Amoebic liver abscess with negative serologic markers for <Emphasis Type="Italic">Entamoeba histolytica</Emphasis>: mind the gap!

A 38-year-old male German traveller returning from Asia presented with fever, night sweats and abdominal complaints. Abdominal ultrasonography revealed several fast-growing abscesses of the liver. Three blood cultures as well as serologic investigations for the detection of antibodies to Entamoeba histolytica, performed on day 3 and 7 after the onset of clinical symptoms, remained negative. Stool microscopy revealed the presence of amoeba cysts compatible with E. histolytica infection. Taking both the amoebic and bacterial etiology of the abscesses into consideration, the patient was treated with metronidazole and ciprofloxacin followed by paromomycin. Antibodies to E. histolytica tested positive shortly after anti-amoebic therapy was initiated. The patient fully recovered, and ultrasound follow-up showed complete resolution of the abscesses within 50 days. This case leads to the conclusion that amoebic liver abscess should be considered despite negative amoeba serology and that ultrasonography is an important diagnostic tool for the early diagnosis of extraintestinal amoebiasis.     

A case of multiple amoebic liver abscesses: clinical improvement after percutaneous aspiration

Amoebic liver abscesses are by far the most common extra-intestinal manifestation of invasive amoebiasis. The classical clinical picture consists of fever, right upper quadrant pain and hepatomegaly. Ultrasound and serology make an early diagnosis possible. Amoebic liver abscesses usually appear singly and are normally situated in the right lobe of the liver. This case report refers to a white Belgian woman, living in an endemic area for amoebiasis, presenting with 25 amoebic liver abscesses, who did not improve clinically despite appropriate anti-amoebic therapy, is described. Only percutaneous drainage of the larger abscesses led to clinical recovery. Amoebic abscess aspiration and evacuation under ultrasonographic guidance is of limited risk, but in experienced hands may enhance clinical recovery, particularly in patients with large abscesses not responding to conservative medical treatment. Aspiration of large abscesses (> 5 cm) is rarely necessary but should be considered if there is no clinical improvement after 3 days of nitroimidazole treatment with amoebicides.     

Hepatic ultrasound in a population with high incidence of invasive amoebiasis: evidence for subclinical,self-limited amoebic liver abscesses

About 10% of successfully treated amoebic liver abscesses (ALA) do not completely resolve and can be detected by ultrasound as typical residual liver lesions. The frequency of these residues should be an indicator for the prevalence of ALA in a given population, and may help to solve the question whether non-clinical, self-healing ALAs occur. We have performed hepatic ultrasound in 1036 adult individuals living in a high-risk area for ALA in Central Vietnam and identified typical ALA residual lesions in about 1.2% of the subjects. As expected, these lesions were associated with positive amoeba serology and were found in 11.9% of individuals with a previous ALA history. However, more than 50% of the residues were identified in individuals who had never developed symptoms suspected for ALA and who never received any ALA specific treatment, suggesting that subclinical, self-limited hepatic amoeba abscesses truly exist.     

Amoebiasis

Amoebiasis is the second leading cause of death from parasitic disease worldwide. The causative protozoan parasite, Entamoeba histolytica, is a potent pathogen. Secreting proteinases that dissolve host tissues, killing host cells on contact, and engulfing red blood cells, E histolytica trophozoites invade the intestinal mucosa, causing amoebic colitis. In some cases amoebas breach the mucosal barrier and travel through the portal circulation to the liver, where they cause abscesses consisting of a few E histolytica trophozoites surrounding dead and dying hepatocytes and liquefied cellular debris. Amoebic liver abscesses grow inexorably and, at one time, were almost always fatal, but now even large abscesses can be cured by one dose of antibiotic. Evidence that what we thought was a single species based on morphology is, in fact, two genetically distinct species--now termed Entamoeba histolytica (the pathogen) and Entamoeba dispar (a commensal)--has turned conventional wisdom about the epidemiology and diagnosis of amoebiasis upside down. New models of disease have linked E histolytica induction of intestinal inflammation and hepatocyte programmed cell death to the pathogenesis of amoebic colitis and amoebic liver abscess.     

