Gastroenterology and Hepatology Board Review: Pearls of Wisdom, Third Edition

Section VIII HEPATOLOGY

CHAPTER 52. Hepatic Infectious Disorders

Neeraj K. Sardana, MD and Nicholas Ferrentino, MD

Image What are the clinical manifestations of amebic liver abscess?

Patients often present with fever and right upper quadrant (RUQ) pain. Serological evaluation may reveal leukocytosis without eosinophilia, elevation in alkaline phosphatase, and elevated transaminases.

Image How is an amebic liver abscess diagnosed?

A patient with the appropriate clinical picture who resides in, or has traveled to, an endemic area should have imaging of the liver. Ultrasound or computed tomography (CT) imaging will reveal a single subcapsular abscess in the right lobe 70%–80% of the time. Multiple abscesses are also possible. This is usually enough to treat a patient presumptively.

Serologic testing can also be performed; indirect hemagglutination (IHA) is most sensitive. Abscess aspiration is sometimes necessary if the cyst is at risk of rupture, there has been no response to antibiotic therapy, or the diagnosis remains unclear.

Image What percentage of patients with an amebic liver abscess have a history of dysentery or diarrhea?

Less than 33%. Although some patients may describe a history of diarrhea in the weeks to months preceding presentation with an amebic liver abscess, less than one-third have concurrent dysentery at the time of diagnosis.

Image True/False: All amoebae are pathogenic.

False. Entamoeba histolytica is pathogenic in about 10% of infected individuals, whereas E. dispar and E. moshkovskii do not cause clinical disease.

Image What are risk factors for developing amebic liver abscess?

• Living in, or traveling to, an endemic area.

• Adult males; possibly due to alcoholic liver damage increasing susceptibility.

• Any condition that compromises cell-mediated immunity, including advanced age, pregnancy, corticosteroid use (or other immunosupression), malignancy, or malnutrition.

Image What is the drug of choice for treatment of an amebic liver abscess?

Nitroimidazoles (eg, metronidazole). Alternative therapies include dehydroemetine and choloroquine. Luminal amebicides (diloxanide furoate, diiodohydroxyquin, or paramomycin) must always be used following one of the above regimens.

Image Which lobe of the liver is more commonly affected by liver abscesses?

The right lobe, probably due to its larger size and blood flow. Abscesses of biliary origin are more commonly bilateral.

Image What is the leading cause of pyogenic liver abscess?

Biliary tract disease such as gallstones or malignant obstruction accounts for 40%–60% of cases. Other important sources include portal vein pyemia (from bowel leakage or peritonitis), trauma, or direct spread from biliary infection.

Image What are the most common organisms isolated from pyogenic liver abscesses?

Most pyogenic liver abscesses are polymicrobial. Gram negatives such as Escherichia coli and Klebsiella pneumoniae are most common; however, isolation of Gram-positive organisms such as EnterococcusStaphylococcus, and Streptococcus has increased in frequency.

Image What is the most common presenting symptom of a pyogenic liver abscess?

Fever, which is present in about 90% of patients. The next most common symptom is RUQ abdominal pain. Nausea, vomiting, anorexia, weight loss, and malaise may also be present.

Image What factors are associated with increased mortality in pyogenic liver abscesses?

Multiple abscesses, associated malignancy, septic shock, fungal infection, presence of jaundice, hypoalbuminemia, leukocytosis, and presence of bacteremia. Advanced age, biliary etiology, and elevated aspartate aminotransferase are no longer considered to be risk factors.

Image How are pyogenic liver abscesses treated?

Drainage and antibiotics are the mainstays of treatment. Needle aspiration is appropriate for solitary collections < 5 cm in diameter. For larger or multiple lesions, percutaneous catheter drainage is preferred. Empiric antibiotics can be used, but the regimen should ultimately be tailored to the eventual culture and sensitivity results.

Image What is the most common infectious cause of hepatic cysts?

Echinococcus granulosus, a species of tapeworm.

Image What organs other than the liver are involved in echinococcal infections?

Kidney, spleen, brain, heart, lungs, and bones.

Image True/False: Most hydatid cysts are asymptomatic.

True. Symptoms are unusual until a cyst reaches about 10 cm. The latency period between infection and symptoms can be up to 50 years. Many patients never become symptomatic.

Image How are hydatid cysts diagnosed?

A combination of imaging and serological tests can be used. Findings on CT, MRI, and ultrasound may be highly suggestive in a patient from an endemic area. Serology can be used to screen for or confirm infection. Enzyme-linked immunosorbent assay (ELISA) and immune hemagglutinin assay (IHA) are used frequently as serologic screening tests.

Image What stages of the malarial (Plasmodium spp.) life cycle involve the liver?

Pre-erythrocytic phase and exo-erythrocytic phase.

Image What hepatic consequences can occur as a result of malaria infection?

Mild jaundice due to hemolysis is common with infection by any Plasmodium spp. Hepatocyte injury, cholestasis, and severe jaundice may occur with P. falciparum infection but not others.

Image Name the causative organisms of visceral leishmaniasis (VL) or “kala-azar”.

Leishmania donovani and L. infantum.

Image What characteristic findings on liver biopsy are seen in cases of VL?

A “peculiar cirrhosis” or so-called Roger’s cirrhosis. This is characterized by severe intralobular fibrosis with normal architecture and no regenerative nodules. This intralobular fibrosis is completely reversible after treatment.

Image True/False: VL in an HIV-infected person is an acquired immunodeficiency syndrome (AIDS)-defining illness.

True. All patients found to have VL should be tested for HIV coinfection.

Image What is the diagnostic procedure of choice in case of VL?

