Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection

Lange, Christian; Moradpour, Darius; Doehring, Alexandra; Lehr, Hans‐Anton; Müllhaupt, Beat; Bibert, Stéphanie; Bochud, Pierre–Yves; Antonino, Anca; Pascual, Manuel; Farnik, Harald; Shi, Ying; Bechstein, Wolf O.; Moench, C.; Hansmann, Martin‐Leo; Sarrazin, Christoph; Lötsch, Jörn; Zeuzem, Stefan; Hofmann, W

doi:10.1016/j.jhep.2010.10.037

Cited by 115 publications

(102 citation statements)

References 26 publications

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“…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.…”

Section: Treatment Of Established Hcv Recurrencementioning

confidence: 99%

“…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.…”

Section: Donor and Recipient Genetic Backgroundmentioning

confidence: 99%

“…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. Therefore, the use of IL28B in donor selection, particularly in the context of live donor LT and in the management of HCV, warrants further study.…”

Section: Donor and Recipient Genetic Backgroundmentioning

confidence: 99%

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

Bunchorntavakul¹,

Reddy²

2014

JCTH

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Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/ progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.

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Section: Treatment Of Established Hcv Recurrencementioning

confidence: 99%

Section: Donor and Recipient Genetic Backgroundmentioning

confidence: 99%

Section: Donor and Recipient Genetic Backgroundmentioning

confidence: 99%

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

Bunchorntavakul¹,

Reddy²

2014

JCTH

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“…However, many patients cannot tolerate curative doses or do not respond to therapy [93][94][95]. Therefore, as it would be ideal to be able to predict which patients would benefit from PEG-IFN plus RBV therapy for recurrent HCV, it was recently reported that variants of the SNPs in or around the IL-28B gene from liver donors are also strongly associated to the degree of graft inflammation and the response to therapy of HCV-infected liver recipients [96][97][98].…”

Section: Molecular Epidemiology Of Hcv-relatedmentioning

confidence: 99%

Evolving Trends in the Hepatitis C Virus Molecular Epidemiology Studies: From the Viral Sequences to the Human Genome

Trinks

Gadano

Argibay

2012

Epidemiology Research International

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Hepatitis C virus (HCV) represents a major worldwide public health problem. The search for the key molecular biomarkers that may provide insight on the basis of the differences in disease progression, severity, and response to therapy is crucial for understanding the natural history of HCV, for estimating the burden of infection and for developing preventive interventions. Initially, molecular epidemiology studies have focused on studying the viral genetic diversity (genotypes, genetic variants, specific nucleotide and amino acid substitutions). However, the clinical heterogeneities of HCV infection and the imperfect predictability of the response to treatment have suggested the need to search for host genetic biomarkers. This led to the discovery of genetic polymorphisms playing a major role in the evolution of infection, as well as in treatment response and adverse effects, such asIL-28B,ITPA, andIP-10. As a consequence, nowadays the focus of molecular epidemiology studies has turned from the viral to the human genome. This paper will cover recent reports on the subject describing the most relevant viral as well as host genetic risk factors analyzed by past and current HCV molecular epidemiology studies.

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“…Lange et al [136] , who also investigated the donor genotype, evidenced that response to antiviral therapy was strongly associated with the donor IL28B major genotype (T/T) but only weakly with the recipient's IL28B genotype [136] . In contrast, other studies have reported that both recipient and donor genotypes seemed to influence the response to Peg-IFN + RBV [137][138][139] .…”

Section: Impact Of Genomic Medicine On Hcv Recurrencementioning

confidence: 99%

Prevention of hepatitis C recurrence after liver transplantation: An update

Carbone

Lenci²,

Baiocchi³

2012

WJGPT

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Hepatitis C related liver failure and hepatocarcinoma are the most common indications for liver transplantation in Western countries. Recurrent hepatitis C infection of the allograft is universal and immediate following liver transplantation, being associated with accelerated progression to cirrhosis, graft loss and death. Graft and patient survival is reduced in liver transplant recipients with recurrent Hepatitis C virus (HCV) infection compared to HCV-negative recipients. Many variables may impact on recurrent HCV liver disease. Overall, excess immunosuppression is believed to be a key factor; however, no immunosuppressive regimen has been identified to be more beneficial or less harmful. Donor age limitations, exclusion of moderately to severely steatotic livers and minimization of ischemic times could be a potential strategy to minimize the severity of HCV disease in transplanted subjects. After transplantation, antiviral therapy based on pegylated IFN alpha with or without ribavirin is associated with far less results than that reported for immunocompetent HCV-infected patients. New findings in the field of immunotherapy and genomic medicine applied to this context are promising.

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Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection

Cited by 115 publications

References 26 publications

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

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

Evolving Trends in the Hepatitis C Virus Molecular Epidemiology Studies: From the Viral Sequences to the Human Genome

Prevention of hepatitis C recurrence after liver transplantation: An update

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