Hepatitis C virus quasi-species dynamics predict progression of fibrosis after liver transplantation

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 (P < .01) 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.