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Nonviral Infections of the Liver
Abbreviations
AIDS
acquired immunodeficiency syndrome
ELISA
enzyme-linked immunosorbent assay
HAART
highly active antiretroviral therapy
HIV
human immunodeficiency virus
HTLV-I
human T-cell leukemia-lymphoma virus I
MRDT
malaria rapid diagnostic test
OPN
osteopontin
PCR
polymerase chain reaction
SEA
soluble egg antigens
Th 1
T helper cell 1
Th 2
T helper cell 2
VL
visceral leishmaniasis
Hepatic dysfunction, presenting either as a hepatitic or as a cholestatic process, may be caused by a great variety of nonviral infectious agents, such as bacteria, fungi, and parasites. These agents may involve the liver directly and exclusively, but more commonly do so as part of a systemic infection reaching the liver through the portal vein, the hepatic artery, or the biliary tract. Systemic infection is suspected as the underlying cause of hepatic dysfunction if the patient has high and prolonged fever with mild transaminase increase and signs of multiple organ dysfunction syndrome. Clinical and histologic evidence of an extrahepatic source may be present. Recognizing systemic infections and distinguishing them from classic viral hepatitis is essential to improving outcomes, which depends largely on early initiation of specific therapy.
There are three major mechanisms of liver injury from the organisms mentioned earlier: (1) direct infection of the hepatic parenchyma; (2) immune-mediated damage caused by an immune response against the infectious agent; and (3) local or systemic inflammatory response induced by the infectious agent or its product such as endotoxin or lipopolysaccharide. Hepatic responses vary depending on the etiologic agent and on the individual’s immune status and inflammatory response. The infection may resolve because of the responses of Kupffer cells and other cells of the innate immunity or lead to hepatocellular or biliary injury, giving rise to a hepatitic or cholestatic clinical picture.
As in viral hepatitis, acute infections caused by nonviral infectious agents may lead to hepatomegaly and frequently to jaundice with variable degrees of hepatocellular injury. This is seen in bacterial infections such as pneumonia, septicemia, and leptospirosis, as well as in protozoal infections such as malaria. Chronic infections or parasitic infections such as schistosomiasis, visceral larva migrans, leishmaniasis, and fascioliasis lead to hepatomegaly, with variable patterns of fibrosis and granulomas, usually with minimal or no jaundice. Infections may lead to space-occupying lesions such as granulomas and abscesses, which tend to present with biochemical cholestasis unaccompanied by jaundice. Hepatomegaly and splenomegaly, especially in the tropics, reflect hyperplasia and hypertrophy of Kupffer cells, which contain phagocytosed pigments such as malarial and schistosomal pigment, sinusoidal lymphocytosis, granulomas, and variable portal inflammation. In the contemporary world of close and frequent global interactions, these manifestations formerly considered “exotic” must be recognized by all pathologists irrespective of global location.
Bacterial Infections
Liver in Sepsis
Approximately one-third of patients with bacterial sepsis have evidence of hepatic involvement, with higher prevalence in patients with preexisting liver disease. Cholestasis is commonly described in patients with bacterial infections caused by gram-negative (eg, Pseudomonas aeruginosa, Escherichia coli ) and gram-positive (eg, Staphylococcus aureus ) organisms. Increase in bilirubin is typically more than in transaminases, with levels as high as 30 to 50 mg/dL having been reported. Fever and leukocytosis with a left shift are common. Blood culture is usually positive, but the septic syndrome may occur even when an etiologic agent is not demonstrable.
The probable mechanism is induction of the systemic inflammatory response syndrome by lipopolysaccharide, which translocates from the gut to sterile organs and blood via the portal venous system. Lipopolysaccharide activates proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1, interleukin-6) that are thought to inhibit the canalicular excretion of conjugated bilirubin. Lipopolysaccharide is initially cleared by hepatic reticuloendothelial system cells; however, the inherent ability of liver clearance is limited, and excessive quantities of lipopolysaccharide induce injury to the liver and other distant organs. Treatment of sepsis-associated hepatic injury consists of treating the underlying infection and supporting vital functions. Antibodies against lipopolysaccharide, tumor necrosis factor, and other novel therapeutic tools are under evaluation.
Pathology
In general, liver histology shows inflammation with variable degrees of polymorphonuclear leucocyte infiltration, cholestasis, and steatosis. In most cases, liver architecture is preserved, with infiltration of edematous portal tract by a mild inflammatory infiltrate of lymphocytes, macrophages, and a variable amount of polymorphonuclear cells, predominantly neutrophils. Hypertrophic and hyperplastic Kupffer cells phagocytose bacterial remnants and red blood cells. Sinusoids may become dilated, especially in zone 3. Intrahepatocytic or canalicular cholestasis may be found. Such a picture is known as nonspecific reactive hepatitis ( eSlide 3.1 ) and is the most common pattern of hepatic involvement in necropsies of patients dying because of bacterial sepsis.
As described by Lefkowitch, cholangitis lenta is an unusual form of intrahepatic cholestasis manifested by inspissated bile within dilated bile ductules without evidence of large bile duct obstruction ( Fig. 18.1 ) ( eSlide 3.3 ). Identification of this pattern of cholestasis in liver biopsy specimens may suggest a great risk of mortality and indicate the need for more aggressive management of the systemic infection.
Pyogenic Abscess
The presence of one or more masses of liquefied necrotic liver parenchyma (liver abscess) may be classified according to etiology: pyogenic and amebic abscesses are the two major types. Whereas amebic abscess (discussed later in this chapter) is more common in developing countries, pyogenic abscesses are much more common in developed nations, where E. coli , Klebsiella , Streptococcus and other bacteria reach the liver through ascending biliary tract infection or by hematogenous spread through the portal venous system or the hepatic artery. ( Fig. 18.2 ). Pyogenic abscesses secondary to ascending cholangitis occur most often because of impairment of bile flow by calculi, stenosis, sclerosing cholangitis, or biliary neoplasia. Bacterial cholangitis, most frequently caused by gram-negative bacilli from the gut, leads to permeation of bile ducts and ductules by polymorphonuclear leukocytes, which may be seen encircling aggregates of bacilli. Multiple periductular microabscesses are found.
Although the portal venous system is less frequently reported as a relevant source of bacterial infection of the liver in Western developed countries, it is a frequent source of infections in less developed areas. Appendicitis, diverticulitis, chronic inflammatory diseases of the intestine, and intraperitoneal abscesses are the originating sites of infection, leading to liver abscesses that may be single, multiple, or multiloculated. Portal phlebitis may be identified in these cases.
Bacterial infection reaching the liver through the hepatic artery results from sepsis, urinary or respiratory tract infections, endocarditis, or osteomyelitis. Among several bacteria, sepsis attributed to Staphylococcus may be considered the prototype of these lesions with several foci of parenchymal necrosis, where gram-positive cocci are intermixed with neutrophils. Other sources of bacterial infections of the liver are contiguous dissemination of gallbladder empyema, acute pleuritis, and perinephric or subphrenic abscesses, as well as hepatic trauma.
A prospective study of 125 patients admitted to the Department of General Surgery of a public hospital in Kolkata, India found a strong correlation of hepatic abscesses with alcohol addiction, history of diabetes mellitus, and low socioeconomic status. Amebic liver abscess was found in 110 cases (88%). Among 15 cases (12%) of pyogenic liver abscess, E. coli was the most frequent bacterial infection. Percutaneous catheter drainage was the most effective method of treatment. There were seven deaths, most of them attributed to diffuse peritonitis caused by rupture of the abscess.
Salmonellosis
Salmonella typhi and Salmonella paratyphi cause an acute systemic disease, enteric fever, which is a major public health problem in less developed areas. An estimated 21 million new infections occur every year and result in approximately 200,000 deaths. Enteric fever affects people of all ages, and it presents clinically with high fever (>40° C), relative bradycardia, and a left-shift of the white blood cell count. Severe cases are usually associated with renal insufficiency, rhabdomyolysis, and disseminated intravascular coagulation.
The severity of illness in individuals with salmonellosis is determined by virulence factors of the infecting strain as well as host properties. Virulence factors of salmonellae are complex and encoded on chromosomes and plasmids. Major host risk factors are immunodeficiency due to human immunodeficiency virus (HIV) infection or immunosuppressive therapy, neoplasms, diabetes and prior antimicrobial therapy. Sickle cell disease, malaria, schistosomiasis, bartonellosis, and pernicious anemia are among the major comorbidities that predispose to salmonellosis.
Pathogenesis
The bacilli gain entry by attaching to specialized epithelial cells (M cells) of the Peyer patches by fimbriae or pili. This is followed by endocytosis leading to bacterial internalization and transport to the lamina propria, where they attract macrophages (typhoidal strains) or neutrophils (nontyphoidal strains). S. typhi disseminate through the mononuclear phagocyte system, mainly to the liver, spleen, and bone marrow. Infection of the gallbladder may lead to a long-term carrier state in which the bacilli are present in bile and secreted to the stool. Nontyphoidal salmonellae generally precipitate a localized response, whereas S. typhi and other especially virulent strains invade deeper tissues via lymphatics and capillaries and elicit a major immune response.
Liver Disease in Salmonellosis
Although clinical hepatitis is evident in less than 25% of cases, liver involvement is almost always present. Jaundice is less frequent (33%) than in acute viral hepatitis. Liver histology shows nonspecific hepatitis with variable degrees of portal tract infiltration by lymphocytes and macrophages. Necroinflammatory foci and nonnecrotizing epithelioid granulomas (typhoid nodules) are interspersed within the parenchyma, with varying degrees of macrovesicular or predominantly microvesicular steatosis.
Diagnosis
Specific diagnosis can be made by culture and/or serology. Treatment includes antibodies (fluoroquinolones) and metabolic support. Long-term therapy may be necessary to eradicate the carrier state.
Brucellosis
Brucellosis, a zoonosis acquired from bovines, is a continuing public health concern in developing countries. Most at risk are workers exposed to animals or animal products infected with gram-negative bacilli from the genus Brucella , most commonly Brucella melitensis, Brucella suis, Brucella canis, and Brucella abortus . General malaise is commonly followed by fever, chills, and headache. Prolonged infection leads to weight loss, pleural effusion, orchiepididymitis, arthritis, meningitis, and hepatosplenomegaly.
Liver Involvement in Brucellosis
Liver involvement is suspected in patients with severe abdominal pain and/or jaundice with abnormalities in serum biochemical markers of liver injury. However, because brucellosis is a systemic infection and bacteria survive within mononuclear phagocytes, the liver, being a major organ of reticuloendothelial system, is probably involved in all cases, even if transaminase levels are normal or only mildly elevated.
Diffuse liver enlargement is rather frequent, whereas hepatic abscesses may sometimes occur ( Fig. 18.3 ). Liver histology may be nonspecific, with focal intraparenchymal collections of lymphocytes and/or macrophages, which may form microgranulomas. Epithelioid granulomas may be present, which when fully developed, may show fibrinoid necrosis. In a prospective Iranian series of 20 cases of acute brucellosis published from Iran, mild (8 cases) or moderate (2 cases) portal inflammation was present in half of all cases (10 cases). Lobular inflammation was found in 12 cases (60%), being mild in 7, moderate in 4 and severe in 1 case respectively. Two cases showed epithelioid granulomata, whereas microgranulomata were identified in 2 other cases. Steatosis was detected in 4 cases (20%).
Diagnosis
Brucellosis is diagnosed by detection of gram-negative coccobacilli from blood cultures incubated in Castaneda medium 6 weeks and agglutination with specific antiserum in patients with occupational exposure to animal products and compatible clinical features.
Legionellosis
Legionellosis, also known as Legionnaire disease, is a pneumonia caused by Legionella pneumophila and characterized by systemic involvement. It has been associated with bilirubin increases in 15% of cases and with slight elevations of aminotransferases. Liver histology reveals minimal changes, with steatosis and focal necrosis. Specific diagnosis can be made by direct immunofluorescence in tissue, by serology or by identification of bacilli in respiratory secretions. Treatment with antibiotics (fluoroquinolones or macrolides) is associated with resolution of the hepatic dysfunction.
Actinomycosis
At least six species of the anaerobic gram-positive bacteria of the genus Actinomyces may infect humans; Actinomyces israelii is the most common. Although frequently found as a saprophyte in palatine tonsils or in the intestines, Actinomyces may lead to blood-borne infections, especially after surgical interventions. Cervicofacial lesions are the most frequent, followed by intraabdominal lesions; thoracic involvement is relatively rare.
Liver Involvement in Actinomycosis
Liver involvement occurs as a complication of intraabdominal infection, especially after surgery or trauma, pancreatitis, pelvic abscesses related to intrauterine devices, and infections of the appendix, anus, and rectum. Infection is evident as an abscess or, more frequently, as a large, solitary mass of confluent abscesses; these abscesses are more frequent at right lobe. Review of the literature found that these lesions are often misdiagnosed as malignancy (20/28, 71.4% cases) on imaging studies because they often appear as a mass lesion. Furthermore, because cultures are positive in only about half of all cases, histologic identification of colonies of long, branching filamentous bacilli (“grains”) is critical for precise diagnosis. The bacterial colonies are associated with an abundant neutrophilic infiltrate and extensive tissue necrosis ( eSlide 18.1 ). The organisms may also be demonstrated with the Brown-Brenn stain and Gomori silver stain.
Syphilis
Liver involvement in syphilis is now much less common than in the past. Even so, congenital syphilis must be considered when there is prominent hepatosplenomegaly in cases of neonatal jaundice or intrauterine death. Histologically, there is giant cell hepatitis with miliary necrosis containing numerous spirochetes, which can be visualized by the Warthin-Starry stain or immunohistochemical staining. Progressive sinusoidal fibrosis ensues, leading to compression and atrophy of hepatocytes ( Fig. 18.4 ) ( eSlide 18.2 ).
In adults, secondary syphilis may present with neutrophilic cholangitis, epithelioid granulomas, or nonspecific focal hepatocyte necrosis. Although rare, tertiary syphilis may involve the liver, presenting as a hepatitic or cholestatic disease. A major finding is the “syphilitic gumma,” an epithelioid granuloma with a necrotic center and thick fibrous wall; these may be single or numerous and may measure up to several centimeters in diameter ( eSlide 18.3 ).
An increase in the number of cases of syphilis has been reported in the United States, especially in homosexual individuals, many of whom are HIV positive. Cholestasis with portal and lobular hepatitis, which may be rich in giant cell hepatocytes, plasma cells and neutrophils is seen. A recent report of three cases depicting syphilitic inflammatory tumors from Massachusetts General Hospital discusses that the abundance of fibroblastic proliferation and plasma cells raises differential diagnoses with immunoglobulin G4 inflammatory pseudotumor, angiomyolipoma, and other spindle cell tumors, including sarcomas. The presence of neutrophilic and plasmacytic infiltrate within the mass lesion, as well as the portal edema and neutrophilic cholangitis in the background liver are important clues favoring the diagnosis of syphilis, which can be confirmed by immunohistochemical staining and serologic tests.
Leptospirosis
Leptospirosis is a worldwide zoonosis caused by bacteria of the family Leptospiraceae, gram-negative spirochetes that comprise 24 serogroups and 250 serovars. Members of the Leptospiraceae infect domestic and wild animals and are transmitted by the urine of rodents and, less commonly, by the urine of other animals. Humans are infected when broken skin or mucous membranes come in contact with contaminated water. Leptospirosis is highly endemic in tropical areas of all continents with an estimated 900,000 new cases each year; epidemics occur in these regions during floods. High-risk groups include workers exposed to contaminated water, such as miners, sewer workers, soldiers, and farmers, mainly on rice and sugar cane plantations. Workers who handle animal tissues or fluids such as veterinarians, butchers, fishermen, slaughterhouse workers, and laboratory personnel are also at risk. Exposure to Leptospira may also occur during recreational activities.
Clinical Manifestations
The severity of the clinical picture varies with the serovar of Leptospira interrogans , the most common of which are Leptospira icterohaemorrhagiae , Leptospira canicola , Leptospira autumnalis , Leptospira hebdomadis , Leptospira australis , and Leptospira pomona . Most natural infections appear 7 to 13 days after exposure. The clinical picture is protean, and the severity of illness varies widely. At one end of the spectrum, leptospirosis can be entirely asymptomatic, whereas at the other, it can cause a severe illness called Weil disease characterized by jaundice, renal failure, and hemorrhage. Many anicteric infections go undetected, although mild forms of the disease are increasingly recognized. Muscle pain may be severe in leptospirosis and is usually localized to the calves. Muscular lesions are responsible for a striking increase in serum creatine phosphokinase, a valuable biochemical clue to the disease.
The second phase (immune phase or period of localization) generally appears after a relatively asymptomatic interval of 1 to 3 days. It is characterized by marked individual variability of the clinical picture. This phase lasts from 2 to 4 days in most patients. It is characterized by lower fever, less severe myalgia, and milder gastrointestinal symptoms. Meningitis and iridocyclitis are more common.
Severe leptospirosis, or Weil disease, is characterized by jaundice, usually associated with renal damage, changes in hemostasis, anemia, and neurologic disturbances, which begin on the second or third day of the illness and reach their peak during the second week. Simultaneous occurrence of renal impairment and jaundice is an important diagnostic clue and also indicates a poor prognosis. Death may result from acute renal failure caused by interstitial nephritis and acute tubular necrosis and, rarely, from acute liver failure. Acute coronary arteritis, myocarditis and inflammation of the conductive system are frequent. Pulmonary involvement affects up to 70% of patients, including alveolar hemorrhage presenting as dyspnea and hemoptysis. Indeed, acute respiratory distress syndrome has emerged as a major cause of death attributed to leptospirosis.
Patients with the severe forms of leptospirosis who survive have an excellent prognosis, with complete recovery and without long-term sequelae. Some patients may continue to harbor leptospires and excrete them in urine, thus acting as a reservoir for the microorganism.
Because leptospirosis is a tropical infection, other infections prevalent in hot and humid regions that cause similar acute manifestations should be excluded. These include the icteric hemorrhagic fevers such as dengue hemorrhagic fever, yellow fever, and hantavirus infection (discussed in Chapter 13 ).
Pathogenesis
Active movement of leptospires and their ability for adhesion to extracellular matrix and to endothelial and epithelial cells of target organs is considered essential to their pathogenicity. Comparative genomic analyses of transport proteins encoded within the genomes of various Leptospira species revealed that the saprophyte L. biflexa possesses a disproportionately high number of secondary carriers for metabolite uptake and environmental adaptability as well as an increased number of inorganic cation transporters providing ionic homeostasis and effective osmoregulation in a rapidly changing environment. In contrast, the virulent L. interrogans and L. borgpetersenii were found to possess far fewer transporters. These two Leptospira pathogens also possess intact sphingomyelinases, holins, and virulence-related outer membrane porins, thus suggesting that pathogenicity might be related to the emergence of a limited set of proteins responsible for host invasion. The liver and renal lesions probably derive from the direct action of the large numbers of leptospires and the products of their lysis. Leptospires seem to attach themselves directly to cells, initiating cellular injury. Lung tissue in patients with leptospirosis usually shows much lower numbers of leptospires; thus pulmonary abnormalities may be a result of circulating toxins produced by the pathogen at distant sites such as the liver combined with the action of cytokines (eg, tumor necrosis factor-alpha).
Although Leptospira is not a classical intracellular pathogen, pathogenic leptospires may reside, at least temporarily, inside both phagocytic and nonphagocytic cells; an understanding of this interaction might lead to better insight into pathogenesis of the disease. The multiorgan dissemination of leptospires is probably a result of rapid cell translocation.
Pathology
Light microscopic alterations are less striking than in the kidney and often disproportionately mild compared with the severity of the clinical picture. The lobular architecture and the limiting plate are always preserved. Liver cells are either swollen or shrunken, and acidophilic bodies are seen. A prominent feature of leptospirosis in the liver is the mitotic activity of hepatocytes, a rare finding in normal livers and in other liver diseases. However, regeneration as evidenced by twin liver cell plates is moderate. Cholestasis is prominent and found both as granules of bile within swollen hepatocytes and Kupffer cells as well as bile plugs in slightly dilated canaliculi. Kupffer cells are usually hypertrophied and hyperplastic throughout the lobule and may show erythrophagocytosis and scanty hemosiderin. In portal tracts, edema is mild or moderate; the inflammatory infiltrate is composed mainly of lymphocytes and histiocytes with smaller numbers of neutrophils and eosinophils ( Fig. 18.5 ) .
In autopsy studies, the liver is enlarged, is congested, and shows a mottled green appearance due to cholestasis. A common finding is the disarray of liver cell plates with a loss of cohesion between hepatocytes ( eSlide 18.4 ). This feature has been variably attributed to severe cellular damage, terminal change, and an artifact caused by autolysis; however, evidence suggests that this feature is an effect of the leptospires or their toxins.
Major histopathologic findings in leptospirosis are similar to the findings in bacterial septicemia, especially those caused by toxin-producing gram-negative microorganisms. Although not pathognomonic, liver cell disarray is very common in leptospirosis, and when present in the appropriate epidemiologic and clinical background, should lead to a search for leptospiral antigen by immunohistochemistry, the gold standard for etiologic diagnosis. Besides the liver, Leptospira may be seen in other organs, especially the kidneys, lungs, and heart, which may all be involved with variable severity, thus giving rise to variability in the clinical presentation.
Rickettsial Infections
Rickettsiae are obligatory intracellular gram-negative bacilli or coccobacilli transmitted from mammalian reservoirs through insects or ticks to humans; these bacteria have a great affinity for human endothelium. Of the several illnesses related to rickettsial infections, Rocky Mountain spotted fever and Q fever may lead to major liver involvement.
