Society: AASLD

Introduction:
Transplantation of hepatitis C (HCV) positive lungs has been shown to be a safe means of combating organ shortages in the era of direct-acting antivirals against HCV. While short-term data is promising, few studies have reported on survival beyond 12 months and incidence of rejection post-transplant.
Our study aimed to compare post-transplant graft survival at 2 years in lung recipients in aviremic recipients (R-) of viremic donors (D+), and to characterize rates of rejection and extra-hepatic manifestations of HCV.
Methods:
Through a retrospective cohort study design, we identified all lung transplants done at our center from January 2018-September 2022 from the UNOS database. Baseline recipient demographics, status at transplant and donor hepatitis status were extracted, both manually and using the UNOS database. Biopsy and management data were obtained to determine incidence of rejection, fibrosing cholestatic hepatitis and extra-hepatic HCV manifestations.
Results:
A total of 479 D- and 31 D+ lung transplants were performed during the study period. Despite apparent difference in crude mortality rate between D+/R- and D-/R- patients, no statistical difference was found (23.33 vs 16.67, p=0.49). Hazard models for post-transplant 2-year mortality revealed D+ status was not a significant mortality predictor (HR 1.17, p=0.7; table 1). Similarly, D+ status did not impact graft failure in our 2-year prediction model (HR 0.65, p=0.5). Subgroup analysis based on recipient and donor HCV status revealed no difference in 2-year patient or graft survival in any subgroup (figure 1). In D+/R- patients, rate of acute cellular rejection (ACR) was 60%, while rates of chronic and antibody-mediated rejection were 6.67% and 16.67% respectively. Post-transplant HCV viremia occurred in 73.3% of cases, with 100% rate of sustained viral response (SVR) at 12 weeks on glecaprevir-pibrentasvir, though 2 patients died prior to SVR. None were documented to develop fibrosing cholestatic hepatitis or extra-hepatic HCV including neuropathy, nephropathy, cryoglobulinemia or dermatitis. None were co-infected with hepatitis B or HIV.
Conclusion:
Consistent with prior data on short term outcomes, donor HCV positivity did not impact mortality or graft failure at 2 years. Relative to prior studies, we report on a larger cohort of lung recipients. Despite theoretical fear of infectious disease transmission with high-risk donors, incidence of extrahepatic manifestations of HCV and fibrosing cholestatic hepatitis, none of these occurred in our cohort. With timely management of viremia, our data support current practice of utilizing organs from HCV+ donors to reduce waitlist times.

Figure 1. Kaplan Meier curves comparing 2-year patient and graft survival in lung recipients on the bases of donor and recipient HCV NAT status.

Figure 1. Kaplan Meier curves comparing 2-year patient and graft survival in lung recipients on the bases of donor and recipient HCV NAT status.

Table 1. Cox proportional hazard models of 2-year patient and graft survival. These demonstrate lack of effect of donor and recipient HCV NAT status on outcomes of interest.

Table 1. Cox proportional hazard models of 2-year patient and graft survival. These demonstrate lack of effect of donor and recipient HCV NAT status on outcomes of interest.

Introduction: The use of hepatitis C (HCV) positive donors for non-HCV viremic liver transplant (LT) recipients is now increasingly widespread with excellent short-term results. Longer term outcomes in this population are not yet readily available. Our aim was to characterize longer term outcomes in a population of HCV non-viremic recipients who received HCV positive grafts.

Methods: Clinical data on adult liver transplant recipients with donor-derived hepatitis C infection were abstracted from January 2016 to December 2020. We recorded post-transplant viremia and SVR rates, liver chemistries, episodes of rejection, biliary strictures, and patient and graft survival. Donor data were abstracted from OPTN and UNET. Patients consented to receiving an organ from an increased-risk donor with a potentially HCV-infected organ prior to transplantation.

