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.

Clinical characteristics and treatment outcomes in a cohort of patients with pyogenic and amoebic liver abscess.

BACKGROUND: We describe the clinical features of a cohort of patients with liver abscesses and investigate relationships between clinical, radiological and microbiological findings and mortality. METHODS: Retrospective review of pyogenic (PLA) or amoebic liver abscesses (ALA) diagnosed and treated at a major infectious diseases department in London over 9 years. RESULTS: One hundred forty-one patient records were identified; 132 (93.6%) had PLA and 9 (6.4%) ALA. No organism was identified in 38.6% (51/132); a single bacterial species was isolated in 47.0% (62/132) of PLA, ≥ 2 in 14.4% (19/132). There was weak evidence of variation in abscess size by type of microorganism, with streptococcal PLA typically larger (p = 0.03 for Streptococcus milleri group, p = 0.05 for non-milleri streptococci). Patients with ALA were younger (median 41, IQR 37-51 years) than those with PLA (median 68, IQR 50.5-78 years) (p = 0.003) and all were male (9/9, 100%, (p = 0.03)), with a history of recent travel in the majority (6/9, 66.7% (p = 0.003)). C-reactive protein was higher in ALA than in PLA (p = 0.06). In the entire cohort, loculation (HR = 2.51 (95% CI 1.00-6.32), p = 0.04) and baseline ALP (HR = 4.78 (95% CI 1.19-19.2) per log10 increase, p = 0.03) were associated with mortality. 16S ribosomal RNA (rRNA) analysis was used in a subset of culture-negative cases and increased the diagnostic yield by 13%. CONCLUSIONS: Clinical or radiological features cannot be used to distinguish between PLA and ALA, or help identify the bacterial cause of PLA. However, ALA is more common in young, male patients with a history of travel. 16S rRNA analysis of abscess fluid has a role in improving microbiological diagnosis in culture-negative cases.

Prevalence of cases of amebic liver abscess in a tertiary care centre in India: A study on risk factors, associated microflora and strain variation of Entamoeba histolytica.

BACKGROUND: Amebiasis, caused by Entamoeba histolytica (E. histolytica), is a significant cause of morbidity and mortality in developing countries. Mortality due to amebiasis is mostly by extra intestinal infections, amebic liver abscess being the most common one. This study was conducted to determine the current epidemiological status, risk factors, associated microflora and strain variation of E. histolytica causing liver abscesses. METHODS/FINDINGS: A total of 115 liver abscess cases comprising of 107 (93%) males and 8 (6.9%) females were included in the study. Microscopic examination of pus samples from the abscesses and species discrimination using nested multiplex PCR showed the presence of E. histolytica in 101 (87.5%) cases. Data collected by face to face interviews using a pre tested questionnaire suggested intake of untreated drinking water (ORs: 6.4, p = 0.002), habit of alcohol consumption (ORs: 4.0, p = 0.019) and lack of urban services (ORs: 0.08, p = 0.017) to be major risk factors associated with E. histolytica infections. The study of associated bacterial flora through aerobic culture of liver aspirates and conventional PCR for detection of anaerobes revealed the presence of Fusobacterium (19, 25.5%), Peptococcus (19, 25.5%), Prevotella (18, 24.3%), Bacteroides (8, 10.8%), Staphylococcus aureus (3, 4%), Escherichia coli (2, 2.7%), Peptostreptococcus (2, 2.7%), Clostridium (2, 2.7%) and Klebsiella pneumoniae (1, 1.3%). Further to study the clonality, genotyping of E. histolytica targeting six tRNA-linked polymorphic STR loci (A-L, D-A, N-K, R-R, STGA -D and S-Q) was carried out which showed the presence of 89 different genotypes in the liver aspirate samples. CONCLUSION: The findings highlight the high prevalence of genetically diverse E. histolytica from the liver abscess cases in this geographical region. Low socio-economic status and habit of alcohol consumption were important predictors of amebic liver abscess.

Outcomes of a conservative approach to management in amoebic liver abscess.

CONTEXT: Unfortunately, there is confusion among the medical community regarding the management of amoebic liver abscess (ALA). Therapeutic options range from simple pharmacotherapy to use of interventions like a needle or catheter aspiration under ultrasound guidance to surgical intervention. There is a plethora of thresholds for parameters such as the maximum diameter of the abscess and volume on ultrasound examination suggested by various authors to serve as a criterion to help to decide when to use which modality in these cases. AIMS: To assess the outcome of patients with uncomplicated ALA treated using a conservative approach. Moreover, to identify factors associated with its failure. SETTINGS AND DESIGN: A prospective, observational study was carried out at a large municipal urban health care center over a period of 3-year (2011-2014) in India. MATERIALS AND METHODS: Patients with uncomplicated ALA were recruited. All patients were managed with pharmacotherapy initially for a period of 72 h. Response to treatment was assessed by resolution of symptoms within the given time frame. Failure to respond was considered an indication for intervention. Needle aspiration was offered to these patients and response assessed within 72 h. Failure to respond to aspiration was considered an indication for catheter drainage. STATISTICAL ANALYSIS USED: Data recorded were entered in a Microsoft Office Excel Sheet and analyzed using the SPSS version 16.0 (IBM). RESULTS: Sixty patients with ALA were included in the study over its duration. Forty-nine (81.67%) patients were managed conservatively, while 11 (18.33%) patients needed an intervention for relief. Patients who required intervention had deranged liver function at presentation, a larger abscess diameter (10.09 ± 2.23 vs. 6.33 ± 1.69 cm P < 0.001) and volume (399.73 ± 244.46 vs. 138.34 ± 117.85 ml, P < 0.001) compared to those who did not need it. Patients that required intervention had a longer length of hospital stay (7.1 ± 2.4 vs. 4.8 ± 0.9 days, P < 0.001). On post hoc analysis, a maximum diameter of >7.7 cm was found to be the optimal criterion to predict the need of intervention in cases of ALA. CONCLUSIONS: A conservative approach is effective in the management of ALA for a majority of patients. Failure of conservative management was predicted by the size of the abscess (maximum diameter >7.7 cm). Even in the cases of failure, a gradual step-up with interventions was found to be safe and effective.

Analysis of the Bacterial Diversity in Liver Abscess: Differences Between Pyogenic and Amebic Abscesses.

Several recent studies have demonstrated that virulence in Entamoeba histolytica is triggered in the presence of both pathogenic and nonpathogenic bacteria species using in vitro and in vivo experimental animal models. In this study, we examined samples aspirated from abscess material obtained from patients who were clinically diagnosed with amebic liver abscess (ALA) or pyogenic liver abscess (PLA). To determine the diversity of bacterial species in the abscesses, we performed partial 16S rRNA gene sequencing. In addition, the E. histolytica and Entamoeba dispar species were genotyped using tRNA-linked short tandem repeats as specific molecular markers. The association between clinical data and bacterial and parasite genotypes were examined through a correspondence analysis. The results showed the presence of numerous bacterial groups. These taxonomic groups constitute common members of the gut microbiota, although all of the detected bacterial species have a close phylogenetic relationship with bacterial pathogens. Furthermore, some patients clinically diagnosed with PLA and ALA were coinfected with E. dispar or E. histolytica, which suggests that the virulence of these parasites increased in the presence of bacteria. However, no specific bacterial groups were associated with this effect. Together, our results suggest a nonspecific mechanism of virulence modulation by bacteria in Entamoeba.

Vagotomy induces deregulation of the inflammatory response during the development of amoebic liver abscess in hamsters.