Examination and culture of splenic needle aspiration has a reported sensitivity of 96%. Bone marrow or lymph nodes can also be aspirated but are less sensitive.

Image What is the drug of choice in the treatment of leishmaniasis?

Liposomal amphotericin B has the highest therapeutic efficacy and the best side effect profile. Second-line agents include pentavalent antimonial compounds (sodium stibogluconate) and conventional amphotericin B deoxycholate, which require increased monitoring of patients for toxicity.

Image Name the schistosomes that affect the liver.

Schistosoma mansoni, S. japonicum, S. mekongi, and S. intercalatum.

Image What are “swimmer’s itch” and “katayama fever”?

Swimmer’s itch is a localized dermatitis, usually on the lower legs or feet, at the site of schistosomal larval entry.

Katayama fever is a hypersensitivity reaction to the heavy burden of schistosomal antigens that coincide with the first 2 weeks of egg production (2–8 weeks after infection). It mimics serum sickness and can be associated with fever, chills, diarrhea, headache, arthralgias, and myalgias.

Image What are typical clinical findings of chronic hepatic schistosomiasis?

Normal liver architecture and cellular function in the presence of portal fibrosis and portal hypertension. Morbidity and mortality are usually related to consequences of ascites or bleeding from esophageal varices.

Image What malignancy is associated with hepatic schistosomiasis?

Follicular lymphoma of the spleen.

Image What is the most useful diagnostic method in the case of active infection with schistosomiasis?

Stool examination for eggs. This becomes negative after successful treatment.

Image What is the drug of choice for schistosomiasis?

Praziquantel.

Image What is the drug of choice to treat the liver flukes, Fasciola hepatica and Fasciola gigantica?

Triclabendazole.

Image Name the malignancy commonly associated with the liver flukes, Clonorchis sinensis and Opisthorchis species?

Cholangiocarcinoma.

Image What characteristic abnormality in liver tests is seen in bacterial sepsis?

Bacterial sepsis and the resulting systemic inflammatory response syndrome (SIRS) can trigger a “parainfectious hepatitis.” Usually there is a cholestatic picture with elevation in bilirubin out of proportion to alkaline phosphatase and aminotransferases. This is commonly caused by E. coli but can be associated with any organism. The source of infection can be intra- or extraabdominal. It is thought that bacterial cell wall endotoxin triggers release of cytokines by bile duct epithelial cells, which in turn affects hepatocyte function.

Image How does Salmonella hepatitis differ from viral hepatitis?

Salmonella hepatitis can be indistinguishable from acute viral hepatitis; however, Salmonella hepatitis is associated with lower peak alanine aminotransferase (ALT) levels and higher peak alkaline phosphatase levels. High fever, relative bradycardia, and a left shift of the leukocyte count favor Salmonella hepatitis.

Image What is Fitz–Hugh–Curtis syndrome?

Perihepatitis occurring as a complication of pelvic gonorrhea or chlamydia infection. It is marked by fever, severe RUQ pleuritic pain, lower abdominal tenderness, and a hepatic friction rub.

Image What is the most common cause of liver-associated enzyme elevation in patients with tuberculosis?

Antituberculous therapy-related hepatotoxicity.

Image What are the manifestations of primary hepatobiliary tuberculosis?

Tuberculomas, ascites, porta-hepatis adenopathy, hepatic abscess, and cholangitis.

Image What group of patients is at high risk of developing a complicated Yersinia infection?

Yersinia is an iron-dependent bacterium that requires exogenous iron for growth. Therefore, patients with hemochromatosis or secondary hemosiderosis are prone to develop hepatic abscesses from Yersinia infection.

Image What stages of syphilis can involve the liver?

Syphilis can involve the liver at any stage. In early syphilis, hepatitis is characterized by elevated alkaline phosphatase with relatively mild elevations in aminotransferases. Late syphilis is uncommon in the current era but is characterized by “gummas,” indolent, and granulomatous-like lesions that can affect any organ. Gummatous hepatitis may be associated with fever, epigastric pain, and tenderness over the liver, and may lead to cirrhosis. Vasculitis or endarteritis related to syphilis infection may also cause liver disease.

Image What is Weil’s disease?

It is a severe icteric form of leptospirosis and is characterized by marked jaundice, azotemia, hemorrhagic phenomena, and hypotension. Minimal elevation of aminotransferases differentiates leptospirosis from acute viral hepatitis.

Image What form of granuloma is seen in Q fever?

Q fever is an infection caused by Coxiella burnetii. When involving the liver, it causes a “doughnut-like” lipogranuloma in which a ring of fibrinoid necrosis and lymphocytes surround a centrally-located fat vacuole. While this lesion is highly suggestive of Q fever, it is not pathognomonic. Similar lesions can be seen in VL, lymphoma, and allupurinol hypersensitivity.

Image What are the most common infections of the liver in AIDS?

Mycobacterium avium complex (MAC) followed by Cryptococcus and cytomegalovirus (CMV).

Image What is the name of the organism known to cause bacillary peliosis hepatitis?

The Gram-negative bacillus, Bartonella henselae. Peliosis hepatis refers to blood-filled cystic changes in hepatic parenchyma that may or may not have an endothelial lining.

• • • SUGGESTED READINGS • • •

Reid-Lombardo KM, Khan S, Sclabas G. Hepatic cysts and liver abscess. Surg Clin North Am. 2010;90(4):679-697.

Kurland JE, Brann OS. Pyogenic and amebic liver abscesses. Curr Gastroenterol Rep. 2004;6(4):273-279.

Benedetti NJ, Desser TS, Jeffrey RB. Imaging of hepatic infections. Ultrasound Q. 2008;24(4):267-278.