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CHAPTER 49 - PARASITIC INFECTIONS OF THE HEPATOBILIARY SYSTEM

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PARASITES CAUSING HEPATOBILIARY INFECTIONS

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1. AMOEBIC LIVER ABSCESS (ALA)

• Important cause of space-occupying lesions of the liver
• Occurs mainly in developing countries
• Caused by Entamoeba histolytica
• About 2-8% of patients with intestinal amoebiasis develop extraintestinal amoebiasis

Pathogenesis

• Transmission: Ingestion of food/water contaminated with E. histolytica cysts
• Attachment: Cysts develop into trophozoites → adhere to intestinal mucosa via Gal/NAG lectin antigen (major virulence factor)
• Invasion: Trophozoites secrete cysteine proteases and hydrolytic enzymes → invasion of intestinal mucosa → erosion and necrosis of small intestine → entry into portal venous system → carried to extraintestinal sites
• Survival: Resistance to complement-mediated lysis (mediated by Gal/NAG lectin antigen) - critical for survival in bloodstream
• Site: Liver is the most common site; followed by lungs, brain, genitourinary tract, spleen
  • Most common hepatic site: posterior-superior surface of right lobe
  • Usually single; rarely multiple

Liver Abscess - Key Features

• Inflammatory response surrounding hepatocytes → abscess formation
• Abscess wall: comprised of necrotic hepatocytes and a few amoebic trophozoites
• Pus: Thick, chocolate-brown - called "anchovy sauce pus"
  • Comprised of necrotic hepatocytes without pus cells
  • Amoebic trophozoites mainly found in last few drops of pus
• Microscopic layers of abscess wall (3 layers):
  1. Inner/central zone - necrotic hepatocytes without amoeba
  2. Middle zone - degenerative hepatocytes, RBC, leukocytes, occasionally amoebic trophozoites
  3. Outer zone - healthy hepatocytes with amoebic trophozoites

Clinical Presentation

• Tender hepatomegaly + fever
• Weight loss, sweating, weakness
• Very rarely jaundice and cough

Complications

• Right-sided abscess: May rupture externally → skin lesions on abdominal wall (amoebiasis cutis) OR rupture into lungs (pulmonary amoebiasis or amoebic pleuritis)
• Rupture below diaphragm → subphrenic abscess + generalized peritonitis
• Left-sided abscess: May rupture into stomach, left pleura, or pericardial cavity
• Hematogenous spread → brain, lungs, spleen, genitourinary organs (painful genital ulcers)

Epidemiology

• Worldwide: ~40-50 million cases/year; majority in developing countries
• Highest prevalence: Tropics - Mexico, India, Central/South America, tropical Asia and Africa
• Most common group: Young adult males (male:female = 9:1)
• Risk factors: Immigrants from endemic areas, crowding, poor hygiene, immunosuppression

Laboratory Diagnosis

Treatment

• Tissue amoebicidal agent (acts on trophozoites) → followed by luminal amoebicidal agent (eradicates intestinal carriage)
• Tissue agents: Metronidazole (750 mg PO or IV for 5-10 days) OR tinidazole/ornidazole (2g PO once)
• Luminal agents: Iodoquinol (20 days) OR paromomycin (10 days)

1. Risk of impending rupture
2. Left lobe liver abscess >10 cm
3. No improvement after anti-protozoan therapy for 5-7 days

Drug Resistance

• Metronidazole resistance reported in E. histolytica
• Multidrug resistance also reported against iodoquinol, diloxanide furoate, emetine

Prevention

• Avoid ingestion of food and water contaminated with human feces
• Treatment of asymptomatic persons

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2. HUMAN ECHINOCOCCOSIS

• Zoonotic disease caused by a cestode - Echinococcus
• Occurs in the following forms:

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CYSTIC ECHINOCOCCOSIS (HYDATID DISEASE)

• Caused by Echinococcus granulosus (dog tapeworm)
• Tissue cestode existing in three morphological forms: adult worm, larva, egg

Morphology

• Adult worm: Resides in dog's intestine; 3-6 mm long; head, neck, strobila comprising 3 proglottids/segments
• Larva (Hydatid cyst): Pathogenic form; produces cystic lesions in liver and other viscera
• Eggs: Infective form; embryo with six hooklets surrounded by embryophore; morphologically similar to Taenia eggs

