BACKGROUND & AIMS: To determine whether HCV quasispecies diversity correlated positively with liver disease progression after orthotopic liver transplantation (OLT). METHODS: We studied 11 patients undergoing OLT for HCV-related cirrhosis with recurrent hepatitis C in 2 groups according to the stage of hepatic fibrosis on follow-up. The mild group had stage 1 or 2 fibrosis; the severe group, stage 3 or 4 fibrosis. HCV quasispecies diversity was assessed by cloning and sequencing in pretransplantation and posttransplantation serum samples. RESULTS: In the mild fibrosis group, intrasample hypervariable region 1 (HVR1) genetic distance and nonsynonymous substitutions increased after OLT, whereas in the severe fibrosis group, these parameters decreased in follow-up. In contrast, intrasample diversity progressed similarly in both groups in the adjacent sequences flanking HVR1. There was an inverse correlation between the stage of hepatic fibrosis and amino acid complexity after OLT. Among all patients, the estimated rate of amino acid change was greater initially and became more constant after 36 months. CONCLUSIONS: After OLT, a more complex HCV HVR1 quasispecies population was associated with mild disease recurrence. Among those patients with severe recurrent hepatitis C, HCV appeared to be under greater immune pressure. The greatest change in viral amino acid sequences occurred in the first 36 months after OLT.
BACKGROUND & AIMS: To determine whether HCV quasispecies diversity correlated positively with liver disease progression after orthotopic liver transplantation (OLT). METHODS: We studied 11 patients undergoing OLT for HCV-related cirrhosis with recurrent hepatitis C in 2 groups according to the stage of hepatic fibrosis on follow-up. The mild group had stage 1 or 2 fibrosis; the severe group, stage 3 or 4 fibrosis. HCV quasispecies diversity was assessed by cloning and sequencing in pretransplantation and posttransplantation serum samples. RESULTS: In the mild fibrosis group, intrasample hypervariable region 1 (HVR1) genetic distance and nonsynonymous substitutions increased after OLT, whereas in the severe fibrosis group, these parameters decreased in follow-up. In contrast, intrasample diversity progressed similarly in both groups in the adjacent sequences flanking HVR1. There was an inverse correlation between the stage of hepatic fibrosis and amino acid complexity after OLT. Among all patients, the estimated rate of amino acid change was greater initially and became more constant after 36 months. CONCLUSIONS: After OLT, a more complex HCV HVR1 quasispecies population was associated with mild disease recurrence. Among those patients with severe recurrent hepatitis C, HCV appeared to be under greater immune pressure. The greatest change in viral amino acid sequences occurred in the first 36 months after OLT.
Authors: Weihua Wang; Jianguo Lin; De Tan; Yanjuan Xu; Elizabeth M Brunt; Xiaofeng Fan; Adrian M Di Bisceglie Journal: Biochem Biophys Res Commun Date: 2011-09-16 Impact factor: 3.575
Authors: Hui Li; Daniel G Sullivan; Nathan Feuerborn; Susan McArdle; Kirubeal Bekele; Sampa Pal; Matthew Yeh; Robert L Carithers; James D Perkins; David R Gretch Journal: Virology Date: 2010-04-18 Impact factor: 3.616
Authors: Hui Li; Brian J McMahon; Susan McArdle; Dana Bruden; Daniel G Sullivan; Dave Shelton; Heike Deubner; David R Gretch Journal: Virology Date: 2008-03-17 Impact factor: 3.616
Authors: Jason T Blackard; Gang Ma; Jeffrey A Welge; Christina M Martin; Kenneth E Sherman; Lynn E Taylor; Kenneth H Mayer; Denise J Jamieson Journal: J Med Virol Date: 2012-02 Impact factor: 2.327