Results: Twenty-eight liver transplant recipients received HCV Ab and/or NAT positive donors. All recipients were non-viremic at the time of transplantation and had confirmed recurrent viremia after transplant. The median waiting list time was 217 days (IQR 11-532), and the median post-transplant follow-up time was 4.2 years (IQR 3.0-5.2). DAA therapy was initiated during a mean time of 31 days post LT with SVR being achieved in all cases (28/28). 11 patients received glecaprevir/pibrentasvir, 8 received sofosbuvir/velpatasvir, 6 received ledipasvir/sofosbuvir, and 1 received daclatasvir/sofosbuvir. There were no cases of graft loss due to HCV recurrence. There was one de novo HCV infection with different genotype post LT that required treatment. Three deaths were noted due to 1) immediate multiorgan failure post LT, 2) complications related to HCC recurrence, and 3) non-HCC solid organ malignancy. The incidence of acute cellular rejection was 25% (7/28) and all cases resolved with treatment. Liver chemistries (AST, ALT, TB, ALP) were normal in 20/29 recipients at last follow-up. Post-transplant biopsies in two patients showed fibrosis, one in setting of antibody-mediated rejection that responded to IVIG and rituximab at month 5 when SVR had been achieved, another due to acute cellular rejection 8 weeks post DAA treatment with follow-up biopsy showing no fibrosis. 8/28 patients developed biliary strictures requiring an average of 6 ERCPs. Compared to our population without donor-derived HCV infection, there were no differences in 5-year graft or patient survival (77.1% v 79.0% patient survival at 5 years, p=0.97) (Figure).

Conclusion: Liver transplantation of HCV-viremic organs into non-HCV-viremic patients with DAA therapy provides excellent long-term outcomes. DAA therapy remains effective in this patient population. Our findings also confirm long-term safety of this strategy.

Background: HCV is a leading cause of HCC. DAA can improve survival of patients with HCV but racial/ethnic disparity data for real-world treatment rates and outcomes of HCV-HCC patients are limited. Thus, we aim to investigate DAA treatment rates and the impact of treatment/SVR on the long-term survival of a large and diverse cohort of HCV-HCC patients.

Methods: We included a total of 6112 HCV-HCC patients from the REAL-HCC registry, a multinational dataset of 5 U.S. and 16 Asia Pacific centers (9 Japan, 3 Taiwan, 2 China, 1 Singapore, 1 South Korea).

Results: The study cohort was 64.2 years in mean age, 68.3% male, and included 54.2% Asian (n=3287), 30.1% White (n=1824), 8.5% Black (n=517), and 7.3% Hispanic (n=441) patients. HCV treatment rate was highest for Asian (35.9%) followed by White (34.9%), Hispanic (30.3%), and lowest for Black (18.7%) (p<0.0001). The majority of HCV treatments were received in 2014 and later for all ethnic groups. Among untreated or non-SVR patients, using Kaplan-Meier method, the 10-year survival rate was worst for Black followed by White, Asian, and Hispanic (log-rank p<0.0001, Figure 1A). However, among treated patients with SVR, long-term survival rates were similar and improved for all racial/ethnic groups (log-rank p=0.44, Figure 1B). In a multivariable Cox proportional hazards regression analysis adjusted for age, sex, race/ethnicity, BCLC staging, HCV treatment, and HCC treatment, untreated and non-SVR patients had more than four times higher risk of mortality compared to treated SVR patients (adjusted hazard ratios [aHR]=4.17, CI: 3.37 – 5.16, p<0.0001).

Conclusion: Treatment rates with DAA were lowest for Black patients with HCV-HCC who also had the worst survival rates if untreated. Racial/ethnic disparities in the long-term survival of HCV-HCC patients resolved among treated patients with SVR. Further efforts are needed to improve treatment rates for racial/ethnic minorities who suffer especially poorer survival if untreated.

Figure 1(A) Untreated/no SVR treatment: Overall survival by race/ethnicity

Figure 1(A) Untreated/no SVR treatment: Overall survival by race/ethnicity

Figure 1(B) SVR treatment: Overall survival by race/ethnicity

Figure 1(B) SVR treatment: Overall survival by race/ethnicity

Hirokazu Takahashi

Appearances