A case of amoebic liver abscess complicated by a gastric fistula cured with oral medication only

A 26-year-old man was admitted to our hospital because of a high-grade fever and abdominal pain. A blood test showed marked inflammation. Enhanced computed tomography (CT) showed an 8.0×6.0cm cystic lesion in the left hepatic lobe. Esophagogastroduodenoscopy showed a huge egg-yolk-like mass in the gastric submucosa in the lesser curvature of the gastric body from the gastric angle. There were 3 ulcers on the mass, out of which milky pus flowed. Trophozoites of Entamoeba histolytica were detected from cultures of the liver abscess and a biopsy of the gastric ulcers. The amoebic dysentery antibody titer was increased 1600 times. An amoebic liver abscess complicated by a gastric fistula was diagnosed. As therapy, oral metronidazole was administered for 2 weeks without percutaneous drainage. The systemic inflammatory findings improved immediately and the abscess decreased markedly in size.     

Ultrasound patterns and frequency of focal liver lesions after successful treatment of amoebic liver abscess

OBJECTIVE: To evaluate the frequency and morphology of residual liver lesions in patients successfully treated for amoebic liver abscess. METHODS: Retrospective ultrasound-based study of 240 adult males from an amoebiasis-endemic area in Vietnam with a documented clinical history of amoebic liver abscess. Subjects were re-examined by hepatic ultrasound 1-13 years after abscess treatment. RESULTS: In 17 subjects (7.1%) focal hypo- or isoechoic areas were identified within the liver with a diameter of 8-48 mm surrounded by a hyperechoic wall. These lesions were associated with positive amoeba serology, were located at the site of the previous abscess and their sonographic appearances corresponded to post-amoebic liver abscess residues. Residues were found in all groups of patients irrespectively of the time-span since the abscess was treated. However, lesions older than 7 years showed some degree of calcification. Otherwise, lesions were apparently inactive, as patients had no clinical symptoms or signs of inflammation and follow-up after one year revealed no changes in size or pattern. CONCLUSION: The vast majority of amoebic liver abscesses resolve to a sonographically normal parenchymal pattern. However, in a small proportion of cases characteristic residues remain. These residues do not require further treatment or diagnostic intervention and should be considered in the differential diagnosis of space-occupying liver lesions, in particular in patients from amoebiasis-endemic areas.     

Amoebiasis: a rare cause of cardiac tamponade.

Cardiac tamponade secondary to perforation of a hepatic amoebic abscess developed six years after the patient had visited an area where Entamoeba histolytica is endemic. He was treated with metronidazole and imipenem, emergency percutaneous catheter drainage, and open surgical drainage.     

Macrophage requirement for host defence against experimental hepatic amoebiasis in the hamster

The role of macrophages in hepatic amoebiasis in hamsters has been investigated by means of their treatment with bacille Calmette-Guérin (BCG) for activation, and with silica for elimination of these cells. Silica-treated animals inoculated intrahepatically with 1 x 10(5) trophozoites of Entamoeba histolytica developed amoebic abscesses in the liver and more metastases to other organs than control animals, and this effect was silica-dose-dependent. In contrast, BCG-treated animals developed significantly smaller abscesses in the liver and fewer metastatic foci. These data suggest that macrophages are involved in host defence against the establishment of amoebic liver abscess and metastatic dissemination of amoebae.     

Observations on the interpretation of amoebic serology in endemic areas

Antibody to Entamoeba histolytica antigen was evaluated in cases of proven and suspected intestinal amoebiasis as well as in extra-intestinal cases from an endemic area. Screening methods included the gel diffusion precipitation test (GD), counter immunoelectrophoresis (CIE) and the indirect haemagglutination test (IHA). Control populations consisting of asymptomatic cyst passers, non-amoebic individuals, patients with giardiasis and cases of enteric fever were also screened using the above tests. All (100%) cases of amoebic liver abscess and 75-80% of hepatic amoebiasis without overt abscess formation could be detected by serology, with good correlation between the tests used. However, the interpretation of serology in cases of proven and suspected intestinal amoebiasis posed two main problems. The presence of low antibody levels even in proven cases and the persistence of antibodies due to past infection was found to reduce the diagnostic efficiency of serology for acute intestinal amoebiasis. There was no statistical difference between intestinal cases and controls when comparing either percentage of cases detected or titre of antibody obtained. The results of this study indicate that serology for acute intestinal amoebiasis can be unreliable; however, it is of undoubted value as an adjunct to clinical diagnosis in cases of hepatic amoebiasis.     