Life Cycle

• Definitive host: Dogs and other canine animals
• Intermediate hosts: Sheep and other herbivores; Man is an accidental intermediate host (dead end)
• Infective form: Eggs
• Mode of transmission: Man acquires infection by ingestion of food contaminated with dog's feces containing E. granulosus eggs
• In duodenum → embryo/oncosphere released → penetrates intestinal wall → enters portal circulation → carried to liver (60-70% of cases) or rarely other organs
• Although majority of embryos are destroyed by host immune response, few escape and develop into fluid-filled hydatid cysts
• This stage is infective to dogs
• Man is a dead end (dogs do not feed on human viscera → cycle stops)
• Development in Dog: Acquire infection by consumption of contaminated viscera of intermediate hosts (sheep) containing hydatid cysts → larva transforms into adult worm → adult worms sexually mature → eggs passed in feces

Hydatid Cyst

• Fluid-filled bladder-like cyst; average size: 3-8 cm
• Cyst wall - 3 layers:
  1. Outer pericyst - host-derived
  2. Middle ectocyst
  3. Inner endocyst
• Brood capsule: Inner side of endocyst gives rise to brood capsules containing protoscolices (future head)
• Hydatid fluid: Clear, pale yellow-colored; antigenic, toxic, anaphylactic
• Hydatid sand: Brood capsules and protoscolices break off and deposit at the bottom
• Fate of hydatid cyst:
  • Spontaneous resolution, OR
  • Rupture → formation of secondary cysts (other organs) OR anaphylactic reaction to hydatid fluid antigens

Clinical Features

• Usually occurs in childhood; manifests in adult life
• Most common site: Liver (60-70%, right lobe) → lung (20%) → kidney, muscle, spleen, soft tissue, brain, bone
• Cysts grow 0.5-1 cm/year; can survive years to decades without symptoms
• Symptoms due to:
  • Pressure effect: Palpable abdominal mass, hepatomegaly, abdominal tenderness, portal hypertension, ascites
  • Obstruction: Daughter cysts erode into biliary tree or bronchus → cholestasis, cholangitis, dyspnea
  • Secondary bacterial infection: Pyogenic abscess in liver
  • Anaphylactic reactions: Cyst leakage/rupture → hypotension, syncope, fever

Epidemiology

• Worldwide; higher incidence from Central Asia
• In India: Andhra Pradesh, Tamil Nadu, Chandigarh, Kashmir, Maharashtra, West Bengal

Laboratory Diagnosis

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ALVEOLAR ECHINOCOCCOSIS

• Caused by Echinococcus multilocularis
• Life cycle similar to E. granulosus but hosts differ:
  • Definitive host: Foxes and wolves
  • Intermediate host: Small wild rodents
  • Man is accidental intermediate host
• Produces alveolar (multilocular) hydatid disease
• Cysts have multiple locules resembling lung alveoli
• Liver most commonly affected (98%)
• Cyst can migrate rapidly to other organs - mimics a malignant tumor
• Geographical distribution: Russia, China, South Europe, North America
• Lab diagnosis and treatment same as for E. granulosus

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NEOTROPICAL ECHINOCOCCOSIS

• Two forms: polycystic (E. vogeli) and unicystic (E. oligarthrus)
• Mainly infect animals; human infection extremely rare
• Reported from South America

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3. TREMATODE INFECTIONS OF THE LIVER

• Fasciola, Clonorchis, and Opisthorchis together called liver flukes
• Fasciola infects liver and bile duct
• Clonorchis and Opisthorchis infect only the bile duct

Life Cycle

• Morphology: Leaf-like adult worms, operculated eggs, larvae in 5 stages
• Definitive host: Man (or animals like sheep for F. hepatica)
• Intermediate hosts:
  • First: Snails
  • Second: Aquatic plant (Fasciola) or crayfish (Clonorchis, Opisthorchis)
• Transmission: Man gets infection by ingestion of second intermediate host carrying metacercaria larvae (infective form)
• Spread: Larvae excyst → penetrate intestinal wall → migrate to liver/bile duct → develop into adult worms → fertilize → eggs passed via bile duct/liver to intestine → excreted in feces (diagnostic form)

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FASCIOLIASIS (Fasciola hepatica)

