ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Evaluation of the adult patient with hepatic granuloma

Evaluation of the adult patient with hepatic granuloma
Literature review current through: Jan 2024.
This topic last updated: Nov 30, 2022.

INTRODUCTION — Granulomas are circumscribed lesions of mainly mononuclear cells that develop in response to antigenic stimuli. Hepatic granulomas may be found incidentally on an otherwise normal liver biopsy or may be caused by systemic diseases (eg, infection, autoimmune disease). Although the granulomas alone rarely affect liver function, it is important to identify an underlying systemic disease since it may have prognostic and therapeutic implications. The initial evaluation typically includes patient history, physical examination, laboratory studies, and granuloma classification based on morphology.

This topic will discuss the evaluation and causes of hepatic granulomas. The diagnosis and management of drug-induced liver injury are discussed separately. (See "Drug-induced liver injury".)

The approach to the patient with a solid liver lesion is presented separately. (See "Approach to the adult patient with an incidental solid liver lesion".)

The diagnosis and management of cystic liver lesions are discussed separately. (See "Diagnosis and management of cystic lesions of the liver".)

Evaluation of the patient with hepatomegaly is discussed separately. (See "Overview of the evaluation of hepatomegaly in adults".)

EPIDEMIOLOGY — Hepatic granulomas are found in approximately 2 to 10 percent of patients who undergo liver biopsy, and one or two isolated granulomas are not typically associated with a symptomatic disease process [1,2].

The most common causes of hepatic granuloma in the United States are sarcoidosis, mycobacterial infection (eg, Mycobacterium tuberculosis), primary biliary cholangitis, and drug-induced liver injury [2]. (See 'Causes' below.)

PATHOLOGIC FEATURES — A granuloma is a circumscribed lesion that forms as a result of an inflammatory reaction in body tissues. It is characterized by a central accumulation of mononuclear cells, primarily macrophages, with a surrounding rim consisting of lymphocytes and fibroblasts. The lesions are distinct from nearby uninvolved tissue (picture 1).

Early in the development of the granuloma, lesions may appear as punched-out clusters of histiocytes or lymphocytes. The granulomas evolve with stimulation of mononuclear cells from a variety of cytokines. Activated macrophages are transformed to resemble epithelial cells (referred to as epithelioid cells), which characteristically have abundant, pale cytoplasm. Adjacent macrophages may fuse, forming multinucleated giant cells. Granulomas infiltrated by eosinophils are suggestive of a drug reaction or parasitic infection. (See 'Causes' below.)

The cells within the granuloma are capable of secreting a variety of proteins. As an example, epithelioid cells from patients with sarcoidosis secrete lysozyme, collagenase, and angiotensin converting enzyme (ACE). Serologic markers of sarcoidosis including ACE are discussed separately. (See "Clinical manifestations and diagnosis of sarcoidosis".)

Granuloma morphology and histology of the liver parenchyma surrounding the granuloma may be helpful for determining the etiology, and this is discussed below. (See 'Initial evaluation' below.)

CAUSES — Granulomas in the liver are associated with infectious and noninfectious causes; however, for some patients, a cause cannot be identified despite diagnostic evaluation including laboratory studies and liver histology [1,3]. In a study including 442 liver biopsies with granulomatous lesions, the most common causes were primary biliary cholangitis (215 cases [49 percent]) and sarcoidosis (37 cases [8 percent]), while an infectious pathogen (eg, Mycobacterium tuberculosis) was found in 15 cases (3 percent) [1].

Infectious causes — Infectious causes of hepatic granuloma include those related to bacterial, fungal, parasitic, and viral infections:

Mycobacterium tuberculosis – Most patients with mycobacterial infections with hematogenous spread (miliary tuberculosis) have hepatic granuloma; in addition, liver involvement may occur in patients with localized extrapulmonary tuberculosis and/or with pulmonary tuberculosis [3,4]. Patients may present with fever, fatigue, anorexia, hepatomegaly, right upper quadrant pain, or they may be asymptomatic [5]. Serum aminotransferases may be minimally elevated, but jaundice is rare. Granulomas are characteristically found in the portal areas and are caseating [3]. With special stains, acid-fast bacilli can occasionally be seen within the granulomas on the liver biopsy specimen. (See "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis".)

