Liver abscess in children
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《美国医学杂志》
Department of Gastroenterology, Rockland Hospital, New Delhi, India
Abstract
Liver abscesses are frequently observed in pediatric clinical practice in tropics and subtropics especially in developing countries. Children have unique set of predisposing factors which have been highlighted. Expected microbiology and setting for unusual organisms are mentioned. Clinical presentations', including importance of location and number of abscesses has been discussed. Role of each modality of treatment clarified. Importance and limitations of investigations and imaging explained, and complications and mortality discussed.
Keywords: Liver abscesses; Predisposing causes; Clinical signs and symptoms
Children with liver abscesses constitute more than 79 per 100,000 pediatric admissions(<12 yrs age) in tertiary care centres in India.[1] In larger series from developing nations(Brazil) it is documented in frequency of approximately 1 out of 140 admissions.[2] However in developed countries it is rare with an incidence of 25 per 100,000 admissions in USA[3] to 11 out of 100,00,00 admissions in Denmark.[4] It is a cause of significant morbidity and mortality. For unknown reasons male children akin to male adults are affected by liver abscesses more than female children.[2],[5]
Predisposing causes of Liver abscesses
Children have unique set of predisposing causes for liver abscesses.
Parasitic Infestations : Parasitic infestations are thought to predispose to pyogenic liver abscesses in children. Almost all parasites including ascariasis, schistosomiasis, fascioliasis, trichuris trichura, necator, ancylostoma and toxocara infestation have been reported as association. Significant increased parasitic infestation has been demonstrated in children with pyogenic liver abscesses when compared with controls from similar background.[6] Experimental studies have shown that bacteremia specially from Staphylococcus species in presence of parasitic infestation predisposes to liver abscess formation.[7] Salmonella More Details infection has also been associated with parasitosis. The pathogenic mechanism is thought to be stimulation of T2 immunity in patients with worm infestations. This is hypothesized to suppress the T1 effector limb thereby compromising phagocyte handling of bacteria and also fungi. This apart, liver granulomas around parasites, their larvae and eggs are believed to trap bacteria in the grannulomatous reaction around them serving as nidus. Tissues from liver biopsies or surgical and autopsy specimens in patients with liver abscesses have documented eggs, larvae, and antigens of parasites.[8],[9] Laboratory clue to an underlying parasitosis is often a peripheral eosinophilia (40% patients), hyper IgE levels, antibodies to various parasites and detection of eggs and larvae in stool. Sometimes tropical myositis may point towards a Toxocara infestation. Appropriate tests are therefore recommended to ascertain such infestation and follow up treatment should be done. Biliary ascariasis associated with cholangitis and liver abscesses continue to be common in endemic areas[2] and in India in Kashmir valley.[10]
Genetic Disorders : (1) Papillon-Leferve syndrome is a rare autosomal recessive disease comprising palmoplantar keratoderma and periodontitis. Pyogenic liver abscess is an increasingly recognized complication.[11]
(2) Chronic Grannulomatous Disease (CGD) is a rare inherited primary immunodeficiency where phagocytes cannot destroy catalase -positive bacteria and Fungi. Defect in phagocytic cells' respiratory bursts lead to life threatening infections including liver abscesses. Fever is the most common presenting symptom. These abscesses are often recurrent, multiple and difficult to treat. Mean age of first abscesses is often mid teens. Commonest micro-organism is staphylococus though gram negative rods, nocardia and fungal infections are also reported. Often surgical resection is more rewarding than percutaneous drainage.[12] Interferon gama therapy may have a role in resistant cases.
(3). Infections and liver abscess has been reported in children with deficiencies in C1 complement. (4). Hyper Immunoglobulin E syndrome is associated with recurrent abscesses involving several organs including liver.
Skin infections : Skin infections are common in children.These provide a source of bacteremia and inoculation of infection in liver. Significant co-relations have been documented between pyogenic liver abscesses and skin infections in some large series of children with liver abscesses.[2],[8] Predominant organism is Staphylococcus aureus. Chromobacterium violaceum in tropics and subtropics can present as skin and liver infection.
Protein Calorie malnutrition : There is likelihood of co-relation with liver abscesses and malnutrition in children. Liver abscesses in children are rare in developed countries whereas they are common in developing countries. Though studies have observed significant proportion of malnutrition in children with liver abscesses,[1],[13] comparision with disease controls in same centres have not given a clear association.[14]
Abdominal infections and Liver abscesses : At the beginning of this century portal route of entry of infections constituted a large proportion of patients with liver abscesses. However this has declined, with increasing ease of diagnosing such infections and treating them. However case reports[15] and series[16] are still published, emphasizing their importance. Previous portal vein catheterization also can predispose to portal pyaemia and liver abscesses. Choledochal cysts can predispose to recurrent cholangitis and liver abscesses in children.[16] Similarly congenital hepatic fibrosis can predispose to cholangitis and liver abscesses.
Post trauma : Trauma predisposes to liver abscesses both by direct injury to liver or by providing habitat for proliferation of organisms elsewhere. Child abuse can sometimes be the cause of sepsis and liver abscesses.[17] Unusual organisms like clostridia can flourish and this needs to be kept in mind.[18]
Microbiology of Liver abscesses
Most of the liver abscesses in children are pyogenic in nature with amoebic liver abscesses constituting 21-30% of cases[13],[20],[21] or more (50%).[22] However in an appropriate epidemiological setting one may see cases of amoebic liver abscesses presenting as neonatal sepsis.[23] Among cases of pyogenic liver abscesses, Staphylococcus is the leading cause in most series.[1],[2],[3],[5],[7],[12],[13],[21] Anaerobes constitute an important proportion of upto 30% of organisms[3],[4],[24] and include microaerophilic streptococci. Gram negative rods like E. coli,[5],[22] and klebsiella[25] are common isolates as are other enterobacter species[4].
Unusual micro-organisms : Fungal hepatic microabscesses either alone or in association with spleenic microabscesses may occur in children with acute leukemia.[26]
Tubercular liver abscesses are rare but are known to occur.[20],[27]
Typhoid fever can have associated hepatic abscesses[28] and in an appropriate setting, cat scratch disease, Brucella More Details, meliodosis, can all be suspected as cause of hepatic and spleenic abscesses usually associated with a systemic dissemination of infection.
Location and number of Liver abscesses : Irrespective of any etiology most of liver abscesses(approx 2/3rd) occur in the right lobe of liver and majority(approx 2/3rd) are solitary.[1],[5],[22],[29],[30],[31],[32] Left lobe abscesses should be treated with caution as they are frequently associated with complications like rupture into peritoneum and pericardium and cause pericardial effusions[29] each of which may be life threatening. Left sided liver abscesses require drainage far more often (85% cases) when compared to right sided lesions[21],[29], even when aetiology is amoebic.[33] Multiple liver abscesses constitute 20- 25 % of all cases.[1],[29],[34] Majority ie 2/3rd of multiple pyogenic liver abscesses are confined to right side of liver.[21] With multiple liver abscesses mortality may be almost twice that in solitary cases.[34] Even patients with amoebic multiple liver abscesses have more complications and mortality.[33] We found in our study that severe clinical presentation, jaundice and left lobe hepatomegaly were markers for multiple amoebic liver abscesses.[35]
Clinical Presentation Signs and Symptoms
Irrespective of pyogenic or amoebic aetiology,fever often with chills, abdominal pain specially in right upper quadrant and tender hepatomegaly are common presenting signs and symptoms.[1],[22],[25],[36] Nausea and vomitings, anorexia, unexplained anemia, and cough with breathing difficulty[37] or simply fever are other common complaints. Whereas fever is the most common symptom in children, afebrile presentations of liver abscesses specially of amoebic aetiology are well known in series of mixed age groups.[38] In one series of amebic liver abscesses, majority i.e. 58% of patients had subacute presentation with right upper quadrant dullache, weight loss, fatigue, anemia and low to moderate grade fever.[29] On the other hand liver abscesses may present as fulminant sepsis[23] or acute abdomen.[39] Clinical presentations do not distinguish amoebic from a bacterial etiology unless there is an obvious precipitating source for eg. abdominal infections. It is uncommon to get a positive history of colitic diarrhoea from patients of amebic liver abscesses.
Investigations
Anemia, leucocytosis and raised sedimentation rates are usual findings on hemogram. Altered liver enzymes specially alkaline phosphatase point to liver as an involved organ. Majority of children have a prolonged prothrombin time.[22] All of these set of investigations do not differentiate amoebic from pyogenic. Blood cultures must be sent but they have lower sensitivity than pus aspirate cultures in identification of culprit organism in pyogenic abscesses.[4],[25] Aspiration of pus for amebic trophozoites is often not helpful[39] in clinching an amebic etiology. However, indirect hemagglutination antibody titres in blood is sensitive in detecting systemic amoebic infection.[40] Indirect fluorescent antibody and ELISA tests are also very useful. Negative amebic serology points strongly to a pyogenic source of infection.
Imaging
Role of USG : USG is the imaging of first choice. It is quick, safe, cheap, and accurate in picking a liver lesion. Appearances of an abscess may be a rounded or an oval lesion which is usually hypoechoic but may have heterogenous echotexture. A solid or heterogenous lesion often evolves into a hypoechoic lesion on subsequent examination.[30] Majority of the abscess have a well defined wall which may be thin or irregular. USG may reveal an intra-abdominal precipitating cause for liver abscess. However USG may miss very small abscesses or abscesses lying in areas of liver difficult to examine when patient co-operation is poor.
Role of CT : CECT is more sensitive in detecting even small abscesses anywhere in liver. Yet it is inconvenient and expensive with risk of contrast nephropathy being always there. A hypo dense lesion with low attenuation areas and an enhancing rim is a classical CECT image. Small hypo echoic lesions in cluster may suggest a beginning of process of coalescence into a single large abscess later.
Role of MRI : Liver abscesses on MRI appear hypo intense on T1 weighted and hyper intense in T2 weighted sequences. On gadolinium enhanced sequences there is early and continued enhancement of wall which persists on delayed images. There is increased peri-abscess tissue enhancement in immediate post-gadolinium images.[41] With all the inconveniences of time and cost attached to MRI, it is at its best of same capability as CECT.
Role of Scintigraphy : If ambiguity arises in diagnosis in an occasional patient with conventional imaging, scintigraphy may help. 111 In labeled leukocyte scintigraphy (ILLS) which shows abscesses as 'hot spots' superimposed on 99mTc labelled scintigraphy which shows abscesses as 'cold spots' are of value in establishing a diagnosis.[42]
Resolution and follow up of abscess on imaging : Of all imaging modalities, USG is best for follow up, although it is not routinely necessary. The abscess cavity takes many months to finally resolve and lags behind clinical resolution by months.[31],[43] Resolution time depends on abscess size, but hypoalbuminemia and anemia at presentation were also found important in our study.[43] It is not at all necessary to retreat or continue treating a clinically quiescent patient with a visible cavity on imaging. Recurrences are rare for amoebic liver abscesses.[44] Recurrences are observed with pyogenic liver abscesses[4] most of which occur within 3 months of treatment. There may be an underlying problem like CGD predisposing recurrence.
Treatment
Medical therapy : At presentation, it is important to resuscitate a sick septic patient with I.V. fluids and other supportive measures. Appropriate analgesics may be essential but NSAIDs should be avoided if intervention is planned. A combination of anti-staphylococcal drug like cloxacillin, an anti-anerobic and anti-amebic drug like metronidazole and an aminoglycoside or cephalosporin for gram negative bacilli is a good initial choice. Therapeutic drainage is not a must in all cases of pyogenic liver abscesses.[1] However experiences with most series suggest that 80-90% pyogenic liver abscesses require some form of drainage.[22],[34] Medical antibiotic cover is additionally required for a period of 3-4 weeks.
95% of amebic abscesses do well on medical therapy alone[44],[45]and require therapy with nitroimidazoles for a total duration of ten days only. Metronidazole is the drug of choice. Oral dose is 30-50mg/kg/d, and i.v. dose is 7.5 mg/Kg/dose 6th hourly.
Role of aspiration : Aspiration is safe, is helpful in diagnosis of abscess and provides material for microbiological assessment. Abscess aspiration (sometimes repeated) in combination with antibiotics has been successfully tried worldwide. In pyogenic liver abscesses, aspiration along with antibiotics help[4],[22] and reasonable results can be achieved. This strategy has been reported to be helpful in amoebic liver abscesses too[46] but in a randomized trial conducted by us, we did not find any added benefit of aspiration in uncomplicated amoebic abscesses[44]. Aspiration must be attempted in solitary,unilocular lesions and on carefully selected patients but if sepsis persists, prompt drainage is required.
Role of percutaneous drainage : Percutaneous drainage has now come to a centrestage in management of liver abscesses that require more than just a medical management. Safety and efficacy of percutaneous abscess drainage in selected patients is now well established. Even multiloculated liver abscesses can be managed with aggressive percutaneous techniques that include disruption of loculations and placement of large bore sump catheters. Percutaneous drainage is indicated when
(a) Volume of abscess is large and there is risk of spontaneous rupture(specially left lobe abscesses). (b) When actual rupture has occurred, then along with abscess cavity drainage of extraneous collection. (c) When there is lack of response to medical therapy with clinical signs of persistent sepsis or enlarging abscesses, or persistent symptoms. (d) When there is evidence of liver failure.
Absence of a secure route is the only contraindication . Good results have been reported in series on children[3],[4],[25]. Failure is mostly due to technical causes like (a) Inappropriate approach into a non- dependant portion of cavity. (b) Failure to recognize and respond to septation. and (c) Premature withdrawal of drains[47]. Catheters should be withdrawn once there is negligible(<10 ml) pus drain per day and when patient is apyrexic. Complications are bacteremia, and bleed externally or into the peritoneum or GIT (haemobilia), and sometimes iatrogenic superinfection.
Role of surgery : Presently surgical drainage is usually reserved for patients ( a ) who have failed percutaneous drainage, ( b ) those who require management for an underlying abdominal problem, ( c ) selected patients with multiple macroscopic abscesses, ( d ) those on steroids and ( e ) patients with ascites.
Transperitoneal approach is the usual method used. This is because the entire liver can be exposed, best drainage site can be determined, multiple abscesses identified with an intraoperative USG, and entire abdomen explored for the primary source of infection. Good results with a low mortality has been reported in literature.[21]
Morbidity and Mortality
Complications : List of possible complications are long. However pleuro- pulmonary complications are the commonest.[48] It may be in form of pleural effusion, empyema, pneumonitis, and hepatopleural or hepato-bronchial fistula. Other complications may be in form of ascites, Budd-Chiari syndrome More Details, intraperitoneal rupture of abscess and peritonitis, intrapericardial rupture, pericardial efusion, septic shock, hemobilia and Jaundice. Rare complication like perforations into a hollow viscus like colon, stomach and duodenum and cerebral amoebiasis are also reported.
Markers of early detection of complications : Patients who present with jaundice, large or multiple abscesses, acute abdomen, liver failure and sepsis have complications more often.[49]
Mortality : Facility of prompt diagnosis with imaging, percutaneous drainage, and better antibiotics have remarkably improved survival in the last three dacades[3]. With modern management most of the series have a mortality of less than 15%.[1],[3],[10],[13],[29],[49]
Markers for mortality : In our study on patients with amoebic liver abscesses, bilirubin levels>3.5 mg/dl, encephalopathy, volume of abscess cavity, number of abscesses, and hypoalbuminemia(<2 gm/dl) were independent risk factors for mortality.[50]
References
1. Kumar A, Srinivasan S, Sharma AK. Pyogenic liver abscess in children-South Indian experiences. J Pediatr Surg 1998 Mar; 33(3) : 417-421.
2. Ferreira MA, Pereira FE, Musso C, Dettogni RV. Pyogenic liver abscess in children: some observations in the Espirito Santo State. Brazil Arq Gastroenterol 1997 Jan-Mar;34(1) : 49-54.
3. Pineiro-Carrero VM, Andres JM. Morbidity and mortality in children with pyogenic liver abscess. Am J Dis Child 1989 Dec; 143(12) : 1424-1427.
4. Hansen PS, Schonheyder HC. Pyogenic hepatic abscess. A 10-year population-based retrospective study. APMIS 1998 Mar;106(3) : 396-402.
5. Wang DS,Chen DS,Wang YZ,Li JS.Bacterial liver abscess in children. J Singapore Paediatric Soc 1989; 31(1-2) : 75-78.
6. Moreira-Silva SF, Leite AL, Brito EF, Pereira F.Nematode infections are risk factors for staphylococcal infection in children. Mem Inst Oswaldo Cruz 2002 Apr; 97(3) : 395-399.
7. Teixeira R, Ferreira MD, Coelho PM, Filho GB, Azevedo Junior GM, Lambertucci JR. Pyogenic liver abscesses and acute schistosomiasis mansoni: report on 3 cases and experimental study. Trans R Soc Trop Med Hyg 1996 May-Jun; 90(3) : 280-283.
8. Teixeira R, Pfeilsticker FJ, Santa Cecilia GD, Nobre V, Fonseca LP et al. Schistosomiasis mansoni is associated with pyogenic liver abscesses in the state of Minas Gerais, Brazil. Mem Inst Oswaldo Cruz 2001; 96 Suppl : 143-146.
9. Pereira FE, Musso C, Castelo JS. Pediatr Dev Pathol 1999 Nov-Dec;2(6) : 537-543. Pathology of pyogenic liver abscess in children.
10. Javid G, Wani NA, Gulzar GM, Khan BA, Shah AH et al. World J Surg. 1999 Nov;23(11):1191-4. Ascaris-induced liver abscess.
11. Almuneef M, Al Khenaizan S, Al Ajaji S, Al-Anazi A. Pyogenic liver abscess and Papillon-Lefevre syndrome: not a rare association. Pediatrics 2003 Jan; 111(1) : e85-88.
12. Lublin M, Bartlett DL, Danforth DN, Kauffman H, Gallin JI, et al. Hepatic abscess in patients with chronic granulomatous disease. Ann Surg 2002 Mar;235(3) : 383-391.
13. Hendricks MK, Moore SW, Millar AJ. Epidemiological aspects of liver abscesses in children in the Western Cape Province of South Africa. J Trop Pediatr 1997 Apr;43(2) : 103-105.
14. Moreira-Silva SF, Pereira FE. Intestinal nematodes, Toxocara infection, and pyogenic liver abscess in children: a possible association. J Trop Pediatr 2000 Jun;46(3) : 167-172.
15. Chang TN, Tang L, Keller K, Harrison MR, Farmer DL, Albanese CT. Pylephlebitis, portal-mesenteric thrombosis, and multiple liver abscesses owing to perforated appendicitis. J Pediatr Surg 2001 Sep;36(9):E19.
16. Slovis TL, Haller JO, Cohen HL, Berdon WE, Watts FB Jr. Complicated appendiceal inflammatory disease in children: pylephlebitis andliver abscess. Radiology 1989 Jun;171(3) : 823-825.
17. Muramatsu Y, Watanabe Y, Fujiwara K, Kazuta K, Soga K et al. Rinsho Hoshasen. 1990 Jun;35(6):761-4. A case of congenital choledochal cyst with prehepatic portal occlusion, liver abscess, and cholelithiasis.
18. Van Dyke DC, Alexander RC, Perlman S, Smith WJ Jr, Dekowski SA. Metastases with osteomyelitis and hepatic abscess occurring in a chaotic family.Fusiform bacterial sepsis. Clin Pediatr (Phila). 1989Sep;28(9) : 423-425.
19. Nachman S, Kaul A, Li KI, Slim MS, San Filippo JA et al. Liver abscess caused by Clostridium bifermentans following blunt abdominal trauma. J Clin Microbiol 1989 May;27(5) : 1137-1138.
20. Guittet V, Menager C, Missotte I, Duparc B, Verhaegen F et al. Hepatic abscesses in childhood: retrospective study about 33 cases observed in New-Caledonia between 1985 and 2003. Arch Pediatr. 2004 Sep;11(9) : 1046-1053.
21. Moore SW, Millar AJ, Cywes S. Conservative initial treatment for liver abscesses in children. Br J Surg 1994 Jun;81(6): 872-874.
22. de Kolster CE, Guerreiro N, de Escalona L, Perdomo G, Marquez R et al. Hepatic abscess in children: analysis of 20 cases. G E N. 1990 Jul-Sep;44(3) : 221-226.
23. Nazir Z, Qazi SH. Amebic liver abscesses among neonates can mimic bacterial sepsis. Pediatr Infect Dis J 2005 May;24(5) : 464-466.
24. Brook I, Fraizer EH. Role of anaerobic bacteria in liver abscesses in children. Pediatr Infect Dis J 1993 Sep;12(9):743-7
25. Tsai CC, Chung JH, Ko SF, Liu PM, Su CT et al. Liver abscess in children: a single institutional experience in southern Taiwan. Acta Paediatr Taiwan 2003 Sep-Oct;44(5) : 282-286.
26. Maxwell AJ, Mamtora H. Fungal liver abscesses in acute leukaemia-a report of two cases. Clin Radiol 1988 Mar;39(2) : 197-201.
27. Essop AR, Segal I, Posen J, Noormohamed N. Tuberculous abscess of the liver. A case report. S Afr Med J 1983 May 21; 63(21) : 825-826.
28. Kumar A, Kapoor R, Chopra K, Sethi GR, Saha MM. Typhoid fever. Unusual hepatic manifestations. Clin Pediatr (Phila). 1989 Feb; 28(2) : 99-100.
29. Moore SW, Lakhoo K, Millar AJ, Cywes S. Left-sided liver abscess in childhood. S Afr J Surg 1994 Dec;32(4) : 145-148.
30. Ahmed L, el Rooby A, Kassem MI, Salama ZA, Strickland GT. Ultrasonography in the diagnosis and management of 52 patients with amebic liver abscess in Cairo. Rev Infect Dis 1990 Mar-Apr;12(2) : 330-337.
31. Ahmed L, Salama ZA, el Rooby A, Strickland GT. Ultrasonographic resolution time for amebic liver abscess. Am J Trop Med Hyg 1989 Oct;41(4) : 406-410.
32. Sharma MP, Dasarathy S, Sushma S, Verma. Long term follow-up of amebic liver abscess: clinical and ultrasound patterns ofresolution. Trop Gastroenterol 1995 Jul-Sep; 16(3) : 24-28.
33. Munoz LE, Botello MA, Carrillo O, Martinez AM. Early detection of complications in amebic liver abscess. Arch Med Res 1992; 23(2) : 251-253.
34. Huang C-J, Pitt HA, Lipsett PA et al. Pyogenic hepatic abscess. Ann Surg 1996; 223 : 600.
35. Sharma MP, Acharya SK, Verma N, Dasarathy S. Clinical profile of multiple amoebic liver abscesses. J Assoc Physicians India. 1990 Nov; 38(11) : 837-839.
36. Nazir Z, Moazam F. Amebic liver abscess in children.Pediatr Infect Dis J 1993 Nov;12(11) : 929-932.
37. Haffar A, Boland FJ, Edwards MS. Amebic liver abscess in children. Pediatr Infect Dis 1982 Sep-Oct;1(5) : 322-327.
38. Gupta RK. Amebic liver abscess: a report of 100 cases. Int Surg 1984 Jul-Sep; 69(3) : 261-264.
39. Ajao OG, Adebo OA. Unruptured amoebic liver abscess presenting as acute abdomen. Trop Doct 1983 Jul; 13(3): 109-111.
40. Hossain A, Bolbol AS, Chowdhury MN, Bakir TM. Indirect hae-m-a-g-glutination (IHA) test in the serodiagnosis of amebiasis. J Hyg Epidemiol Microbiol Immunol 1989; 33(1) : 91-97.
41. Balci NC, Semelka RC, Noone TC, Siegelman ES, de Beeck BO et al. Pyogenic hepatic abscesses: MRI findings on T1- and T2-weighted and serial gadolinium-enhanced gradient-echo images. J Magn Reson Imaging 1999 Feb; 9(2) : 285-290.
42. Terauchi T, Uno K, Ozaki M, Arimizu N. Usefulness of 111In labeled leukocytes scintigraphy combined with 99mTc phytate liver scintigraphy for diagnosis of hepatic abscess comparing with CT and US. Nippon Igaku Hoshasen Gakkai Zasshi 1992 Apr 25;52(4) : 491-496.
43. Sharma MP, Dasarathy S, Sushma S, Verma N. Long term follow-up of amebic liver abscess: clinical and ultrasound patterns of resolution. Trop Gastroenterol 1995 Jul-Sep; 16(3) : 24-28.
44. Sharma MP, Rai RR, Acharya SK, Ray JC, Tandon BN. Needle aspiration of amoebic liver abscess. BMJ 1989 Nov 25;299(6711) : 1308-1309.
45. Omanga U, Mashako M. Amoebic liver abscess in children (study of 47 cases observed from 1964 to 1979. Med Trop (Mars). 1981 Jul-Aug;41(4) : 425-430.
46. Mehnaz A, Ali SM. Liver abscess in children-not an uncommon problem. J Pak Med Assoc 1991 Nov;41(11) : 273-275.
47. Lang EK, Springer RM, Glorioso LW 3rd, Cammarata CA. Abdominal abscess drainage under radiologic guidance: causes of failure. Radiology 1986 May;159(2) : 329-336.
48. Lyche KD, Jensen WA, Kirsch CM, Yenokida GG, Maltz GS et al. Pleuropulmonary manifestations of hepatic amebiasis. West J Med 1990 Sep;153(3) : 275-278.
49. Munoz LE, Botello MA, Carrillo O, Martinez AM. Arch Med Res 1992; 23(2) : 251-253. Early detection of complications in amebic liver abscess.
50. Sharma MP, Dasarathy S, Verma N, Saksena S, Shukla DK. Prognostic markers in amebic liver abscess: a prospective study. Am J Gastroenterol 1996 Dec; 91(12) : 2584-2588.(Sharma MP, Kumar Arvind)
Abstract
Liver abscesses are frequently observed in pediatric clinical practice in tropics and subtropics especially in developing countries. Children have unique set of predisposing factors which have been highlighted. Expected microbiology and setting for unusual organisms are mentioned. Clinical presentations', including importance of location and number of abscesses has been discussed. Role of each modality of treatment clarified. Importance and limitations of investigations and imaging explained, and complications and mortality discussed.
Keywords: Liver abscesses; Predisposing causes; Clinical signs and symptoms
Children with liver abscesses constitute more than 79 per 100,000 pediatric admissions(<12 yrs age) in tertiary care centres in India.[1] In larger series from developing nations(Brazil) it is documented in frequency of approximately 1 out of 140 admissions.[2] However in developed countries it is rare with an incidence of 25 per 100,000 admissions in USA[3] to 11 out of 100,00,00 admissions in Denmark.[4] It is a cause of significant morbidity and mortality. For unknown reasons male children akin to male adults are affected by liver abscesses more than female children.[2],[5]
Predisposing causes of Liver abscesses
Children have unique set of predisposing causes for liver abscesses.
Parasitic Infestations : Parasitic infestations are thought to predispose to pyogenic liver abscesses in children. Almost all parasites including ascariasis, schistosomiasis, fascioliasis, trichuris trichura, necator, ancylostoma and toxocara infestation have been reported as association. Significant increased parasitic infestation has been demonstrated in children with pyogenic liver abscesses when compared with controls from similar background.[6] Experimental studies have shown that bacteremia specially from Staphylococcus species in presence of parasitic infestation predisposes to liver abscess formation.[7] Salmonella More Details infection has also been associated with parasitosis. The pathogenic mechanism is thought to be stimulation of T2 immunity in patients with worm infestations. This is hypothesized to suppress the T1 effector limb thereby compromising phagocyte handling of bacteria and also fungi. This apart, liver granulomas around parasites, their larvae and eggs are believed to trap bacteria in the grannulomatous reaction around them serving as nidus. Tissues from liver biopsies or surgical and autopsy specimens in patients with liver abscesses have documented eggs, larvae, and antigens of parasites.[8],[9] Laboratory clue to an underlying parasitosis is often a peripheral eosinophilia (40% patients), hyper IgE levels, antibodies to various parasites and detection of eggs and larvae in stool. Sometimes tropical myositis may point towards a Toxocara infestation. Appropriate tests are therefore recommended to ascertain such infestation and follow up treatment should be done. Biliary ascariasis associated with cholangitis and liver abscesses continue to be common in endemic areas[2] and in India in Kashmir valley.[10]
Genetic Disorders : (1) Papillon-Leferve syndrome is a rare autosomal recessive disease comprising palmoplantar keratoderma and periodontitis. Pyogenic liver abscess is an increasingly recognized complication.[11]
(2) Chronic Grannulomatous Disease (CGD) is a rare inherited primary immunodeficiency where phagocytes cannot destroy catalase -positive bacteria and Fungi. Defect in phagocytic cells' respiratory bursts lead to life threatening infections including liver abscesses. Fever is the most common presenting symptom. These abscesses are often recurrent, multiple and difficult to treat. Mean age of first abscesses is often mid teens. Commonest micro-organism is staphylococus though gram negative rods, nocardia and fungal infections are also reported. Often surgical resection is more rewarding than percutaneous drainage.[12] Interferon gama therapy may have a role in resistant cases.
(3). Infections and liver abscess has been reported in children with deficiencies in C1 complement. (4). Hyper Immunoglobulin E syndrome is associated with recurrent abscesses involving several organs including liver.
Skin infections : Skin infections are common in children.These provide a source of bacteremia and inoculation of infection in liver. Significant co-relations have been documented between pyogenic liver abscesses and skin infections in some large series of children with liver abscesses.[2],[8] Predominant organism is Staphylococcus aureus. Chromobacterium violaceum in tropics and subtropics can present as skin and liver infection.
Protein Calorie malnutrition : There is likelihood of co-relation with liver abscesses and malnutrition in children. Liver abscesses in children are rare in developed countries whereas they are common in developing countries. Though studies have observed significant proportion of malnutrition in children with liver abscesses,[1],[13] comparision with disease controls in same centres have not given a clear association.[14]
Abdominal infections and Liver abscesses : At the beginning of this century portal route of entry of infections constituted a large proportion of patients with liver abscesses. However this has declined, with increasing ease of diagnosing such infections and treating them. However case reports[15] and series[16] are still published, emphasizing their importance. Previous portal vein catheterization also can predispose to portal pyaemia and liver abscesses. Choledochal cysts can predispose to recurrent cholangitis and liver abscesses in children.[16] Similarly congenital hepatic fibrosis can predispose to cholangitis and liver abscesses.
Post trauma : Trauma predisposes to liver abscesses both by direct injury to liver or by providing habitat for proliferation of organisms elsewhere. Child abuse can sometimes be the cause of sepsis and liver abscesses.[17] Unusual organisms like clostridia can flourish and this needs to be kept in mind.[18]
Microbiology of Liver abscesses
Most of the liver abscesses in children are pyogenic in nature with amoebic liver abscesses constituting 21-30% of cases[13],[20],[21] or more (50%).[22] However in an appropriate epidemiological setting one may see cases of amoebic liver abscesses presenting as neonatal sepsis.[23] Among cases of pyogenic liver abscesses, Staphylococcus is the leading cause in most series.[1],[2],[3],[5],[7],[12],[13],[21] Anaerobes constitute an important proportion of upto 30% of organisms[3],[4],[24] and include microaerophilic streptococci. Gram negative rods like E. coli,[5],[22] and klebsiella[25] are common isolates as are other enterobacter species[4].
Unusual micro-organisms : Fungal hepatic microabscesses either alone or in association with spleenic microabscesses may occur in children with acute leukemia.[26]
Tubercular liver abscesses are rare but are known to occur.[20],[27]
Typhoid fever can have associated hepatic abscesses[28] and in an appropriate setting, cat scratch disease, Brucella More Details, meliodosis, can all be suspected as cause of hepatic and spleenic abscesses usually associated with a systemic dissemination of infection.
Location and number of Liver abscesses : Irrespective of any etiology most of liver abscesses(approx 2/3rd) occur in the right lobe of liver and majority(approx 2/3rd) are solitary.[1],[5],[22],[29],[30],[31],[32] Left lobe abscesses should be treated with caution as they are frequently associated with complications like rupture into peritoneum and pericardium and cause pericardial effusions[29] each of which may be life threatening. Left sided liver abscesses require drainage far more often (85% cases) when compared to right sided lesions[21],[29], even when aetiology is amoebic.[33] Multiple liver abscesses constitute 20- 25 % of all cases.[1],[29],[34] Majority ie 2/3rd of multiple pyogenic liver abscesses are confined to right side of liver.[21] With multiple liver abscesses mortality may be almost twice that in solitary cases.[34] Even patients with amoebic multiple liver abscesses have more complications and mortality.[33] We found in our study that severe clinical presentation, jaundice and left lobe hepatomegaly were markers for multiple amoebic liver abscesses.[35]
Clinical Presentation Signs and Symptoms
Irrespective of pyogenic or amoebic aetiology,fever often with chills, abdominal pain specially in right upper quadrant and tender hepatomegaly are common presenting signs and symptoms.[1],[22],[25],[36] Nausea and vomitings, anorexia, unexplained anemia, and cough with breathing difficulty[37] or simply fever are other common complaints. Whereas fever is the most common symptom in children, afebrile presentations of liver abscesses specially of amoebic aetiology are well known in series of mixed age groups.[38] In one series of amebic liver abscesses, majority i.e. 58% of patients had subacute presentation with right upper quadrant dullache, weight loss, fatigue, anemia and low to moderate grade fever.[29] On the other hand liver abscesses may present as fulminant sepsis[23] or acute abdomen.[39] Clinical presentations do not distinguish amoebic from a bacterial etiology unless there is an obvious precipitating source for eg. abdominal infections. It is uncommon to get a positive history of colitic diarrhoea from patients of amebic liver abscesses.
Investigations
Anemia, leucocytosis and raised sedimentation rates are usual findings on hemogram. Altered liver enzymes specially alkaline phosphatase point to liver as an involved organ. Majority of children have a prolonged prothrombin time.[22] All of these set of investigations do not differentiate amoebic from pyogenic. Blood cultures must be sent but they have lower sensitivity than pus aspirate cultures in identification of culprit organism in pyogenic abscesses.[4],[25] Aspiration of pus for amebic trophozoites is often not helpful[39] in clinching an amebic etiology. However, indirect hemagglutination antibody titres in blood is sensitive in detecting systemic amoebic infection.[40] Indirect fluorescent antibody and ELISA tests are also very useful. Negative amebic serology points strongly to a pyogenic source of infection.
Imaging
Role of USG : USG is the imaging of first choice. It is quick, safe, cheap, and accurate in picking a liver lesion. Appearances of an abscess may be a rounded or an oval lesion which is usually hypoechoic but may have heterogenous echotexture. A solid or heterogenous lesion often evolves into a hypoechoic lesion on subsequent examination.[30] Majority of the abscess have a well defined wall which may be thin or irregular. USG may reveal an intra-abdominal precipitating cause for liver abscess. However USG may miss very small abscesses or abscesses lying in areas of liver difficult to examine when patient co-operation is poor.
Role of CT : CECT is more sensitive in detecting even small abscesses anywhere in liver. Yet it is inconvenient and expensive with risk of contrast nephropathy being always there. A hypo dense lesion with low attenuation areas and an enhancing rim is a classical CECT image. Small hypo echoic lesions in cluster may suggest a beginning of process of coalescence into a single large abscess later.
Role of MRI : Liver abscesses on MRI appear hypo intense on T1 weighted and hyper intense in T2 weighted sequences. On gadolinium enhanced sequences there is early and continued enhancement of wall which persists on delayed images. There is increased peri-abscess tissue enhancement in immediate post-gadolinium images.[41] With all the inconveniences of time and cost attached to MRI, it is at its best of same capability as CECT.
Role of Scintigraphy : If ambiguity arises in diagnosis in an occasional patient with conventional imaging, scintigraphy may help. 111 In labeled leukocyte scintigraphy (ILLS) which shows abscesses as 'hot spots' superimposed on 99mTc labelled scintigraphy which shows abscesses as 'cold spots' are of value in establishing a diagnosis.[42]
Resolution and follow up of abscess on imaging : Of all imaging modalities, USG is best for follow up, although it is not routinely necessary. The abscess cavity takes many months to finally resolve and lags behind clinical resolution by months.[31],[43] Resolution time depends on abscess size, but hypoalbuminemia and anemia at presentation were also found important in our study.[43] It is not at all necessary to retreat or continue treating a clinically quiescent patient with a visible cavity on imaging. Recurrences are rare for amoebic liver abscesses.[44] Recurrences are observed with pyogenic liver abscesses[4] most of which occur within 3 months of treatment. There may be an underlying problem like CGD predisposing recurrence.
Treatment
Medical therapy : At presentation, it is important to resuscitate a sick septic patient with I.V. fluids and other supportive measures. Appropriate analgesics may be essential but NSAIDs should be avoided if intervention is planned. A combination of anti-staphylococcal drug like cloxacillin, an anti-anerobic and anti-amebic drug like metronidazole and an aminoglycoside or cephalosporin for gram negative bacilli is a good initial choice. Therapeutic drainage is not a must in all cases of pyogenic liver abscesses.[1] However experiences with most series suggest that 80-90% pyogenic liver abscesses require some form of drainage.[22],[34] Medical antibiotic cover is additionally required for a period of 3-4 weeks.
95% of amebic abscesses do well on medical therapy alone[44],[45]and require therapy with nitroimidazoles for a total duration of ten days only. Metronidazole is the drug of choice. Oral dose is 30-50mg/kg/d, and i.v. dose is 7.5 mg/Kg/dose 6th hourly.
Role of aspiration : Aspiration is safe, is helpful in diagnosis of abscess and provides material for microbiological assessment. Abscess aspiration (sometimes repeated) in combination with antibiotics has been successfully tried worldwide. In pyogenic liver abscesses, aspiration along with antibiotics help[4],[22] and reasonable results can be achieved. This strategy has been reported to be helpful in amoebic liver abscesses too[46] but in a randomized trial conducted by us, we did not find any added benefit of aspiration in uncomplicated amoebic abscesses[44]. Aspiration must be attempted in solitary,unilocular lesions and on carefully selected patients but if sepsis persists, prompt drainage is required.
Role of percutaneous drainage : Percutaneous drainage has now come to a centrestage in management of liver abscesses that require more than just a medical management. Safety and efficacy of percutaneous abscess drainage in selected patients is now well established. Even multiloculated liver abscesses can be managed with aggressive percutaneous techniques that include disruption of loculations and placement of large bore sump catheters. Percutaneous drainage is indicated when
(a) Volume of abscess is large and there is risk of spontaneous rupture(specially left lobe abscesses). (b) When actual rupture has occurred, then along with abscess cavity drainage of extraneous collection. (c) When there is lack of response to medical therapy with clinical signs of persistent sepsis or enlarging abscesses, or persistent symptoms. (d) When there is evidence of liver failure.