Rocky Mountain Spotted Fever
This disease, caused by Rickettsia rickettsii, occurs in all areas of the American continent, and it is transmitted to humans through tick bites. After an incubation period of about 7 days, an initial nonspecific flulike illness occurs with exanthematous rash, fever, and malaise, lasting about 3 days. This is followed by more severe vascular infection, which may lead to petechial or purpuric hemorrhage. Increased vascular permeability may lead to loss of plasma volume, hypotension, and even shock syndrome.
Liver Disease in Rocky Mountain Spotted Fever
Liver involvement is reported in up to one-third of infected patients, usually presenting as moderately increased aminotransferase levels. Jaundice is rare in cases from the United States, but a study of 118 cases from Brazil found jaundice in 31% of patients. Remarkably, lethality in this study was 37%, in many cases because of major respiratory and vascular involvement. Recent phylogenetic analysis revealed that the Central/South American isolates showed low polymorphism and formed a clade distinct from two North American clades, with the latter clades demonstrating greater in-branch polymorphism.
As in all organs, endothelial cells are directly infected by rickettsiae. Edematous portal spaces are infiltrated by lymphocytes, macrophages, and polymorphs. Vasculitis characterized by a predominantly mononuclear infiltration of vessel walls and intravascular fibrin thrombi is seen. Nonspecific parenchymal lesions encompass focal necrosis of hepatocytes and hypertrophy of Kupffer cells, which may show erythrophagocytosis. Specific diagnosis may be achieved by detection of rickettsial antigen in the cytoplasm of infected endothelial cells in the liver or in other organs, including the skin ( Fig. 18.6 ).
Q Fever
Coxiella burnetii , the causative agent of Q fever, is found worldwide but is more prevalent in dry regions. Peridomiciliary animals such as cows and goats are major reservoirs, although cats and dogs may also transmit the agent. Humans are infected by inhalation, leading to systemic dissemination through the blood circulation. Most infections are asymptomatic. Symptomatic infections present abruptly with high fever, chills, headache, myalgia, anorexia, and, frequently, cutaneous rash. Pneumonia, endocarditis, meningitis, and osteomyelitis may ensue, and liver involvement may be found in up to one-third of patients.
Liver Involvement in Q Fever
When there is a tender, enlarged liver, histologic findings include lobular granulomas, which may be fibrin-ring granulomas or epithelioid granulomas; the former consist of a central fat vacuole surrounded by a ring of fibrin followed by groups of macrophages. Epithelioid granulomas, whether or not they are necrotic, are also found and necessitate the exclusion of tuberculosis and other infections. Although characteristic, the fibrin-rich granuloma is not specific for Q fever, diagnosis relies on serologic demonstration of rising titers of complement-fixing antibodies 2 to 3 weeks after the infection. Reverse transcription polymerase chain reaction has been found to be promising in centers where it is available.
Chlamydial Infection
Peritonitis involving the Glisson capsule may complicate genital infection with Chlamydia trachomatis (or, less frequently, by Neisseria gonorrhoeae ), especially in younger women. This condition clinically simulates biliary tract disease, with high fever and right hypochondrial pain.
Histopathologic findings are nonspecific, with focal hepatocytic necrosis and minor mixed infiltrate with lymphocytes and neutrophils. Similar minor liver involvement may occur in infections with Chlamydia psittaci , which causes pneumonia.
Mycobacterial and Fungal Infections
Liver infection by Mycobacterium species, especially Mycobacterium tuberculosis , Mycobacterium avium , and Mycobacterium leprae , as well as by fungi such as Aspergillus species, Candida species, Cryptococcus neoformans , Blastomyces dermatitidis , Paracoccidioides brasiliensis , and Histoplasma capsulatum lead to granulomatous hepatitis. These are discussed in Chapter 19 .
Protozoal Infections
Amebiasis
Amebiasis is caused by Entamoeba histolytica , a worldwide protozoan, which is most prevalent in tropical regions, where it is a major public health problem, especially in conditions of poor sanitation. About 10% of the world population may be infected with E. histolytica , and about 8.5% of infected patients are estimated to harbor hepatic pseudoabscesses. Infection is transmitted by the oral-fecal route through contaminated water and food or even from person to person.
Diagnosis of intestinal amebiasis is made by serology or by morphologic and antigenic identification of E. histolytica cysts or trophozoites in feces, aspirated samples, touch preparations, or mucosal biopsies. Ultrasound imaging supported by serologic enzyme-linked immunosorbent assay (ELISA) tests is presently the preferred diagnostic tool; it is positive in 90% to 95% of patients with extraintestinal amebiasis.
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