Data Sources and Searches
We selected eligible studies by searching the PubMed and EMBASE electronic databases using pre-determined search engines (Table S1) from 1 January 2007 to 17 April 2021. Although the DAA era began in 2013, we opted to begin our search in 2007 as this marked the date that DAA therapies were first mentioned in the literature. Our primary goal was to assess the outcomes of HCV seronegative recipients who received HCV viraemic solid allografts.
We conducted a systematic review following the PRISMA Statement. Two independent reviewers (TJ and TR) selected studies that addressed post-transplant outcomes in a confirmed HCV viraemic allograft to an uninfected recipient following inclusion and exclusion criteria (Box S1). A third reviewer resolved disagreements (RH).
Study Outcomes, Data Extraction, and Synthesis, Quality Assessment
We assessed these solid organ transplants (SOT): kidney, heart, liver and lung. Bowel and pancreas transplants were not included due to a limited number of studies. Simultaneous liver-kidney or heart-kidney patients were included in the liver or heart category, respectively. We defined viral relapse as a decrease in HCV viral load until it is undetectable while on treatment, followed by a detectable HCV viral load after completion of therapy.
For each study, we extracted virological, graft and patient outcomes. We also assessed details about barriers to DAA access.
We determined virological response (SVR12) by the number of patients receiving NAT-positive allografts who had negative viral load checked 12 weeks after the completion of antiviral therapy (eligible for SVR12 check). We defined them as not eligible for SVR12 if the transplant recipients: (a) did not receive DAA treatment, (b) they were still undergoing treatment at the time of the publication of the report or (c) the patients were awaiting 12 weeks post-treatment to measure SVR (Table S2). We extracted the authors' definition of graft outcomes, including delayed graft function, failure and rejection. We defined patient's outcomes as other medical complications previously described or patient's survival. We also reported barriers in the access of DAA (e.g. appeal, payors) (Table S3).
We provided counts, medians with percentile 25th-75th or range as clinically appropriate in each SOT to provide a summary estimate. We elected not to pursue a meta-analysis because there was significant heterogeneity in reporting clinical outcomes and opted to provide a qualitative summary.
We independently assessed the articles' methodological quality using the Newcastle-Ottawa Quality Assessment Scale (NOS) with a maximum score of 8, defining good methodological quality when NOS≥ 4 (Tables S4 and S5).
Aliment Pharmacol Ther. 2021;54(5):571-582. © 2021 Blackwell Publishing