• Reported worldwide; particularly in sheep-raising countries (Peru, Bolivia, Chile); extremely rare in India
• Clinical features: Metacercaria larvae migrate to liver → right upper quadrant pain, hepatomegaly → bile duct → obstruction, dilatation, biliary cirrhosis; does NOT cause malignancies
• Stool microscopy: Large operculated eggs: 130-150 µm × 63-90 µm; similar to F. buski
• Other diagnostic tests: ELISA, western blot, PCR-based molecular methods, CT scan, MRI
• Treatment: Triclabendazole is drug of choice
• Prevention: Sanitary disposal of sewage, snail host control, avoid raw water plants

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FASCIOLA GIGANTICA

• Closely related to F. hepatica; common parasite of herbivores (cattle); human infection rare
• Eggs morphologically similar but larger in size
• Life cycle, clinical features, lab diagnosis, and treatment same as F. hepatica

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CLONORCHIASIS AND OPISTHORCHIASIS

• Clonorchis sinensis (Chinese/oriental liver fluke): Found primarily in Eastern Asia (China)
• Opisthorchis viverrini: Southeast Asia; not reported in India yet
• Clinical features (heavy/chronic worm burden): Mechanical obstruction of bile duct →
  • Cholangitis, dilatation, fibrosis of bile duct
  • Cholangiocarcinoma (bile duct carcinoma)
  • O. viverrini can also cause hepatocellular carcinoma
• Stool microscopy: Flask-shaped eggs; Clonorchis: 28-35 µm × 12-19 µm; Clonorchis and Opisthorchis eggs are morphologically indistinguishable
• Treatment: Praziquantel is drug of choice
• Prevention: Sanitary sewage disposal, snail control, avoid raw/undercooked freshwater fish

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4. HEPATOSPLENIC SCHISTOSOMIASIS

• Lodging of Schistosoma mansoni and S. japonicum eggs in the liver → granuloma formation and fibrosis
• Called Symmers pipestem fibrosis

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5. LARVA MIGRANS

• Nematodes of lower animals occasionally infect man → larva migrans (LM)
• In humans: larvae cannot complete normal development (humans are unusual host) → life cycle arrested → larvae wander aimlessly in body

Two Types in Humans:

• Larva migration in skin and subcutaneous tissue

• Larva migrates to viscera → life cycle arrested
• Primarily caused by Toxocara (less frequently by other helminths)
  • Two species: T. canis (dog roundworm) and T. cati (cat roundworm)
  • Transmission: ingestion of embryonated eggs (infective form) contaminated in soil → eggs develop into larvae → penetrate intestinal wall → carried via portal circulation to liver
• Other agents:
  • Gnathostoma spinigerum: Creeping eruption, eosinophilic meningoencephalitis, ocular larva migrans
  • Angiostrongylus cantonensis: Eosinophilic meningitis
  • Angiostrongylus costaricensis: Abdominal infection
  • Anisakis: Eosinophilic granuloma of bowel
  • Baylisascaris procyonis: Eosinophilic meningitis
• Toxocara mainly affects the liver → visceral larva migrans (VLM) or eye → ocular larva migrans (OLM)
• Diagnosis: ELISA using excretory-secretory antigen of T. canis - highly sensitive and specific; biopsy of tissue (liver, lungs, brain) may occasionally reveal larvae
• Treatment: Albendazole or mebendazole with glucocorticoids

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6. RARE PARASITIC INFECTIONS OF THE LIVER

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QUICK REVISION - HIGH YIELD POINTS

• Anchovy sauce pus = ALA (thick chocolate-brown, no pus cells)
• Definitive host for Echinococcus = Dog
• Alveolar hydatid = E. multilocularis
• Water lily sign on imaging = Hydatid cyst
• Casoni test = obsolete; Type I hypersensitivity
• Most common agent of VLM = Toxocara canis
• Cholangiocarcinoma associated with = Clonorchis sinensis
• Triclabendazole = Drug of choice for Fasciola
• Praziquantel = Drug of choice for Clonorchis/Opisthorchis
• Symmers pipestem fibrosis = Hepatosplenic schistosomiasis
• Male:Female ratio in ALA = 9:1 (young adult males)
• Most common site in hydatid = Right lobe of liver (60-70%)
• E. granulosus most common genotype in India = Type 1