Absence of a secure route is the only contraindication . Good results have been reported in series on children[3],[4],[25]. Failure is mostly due to technical causes like (a) Inappropriate approach into a non- dependant portion of cavity. (b) Failure to recognize and respond to septation. and (c) Premature withdrawal of drains[47]. Catheters should be withdrawn once there is negligible(<10 ml) pus drain per day and when patient is apyrexic. Complications are bacteremia, and bleed externally or into the peritoneum or GIT (haemobilia), and sometimes iatrogenic superinfection.
Role of surgery : Presently surgical drainage is usually reserved for patients ( a ) who have failed percutaneous drainage, ( b ) those who require management for an underlying abdominal problem, ( c ) selected patients with multiple macroscopic abscesses, ( d ) those on steroids and ( e ) patients with ascites.
Transperitoneal approach is the usual method used. This is because the entire liver can be exposed, best drainage site can be determined, multiple abscesses identified with an intraoperative USG, and entire abdomen explored for the primary source of infection. Good results with a low mortality has been reported in literature.[21]
Morbidity and Mortality
Complications : List of possible complications are long. However pleuro- pulmonary complications are the commonest.[48] It may be in form of pleural effusion, empyema, pneumonitis, and hepatopleural or hepato-bronchial fistula. Other complications may be in form of ascites, Budd-Chiari syndrome More Details, intraperitoneal rupture of abscess and peritonitis, intrapericardial rupture, pericardial efusion, septic shock, hemobilia and Jaundice. Rare complication like perforations into a hollow viscus like colon, stomach and duodenum and cerebral amoebiasis are also reported.
Markers of early detection of complications : Patients who present with jaundice, large or multiple abscesses, acute abdomen, liver failure and sepsis have complications more often.[49]
Mortality : Facility of prompt diagnosis with imaging, percutaneous drainage, and better antibiotics have remarkably improved survival in the last three dacades[3]. With modern management most of the series have a mortality of less than 15%.[1],[3],[10],[13],[29],[49]
Markers for mortality : In our study on patients with amoebic liver abscesses, bilirubin levels>3.5 mg/dl, encephalopathy, volume of abscess cavity, number of abscesses, and hypoalbuminemia(<2 gm/dl) were independent risk factors for mortality.[50]
References
1. Kumar A, Srinivasan S, Sharma AK. Pyogenic liver abscess in children-South Indian experiences. J Pediatr Surg 1998 Mar; 33(3) : 417-421.
2. Ferreira MA, Pereira FE, Musso C, Dettogni RV. Pyogenic liver abscess in children: some observations in the Espirito Santo State. Brazil Arq Gastroenterol 1997 Jan-Mar;34(1) : 49-54.
3. Pineiro-Carrero VM, Andres JM. Morbidity and mortality in children with pyogenic liver abscess. Am J Dis Child 1989 Dec; 143(12) : 1424-1427.
4. Hansen PS, Schonheyder HC. Pyogenic hepatic abscess. A 10-year population-based retrospective study. APMIS 1998 Mar;106(3) : 396-402.
5. Wang DS,Chen DS,Wang YZ,Li JS.Bacterial liver abscess in children. J Singapore Paediatric Soc 1989; 31(1-2) : 75-78.
6. Moreira-Silva SF, Leite AL, Brito EF, Pereira F.Nematode infections are risk factors for staphylococcal infection in children. Mem Inst Oswaldo Cruz 2002 Apr; 97(3) : 395-399.
7. Teixeira R, Ferreira MD, Coelho PM, Filho GB, Azevedo Junior GM, Lambertucci JR. Pyogenic liver abscesses and acute schistosomiasis mansoni: report on 3 cases and experimental study. Trans R Soc Trop Med Hyg 1996 May-Jun; 90(3) : 280-283.
8. Teixeira R, Pfeilsticker FJ, Santa Cecilia GD, Nobre V, Fonseca LP et al. Schistosomiasis mansoni is associated with pyogenic liver abscesses in the state of Minas Gerais, Brazil. Mem Inst Oswaldo Cruz 2001; 96 Suppl : 143-146.
9. Pereira FE, Musso C, Castelo JS. Pediatr Dev Pathol 1999 Nov-Dec;2(6) : 537-543. Pathology of pyogenic liver abscess in children.
10. Javid G, Wani NA, Gulzar GM, Khan BA, Shah AH et al. World J Surg. 1999 Nov;23(11):1191-4. Ascaris-induced liver abscess.
11. Almuneef M, Al Khenaizan S, Al Ajaji S, Al-Anazi A. Pyogenic liver abscess and Papillon-Lefevre syndrome: not a rare association. Pediatrics 2003 Jan; 111(1) : e85-88.
12. Lublin M, Bartlett DL, Danforth DN, Kauffman H, Gallin JI, et al. Hepatic abscess in patients with chronic granulomatous disease. Ann Surg 2002 Mar;235(3) : 383-391.
13. Hendricks MK, Moore SW, Millar AJ. Epidemiological aspects of liver abscesses in children in the Western Cape Province of South Africa. J Trop Pediatr 1997 Apr;43(2) : 103-105.
14. Moreira-Silva SF, Pereira FE. Intestinal nematodes, Toxocara infection, and pyogenic liver abscess in children: a possible association. J Trop Pediatr 2000 Jun;46(3) : 167-172.
15. Chang TN, Tang L, Keller K, Harrison MR, Farmer DL, Albanese CT. Pylephlebitis, portal-mesenteric thrombosis, and multiple liver abscesses owing to perforated appendicitis. J Pediatr Surg 2001 Sep;36(9):E19.
16. Slovis TL, Haller JO, Cohen HL, Berdon WE, Watts FB Jr. Complicated appendiceal inflammatory disease in children: pylephlebitis andliver abscess. Radiology 1989 Jun;171(3) : 823-825.
17. Muramatsu Y, Watanabe Y, Fujiwara K, Kazuta K, Soga K et al. Rinsho Hoshasen. 1990 Jun;35(6):761-4. A case of congenital choledochal cyst with prehepatic portal occlusion, liver abscess, and cholelithiasis.
18. Van Dyke DC, Alexander RC, Perlman S, Smith WJ Jr, Dekowski SA. Metastases with osteomyelitis and hepatic abscess occurring in a chaotic family.Fusiform bacterial sepsis. Clin Pediatr (Phila). 1989Sep;28(9) : 423-425.
19. Nachman S, Kaul A, Li KI, Slim MS, San Filippo JA et al. Liver abscess caused by Clostridium bifermentans following blunt abdominal trauma. J Clin Microbiol 1989 May;27(5) : 1137-1138.
20. Guittet V, Menager C, Missotte I, Duparc B, Verhaegen F et al. Hepatic abscesses in childhood: retrospective study about 33 cases observed in New-Caledonia between 1985 and 2003. Arch Pediatr. 2004 Sep;11(9) : 1046-1053.
21. Moore SW, Millar AJ, Cywes S. Conservative initial treatment for liver abscesses in children. Br J Surg 1994 Jun;81(6): 872-874.
22. de Kolster CE, Guerreiro N, de Escalona L, Perdomo G, Marquez R et al. Hepatic abscess in children: analysis of 20 cases. G E N. 1990 Jul-Sep;44(3) : 221-226.
23. Nazir Z, Qazi SH. Amebic liver abscesses among neonates can mimic bacterial sepsis. Pediatr Infect Dis J 2005 May;24(5) : 464-466.
24. Brook I, Fraizer EH. Role of anaerobic bacteria in liver abscesses in children. Pediatr Infect Dis J 1993 Sep;12(9):743-7
25. Tsai CC, Chung JH, Ko SF, Liu PM, Su CT et al. Liver abscess in children: a single institutional experience in southern Taiwan. Acta Paediatr Taiwan 2003 Sep-Oct;44(5) : 282-286.
26. Maxwell AJ, Mamtora H. Fungal liver abscesses in acute leukaemia-a report of two cases. Clin Radiol 1988 Mar;39(2) : 197-201.
27. Essop AR, Segal I, Posen J, Noormohamed N. Tuberculous abscess of the liver. A case report. S Afr Med J 1983 May 21; 63(21) : 825-826.
28. Kumar A, Kapoor R, Chopra K, Sethi GR, Saha MM. Typhoid fever. Unusual hepatic manifestations. Clin Pediatr (Phila). 1989 Feb; 28(2) : 99-100.
29. Moore SW, Lakhoo K, Millar AJ, Cywes S. Left-sided liver abscess in childhood. S Afr J Surg 1994 Dec;32(4) : 145-148.
30. Ahmed L, el Rooby A, Kassem MI, Salama ZA, Strickland GT. Ultrasonography in the diagnosis and management of 52 patients with amebic liver abscess in Cairo. Rev Infect Dis 1990 Mar-Apr;12(2) : 330-337.
31. Ahmed L, Salama ZA, el Rooby A, Strickland GT. Ultrasonographic resolution time for amebic liver abscess. Am J Trop Med Hyg 1989 Oct;41(4) : 406-410.
32. Sharma MP, Dasarathy S, Sushma S, Verma. Long term follow-up of amebic liver abscess: clinical and ultrasound patterns ofresolution. Trop Gastroenterol 1995 Jul-Sep; 16(3) : 24-28.
33. Munoz LE, Botello MA, Carrillo O, Martinez AM. Early detection of complications in amebic liver abscess. Arch Med Res 1992; 23(2) : 251-253.
34. Huang C-J, Pitt HA, Lipsett PA et al. Pyogenic hepatic abscess. Ann Surg 1996; 223 : 600.
35. Sharma MP, Acharya SK, Verma N, Dasarathy S. Clinical profile of multiple amoebic liver abscesses. J Assoc Physicians India. 1990 Nov; 38(11) : 837-839.
36. Nazir Z, Moazam F. Amebic liver abscess in children.Pediatr Infect Dis J 1993 Nov;12(11) : 929-932.
37. Haffar A, Boland FJ, Edwards MS. Amebic liver abscess in children. Pediatr Infect Dis 1982 Sep-Oct;1(5) : 322-327.
38. Gupta RK. Amebic liver abscess: a report of 100 cases. Int Surg 1984 Jul-Sep; 69(3) : 261-264.
39. Ajao OG, Adebo OA. Unruptured amoebic liver abscess presenting as acute abdomen. Trop Doct 1983 Jul; 13(3): 109-111.
40. Hossain A, Bolbol AS, Chowdhury MN, Bakir TM. Indirect hae-m-a-g-glutination (IHA) test in the serodiagnosis of amebiasis. J Hyg Epidemiol Microbiol Immunol 1989; 33(1) : 91-97.
41. Balci NC, Semelka RC, Noone TC, Siegelman ES, de Beeck BO et al. Pyogenic hepatic abscesses: MRI findings on T1- and T2-weighted and serial gadolinium-enhanced gradient-echo images. J Magn Reson Imaging 1999 Feb; 9(2) : 285-290.
42. Terauchi T, Uno K, Ozaki M, Arimizu N. Usefulness of 111In labeled leukocytes scintigraphy combined with 99mTc phytate liver scintigraphy for diagnosis of hepatic abscess comparing with CT and US. Nippon Igaku Hoshasen Gakkai Zasshi 1992 Apr 25;52(4) : 491-496.
43. Sharma MP, Dasarathy S, Sushma S, Verma N. Long term follow-up of amebic liver abscess: clinical and ultrasound patterns of resolution. Trop Gastroenterol 1995 Jul-Sep; 16(3) : 24-28.
44. Sharma MP, Rai RR, Acharya SK, Ray JC, Tandon BN. Needle aspiration of amoebic liver abscess. BMJ 1989 Nov 25;299(6711) : 1308-1309.
45. Omanga U, Mashako M. Amoebic liver abscess in children (study of 47 cases observed from 1964 to 1979. Med Trop (Mars). 1981 Jul-Aug;41(4) : 425-430.
46. Mehnaz A, Ali SM. Liver abscess in children-not an uncommon problem. J Pak Med Assoc 1991 Nov;41(11) : 273-275.
47. Lang EK, Springer RM, Glorioso LW 3rd, Cammarata CA. Abdominal abscess drainage under radiologic guidance: causes of failure. Radiology 1986 May;159(2) : 329-336.
48. Lyche KD, Jensen WA, Kirsch CM, Yenokida GG, Maltz GS et al. Pleuropulmonary manifestations of hepatic amebiasis. West J Med 1990 Sep;153(3) : 275-278.
49. Munoz LE, Botello MA, Carrillo O, Martinez AM. Arch Med Res 1992; 23(2) : 251-253. Early detection of complications in amebic liver abscess.
50. Sharma MP, Dasarathy S, Verma N, Saksena S, Shukla DK. Prognostic markers in amebic liver abscess: a prospective study. Am J Gastroenterol 1996 Dec; 91(12) : 2584-2588.(Sharma MP, Kumar Arvind)