Fungal diseases – Fungal infections with liver involvement typically occur in the setting of disseminated disease in immunocompromised patients. Infected patients may have abdominal pain, hepatomegaly, and abnormal liver biochemical tests. Fungal infections associated with hepatic granulomas include:

Histoplasmosis: Most cases of histoplasmosis in the United States are acquired in the midwestern and central part of the country [6]. (See "Pathogenesis and clinical manifestations of disseminated histoplasmosis" and "Diagnosis and treatment of disseminated histoplasmosis in patients without HIV".)

Coccidioidomycosis: Most cases of coccidioidomycosis in the United States are acquired in the southwestern part of the country. (See "Manifestations and treatment of nonmeningeal extrathoracic coccidioidomycosis" and "Primary pulmonary coccidioidal infection".)

Candidiasis: Patients with hepatic candidiasis typically have a liver biopsy specimen showing granulomatous inflammatory reaction with necrotic central areas [5,7]. (See "Chronic disseminated candidiasis (hepatosplenic candidiasis)".)

Q fever – Q fever is caused by exposure to Coxiella burnetii, a rickettsial agent that infects cows, goats, and sheep. Organisms may be inhaled, ingested, or acquired through tick bites. Acute infection may include flu-like illness (eg, fever, headache), pneumonia, and hepatitis. Patients with liver involvement may present with hepatomegaly and transaminitis, and liver biopsy may demonstrate granuloma with a ring of fibrinoid necrosis surrounded by lymphocytes and histiocytes (fibrin-ring granuloma) [8,9].

Brucellosis – Brucellosis (also called undulant, Mediterranean, or Malta fever) is a zoonotic infection transmitted to humans from infected animals (eg cattle, sheep, goats, pigs) by ingestion of food products (unpasteurized dairy products) or by occupational exposure. Symptoms include fever, malaise, sweats, and arthralgias. The onset of symptoms of brucellosis may be abrupt or insidious, developing over several days to weeks. Symptoms can last for months with periods in which patients feel relatively well (hence the name "undulant" fever). Physical findings, when present, are usually limited to minimal lymphadenopathy and occasionally hepatosplenomegaly [10]. Liver biopsy may demonstrate noncaseating granulomas in patients infected with Brucella abortus and Brucella melitensis [11].

The clinical manifestations, diagnosis, and treatment of brucellosis are discussed separately. (See "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Brucellosis: Treatment and prevention".)

HIV infection – Patients with untreated HIV infection are at risk for several opportunistic infections that have been associated with hepatic granulomas. Examples of opportunistic infections affecting patients with reduced cell-mediated immunity include Mycobacterium tuberculosis, Mycobacterium avium complex (MAC), and toxoplasmosis. (See "Overview of prevention of opportunistic infections in patients with HIV".)

Other infections – Parasitic infections associated with hepatic granuloma include schistosomiasis [12,13], visceral leishmaniasis [14], and rarely, Enterobius vermicularis (pinworm) [15] or toxoplasmosis.

Hepatic granulomas infrequently occur in patients with viral infections, but have been associated with Epstein-Barr virus (EBV), cytomegalovirus, chronic hepatitis B virus, and hepatitis C virus infections [3,16-19].

Noninfectious causes

Sarcoidosis — Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by the formation of nonnecrotizing (ie, noncaseating) granulomas. Most patients are asymptomatic and have only liver biochemical abnormalities (eg, elevated alkaline phosphatase and gamma-glutamyl transpeptidase) [20,21]. Patients with hepatic granulomas and sarcoidosis rarely develop chronic liver disease such as chronic cholestasis, cirrhosis, and/or portal hypertension. (See "Gastrointestinal, hepatic, pancreatic, and peritoneal sarcoidosis", section on 'Hepatic'.)

