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Infectious Diseases in Clinical Practice:
doi: 10.1097/01.idc.0000219052.43299.c1
Case Reports

Fever of Unknown Origin (FUO): Multiple Amebic Liver Abscesses in a Patient With Hepatitis C

Mohan, Sowjanya S. MD; Klein, Natalie C. MD; Cunha, Burke A. MD

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Author Information

Infectious Disease Division, Winthrop-University Hospital, Mineola, NY and State University of New York School of Medicine, Stony Brook, NY.

Address correspondence and reprint requests to Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501. E-mail: rholobig@winthrop.org

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Abstract

Abstract: Although amebic liver abscesses are usually single, multiple abscesses may occur in up to 20% of patients. We present a case of multiple amebic liver abscesses occurring in a patient successfully treated for hepatitis C, who presented with a fever of unknown origin.

Amebiasis is an infection caused by Entamoeba histolytica, which is a tissue-invading ameba. It is a leading cause of diarrheal disease worldwide and is a major cause of mortality and morbidity, especially in children. Other species of Entamoeba are nonpathogenic and can also be found in stool examination (eg, Entamoeba dispar and Entamoeba moshkovskii).1

The pathogenesis of E. histolytica usually involves ingestion of the cyst form from food or water contaminated with feces. Some cases, as in sexually active homosexual or bisexual males, may be transmitted by fecal-oral contact. The organism excystates in the intestinal lumen and produces trophozoites, which use lectin to adhere to the colonic mucosa of the large intestine. The trophozoite then reproduces asexually (clonally), and the aggregation of the organisms induces encystations and excretion of the cyst in the feces, thus perpetuating the cycle.2

Most infections with E. histolytica are asymptomatic but can cause dysentery or extraintestinal disease. Extraintestinal disease can present as a liver abscess or pulmonary involvement in the form of a ruptured liver cyst causing empyema or cardiac involvement by rupture of an abscess into the pericardium. Cerebral involvement is a rare occurrence, mostly secondary to hematogenous spread of the organism. Extraintestinal manifestations of E. histolytica infection are rare, but among these, the amebic liver abscess is the most common presentation.3

We present a case of a young man successfully treated for hepatitis C virus (HCV) infection, who presented with fever of unknown origin, and was found to have multiple liver abscesses due to E. histolytica.

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CASE REPORT

A 55-year-old man presented to the emergency department with complaints of fever at home for the past 2 12 months. The fever was associated with night sweats and chills, as well as generalized myalgias. He reported no associated diarrhea, vomiting, cough, headache, or other systemic complaints. His medical history was significant for hepatitis C which had been successfully treated with polyethylene glycol-interferon and ribavirin 6 months before admission. A pretreatment liver biopsy revealed chronic hepatitis C with mild periportal inflammation and moderate lobular inflammation, and necrosis (grade 2-3), and no fibrosis (stage 0). The patient's HCV genotype was 3a, and his HCV RNA was 113,000 IU/mL. The patient was treated with Pegasys 180 μg with Copegus and tolerated treatment without any major side effects. At completion of treatment and 6 months later, he was HCV RNA negative.

The patient traveled to Thailand 4 months after completing polyethylene glycol-interferon and ribavirin. On his return, he complained of diarrhea and was treated empirically with 10 days of metronidazole. After therapy, 3 stool samples were negative for culture, and ova and parasites.

His social history revealed that he was bisexual and had an encounter approximately 11 weeks before presentation when he engaged in unprotected homosexual intercourse. He reported being human immunodeficiency virus (HIV) negative.

On physical examination, he was a moderately built man in no acute distress. His temperature was 100.2°F, pulse 102/min, and blood pressure 126/77 mm Hg. His physical examination was unremarkable except for mild hepatosplenomegaly and right upper quadrant tenderness on deep palpation.

Laboratory data showed a white blood cell count of 11.8 k/mm3 (polymorphonuclear leukocytes, 81%; lymphocytes, 11%; and monocytes, 8%); the platelet count was 452 k/mm3. The erythrocyte sedimentation rate was 115 mm/h, and he had slightly elevated liver enzymes with an aspartate aminotransferase of 71 U/L (normal, 2-35 U/L), an alanine aminotransferase of 93 U/L (normal, 2-40 U/L), and an alkaline phosphatase of 156 U/L (normal, 20-125 U/L). Serum ferritin was markedly elevated at 726 ng/mL (normal, 20-345 ng/mL).

