LIVER INFECTIONS

Tropical Medicine Department

Ain Shams University
Learning outcomes:
❑Classify and enumerate different infections involving
the liver.
❑ Discuss parasitology and microbiology of causative organisms causing
hepatic abscess.
❑Explain pathogenesis of hepatic abscess.
❑Describe clinical features of hepatic abscess.
❑Outline diagnosis and treatment of hepatic abscess.
❑Discuss complications of hepatic abscess.
❑Know the prognosis of hepatic abscess.
 Clinical scenario
• 51 year old female patient presented with progressive abdominal
pain for 3 days.

• The condition started with chest pain 3 days ago , and then became
diffuse severe abdominal pain with abdominal distension.
The patient had chronic hepatitis B virus infection.
• Personal History: shrimp allergy
• Past history: Mitral valve prolapse with medical control,
 Examination
• The patient had jaundice and pallor.
• Decrease air entry on basal lung zones
• Abdomen: distended with diffuse tenderness and rebound.
 Investigations
• Leucocytosis, neutrophilia with shift to the left.
• Microcytic hypochromic anaemia.
• CRP elevated
• Liver enzymes: GOT [0-40 IU/L] 72 ↑ GPT [0-40 IU/L] 72 ↑
• ↓ PT [10.7-13.0 sec.] 14.70 sec
• ↑ Bilirubin D [0.0-0.4 mg/dl ] 1.3 ↑ Bilirubin T [0.2-1.2
mg/dl ] 2.0 ↑

• Explain abnormal findings.

 Imaging
• Solitary lesion in right lobe of the liver

• What is your differential diagnosis?

Image-Differential Diagnosis Focal decreased-
attenuation mass in liver
• Cyst (Echinococcal cyst, polycystic disease)

• Abscess (pyogenic abscess, amebic abscess, fungal abscess)

• Neoplasm (e.g. cavernous hemangioma, HCC)

• Trauma
In this lecture we will focus on:

•Amebic liver abscess.

•Hydatid liver disease.

•Pyogenic liver abscess.

 Amebic liver abscess
➢Amebic abscess are common in areas of the world where Entamoeba
histolytica is endemic.

➢Amebic liver abscess is the most common form of extraintestinal

amebiasis.

➢ It occurs in 5% of patients with symptomatic intestinal amebiasis and

appears 1 to 3 month after disappearance of dysentery.
 Parasitology
• Causative organism: E. histolytica.
• The infective form is the cyst which is ingested. Excystation
occurs in the small intestine, the trophozoites infects the
colon and may cause inflammation and dysentery, ameba
spread to the liver via portal circulation
• The cyst is able to survive outside the body for weeks
whereas the trophozoites are degenerated in minutes.
E. Histolytica life cycle
 Spread of infection
Spread is by the fecal-oral route and is increased by the following:
- Poor sanitation
- Contamination of food by flies
- Unhygienic food handling
- Unclean water
- Use of human feces as fertilizer
 Pathogenesis
• In the liver E. histolytica lyses the host tissue by proteolytic enzymes,
the hepatic lesion is a well demarcated abscess consisting of necrotic
liver and usually affecting the right lobe.

• The abscess contains acellular debris (anchovy sauce, mixture of

sloughed liver cells, blood, chocolate brown colour, thick in
consistency)

• amebic trophozoites are found only at the periphery of the lesion.

 Clinical features
- ALA manifests with amebic colitis in fewer than 10% of cases.
- Patients may have a past history of diarrhea or dysentery and a history of recent travel to endemic
areas is usual.
- E.histolytica can be isolated from the stool in approximately 50% of cases

Symptoms:
- Fever, rigors ,night sweats
- Nausea, anorexia ,malaise.
- Right upper quadrant abdominal pain, pain might be referred ti right shoulder in case of superior
surface abscess.
- Chest symptoms: dry cough and pleuritic pain.
- Diaphragmatic irritation: shoulder tip pain, hiccups.
- Anemia and loss of weight.
Physical examination:
➢Fever.
➢Tender hepatomegaly.
➢Dull right base usually from raised hemidiaphragm, crackles at right base and
plural rub.
➢Jaundice and peritonitis or pericardial rub are rare and poor prognostic signs.
 LABORATORY Diagnosis
- CBC shows leukocytosis without eosinophilia and mild
anemia. Elevated erythrocyte sedimentation rate (ESR)
- Liver functions tests: Elevated liver enzymes & mildly
elevated bilirubin level and ALP but uncommon.
•Stool Microscopy:
- Microscopic examination of fresh stool smears for trophozoites
that contain ingested red blood cells. Stool leukocytes may
be found.
- Stool examination findings in patients with amebic liver
abscess are usually negative.
• Serological tests:
The detection of antibodies is the mainstay of diagnosis of invasive
amoebiasis.
➢Antigen detection: Enzyme-linked immunosorbent assay (ELISA) is used to
detect antigens from E histolytica in stool samples.

➢Antibody detection: indirect hemagglutination test and Complement

fixation test: Serum antibodies against amoebae are present in 70-90%
of individuals with symptomatic intestinal E histolytica infection and in
99% of individuals with liver abscess who have been symptomatic for
longer than 1 week. it remain positive for a prolonged period after
treatment.
 RADIOLOGICAL DIAGNOSIS
Ultrasonography and CT scanning:
- Sensitive but nonspecific for amebic liver abscess. Ultrasonography is preferred for the
evaluation of amebic liver abscess because of its low cost, rapidity, and lack of adverse
effects:
- Round or oval single lesion sometimes multiple
- Hypoechoic compared with normal liver
- Peripheral lesion
Chest radiography:
may reveal an elevated right hemidiaphragm and a right-side pleural effusion or blunting
right costophrenic angle in patients with amebic liver abscess.
Magnetic resonance imaging: may be done
Amebic liver abscess
 Gastrointestinal endoscopy and biopsy

Rectosigmoidoscopy and colonoscopy with biopsy can be

done.
 Complications
➢Complications of amebic liver abscess rupture include the following:
- Intraperitoneal causing ascites and peritonitis.
- Intrathoracic causing hepatobronchial fistula, lung abscess and
empyema.
- Intrapericardial rupture causing pericarditis and cardiac tamponade.
- Secondary infection.
- Dissemination and formation of brain abscess.
- Other rare: IVC obstruction, budd-chiari syndrome.
 Medical treatment
Patients with suspected ALA should be started on therapy while awaiting serologic confirmation.
• Two classes of drugs are used in the treatment of amoebic infections:
❖ Luminal amoebicides as paromomycin (25 mg per kg 3TD for 10 days) or diloxanide furoate (500mg 3 times a
day for 10 days). Metronidazole is both tissue and luminal amoebicide
❖ Tissue amoebicides as metronidazole (750-800mg 3 times a day for 10 days), tinidazole (2 gm per day for 3
days), nitazoxanide, chloroquine and dehydroemetine.
❖ In endemic areas, asymptomatic infections are not treated.
❖ Amebic liver abscess of up to 10 cm can be cured with metronidazole without drainage.
❖ Clinical defervescence should occur during the first 3-4 days of treatment.
❖ Failure of metronidazole therapy may be an indication for surgical intervention.
 Surgical intervention
Surgical intervention is usually indicated in amebic liver abscess in the
following clinical scenarios:
- Uncertain diagnosis (possibility of pyogenic liver abscess)
- Failure to respond to metronidazole after 4 days of treatment
- Empyema after amebic liver abscess rupture
- Large left-side amebic liver abscess representing risk of rupture in
the pericardium
- Severely ill patient with imminent amebic liver abscess rupture.
 Percautenous drainage
Unlike pyogenic liver abscess, uncomplicated amebic liver abscess
generally responds to medical therapy alone; drainage is seldom
necessary and is usually best avoided. Its indications include:
1-Presence of a left-lobe abscess more than 10 cm in diameter
2-Impending rupture and abscess that does not respond to medical
therapy within 3-5 days.
3-To rule out a pyogenic abscess, particularly with multiple lesions.
Aspirated material:
- Yellow to dark brown.
- Odorless.
- Pus consisting mainly of aceullar debris most ameba
are found in the abscess wall.
- Absence of bacteria on culture.
- Definitive diagnosis is made by finding invasive
trophozoites on microscopic exam from tissue or pus
obtained from the abscess or culture but the yield is
low.
PERCUTENOUS drainage
 Prognosis
➢Mortality has fallen below 1% for patients with uncomplicated
amebic liver abscess.
➢Delay in diagnosis may result in abscess rupture with a high mortality
rate.
➢ Previous infection and treatment will not protect against future
colonization or recurrent invasive amebiasis.
➢Complete radiological resolution may take up to 2 years and repeated
imaging is not helpful.
Hydatid Cyst
➢Hydatid cystic disease has a world wide distribution and is
endemic in many sheep- and cattle-rearing regions of the
world.

➢Hydatid disease is a chronic and potentially dangerous

condition that is often overlooked as a cause of abdominal
pain and hepatic disease.
 Parasitology
➢ Echinococcus granulosus is a 3-6 mm tapeworm (zoonotic cestode).
➢ A carniovorous host, usually a dog becomes infected by eating the viscera of
infected sheep that contains hydatid cyst.
➢ Scolices from the cysts adhere to the small intestine of the dog and develop
into the tapeworm.
➢ Dogs excrete E. granulosus eggs in feces and are viable in the environment for
several weeks.
➢ Eggs are ingested by humans either from contamination of soil and foodstuffs
or from the dogs coat and they hatch in the intestine to form onchospheres
(subsequently a cyst) that invade tissue to enter the portal circulation.
➢ Cysts can form in any organs, most commonly the liver(50% to 70%).Cysts
consist of a germinal layer that buds asexually to form daughter cysts which
contain protoscolices the infective forms that are ingested by the definitive
host.
➢ Another species of Echinococcus multilocularis is associated with alveolar cyst
disease and is found in more temperate regions of Europe and North America.
Life cycle of hydatid cyst
Hydatid cyst
 Pathogenesis
➢Spread of the onchospheres is through the blood stream usually the portal
circulation and results in hepatic diseases , other sites are as follows:
- Lung(20% to 30%).
- Bone(less than 10%).
- Brain.
- Heart.
➢Cysts enlarge slowly and cause tissue damage directly or by compromising
the blood supply.The parasite causes a host response to form collagenous
capsule around the germinal layer. This capsule may calcify and often no
host inflammatory response occurs.
 Clinical Features
➢Symptoms:
- Cysts may be asymptomatic and often become symptomatic only after decades because
of their slow growth , symptoms are caused by pressure effects when the cyst reaches a
size of 8-10 cm.
- Symptoms may follow cyst rupture or leakage (fever and hypotension)
- The presentation of a secondary infection of a hydatid cyst resembles the presentation of
a pyogenic abscess.

➢Signs:
- Tender mass (mostly occur in the lower part of the right lobe)
- Chest signs especially at the right base
- Fever
- Jaundice
 DIAGNOSIS
The diagnosis depends on the clinical, radiological and ultrasound findings in a patient who has lived in
close contact with dogs in an endemic area
1- Laboratory findings:
- Elevated serum alkaline phosphatase
- Peripheral esinophillia in 30% of patients
- Elevated serum billirubin level(uncommon)
2- Diagnostic imaging:
- chest film :elevation of the right hemi diaphragm , cysts may be visible in the lung , calcification of
hepatic cyst may be visible below the diaphragm.
- Ultrasonography: cysts may be anechoic, Typically round, septate or daughter cysts are often
visible, separation of germinal membrane may be seen (Water-Lily sign), calcification of cyst wall and
hydatid sand.
- CT scan and MRI
Abdominal CT - Liver Hydatid Cyst
Abdominal CT - Liver Hydatid Cyst
Hydatid cyst in the right lung.
3-Serological testing:
Indirect haemagglutination and ELISA are 75% to 94% sensitive in liver
cysts. Specifity is lower and needs confirmatory test.
4-Examination of aspirated fluid or resected cysts may reveal the
presence of hydatid sand (microscopic protoscolices) which often
have visible hooklets.
Complications:
1- Leakage or rupture of cyst (sometimes iatrogenic from aspiration of
undiagnosed hydatid cyst) may result in the following:
- Allergic reaction, including anaphylaxis (may be fatal)
- Dissemination of disease
- Cholangitis if cyst ruptures into the biliary tract
- Hemoptysis and secondary infection if bronchial rupture

2- Secondary infection of cyst behaves like a pyogenic abscess

Treatment:
Therapeutic options depend on the classification of the cyst
1- Surgery: the treatment of choice for symptomatic cysts ,complex cysts,
such as larger cysts with daughter cysts, peripheral cysts at risk of rupture
and infected cysts, surgical options include the following:
- Radical surgery: pericystectomy or hepatic resection.
- Conservative surgical treatment through unroofing and management of
the residual cavity.
- Laparoscopic procedures.
Regardless of the type of surgical technique used the combination of surgery
with drug therapy is the safest and most effective approach. Secondary
infected abscess should be treated as a pyogenic liver abscess.
2-Drug therapy:
• Used preoperative to limit the risk of intraoperative dissemination, in
conjunction with mechanical drainage procedures also used for
patients with inoperable hydatid cyst.
• Cysts less than 5 cm medical treatment for 6 months.
a. Albendazole is the drug of choice:400 mg 12-hourly orally for 3
months initially or
b. Mebendazole and Praziquantel are alternatives.
• used as cysticidal agents and as such, has an important role
preoperatively.
3-Percutenous drainage: are minimally invasive procedures of choice in
patients in whom surgery is not an option (size more than 5 cm)
- PAIR(puncture, aspiration, installation of cysticidal agents, hypertonic
saline or ethanol , for 5-10 minutes and reaspirated).
- Drug therapy starting before aspiration and continuing for 1 month
after percutaneous therapy is required.
PYOGENIC LIVER ABSCESS
 Pathophysiology
• The liver receives blood from both systemic and portal circulations.
Increased susceptibility to infections would be expected given the
increased exposure to bacteria. However, Kupffer cells lining the
hepatic sinusoids clear bacteria so efficiently that infection rarely
occurs.
Sources of pyogenic liver abscess:
 Etiology
• Polymicrobial involvement is common, with Escherichia
coli and Klebsiella pneumoniae being the two most frequently
isolated pathogens
 Prognosis
• Untreated, pyogenic liver abscess remains uniformly fatal. With timely
administration of antibiotics and drainage procedures, mortality
currently occurs in 5-30% of cases. The most common causes of death
include sepsis, multiorgan failure, and hepatic failure.
Clinical manifestation
• Fever, malaise, right upper quadrant pain
• Cough or hiccough due to diaphragmatic irritation.
• Tender hepatomegaly (mass may be palpable).
• Decreased breath sounds in the right basilar lung zones, with signs of
atelectasis and effusion on examination or radiologically, may be
present.
 Complications
• Sepsis
• Empyema resulting from contiguous spread or intrapleural rupture of
abscess
• Rupture of abscess with resulting peritonitis.
 Investigations
• CBC: neutrophilia, anemia.
• Blood culture.
• Imaging: abdominal ultrasound and CT
• Percutaneous Aspiration and Drainage: diagnostic, therapeutic
 Treatment
• Antibiotic therapy as a sole treatment modality is not routinely
advocated. Used in combination with drainage or surgery for long
duration from 6 to 12 weeks.
• percutaneous drainage
• Surgery: indicated in the following cases signs of peritonitis; existence
of a known abdominal surgical pathology (eg, diverticular abscess);
failure of previous drainage attempts; and the presence of a
complicated, multiloculated, thick-walled abscess with viscous pus.