While sarcoid granulomas are often located in the portal tract, there are no specific laboratory or histopathologic findings that can establish the diagnosis of hepatic sarcoidosis. Thus, for patients with suspected sarcoidosis, additional evaluation for other possible causes of hepatic granuloma (eg, infection) is typically performed. The clinical manifestations and diagnosis of pulmonary sarcoidosis is discussed separately. (See "Clinical manifestations and diagnosis of sarcoidosis".)

Management of patients with hepatic sarcoidosis is discussed separately. (See "Gastrointestinal, hepatic, pancreatic, and peritoneal sarcoidosis", section on 'Treatment'.)

Autoimmune disorders — Autoimmune disorders associated with hepatic granuloma include:

Primary biliary cholangitis – Primary biliary cholangitis (PBC) is characterized by an ongoing immunologic attack on the intralobular bile ducts that results in cholestasis and may eventually lead to cirrhosis and liver failure. PBC is rare, and most patients are women who are diagnosed between 30 and 65 years of age and who have elevated alkaline phosphatase levels and positive antimitochondrial antibodies. The clinical manifestations and diagnosis of PBC are discussed separately. (See "Clinical manifestations, diagnosis, and prognosis of primary biliary cholangitis".)

Other autoimmune disorders – Hepatic granulomas have been reported in patients with granulomatosis with polyangiitis [22]. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations and diagnosis".)

Drug-induced liver injury — Adverse drug reactions have been associated with hepatic granulomas, and drugs most commonly implicated are allopurinol, sulfa drugs, and quinidine (table 1) [3]. For patients with drug-induced liver injury, liver biopsy findings typically include hepatocellular injury and/or cholestatic changes. (See "Drug-induced liver injury".)

Granulomatous hepatitis is a rare complication of intravesical Bacillus Calmette-Guerin (BCG) therapy in patients with bladder cancer. (See "Infectious complications of intravesical BCG immunotherapy".)

Fibrin-ring granulomas have been reported with some drug reactions including allopurinol and immune checkpoint inhibitors [23]. (See "Hepatic, pancreatic, and rare gastrointestinal complications of immune checkpoint inhibitor therapy", section on 'What is the role of liver biopsy?'.)

Idiopathic — The etiology of hepatic granulomas for some symptomatic patients may remain uncertain despite diagnostic evaluation. The exact proportion of hepatic granulomas of uncertain etiology is unknown but is probably in the range of 10 to 35 percent [1]. The term "idiopathic granulomatous hepatitis" refers to a syndrome characterized by a nonacute febrile illness, myalgias, hepatosplenomegaly, and arthralgias of unclear etiology in patients with hepatic granulomas [24]. Laboratory findings are nonspecific and may include elevated inflammatory markers (eg, C-reactive protein). (See 'Patients with nondiagnostic testing' below.)

Other causes — Other conditions associated with hepatic granuloma include:

Malignancy – Hodgkin lymphoma, and to a lesser extent non-Hodgkin lymphoma, have been associated with hepatic granulomas [25,26]. Areas of the liver that are affected by granuloma formation may or may not have involvement of the lymphoma. The presence of granulomas does not influence staging of Hodgkin lymphoma. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults".)

Foreign body granulomatosis – Patients with talc (hydrous magnesium silicate) pulmonary granulomatosis may also have liver involvement, and this is discussed separately. (See "Foreign body granulomatosis".)

INITIAL EVALUATION

When is further evaluation indicated? — For patients with hepatic granuloma, the need for additional testing depends on whether the underlying cause can be identified based on the patient's history and/or initial testing (eg, liver biopsy). For example, further diagnostic testing is indicated for:

Symptomatic patients with hepatic granuloma of unknown etiology.

Symptomatic patients with a suspected etiology based on initial testing (eg, hepatic granulomas on thoracic computed tomography [CT] in a patient with known or suspected pulmonary sarcoidosis). Further testing is performed to confirm the etiology of the granuloma and exclude other causes (eg, infections). (See "Gastrointestinal, hepatic, pancreatic, and peritoneal sarcoidosis", section on 'Hepatic'.)

For patients with suspected systemic or pulmonary infection (eg, tuberculosis), an expedited evaluation is performed, and the diagnostic evaluation for patients with tuberculosis is discussed separately. (See "Diagnosis of pulmonary tuberculosis in adults".)

However, further testing is not typically performed for:

Patients with known liver disease that is associated with hepatic granuloma (eg, primary biliary cholangitis)

Patients who undergo liver biopsy that demonstrated granuloma(s) and also identified the underlying disease (eg, hepatic candidiasis) (see "Chronic disseminated candidiasis (hepatosplenic candidiasis)", section on 'Diagnosis')

Patients who are asymptomatic (ie, no symptoms suggestive of systemic or hepatobiliary disease) and have normal liver biochemistries (see 'Clinical presentation' below)

Clinical presentation — The patient's clinical presentation and history may help narrow the list of possible causes of granuloma and includes:

Symptoms of systemic disease (eg, fever, sweats, anorexia, weight loss)

Symptoms and signs of hepatobiliary disease (eg, abdominal pain, jaundice, pruritus)

Risk factors for exposure to potential hepatotoxins (eg, medications)

Risk factors for exposure to infectious agents (eg, patients living in or returning from endemic areas) (see 'Infectious causes' above and "Evaluation of fever in the returning traveler")

Risk factors for opportunistic infection (eg, use of immunosuppressive medications, HIV infection)

The clinical presentation of hepatic granuloma includes a spectrum from asymptomatic patients with an incidental finding on an otherwise normal liver biopsy specimen to patients who are symptomatic from underlying systemic or hepatobiliary disease (eg, infection, drug-induced liver injury, primary biliary cholangitis) [16]. The granuloma itself does not typically produce any symptoms, whereas the clinical features reflect the underlying disease and its severity. For example, systemic symptoms such as fever, sweats, and weight loss may be seen in patients with tuberculosis or other infectious causes. Liver fibrosis with portal hypertension and cirrhosis is uncommon but may be seen in patients with primary biliary cholangitis and schistosomiasis.

Physical examination — For patients with hepatic granuloma, physical examination includes assessment of:

Liver size and consistency (see "Overview of the evaluation of hepatomegaly in adults", section on 'Examining the liver')

Spleen size

Abdominal distension and ascites

Stigmata of chronic liver disease (eg, spider angiomata) (see "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis")

Laboratory and imaging studies — Laboratory testing is performed to look for abnormalities in liver biochemistries or function and to contribute to the infectious work up. For most patients, we obtain the following tests (or review testing that had been obtained previously):

Serum aminotransferases: alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

Alkaline phosphatase

Total bilirubin

Serum albumin

Prothrombin time/international normalized ratio

Angiotensin-converting enzyme (ACE)

Antimitochondrial antibody

Interferon-gamma release assay (eg, QuantiFERON-TB Gold In-Tube assay) or tuberculin skin test

Ultrasound of the liver

For patients with respiratory symptoms or suspected pulmonary disease (eg, sarcoidosis), chest radiograph

Some patients with hepatic granuloma are asymptomatic but have laboratory abnormalities (eg, elevated serum aminotransferases and/or elevated alkaline phosphatase). Elevations in aminotransferases (ALT, AST) typically are not greater than two times the upper limit of normal.

Imaging including plain radiographs, liver ultrasound, computed tomography, and magnetic resonance imaging (MRI) may demonstrate calcification in chronic granulomas; however, imaging often does not establish the underlying cause [27].

Role of liver biopsy — The liver biopsy specimen is evaluated for characteristics of and possible cause for granuloma. Most patients with hepatic granulomas have undergone liver biopsy (ie, the granuloma was identified based on the biopsy specimen). For symptomatic patients with hepatic granuloma based on imaging alone and with elevated liver tests (eg, alkaline phosphatase), we typically obtain a liver biopsy as part of the evaluation. However, identifying hepatic granuloma on imaging alone in the absence of symptoms is uncommon.

Histopathologic findings — Examination of the liver biopsy specimen in patients with hepatic granuloma includes:

Culture and special staining for acid-fast bacilli, fungi, and other organisms. (See "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis", section on 'Diagnostic tools'.)

