Increased Risk of Severe Hepatitis C Virus Recurrence After Liver Transplantation in Patients With a T Allele of IL28B rs12979860

Cisneros, Elisa; Baños, I.; Cítores, M.J.; Duca, Ana; Salas, Clara; Noblejas, Ana; Cañizares, M. Carmen; Millán, Isabel; Cuervas-Mons, Valentín; Vilches, Carlos

doi:10.1097/tp.0b013e31825668f6

Cited by 21 publications

(15 citation statements)

References 26 publications

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“…Although recipient rs12979860 CC genotype confers higher rates of spontaneous and treatment-related HCV clearance in the non-transplant setting, here, we found that receiving a donor liver with the rs12979860 CC genotype is associated with increased risk of severe recurrent HCV after LT. This finding is supportive of two recent smaller studies where donor rs12979860 CC was associated with unfavorable post-LT events (higher risk for recurrent cirrhosis, need for retransplantation or death) and donor rs12979860 T allele with favorable post-LT events (lower risk for advanced fibrosis within 5 years)[21, 22]. Similarly, for rs8099917 (for which in the non-transplant setting the TT genotype is favorable) in our study the TT donor was associated with increased rather than reduced risk of severe HCV after LT.…”

Section: Discussionsupporting

confidence: 85%

“…The relevance of IL28B polymorphisms (rs12979860 or rs8099917) to the severity of HCV recurrence and outcome after LT has been only incompletely characterized in five small single-center studies that included both donor and recipient DNA analysis[17-21]. In the largest of these studies an unfavorable genotype (rs12979860 TT) in the recipient was associated with more aggressive recurrent HCV, whereas a favorable genotype (rs12979860 CC) in the donor or recipient was associated with higher response rates to HCV treatment[17].…”

Section: Introductionmentioning

confidence: 99%

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Differential effects of donor and recipient IL28B and DDX58 SNPs on severity of HCV after liver transplantation

Biggins

Trotter

Gralla

et al. 2013

Journal of Hepatology

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Background & Aims IL28B single nucleotide polymorphisms are strongly associated with spontaneous HCV clearance and treatment response in non-transplant populations. A DDX58 single nucleotide polymorphism is associated with the antiviral response of innate lymphocytes. We aimed to evaluate the associations of donor and recipient IL28B (rs12979860 and rs8099917) and DDX58 (rs10813831) genotypes with severity of HCV recurrence after liver transplantation. Methods In a case-control study of 523 liver transplantation recipients with HCV, we matched severe with mild recurrent HCV based on 2-year clinical and histologic follow-up. A total 440 liver transplantation recipients (severe, n=235; mild, n=205) with recipient DNA and 225 (severe, n=123; mild, n=102) with both recipient and donor DNA were analyzed. Results IL28B [rs12979860, non-CC (vs.CC) and rs8099917, non-TT (vs.TT)] in the recipient-only analysis had higher risk of severe recurrent HCV [OR 1.57 and 1.58, p<0.05]. However, for the 225 with donor and recipient DNA, IL28B rs12979860 CC (vs. non-CC) and rs8099917 TT (vs.non-TT) and DDX58 rs10813831 non-GG (vs. GG) was associated with more (not less) severe recurrent HCV. The greatest risk of severe recurrent HCV was for rs12979860 CC donors in non-CC recipients (OR 7.02, p<0.001,vs. non-CC donor/recipient) and for rs8099917 TT donors in non-TT recipients (OR 5.78, p=0.001, vs. non-TT donor/recipient). These associations persisted after controlling for donor age, donor race and donor risk index. Conclusions IL28B and DDX58 single nucleotide polymorphisms that are favorable when present in the non-transplant setting or in the recipient are unfavorable when present in a donor liver graft.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Differential effects of donor and recipient IL28B and DDX58 SNPs on severity of HCV after liver transplantation

Biggins

Trotter

Gralla

et al. 2013

Journal of Hepatology

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“…Eurich et al found no association with rs8099917 post-LT fibrosis progression, yet observed higher inflammation and higher ALT levels with the G allele (27). For rs1297860, several studies have now found the T allele to be associated with more rapid fibrosis progression (25, 28, 29). However, Lange et al found no association with post-LT viremia or aminotransferase levels and this recipient genotype (26).…”

