Emma Whitcomb1, Won-Tak Choi2, Keith R Jerome3, Linda Cook4, Charles Landis5, Joseph Ahn6, Helen S Te7, Jamak Esfeh8, Ibrahim A Hanouneh9, Stephen C Rayhill10, William Gibson11, Thomas Plesec12, Jamie Koo13, Hanlin L Wang14, John Hart15, Rish K Pai16, Maria Westerhoff17. 1. Department of Pathology and Laboratory Medicine, Calgary Laboratory Services, University of Calgary, Calgary, Alberta, Canada. Electronic address: Emma.whitcomb@cls.ab.ca. 2. Department of Pathology and Laboratory Medicine, University of California San Francisco, San Francisco, California. 3. Department of Laboratory Medicine, University of Washington, Seattle, Washington; Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington. 4. Department of Laboratory Medicine, University of Washington, Seattle, Washington. 5. Department of Medicine, University of Washington, Seattle, Washington. 6. Department of Medicine, Oregon Health and Science University, Portland, Oregon. 7. Department of Medicine, University of Chicago Medical Center, Chicago, Illinois. 8. Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio. 9. Minnesota Gastroenterology, Eagan, Minnesota. 10. Department of Surgery, University of Washington, Seattle, Washington. 11. Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee. 12. Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio. 13. Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California. 14. Department of Pathology and Laboratory Medicine, University of California Los Angeles Health, Los Angeles, California. 15. Department of Pathology, University of Chicago Medical Center, Chicago, Illinois. 16. Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, Arizona. 17. Department of Pathology, University of Washington, Seattle, Washington.
Abstract
BACKGROUND & AIMS: Most patients, even those who have received a liver transplant, achieve a sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection. Little is known about the histologic features of liver biopsy specimens collected after SVR, particularly in patients who have received a liver transplant. We aimed to better characterize the histologic features of allograft liver biopsy specimens from patients who achieved SVR to anti-HCV therapy after liver transplantation. METHODS: We performed a retrospective analysis of 170 allograft liver biopsy specimens from 36 patients who received a liver transplant for chronic HCV infection, had recurrent HCV infection after transplantation, and subsequently achieved SVR (collected from 1999 through 2015 at 4 medical centers). SVR was defined as an undetectable serum HCV RNA level 24 weeks after completion of HCV treatment. A total of 65 biopsy specimens were post-SVR (at least 1 post-SVR from each patient; some biopsy specimens were collected at later time points from a subset of patients). We performed polymerase chain reaction analysis for HCV RNA on a subset of the biopsy specimens (28 collected before SVR and 32 after SVR). RESULTS: Of the 65 post-SVR biopsy specimens, 45 (69%) had histologic features of active HCV infection. Of the initial post-SVR biopsy specimens collected from each of the 36 patients, 32 (89%) showed these changes. For patients with more than 1 post-SVR biopsy specimen, 6 (46%) had no change in fibrosis between biopsies, and fibrosis worsened for 3 patients (23%) based on their most recent biopsy. The HCV RNA level was undetectable in 31 of the 32 biopsy specimens analyzed by polymerase chain reaction. CONCLUSIONS: In a retrospective analysis of allograft liver biopsy specimens from patients who achieved SVR after a liver transplant for chronic HCV infection, histologic changes associated with active HCV were present in 69% and fibrosis continued to progress in 23%, despite the lack of detection of HCV RNA. Pathologists should be aware of patients' SVR status when analyzing liver biopsy specimens to avoid diagnoses of chronic HCV-associated hepatitis. Because of the persistent inflammatory activity and fibrosis after SVR, clinicians should continue to monitor patients carefully after SVR to anti-HCV therapy.
BACKGROUND & AIMS: Most patients, even those who have received a liver transplant, achieve a sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection. Little is known about the histologic features of liver biopsy specimens collected after SVR, particularly in patients who have received a liver transplant. We aimed to better characterize the histologic features of allograft liver biopsy specimens from patients who achieved SVR to anti-HCV therapy after liver transplantation. METHODS: We performed a retrospective analysis of 170 allograft liver biopsy specimens from 36 patients who received a liver transplant for chronic HCV infection, had recurrent HCV infection after transplantation, and subsequently achieved SVR (collected from 1999 through 2015 at 4 medical centers). SVR was defined as an undetectable serum HCV RNA level 24 weeks after completion of HCV treatment. A total of 65 biopsy specimens were post-SVR (at least 1 post-SVR from each patient; some biopsy specimens were collected at later time points from a subset of patients). We performed polymerase chain reaction analysis for HCV RNA on a subset of the biopsy specimens (28 collected before SVR and 32 after SVR). RESULTS: Of the 65 post-SVR biopsy specimens, 45 (69%) had histologic features of active HCV infection. Of the initial post-SVR biopsy specimens collected from each of the 36 patients, 32 (89%) showed these changes. For patients with more than 1 post-SVR biopsy specimen, 6 (46%) had no change in fibrosis between biopsies, and fibrosis worsened for 3 patients (23%) based on their most recent biopsy. The HCV RNA level was undetectable in 31 of the 32 biopsy specimens analyzed by polymerase chain reaction. CONCLUSIONS: In a retrospective analysis of allograft liver biopsy specimens from patients who achieved SVR after a liver transplant for chronic HCV infection, histologic changes associated with active HCV were present in 69% and fibrosis continued to progress in 23%, despite the lack of detection of HCV RNA. Pathologists should be aware of patients' SVR status when analyzing liver biopsy specimens to avoid diagnoses of chronic HCV-associated hepatitis. Because of the persistent inflammatory activity and fibrosis after SVR, clinicians should continue to monitor patients carefully after SVR to anti-HCV therapy.
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