVA

649.2

421.8

169.3

0

100

200

300

400

500

600

700

A B CCTP SCORE

GRAPH.19-Comparing CTP score with platelet /spleen ratio

80

Tab.34- Comparing CTP score with Right lobe

diameter

RT LOBE

DIAMETER

CTP SCORE MEAN SD

A 141.67 13.27

B 143.38 9.87

C 147.15 9.49

P VALUE - 0.384

NON SIGNIFICANT

ANOVA

134

144.3

148.1

145.2

125 130 135 140 145 150

ZERO

ONE

TWO

THREE

GRAPH.20-Comparing varices grading with Right lobe diameter

81

Tab.35- Comparing varices grading with

platelet count

PLATELET

COUNT

VARICES GRADE MEAN SD

ZERO 100500 41719

ONE 38076 36518

TWO 31705 29546

THREE 28411 20633

P VALUE - 0.017

SIGNIFICANT

ANOVA

141.67

143.38

147.15

138 139 140 141 142 143 144 145 146 147 148

A

B

C

CTP

SCO

RE

GRAPH.21-Comparing CTP score with Right lobe diameter

82

Patients with grade III varices had mean Platelet count of 28411 and

grade II varices had a mean count of 31705. The mean score of grade I

varices is around 38076.The relationship with platelet count and EV was

significant as the p value is around 0.017.

Tab.36- Comparing varices grading with

platelet count

PLATELET

COUNT

CTP SCORE MEAN SD

A 79000 47507

B 55000 32812

C 23212 19617

P VALUE - 0.001

SIGNIFICANT

ANOVA

1005

00

3807

6

3170

5

2841

1

Z E R O O N E T W O T H R E E

VARICES GRADE

GRAPH.22-Comparing varices grading with platelet count-

83

When platelet count was compared with CTP score the p value was

significant 0.001. The mean count for CTP – C is 23212, CTP –B is

55000 and CTP – 79000.

79000

55000

23212

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

A B C

CTP SCORE

GRAPH.23-Comparing CTP score with platelet count

84

DISCUSSION This study was conducted in Coimbatore medical college hospital from

July 2016 to July 2017. A total of 50 cases were studied. The clinical and

diagnostic findings of this study are compared with our studies in

literature here.

PREVALENCE:

About 300 patients are admitted in Coimbatore Medical College Hospital

every year. It was around 20 cases every month. A sample of 50 cases

was collected for this study.

AGE OF THE PATIENT-

In the study predominant population was between the age group 51 to 60

years (44%) followed by the age group 41 to 50 years (36%), very few

were below the age of 40 years (4%). And the findings of this study is

consistent with other studies conducted elsewhere.

Authors Predominant Age group

Waleed K. Al-Hamoudi et al64 57.2 ± 15.3

Alempijevic et al65 55.14±7.71

El Makarem et al66 51.09 ± 5.1

Borro, et al67 62

Montasser et al68 53.9 ± 8.3

Bulat et al69 52.32 ± 13.60

Cherian et al70 42

Present study 51-60

85

GENDER DISTRIBUTION OF THE PATIENTS -

Similar to other studies done, this the study more than 4/5 of the cases

were male rest were female cases. This is mainly because predominant of

the study population were alcoholics and they were predominantly males.

Authors Male and female

Alempijevic et al 74/12

El Makarem et al 63.4% and 36.6 %

Borro, et al 62/27

Montasser et al 56/19

Bulat et al 62/32

Cherian et al 104/75

Present study 82 % and 18 %

ETIOLOGY-

Most of the patients were alcoholics – 76% and among the rest

cryptogenic cause was around 15 % followed hepatitis viral infection. 6

% of patients had HBV and 4 % of patients had HCV. This reflects the

prevalence of alcohol consumption in the population from which the

study group was sampled.

86

THROMBOCYTOPENIA AND VARICES.

Invariably the study population has thrombocytopenia which was similar

to other studies. Thrombocytopenia also had significant relationship

between the CTP score and grading of varices. The p value was 0.001 and

0.017 respectively.

Authors Platelet count and EV

Waleed K. Al-Hamoudi et al p value – 0.004

Alempijevic et al p value - 0.987

El Makarem et al p value - 0.001

Borro, et al p value - 0.0001

Cherian et al p value - 0.003

Present study p value - 0.017

PLATELET COUNT AND /SPLEEN DIAMETER RATIO AND

VARICES-

Patients who had large EV grade III varices also had a low Platelet /

spleen ratio with a mean of 190. This was similar to the studies and the p

value is 0.002.

Authors p value

El Makarem et al 0.739

Borro, et al 0.0001

Bulat et al 0.01

Cherian et al 0.001

Present study 0.002

87

RIGHT LOBE DIAMETER /ALBUMIN RATIO AND VARICES-

Bulat et al demastrated a significant relation between the presence of EV

and size ( p valu <0.01) whereas in the present study similar results were

observed with significant p value of around 0.05.

FIBROSCAN AND VARICES-

In the study those patients with grade III varices had mean Fibroscan

score of 62.43 and grade II varices had a mean score of 44.77. The mean

score of grade I varices is around 38.34.The relationship with Fibroscan

and EV was significant as the p value is around 0.001. The results suggest

that the increased liver stiffness has a direct correlation with severity of

PHT. Moreover, When Fibroscan was compared with CTP score the p

value was significant 0.003. Waleed K. Al-Hamoudi et al showed that

Fibroscan had a positive correlation when compared to the grade of EV

(γ= 0.747, P<0.001).

PARAMETERS R VALUE

FIBROSCAN 0.523

RT LOBE/ALB DIAMETER 0.095

PLATELET/SPLEEN RATIO 0.076

PLATELET COUNT 0.082

88

With the r value > 0 in all the parameters when compared with EV, it can

be implied that the above parameters have a positive correlation with EV.

CTP SCORE AND VARICES-

All the above mentioned non -invasive parameters had significant

correlation with CTP score based on the Pearson correlation. Similar to

the studies done previously those patients with higher score had larger

varices.

PEARSON CORRELATION WITH CTP

PARAMETERS R VALUE P VALUE SIGNIFICANT

FIBROSCAN 0.468 0.002 YES

RT LOBE/ALB RATIO 0.466 0.001 YES

PLATELET/SPLEEN RATIO 0.602 0.001 YES

RT LOBE DIAMETER 0.199 0.171 NO

PLATELET COUNT 0.567 0.001 YES

89

SUMMARY

50 patients with liver disease were admitted to Coimbatore Medical

College Hospital between July 2016 – July 2017 were included in the

study.

Commonest age group involved is above 51-60 years.

Males are the most common to present with EV.

Majority of patients were alcoholics and they were the most common

cause for PHT.

48% had severe thrombocytopenia of countless than twenty thousand.

56% had spleen size of less than 130mm.

4% did not had EV, 26% had Grade I varices,34% had Grade II varices

and 36% had Grade III varices.

Higher Fibroscan score is associated with larger varices.

Low platelet count was seen in Grade III varices.

When the Right lobe diameter albumin ratio was high the varices were

also larger.

Those patients with lower platelet count spleen diameter ratio had larger

varices

Overall the non-invasive parameters had a significant ability to predict

and also identify the estimated grading of variceal size.

90

CONCLUSION

This study has study has revealed that the newer parameter transient

elastography or Fibroscan is far more better predictor of presence of

varices and also the size of varices when compared to other parameters.

However the study has also reiterated the fact that older and often used

non-invasive parameters like platelet count / spleen diameter ratio and

platelet count are also much better when compared to the Right lobe

diameter / albumin ratio.

These parameters can be used in situations where the invasive endoscopic

examination is not possible due to non-availability or contraindicated.

Patients who satisfy the criteria can be started on early treatment with

prophylactic beta-blocker therapy. These parameters can also be used to

identify those patients who may have larger varices which needs an

endoscopic intervention. This can avoid the overburden cases requiring

endoscopy.

91

LIMITATIONS

The study was based at a single academic center and the sample size was

small when compared to incidence of liver diseases. Further studies with

large sample size are required in India to evaluate and postulate the other

predictors of EV like portal vein Doppler.

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ANNEXURE-1

PROFORMA

NAME AGE

OCCUPATION SEX

SOCIO ECONOMIC STATUS

IP NO

ADDRESS

CHIEF COMPLAINTS

PRESENT HISTORY

1. HAEMATEMESIS 2. MELENA 3. ALTERED BOWEL

HABITS 4. ABDOMINAL

DISTENSION 5. PEDAL EDEMA 6. YELLOWISH

DISCOLORATION 7. ALTERED SLEEP 8. LOSS OF

CONSCIOUSNESS 9. OLIGURIA 10. DYSPNEA

Yes/no

Duration Other features

PAST HISTORY

1. SHT 2. DM 3. CAD 4. TB 5. EPILEPSY/CVA 6. LIVER DISEASES

Duration Treatment

PERSONAL HISTORY

1. ALCOHOL CONSUMPTION-

2. SMOKING 3. DIET 4. DRUG INTAKE

Quantity - Duration

GENERAL EXAMINATION

BP

PR

SPO2

TEMP

RR

CONSCIOUS LEVEL-

PALLOR

ICTERUS-

DYSPNEA-

PEDAL EDEMA-

SYSTEM EXAMINATION –

CVS

RS

ABD

CNS

BASE LINE INVESTIGATIONS-

CBC RFT LFT

SPECIAL BLOOD INVESTIGATIONS

Prothrombin time

HBsAg Anti HCV

RADIOLOGICAL INVESTIGATIONS

USG SPLEEN DIAMETER

RIGHT LOBE

DIAMTER

RATIOS and SCORE

Right lobe/albumin

Platelet /spleen

daimater

CTP SCORE

FIBROSCAN

ENDOSCOPY VARICES GRADE-

OTHER FINDINGS

FINAL DIAGNOSIS

TREATMENT

ANNEXURE -2

CONSENT FORM

Yourself Mr./Mrs./Ms……………………………….. are being

asked to be a participant in the research study titled “A study to

compare the efficacy of noninvasive predictors of esophageal

varices in patients with portal hypertension”in CMC Hospital,

Coimbatore, conducted by DR.SRINIVASAN KARTHIKEYAN

M.D., Post Graduate Student, Department of General Medicine,

Coimbatore Medical College. You are eligible after looking into the

inclusion criteria. You can ask any question you may have before

agreeing to participate.

Research Being Done A study to compare the efficacy of non-invasive predictors of

esophageal varices in patients with portal hypertension

Purpose of Research

To study clinical and investigative profile of patients with PHT.

To study the predictive power and compare the noninvasive investigative parameters for detection of esophageal varices in patients with PHT as compared to invasive parameter

Decline from Participation You have the option to decline from participation in the study

existing protocol for your condition.

Privacy and Confidentiality

Privacy of individuals will be respected and any information about

you or provided by you during the study will be kept strictly

confidential.

Authorization to publish Results Results of the study may be published for scientific purposes and/or

presented to scientific groups, however you will not be identified.

Statement of Consent

I volunteer and consent to participate in this study. I have read the

consent or it has been read to me. The study has been fully explained

to me, and I may ask questions at any time.

------------------------------- -------------------------------

Signature /Left thumb impression Date

(volunteer)

-------------------------------- -------------------------------

Signature of witness Date

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JAFFER 56 M AB P AB AB 12.5 4300 45000 3.4 1.5 1.7 35 35 98 13 45 1.4 138 3.5 160 281.25 159 29 35 43.4 5.48 B 2

KANNAN 42 M AB AB P AB 13.1 6600 99000 8.4 3.4 5 121 96 45 11.2 54 0.5 141 3.3 110 900 148 33 26 38.7 4.48 B 2

KARTHIKEYAN 46 M AB AB P AB 7.6 7900 35000 7.8 3.6 4.2 230 132 95 12.4 96 0.9 136 3.4 150 233 148 22 28 39.2 6.72 B 2

THURAIKANNAN 47 M P AB AB AB 8.7 9300 8000 5.6 3.2 2.4 200 123 89 19.1 102 0.8 126 4.1 140 57.14 136 18 22 53.2 7.55 C 2

SUBBURAJALU 58 M P AB AB AB 9 3600 17000 2.3 1 1.3 89 60 32 15.2 42 1.6 136 5 134 126.86 156 22 26 44.6 7.09 C 2

SIVAGNAM 55 M P AB AB AB 10.5 4800 13000 3.2 1.3 1.9 65 55 65 16.4 36 1.5 138 3.6 144 90.2 169 16 20 50.6 10.56 C 2

SHAKTHIVEL 59 M P AB AB AB 13 9600 16000 1.7 1.5 0.2 55 40 30 17.4 98 1.1 130 3.7 126 126.98 138 15 23 53.6 9.2 C 2

SRI RANGAN 62 M P AB AB AB 13 13000 5000 2.1 0.7 1.4 63 45 25 22.4 113 1.2 128 5.7 136 36.76 155 15 22 53.4 10.33 C 2

ANTONY 53 M P AB AB AB 14 14000 8000 9.2 5.4 3.8 121 82 36 35.3 164 0.7 131 5.1 126 63.49 145 22 26 48.4 6.59 C 2

THAMEEM 55 M P AB AB AB 9.8 10000 15000 10.1 5.5 4.6 165 102 65 26.5 102 1.1 141 4.9 129 116.27 136 20 31 49.6 6.8 C 2

ARUMUGAM 64 M P AB AB AB 13.2 6400 12000 3.2 1.3 1.9 135 85 75 23.1 26 2.4 144 5.9 128 93.75 146 21 28 46.4 6.95 C 2

MURUGNATHAM 41 M P AB AB AB 9.9 5700 8000 4.6 2.2 2.4 178 96 100 36.7 39 2.7 136 6.4 104 76.92 136 19 20 52.4 7.15 C 2

BALU GOUNDER 47 M P AB AB AB 9.5 6300 12000 5.3 3.6 1.7 165 110 97 19.5 46 1.8 138 4.3 110 109.09 152 14 22 42.4 10.85 C 1

SHEIRF 46 M P AB AB AB 7.8 5800 13000 6.5 3.2 3.3 138 75 77 13.9 66 0.9 139 3.6 120 108.33 144 22 28 39.4 6.54 C 1

LENIN 43 M P AB AB AB 8.9 9800 9000 31.7 15.8 15.9 555 462 121 36.4 54 1 130 3.6 124 72.58 169 16 20 36.9 10.56 C 1

PICHAI 55 M P AB AB AB 13.6 3600 16000 23.6 12.3 11.3 336 234 134 37.1 74 1.1 143 4.1 135 118.51 136 33 24 29.5 4.12 C 1

IBRAHIM 68 M P AB AB AB 10.3 2200 11000 15.6 8.6 7 201 178 134 26.5 89 1.2 145 4.4 126 88.09 147 30 22 43.3 4.9 C 1

KARTHIKEYAN 53 M P AB AB AB 13.5 3500 13000 17.9 10.7 7.2 196 165 99 23.4 32 1.6 148 5.1 98 132.65 136 27 23 34.9 5.03 C 1

SUMAN NAIR 41 M P AB AB AB 11.3 4300 36000 5.6 3.8 1.8 102 112 78 13.1 20 1.4 135 5.2 111 324.32 135 25 23 35.4 5.4 B 1

WILSON 46 M P AB AB AB 9 6600 33000 6.4 4.7 1.7 135 86 101 11.5 63 0.5 134 4.7 104 317.3 154 29 20 36.5 5.31 B 1

VASUDEVAN 55 M P AB AB AB 7.8 7900 47000 3.5 2.1 1.4 89 77 103 13.5 36 0.9 136 4.9 138 340.57 144 28 26 41.5 5.14 B 1

JOSE 66 M P AB AB A 8.6 9300 39000 4.6 3.1 1.5 88 76 56 17.5 36 0.8 146 3.9 127 307.08 124 26 22 40.6 4.76 B 1

B

PARASURAMAN 49 M P AB AB AB 9.5 3600 110000 2.7 1.5 1.2 45 43 69 14.3 46 1.6 135 3.4 133 827.06 135 36 24 38.7 3.75 B 1

MURUGAN 60 M P AB AB AB 12.3 4800 120000 3.1 1.9 1.2 56 52 32 13.1 52 1.5 139 3.7 153 784.31 144 24 30 39.7 6 B 1

ANTHONY 55 M P AB AB AB 9.9 9600 71000 6.7 3.5 3.2 90 88 78 11.3 55 1.1 136 4.4 98 724.48 134 34 29 26.4 3.94 A 0

PARAVATHY 57 F P AB AB AB 5.5 4400 57000 8.4 5.3 3.1 92 77 64 16.2 53 1.2 138 4.5 108 527.77 154 22 24 32.5 7 B 2

SHEETHAL 47 F AB AB P AB 8.6 3600 64000 6.4 2.7 3.7 97 64 56 13.8 99 0.7 140 4.6 134 477.61 155 21 22 36.9 7.38 C 2

JAMILA 46 F AB P AB AB 7.5 7900 36000 4.9 2.5 2.4 98 69 97 19.7 39 2.1 136 4.8 123 292.68 144 17 26 34.6 8.47 C 2

SARASWATHI 49 F AB P AB AB 10.3 3700 12000 17.6 9.7 7.9 164 134 101 16.5 45 1.8 137 5.1 101 118.81 146 16 29 38.2 9.12 C 2

THEIVANIYAMMAL 52 F AB P AB AB 8.6 2100 130000 5.3 2.9 2.4 44 54 26 17.5 55 0.5 142 5 131 992.36 134 36 25 24.5 3.72 A 0

LALITHA 56 F AB P AB AB 9.6 4900 21000 6.8 4.1 2.7 135 147 65 13 16 1.3 143 4.8 126 166.66 147 19 22 55.6 7.73 C 3

SUBBAMAL 53 F AB P AB AB 13.2 11000 45000 7.5 3.6 3.9 86 79 55 12.4 22 1.5 146 3.6 139 323.74 157 27 25 63.4 5.81 C 3

THAVAMANI 59 F AB AB AB P 11.3 8900 36000 6.9 3.7 3.2 145 134 99 14 32 0.9 144 3.4 156 230.76 157 26 31 39.7 6.03 A 1

Abbreviations for Master chart

AB - Absent

P - Present

HBV - Hepatitis B Virus

HCV- Hepatitis C Virus

SGOT - Serum glutamic-oxaloacetic transaminase

SGPT - Serum glutamate-pyruvate transaminase

PT – Prothrombin time

CTP - Child–Turcotte–Pugh score