Visualizing with polarizing light microscopy (occasionally foreign body talc granulomas will be identified).

Granuloma morphology and location in addition to other liver biopsy findings may be helpful for determining the etiology (table 2) [1] (see 'Pathologic features' above):

Necrosis: Necrotic (caseating) granulomas are commonly associated with tuberculosis, whereas nonnecrotic (noncaseating) granulomas are often associated with sarcoidosis, and less commonly, with primary biliary cholangitis.

Location: Most granulomas occur in the liver parenchyma, while portal granulomas are often associated with specific diseases (eg, primary biliary cholangitis, sarcoidosis).

Liver parenchyma surrounding the granuloma: The liver parenchyma surrounding the granuloma may suggest an underlying etiology (eg, lymphoma). (See 'Other causes' above.)

Microorganisms: In addition to the granulomatous reaction, fungal organisms or schistosome eggs may be seen in liver biopsy specimens.

Histopathologic examination of the liver and interpretation of liver biopsy specimens are discussed in more detail separately. (See "Interpretation of nontargeted liver biopsy findings in adults".)

PATIENTS WITH NONDIAGNOSTIC TESTING

Specialty consultation — Consultation with a hepatology specialist is indicated for symptomatic patients with hepatic granuloma of uncertain etiology despite initial evaluation.

Patients with suspected tuberculosis — For patients with hepatic granuloma in whom a diagnosis of tuberculosis is suspected but not confirmed (ie, patients with fever, sweats), consultation with an infectious disease specialist is indicated for further evaluation and for consideration of antituberculosis therapy. (See 'Initial evaluation' above and 'Infectious causes' above.)

Antibiotic therapy for tuberculosis is discussed separately. (See "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis".)

The rationale for this approach is that some patients initially diagnosed with idiopathic granulomatous hepatitis have been subsequently diagnosed with an underlying infection such as tuberculosis. Treatment with immunosuppressive medications such as prednisone may result in more severe infection. (See "Epidemiology and pathology of miliary and extrapulmonary tuberculosis" and 'Idiopathic granulomatous hepatitis' below.)

Idiopathic granulomatous hepatitis

Initial management — For some symptomatic patients, the etiology of hepatic granuloma may remain uncertain despite diagnostic evaluation, and this condition is termed idiopathic granulomatous hepatitis [28-30]. (See 'Idiopathic' above.)

For such patients, we begin a course of oral glucocorticoid therapy (eg, prednisone 20 to 40 mg daily). Patients treated with glucocorticoids typically have rapid symptomatic improvement (ie within a few days), while elevated liver biochemistries resolve within several months. For patients with symptomatic improvement, the prednisone dose is gradually tapered over four to eight weeks. (See "Pharmacologic use of glucocorticoids".)

For patients who respond to oral glucocorticoids, the long-term prognosis is good, although relapse of symptoms (eg, fever, myalgias) after discontinuing glucocorticoids is not uncommon. Thus, patients who develop recurrent symptoms after completing the initial course of glucocorticoids are typically given a second course of glucocorticoids for four to eight weeks.

Evidence supporting the use of glucocorticoids for idiopathic granulomatous hepatitis are limited to case reports and small case series [31-33].

Subsequent therapy — For patients who do not respond or cannot tolerate glucocorticoids, data from case reports and small case series suggested that possible therapeutic alternatives include infliximab [34] and methotrexate [35]. For example, in a case series of seven patients with idiopathic granulomatous hepatitis who were treated with methotrexate, fever resolved in all seven patients within three months, while fatigue and anorexia improved in six patients (86 percent). In addition, granulomas resolved in four patients in whom a liver biopsy was repeated.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Focal liver lesions".)

SUMMARY AND RECOMMENDATIONS

Hepatic granulomas are found in approximately 2 to 10 percent of patients who undergo liver biopsy, and one or two granulomas in the setting of otherwise normal liver histology are not typically associated with a symptomatic disease process. (See 'Epidemiology' above.)

A granuloma is a circumscribed lesion that forms as a result of an inflammatory reaction in body tissues. It is characterized by a central accumulation of mononuclear cells, primarily macrophages, with a surrounding rim consisting of lymphocytes and fibroblasts (picture 1). (See 'Pathologic features' above.)

