Amoebic Liver Abscess

MP Sharma*, Vineet Ahuja**

C L I N I C A L M E D I C I N E JIACM 2003; 4(2): 107-11

* Professor, ** Assistant Professor, Department of Gastroenterology,All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029.

The intestinal protozoa have gained importance during

recent years as a result of increasing world travel,

economic globalisation, and the growing number of

chronically immunosuppressed people. AIDS and the

increasing use of organ transplants have led to a new

population at risk for protozoal infection. Protozoa that

infect the gastrointestinal tract include the parasite

Entamoeba histolytica, Giardia lamblia – the most common

cause of waterborne disease outbreaks, and the large

group of spore forming parasites (Cryptosporidia,

Cyclospora, Isospora, and Microsporidia) that share a green

algae symbiont and a predilection for causing chronic

diarrhoea in immunocompromised persons. Of these

intestinal protozoa, Entamoeba histolytica is one of the

most prevalent intestinal protozoa in developing

countries.

Amoebiasis is the infection of the human gastrointestinal

tract by Entamoeba histolytica, a parasite that is capable

of invading the intestinal mucosa and may spread to other

organs, mainly the liver. Entamoeba dispar, an amoeba

morphologically similar to E. histolytica also colonises the

human gut and has been recognised recently as a separate

species with no disease potential1-4. The acceptance of E.

dispar as a distinct but closely related protozoan species

has had a major implication in the epidemiology of

amoebiasis, since most asymptomatic infections are now

attributed to this non-invasive amoeba. E. histolytica

infection may have intestinal as well as extra-intestinal

manifestations (Table I). This review shall address amoebic

liver abscess which is the commonest extra-intestinal

manifestation.

Amoebic liver abscess

It is an inflammatory space- occupying lesion of the liver

caused by Entamoeba histolytica. The incidence of ALA has

been reported to vary between 3% and 9% of all cases of

amoebiasis5. In India ALA is endemic. The diagnosis of this

condition has undergone major changes after the advent

of advances in imaging and molecular biology techniques.

This has also enabled a reappraisal of the disease with

recognition of the wide variety of clinical presentations

and multitude of complications.

Table I : Clinical syndromes associated with E.histolytica infection.

Intestinal amoebiasis

Asymptomatic cyst passers

Acute amoebic colitis

- Mucosal disease

- Transmural disease

- Ulcerative postdysentric colitis

Appendicitis

Amoeboma

Amoebic stricture

Extraintestinal amoebiasis

Amoebic liver abscess

Perforation and peritonitis

Pleuropulmonary amoebiasis

Amoebic pericarditis

Cutaneous amoebiasis

It has been observed that the classical description of an

ALA needs to be modified due to a large number of

patients who present with variants6,7. This may be due to

a better understanding of the pathogenesis and

presentation of the disease or changing patterns of the

disease. Long-term follow up of patients has helped in

identifying the factors affecting the healing pattern.

Separation of patients at high risk is of clinical relevance

so that more aggressive treatment can be instituted.

Clinical presentation

Amoebic liver abscess occurs most commonly in the age

group of 20 to 45 years. It has been noted infrequently at

108 Journal, Indian Academy of Clinical Medicine � Vol. 4, No. 2 � April-June 2003

the extremes of age and is seven to nine times more

common in males. ALA may present as an acute process

or as a chronic indolent disease. It has been classified by

the duration of illness and severity into :

i. Acute – Acute benign

– Acute aggressive

ii. Chronic – Chronic benign

– Chronic accelerated

Most patients present with an acute illness and duration

of symptoms less than 2 weeks. The main presenting

features are abdominal pain, fever, and anorexia.

Abdominal pain is usually moderate and localised to the

right upper quadrant or to the epigastrium. Diffuse

abdominal pain, pleuritic chest pain, and radiation of right

upper quadrant pain to the right shoulder are not

uncommon. Epigastric pain is commonly seen in left lobe

abscesses. Fever is of moderate degree in most instances,

while high fever with chills is suggestive of secondary

bacterial infection. Cough with or without expectoration

and pleuritic chest pain is also seen in ALA.

During the course of illness one-third of patients may

develop clinical jaundice. Severe icterus is usually due to

a large abscess or multiple abscesses, or to an abscess

situated at the porta hepatis8. Jaundice raises diagnostic

problems and brings in the possibilities of intra-hepatic

obstruction or viral hepatitis. Diarrhoea and weight loss

are not commonly seen. Unfortunately diarrhoea is such

a common complaint in the tropics that it may not be

given adequate consideration by the patient. Tender

hepatomegaly is detected in upto 80% of patients. The

liver surface is generally smooth. Upper abdominal

guarding and rigidity is seen in a minority of cases with

features of generalised peritonitis. Toxaemia and

septicaemia may be present.

However, it is the protean manifestations of the variants

that may be a source of consternation to the clinician. A

left lobe abscess may manifest as toxaemia, deep jaundice,

and encephalopathy. Ascites developing in a patients with

ALA suggests development or presence of inferior vena

cava obstruction, and cough with copious expectoration

suggests rupture into the communication with the right

lower lobe bronchus.

Variants9

ALA usually occurs in the right lobe of the liver and is

solitary (30% - 70%). Unusual presentations include

multiple abscesses, left lobe abscesses, abscesses

presenting as compressive lesion, and abscesses rupturing

into viscera. These are clinically important due to the

curable nature of this disease and potentially fatal

outcome in untreated abscesses.

Multiple liver abscesses : Fifteen per cent of patients may

have multiple abscesses. They present with fever, toxaemia,

deep jaundice, and encephalopathy. Toxaemia is

suggestive of an added bacterial infection leading to a

more severe disease. E.coli and Klebseilla are the

commonly cultured organisms. These patients present

with a clinical picture indistinguishable from hepatic

encephalopathy due to acute hepatocellular failure.

Hepatic encephalopathy in ALA patients possibly results

from combination of right hepatic vein occlusion,

pylophlebitis, and occlusion of several portal vein

radicles10,11.

Left lobe abscess : Thirty-five per cent of patients present

with a left lobe abscess. Half of these have associated

lesions in the right lobe while the remaining have solitary

left lobe abscess12. These patients have longer duration of

symptoms (3-4 weeks) and fever is less commonly

observed as compared to right lobe abscesses. It may

present as a large epigastric mass with minimal movement

with respiration. Often, to the clinician’s despair, it has been

confused with pseudocyst of pancreas. These patients also

have weight loss with poor hepatic localisation of

symptoms. Complications like peritonitis and toxaemia are

significantly more common in left lobe abscess. Needle

aspiration may be more rewarding in combination with

anti-amoebic drugs. A high index of suspicion and early

diagnosis are important for proper management.

Compression lesions : A posteriorly located ALA in the

right lobe may present as inferior vena cava

obstruction or hepatic outflow obstruction13. This is

suggested by bilateral pedal oedema, ascites, visible

veins on anterior and posterior abdominal wall, along

with clinical, radiological, and serological features of

ALA. These features disappear after aspiration of the

abscess.

Journal, Indian Academy of Clinical Medicine � Vol. 4, No. 2 � April-June 2003 109

Extension of the abscess : Leakage of the abscess may

occur into the pleural cavity, with empyema thoracis. Intra-

abdominal extension following perforation into the

peritoneal cavity is usually associated with shock and

generalised peritonitis and may occur in upto 7% of cases.

Rupture into the colon and biliary tree has also been

reported. A subhepatic collection may also be localised

and walled off. Such presentations have however been

rare and form a small number of cases in any series in ALA.

The above clinical patterns have been described more

frequently with the routine availability of ultrasound and

serological assays. These clinical variants are important

because of their therapeutic and prognostic significance

with the best outcome occurring in patients with solitary

abscess.

Diagnosis

Ultrasound is very useful for diagnosis of amoebic liver

abscess. The classic appearance is a non-homogeneous,

hypoechoic, round or oval mass with well defined borders.

Complete resolution of an amoebic liver abscess may take

upto two years. Occasionally, percutaneous diagnostic

needle aspiration may be needed to differentiate between

amoebic and pyogenic liver abscess.

Serology : Serum antibodies to amoebae develop only

during E. histolytica infection and not during E. dispar

infection. The absence of serum antibodies to E. histolytica

after 1 week of symptoms is strong evidence against the

diagnosis of invasive amoebiasis of the colon or liver.

Serum antibodies to amoebae are detected in 85-95% of

all patients who present with invasive amoebiasis or liver

abscess. However, as antibodies persist for many years,

ELISA or IHA cannot differentiate acute from remote

infection in areas of high endemicity. Purified native and

recombinant parasitic antigens have been utilised in

serological studies with good results. More than 95% of

the patients with amoebic liver abscess have serum

antibodies to the 170 KD subunit of the galactose

inhibitable adherence lectin. This antigen is highly specific

for differentiating acute phase serum from convalescent

phase serum in areas of high endemicity.

Newer methods : Newer diagnostic strategies involve

detection of protein antigens in faeces or serum by

monoclonal antibodies and detection of parasitic DNA by

use of nucleotide probes and PCR amplification. A

commercial ELISA kit that uses monoclonal antibodies

directed against an amoebic adherence lectin and

accurately differentiates the true pathogen E. histolytica

from E. dispar has recently been developed for clinical

use14. Detection of amoebic lectin antigen in serum

samples from patients with amoebic liver abscess is also

more than 95% sensitive if used prior to treatment with

metronidazole.

Medical therapy

Medical therapy may be instituted using either a single

agent or a combination of drugs for the extra-luminal

parasite. Amoebicidal drugs(Table II) may be classified into

3 groups : luminal, tissue, and mixed amoebicides.

