HCV Status and Kidney Transplantation Outcomes

In the general population in the United States, the prevalence of hepatitis C virus (HCV) is ~1%; the prevalence among patients on hemodialysis ranges between 3% and 14%. Current US practice guidelines call for screening of all dialysis patients for HCV infection by testing for anti-HCV antibody and, more recently, HCV RNA to confirm chronic infection.

For many patients with kidney failure, transplantation is the ideal therapy. However, there are few data available on outcomes among HCV-seropositive dialysis patients because HCV serostatus for wait-listed patients is not included in national registry data (i.e., the Organ Procurement and Transplantation Network [OPTN] and the US Renal Data System).

Deidre Sawinski, MD, and colleagues recently conducted a retrospective cohort study designed to examine the association between HCV serostatus and dialysis survival and kidney transplantation. The researchers also sought to determine whether kidney transplantation offered a survival benefit versus remaining on the waitlist among HCV-seropositive patients. Finally, the study assessed the impact of transplantation with an HCV-seropositive donor kidney on survival compared with waiting for a kidney from an HCV-negative donor. Results of the study were reported in the American Journal of Kidney Diseases [2019;73(6):815-826].

The study cohort included adults ≥18 years of age who were incident and prevalent patients receiving outpatient dialysis therapy between January 1, 2004, and December 31, 2014, at facilities in the United States managed by a large national dialysis provider (DaVita). Exclusion criteria were patients with indeterminate HCV serostatus and/or HIV infection. Using five different identifiers, clinical data from DaVita were linked to data from the OPTN: Social Security number, date of birth, first name, last name, and sex.

The primary exposure was HCV antibody status; results of assessment were reported as positive, negative, or indeterminate. The primary outcomes of interest were (1) mortality on dialysis therapy; (2) wait-listing for kidney transplantation; (3) kidney transplantation; and (4) estimated survival benefit from kidney transplantation versus remaining on the transplant waitlist. Secondary outcomes included removal from the waitlist.

A total of 442,171 adult maintenance dialysis patients had a defined HCV serostatus; of those, 410,547 were HCV seronegative and 31,624 were HCV seropositive.  Patients in the seropositive group were younger (median age, 56 vs 64 years; P<.001), more likely to be male (65.9% vs 54.4%; P<.001), and more likely to be African American (54% vs 29.1%; P<.001) than patients in the HCV seronegative group. Patients who were HCV seropositive were twice as likely to have Medicaid as their primary insurance (7.4% vs 3.3%; P<.001) than those in the HCV seronegative group.

The majority of the cohort received in-center hemodialysis; the most common vascular access was central venous catheter. In the HCV-seropositive group, median serum albumin and platelet count values were lower than in the HCV-seronegative group; the differences were not clinically significant.

There was an association between ICV seropositivity and increased risk for death on dialysis therapy (adjusted hazard ratio [aHR], 1.09; 95% confidence interval [CI], 1.07-1.11). Median follow-up was 652 days. In secondary analyses limited to hemodialysis patients or including the Fibrosis-4 index, results were similar. The most commonly reported causes of death were cardiovascular disease (33% HCV-seropositive vs 35.8% HCV-seronegative) and infection (8.5% HCV-seropositive vs 7.7% HCV-seronegative). In the HCV-seropositive cohort, patient death was attributed to liver disease in 3.3% of the cohort versus 0.6% in the seronegative patients (P<.001).

Following application of exclusion criteria, the researchers analyzed 410,804 patients regarding wait-listing (29,263 HCV-seropositive and 381,541 HCV-seronegative). In the seronegative cohort, median time to wait-listing was 354 days compared with 473 days in the seropositive cohort (P<.001). There was an association between HCV seropositivity and a lower likelihood of wait-listing for kidney transplant (aHR, 0.67; 95% CI, 0.61-0.74). The association remained consistent in models accounting for death as a competing risk for wait-listing and in secondary analyses.

A total of 51,625 patients were wait-listed for a kidney transplant. Of those, 16,490 seronegative and 1117 seropositive patients underwent transplantation. There was no significant difference between the groups in overall time to transplantation (507 days for HCV seronegative vs 433 days for HCV seropositive, P=.6). However, the time to transplantation was significantly shorter for recipients of HCV-seropositive kidneys (251 days; P<.002). In both unadjusted and adjusted analyses, there was no significant association between patient HCV seropositivity and rate of transplantation (aHR, 1.11; 95% CI, 0.97-1.28).

Compared with remaining on the waitlist, there was an association between kidney transplantation and decreased risk for death among the HCV-seropositive patients; this benefit was achieved by 9 months following transplantation. By year 3, the adjusted hazard of death associated with transplantation compared with remaining on the waitlist was 0.42 (95% CI, 0.27-0.63). Of the 1117 seropositive recipients, 394 received kidneys from HCV-seropositive donors; survival benefit with transplantation was independent of donor HCV serostatus (aHR for death at 3 years, 0.42 (95% CI, 0.25-0.72) for kidneys from HCV-seronegative donors versus 0.52 (95% CI, 0.30-0.93) for kidneys from HCV-seropositive donors.

Study limitations cited by the authors included lack of data for HCV viral loads and incomplete data on severity of liver disease.

“In conclusion, this study provides important and comprehensive insights into outcomes for HCV-seropositive patients with end-stage renal disease on the spectrum from maintenance dialysis therapy through kidney transplantation. HCV-seropositive patients are younger yet experience a slightly higher adjusted rate of death on dialysis therapy. They have diminished access to the transplant waiting list, but those who undergo transplantation rapidly achieve a significant survival benefit. The survival benefit from kidney transplantation among HCV-seropositive patients suggests that removing barriers to wait-listing for this patient group should be a priority for providers. The benefit in accepting an HCV-infected organ over waiting for an HCV-negative one should encourage patients to carefully consider post-transplantation HCV treatment,” the researchers said.

Takeaway Points

1. In the United States, among patients with chronic kidney disease, the prevalence of hepatitis C virus infection is substantially higher than in the general population. Researchers conducted a retrospective cohort study to examine dialysis survival and transplantation outcomes in patients with CKD who were HCV seropositive.
2. There was an association between HCV seropositivity and a small elevation in the rate of death and a substantially lower rate of entry onto the kidney transplant waitlist.
3. Compared with remaining on the waitlist, receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year post-transplantation time point.