title: Evolution of the NS3 and NS5B regions of the hepatitis C virus during disease recurrence after liver transplantation.
abstract: In patients with hepatitis C virus (HCV)-related cirrhosis, infection recurrence is universal after liver transplantation (LT). The relevance of host and virus-related factors on the outcome of hepatitis C recurrence is poorly understood. This study analyzed the relationship between the genetic evolution of the Non-Structural (NS)3 protease and NS5B polymerase regions of HCV and the severity of hepatitis C recurrence. Thirty-three patients were classified as having mild (n = 16) or severe recurrence (n = 17), according to the degree of fibrosis in liver biopsies obtained 1 year after transplantation. Viral load and consensus sequences of the NS3 and NS5B domains were determined in a pre-LT and in four post-LT sequential serum samples. At week 12 after LT, viremia was significantly higher in patients with severe recurrence. NS3 and NS5b regions evolved independently after LT. The genetic evolution of NS3 domain was not related to the severity of the recurrence. However, the diversification in the NS5B region later than 12 weeks after LT was greater in patients with mild than in those with severe recurrence, suggesting a stronger immune pressure in the first group. These observations highlight the complex interplay between viral evolution and clinical outcomes in the LT setting.
authors.affiliation: Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Ciberehd and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Massaguer
authors.forename: S
authors.initials: S
authors.lastname: Ramírez
authors.forename: J A
authors.initials: JA
authors.lastname: Carrión
authors.forename: P
authors.initials: P
authors.lastname: González
authors.forename: J M
authors.initials: JM
authors.lastname: Sánchez-Tapias
authors.forename: X
authors.initials: X
authors.lastname: Forns
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000473:pathology / Q000601:surgery / Q000821:virology*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011184:Postoperative Period; D011379:Prognosis; D012367:RNA, Viral / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase; D012008:Recurrence; D012189:Retrospective Studies; D012720:Severity of Illness Index; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D012367:RNA, Viral; D012324:RNA-Dependent RNA Polymerase; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus