Liver abscess: diagnostic and management issues found in the low resource setting.

INTRODUCTION: Liver abscesses are mainly caused by parasitic or bacterial infection and are an important cause of hospitalization in low-middle income countries (LMIC). The pathophysiology of abscesses is different depending on the etiology and requires different strategies for diagnosis and management. This paper discusses pathophysiology and epidemiology, the current diagnostic approach and its limitations and management of liver abscess in low resource settings. SOURCES OF DATA: We searched PubMed for relevant reviews by typing the following keywords: 'amoebic liver abscess' and 'pyogenic liver abscess'. AREAS OF AGREEMENT: Amoebic liver abscess can be treated medically while pyogenic liver abscess usually needs to be percutaneously drained and treated with effective antibiotics. AREAS OF CONTROVERSY: In an LMIC setting, where misuse of antibiotics is a recognized issue, liver abscesses are a therapeutic conundrum, leaving little choices for treatment for physicians in low capacity settings. GROWING POINTS: As antimicrobial resistance awareness and antibiotic stewardship programs are put into place, liver abscess management will likely improve in LMICs provided that systematic adapted guidelines are established and practiced. AREAS TIMELY FOR DEVELOPING RESEARCH: The lack of a quick and reliable diagnostic strategy in the majority of LMIC makes selection of appropriate treatment challenging.

Adrenergic regulation during acute hepatic infection with Entamoeba histolytica in the hamster: involvement of oxidative stress, Nrf2 and NF-KappaB.

Oxidative stress and transcriptional pathways of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) are critically involved in the etiopathology of amebic liver abscess (ALA). In this work, we studied the relationship between the adrenergic nervous system and ALA in the hamster. ALA was visible at 12 h of infection. While 6-hydroxidopamine (6-OHDA) decreased infection, propranolol (ß-adrenergic blocker) treatment was associated with less extensive liver damage, and phentolamine treatment (α-adrenergic blocker) significantly reduced ALA compared to 6-OHDA and propranolol. Serum enzymatic activities of alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γ-GTP) were increased at 12 h post-infection. Chemical denervation and α and ß-adrenergic blockers decreased ALT to normal levels, while 6-OHDA and propranolol showed a trend to decrease γ-GTP but phentolamine significantly reduced γ-GTP. Amebic infection increased oxidized glutathione (GSSG) and decreased both reduced glutathione (GSH) and the GSH/GSSG ratio. Propranolol and 6-OHDA showed a tendency to decrease GSSG. However, GSH, GSSG and GSH/GSSG returned to normal levels with phentolamine. Furthermore, amebic infection increased pNF-κB and interleukin-1ß (IL-1ß), and showed a tendency to decrease hemoxigenase-1 (HO-1), but not Nrf2. Chemical denervation showed a trend to decrease pNF-κB and IL-1ß, and neither Nrf2 nor HO-1 increased significantly. In addition, NF-κB and IL-1ß were attenuated by propranolol and phentolamine treatments, although phentolamine showed significant overexpression of Nrf2 and HO-1. This suggests that the adrenergic system may be involved in oxidative stress and in modulation of the Nrf2 and NF-κB pathways during ALA development.

Recurrent amebic liver abscesses over a 16-year period: a case report.

BACKGROUND: Amebic liver abscess is a rare disease in high-income countries. Recurrence of amebic liver abscess is even rarer with only a few previous reports. Here we present a patient who developed three subsequent amebic liver abscesses over a sixteen-year period. CASE PRESENTATION: A Caucasian male developed recurrent amebic liver abscesses, when aged 23, 27 and 39 years. Only on the first occasion did this coincide with a recent visit to the tropics. The patient received adequate treatment during each episode. Possible explanations are persistent asymptomatic carrier state, cysts passage in his family, re-infection or chance. CONCLUSION: We describe the unusual case of a healthy male who developed recurrent amebic liver abscesses over a long period despite adequate treatment. Possible pathophysiological explanations are explored.

Morphological Findings in Trophozoites during Amoebic Abscess Development in Misoprostol-Treated BALB/c Mice.

