title: Evolution of fibrosis during HCV recurrence after liver transplantation--influence of IL-28B SNP and response to peg-IFN and ribavirin treatment.
abstract: The IL-28 gene is associated with sustained viral response (SVR) after treatment with peg-IFN and ribavirin in liver transplant recipients with chronic hepatitis C genotype 1 infection. We analysed the importance of recipient and donor IL-28B genotype for response to treatment and fibrosis progression in 54 liver transplant recipients. Fibrosis stage (F) was defined as mild when F≤2 and severe when F≥3 in a liver biopsy or according to liver elasticity analysis. We found a significantly lower prevalence of IL-28B SNP CC in the recipients (22%) than in the donors (67%), P<0.0001. SVR was seen in 61% of the recipients with mild and 27% with severe fibrosis pretreatment, P=0.01. Recipients with IL-28 CC and non-CC had mild fibrosis in 64% and 38% prior to treatment, P=0.13. At follow-up, after treatment, significantly more recipients with CC had mild fibrosis than non-CC recipients (75% versus 32%, P=0.0072), and all with CC and SVR had mild fibrosis. The strongest baseline factor predicting SVR was genotype. Hence, 13/19 (68%) genotype non-1 patients reached SVR versus only 9/35 (26%) genotype 1 patients, P=0.0022. In summary, we found that liver transplant recipients with IL-28B CC tended to have less advanced fibrosis prior to and significantly less after SOC treatment and that all recipients with IL-28B CC who achieved SVR had mild fibrosis at follow-up. A significantly higher SVR rate was achieved in recipients with mild than severe fibrosis pretreatment and with genotype non-1 than 1 infection. Our findings indicate that treatment for post-transplant HCV recurrence should be offered before advanced fibrosis is seen in the recipient.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Ackefors
authors.forename: J
authors.initials: J
authors.lastname: Nyström
authors.forename: A
authors.initials: A
authors.lastname: Wernerson
authors.forename: H
authors.initials: H
authors.lastname: Gjertsen
authors.forename: A
authors.initials: A
authors.lastname: Sönnerborg
authors.forename: O
authors.initials: O
authors.lastname: Weiland
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000473:pathology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*; D012720:Severity of Illness Index; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: IL-28B; hepatitis C virus; liver transplantation; peg-IFN; ribavirin