Interferon treatment of hepatitis C virus (HCV) infection after liver transplantation (LT) can result in immune-mediated graft dysfunction (IGD). The occurrence of, risk factors for, and outcomes of IGD with direct-acting antiviral (DAA) therapy have not been reported. We conducted a multicenter study of HCV+LT recipients who did or did not develop DAA-IGD (1 case: 2 controls-33 vs 66). Among all treated between 2014 and 2016, DAA-IGD occurred in 3.4% (33/978). IGD occurred only after treatment completion (76.0 [IQR, 47.0;176]). Among those treated, 48% had plasma cell hepatitis, 36% acute cellular rejection, 6% chronic rejection, and 9% combined findings. Median time to liver enzyme resolution was 77.5 days (IQR, 31.5;126). After diagnosis, hospitalizations, steroid-induced hyperglycemia, and infection occurred in a higher percentage of cases vs controls (33% vs 7.5%, 21% vs 1.5%, 9% vs 0%; all P < .05). Only one IGD patient died and none required retransplant. A multivariate regression analysis found that liver enzyme elevations during and soon after DAA therapy completion correlated with subsequent IGD. In conclusion, while DAA-IGD is uncommon, liver enzyme elevations during or after DAA therapy may be a sign of impending IGD. These indicators should guide clinicians to diagnose and treat IGD early before the more deleterious later clinical presentation.

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The shortage of livers has led most transplant centers to use extended criteria donors. Hepatitis C virus (HCV) RNA-positive donor organs are typically not given to patients who have cleared HCV. A 64-year-old male with chronic hepatitis C, genotype 1b was listed for LT with hepatocellular carcinoma. While on the waiting list, the patient was treated with sofosbuvir, ledipasvir, and ribavirin and achieved an HCV RNA <15 IU/mL by week 10. At week 18 of a planned 24-week treatment course, the patient under-went deceased-donor LT and received an organ from an anti-HCV-positive donor. Treatment was stopped at LT. At week 3 post LT, HCV RNA was detectable and revealed a genotype 3 HCV infection, compatible with transplantation of an organ with established infection. With retreatment with sofosbuvir, daclatasvir, and ribavirin for 12 weeks, the patient achieved a sustained virologic response. This report highlights how antiviral therapies can be used to optimize the outcomes of HCV-infected transplant patients.

It is well documented that Physician Assistants (PAs) and Nurse Practitioners (NPs), collectively known as Advanced Practice Providers (APPs), have a beneficial role beyond the field of primary care. APPs broad spectrum of knowledge make them particularly well suited for specializing in complex fields such as transplant. Variations in practice across transplant centers lead to questions regarding optimal use of APPs. Using job descriptions from transplant centers currently employing APPs, we sought to examine the critical role of transplant APPs beyond clinical care alone. In this review, we explore not only the general training of APPs and current utilization of APPs in transplant, but also safety, cost effectiveness, and comparison of APPs to other transplant providers. We aimed to highlight the importance of recruitment and retention of transplant specific trained APPs to provide continuity in transplant programs. Additionally, APPs expansion into transplant research, quality improvement, leadership, and management must be considered. We challenge transplant centers utilizing APPs to consider these important aspects when seeking ways to expand and optimize the critical role APPs provide on the transplant team.

There is a paucity of data on nodular regenerative hyperplasia after liver transplant. We aim to define the clinical disease trajectory and identify predictors of outcome for this rare diagnosis. This is a retrospective review of postulated risk factors and outcome in patients with nodular regenerative hyperplasia. Patients were classified as having a late presentation if nodular regenerative hyperplasia was diagnosed &gt; 48 months from transplant, and symptomatic if portal hypertensive symptoms were present. Forty-nine of 3,711 (1.3%) adult recipients developed nodular regenerative hyperplasia, and mortality was 32.7% with an average follow up of 84.6 months. The MELD-Na 6 months after diagnosis did not change significantly. Patients with symptomatic portal hypertension at the time of diagnosis had a significantly higher risk of mortality (51.8%) compared to patients with liver test abnormalities alone (10.5%). 44.9% of patients had no previously postulated risk factor. Anastomotic vascular complications do not appear to be the etiology in most patients. The results suggest the vast majority of patients presenting with liver test abnormalities alone have stable disease and excellent long term survival, in contrast to the 56.3% mortality seen in patients that present more than 48 months after LT with symptomatic portal hypertension at diagnosis.

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With the current standard dose and duration of pegylated interferon (PEG-IFN) and ribavirin (RBV), a sustained virologic response (SVR) is obtained in about 40% to 45% of patients with hepatitis C virus genotype 1. Few baseline characteristics can be modified to enhance response rates, so the focus of recent studies has been on whether increasing the dose and duration of treatment can improve SVR rates. Emerging data support consideration of higher-dose RBV and possibly higher doses of PEG-IFN. Additionally, for those not achieving a complete early virologic response, extending treatment from 48 to 72 weeks reduces relapse rates and improves sustained responses. Adherence remains an important "on-treatment factor" influencing responses, but studies are inconsistent in terms of what the "critical" cutoff for dose reductions is. At present, the best strategy to maximize SVR rates for genotype 1 and other "difficult-to-treat" populations includes determining whether any baseline factors can be modified before treatment, maximizing adherence, considering use of higher drug doses, and adjusting treatment duration based on early virologic responses.

Direct-acting antivirals therapy in HCV patients off IS post-LT can be successfully undertaken without the need to restart IS.