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ORIGINAL RESEARCH ARTICLE

Metronidazole treatment for acute phase amoebic liver


abscess in patients co-infected with HIV
K Ohnishi

MD PhD

and F Uchiyama-Nakamura

MD PhD

Department of Infectious Diseases, Tokyo Metropolitan Bokutoh General Hospital, Sumida City, Tokyo 130-8575, Japan

Summary: Metronidazole is the drug of choice for invasive amoebiasis; however, it is not known whether its dose or duration
require modification in HIV infection when treating invasive amoebiasis. Seven HIV-positive patients with acute phase amoebic liver
abscess were treated with daily oral administration of 1500 mg of metronidazole for 10 days. None of the patients required abscess
drainage, and metronidazole was effective in all patients without serious side-effects. The CD4 cell count or HIV viral load did not
appear to influence the efficacy of metronidazole therapy.
Keywords: HIV, invasive amoebiasis, amoebic liver abscess, treatment, metronidazole

INTRODUCTION
The protozoan Entamoeba histolytica is distributed worldwide,
symptomatic infection can lead to colitis, liver abscesses,
lung abscesses or brain abscesses. E. histolytica infection has
a low incidence among people living with HIV (PLWH) in
the USA1 and Italy;2,3 a high prevalence of low pathogenic
potential E. histolytica strains have been reported in both
HIV-infected and uninfected people in Mexico.4 Invasive
amoebiasis due to E. histolytica is thought to be rare in PLWH
in some areas of the world; however, invasive amoebiasis is
an important gastrointestinal or hepatic problem for PLWH
in some Far Eastern countries, including Japan.5 8 Amoebic
liver abscess, the most common extraintestinal lesion of
E. histolytica infection, is usually treated with oral metronidazole, but it is not known whether the dose or duration should
be modied according to the CD4 count or viral loads in
PLWH. This report examines the treatment of patients with
acute phase amoebic liver abscess co-infected with HIV and
the efcacy of metronidazole according to HIV surrogate
markers.

PATIENTS AND METHODS

and the remaining patients sexual history was unknown.


None had histories of injection drug use or receipt of blood products. The mean CD4 cell count was 263 cells/mm3 (range 23
415/mm3). Four patients had solitary abscesses and three had
multiple abscesses. The abscesses ranged in size from 25 to
90 mm as measured by computed tomography (CT) scanning
or abdominal ultrasonography. The diagnostic criteria for
amoebic liver abscess comprised: evidence of an intrahepatic
abscess showing a smooth wall conrmed by abdominal
CT scanning and high a titre of serum antibodies against
E. histolytica by a uorescence antibody technique or enzymelinked immunosorbent assay.

Methods
The medical records of the patients mentioned above were
reviewed, and the effectiveness of metronidazole was investigated. We dened treatment to be effective if the symptoms
of patients disappeared during the period of metronidazole
administration, and the size of the liver abscess (measured
just prior to commencement of metronidazole) was reduced
when measured after completion of metronidazole therapy.

RESULTS

Patients
Seven HIV-infected patients with acute phase amoebic liver
abscess were admitted to our hospital department and treated
with daily oral administration of 1500 mg of metronidazole
for 10 days between January 2000 and December 2008. None
of them required abscess drainage. The proles of the patients
are shown in Table 1. All patients were Japanese and had
acquired their amoebiasis and HIV infection in Japan. Six of
the seven patients were men who had sex with men (MSM)

Oral administration of metronidazole at daily doses of 1500 mg


for 10 days was effective in all patients and no serious sideeffects were reported. The response to the treatment was
similar to that seen in non-HIV-infected amoebic liver abscess
patients, and the CD4 cell count or HIV viral load at the
beginning of metronidazole administration did not modulate
the efcacy of therapy.

DISCUSSION
Correspondence to: Dr K Ohnishi
Email: infection@bokutoh-hp.metro.tokyo.jp

Six hundred and forty-six cases of amoebiasis (560 men and 86


women) due to E. histolytica acquired through sexual contact
DOI: 10.1258/ijsa.2009.009264. International Journal of STD & AIDS 2012; 23: e1 e3

e2

International Journal of STD & AIDS

Volume 23

August 2012

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Table 1

(a) Profiles of the patients with amoebic liver abscess; (b) profiles of the patients

(a)
Case

Age (years)

Gender

Height (cm)

Body weight (kg)

CD4 (cells/mm3)

1
2
3
4
5
6
7

59
39
42
43
38
58
38

M
M
M
M
M
M
M

162
165
164
166
168
160
167

63
52
62
55
61
61
55

310
23
400
213
270
207
415

HIV-RNA (copies/mL)
50
1.2  105
7.6  105
3.8  104
,50
1.6  106
9.6  103

MSM

On ART

2
2
2

2
2

(b)
Case

Size of abscess (main liver segment)

No of abscesses

Complications and co-morbidities

1
2
3
4
5
6
7

90 mm
60 mm
90 mm
25 mm
80 mm
80 mm
40 mm

1
1
5
3
1
41
1

Hepatitis C, hepatic cirrhosis


Intestinal amoebiasis, miliary tuberculosis, syphilis
Syphilis
Intestinal amoebiasis, syphilis

Syphilis

(S4)
(S6)
(S5)
(S7)
(S5, 6)
(S5, 6)
(S2)

MSM men who have sex with men; ART antiretroviral therapy; M male; ART antiretroviral therapy
The largest diameter (the largest abscess) in cases of multiple abscesses

were reported in Japan from January 2003 to December 2006,


and 326 of them were thought to have acquired their
E. histolytica infection due to malemale sexual contact.9
However, the number of infected patients who were MSM
may actually be higher considering the high male-to-female
ratio of cases. Transmission of E. histolytica is thought to take
place through the ingestion of cysts during close physical or
sexual contact between MSM.
The cumulative total of HIV cases in Japan has been reported
to be 13,894 (11,447 men and 2447 women) excluding those
infected through coagulation factor products from 1985 to
2007,10 but the true number of PLWH is thought to be higher
than the reported numbers. In 2007, 1082 new HIV cases
(1007 men and 75 women) who had not developed AIDS and
418 new AIDS patients (377 men and 41 women) were reported
in Japan, and among Japanese HIV cases aged 15 49 years old,
the proportion of men infected from homosexual sex exceeded
70%.10 From these data, it is possible to surmise that
HIV-infected men, compared with HIV-negative men, are at
higher risk for invasive amoebiasis in Japan. Amoebic liver
abscess should be considered in the differential diagnosis for
all HIV-infected men, especially MSM, with a liver abscess in
Japan.
It has been reported that thymus-dependent immunity plays
an important role in the response of hamsters to infection with
E. histolytica,11 and it is well known that an HIV infection can
result in the impairment of cell-mediated immunity. Thus,
amoebic liver abscess patients co-infected with HIV may be
more likely to have a protracted course without appropriate
therapy according to these reports. However, the depletion of
CD4 cells signicantly diminished both the E. histolytica
burden and inammation in the mouse model of amoebic
colitis,12 and the clinical presentation of the amoebic liver
abscess in ve HIV-infected patients was similar to that
reported in non-HIV-infected patients.13 Whether invasive
amoebiasis becomes a more serious problem in HIV-infected
persons with low CD4 cell counts remains unclear.
Amoebic liver abscess is an emerging parasitic disease and
may be fatal without appropriate treatment in both

HIV-infected and uninfected persons. Although dose and duration of metronidazole were not described, good therapeutic
results were reported with a combination of metronidazole
and drainage in two amoebic liver abscess patients co-infected
with HIV with CD4 counts of 421 and 429 cells/mm3, respectively,14 and by the administration of metronidazole in ve
amoebic liver abscess patients co-infected with HIV whose
CD4 cell counts were 220370 cells/mm3.13 Our study
revealed that a daily oral administration of metronidazole at a
dose of 1500 mg for 10 days, which is the standard therapeutic
regimen against acute phase amoebic liver abscess in adult
patients in immunocompetent persons in Japan, is also effective
against acute phase amoebic liver abscess patients with HIV
co-infection. This occurred in spite of CD4 cell counts and
HIV viral loads that ranged from 23 to 415 cells/mm3 and
,50 copies/mL to 1.6  106 copies/mL, respectively. This
case series suggests that the effectiveness of metronidazole
was not interfered with by the number of CD4 cell and HIV
viral loads, and that neither a change in daily dose nor duration
is needed in advanced HIV. None of our patients underwent
abscess drainage and clinical cure was obtained with only
metronidazole therapy. Although dependent on the site of the
abscess in the liver, drainage seems unnecessary in abscesses
of ,90 mm diameter in general, though further studies
guiding abscess drainage in cases of amoebiasis are needed.

CONCLUSION
Oral administration of metronidazole at a daily dose of 1500 mg
for 10 days is effective against amoebic liver abscess in spite of
HIV co-infection, and the CD4 count or HIV viral load showed
no inuence on the efcacy of the metronidazole therapy.
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Ohnishi and Uchiyama-Nakamura Amoebic liver abscess in HIV infection

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(Accepted 28 June 2009)

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