Subject(s)
Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Fluorenes/therapeutic use , Hepatitis C, Chronic/drug therapy , Imidazoles/therapeutic use , Simeprevir/therapeutic use , Sofosbuvir/therapeutic use , Aged , Aged, 80 and over , Carbamates , Drug Therapy, Combination , Fatigue/chemically induced , Female , Humans , Male , Pruritus/chemically induced , Pyrrolidines , Recurrence , Sleep Initiation and Maintenance Disorders/chemically induced , Sustained Virologic Response , Treatment Outcome , Valine/analogs & derivativesABSTRACT
There have been few detailed studies of viral kinetics after liver transplantation (LT), and conflicting data have been reported on viral loads and the severity of recurrent hepatitis C virus (HCV) disease. This long-term study aimed to examine (1) the impact of HCV RNA levels at specific points in time within the first year and (2) the influence of interleukin-28B (IL-28B) genotypes on patient outcomes and the severity of recurrent HCV disease. The viral loads were measured 2, 4, 12, 24, and 48 weeks after LT, and the recipient/donor IL-28B genotypes of 164 patients were determined. A Cox regression analysis showed that the viral load at week 2 was an independent negative predictor of recipient outcomes. A week 2 viral load ≥ 6.0 log(10) IU/mL was significantly associated with reduced patient survival. After a mean follow-up of 6.5 years, 21 of 164 patients (12.8%) developed a cholestatic type of HCV recurrence and/or rapidly progressed to cirrhosis within 1 year. A multivariate binary regression analysis showed that HCV viremia at week 2 and a non-C/C recipient IL-28B genotype were independent risk factors for cholestatic recurrent HCV. No predictive factors could be found for the occurrence of recurrent liver cirrhosis 5 and 10 years after LT. Our study shows that the HCV RNA level at week 2 and the recipient IL-28B genotype are independent, statistically significant risk factors for post-LT cholestatic HCV, and it emphasizes the importance of viral load monitoring and IL-28B genotyping for identifying HCV recipients at risk for severe HCV recurrence.
Subject(s)
Hepatitis C, Chronic/genetics , Interleukins/genetics , Interleukins/immunology , Liver Transplantation/immunology , Postoperative Complications/genetics , Viral Load/immunology , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Disease Progression , Female , Genotype , Graft Survival/immunology , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/mortality , Humans , Interferons , Liver Transplantation/mortality , Male , Middle Aged , Postoperative Complications/mortality , Postoperative Complications/virology , Predictive Value of Tests , Recurrence , Retrospective Studies , Risk Factors , Survival Analysis , Young AdultABSTRACT
Structural identity between a recombinant transferrin mutant (N413Q, N611Q) secreted from Saccharomyces cerevisiae and the native protein was shown by CD analysis and immunodiffusion assays against anti-hSTf. The ability of the recombinant protein to bind iron was confirmed by urea-PAGE and EPR analysis of the iron-saturated protein revealed the characteristic holo-transferrin spectrum, indicating conservation of both iron-binding sites. The integrity of the unglycosylated recombinant protein indicates that such protein could be a valuable tool not only for structure-function characterisation but also crystallisation assays. In addition, the recombinant transferrin was found to be as effective as native transferrin as a growth factor in cell culture medium.