BACKGROUND: The parasympathetic nervous system modulates the immune response in the abdominal-pelvic gut through the vagus nerve, which releases acetylcholine. This endogenous ligand acts on α7 nicotinic receptors expressed on immune cells. OBJECTIVE: To study the mechanism of the production and regulation of cytokines in parasympathectomized and control hamsters during the development of amoebic liver abscesses (ALA) caused by Entamoeba histolytica. METHODOLOGY: Six- to 8-week-old male hamsters with and without vagotomy were used in a model of ALA. The animals were infected with trophozoites (350,000; HM1:IMSS strain) via the intrahepatic route and sacrificed at 6, 12, and 24 h and at 2, 4, and 7 days postinfection. Immune parameters were recorded at each time point using morphometric techniques including immunofluorescence and immunohistochemistry assays. These parameters included signal transducer and activator of transcription 3 (STAT3) levels, pro- and anti-inflammatory cytokine levels, and nuclear factor-κB (NFκB) activation in neutrophils and macrophages. RESULTS: Compared to the control groups, the vagotomized (VAG) hamsters showed a significant increase in NFκB activation in neutrophils and macrophages, and higher levels of interleukin (IL)-1ß, IL-6, interferon-γ, and tumor necrosis factor-α. VAG hamsters showed an increase in the expression of IL-8 and phosphorylated STAT3 during the first 24 h postinfection as well as slightly increased levels of transforming growth factor-ß on days 2-7 postinfection. No significant differences were demonstrated in the levels of IL-10. CONCLUSIONS: These results suggest that the vagus nerve plays an important role in the regulation of inflammation during ALA formation.

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.

Single and multiple liver abscesses in adults in Delhi are amoebic in origin: a clinical and microbiological study.

Single and multiple liver abscesses in Delhi are predominantly amoebic and must be distinguished from pyogenic abscesses which frequently require drainage. Mixed abscesses are larger, harbouring Gram negative rods. Multiple abscesses are not always pyogenic and presence of bacteria does not imply a primary pyogenic source.

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.

Loop-mediated isothermal amplification (LAMP) assay for rapid detection of Entamoeba histolytica in amoebic liver abscess.

Amoebic liver abscess (ALA) is the most common extra intestinal manifestation of invasive amoebiasis caused by Entamoeba histolytica. The lack of early and accurate diagnostic test to differentiate various causes of liver abscess necessitates more reliable laboratory diagnostic test. The present study was conducted to assess the applicability of Loop-Mediated Isothermal Amplification (LAMP) assay for detection of E. histolytica in ALA cases. Fifty patients (n = 50) with clinical suspicion of ALA were enrolled in the study. All the clinical samples were subjected to conventional PCR assay. LAMP assay was standardized and the results were compared with that of PCR assay. Out of fifty pus samples thirty-six (72 %, 36/50) were positive for E. histolytica with conventional PCR assay and forty-one (82 %, 41/50) were positive by LAMP assay. Thus, five additional positive cases, missed by conventional PCR were positive with LAMP assay. Apart from rapidity, operational simplicity of LAMP assay high specificity and sensitivity, one-step amplification, higher yield and immediate visual detection may serve as a better diagnostic tool for diagnosis of ALA.

Absceso hepático amebiano en el embarazo: reporte de un caso / Amebic liver abscess in pregnancy: a case report

La asociación de absceso hepático amebiano y embarazo es poco frecuente y se asocia a un aumento de la morbilidad y mortalidad materna. Presentamos el caso de una paciente de 33 años, cursando un embarazo de 35 semanas, que ingresó a nuestro servicio con el diagnóstico de absceso hepático, cuya etiología fue E. histolytica.

The appearance of amebic liver abscess in pregnancy is uncommon and is associated to increased maternal morbidity and mortality. We report the case of 33 years old woman, with a 35 weeks pregnancy that was admitted in our Hospital with the diagnosis of liver abscess, whose etiology was E. histolytica.

Host-microbe interactions and defense mechanisms in the development of amoebic liver abscesses.

