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.

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

“…3 Baseline factors associated with SVR included non-1 genotype, previously untreated, low baseline HCV-RNA, adherence to therapy, and donor IL28B genotype CC. 8,10,21,43,[45][46][47] On-treatment predictors matched those in the non-transplant setting; achievement of rapid virological response (RVR) was a good predictor of SVR, and failure to achieve EVR was highly predictive for non-SVR. 43,48 The use of DAA with PEG-IFN and RBV in the management of post-transplant recurrent HCV is challenging.…”

“…85 Following LT, IL28B polymorphisms have been associated with histological recurrence and treatment response. 8,10,46,47 Recipient CC genotype has been shown to be an independent predictor of delayed HCV recurrence at two and five years after LT and was associated with slower progression of fibrosis. 8,10 Following HCV recurrence, treatment response has a stronger association with the CC genotype of the donor than the recipient.…”

“…8,10,46,47 Recipient CC genotype has been shown to be an independent predictor of delayed HCV recurrence at two and five years after LT and was associated with slower progression of fibrosis. 8,10 Following HCV recurrence, treatment response has a stronger association with the CC genotype of the donor than the recipient. 21,46,47 Although IL28B polymorphisms predict post-LT recurrence and clearance of HCV, these findings have not yet been demonstrated to improve graft or patient survival.…”

“…7 HCV recurrence is almost universal and its severity depends on several host, viral, donor, and transplant factors (Table 1). 2,[8][9][10] Following LT, the liver graft is re-infected upon reperfusion, and is accompanied by a rise in HCV viral load that peaks around 3-4 months. Most patients develop features of acute hepatitis between 4 and 12 weeks after LT. 4 Though serum transaminases and HCV-RNA generally settle down to normal or near normal range, spontaneous viral clearance has not been observed.…”

The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment strategies

“…These rates are estimates based on clinical trials with~5-10% adjustment for real-life SVR, and reflect both treatment-naïve and -experienced patients. For baseline and first wave scenarios, the real-life data were retrieved from the Swedish InfCare Hepatitis database (personal Communication, Dr Ola Weiland, Karolinska University Hospital, Stockholm, Sweden) and/or publications from Sweden when available, otherwise from other Western countries [33][34][35][36][37]. Estimated SVR rates from the liver transplanted were used, due to lack of data.…”