Latex agglutination test for amoebiasis in Pakistani patients with chronic 'obscure' liver enlargements.

The latex agglutination test for amoebiasis was done in 50 Pakistani patients in whom a clinical diagnosis of chronic non-supparative amoebic hepatitis was made on the basis of liver enlargement associated with chronic recurrent abdominal disturbance. The serological test was negative in 32 (64%) and positive in 18 (36%). Examination of stool specimens showed a higher frequency of E. histolytica in serology positive patients. The liver biopsy findings were variable and included normal histology in 40 percent and non-specific changes in another 34 per cent of the patients. There was evidence of early abscess formation in one patient with a strongly positive serological reaction. Chronic liver enlargements in this region form a heterogenous group and the existence of chronic non-suppurative amoebic hepatitis as a clinico-pathological entity remains doubtful.     

Cholangiocarcinoma masquerading as liver abscess

A 60-year-old man from Eastern Thailand was admitted to hospital because of right upper quadrant abdominal pain and fever. Ultrasonographic examination revealed two cavitary lesions in the right lobe of the liver. Needle aspiration obtained 110 ml of anchovy sauce-like pus which showed no bacteria on gram stain and routine culture. Serological test for E. histolytica antibody was negative. Initially, the patient responded well to metronidazole. Two weeks later, the symptoms recurred and sonography revealed one large cavitary lesion with three adjacent locules in the right lobe of the liver. Repeated needle aspiration again showed anchovy sauce-like pus which grew Enterobacter agglomerans. O. viverrini ova were detected in the stool. Laparotomy revealed histologically proven cholangiocarcinoma. This report indicates that O. viverrini infection associated with CCC can masquerade as liver abscess.     

Detection of Entamoeba histolytica trophozoites in liver pus by the indirect fluorescent antibody test for the aetiological diagnosis of amoebic liver abscess

The indirect fluorescent antibody test was used to detect trophozoites of Entamoeba histolytica in liver pus aspirated from patients with amoebic liver abscess. The test can be carried out in no more than two hours. Trophozoites with fluorescence were observed in 17 of the 18 patients with amoebic liver abscesses who were studied. Cells with fluorescence were not found in any negative control specimens from patients with bacterial liver abscess, primary liver cancer, cirrhosis or tuberculous peritonitis. These results indicate that this sensitive, specific and rapid test is very useful in aetiological diagnosis of amoebic liver abscess.     

The innate immune response to Entamoeba histolytica lipopeptidophosphoglycan is mediated by toll-like receptors 2 and 4

Entamoeba histolytica is a human pathogen that may invade the intestinal mucosa, causing amoebic colitis or hepatic abscesses when the trophozoites travel through the portal circulation to the liver. Lipopeptidophosphoglycan (LPPG) is a molecular pattern of E. histolytica recognized by the human immune system. Here we report that LPPG is exposed on the cell surface of E. histolytica trophozoites, and is recognized by the host through toll-like receptor (TLR) 2 and TLR4. Correspondingly, human embryonic kidney (HEK)-293 cells were rendered LPPG responsive through overexpression of TLR2 or TLR4/MD2. Moreover, co-expression of CD14 enhanced LPPG signal transmission through TLR2 and TLR4. The interaction of LPPG with TLR2 and TLR4 resulted in activation of NF-kappaB and release of interleukin (IL)-10, IL-12p40, tumour necrosis factor (TNF)-alpha, and IL-8 from human monocytes. Consistent with these findings, responsiveness of mouse macrophages lacking TLR2 expression (TLR2-/-) or functional TLR4 (TLR4d/d) to E. histolytica LPPG challenge was impaired while double deficient macrophages were unresponsive. In contrast to wild-type control and TLR2-/- animals succumbing to lethal shock syndrome, TLR4d/d mice were resistant to systemic LPPG challenge-induced pathology.     