SUMMARY: Amoebiasis by Entamoeba histolytica is a major public health problem in developing countries and leads to several thousand deaths per year. The parasite invades the intestine (provoking diarrhea and dysentery) and the liver, where it forms abscesses (amoebic liver abscesses [ALAs]). The liver is the organ responsible for filtering blood coming from the intestinal tract, a task that implies a particular structure and immune features. Amoebae use the portal route and break through the sinusoidal endothelial barrier to reach the hepatic parenchyma. When faced with systemic and cell-mediated defenses, trophozoites adapt to their new environment and modulate host responses, leading to parasite survival and the formation of inflammatory foci. Cytopathogenic effects and the onset of inflammation may be caused by diffusible products originating from parasites and/or immune cells either by their secretion or by their release after cell death. Liver infection thus results from the interplay between E. histolytica and hepatic cells. Despite its importance in terms of public health burden, the lack of integrated data on ALA genesis means that we have only an incomplete description of the initiation and development of hepatic amoebiasis. Here, we review the main steps of ALA development as well as the responses triggered in both the host and the parasite. Transcriptome studies highlighted parasite factors involved in adherence to human cells, cytopathogenic effects, and adaptative and stress responses. An understanding of their role in ALA development will help to unravel the host-pathogen interactions and their evolution throughout the infection.

Changes in bacterial profile during amebiasis: demonstration of anaerobic bacteria in ALA pus samples.

Little is known about the changes in gut resident flora during amebic colitis and amebic liver abscess (ALA) caused by Entamoeba histolytica infection. Fecal samples from ALA patients, from healthy E. histolytica negative and positive (asymptomatic) individuals, and from pre- and post-metronidazole-treated healthy volunteers and pus samples from ALA patients were tested for the presence of various bacterial genera using 16S rRNA-based primers. Statistically significant reduction in Lactobacillus due to E. histolytica infection was observed in asymptomatic individuals and ALA patients. On the other hand, reduction in Bacteroides, Bifidobacterium, and Clostridium in the same samples was due to metronidazole treatment. Two anaerobic genera, viz. Bacteroides and Peptostreptococcus, were detected in ALA pus samples, and this observation is unprecedented. In addition, PCR revealed metronidazole resistance genes in fecal and pus samples of metronidazole-treated individuals. Re-examination of the ameba-bacterium relationship in amebiasis is suggested.

Endoscopic biliary drainage in patients with amebic liver abscess and biliary communication.

BACKGROUND: Percutaneous drainage or surgery is required when amebic liver abscess (ALA) fails to respond to medical management. In some of these patients, non-response may be due to communication of ALA with the biliary tree. This report describes our experience with the use of endoscopic biliary draining in such patients. METHODS: Medical records of patients with ALA undergoing either needle aspiration or percutaneous pigtail drainage were retrieved; the indications for drainage were: abscess volume exceeding 250 mL, a thin rim of tissue (< 1 cm thick) around the abscess, systemic toxic features and failure to improve on medical treatment. Patients with abscess drain output >25 mL/day persisting for 2 weeks or presence of bile in the drain fluid underwent endoscopic biliary drainage. RESULTS: A total of 115 patients with ALA underwent percutaneous treatment. None of the 25 patients with needle aspiration needed any further treatment. Of the 90 who underwent catheter drainage, the catheter could be removed within one week in 77 patients; the remaining 13 patients (median age 42 years, range 24-65; all men) had an abscess-biliary communication. In them, the median catheter output was 88 mL/day (range 45-347) and 54 mL/day (28-177) at 2 days and 2 weeks after catheter placement. The drain fluid contained bile in all 13 patients and in addition contained pus in 10 patients. Eleven patients had a solitary abscess and two had multiple abscesses. Cholangiogram showed biliary communication in all 13 patients. All patients were treated with placement of 10F biliary endoprosthesis or 10F nasobiliary drain. Pigtail catheter was removed within 1 week in 11 of 13 patients. CONCLUSION: In patients with amebic liver abscess communicating with the biliary tree, biliary stenting may hasten clinical recovery and allow early removal of liver abscess catheter drain.

Detection of Entamoeba histolytica using polymerase chain reaction in pus samples from amebic liver abscess.

