188

TRANSACTIONS

OF THH

ROYU

The pathology
B.

SOCIETY

OF TROPICAL

MEDICINE

AND HYGIENE,

VOL.

73, No.

2, 1979

and pathogenesis bf fatal hepatic amoebiasis-a

based on 79 autopsy cases

study

K. AIKAT, S. R. BHUSNURMATH, A. K. PAL, P. N. CHHUTTANI AND D. V. DATTA

Departments qf Pathology and Medicine, Postgraduate Institute

Chundigarh-lfS0072, India

Summary

The present study is based on a retrospective

analysis of 79 autopsy cases of hepatic amoebiasis.
An attempt has been made to reconstruct the
sequence of events starting from intestinal infection
to invasion and transport of amoebae along the
radicles of the portal veins, the formation of early
Zahns infarct and the proliferation of amoebae in
such foci leading to the formation of small abscesses
The coalescenceof small abscessesgives rise to the
apparently large abscesses. Apart from direct
contiguity, more distant extension leading to a
satellite abscessis due to involvement of the hepatic
and/or portal venous radicles. It seemsthat obstruction of the hepatic vein contributes substantially
towards the enlargement of the liver and its
exaggerated nutmeg appearance. Signs and symptoms of hepatic vein obstruction sometimes overshadow the abscess pathology. Thrombosis or
pressure of a neighbouring abscess over the portal
vein obstruction sometimes overshadow the abscess
pathology. Thrombosis or pressure of a neighbouring abscessover the portal vein and bile-duct lead to
development of portal hypertension and jaundice.
Both cell-mediated and humoral immunity are
depressed in fatal cases of hepatic amoebiasis.

qf Medical

Education and Research,

enlargement and tenderness of the liver? There has

been speculation, based on indirect evidence, as to
the possible explanation of some of these points.
It is, therefore, necessary to have a rational and
scientific approach towards this very important
complication of amoebiasis.
The present communication is a retrospective
analysis of 79 cases of fatal amoebiasis, of which
only 40% were correctly diagnosed during life.
This has happened in an institution where amoebic
liver abscessis a high suspect in any caseof tender
enlarged liver.
Materials

and methods

The autopsy material from 79 cases of hepatic

amoebiasis encountered at the Postgraduate Iistitute of Medical Education and Research. Chandigarh during the years 196575 was carefully analysed
with particular reference to lesions in the intestine,
the liver and such other organs which were involved
in the amoebic process. Whenever necessary,
multiple sections or blocks were taken. Serial
sections were stained with haemotoxylin and eosin,
iron haematoxylin, P.A.S. and silver impregnation
methods. The results of diagnostic serological tests
and tests for cell mediated immunity were available
from the Parasitology Division.

Introduction

While it is true that considerable advances have

been made in the understanding of hepatic amoebiasis there are several points which need elucidation.
It is perhaps true that in most instances of invasive
amoebiasis affecting the intestine, amoebae reach
the liver floating along the portal circulation. In
most of such cases these are effectively dealt with
by the macrophage function in conjunction with
cell mediated and humoral immunity. It is, therefore, necessary to determine whether humoral and
cell-mediated immunity are significantly affected
in fatal cases of hepatic amoebiasis.
There is considerable controversy regarding the
process of evolution of the abscess-Zahns infarct
{PALMER,
1938) Grails granuloma (DEMICHELE,
1962). tubercle (COUNCILMAN & LAFLEUR. 1891)
and amoebic hepatitis (ROGERS, 1922 and D~XIADE~
et al., 1961) have all been suspect as the earliest
lesion. Is the large abscess a consequence of confluence of a number of smaller abscesses,or is it a
progressive circumferential enlargement of a single
abscess? How frequent are the vascular lesions
affecting portal and hepatic venous radicles? What
is their significance and pathogenetic role for further
extension of the abscess, porn4 hvpertension.

Observations

The number and location of the abscessesand the

various complications are presented in Tables i
and II.
Intestinal ulcers could be demonstrated in 62%
of cases. Caecum and ascending colon were the
most common sites involved. Perforations were
observed mostly in the region of the caecum
(15 cases). The bowel appeared gangrenous in the
more severe lesions.
Entry of amoebae into vessels appeared to be a
fairly frequent occurrence. Fig. 1 illustrates
amoebae in the venules. The frequency of demonstration of amoebae in the venules depended on the
care with which sections at the baseof the ulcer were
studied. It was not always possible to identify the
preformed spaces. Some of them may well have
been lymphatics. However, careful examination of
the lymph glands-mesenteric and porta hepatis
failed to reveal either amoebae or any lesion
suggestive of amoebic aetiology.
Liver-Gross

appearance

This varied from case to case. The abscessitself

presented classical features like yellowish creamy

B.

Table
I-l?athology
and
hepatic amoebiasis-number

pathogenesis
and location

K.

AIKAT

et al.

189

of
of

Fig. 1. Photomlcrograph
from
submucosa
of
showing
an amoeba in a preformed
space (P.A.S.

