TY - JOUR
T1 - Hepatitis C virus quasi-species dynamics predict progression of fibrosis after liver transplantation
AU - Arenas, Juan I.
AU - Gallegos-Orozco, Juan F.
AU - Laskus, Tomasz
AU - Wilkinson, Jeff
AU - Khatib, Amer
AU - Fasola, Carlos
AU - Adair, Debra
AU - Radkowski, Marek
AU - Kibler, Karen V.
AU - Nowicki, Marek
AU - Douglas, David
AU - Williams, James
AU - Netto, George
AU - Mulligan, David
AU - Klintmalm, Goran
AU - Rakela, Jorge
AU - Vargas, Hugo E.
N1 - Funding Information:
Received 20 June 2003; accepted 18 November 2003; electronically published 10 May 2004. Financial support: Spanish Association for the Study of Liver Disease (grant to J.I.A.); Edson Foundation (H.E.V. and J.R.); National Institutes of Health (grants R03DK063175 to H.E.V. and R01DA013760 to J.R.). Reprints or correspondence: Dr. Hugo E. Vargas, Mayo Clinic Scottsdale, 13400 E. Shea Blvd., SCJRB 3-363, Scottsdale, AZ 85259 (vargas.hugo@mayo.edu).
PY - 2004/4/1
Y1 - 2004/4/1
N2 - Background. The dynamics of hepatitis C virus (HCV) quasi species in the E2 region may correlate with the course of infection after orthotopic liver transplantation (OLT). Methods. Thirty-four patients who underwent transplantation for HCV-related cirrhosis were studied. Serum and liver samples were available before OLT and at 1 week, 4 months, and 1 year after OLT. Patients were divided into group 1 (Knodell/Ishak fibrosis stage [FS] at 1 year, <2) and group 2 (FS at 1 year, ≥2). Complexity was estimated by the number of bands in a single-strand conformational polymorphism assay, whereas diversity was measured by Shannon entropy (SE) and median mobility shift (MMS) values derived from the heteroduplex mobility assay. Diversity dynamics were measured at transmission (before OLT vs. 1 week after OLT) and after OLT (1 week after OLT vs. 1 year after OLT). Results. Complexity was higher in group 1 patients than in group 2 patients before OLT (P < .02) and at 1 week after OLT (P < .04). Diversity decreased in group 1 at transmission, as measured by either SE (P < .01) or MMS (P < .04). However, diversity increased in this group after OLT, as measured by SE (P < .03) or MMS (P < .02). FS at 1 year after OLT correlated with transmission changes, as measured by SE (r = 0.642, P < .0001) and MMS (r = 0.443, P < .04), and with post-OLT changes (for SE: r = -0.583, P < .01; for MMS: r = -0.536, P < .01). Conclusions. HCV complexity and diversity in the E2 region correlated with the severity of recurrence of HCV infection after OLT. Increased diversity of quasi species at transmission correlated with a higher FS at 1 year. However, increased diversity of quasi species in the post-OLT period correlated with a lower FS at 1 year. The dynamics of HCV quasi species in patients who undergo transplantation are predictive of outcome.
AB - Background. The dynamics of hepatitis C virus (HCV) quasi species in the E2 region may correlate with the course of infection after orthotopic liver transplantation (OLT). Methods. Thirty-four patients who underwent transplantation for HCV-related cirrhosis were studied. Serum and liver samples were available before OLT and at 1 week, 4 months, and 1 year after OLT. Patients were divided into group 1 (Knodell/Ishak fibrosis stage [FS] at 1 year, <2) and group 2 (FS at 1 year, ≥2). Complexity was estimated by the number of bands in a single-strand conformational polymorphism assay, whereas diversity was measured by Shannon entropy (SE) and median mobility shift (MMS) values derived from the heteroduplex mobility assay. Diversity dynamics were measured at transmission (before OLT vs. 1 week after OLT) and after OLT (1 week after OLT vs. 1 year after OLT). Results. Complexity was higher in group 1 patients than in group 2 patients before OLT (P < .02) and at 1 week after OLT (P < .04). Diversity decreased in group 1 at transmission, as measured by either SE (P < .01) or MMS (P < .04). However, diversity increased in this group after OLT, as measured by SE (P < .03) or MMS (P < .02). FS at 1 year after OLT correlated with transmission changes, as measured by SE (r = 0.642, P < .0001) and MMS (r = 0.443, P < .04), and with post-OLT changes (for SE: r = -0.583, P < .01; for MMS: r = -0.536, P < .01). Conclusions. HCV complexity and diversity in the E2 region correlated with the severity of recurrence of HCV infection after OLT. Increased diversity of quasi species at transmission correlated with a higher FS at 1 year. However, increased diversity of quasi species in the post-OLT period correlated with a lower FS at 1 year. The dynamics of HCV quasi species in patients who undergo transplantation are predictive of outcome.
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U2 - 10.1086/386338
DO - 10.1086/386338
M3 - Article
C2 - 15143471
AN - SCOPUS:2542478765
SN - 0022-1899
VL - 189
SP - 2037
EP - 2046
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -