Impact of Everolimus-based Immunosuppression on Renal Function in Liver Transplant Recipients.

BACKGROUND: Calcineurin inhibitors have been implicated in acute and chronic kidney disease after liver transplant (LT). Everolimus (EVR) is a mammalian target of rapamycin inhibitor efficacious in preventing acute cellular rejection while preserving renal function among LT recipients. We evaluated the benefits on renal function of EVR immunosuppression in LT recipients. METHODS: We performed a retrospective and observational study in 477 LT recipients in Virgen de las Nieves Hospital from 2002 to 2019 on the use of EVR with tacrolimus minimization or withdrawal in LT recipients with renal dysfunction. The study included 100 patients starting EVR (20.96%); in 66 (66%) the indication was renal dysfunction. The change in renal function was assessed by estimated glomerular filtration rate. Statistical analyses were performed using SPSS 17.0 software (IBM, Munich, Germany). RESULTS: Fifty 8 patients received mycophenolate mofetil (87.8%), and tacrolimus therapy was stopped in 27 patients (40.9%). Induction therapy with basiliximab was administered in 41 patients (62.12%). There was significant difference between estimated glomerular filtration rate at the time of starting EVR and the first month at last follow-up (49.42 mL/min/1.73 m2 vs 75.27 mL/min/1.73 m2; P < .001) and at end of follow-up (24 months) (49.42 mL/min/1.73 m2 vs 64.32 mL/min/1.73 m2; P = .001). The rate of incidence of adverse events was 48.48% (32/66). Seven patients died during follow-up (10.6%), but there were no EVR-related deaths. Eleven patients (16.6%) developed biopsy-proven acute rejection. CONCLUSION: This study showed that EVR is associated with a beneficial effect on glomerular filtration rate in both the short and long term in LT recipients.

Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment.

AIM: To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODS: Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). RESULTS: For both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). CONCLUSION: The obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.

Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV-infected children.

UNLABELLED: The vertical transmission of hepatitis C virus (HCV-VT) is a major route of HCV infection in children, but the risk factors remain incompletely understood. This study analyzed the role of interleukin 28B (IL28B) in HCV-VT and in the spontaneous clearance of HCV among infected infants. Between 1991 and 2009, 145 mothers were recruited for this study: 100 were HCV-RNA+ve / human immunodeficiency virus negative (HIV-ve), with 128 children, and 33 were HCV-RNA-ve/HCV antibody+ve, with 43 children. The infants were tested for HCV-RNA at birth and at regular intervals until the age of 6 years. IL28B (single nucleotide polymorphism rs12979860) was determined in the mothers and children. HCV-VT was assumed when children presented HCV-RNA+ve in two subsequent blood samples. HCV-VT-infected infants were categorized as: (1) transient viremia with posterior HCV-RNA-ve and without serum-conversion; (2) persistent infection with serum-conversion. Of the 31 mothers with CC polymorphism, 19 (61%) were HCV-RNA+ve, whereas among the 68 mothers with non-CC polymorphism, 56 (82%) were HCV-RNA+ve. In all, 26 of 128 (20%) infants born to the HCV-RNA+ve mothers acquired HCV infection, but only 9 (7%) were chronically infected. The rate of HCV-VT was higher among the mothers with higher HCV viremia. No HCV-VT was detected in the HCV-RNA-ve women. Neither the mothers' nor the childrens' IL-28 status was associated with an increased risk of HCV-VT. The factors influencing viral clearance among the infected children were genotype non-1 and genotype CC of IL28B. In logistic regression, child CC polymorphism was the only predictor of HCV-clearance in HCV genotype-1. CONCLUSION: High maternal viral load is the only predictive factor of HCV-VT. IL28B plays no role in HCV-VT, but IL28B CC child polymorphism is associated independently with the spontaneous clearance of HCV genotype-1 among infected children.