During amoebic liver abscess (ALA) formation in susceptible animals, immune response is regulated by prostaglandin E2 (PGE2) dependent mechanisms. The aim of this study was to analyze the effect of misoprostol (MPL), a PGE1 analogue, on ALA formation in BALB/c mice. Male mice from BALB/c strain were intrahepatically infected with 7.5 × 10(5) trophozoites of E. histolytica strain HM1:IMSS and treated with 10(-4) M of MPL daily until sacrifice at 2, 4, and 7 days postinfection (p.i.). ALA formation was evaluated at 2, 4, and 7 days postinfection; trophozoite morphology was analyzed using immunohistochemistry and image analysis. Results showed an increase in frequency of ALA formation in infected and MPL-treated mice only at 2 days p.i. (P = 0.03). A significant diminution in the size of trophozoites was detected in abscesses from mice independently of MPL treatment (from 5.8 ± 1.1 µm at 2 days p.i. to 2.7 ± 1.9 µm at 7 days p.i.) compared with trophozoites dimensions observed in susceptible hamsters (9.6 ± 2.7 µm) (P < 0.01). These results suggest that MPL treatment may modify the adequate control of inflammatory process to allow the persistence of trophozoites in the liver; however, natural resistance mechanisms cannot be discarded.

Common presentation of amebic liver abscess - a study in a tertiary care hospital in Bangladesh.

Amebic liver abscess is a tropical disease. It is not uncommon in Bangladesh. Given the often nonspecific nature of complains related to amebic liver abscess, this study was carried out to identify the most common presentation. This hospital based cross sectional study was carried out in 30 cases of amebic liver abscess in the Department of Medicine, Gastroenterology and Hepatology, Comilla Medical College Hospital, Bangladesh. Clinical and laboratory informations were recorded including symptoms, signs, location and number of abscess. Among 30 patients, 27 were male (90%) and 3 female (10%), mean age of male and female were 42±11 and 52±8 respectively. Common clinical symptoms were fever (93%) and abdominal pain (93%). Common signs were right upper quadrant tenderness (60%), hepatomegaly (67%). Most of the patient had single abscess (80%) and location of abscess was predominantly in the right lobe (77%). Radiological abnormality on x-ray chest was present in 30% cases. Common clinical presentation of amebic liver abscess patients were fever and right upper abdominal pain. Duration of symptoms was more than two weeks in most cases.

False-negative serologies in amebic liver abscess: report of two cases.

Amebiasis, the parasitic disease caused by Entamoeba histolytica, may result in extra-intestinal diseases among which liver abscess is the most common manifestation. We report two cases of amebic liver abscess illustrating the inequal sensitivity of serologic tests detecting anti-amebic antibodies.

Liver abscess presentation and management in Saudi Arabia and the United Kingdom.

BACKGROUND AND OBJECTIVES: Liver abscess (LA) is a well-described disease in the medical literature; however, information about its characteristics and outcome in the Middle East is lacking. We compared the mode of presentation, risk factors, management and outcome of LA patients in Saudi Arabia with cases from the United Kingdom (UK). DESIGN AND SETTING: Retrospective review of LA patients from three tertiary care centers (2 from Saudi Arabia and 1 from the UK) over a period of 10 years, from 1995 to 2005. PATIENTS AND METHODS: Data collected included demographic characteristics; clinical presentation; biochemical, microbiological and radiological findings; treatment modalities; and outcome. RESULTS: A total of 83 patients were diagnosed with LA, including 48 patients from Saudi Arabia and 35 patients from the UK. The mean (SD) age was 45.2 (20.3) years for those from Saudi Arabia and 55.4 (18.8) years for those from the UK (P=.022). The majority of the patients were males (70% from Saudi Arabia and 80% from the UK). Upper abdominal pain and fever were the commonest symptoms, each reported in 87% of the cases. Alkaline phosphatase elevation was the commonest liver function abnormality, seen in 66 (80%) patients. Organisms were isolated in 43 (52%) cases and the majority of these were coliforms (58%). Amebic liver abscesses occurred in 19 (23%) patients and all of those patients were either from or had traveled recently to the Indian subcontinent. Complete resolution of the abscesses was achieved in 66 (80%) patients with aspiration and/or antibiotics, and 9 (10.8%) patients died. On multivariate analysis, underlying malignancy, hypotension and chest signs at presentation were predictors of poor outcome (P=.008, .029 and .001, respectively). CONCLUSIONS: Successful resolution of LA is achievable in the majority of the cases, although underlying malignancy is associated with poor outcome. Amebic liver abscesses must be considered in patients with a history of travel to endemic areas.

Modulation of amoebic hepatic abscess by the parasympathetic system.

The neuro-immune network, in which the vagus nerve is involved, provides feedback between its afferent branches for signalling central nervous system from sites of injury through cytokines and its efferent branches, which release acetylcholine, an anti-inflammatory neurotransmitter. For gain insight into the parasympathetic mechanisms participating in the inflammatory response in the liver, we studied the effects of a vagotomy on the innate immune response in hamsters with amoebic liver abscess. At 7 days post-infection, compared to the control, liver parasympathectomy resulted in a larger abscess size, a greater production of collagen fibres, fewer trophozoites, increased serum levels of IL-10 and IFN-γ and increased numbers of IL-10 and IFN-γ-positive cells in situ, with no change in the number of macrophages and NK cells. Data indicate that the vagotomy disrupted the inflammatory response, causing an increase in the response against infection, then could favour the innervation of the liver by the sympathetic nervous system and would then take the control of the immune response by stimulating the conversion of macrophages to epithelioid cells; and through increased IL-10 production would induce the hepatic stellar cells to become myofibroblast collagen producer cells, thus forming a barrier of collagen and blocking trophozoite migration.

Identification of an avirulent Entamoeba histolytica strain with unique tRNA-linked short tandem repeat markers.

Highly polymorphic, non-coding short tandem repeats (STR) are scattered between the tRNA genes in Entamoeba histolytica in a unique tandemly arrayed organization. STR markers that correlate with the virulence of individual E. histolytica strains have recently been reported. Here we evaluated the usefulness of tRNA-linked STR loci as genetic markers in identifying virulent and avirulent strains of E. histolytica from 37 Japanese E. histolytica samples (12 diarrheic/dysenteric, 20 amebic liver abscess (ALA), and 5 asymptomatic cases). Twenty three genotypes, assigned by combining the STR sequence types from all 6 STR loci, were identified. One to 8 new STR sequence types per locus were also discovered. Genotypes found in asymptomatic isolates were highly polymorphic (4 out of 5 genotypes were unique to this group), while in symptomatic isolates, almost half of the genotypes were shared between diarrhea/dysentery and ALA. One asymptomatic isolate (KU27) showed unique STR patterns in 4 loci. This strain, though associated with the typical pathogenic zymodeme II, failed to induce amebic liver abscess by animal challenge, which suggests that inherently avirulent E. histolytica strains exist, that are associated with unique genotypes. Furthermore, STR genotyping and in vivo challenge of 2 other asymptomatic isolates (KU14 and KU26) verified the covert virulence of these strains.

Amoebic liver abscess: experience in a south Asian country.

Amoebic liver abscess (ALA) is endemic in south Asian countries. The current study was undertaken in order to evaluate the clinical spectrum, management and outcome of ALA at an urban tertiary care hospital in Pakistan. The chart notes of 232 ALA patients admitted from 1 January 2000 to 31 August 2007 were retrospectively reviewed. The most frequent clinical findings included: fever (96.5%); right upper abdomen pain (80.2%); liver tenderness (73.5%); tachycardia (61.6%); hepatomegaly (60%); nausea and vomiting (42%); and jaundice (23.9%). The duration of symptoms was less than 14 days in 70% . Ultrasound examinations revealed 69% of the abscesses were in the right lobe, 19% in the left lobe and 12% in both lobes. The size of the abscess was greater than 5.0 cm in 83%. Seventy-seven percent of the patients had a single abscess and 23% had multiple abscesses. Ultrasound-guided therapeutic aspiration was performed in 64%, but 36% were treated with antibiotics alone. Metronodazole was the most frequently used antibiotic. However, various combinations of antibiotics were also used without any obvious justification.

Pathophysiology of jaundice in amoebic liver abscess.

