Fibrosing cholestatic hepatitis after kidney transplantation from HCV-viremic donors to HCV-negative recipients: A unique complication in the DAA era

Abstract

Fibrosing cholestatic hepatitis (FCH) posttransplantation can lead to graft failure and death. In the era of direct acting antiviral therapy (DAA), several studies have demonstrated the efficacy and safety of transplanting hepatitis C virus (HCV)–positive allografts into HCV‐negative recipients. In this case series, we present two cases of HCV‐negative recipients who underwent kidney transplantation from viremic donors and developed FCH. Both patients presented after transplant with abnormal liver function tests and HCV viral loads of greater than 100 000 000 IU/mL. FCH was diagnosed by histology and/or clinical data. Both patients were started on DAA therapy within 24 hours of admission with improvement in LFTs. One patient has undetectable HCV 12 weeks after completing treatment and the other patient has undetectable HCV after completing DAA treatment. The introduction of DAAs has changed the landscape of solid organ transplantation with the potential to expand the donor pool and increase access to organs. While HCV viremic organs have tremendous potential to increase access to a scarce resource, FCH is a potentially fatal complication and therefore clinicians must maintain a high index of suspicion for this unique complication.

Liver, simultaneous liver‐kidney, and kidney transplantation from hepatitis C‐positive donors in hepatitis C‐negative recipients: A single‐center study

“…Immediate treatment is generally unnecessary outside of rare clinical scenarios including the development of FCH or de novo membranoproliferative GN. Data from published case series suggest that urgent treatment with DAAs in these instances can lead to rapid resolution of HCV infection with no long‐term untoward outcomes …”

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…Emerging data suggest that initiating prophylactic/ preemptive DAA therapy before viremia occurs reduces the likelihood of complications, such as fibrosing cholestatic hepatitis. (359,(373)(374)(375)(376) The prophylactic/preemptive approach may also allow for a shorter duration of DAA treatment, (359,377) although this is not currently recommended outside of a clinical trial setting.…”

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients

“…In one case report, 2 patients developed fibrosing cholestatic hepatitis post-kidney transplant due to donor-derived HCV transmission. 34 In another larger study (N = 53) of posttransplant therapy started after 8 weeks of kidney transplant, one patient developed fibrosing cholestatic hepatitis amd an additional 20% patients developed significant elevations in alanine transaminase. 35 Taken together, our findings support the concept of a prophylactic strategy that might offer advantages with regards to allo-sensitization as well as minimization of the risk of acute liver injury.…”

“…Recent studies also suggest that significant delay in initiation of DAA therapy might be detrimental in other ways. In one case report, 2 patients developed fibrosing cholestatic hepatitis post–kidney transplant due to donor‐derived HCV transmission . In another larger study (N = 53) of posttransplant therapy started after 8 weeks of kidney transplant, one patient developed fibrosing cholestatic hepatitis amd an additional 20% patients developed significant elevations in alanine transaminase .…”