Hepatic granulomas are associated with infectious and noninfectious causes. The most common causes of hepatic granuloma in the United Sates are sarcoidosis, mycobacterial infection, primary biliary cholangitis, and drug-induced liver injury. (See 'Causes' above.)

The clinical presentation of hepatic granuloma includes a spectrum from asymptomatic patients with an incidental finding on otherwise normal liver biopsy specimen to patients who are symptomatic from underlying systemic or hepatobiliary disease. The granuloma itself does not typically produce any symptoms, whereas the clinical features reflect the underlying disease and its severity. (See 'Clinical presentation' above.)

For symptomatic patients with hepatic granuloma, the initial evaluation includes obtaining a history to identify symptoms of and risk factors for underlying disease, performing a physical examination, and obtaining diagnostic studies including liver biochemical tests, angiotensin-converting enzyme (ACE) level, and antimitochondrial antibody, interferon-gamma release assay, and liver ultrasound. For patients with respiratory symptoms or suspected pulmonary disease (eg, sarcoidosis), chest radiograph is also obtained. (See 'Initial evaluation' above.)

The liver biopsy specimen is evaluated for characteristics of and possible cause for the granuloma(s) (table 2). Most patients with hepatic granulomas have undergone liver biopsy (ie, the granuloma was identified based on the biopsy specimen). For symptomatic patients with hepatic granuloma based on imaging alone and with elevated liver tests (eg, alkaline phosphatase), we typically obtain a liver biopsy as part of the evaluation. (See 'Role of liver biopsy' above.)

For symptomatic patients with hepatic granuloma of uncertain etiology despite diagnostic evaluation, our approach to management includes (see 'Patients with nondiagnostic testing' above):

For patients with suspected tuberculosis, an infectious disease consultation is obtained for consideration of antituberculosis therapy.

For patients without suspected tuberculosis, we suggest a course of oral glucocorticoid therapy (Grade 2C). We typically use prednisone 20 to 40 mg daily and gradually taper the dose over four to eight weeks.