BACKGROUND AND OBJECTIVE: Direct demonstration of Entamoeba histolytica by conventional microscopy and in vitro culture in pus obtained from amebic liver abscess (ALA) is often unsuccessful. We evaluated polymerase chain reaction (PCR) for detection of E. histolytica DNA in such pus. METHODS: Species-specific primers were used for the amplification of E. histolytica DNA from liver pus obtained from 30 patients with ALA. Patients with pyogenic liver abscess and sterile (autoclaved) pus spiked with Entamoeba dispar and bacteria (Escherichia coli, Klebsiella spp. and Bacteroides spp.) were used as negative controls. RESULTS: PCR was positive in 83% of pus specimens from patients with ALA, and was negative in all 25 pus specimens obtained from pyogenic abscess and autoclaved pus spiked with known bacteria. Sensitivity and specificity of PCR were 83% and 100%, respectively. The overall positivity of PCR was higher compared to serological tests. CONCLUSION: PCR may be a more reliable and better alternative diagnostic modality for ALA.

Mucosal immunity to asymptomatic Entamoeba histolytica and Entamoeba dispar infection is associated with a peak intestinal anti-lectin immunoglobulin A antibody response.

We monitored 93 subjects cured of amebic liver abscess (ALA) and 963 close associate controls in Durban, South Africa, and determined by enzyme-linked immunosorbent assay that the intestinal immunoglobulin A (IgA) antibody response to the Entamoeba histolytica galactose-inhibitable adherence lectin is most accurately represented by a complex pattern of transitory peaks. One or more intestinal anti-lectin IgA antibody peaks occurred in 85.9% of ALA subjects over 36 months compared to 41.6% of controls (P < 0.0001). ALA subjects exhibited a greater number of anti-lectin IgA antibody peaks (P < 0.0001) than controls. In addition, their peak optical density values were higher (peak numbers 1 to 3, P < 0.003), peaks were of longer duration (for peaks 1 and 2, P

[Diagnosis and treatment of acute amebian liver abscess with laparoscopic method].

Laparoscopic surgical treatment was performed at 55 patients with acute amebian liver abscess. The diagnosis of acute amebian liver abscess was verified with clinical, serological, echoscopic, x-ray and CT methods. The laparoscopic method permits to sanify the abscess cavity of any localization. All the 55 patients have been discharged in good health. Laparoscopic method is maximally rational, associated with minimal surgical trauma, permits to decrease hospital stay and period of postoperative rehabilitation.

Causative agents of liver abscess in HIV-seropositive patients: a 10-year case series in Thai hospitalized patients.

Liver abscess is an important tropical gastrointestinal disorder. HIV seropositive patients show relative immunosuppression and are more susceptible to infection, including liver abscess. This retrospective case review was made on 23 patients who were diagnosed as HIV seropositive with liver abscess in Bangkok, Thailand. We demonstrated the high rate of amoebic liver abscess in our series (17.4%) from fresh smear with five cases of tuberculosis and one case of Nocardosis. The rates of positive bacterial culture were 17.4% from blood and 47.8% from pus. Gram-negative aerobes were the major abscess pathogens in our series. Among Gram-negative aerobes, Klebsiella was the most significant microorganism, followed by Escherichia coli and Pseudomonas aeruginosa.

Biological aspects of a Brazilian strain of Entamoeba dispar.

A strain of Entamoeba dispar was characterized by clinical diagnosis, serological and electrophoretical isoenzyme analysis and by the polymorphism of a 482 bp genomic fragment analysis. The pathogenesis and virulence of this strain was investigated considering the experimental infection in hamster livers in association with the original intestinal microbiota. Liver lesions were observed in hamsters experimentally infected with trophozoites from xenic cultures, but not from the monoxenic cultures. Moreover, clones obtained from re-isolated strain Wil1R1 showed a distinct biological behavior. In fact, animals inoculated with Wil1R1ClB3 showed an intense acute inflammatory reaction with destructive focal hepatic lesions. These lesions were characterized as amebic abscesses. The association between bacteria and ameba has been fairly well studied because it affects the pathogenicity of the amebas and has important therapeutic implications. In this study, we demonstrated that E. dispar in association with the original microbiota is able to produce lesions in hamster liver in spite of its having been considered to be non-pathogenic in the hamster model. Based on these results we suggest that diagnosis of amebiasis needs to be made with more care and that clinical and therapeutical procedures need to be revised.