Effect of Hepatitis C Treatment on Renal Function in Liver Transplant Patients.

Background and Aims: Hepatitis C Virus (HCV) is uniformly recurrent after liver transplant (LT) and recurrence is associated with an increased risk of mortality. Immunosuppressive medications increase the risk of chronic kidney disease, and the presence of chronic kidney disease presents a challenge for HCV treatment in LT recipients. The aim of this study was to assess changes in glomerular filtration rates (GFRs) of LT recipients receiving HCV treatment. Methods: This is a retrospective study of LT patients who received HCV treatment between 2015 and 2016 (n = 60). The outcomes of interest were differences in serum creatinine levels and in GFR, measured at treatment initiation and at 24 weeks after treatment. The average age of the patients was 59 years-old, and 17% were cirrhotic and 67% were treatment-experienced. All patients received sofosbuvir/ledipasvir without ribavirin. Results: All patients achieved sustained virologic response at 12 weeks after treatment (SVR12). At baseline, 55% of patients had GFR <60 mL/min per 1.73 m2. Among those patients, GFR did not change in 18%, 33% had improved GFR, and 48% had worsened GFR. Up to 45% of the patients had a GFR >60 mL/min per 1.73 m2. Among those patients, GFR did not change in 81%, and 19% had worsened GFR. In the entire cohort, 65% of patients had improved or stable GFR and 35% had worsened GFR. The average change in serum creatinine between baseline and 24 weeks was 0.10 (p = 0.18). Conclusions: This study showed improved or unchanged GFR in 65% and worsened GFR in 35% of LT recipients who achieved SVR12. Worsening of GFR was more frequently encountered in those with impaired renal function at baseline. Caution should be used when treating HCV in LT recipients, especially those with baseline status of renal impairment.

Ledipasvir/sofosbuvir without ribavirin is effective in the treatment of recurrent hepatitis C virus infection post-liver transplant.

BACKGROUND/AIM: Recurrent hepatitis C virus infection is a challenging complication post-liver transplant. Current guidelines recommend the combination of ribavirin and ledipasvir/sofosbuvir for 12 weeks for the treatment of recurrent HCV genotype 1 post-liver transplant. Data are limited on the use of ledipasvir/sofosbuvir without ribavirin. The aim of this study was to evaluate the use of ledipasvir/sofosbuvir without ribavirin for the treatment of recurrent hepatitis C virus post-liver transplant. METHODS: This is a retrospective study of liver transplant patients who received ledipasvir/sofosbuvir without ribavirin for the treatment of recurrent hepatitis C virus in our liver center from 2014 to 2016. RESULTS: A total of 60 patients were enrolled of which 70% were male, 88% Caucasian, age 60 ± 7 years, 15% cirrhotic, and 45% treatment-experienced with recurrent hepatitis C virus infection genotype 1 post-liver transplant. Treatment duration varied from 8 to 24 weeks. There were no serious adverse events and no discontinuation of treatment. A total of 71% of patients had undetectable serum hepatitis C virus at 4 weeks. However, irrespective of treatment duration, 100% of patients had undetectable serum hepatitis C virus at the end of treatment and 100% of patients achieved sustained viral response at 12 weeks. CONCLUSION: Ledipasvir/sofosbuvir without ribavirin is an effective treatment of recurrent hepatitis C virus infection post-liver transplant. The entire group achieved sustained viral response at 12 weeks irrespective of the length of treatment. The combination of ledipasvir/sofosbuvir was well tolerated without serious adverse effects or discontinuation.

The global impact of drug resistance.

Measuring the impact of drug resistance is an important step in understanding the scope of the problem and formulating policies to limit the emergence and spread of resistant organisms. Studies have focused on measuring the increased costs, morbidity, and mortality in patients with infections due to resistant versus susceptible organisms. These have generally found that resistance worsens outcomes. By focusing only on infected patients, however, they may understate the impact of resistance. It is important to recognize that resistance also affects the treatment of individuals with nonresistant organisms. In areas with high rates of resistance, physicians and governments have changed empiric therapy for malaria, tuberculosis, acute respiratory infections, and other diseases, increasing overall treatment costs. In some instances, these costs may exceed those attributable to treatment failure.