Duodohydroxyquin, diloxanide furoate, and paromomycin

are luminal amoebicides. The amoebicides effective in

tissues are emetine and dehydroemetine, which act in the

liver, intestinal wall; alongwith chloroquine which acts only

in the liver. Emetine and dehydroemetine because of their

cardiotoxicity are currently not used. Amoebicides

effective in both tissues and the intestinal lumen include

nitroimidazole derivatives-metronidazole, tinidazole, and

ornidazole. They are the drugs of choice in invasive

amoebiasis. Oral or intravenous metronidazole or

tinidazole also leads to rapid clinical improvement of

amoebic liver abscess15. This drug should be followed by

a luminally active drug.

Table II : Pharmacotherapy for E. histolytica infection

in adults.

� Intraluminal Diloxanide furoate 500 mg tid X 20 days

infection Paromomycin 30 mg/kg/day X 10 days

(in 3 divided doses)

Iodoquinol 650 mg tid X 20 days

� Invasive Metronidazole 800 mg tid X 5 days

colitis Tinidazole 1 gm bd X 3 days

� Amoebic Metrinidazole 800 mg tid PO X 10 days

liver abscess (500 mg qid IV)

Nitroimidazoles (including metronidazole) are effective

in over 90% of cases. Therapy should continue for at least

10 days. Relapses have been reported with this duration

of therapy and the drug may be administered for upto 3

110 Journal, Indian Academy of Clinical Medicine � Vol. 4, No. 2 � April-June 2003

weeks. The dose of metronidazole is 40 mg/kg/day in

divided dosages. Tinidazole has been used in a dosage of

1.2 g per day for 7 days , but this dosage has not been

firmly established. Chloroquine, emetine, and

dehydroemetine may also be used. Single-agent therapy

with metronidazole yields excellent results and the

alternative toxic drugs are indicated rarely and used

mostly in seriously ill patients when the risk of failure of

therapy is unacceptable. The response to anti-amoebic

drugs is usually evident within 48-72 hours with the

subsidence of toxaemia, abdominal pain, anorexia,

jaundice, guarding, and tenderness in the right

hypochondrium, and hepatomegaly.

Aspiration or drainage of abscess

Routine aspiration of liver abscess is not indicated for

diagnostic or therapeutic purpose16. A combination of

ultrasonographic finding with a positive serology in the

appropriate clinical setting is adequate to start drug

therapy. Aspiration has been indicated in the following

circumstances: lack of clinical improvement in 48-72 hours,

left lobe abscess, thin rim of liver tissue around the abscess

(< 10 mm) and seronegative abscesses17. The aspirate is

anchovy sauce type in half of the patients. The chocolate

colour is due to admixture of blood with liver tissue.

Anti-amoebic therapy alone is as effective as routine

needle aspiration combined with anti-amoebic therapy

in the treatment of patients with uncomplicated amoebic

liver abscess18,19.

Surgical intervention

Open surgical drainage is rarely indicated and may be

required in the setting of a large abscess with a poor yield

on needle aspiration or clinical deterioration despite

attempted needle aspiration, and in complicated ALA.

Surgical mortality is, however, very high. Hence, it should

only be used when the cavity has ruptured into adjacent

viscera or peritoneum.

Long term follow-up

After clinical cure, patients show few symptoms and

sonographic follow-up demonstrates evidence of

persistent hypoechoic lesion20. The mean time for

disappearance of the sonographic abnormality is 6-9

months. Relapses are very uncommon and the

sonographic abnormality does not warrant continued

therapy. The patterns of resolution that have been seen

on sonographic follow-up include: type I, where complete

disappearance of the cavity occurs within 3 months

(29.8%); type II, where a rapid reduction till 25% of the

original cavity size and then a delayed resolution occurs

(5.9%).

Factors influencing healing time include the size of

abscess cavity at admission, hypoalbuminaemia, and

anaemia. The type of clinical presentation, nature of

therapy, number or location of abscesses, and time for

clinical resolution of multiple liver abscesses are similar

to those of solitary abscess and the number of abscesses

does not significantly influence the healing patterns or

rates. The total abscess volume of all the cavities is the

most important factor that influences resolution time in

multiple abscesses. As clinical resolution does not

correlate with ultrasonographic resolution, therefore

clinical criteria, rather than ultrasonography, should

monitor the result of therapy.

Prognostic markers

There are two major categories of patients with ALA: those

with a good prognosis and those with a poor prognosis.

These groups can be easily identified by evaluation of

clinical, biochemical, and sonographic criteria. Bilirubin

level > 3.5 mg/dL, encephalopathy, volume of abscess

cavity, and hypoalbuminaemia (serum albumin level < 2.0

g/dL) are independent risk factors for mortality21. The

duration of symptoms and the type of treatment do not

influence mortality.

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