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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