Section: Discussionmentioning

confidence: 99%

“…Other gene regions have also been implicated in fibrosis progression, including the DEAD box protein 5 (DDX5) (19, 20), PNPLA3 (21–23), and suppressor of cytokine signaling-3 (SOC-3) (24). However, only limited studies have focused on contribution of host genetics to fibrosis progression in HCV-related LT. Studies focusing on the IL28B region and HCV-related LT have produced conflicting results (25–29). These studies have used different IL28B SNVs, often focusing only one SNV, and have used different phenotypes, which makes comparison of results difficult.…”

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confidence: 99%

Association of Genetic Variants With Rapid Fibrosis

et al. 2014

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Background Recurrence of hepatitis C, the main indication for liver transplantation in the United States, leads to rapid fibrosis progression and worse outcomes compared to other indications. While clinical variables play a role, they are insufficient to explain all inter-patient variability in posttransplant fibrosis progression. Genetic factors associated with hepatitis C virus (HCV) outcomes have been identified, but limited studies have been conducted in the context of HCV-related liver transplantation. Therefore, the purpose of this study was to examine candidate genes related to the immune response and rate of fibrosis in subjects undergoing liver transplantation for HCV. Methods One hundred twelve recipients with detailed posttransplant fibrosis and clinical information were genotyped using 25 single nucleotide variants (SNVs), including five SNVs within the IL28B gene region. Associations between SNVs and rapid fibrosis progression were performed controlling for pertinent clinical variables and haplotype analyses for the IL28B gene were completed. Results Significant multivariable associations were found for rs8099917 (IL28B), rs1991401 (DDX5), rs4969168 (SOC3), and rs7976497 (MLEC). The minor allele was protective against rapid fibrosis progression for the IL28B SNV (G allele), MLEC SNV (T allele), and DDX5 SNV (G allele). For the SOC3 SNV, the minor allele (A) increased the risk for rapid fibrosis progression. Additionally, two recipient haplotype structures for IL28B were significantly associated with rapid fibrosis progression. Conclusions These findings indicate that recipient genetic factors play a role in posttransplant HCV-related fibrosis progression. Molecular studies of these pathways may elucidate the pathogenesis of posttransplant fibrosis progression and provide risk prediction markers.

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“…It was reported that any genetic variants that affect OAS1 activity could be important determinants of susceptibility/resistance to antiviral treatment and to virus-related disease progression [14]. Recently it was demonstrated that IL-28 β SNPs play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance [11, 15, 16]. …”

Section: Introductionmentioning

confidence: 99%

Predictors of Disease Recurrence Post Living Donor Liver Transplantation in End Stage Chronic HCV Patients

et al. 2014

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HCV recurrence represents a universal phenomenon after liver transplantation. In this study Fifty HCV patients who underwent living donor liver transplantation were enrolled and factors that may accelerate HCV reinfection of the allograft such as donor's age and degree of liver steatosis, recipient's age, gender, BMI, MELD score, liver functions, HCV viral load, type of immunosuppressive drug, and genetic polymorphisms of IL28B, OAS, and IL1B were studied. The results of disease-free survival (DFS) rates showed inverse correlation with the recipient's postoperative levels of ALT, AST, ALP (P < 0.001, <0.001, and 0.006 resp.) as well as pre- and postoperative titers of HCV RNA (P < 0.003 and <0.001 resp.). Recipient's IL28B SNP was a significant factor in predicting postoperative DFS (P < 0.025). However, SNPs in OAS and IL1B genes had no apparent correlation with DFS. Cox proportional hazards model revealed that patients with elevated levels of ALT, preoperative viral titers, IL28B CT, and IL28B TT were 8.28, 4.22, 3.35, and 1.36 times, respectively, more likely to develop recurrence. In conclusion IL28B SNP, ALT level, and preoperative HCV titer besides proper choice of immunosuppressant are helpful for predicting posttransplant HCV recurrence and DFS.

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Increased Risk of Severe Hepatitis C Virus Recurrence After Liver Transplantation in Patients With a T Allele of IL28B rs12979860

Abstract: The recipient IL28B rs12979860 genotype has a major influence on the posttransplantation course of HCV infection, being a valuable biomarker for patient care in liver transplantation.

Cited by 21 publications

References 26 publications

Differential effects of donor and recipient IL28B and DDX58 SNPs on severity of HCV after liver transplantation

Differential effects of donor and recipient IL28B and DDX58 SNPs on severity of HCV after liver transplantation

Association of Genetic Variants With Rapid Fibrosis

Predictors of Disease Recurrence Post Living Donor Liver Transplantation in End Stage Chronic HCV Patients

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