Causes Of Hepatic Granulomas Research Articles

S2745 Chronic Lymphocytic Leukemia: An Unusual Cause of Hepatic Granulomas

Introduction: Hepatic granulomas (HG) are localized collections of inflammatory cells, found in 2 to 10% of patients who undergo liver biopsy. HG has a wide differential and, in some cases, may not lead to a definitive diagnosis. We present a rare case of chronic lymphoid leukemia (CLL) presenting as HG. Case Description/Methods: 70-year-old male with past history of CLL presented with fever, chills and night sweats for 2 weeks. Admission labs were significant for WBC count 25 and elevated LFTs with total bilirubin 3.67, Alkaline phosphatase 281, AST 41 and ALT 144. CT liver protocol showed diffuse hypodense liver lesions, classified as LIRADs 3 indeterminate lesions. MRI was contraindicated due to incompatible hardware. Infectious work up including cultures, viral and tick serologies, and acute and chronic liver serologies were negative and patient was observed off antibiotics and discharged. Subsequent liver biopsy revealed nodules of necrotizing granulomas but negative for CLL, Richter transformation, fungal or TB on special stains. Work up was expanded to rule out autoimmune causes, fungal, atypical viral, TB infections, hemochromatosis and sarcoidosis as a cause of HG, all of which resulted negative. Due to unclear diagnosis and persistent abnormal liver imaging, repeat liver biopsy was performed which revealed periportal and sinusoidal atypical lymphoid infiltrate with necrotizing granulomatous inflammation. Flow cytometry showed small CD 19+ B cells, consistent with CLL. This upstaged patient’s disease to Rai stage 2 and he was started on chemotherapy, which normalized LFTs and improved symptoms. Discussion: HG remains a diagnostic challenge for many clinicians. Common malignancies associated with hepatic granulomas are lymphoma, renal cell carcinoma and liver metastasis. CLL is not a well defined cause of hepatic granuloma. Other causes include drugs, bacterial, fungal, viral or parasitic infections, autoimmune disorders, TB and sarcoidosis. The histologic subtypes (caseating vs non caseating) may give a clue to the diagnosis. Progressive fibrosis, portal hypertension, and cirrhosis can rarely develop if not identified early. In patients with CLL, liver involvement may upstage the disease, necessitating more aggressive treatment. Assessment for associated clinical symptoms, targeted lab and radiological investigations, and characterization of the morphology and localization of granulomas will usually lead to a definitive diagnosis and appropriate treatment.

Hepatic Granulomas: A Review With Emphasis on Infectious Causes.

Many diseases that cause granulomas or granulomatous inflammation involve the liver. Some of these disease processes are intrinsic hepatic diseases, whereas others are disseminated systemic diseases that involve the liver as well as other organs. To review the evaluation of granulomas in the liver with an emphasis on infectious causes, as well as the use of special stains, serologic studies, and molecular diagnostic techniques. Pertinent noninfectious causes of hepatic granulomas that are in the differential diagnosis are also discussed. Literature review and cases acquired during years of practice. A wide variety of infectious and noninfectious entities cause hepatic granulomas.

Multi-organ failure with atypical liver granulomas following intravesical Bacillus Calmette-Guerin instillation

Bacillus Calmette-Guerin (BCG) intravesical instillation has been adopted in the treatment of patients with superficial bladder cancer. BCG-induced disseminated infection, though rare, has been associated with the histological finding of epithelioid granulomas in different organs, including the liver. We report the case of an adult patient with multi-organ failure, who developed sepsis, acute respiratory failure and acute hepatic failure with encephalopathy whose liver biopsy confirmed the presence of atypical, granulomatous-like lesions. Recovery was observed only after empirical therapy for Mycobacterium bovis with isoniazid, rifampicin, ethambutol and steroids was introduced. This case highlights the importance of a thorough patient assessment in order to exclude other more common causes of hepatic granulomas and to confirm diagnosis. Histological findings may be non-specific when the liver is involved in BCG-induced disseminated infection.

Étiologies et évolution des hépatites granulomateuses : étude rétrospective de 21 cas consécutifs

Purpose To assess the etiologies and outcome of liver granulomatosis. Methods We analyzed all consecutive liver granulomatosis diagnosed in our internal medicine department from 2000 to 2008. Results Among 471 liver biopsies, 21 disclosed evidence of liver granulomatosis (4.5%), in sixteen women (76%) and five men, with a median age of 41 years. Thirteen were caucasians (62%). At the time of diagnosis, six (28.5%) had isolated abnormal liver function tests, and fifteen (71.4%) presented with clinical manifestations. The underlying cause was identified in 18 cases (85.7%). Eleven (52.3%) were systemic diseases: five (23.8%) primary biliary cirrhosis, two (9.5%) primary sclerosing cholangitis, two (9.5%) common variable immunodeficiency, one (4.7%) Sjögren's syndrome, and one (4.7%) Behçet's disease. Two (9.5%) patients had sarcoidosis. Three (14.3%) liver granulomatosis were of infectious origin (tuberculosis, schistosomiasis, and hepatitis C virus), two (9.5%) were neoplastic (Hodgkin's lymphoma and liver cell adenoma), and three (14.3%) were idiopathic. With a median of 38 months of follow-up, four patients (19%, two common variable immunodeficiency and two sarcoidosis) developed portal hypertension, independently of cirrhosis. One patient died of cryptococcosis. Conclusion In accordance with other European studies, systemic diseases are the main causes of hepatic granulomas. Liver granulomatosis related to common variable immunodeficiency and sarcoidosis are at risk of portal hypertension.

