Early emergence of anti-HCV antibody implicates donor origin in recipients of an HCV-infected organ.

Hepatitis C virus (HCV) seroconversion among HCV-uninfected transplant recipients from HCV-infected (NAT+/Antibody+) or HCV-exposed (NAT-/Antibody+) donors has been reported. However, the origin of anti-HCV antibody and the implications of seroconversion remain unknown. We longitudinally tested plasma from HCV-uninfected kidney (n = 31) or heart transplant recipients (n = 9) of an HCV NAT+ organ for anti-HCV antibody (both IgG and IgM isotypes). Almost half of all participants had detectable anti-HCV antibody at any point during follow-up. The majority of antibody-positive individuals became positive within 1-3 days of transplantation, and 6 recipients had detectable antibody on the first day posttransplant. Notably, all anti-HCV antibody was IgG, even in samples collected posttransplant day 1. Late seroconversion was uncommon (≈20%-25% of antibody+ recipients). Early antibody persisted over 30 days in kidney recipients, whereas early antibody dropped below detection in 50% of heart recipients within 2 weeks after transplant. Anti-HCV antibody is common in HCV-uninfected recipients of an HCV NAT+ organ. The IgG isotype of this antibody and the kinetics of its appearance and durability suggest that anti-HCV antibody is donor derived and is likely produced by a cellular source. Our data suggest that transfer of donor humoral immunity to a recipient may be much more common than previously appreciated.

Transplanting hepatitis C virus-infected hearts into uninfected recipients: A single-arm trial.

The advent of direct-acting antiviral therapy for hepatitis C virus (HCV) has generated tremendous interest in transplanting organs from HCV-infected donors. We conducted a single-arm trial of orthotopic heart transplantation (OHT) from HCV-infected donors into uninfected recipients, followed by elbasvir/grazoprevir treatment after recipient HCV was first detected (NCT03146741; sponsor: Merck). We enrolled OHT candidates aged 40-65 years; left ventricular assist device (LVAD) support and liver disease were exclusions. We accepted hearts from HCV-genotype 1 donors. From May 16, 2017 to May 10, 2018, 20 patients consented for screening and enrolled, and 10 (median age 52.5 years; 80% male) underwent OHT. The median wait from UNOS opt-in for HCV nucleic-acid-test (NAT)+ donor offers to OHT was 39 days (interquartile range [IQR] 17-57). The median donor age was 34 years (IQR 31-37). Initial recipient HCV RNA levels ranged from 25 IU/mL to 40 million IU/mL, but all 10 patients had rapid decline in HCV NAT after elbasvir/grazoprevir treatment. Nine recipients achieved sustained virologic response at 12 weeks (SVR-12). The 10th recipient had a positive cross-match, experienced antibody-mediated rejection and multi-organ failure, and died on day 79. No serious adverse events occurred from HCV transmission or treatment. These short-term results suggest that HCV-negative candidates transplanted with HCV-infected hearts have acceptable outcomes.

Twelve-Month Outcomes After Transplant of Hepatitis C-Infected Kidneys Into Uninfected Recipients: A Single-Group Trial.

Background: Organs from hepatitis C virus (HCV)-infected deceased donors are often discarded. Preliminary data from 2 small trials, including THINKER-1 (Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients), suggested that HCV-infected kidneys could be safely transplanted into HCV-negative patients. However, intermediate-term data on quality of life and renal function are needed to counsel patients about risk. Objective: To describe 12-month HCV treatment outcomes, estimated glomerular filtration rate (eGFR), and quality of life for the 10 kidney recipients in THINKER-1 and 6-month data on 10 additional recipients. Design: Open-label, nonrandomized trial. (ClinicalTrials.gov: NCT02743897). Setting: Single center. Participants: 20 HCV-negative transplant candidates. Intervention: Participants underwent transplant with kidneys infected with genotype 1 HCV and received elbasvir-grazoprevir on posttransplant day 3. Measurements: The primary outcome was HCV cure. Exploratory outcomes included 1) RAND-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) quality-of-life scores at enrollment and after transplant, and 2) posttransplant renal function, which was compared in a 1:5 matched sample with recipients of HCV-negative kidneys. Results: The mean age of THINKER participants was 56.3 years (SD, 6.7), 70% were male, and 40% were black. All 20 participants achieved HCV cure. Hepatic and renal complications were transient or were successfully managed. Mean PCS and MCS quality-of-life scores decreased at 4 weeks; PCS scores then increased above pretransplant values, whereas MCS scores returned to baseline values. Estimated GFRs were similar between THINKER participants and matched recipients of HCV-negative kidneys at 6 months (median, 67.5 vs. 66.2 mL/min/1.73 m2; 95% CI for between-group difference, -4.2 to 7.5 mL/min/1.73 m2) and 12 months (median, 72.8 vs. 67.2 mL/min/1.73 m2; CI for between-group difference, -7.2 to 9.8 mL/min/1.73 m2). Limitation: Small trial. Conclusion: Twenty HCV-negative recipients of HCV-infected kidneys experienced HCV cure, good quality of life, and excellent renal function. Kidneys from HCV-infected donors may be a valuable transplant resource. Primary Funding Source: Merck.