1 RLLLBL
SINGLE
0

TOTAL

q RIGHT

1 RL LL BL
TWO
LOBE

an amoebic
x 90).

ulcer

T RLLL BI
MULTIPLE
CZ LEFT

LOBE

n BUTH

LOBES

necrotic material in the centre with a varymg

admixture of sloughed-out liver tissue. The classical
anchovy sauce colour was seen in only four cases.
The wall of the abscess was shaggy, merging
imperceptibly with the adjoining parenchyma which
showed a variety of changes. There were 10 cases
which showed a well formed fibrous wall indicating
chronicity as well as secondary infection. Serial
slicing of the liver at intervals of one to two cm
revealed that what originally seemed to be a solitary
abscesswas, in fact, formed by the coalescenceof a
number of smaller abscesses(Fig. 2).
Table II-Pathology
and
pathogenesis
hepatic
amoebiasis-complications

of

Fig. 2. Cut surface

of liver
showing
smaller
abscesses leading
to formation

confluence
of a number
of large abscess.

of

Portal and hepatic venous thrombosis were

demonstrated in a large percentage of cases (29 *5
and 27 *5 7). The occurrence of small portal vein
thrombosis leading to Zahns infarct could be
demonstrated frequently, particularly in areaswhere
the abscesswas extending. The thrombosis of large
portal and hepatic veins appeared to be due to
direct extension of inflammation from the neighbourhood of a large adjacent abscess (Fig. 3). On

Fig. 3. Large
amoebic
pression
and thrombosis

abscess at the porta

of portal
vein.

hepatitis

causing

com-

190

PATHOLOGY

AND PATHOGENESIS

the other hand, thrombosis of small portal venous

radicles away from the immediate vicinity of the
abscess resulted in small Zahns infarcts, colonization with amoebae and the beginning of a microscopic abscess.
Liver-satellite

OF FATAL

HEPATIC

AMOEBIASIS

wall, adjacent to it or away from it. Certain lesions,

which appeared to be the earliest changes, could be
detected in the sections away from the abscess.The
earliest lesion (Fig. 5) was thrombosis of the minute

lesions

When the liver was sliced serially, careful gross

scrutiny usually revealed scattered yellowish-looking
tiny nodules a few cm away from the wall of the
abscess (Fig. 4). These represent early amoebic
abscesses with skip areas between them and the
main abscess. The tense normal-looking areas of
parenchyma away from the abscessusually showed
non-specific changes, reactive Kupffer cell hyperlasia, inflammatory cells in the sinusoids and a
variable degree of portal infiltrates.

Fig. 5. Photomicrograph
of liver showing thrombosis
radicle of portal vein (H & E x 90).

Fig. 4. Large amoebic liver abscess on right

satellite abscesses on left side.

of a small

side with multiple

There were some significant pointers to indicate a

basic failure of immunological defence mechanisms :
(i) Among the cases investigated for amoebic
serology (haemagglutination-inhibition
test and
counter immune-electrophoresis) only one third
gave a positive reaction. On the other hand clinically
proved casesof non-fatal hepatic amoebiasis gave a
positivity of over 90% (-JAN
et aE. , 1975).
(ii) Two cases were encountered with immune
depression having widespread amoebiasis which was
clinically undetected. One was an adult male who,
for some undetermined reasons, was put on prolonged corticosteroid therapy. He had simultaneous
pulmonary tuberculosis and widely disseminated
hepatic arnoebiasis. The second was a paediatric
case who had thymic-lymphopenia and severe
malnutrition and had undetected hepatic amoebiasis
and a non-reactive tuberculosis.
(iii) GANGULY (personal communication) from
this Institute has clearly demonstrated a defective
cell-mediated immunity in clinical cases of extraintestinal amoebiasis.

Fig. 6. Photomicrograph
35).

of liver showing Zahns infarct. (H & E x

Liver histology

A wide spectrum of histological changes was

observed. The type of changes seen varied, depending on whether the block was taken from the abscess

Fig. 7. Photomicrograph of liver with abscess on the right showing

many dark staining amoebae; on left is a thrombosis of an hepatic
vein radicle (P.A.S. x 35).

B. K. AIKAT et al.

radicles of the portal vein in the portal tract. Amoebae

were demonstrated in some such foci. The effect
of this thrombosis was reflected in small microscooic areas of Zahns infarct (Fig. 6). Amoebae
weie demonstrated in these infarcts and there was
softening and lysis of the wall of the venules indicating migration from the lumen of the venules to the
infarct. Digestion of this infarcted area had led to
minute abscesses. The presence of these microabscesses was associated with thrombosis
of
neighbouring
radicles of the hepatic (Fig. 7) and
portal veins leading to further areas of necrosis. It
was possible to demonstrate amoebae in the sinusoids of the surrounding apparently healthy liver
parenchyma (Fig. 8). Further, in some areas away
from the abscess minute areas of necrotic foci could
be demonstrated which appeared to be the effect of
such amoebae migrating in the sinusoids. Such
areas also showed amoebae indicating colonization
by the organisms. The fusion of these tiny microscopic abscesses was seen to give rise to tiny visible
lesions. Apart from changes specific for amoebiasis,
there were other histological changes which, by
and large, were non-specific, such as bile-duct
proliferation,
Kupffer
cell hyperplasia,
spotty
necrosis and fibrosis. Non-specific granulomatous
hepatitis in the region of portal tracts was seen in
10% cases. In none of these could amoebae be
demonstrated.

