title: Impact of EGF, IL28B, and PNPLA3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study.
abstract: Hepatitis C virus (HCV) infection is accelerated following liver transplantation (LT). Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non-transplant hepatitis C, but allograft population data are limited. We sought to determine the role of these SNPs in 264 patients with HCV who underwent LT between 1990 and 2008. Genotypes were determined from donor wedge/allograft biopsies and recipient explants. Cox proportional hazards model was used to assess time to cirrhosis, liver-related death, and retransplantation, adjusting for donor age and sustained virological response (SVR). Over a median follow-up of 6.3 yr, a trend toward increased progression to graft cirrhosis was observed among recipients of an EGF non-AA vs. AA donor liver (adjusted HR 2.01; 95% CI 0.93-4.34; p = 0.08). No other genotypes predicted cirrhosis development or graft survival. The CC IL28B variant in both recipients and donors was associated with increased rate of SVR (R-CC/D-CC 8/12[67%], R-non-CC/D-CC or R-CC/D-non-CC 23/52[44%], R-non-CC/D-non-CC 12/45[27%], p linear trend = 0.009). Recipient EGF, IL28B, and PNPLA3, and donor IL28B and PNPLA3 genotypes do not predict adverse outcomes in HCV LT recipients. A potential association exists between donor EGF genotype and cirrhosis.
authors: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors: Jessica L
authors: JL
authors: Mueller
authors: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors: Lindsay Y
authors: LY
authors: King
authors: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors: Kara B
authors: KB
authors: Johnson
authors: Division of Gastroenterology, Department of Medicine, Boston Medical Center, Boston, MA, USA.
authors: Tian
authors: T
authors: Gao
authors: Division of Gastroenterology, Department of Medicine, University of Pennsylvania Health System, Philadelphia, PA, USA.
authors: Lauren D
authors: LD
authors: Nephew
authors: Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Beth Israel Deaconness Medical Center, Boston, MA, USA.
authors: Darshan
authors: D
authors: Kothari
authors: Division of Gastroenterology, Department of Medicine, Lahey Hospital & Medical Center, Burlington, MA, USA.
authors: Mary Ann
authors: MA
authors: Simpson
authors: Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA.
authors: Hui
authors: H
authors: Zheng
authors: Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors: Lan
authors: L
authors: Wei
authors: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors: Kathleen E
authors: KE
authors: Corey
authors: Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors: Joseph
authors: J
authors: Misdraji
authors: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Joon Hyoek
authors: JH
authors: Lee
authors: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors: M Valerie
authors: MV
authors: Lin
authors: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors: Neliswa A
authors: NA
authors: Gogela
authors: Harvard Medical School, Boston, MA, USA.|Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors: Bryan C
authors: BC
authors: Fuchs
authors: Harvard Medical School, Boston, MA, USA.|Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors: Kenneth K
authors: KK
authors: Tanabe
authors: Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Lahey Hospital & Medical Center, Burlington, MA, USA.
authors: Fredric D
authors: FD
authors: Gordon
authors: Harvard Medical School, Boston, MA, USA.|Division of Gastroenterology, Department of Medicine, Beth Israel Deaconness Medical Center, Boston, MA, USA.
authors: Michael P
authors: MP
authors: Curry
authors: Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors: Raymond T
authors: RT
authors: Chung
mesh_terms: D000328:Adult; D064591:Allografts; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D015331:Cohort Studies; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006084:Graft Rejection / Q000188:drug therapy / Q000209:etiology; D006085:Graft Survival; D016174:Hepacivirus / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000601:surgery* / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D016031:Liver Transplantation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous; D055815:Young Adult; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000998:Antiviral Agents; D004815:Epidermal Growth Factor; D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: cirrhosis; hepatitis C virus; single nucleotide polymorphism; sustained virological response; transplantation