Corresponding Author:
Sasan D Noveir
10833 Le Conte Ave
Los Angeles, CA 90095
dnoveir@mednet.ucla.edu
Key words: Entamoeba histolytica; Liver Abscess, Amebic;
Amebiasis; Paromomycin; Parasitic Diseases
Word Count: 1205
Figures : 2
Tables: 1
Acknowledgments: none
Funding sources: None
Author reports no conflicts of interest.
All authors consent to publication
Key Clinical Message:
Amebic liver abscesses should be considered in adult males with fever,
right upper quadrant pain, and weight loss with a history of travel to
endemic areas. Effective treatment includes metronidazole followed by
paromomycin.
Background:
Amebiasis is an intestinal infection with fecal-oral transmission caused
by Entamoeba histolytica , a parasitic amoeba. Infection is
asymptomatic in 80% of cases but can present with abdominal pain,
diarrhea, or constitutional symptoms. Extraintestinal manifestations of
amebiasis can occur from invasive infection, with amebic liver abscess
(ALA) being the most common complication.1 While rates
of asymptomatic amebiasis are equal in both sexes, ALAs are more
prevalent in men.2 Risk factors for infection include
travel to endemic areas with poor sanitary conditions, usually from
contaminated food or water. Clinical manifestation of the disease
typically occurs 8-20 weeks after exposure but can occur decades after
initial exposure.3 The length of stay during endemic
areas is not associated with an increased risk of amebic liver abscess,
underscoring the importance of a complete travel
history.3
Individuals with ALA often present acutely with fever, right upper
quadrant pain, and, occasionally, cough. Subacute anorexia and weight
loss are also reported, with diarrhea notably
absent.1,4 Radiographically, ALAs are variably-sized
solitary collection in the right hepatic lobe, resultant from
preferential portal circulatory system of the right colon.5 Common complications of ALA include transudative
pleural effusions or abscess rupture leading to pleuropulmonary
amoebiasis with a possible misdiagnosis of bacterial pneumonia.5 Rarely, the mechanical compression and inflammation
of amebic liver abscess cause hepatic vein and inferior vena cava
thrombosis.6
Diagnosis of ALA is challenging and relies on imaging and serologicalE. histolytica testing in the appropriate clinical context.
Polymerase chain reaction (PCR) of liver aspirate may be helpful, as
stool PCR can be negative without concurrent amebic
colitis.1 Treatment of ALA includes a ten-day regimen
of metronidazole 750 mg orally three times a day followed by an
intraluminal amebicide, such as a ten-day regimen of paromomycin 10mg/kg
orally three times a day. Decompression is not required but may be
helpful to confirm the diagnosis or if there is a concern for rupture or
lack of response to medical therapy. 7
Case Summary:
A previously healthy 66-year-old man was admitted to the hospital for
workup of recurrent culture-negative liver abscesses refractory to
meropenem therapy. He presented with his fifth occurrence of hepatic
abscess over the past five years (Figure 1) . The patient lives
independently in urban Nevada, with no exposure to animals or engagement
in outdoor activities. There is no history of housing instability or
incarceration. His sexual history included insertive vaginal intercourse
with barrier protection with female partners. His only travel outside
the United States was an uneventful five-day trip to Mexico 30 years
ago. Several months before his first liver abscess, he used subcutaneous
synthetic analogues of growth hormone-releasing hormone (GHRH) for
muscle building. His index presentation was a subacute history of fever,
chills, and fatigue, where he was found to have a liver abscess and
treated with 14 days of ertapenem.
One month following ertapenem therapy, he presented with similar
constitutional symptoms and was found to have recurrent hepatic abscess
formation. He was treated with six weeks of meropenem. SerumEntamoeba histolytica antibody was positive, and he completed a
ten-day course of metronidazole 500 mg orally thrice daily. It is
unclear whether he completed paromomycin after that.
