The Impact of Direct-Acting Antiviral Agents on Liver and Kidney Transplant Costs and Outcomes

D. A. Axelrod; M. A. Schnitzler; T. Alhamad; F. Gordon; R. D. Bloom; G. P. Hess; H. Xiao; M. Nazzal; D. L. Segev; V. R. Dharnidharka; A. S. Naik; N. N. Lam; R. Ouseph; B. L. Kasiske; C. M. Durand; K. L. Lentine

Disclosures

American Journal of Transplantation. 2018;18(10):2473-2482. 

In This Article

Results

Between 2007 and 2016, 58 509 LTs were performed; pharmacy claims data for at least 1 year after transplant were available for 41 690 (71%) of these (Table 1). Among patients with claims, 15 671 (38%) were HCV donor negative and recipient positive (D-/R+), 1468 (3.5%) were D+/R+, and 47 (0.1%) were recorded as D+/R-. In the same period, 157 873 KTs were performed; pharmacy claims data were available for 121 800 (71%). In this population, 3681 (3.0%) were D-/R+, 1738 (1.4%) were D+/R+, and 294 (0.2%) were D+/R-.

Use of HCV Treatment

Overall, 12.9% of patients undergoing LT received HCV medications within 3 years after transplant. Among serologic subgroups, treatment prevalence varied from 0.75% of HCV D-/R- patients to 35.2% of D+/R+ patients (Figure 1A). In the pre-DAA era, 4.0% of HCV D+/R+ and 5.5% of D-/R+ received HCV treatment within 1 year. Post-DAA, 13.5% of D+/R+ patients and 4.4% of D-/R+ patients received treatment within 1 year. By 3 years, 17.0% D+/R+ and 17.1% D-/R+ patients received treatment in the pre-DAA era. Post-DAA, 15.3% of D+/R+ and 5.5% of D-/R+ recipients had received treatment at the end of follow-up (2.3 years and 2.6 years, respectively). Clinical factors associated with use of HCV treatments pre-DAA include male sex (adjusted hazard ratio [aHR] 0.830.911.00), diabetes (aHR 0.800.890.98), hypertension (aHR 1.031.131.25), higher model for end-stage liver disease (MELD) score (15–30, aHR 1.011.101.20; >30, aHR 1.001.181.38 vs MELD<15), and black race (aHR 0.720.810.90). Post-DAA, donor HCV+ status (aHR 1.661.952.29), higher MELD score (15–30, aHR 1.231.421.65; >30, aHR 1.431.812.28), and black race (aHR 0.650.790.96) were associated with the likelihood of HCV treatment (Table S2A).

Figure 1.

(A) Incidence of HCV treatment after liver transplant, by donor-recipient serostatus and DAA era. (B) Incidence of HCV treatment after kidney transplant. D, donor; DAA, direct-acting antiviral; HCV, hepatitis C virus; R, recipient; Tx, transplant [Color figure can be viewed at wileyonlinelibrary.com]

The impact of payer on LT recipient access differed by DAA era. Pre-DAA, HCV+ LT recipients with private insurance were equally likely to be treated with HCV medications (Figure 2A). After adjustment for donor and recipient characteristics, HCV+ recipients with private insurance were somewhat more likely to be treated (aHR 1.011.101.19). However, in the post-DAA era, both D+/R+ and D-/R+ recipients with private insurance were significantly less likely to receive HCV treatment (Figure 2B). Nearly 20% of D+R+ recipients with public insurance, compared with 11% of recipients with private insurance (P < .0001), received treatment. After adjustment for other donor and recipient characteristics, D+/R+ recipients with private insurance were 45% less likely than publicly insured recipients to receive HCV treatment (aHR 0.430.550.71, P < .0001). Among D-/R+ recipients, 6.2% with public insurance received DAA treatment, compared with 5.0% with private insurance (aHR 0.740.840.96, P = .01).

Figure 2.