  1. Drebber U, Kasper HU, Ratering J, et al. Hepatic granulomas: histological and molecular pathological approach to differential diagnosis--a study of 442 cases. Liver Int 2008; 28:828.
  2. Lagana SM, Moreira RK, Lefkowitch JH. Hepatic granulomas: pathogenesis and differential diagnosis. Clin Liver Dis 2010; 14:605.
  3. Choi EK, Lamps LW. Granulomas in the Liver, with a Focus on Infectious Causes. Surg Pathol Clin 2018; 11:231.
  4. Flamm SL. Granulomatous liver disease. Clin Liver Dis 2012; 16:387.
  5. Lamps LW. Hepatic Granulomas: A Review With Emphasis on Infectious Causes. Arch Pathol Lab Med 2015; 139:867.
  6. Lamps LW, Molina CP, West AB, et al. The pathologic spectrum of gastrointestinal and hepatic histoplasmosis. Am J Clin Pathol 2000; 113:64.
  7. Johnson TL, Barnett JL, Appelman HD, Nostrant T. Candida hepatitis. Histopathologic diagnosis. Am J Surg Pathol 1988; 12:716.
  8. Fournier PE, Marrie TJ, Raoult D. Diagnosis of Q fever. J Clin Microbiol 1998; 36:1823.
  9. Anderson A, Bijlmer H, Fournier PE, et al. Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group. MMWR Recomm Rep 2013; 62:1.
  10. Pappas G, Akritidis N, Bosilkovski M, Tsianos E. Brucellosis. N Engl J Med 2005; 352:2325.
  11. Akritidis N, Tzivras M, Delladetsima I, et al. The liver in brucellosis. Clin Gastroenterol Hepatol 2007; 5:1109.
  12. Hams E, Aviello G, Fallon PG. The schistosoma granuloma: friend or foe? Front Immunol 2013; 4:89.
  13. Shaker Y, Samy N, Ashour E. Hepatobiliary Schistosomiasis. J Clin Transl Hepatol 2014; 2:212.
  14. Moreno A, Marazuela M, Yebra M, et al. Hepatic fibrin-ring granulomas in visceral leishmaniasis. Gastroenterology 1988; 95:1123.
  15. Daly JJ, Baker GF. Pinworm granuloma of the liver. Am J Trop Med Hyg 1984; 33:62.
  16. Tahan V, Ozaras R, Lacevic N, et al. Prevalence of hepatic granulomas in chronic hepatitis B. Dig Dis Sci 2004; 49:1575.
  17. Ozaras R, Tahan V, Mert A, et al. The prevalence of hepatic granulomas in chronic hepatitis C. J Clin Gastroenterol 2004; 38:449.
  18. Nenert M, Mavier P, Dubuc N, et al. Epstein-Barr virus infection and hepatic fibrin-ring granulomas. Hum Pathol 1988; 19:608.
  19. Lobdell DH. 'Ring' granulomas in cytomegalovirus hepatitis. Arch Pathol Lab Med 1987; 111:881.
  20. Watanabe T, Jodo S. Hepatic sarcoidosis. CMAJ 2018; 190:E988.
  21. Kumar M, Herrera JL. Sarcoidosis and the Liver. Clin Liver Dis 2019; 23:331.
  22. Holl-Ulrich K, Klass M. Wegener s granulomatosis with granulomatous liver involvement. Clin Exp Rheumatol 2010; 28:88.
  23. Everett J, Srivastava A, Misdraji J. Fibrin Ring Granulomas in Checkpoint Inhibitor-induced Hepatitis. Am J Surg Pathol 2017; 41:134.
  24. Simon HB, Wolff SM. Granulomatous hepatitis and prolonged fever of unknown origin: a study of 13 patients. Medicine (Baltimore) 1973; 52:1.
  25. Kadin ME, Donaldson SS, Dorfman RF. Isolated granulomas in Hodgkin's disease. N Engl J Med 1970; 283:859.
  26. Braylan RC, Long JC, Jaffe ES, et al. Malignant lymphoma obscured by concomitant extensive epithelioid granulomas: report of three cases with similar clinicopathologic features. Cancer 1977; 39:1146.
  27. Ros PR.. Diseases of the Abdomen and Pelvis 2018-2021: Diagnostic Imaging - IDKD Book, Hodler J, Kubik-Huch RA, von Schulthess GK. (Eds), Springer, Cham (CH) 2018.
  28. Sartin JS, Walker RC. Granulomatous hepatitis: a retrospective review of 88 cases at the Mayo Clinic. Mayo Clin Proc 1991; 66:914.
  29. Tofteland ND, Nassif II. Abnormal liver enzymes in a patient with Crohn's disease, psoriatic arthritis, and recurrent pancreatitis. Answer to the clinical challenges and images in GI question: image 5: Idiopathic granulomatous hepatitis. Gastroenterology 2010; 139:e14.
  30. Patedakis Litvinov BI, Pathak AP. Granulomatous hepatitis in a patient with Crohn's disease and cholestasis. BMJ Case Rep 2017; 2017.
  31. Lee YH, Choi CH, Lee NS, et al. Idiopathic granulomatous hepatitis manifested with fever of unknown origin. Korean J Intern Med 1996; 11:161.
  32. Zoutman DE, Ralph ED, Frei JV. Granulomatous hepatitis and fever of unknown origin. An 11-year experience of 23 cases with three years' follow-up. J Clin Gastroenterol 1991; 13:69.
  33. Penchas S, Ligumski M, Eliakim M. Idiopathic granulomatous hepatitis with a prolonged course: effect of corticosteroid therapy. Digestion 1978; 17:46.
  34. Wilson PA, Gan L, King S. Granulomatous hepatitis with hepatic mass lesions and a response to infliximab. Intern Med J 2015; 45:783.
  35. Knox TA, Kaplan MM, Gelfand JA, Wolff SM. Methotrexate treatment of idiopathic granulomatous hepatitis. Ann Intern Med 1995; 122:592.
Topic 3582 Version 23.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