CLINICAL MEDICINE

JIACM 2003; 4(2): 107-11

Amoebic Liver Abscess MP Sharma*, Vineet Ahuja** 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

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

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

ii.

–

Acute benign

–

Acute aggressive

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.

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.

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.

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.

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.

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.

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Extension of the abscess : Leakage of the abscess may occur into the pleural cavity, with empyema thoracis. Intraabdominal 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

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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 colitis




Amoebic Metrinidazole 800 mg tid PO X 10 days liver abscess (500 mg qid IV)

Metronidazole 800 mg tid X 5 days Tinidazole 1 gm bd X 3 days

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

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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.

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.

References 1.

Anonymous. Entamoeba taxonomy. Bull WHO 1997; 75: 2912.

2.

Clark CG. Entamoeba dispar, an organism reborn. Trans R Soc Trop Med Hyg 1998; 92: 361-4. Diamond LD et al . A redescription of of Entamoeba histolytica Schaudinn, 1903 (emended Walker, 1911) separating it from Entamoeba dispar Brumpt, 1925 J Eukaryot, Microbil. 40: 340-4. Martnez-Palomo A. Parasitic amebas of the intestinal tract, Parasitic Protozoa, eds Kreier JP, Baker JT, Academic Press, San Diego. 1993; 65-141.

3.

Long term follow-up After clinical cure, patients show few symptoms and sonographic follow-up demonstrates evidence of persistent hypoechoic lesion 20 . The mean time for

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5.

Peters RS, Gitlin N, Libke RD. Amebic liver diseases. Ann Rev Med 1982; 32: 161-74.

6.

Sharma MP, Ahuja V. Amoebic liver abscess: clinician’s perspective. Bombay Hosp J 1997; 39: 615-9.

7.

Sharma MP, Dasarathy S, Sushma S, Verma N. Variants of amebic liver abscess. Arch Med Res 1997; 28: S272-73.

8.

Data DV, Saha S, Singh SA, Aikat BK, Chuttani PN. The clinical pattern and prognosis of patients with amebic liver abscess and jaundice. Am J Dig Dis 1973; 18: 883-98.

16. Sharma MP, Rai RR, Acharya SK.Needle aspiration in amoebic liver abscess. Br Med J 1989; 299: 1309-9.

9.

Sharma MP, Sarin SK. Amoebic liver abscess in a north Indian hospital – current trends. Br J Clin Pract 1987; 41: 789-93.

17. Dela Rey Nel J, Simjee AE, Patel A. Indication for aspiration of amoebic liver abscess. S Afr Med J 1989; 75: 373-6.

10. Sharma MP,Verma N, Acharya SK. Clinical profile of multiple liver abscesses. J Assoc Physicians India 1990; 38: 837-9.

18. Sharma MP, Dasarathy S. Amoebic liver abscess. Trop Gastroenterol 1993; 14: 3-9.

11. Kapoor OP, Joshi R. Multiple amoebic liver abscess. A study of 56 cases. J Trop Med Hyg 1992; 75: 4-6.

19. Sharma MP, Ahuja V. Management of amebic liver abscess. Arch Med Res 2000; 31: S4-5.

12. Sharma MP, Sarin SK, Acharya SK. Left lobe amebic abscess of liver – A distinct clinical entity. J Assoc Physicians India 1984; 32: 477.

20. Sharma MP, Dasarathy S, Sushma S, Verma N. Long term follow up of amoebic liver abscess: clinical and ultrasound patterns of resolution. Trop Gastroenterol 1995; 16: 24-8.

13. Sharma MP, Sarin SK. Interior vena caval obstruction due to amoebic liver abscess. J Assoc Physicians India 1990; 30: 243.

21. Sharma MP, Dasarathy S, Verma N, Sushma S, Shukla DK. Prognostic markers in amebic liver abscess: a prospective study. Am J Gastroenterol 1996; 91: 2584-8.

14. Haque R et al. Diagnosis of amebic liver abscess and

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intestinal infection with the TechLab Entamoeba histolytica II antigen detection and antibody tests. J Clin Microbiol 2000; 38: 3235-9. 15. Irusen EM et al. Asymptomatic intestinal colonisation by pathogenic Entamoeba histolytica in amebic liver abscess : prevalence, response to therapy and pathogenic potential. Clin Infect Dis 1992; 14: 889-93.

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