The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34–70 years), median creatinine of 1.2 mg/dL (0.66–1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection.

Background & Aims Patients with acute liver failure (ALF) have high mortality and frequently require liver transplantation (LT); few reliable prognostic markers are available. Levels of M30, a cleavage product of cytokeratin-18 caspase, are significantly increased in serum samples from patients with ALF who die or undergo LT. We developed a prognostic index for ALF based on level of M30 and commonly measured clinical variables (called the ALFSG index), and compared its accuracy with that of the King’s College criteria (KCC) and model for end stage liver disease (MELD). We also validated our model in an independent group of patients with ALF. Methods Serum levels of M30 and M65 antigen (the total cytokeratin-18 fragment, a marker of apoptosis and necrosis) were measured on 3 of the first 4 days following admission of 250 patients with ALF. Logistic regression was used to determine if the following factors, measured on day 1, were associated with LT or death: age, etiology; coma grade; international normalized ratio (INR); serum pH; body mass index; levels of creatinine, bilirubin, phosphorus, arterial ammonia, and lactate; and log10M30 and log10M65. The area under the receiver operating characteristic (AUROC) was calculated for the ALFSG and other indices. Results Coma grade, INR, levels of bilirubin and phosphorus, and log10 M30 value at study entry most accurately identified patients that would require LT or die. The ALFSG index identified these patients with 85.6% sensitivity and 64.7% specificity. Based on comparison of AUROC values, the ALFSG Index (AUROC 0.822) better identified patients most likely to require LT or die than the KCC (AUROC 0.654) or MELD (AUROC 0.704) (P=.0002 and P=.0010, respectively). We validated these findings in a separate group of 250 patients with ALF. Conclusions The ALFSG Index, a combination of clinical markers and measurements of the apoptosis biomarker M30, better predicts outcomes of patients with ALF than the KCC or MELD. ClinicalTrials.gov NCT00518440

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Depression is a common problem among patients awaiting organ transplantation, but little is known about the impact of depression and its treatment on the outcomes of liver transplantation. In this retrospective cohort analysis, we studied all patients over 18 years of age who underwent liver transplantation during a 5-year period (2004)(2005)(2006)(2007)(2008) at a single center. Among 179 recipients, 65 patients had depression, as defined by a health care provider assessment, before transplantation. Depression was defined as past or active depression or an adjustment disorder. The associations between pretransplant depression and various outcomes (time to death, graft failure, first acute cellular rejection episode, first infection, and first rehospitalization) were assessed. In the entire sample, more patients with depression required posttransplant psychiatric care (37% versus 18%); the adjusted hazard ratio was 2.28 (1.27-4.11). The rates of other outcomes, including hospital readmission, acute cellular rejection, graft failure, mortality, and infection, were similar for patients with depression and patients without depression. Among those with depression, patients on antidepressants at the time of transplantation had acute cellular rejection less frequently than those not taking antidepressants (13% versus 40%); the adjusted hazard ratio was 0.14 (0.03-0.62). The rates of other outcomes were similar between these 2 groups. These data indicate that depression affects posttransplant psychiatric morbidity but not other medical outcomes of liver transplantation. Pharmacological treatment of depression may significantly reduce the incidence of acute cellular rejection in patients undergoing liver transplantation. However, future prospective studies of mental health and liver transplantation are required to definitively assess the effects of antidepressant medications on medical outcomes.