(A) Incidence of HCV treatment after liver transplant in the pre-DAA era, by donor-recipient serostatus and payer. (B) Incidence of HCV treatment after liver transplant in the post-DAA era, by donor-recipient serostatus and payer. (C) Incidence of HCV treatment after kidney transplant in the pre-DAA era, by donor-recipient serostatus and payer. (D) Incidence of HCV treatment after kidney transplant in the post-DAA era, by donor-recipient serostatus and payer. D, donor; DAA, direct-acting antiviral; HCV, hepatitis C virus; R, recipient; Tx, transplant [Color figure can be viewed at wileyonlinelibrary.com]

As expected, HCV treatment was substantially less common in KT recipients; overall, 1.4% received HCV treatments within 3 years of transplant. Utilization was highest, at 22.8%, for D+R+ recipients; 11.3% of D-/R+ recipients received treatment (Figure 1B). Pre-DAA, 2.8% of D-/R+ and 5.5% of D+R+ recipients received treatment with HCV medications within 3 years. Post-DAA, 3.9% of D-/R+ and 12.9% of D+/R+ recipients received treatment (P < .0001). Differences by payer in the post-DAA era were modest. Among D+R+ recipients, 13.5% with public insurance received treatment compared with 11.5% with private insurance (P = .35). Among D-/R+ recipients, 4.3% with public insurance received treatment, compared with 2.9% with private insurance (P = .05). After adjustment for donor and recipient characteristics, HCV treatment in R+ D+ KT patients was more likely than D- patients before and after DAA introduction (Pre-DAA: aHR 1.432.02 2.84 vs Post DAA aHR: 2.312.93 3.71). In the post-DAA era, other patients whose race was not black or white and older patients were more likely to be treated (Table S2B).

Impact of HCV Treatment on Patient and Graft Survival

LT outcomes among all HCV+ recipients have improved in the post-DAA era (Figure 3A). Among all HCV+ LT recipients, after adjustment for donor and recipient characteristics, HCV requiring treatment pre-DAA was associated with a significantly higher risk of posttransplant mortality (aHR 1.471.681.91, P < .0001) and all-cause graft failure (aHR 1.641.852.10, P < .0001) (Figure 4A). In contrast, there was not increased risk of death or graft failure post-DAA (aHR for death: 0.740.941.19, P = .61; aHR for graft failure: 0.740.941.19, P = .62) (Figure 4; Table S3A). In D-/R+ recipients, HCV treatment pre-DAA was not associated with an increased risk of death (P = .96) or graft failure (P = .40). Among D+/R+ post-DAA, the reduction in the risk of death (aHR 0.340.671.32, P = .25) and graft failure (aHR 0.320.641.26, P = 0.20) within 3 years of transplant was not statistically significant (Table S3B).

Figure 3.

(A) HCV D+/R+ liver recipient survival, by DAA era. (B) HCV D+/R+ kidney recipient survival, by DAA era. D, donor; DAA, direct-acting antiviral; HCV, hepatitis C virus; R, recipient; Tx, transplant [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4.

(A) HCV+ liver recipient relative risks of death and graft loss, by DAA era. (B) HCV+ kidney recipient relative risks of death and graft loss, by DAA era. ACGF, All Cause Graft Failure; DAA, direct-acting antiviral; HCV, hepatitis C virus [Color figure can be viewed at wileyonlinelibrary.com]

Among HCV+ KT recipients, there was no significant improvement in unadjusted patient survival post-DAA compared with pre-DAA (Figure 3B). In the adjusted analysis, pre-DAA HCV treatment was associated with a non-statistically significant increased risk of death (aHR0.67 1.804.87, P = .25) and graft failure (aHR 0.711.613.62, P = .24) (Figure 4B; Table S4A). There was a nonsignificant protective effect of treatment for KT recipients post-DAA for mortality (aHR 0.370.661.18, P = .16) and graft failure (aHR 0.490.791.27, P = .33) (Table S3; Table S4A). Among D+R+ KT recipients, DAA treatment was associated with nonsignificant reduction in graft failure (aHR 0.270.54 1.07, P = .08) and a statistically significant lower risk of death after KT (0.190.430.95, P = .04). (Table S4B)

Economic Analysis

The cost of HCV treatment increased dramatically for LT and KT recipients in the DAA era. The mean direct cost of HCV treatment for D+R+ recipients after LT increased from $9772 USD pre-DAA to $120 096 USD in 2014-2017 (P < .0001). For KT, cost of treatment increased from $4489 USD to $106 747 USD (P < .0001).

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