Pyogenic liver abscess caused by Fusobacterium in a 21-year-old immunocompetent male

A 21-year-old male with no significant past medical history, presented with right upper quadrant(RUQ) abdominal pain along with fevers and chills. Lab work revealed leukocytosis, anemia, and slightly elevated alkaline phosphatase. Viral serology for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative and he was immunocompetent.Computed tomography imaging revealed hepatic abscesses, the largest measuring 9.5 cm. Empiric antibiotics were started and percutaneous drains were placed in the abscesses. Anaerobic cultures from the abscesses grew Fusobacterium nucleatum. This is a gram negative anaerobic bacteria; a normal flora of the oral cavity. Fusobacterium is most commonly seen in Lemiere’s disease, which is translocation of oral bacteria to the internal jugular vein causing a thrombophlebitis and subsequent spread of abscesses. Our patient did not have Lemiere’s, and is the first case described of fusobacterium pyogenic liver abscess in a young immunocompetent male with good oral hygiene. This case was complicated by sepsis, empyema, and subsequent abscesses located outside the liver. These abscesses’ have the propensity to flare abruptly and can be fatal. This case not only illustrates fusobacterium as a rare entity for pyogenic liver abscess, but also the need for urgent diagnosis and treatment. It is incumbent on physicians to diagnose and drain any suspicious hepatic lesions. While uncommon, such infections may develop without any overt source and can progress rapidly. Prompt drainage with antibiotic therapy remains the cornerstone of therapy.     

Role of neutrophils in innate resistance to Entamoeba histolytica liver infection in mice

In order to define the role of neutrophils in the innate resistance to Entamoeba histolytica liver infection in mice, we examined the pattern of liver lesion induced by direct injection of  E. histolytica trophozoites in normal mice and in neutrophil-depleted mice. A variety of histological lesions were found, the extent of liver damage was considerably higher in the neutrophil-depleted mice. Livers from neutrophil-depleted mice displayed areas of liquefactive (lytic) necrosis containing a large number of amoebae and absence of neutrophils or mononuclear cells. By contrast, in the liver of normal mice, neutrophils were seen associated to E. histolytica at early stages of infection. In both mouse groups, areas of TUNEL-positive dead hepatocytes were observed and a characteristic internucleosomal banding pattern of genomic DNA consistent with apoptosis was detected in DNA harvested from amoebic liver lesions. These data suggest that neutrophils play an important role in the mechanisms of resistance to amoebic liver infection in mice. In addition, our histological analysis suggests that E. histolytica is capable of producing liver damage in the absence of inflammatory cells .     

Right hepatectomy for pyogenic liver abscesses with true multiloculation

We report the case of a 61-year-old woman with cryptogenic liver abscesses who had been profoundly ill with severe upper abdominal pain, impaired consciousness, prostration, continuous high fever secondary to sepsis, and thrombocytopenia (platelets, 1–5 × 10⁴/mm³) since admission. Ultrasonograms and computed tomograms revealed two separate multiloculated lesions in the right lobe of the liver, consistent with the liver abscesses. Immediately after diagnosis, percutaneous abscess drainage was performed under ultrasonographic guidance; however, only a small amount of pus was drained, prompting continuous irrigation of the abscess cavity. Four days later, transcatheter hepatic arterial infusion of antibiotics was attempted. However, the abscesses had enlarged and her general condition had worsened. On hospital day 8, she underwent right hepatectomy because the multiloculated lesions were refractory to drainage. The operation was successful in terms of hepatectomy, although she continued to suffer from sepsis, secondary right subphrenic abscess formation, and prolonged thrombocytopenia with associated coagulation disorders for two months. Examination of multiple cross sections of the resected specimen disclosed that the lesions consisted of aggregations of multiple small locules. There was no communication between the locules and there were true septations, rather than multiloculated lesions with pseudoseptations. The patient has been well for 2 years without recurrent abscess of the liver or any infectious disease.     

Immunization with a tetramer derivative of an anti-inflammatory pentapeptide produced by Entamoeba histolytica protects gerbils (Meriones unguiculatus) against experimental amoebic abscess of the liver

Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with several anti-inflammatory properties, including the inhibition of human monocyte locomotion (Monocyte Locomotion Inhibitory Factor (MLIF)). A construct displays the same effects as the native material. It remains to be seen if MLIF is used, or even produced in vivo by the tissue-invading parasite. If MLIF were to be relevant in invasive amoebiasis, immunizing against it could diminish this parasite advantage and prevent lesions. KLH-linked MLIF mixed with Freund's adjuvant was too aggressive an immunizing material to answer this question. However, immunization with a tetramer of MLIF (but not a scrambled version of MLIF) around a lysine core (MLIF-MAPS), that displays increased antigenicity, yet lacks excessive innate immunity activation, completely protects gerbils against amoebic abscess of the liver caused by the intraportal injection of virulent E. histolytica. Liver abscesses caused by Listeria monocytogenes were not prevented. Invasive E. histolytica may produce the parent protein of MLIF in vivo, and if appropriately cleaved, it may play a role in invasive amoebiasis. MLIF may join new vaccination strategies against amoebiasis.     

阿米巴肝脓肿的诊断与治疗--附36例报告

目的分析阿米巴肝脓肿的临床特点、诊治及转归情况.方法采用回顾性方法对36例阿米巴肝脓肿患者的临床资料进行分析.结果患者的主要临床表现为上腹痛(86.1%)、发热(86.1%)、肝肿大伴触痛(83.3%)和右肋间压痛(58.3%).实验室检查可见外周血白细胞升高(61.1%)、血沉增快(88.5%)等.92.6%的患者血阿米巴抗体阳性.超声检查示75%为单个脓肿、75%为右叶肝脓肿.所有患者均者用甲硝唑治疗,其中27例患者还同时进行肝脓肿穿刺引流.经治疗后,痊愈10例,显效25例,总有效率97.2%.有1例患者死于肝功能衰竭.结论单用药物治疗对于小肝脓肿疗效好,如肝脓肿较大可同时行脓肿穿刺引流.     

Causative agents of liver abscess in those with liver cirrhosis: a 10-year case review of hospitalized patients in Thailand

Although patients with cirrhosis of the liver show relative immunosuppression and therefore have increased susceptibility to most infections, they rarely develop liver abscesses. In a retrospective case review, the pathogens causing the liver abscesses observed, between January 1992 and December 2001 at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, in 44 hospitalized patients diagnosed as cases of liver cirrhosis were investigated. The most common clinical symptoms and signs of the abscesses--abdominal pain (80%), fever and chills (73%), and abdominal tenderness (73%)--were similar to those seen in non-cirrhotic patients with abscesses. The frequency of liver abscess among the cirrhotic patients was low (0.46%). Most (71%) of the abscesses were in the right lobe and most (71%) of those with abscesses only had a single abscess. Surprisingly, many of the abscesses (36%) were apparently caused by amoebae. Bacterial pathogens were identified in eight patients (18%) by blood culture and 15 (34%) patients by pus culture. Seven (16%) of the blood cultures and 13 (30%) of the pus contained Gram-negative aerobes, indicating that such pathogens, particularly Klebsiella pneumoniae (in six pus and six blood cultures) and Escherichia coli (in three pus cultures and one blood), were the most common causes of the bacterial abscesses. Pus culture appeared more successful than blood culture for bacterial abscesses, and amoebic abscesses could always be identified by direct microscopical examination of pus samples. Aspiration of liver abscesses, to obtain pus samples for culture and microscopy, is therefore recommended.     

Features distinguishing amoebic from pyogenic liver abscess: a review of 577 adult cases

Distinguishing amoebic from pyogenic liver abscesses is crucial because their treatments and prognoses differ. We retrospectively reviewed the medical records of 577 adults with liver abscess in order to identify clinical, laboratory, and radiographic factors useful in differentiating these microbial aetiologies. Presumptive diagnoses of amoebic (n = 471; 82%) vs. pyogenic (n = 106; 18%) abscess were based upon amoebic serology, microbiological culture results, and response to therapy. Patients with amoebic abscess were more likely to be young males with a tender, solitary, right lobe abscess (P = 0.012). Univariate analysis found patients with pyogenic abscess more likely to be over 50 years old, with a history of diabetes and jaundice, with pulmonary findings, multiple abscesses, amoebic serology titres <1:256 IU, and lower levels of serum albumin (P < 0.04). Multivariate logistic regression analysis confirmed that age >50 years, pulmonary findings on examination, multiple abscesses, and amebic serology titres <1:256 IU were predictive of pyogenic infection. Several clinical and laboratory parameters can aid in the differentiation of amebic and pyogenic liver abscess. In our setting, amebic abscess is more prevalent and, in most circumstances, can be identified and managed without percutaneous aspiration.