Jaundice in patients with amoebic liver abscess is a frequent occurrence. However, the pathophysiology of jaundice in these patients is not fully understood. Hepatic necrosis leads to damage to bile ducts as well as various vascular structures, which in turn leads to biliovascular fistula and jaundice. We studied the mechanism of jaundice in patients with amoebic liver abscess. We prospectively evaluated 12 patients with amoebic liver abscess and jaundice from February 2002 to August 2007. All patients underwent various investigations, including imaging studies. There were 11 males and 1 female patient with a mean age of 41.3 years. Mean duration of illness before presentation was 13.8 days. All patients had fever and jaundice. We detected damaged hepatic veins and bile ducts in all patients with amoebic liver abscess causing biliovascular fistula and hyperbilirubinemia, which reverted to normal after biliary diversion with nasobiliary drainage. Jaundice in patients with amoebic liver abscess is caused by biliovascular fistula resulting from hepatic necrosis leading to damage to bile ducts and hepatic veins.

[Nitric oxide participation during amoebic liver abscess development]. / Participacion del oxido nitrico durante el desarrollo del absceso hepatico amebiano.

Nitric oxide participates in both physiological and pathophysiological functions, and it plays an important role in the mammalian immune system in killing or inhibiting the growth of many pathogens, including parasites, viruses and bacteria. Entamoeba histolytica is a protozoan parasite that causes amoebiasis, which is characterized by intestinal damage and amoebic liver abscess development. The development of amoebic liver abscess in hamsters is similar to that in humans, whereas mice are resistant to amoebic liver abscess development due to an increase in nitric oxide production. Unlike in mice, amoebic liver abscess development in hamsters is due to an excess in nitric oxide production or possibly to a greater susceptibility of the hamster to damage caused by nitric oxide. Therefore, it could be important to elucidate if, in humans, an excess in nitric oxide production favors amoebic liver abscess development.

Evidence for a link between parasite genotype and outcome of infection with Entamoeba histolytica.

The factors determining whether a person infected with Entamoeba histolytica develops disease remain obscure. To investigate whether the parasite genome contributes to the outcome, we have investigated the distribution of parasite genotypes among E. histolytica-infected individuals in Bangladesh. Samples were obtained from individuals who either were asymptomatic, had diarrhea/dysentery, or had developed a liver abscess. Genotypes were determined by using six tRNA-linked polymorphic markers, and their distributions among the three sample groups were evaluated. A significant population differentiation in the genotype distribution was found for four of the six individual markers as well as for the combined genotypes, suggesting that the parasite genome does contribute in some way to the outcome of infection with E. histolytica. The markers themselves do not indicate the nature of the underlying genetic differences, but they may be linked to loci that do have an impact on the outcome of infection.

Participación del óxido nítrico durante el desarrollo del absceso hepático amebiano / Nitric oxide participation during amoebic liver abscess development

El óxido nítrico participa en funciones fisiológicas y fisiopatológicas, así como en el mecanismo de defensa del sistema inmunológico de mamíferos contra parásitos, virus y bacterias. La Entamoeba histolytica es un parásito protozoario causante de la amebiasis, la cual se caracteriza por el daño intestinal y la formación del absceso hepático amebiano (AHA). El desarrollo del absceso hepático amebiano en el hámster es similar al que desarrolla el humano, mientras que el ratón es resistente a la formación de este absceso, debido a un incremento en la producción de óxido nítrico. A diferencia del ratón, el desarrollo del absceso hepático amebiano en el hámster es debido a un exceso en la producción de óxido nítrico o posiblemente a una mayor susceptibilidad del hámster al daño producido por el óxido nítrico. Por lo tanto, sería importante realizar más estudios para determinar si en el humano, un exceso en la producción de óxido nítrico favorece la formación del absceso hepático amebiano.(AU)

Nitric oxide participates in both physiological and pathophysiological functions, and it plays an important role in the mammalian immune system in killing or inhibiting the growth of many pathogens, including parasites, viruses and bacteria. Entamoeba histolytica is a protozoan parasite that causes amoebiasis, which is characterized by intestinal damage and amoebic liver abscess development. The development of amoebic liver abscess in hamsters is similar to that in humans, whereas mice are resistant to amoebic liver abscess development due to an increase in nitric oxide production. Unlike in mice, amoebic liver abscess development in hamsters is due to an excess in nitric oxide production or possibly to a greater susceptibility of the hamster to damage caused by nitric oxide. Therefore, it could be important to elucidate if, in humans, an excess in nitric oxide production favors amoebic liver abscess development.(AU)