Hepatic Granulomas, With an Emphasis on Infectious Causes

Granulomas are aggregates of macrophages, often admixed with other inflammatory cells, which usually result from chronic antigen presentation. Many diseases that produce granulomas involve the liver. Some are intrinsic hepatic diseases, whereas others are disseminated systemic diseases that involve the liver and other organs. Hepatic granulomas are reportedly present in 2% to 10% of all liver biopsy specimens examined in general practice, and of those supposedly as many as 36% have no discoverable etiology even after extensive evaluation of the specimen. This review focuses on the diagnosis of granulomas in infectious diseases affecting the liver, including use of special stains, serologic studies, and molecular diagnostic techniques, and discusses pertinent noninfectious causes of hepatic granulomas that are in the differential diagnosis.

Development of hepatic granulomas in patients receiving pegylated interferon therapy for recurrent hepatitis C virus post liver transplantation

Infrequently, hepatitis C (HCV) appears to be the cause of hepatic granulomas. Interferon therapy for HCV has been increasingly associated with the development of sarcoidosis. We sought to determine the incidence of hepatic granulomas in patients with recurrent HCV post liver transplantation (LT). Between 1994 and 2005, 820 patients were transplanted for HCV at our institution. The pathology database was searched for patients having recurrent HCV and granulomas. At Mount Sinai Medical Center, protocol biopsies have been performed for the last 2 years in patients receiving pegylated interferon-alpha2b and ribavirin (PEG) for recurrent HCV. Review of slides from explanted livers, pre- and post-perfusion biopsies, and all allograft biopsies were evaluated. Lipogranulomas were excluded because of their frequent association with steatosis. A total of 10,225 liver biopsies were performed on HCV patients, and 25 (0.24%) showed non-caseating epithelioid granulomas. Hepatic granulomas were detected in 14 post-LT HCV patients; 9 patients received PEG. Typically, only 1 lobular granuloma was found. None of these patients had granulomas in the native liver or in any biopsy before interferon therapy; 6/9 patients had undetectable HCV-RNA levels, and 4 had sustained viral response. No other cause for granuloma formation was identified in the 6 patients. Hepatic granulomas are infrequently found in HCV liver biopsies and rarely found in post-LT biopsies with recurrent HCV. When present, they occur more commonly in patients receiving and virologically responding to PEG therapy. The presence of granulomas in patients with HCV being treated with PEG may not warrant an extensive etiologic work-up for granulomatous hepatitis unless otherwise clinically indicated.

HEPATIC GRANULOMAS AND HEPATIC SARCOIDOSIS

The causes of hepatic granulomas are numerous and their identification can be difficult. Sarcoidosis is a main cause of hepatic granulomas. The mechanisms that initiate the formation of sarcoid granulomas are unknown. This article discusses the pathology of hepatic sarcoidosis and hepatic granulomas.

Isolated hepatic granuloma mimicking congenital simple cyst of the liver possibly caused by tuberculosis

A case of hepatic granuloma resembling a simple cystic lesion of the liver in computed tomography with clinical manifestation of erythema nodosum is presented. The causes of hepatic granulomas and the importance of liver biopsy or exploratory laparotomy in their diagnosis are discussed with a review of the literature.

Chronic Granulomatous Hepatitis

Three cases are described in which a chronic relapsing febrile illness was associated with granulomas in the liver. None of the known causes of hepatic granulomas was present in these patients. In two cases there was clinical improvement after corticosteroid treatment and this was associated with resolution of the histological changes on liver biopsy. These three cases support the concept that chronic granulomatous hepatitis of unknown aetiology is a distinct entity.

Injectable Fluid Silicone Therapy

Four patients who had received silicone injections had the following complications: migration, hepatic disease manifested as granulomatous hepatitis (previously undescribed, to our knowledge), hypopigmentation, and death. Silicone should now be considered as a possible cause of hepatic granulomas in an appropriate host.

GRANULOMATOUS HEPATITIS ASSOCIATED WITH ACUTE CYTOMEGALOVIRUS INFECTION

Abnormal liver-function tests are characteristic of acquired cytomegalovirus (C.M.V.) infection. Previous descriptions of liver-biopsy specimens in published reports on C.M.V. mononucleosis have not described hepatic granulomas. A previously healthy young adult who had well-defined granulomas in a liver-biopsy specimen obtained during acute C.M.V. infection is reported. The diagnosis was confirmed by isolation of the virus as well as increases in complement fixation and IgM and IgG indirect fluorescent-antibody titres. Most other known causes of hepatic granulomas were excluded. Acquired C.M.V. should be included in the differential of granulomatous hepatitis.