The patient was admitted for fever of unknown origin. Blood cultures, stool cultures, and 3 stool specimens for ova and parasites were negative. The patient continued to have low-grade temperatures (100-100.5°F) while in the hospital, accompanied by drenching night sweats. An enzyme-linked immunosorbent assay (ELISA) HIV test, p24 antigen, and a quantitative HIV polymerase chain reaction were negative. An abdominal computed tomography (CT) scan revealed multiple liver abscesses. (Fig. 1) The largest abscess measured 5.6 × 5.7 cm and the smallest 1.8 × 3 cm. Given his travel history, he was empirically started on metronidazole, 500 mg intravenously every 6 hours, along with piperacillin/tazobactam, 4.5 g intravenously every 8 hours. The following day, he underwent a CT-guided aspiration of one of the abscesses. The aspirate was thick, brown/red, and purulent. Abscess fluid Gram stain, as well as cultures were negative. Subsequently, the patient's E. histolytica ELISA was positive at a titer of 6.1 (normal, <1.1). He was switched to metronidazole, 750 mg (per os) every 8 hours, and he continued to improve clinically. He continued a 2-week course of metronidazole followed by a 1-week course of paromomycin, 500 mg (per os) every 98 hours. A repeat CT scan of the abdomen one month later showed marked reduction in the size of the hepatic abscesses, and a CT scan performed one year later showed complete resolution of the liver abscesses.

Figure 1
Figure 1
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DISCUSSION

Amebiasis is an infection with the protozoan parasite E. histolytica. The study by Walsh published in 1986 estimated that as of 1981, there were 36 million people with clinically active amebiasis worldwide. There are 40 to 100,000 deaths each year from amebiasis, making it the third leading cause of death due to a parasitic infection, with the leading causes being malaria and schistosomiasis.4

E. histolytica was first described by Fedor Losch in 1875. He described a motile trophozoite in a Russian laborer's stools. Subsequently, Councilman and Lafleur described the organism in a sterile liver abscess and called it "Amoeba dysenteriae." Two years later, Quincke and Roos completed the life cycle of the organism by identifying the cyst form.

Peter Sargeaunt from the London School of Hygiene and Tropical Medicine suggested in 1982 that through his method of isoenzyme electrophoresis, there were 2 morphologically identical species of ameba, known together as E. histolytica. This was suggested by Emile Brumpt previously and subsequently confirmed by Dr Sargeaunt. The distinction is now made between the 2 species as E. histolytica and E. dispar. E. histolytica is the species that causes invasive amebiasis, whereas E. dispar is widely believed to be a commensal organism in the gastrointestinal tract.5,6

Infection with E. histolytica can range from an asymptomatic colonization to complications such as liver abscess and other organ involvement. The cyst enters the host most commonly through fecally contaminated food/water or less commonly via sexual contact between bisexual/homosexual males. Dysentery and colitis develop when the cyst excystates into trophozoites in the bowel, involving extracolonic sites such as the liver or brain via hematogenous spread.2

The most common presentation of extraintestinal amebiasis is amebic liver abscess with right upper quadrant pain and fever. Patients who present with a chronic illness lasting more than 2 weeks, report weight loss but only 30% have fever. The most serious complication of an amebic liver abscess is rupture which can lead to pleuropulmonary amebiasis, if the abscess ruptures into the pleural cavity or peritoneal amebiasis if the rupture occurs intraperitoneally. Cardiac involvement can also be seen with rupture of a liver abscess into the pericardium. Cerebral amebiasis is an extremely rare event and usually an autopsy finding. Renal amebiasis presenting as a renal abscess is extremely rare.7

Although 80% of amebic liver abscesses present as a single abscess in the right lobe of the liver, multiple amebic abscesses may occur in up to less than 20%.8,9 Therefore, it is important to consider the diagnosis of amebic liver abscess in patients presenting with multiple hepatic abscesses and distinguish them from pyogenic liver abscesses. Pyogenic liver abscesses are usually multiple and are usually foul smelling. Organisms and white blood cells are readily seen on Gram stain. In a patient with multiple abscesses, aspiration may be needed to differentiate between an amebic abscess and a pyogenic abscess. The different clinical and diagnostic features of pyogenic and amebic liver abscesses are presented in tabular form (Table 1).

Table 1
Table 1
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Amebic liver abscesses are slow to resolve and may initially increase in size despite appropriate therapy. Most of the lesions usually resolve within 6 months on ultrasound but may take as long as a year.

