Faculty Bibliography

RATIONALE & OBJECTIVE/OBJECTIVE:Patient education and decision support tools could facilitate decisions around the timing of antiviral therapy in patients living with both hepatitis C virus (HCV) infection and chronic kidney disease (CKD). We previously developed a tool through the HELP (Helping Empower Liver and Kidney Patients) study. This article evaluates the preliminary efficacy and usability of the tool among participants with both HCV infection and CKD. STUDY DESIGN/METHODS:Pre-post study pilot evaluation. SETTING & PARTICIPANTS/METHODS:Participants were at least 18 years old, were English speaking, and had a diagnosis of chronic HCV infection and CKD; they were seen in CKD clinics, dialysis units, and/or hepatology and liver transplantation clinics. INTERVENTION/METHODS:Electronic patient decision support tool. OUTCOMES/RESULTS:Participants' change in knowledge, certainty about choice, decision self-efficacy, patients' treatment preferences, and tool usability. RESULTS:0.48). LIMITATIONS/CONCLUSIONS:Single-site pilot study to explore preliminary tool efficacy and usability. CONCLUSIONS:This study suggests that a decision tool may support informed patient-centered choices among patients with HCV infection and CKD. Future studies should evaluate ways to improve care decisions in a larger sample using both paper-based and electronic materials. FUNDING/BACKGROUND:Merck & Co, Inc, Kenilworth, NJ. TRIAL REGISTRATION/BACKGROUND:Registered at clinicaltrials.gov with study number NCT03426787.

Hepatitis C direct acting antiviral (DAA) therapy has evolved so that infected patients with advanced chronic kidney disease (CKD) can now anticipate the opportunity for sustained virologic response equivalent to that of the broader population of patients with hepatitis C. This has revolutionized the field of transplantation as it relates to renal transplant candidates with hepatitis C and the use of grafts from hepatitis C virus (HCV) viremic donors. In treating this population of patients, special consideration must be given to the timing of anti-viral therapy and drug-drug interactions. Herein we review the pharmacokinetics of HCV DAA therapy in the setting of CKD and chronic renal replacement therapy. Highlighted are drug/drug interactions with special attention to therapies utilized in advanced CKD and immunosuppressants.

BACKGROUND & AIMS/OBJECTIVE:We aimed to evaluate the safety and effectiveness of 12 or 24 weeks treatment with ledipasvir and sofosbuvir, with or without ribavirin, in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis in routine clinical practice. Patients were followed in a multi-center, prospective, observational cohort study (HCV-TARGET). METHODS:We collected data from 667 treatment-experienced adults with chronic genotype 1 HCV infection who began treatment with ledipasvir and sofosbuvir, with or without ribavirin, from 2011 through September 15, 2016, according to the regional standards of care, at academic (n = 39) and community (n = 18) centers in the United States, Canada, Germany, and Israel. Information was collected from medical records and abstracted into a unique centralized data core. Independent monitors systematically reviewed data entries for completeness and accuracy. Demographic, clinical, adverse event, and virologic data were collected every 12 weeks during treatment and during the follow-up period. The primary efficacy endpoint was sustained virologic response, defined as a level of HCV RNA below the lower limit of quantification or undetectable at a minimum 64 days after the end of treatment (SVR12). The per-protocol population (n = 610) was restricted to patients who completed 12 or 24 weeks of treatment (±2 weeks) and had final virologic outcomes available. RESULTS:The per-protocol analysis revealed that 579 patients (93.8%) achieved an SVR12, including 50/51 patients who received ledipasvir and sofosbuvir for 12 weeks (98%), 384/408 patients who received ledipasvir and sofosbuvir for 24 weeks (94.1%), 68/70 patients who received ledipasvir and sofosbuvir with ribavirin for 12 weeks (97.1%), and 57/60 patients who received ledipasvir and sofosbuvir with ribavirin for 24 weeks (95%). On multivariate analysis, neither treatment duration nor the addition of ribavirin was associated with SVR12. Compensated cirrhosis (odds ratio [OR] compared to decompensated cirrhosis, 2.41; 95% CI, 1.16-5.02), albumin ≥ 3.5 g/dL (OR, 3.15; 95% CI 1.46-6.80), or total bilirubin ≤ 1.2 mg/dL (OR 3.34; 95% CI, 1.59-7.00) were associated with SVR12. CONCLUSIONS:In an analysis of safety and effectiveness data from the HCV-TARGET study, we found treatment with ledipasvir and sofosbuvir, with or without ribavirin, to be effective and well tolerated by treatment-experienced patients with genotype 1 HCV infection and compensated cirrhosis. There were no significant differences in rate of SVR12 among patients treated with ledipasvir and sofosbuvir for 12 or 24 weeks, with or without ribavirin. Patients with decompensated cirrhosis appear to benefit from the addition of ribavirin or extension of ledipasvir and sofosbuvir treatment to 24 weeks. ClinicalTrials.gov no: NCT10474811.

Kaposi sarcoma (KS) may rarely occur in transplant recipients through primary human herpesvirus-8 (HHV-8) infection from a seropositive donor. This report describes a patient who developed hepatic KS after receiving a split liver transplant from an HHV-8-positive donor. The recipient was treated with liposomal doxorubicin after reduction in immunosuppression led to acute cellular rejection. This treatment achieved regression of KS while preserving allograft function, demonstrating a successful therapeutic strategy for this malignancy.

Treatment for chronic viral hepatitis C has advanced dramatically to current standard of care all-oral direct-acting antiviral regimens with relatively short treatment duration and high efficacy. Patients with comorbid end-stage renal disease have constituted a "special patient population" with data and treatment options lagging behind that of the broader population of patients with chronic hepatitis C until recently. Herein we review the current evidence base for direct-acting antiviral therapy in this population. We provide a suggested algorithm for the evaluation of such patients for therapy. We highlight special considerations in regards to the choice of regimen, duration, and timing in regards to potential kidney transplantation.

PURPOSE OF REVIEW:Strategies are needed to reduce waitlist mortality and increase transplantation rates. Advances in hepatitis C therapy has allowed the transplant community to look toward utilization of grafts from hepatitis C viremic donors to expand the organ pool. Use of such grafts for hepatitis C-negative patients is being evaluated and debated, and early trial data are emerging. RECENT FINDINGS:Both hepatitis C antibody-positive/nucleic acid test-negative and viremic donors are currently underutilized. Outcomes for viral hepatitis C (HCV) viremic transplant recipients are improving in the setting of direct-acting antiviral therapy. Optimization of graft utilization from HCV 'positive' donors and expansion to use of viremic donors for HCV-negative recipients will likely reduce waitlist mortality and result in net overall reduction in healthcare expenditures. SUMMARY:Herein, we provide a review of recent advancements relating to hepatitis C in solid organ transplant and outline future directions. A primary future focus will be data collection of outcomes of transplantation of grafts from HCV 'viremic' donors to nonviremic recipients in formal clinical trial protocols.