Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68-88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in | 3047 MOLNAR et AL.
To evaluate the efficacy and tolerability of tiagabine, a selective γ-aminobutyric acid (GABA) reuptake inhibitor, in adults with generalized anxiety disorder (GAD). Method: This 8-week, randomized, doubleblind, multicenter, placebo-controlled study enrolled patients with GAD (DSM-IV). Tiagabine was initiated at 4 mg/day and then flexibly dosed twice a day to a maximum dose of 16 mg/day. Study drug was tapered after week 8 in decrements of 2 mg every other day. Efficacy assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and Sheehan Disability Scale. Adverse events, sexual functioning, and change in depressive symptoms were monitored. Data were collected from May 2003 to January 2004. Results: A total of 266 patients (tiagabine, N = 134; placebo, N = 132) were included in safety analyses; 260 patients (tiagabine N = 130; placebo N = 130) were included in efficacy analyses. Tiagabine reduced symptoms of GAD according to the observed case and mixed models repeated-measures (MMRM) analyses but not the primary last-observation-carried-forward (LOCF) analysis. At final visit, the reduction from baseline in mean HAM-A total score was 11.8 for tiagabine, compared with 10.2 for placebo (LOCF analysis, p = .27). In a post hoc MMRM analysis, a significant difference in the mean reduction in HAM-A total score over the efficacy evaluation period was found, favoring tiagabine over placebo (p < .01). Tiagabine had an early onset of effect, as shown by significant reduction from baseline in mean HAM-A total score compared with placebo at week 1 (observed cases, p < .05). Tiagabine was generally well tolerated and not associated with changes in sexual functioning or depressive status. Symptoms of a discontinuation syndrome during taper were not observed. Conclusion: The primary LOCF analysis was negative; however, results from the observed case and MMRM analyses suggest that tiagabine may be a useful treatment option for adult patients diagnosed with GAD. These findings warrant further evaluation in randomized clinical studies.
Background
The virologic and histologic outcomes of a hepatitis C virus (HCV)–infected liver graft into an HCV‐negative recipient are not well understood. We aimed to evaluate the sustained virologic response (SVR) rate and the liver histology at 1 year post‐Orthotopic liver transplantation (OLT) with an HCV‐infected graft.
Methods
A total of 33 patients received the HCV antibody (Ab)+/nucleic acid amplification test (NAT)+ graft. Of these patients, 23 were HCV‐negative recipients and 10 were HCV‐positive recipients. The 1‐year biopsy data were available for 24 patients: 15 patients in HCV‐negative group who received an HCV Ab+/NAT+graft and 9 patients in HCV‐positive group who received an HCV Ab+/NAT+ graft. Patients with (+) HCV ribonucleic acid (RNA) were started on direct‐acting antiviral (DAA) treatment approximately 107 days after OLT using either a Glecaprevir‐Pibrentasvir or Sofosbuvir‐Velpatasvir or Sofosbuvir‐Ledipasvir.
Results
All patients (n = 33) were treated with DAA and achieved SVR. The 1‐year post‐OLT liver biopsies were available in 24 patients: 9 patients had F1 and F2 fibrosis and 17 patients had minimal to moderate inflammation. There was no statistical difference in fibrosis and inflammation between the HCV‐negative vs. HCV‐positive recipients. All patients who received the NAT+ graft developed viremia and subsequently achieved SVR with treatment.
Conclusion
At 1 year protocol liver biopsy, patients had inflammation consistent with viral hepatitis despite the successful eradication of HCV.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.