Three years after his second episode, he was hospitalized with fever,
chills, fatigue, and severe dyspnea. He was found to have
methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and
empyema. Cross-sectional imaging revealed recurrence of a liver abscess,
which was aspirated with MRSA. Following percutaneous drainage, a 4-week
course of intravenous vancomycin was administered with radiographic
improvement. Studies for Entamoeba were not sent as it was believed his
liver abscess was pyogenic from MRSA.
One year later, he was found to have recurrence of culture-negative
hepatic collection. Despite completing ertapenem for six weeks and
current treatment of meropenem for three weeks with patent percutaneous
drains, serial cross-sectional imaging demonstrated a previously drained
right lobe abscess cavity, a new right lobe abscess, and a thrombus of
the anterior segment right hepatic vein (Figure 2 ).
The patient was admitted to the hospital for evaluation of this new
liver abscess with adjacent thrombus. The patient noted 60 pounds of
weight loss throughout the last five years but had no abdominal pain,
diarrhea, bloody stools, nausea, or vomiting. Physical examination was
non-contributory. Laboratory investigations were only significant for
normocytic anemia and mildly elevated alkaline phosphatase. Aspiration
of the enlarging hepatic collection was negative for bacteria, acid-fast
bacilli, and fungus. Doxycycline was added to meropenem for acellular
coverage. Esophagogastroduodenoscopy, colonoscopy, and magnetic
resonance enterography did not demonstrate evidence of malignancy or
inflammatory bowel disease. Polymerase chain reaction (PCR) of stool and
the liver abscess were positive for Entamoeba histolytica .
Antibacterials were discontinued, and the patient was discharged with a
ten-day course of metronidazole 750 mg orally thrice daily, followed by
ten days of paromomycin 1000 mg orally thrice daily. Repeat stool PCR
four weeks after treatment was negative for stool ova and parasites.
Discussion:
There are several possible considerations for the recurrent nature of
the patient’s liver abscesses. The initial treatment with metronidazole
at 500 mg thrice daily may have been subtherapeutic as current
guidelines recommend dosing at 750 mg thrice daily. Moreover,
metronidazole therapy alone is insufficient without a subsequent luminal
agent to treat asymptomatic colonization (Table
1).8-10 One study in India found a recurrence rate of
9% within two years among patients not treated with a luminal
agent.11 Another study showed a 72% prevalence of
asymptomatic luminal colonization of E. histolytica at initial
presentation of ALA. Of these patients with concomitant intestinal
infection, treatment with metronidazole was insufficient to eradicate
intestinal infection in greater than 50% of patients despite resolution
of the liver abscess.12 E. histolytica has also
been shown to develop metronidazole resistance in vitro, but the rates
of resistance in practice are unclear.13 Another
possibility considered for the patient’s recurrence was close contact
with an asymptomatic carrier, such as his family. However, the patient’s
family tested negative for the stool E. histolytica antigen.
It is uncertain when the patient was initially infected with E.
histolytica. While his use of exogenous GHRH preceded his first liver
abscess, it remains unclear whether GHRH increased his susceptibility to
ALA recurrence, particularly as he continued to have recurring episodes
of abscesses without repeated travel to endemic regions. It is possible
that while the patient may not have cleared his initial infection, his
exogenous GHRH use may have contributed to the number of relapsing liver
abscesses. Endogenous male hormones such as testosterone may contribute
to these gender differences as mice models show testosterone level
determines susceptibility to ALA.14 The relationship
between GHRH and ALA has not been studied, but it may play a role
similar to testosterone in increasing susceptibility.
Conclusion:
We describe a case of recurrent amebic liver abscesses in a patient
previously treated with metronidazole without repeated travel to an
endemic area. Despite treatment with a 10-day course of metronidazole
four years ago for ALA, the patient developed three additional episodes
of liver abscesses, ultimately found to be from amebiasis. This case
highlights the importance of using appropriately dosed metronidazole,
followed by an intraluminal agent for effective treatment of ALAs.
Imaging and serology are necessary for diagnosis, but PCR testing of
stool and abscess fluid is helpful. Drainage is not necessary but may be
helpful in complicated amebic liver abscesses.
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Figure 1. Representation of liver abscess recurrences.