Approximately 90% of patients infected with E. histolytica (clinical or asymptomatic) develop antibodies. The antibodies can be detected by indirect hemagglutination, ELISA, or agar gel diffusion. Diagnosis based on indirect hemagglutination does not differentiate between an active and a past infection because antibodies can be detected up to 10 years after an acute infection. When using ELISA, as in our patient, the test tends to revert back to negative within months of an active infection, so that a positive titer is more likely to reflect an acute infection. Patients develop detectable antibody within a few days to 2 weeks after an acute infection.8,10

The preferred drug for the treatment of extraintestinal amebiasis is metronidazole. It is completely absorbed orally and has a cure rate of 90% in most cases.11 Although metronidazole has been widely used for the treatment of amebiasis, there has been no reported resistance. Metronidazole does not, however, eliminate intestinal carriage and therefore treatment should always be followed by an intraluminal agent (eg, diloxanide furoate, paromomycin, iodoquinol). Tinidazole has been approved in the United States as an alternative drug for the treatment of amebiasis but must also be followed by an intraluminal agent.12,13

Although amebic liver abscesses usually present as a single abscess in the right lobe of the liver, multiple amebic abscesses may occur in up to 20% of patients.14 In one series of patients in India, multiple abscesses were seen in 27% of patients.14 One patient with 25 amebic liver abscesses did not improve clinically until after percutaneous aspiration of the larger abscesses.15 In one group of Indian patients, 50% failed to respond to metronidazole and required aspiration of the abscess.14

Our patient had recently completed therapy for hepatitis C. There is one case report of a patient in Japan with chronic hepatitis C who developed fever and multiple liver abscesses 14 days after beginning interferon therapy.15,16 Interferon therapy probably was responsible for converting subclinical infection into symptomatic amebic liver abscesses.

Our patient had successfully completed hepatitis C therapy 7 months before presentation. Although hepatitis C is not known to predispose to amebic liver abscesses, it is unclear whether recent treatment with interferon may have played a role in this case. Although amebic abscesses are usually single, multiple abscesses may occur in a significant proportion of cases. Using modern imaging, technology has revealed multiple amebic abscesses in a high frequency of cases.8,17

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REFERENCES

1. Sargeaunt PG, Williams JE, Greene JD. The diffentiation of invasive and non-invasive Entamoeba histolytica by isoenzyme electrophoresis. Trans R Soc Trop Med Hyg. 1978;72:519.

2. Haque R, Huston C, Hughes M, et al. Amebiasis. N Engl J Med. 2003;348:1565-1573.

3. Maltz G, Knauer CM. Amebic liver abscess: a 15-year experience. Am J Gastroenterol. 1991;86:704.

4. Li E, Stanley SL. Amebiasis. Gastroenterol Clin North Am. 1996;25:471.

5. Strickland TG. Hunter's Tropical Medicine and Emerging Infectious Diseases. 8th ed. Philadelphia, PA: WB Saunders; 2000:577-588.

6. Jackson TF. Entamoeba histolytica and Entamoeba dispar are distinct species: clinical, epidemiological and serological evidence. Int J Parasitol. 1998;28:181.

7. Thorsen S, Tonne-Rasmussen J, Petersen E, et al. Extra-intestinal amebiasis: clinical presentation in a non-endemic setting. Scand J Infect Dis. 1993;25:747.

8. Katzenstein D, Rickerson V, Braude A. New concepts of amebic liver abscess derived from hepatic imaging, serodiagnosis, and hepatic enzymes in 67 consecutive cases in San Diego. Medicine. 1982;61:237.

9. Adams EB, MacLeod IN. Invasive amebiasis. Amebic dysentery and its complications. Medicine. 1977;56:315.

10. Radin DR, Ralls PW, Colletti PM, et al. CT of amebic liver abscess. Am J Roentgenol. 1988;150:1297-1301.

11. LeBolt SA, Jurado R, Healy GR, et al. Hepatocellular carcinoma simulating amebic liver abscess: report of a case and analysis of current diagnostic methods. Am J Gastroenterol. 1985;80:639-642.

12. Samuelson JC, Burke A, Courval JM. Susceptibility of an emetine-resistant mutant of Entamoeba to multiple drugs and to channel blockers. Antimicrob Agents Chemother. 1992;36:2392-2397.

13. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. A Reference Guide to Fetal and Neonatal Risk. 4th ed. Baltimore, MD: Williams and Wilkins; 1994:585-587.

14. Khanna S, Chaudhary D, Kumar A, et al. Experience with aspiration in cases of amebic liver abscess in an endemic area. Eur J Clin Microbiol Infect Dis. 2005;24:428-430.

15. Soentjens P, Ostyn B, Clerinx J, et al. A case of multiple amoebic liver abscesses: clinical improvement after percutaneous aspiration. Acta Clin Belg. 2005;60:28-32.

16. Matsuo T, Shinzawa H, Sugahara K, et al. Case report: a patient who developed an amebic liver abscess during treatment with interferon. J Gastroenterol Hepatol. 1998;13:1068-1071.

17. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 6th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2005:3105.

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