Fig. 8. Photomicrographof IIVWshowingan amoebain relatively

healthy sinusoidsawayfrom main abscess.(P.A.S. x 90).

Discussion
Intestinal ulcers could be demonstrated in as
many as 62/u of the cases. In most cases amoebae
could be demonstrated within the venules or similar
preformed
spaces (lymphatics)
in ulcer beds.
Sections and aspirations from lymph nodes from
the mesenteric group and the porta hepatis failed
to reveal any amoebae in the lymphatic system. It is
very likely that amoebae cannot survive in the
adverse immunological environment of the lymphoreticular tissue. One of the authors (BKA) has
repeatedly demonstrated amoebae in the venules in
amoebic colitis without any complicating
hepatic
abscess. This indicates that in the natural history of

191

intestinal infection it is not unusual for the amoebae

to float along the portal stream into the liver. When
the organisms are few and resistance is adequate,
these are easily sequestered. It has recently been
shown (STUART, 1975) that the Kupffer cells of the
liver have the unique property of sequestering and
degrading antigens and make them non-immunogenic.
MAHAJAN, 1975, has reported positive serological
tests in about 90 to 95% of clinical cases of henatic
amoebiasis from this Institute. On the other hand,
positive serology was present in only 30% of the
fatal cases investigated. This suggests that there was
perhaps sequestration of antigens without stimulation to form antibody or failure of T-helper cells.
It will be evident from the observations of GANGULY
(1976) that there is a significant depression of cellmediated immunity in amoebic liver abscess cases
from this Institute. When the amoebae reach the
liver and cannot be sequestered and dealt with
normally, due either to an overwhelming infection
or depressed
immunological
activity due to mal.:
chronic alcoholism,
avitaminosis
and
nutrition,
other dietetic features (ELSDON-DEW, 1959; FEE &
FEDORUK, 1960;
MO&OE,
1976) the organism
produces thrombosis in a small radicle of the portal
vein. A Zahns infarct is the immediate consequence.
This forms an excellent nidus in which the amoebae
grow and a small abscess is formed consisting of
necrotic tissue, a large number of parasites and very
little reactive inflammation.
Splenomegaly and portal hypertension
can be
due either to thrombosis of a large branch of the
hepatic vein or to thrombosis of the portal vein
(GULATI et al., 1967). Hepatic vein thrombosis leads
to congestion and tender enlargement of the liver
and sometimes produces features of acute hepatic
vein thrombosis. The satellite abscess often seen at
a distance from the original large abscess must be
the result of a vascular phenomenon. RANNANVARE
(1969) observed early necrotic lesions with amoebae
in them are not found in the liver in man. We are
in total disagreement with this view. Amoebae
could easily be demonstrated in the early focal
lesion and we have not encountered a single instance
of calcified or encapsulated healed lesions, as
described by RANNANVARE, in the 79 autopsies we
have studied meticulously. Also, we have not been
able to find granuloma with amoebae in it. The
10:; of cases showing granulomatous hepatitis are
possibly due to a non-specific reaction to many
agents entering the portal circulation through the
ulcer bed. Thus the study does not support a
tubercle
or granuloma
as the earliest lesion
(COUNCILMAN
1962).

&

LAFLEUR,

189 1;

DEMICHELE,

The present material

being from autopsies
necessarily deals with the more severe manifestations of the disease. The finding of vascular complications and immunological
aberrations
assumes
considerable significance. It has been possible in
this study to demonstrate objectively some of the
mechanisms of evolution and extension of amoebic
liver abscess. Lastly we should like to emphasize
the important invasive properties of the amoebae
which may be equally relevant in pathogenesis
(EATON et al., 1970).

192

PATHOLOGY

AND PATHOGENBSIS

OF FATAL

Reports, No. 2, P. 395.

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Monroe, L. S. (1976). Amoebiasis. In: Gastroenterology, Vol. 4, Chapter 154. Philadelphia;

W. B. Saunder & Co., p. 195.
Palmer, R. B. (1938). Changes in liver in amoebic
dysentery with special reference to the origin of
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Rannanvare, M. M. (1969). Evolution of amoebic
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Stuart, A. E. (1975). Reticula endothelial system.
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Acta Medica Ztalica. 17. 235.

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N., Tilakos, M. &
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Accepted for publication

CORRIGENDA
Vol.

72, No. 3

p. 243, column 1, References:

Essien, E. S. A. (1977) should read as
follows :
Essien, E. S. (1977). Water supply in rural area: an
experience in Malumfashi. Nigerian Medical
Journal (to be published).
Volume

72, No. 5

pp. i and 467, Authors:

for D. Karamine read D. Katamine
p. 450, column 1, line 37
should read :
PB

a2 n2 r31
r32

121

p. 450, column 2, line 18

should read :

Cl2

PR =Cl

Vol.

c2

73, No. 1

p. 124 Symposium on cholera:

line 5>for he read I

22nd June, 1978.