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.


OBJECTIVE
We sought to determine the incidence of hepatic granulomas in patients with recurrent HCV post liver transplantation (LT).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Fiel
M I
MI
The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, The Mount Sinai Medical Center, New York, New York 10029, USA. mariaisabel.fiel@mountsinai.org
Shukla
D
D
Saraf
N
N
Xu
R
R
Schiano
T D
TD
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D006099:Granuloma / Q000209:etiology*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012008:Recurrence; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D012507:Sarcoidosis / Q000139:chemically induced
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin