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

Fiel, M. Isabel; Shukla, Deepak; Saraf, Neeraj; Xu, Ruliang; Schiano, Thomas D.

doi:10.1111/j.1399-3062.2007.00258.x

Cited by 22 publications

(4 citation statements)

References 35 publications

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“…Both of which are regulated by γ-interferon and thus are consistent with our observations. Finally, more than 60 patients have developed granulomatous disease subsequent to treatment with various interferons [37; 38; 39]. This clinical condition mimics sarcoidosis.…”

Section: Discussionmentioning

confidence: 99%

Hypothesis: Sarcoidosis is a STAT1-mediated disease

Rosenbaum

Pasadhika

Crouser

et al. 2009

Clinical Immunology

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Immunologic pathways involved in sarcoidosis pathogenesis are largely unknown. We hypothesized that patients with sarcoidosis have characteristic mRNA profiles. Microarray analysis of gene expression was done on peripheral blood (12 patients,12 controls), lung (6 patients, 6 controls) and lymph node (8 patients, 5 controls). Comparing peripheral blood from patients with sarcoidosis to controls, 872 transcripts were upregulated and 1039 were downregulated at ≥ 1.5-fold change and a significant q value. Several transcripts associated with interferon and STAT1 were upregulated. Lung and lymph node analyses also showed dramatic increases in STAT1 and STAT1-regulated chemokines. Granulomas in lymph nodes of patients with sarcoidosis expressed abundant STAT1 and phosphorylated STAT1. STAT1 might play an important role in sarcoidosis. This novel hypothesis unites seemingly disparate observations with regard to sarcoidosis including implication of a casual role for interferons, a suspected infectious trigger, TH1 predominating lymphocytes in bronchoalveolar lavage, and the association with hypercalcemia.

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Section: Discussionmentioning

confidence: 99%

Hypothesis: Sarcoidosis is a STAT1-mediated disease

Rosenbaum

Pasadhika

Crouser

et al. 2009

Clinical Immunology

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“…In the setting of post-transplant granulomas, it is important to remember that the treatment itself can lead to granulomas from drug reaction, and predispose patients to develop opportunistic infections that can cause liver granulomas. 7 , 46 , 47 In cases of sarcoidosis co-existing with hepatitis C, granulomas may be due to hepatitis C, or may have been induced by prior exposure to interferon therapy for hepatitis C. 48 …”

Section: Differential Diagnosismentioning

confidence: 99%

Hepatic Sarcoidosis

Tadros

Forouhar

2016

JCTH

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Sarcoidosis is a multisystem disease characterized by the presence of non-caseating granulomas in affected organs. Pulmonary involvement is the most common site of disease activity. However, hepatic involvement is also common in sarcoidosis, occurring in up to 70% of patients. Most patients with liver involvement are asymptomatic. Therefore, the majority of cases are discovered incidentally, frequently by the finding of elevated liver enzymes. Pain in the right upper quadrant of the abdomen, fatigue, pruritus, and jaundice may be associated with liver involvement. Portal hypertension and cirrhosis are complications linked to long-standing hepatic sarcoidosis. Liver biopsy is usually required to confirm the diagnosis. It is important to differentiate hepatic sarcoidosis from other autoimmune and granulomatous liver diseases. Not all cases of hepatic sarcoidosis require treatment. For symptomatic patients, the first line treatment includes corticosteroids or ursodeoxycholic acid. Various immunosuppressant agents can be used as second line agents. Rarely, severe cases require liver transplantation.

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“…There have also been case reports describing the development of hepatic granulomatous disease after the initiation of interferon therapy, perhaps related to the effect of interferon on immune activation. The granulomas in these patients may represent activation of subclinical sarcoidosis during treatment of their HCV disease [29]. Granulomatous disease associated with HCV infection has been linked with a higher mortality rate [13,30].…”

Section: Hepatitis Cmentioning

confidence: 99%

Granulomatous liver disease

Bhardwaj¹,

Saxena²,

Kwo

2009

Curr Gastroenterol Rep

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Hepatic granulomas are often encountered on liver biopsy and may represent a primary hepatic process, a manifestation of a systemic illness, or an innocent finding of no clinical relevance. Hepatic granulomas are a unique inflammatory response that may be idiopathic or may be a response to a bacterial, fungal, viral, or parasitic infection; a manifestation of drug-induced liver injury; or a manifestation of underlying malignancy. When granulomas are found on liver biopsy, clinicians must correlate the histologic findings with historical and clinical data to help provide an accurate diagnosis and guide management. Therapy may be warranted, either directly for the granulomatous inflammation of the liver or for a systemic process. For some patients, observation may be the most appropriate form of management.

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

Cited by 22 publications

References 35 publications

Hypothesis: Sarcoidosis is a STAT1-mediated disease

Hypothesis: Sarcoidosis is a STAT1-mediated disease

Hepatic Sarcoidosis

Granulomatous liver disease

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