Interactions and implications of Fuzzy-Trace theory for risk taking behaviors in bipolar disorder.

BACKGROUND: According to Fuzzy-Trace Theory (FTT), qualitative, bottom-line, "gist" reasoning leads to less risk taking and more mature decision-making, less easily swayed by emotions than quantitative, detail-oriented, "verbatim" reasoning. In Bipolar disorder deleterious risky behaviors are common. Prior research confirmed the relationships posited between FTT and risk taking. We aim to understand whether FTT acts upon risk taking in the manner proposed in the FTT framework, namely, that (a) gist "values" mediate the role of "categorical gist". Furthermore, the roles of mania and impulsivity, cited as factors for risk-taking, remain to be clarified. In this study, we investigate if (b) manic symptoms and impulsivity moderate these relationships. METHODS: Participants (N = 105) completed an online survey including demographics, clinical variables, symptomatology, FTT, risk taking and risk perception. RESULTS: Mediational models indicated that (a) Gist Values mediated Categorical Gist's effect on risk taking, as expected by the FTT framework. (b) Impulsivity moderates risk taking, but manic-type symptomatology does not. LIMITATIONS: Voluntary, self-report surveys may have low participant motivation and limit the diagnostic validity and the inpatient generalizability of the results. CONCLUSIONS: The results move beyond a focus on mood-related aspects of Bipolar disorder and confirm the importance of understanding reasoning processes like FTT in combination with impulsivity, as potential behavioral factors of risk taking in Bipolar disorder. The clarifications on FTT's functioning as a mechanism prescribe possible openings for more efficacious reduction of risky behaviors through behavioral interventions focusing on value creation.

Decision-making and risk in bipolar disorder: A quantitative study using fuzzy trace theory.

OBJECTIVES: This study characterizes risk-taking behaviours in a group of people with a self-reported diagnosis of BD using fuzzy trace theory (FTT). FTT hypothesizes that risk-taking is a 'reasoned' (but sometimes faulty) action, rather than an impulsive act associated with mood fluctuations. DESIGN: We tested whether measures of FTT (verbatim and gist-based thinking) were predictive of risk-taking intentions in BD, after controlling for mood and impulsivity. We hypothesized that FTT scales would be significant predictors of risk-taking intentions even after accounting for mood and impulsivity. METHODS: Fifty-eight participants with BD (age range 21-78, 68% female) completed a series of online questionnaires assessing risk intentions, mood, impulsivity, and FTT. RESULTS: Fuzzy trace theory scales significantly predicted risk-taking intentions (medium effect sizes), after controlling for mood and impulsivity consistent with FTT (part range .26 to .49). Participants with BD did not show any statistically significant tendency towards verbatim-based thinking. CONCLUSIONS: Fuzzy trace theory gist and verbatim representations were both independent predictors of risk-taking intentions, even after controlling for mood and impulsivity. The results offer an innovative conceptualization of the mechanisms behind risk-taking in BD. PRACTITIONER POINTS: Risk-taking behaviour in bipolar disorder is not just a consequence of impulsivity. Measures of fuzzy trace theory help to understand risk-taking in bipolar disorder. FTT measures predict risk-taking intentions, after controlling for mood and impulsivity.