Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients.

OBJECTIVES: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.

Use of Hepatitis C Nucleic Acid Test-Positive Liver Allografts in Hepatitis C Virus Seronegative Recipients.

Because of underutilization of liver allografts, our center previously showed that hepatitis C virus (HCV) antibody-positive/nucleic acid test (NAT)-negative livers when transplanted into HCV nonviremic recipients were safe with a 10% risk of HCV transmission. Herein, we present our single-center prospective experience of using HCV NAT+ liver allografts transplanted into HCV NAT- recipients. An institutional review board-approved matched cohort study was conducted examining post- liver transplantation (LT) outcomes of HCV- patients who received HCV NAT+ organs (treatment group) compared with matched recipients with HCV NAT- organs (matched comparator group) between June 2018 to October 2019. The primary endpoint was success of HCV treatment and elimination of HCV infection. The secondary outcomes included the 30-day and 1-year graft and patient survival as well as perioperative complications. There were 32 recipients enrolled into each group. Because of 1 death in the index admission, 30/31 patients (97%) were given HCV treatment at a median starting time of 47 days (18-140 days) after LT. A total of 19 (63%) patients achieved sustained virological response at week 12 (SVR12). Another 6 patients achieved end-of-treatment response, while 5 remained on therapy and 1 is yet to start treatment. No HCV treatment failure has been noted. There were no differences in 30-day and 1-year graft and patient survival, length of hospital stay, biliary or vascular complications, or cytomegalovirus viremia between the 2 groups. In this interim analysis of a matched cohort study, which is the first and largest study to date, the patients who received the HCV NAT+ organs had similar outcomes regarding graft function, patient survival, and post-LT complications.

Use of Hepatitis C Virus Antibody-Positive Donor Livers in Hepatitis C Nonviremic Liver Transplant Recipients.

BACKGROUND: Given the shortage of available liver grafts, transplantation (LTx) of hepatitis C virus antibody-positive, nucleic acid test-negative (HCV Ab+/NAT-) livers into nonviremic HCV recipients can expand the donor pool. Having previously described the sentinel experience of HCV Ab+/NAT- allografts in nonviremic recipients, we report the growth and extended follow-up of this program for 55 patients compared with recipients of Public Health Services (PHS) increased-risk donor HCV Ab-/NAT- allografts. STUDY DESIGN: A prospective review of all HCV nonviremic LTx patients receiving HCV Ab+/NAT- organs between March 2016 and August 2018 was performed. All HCV Ab+/NAT- organ recipients underwent HCV testing at 3 months and 1-year post-LTx to determine HCV transmission. RESULTS: Fifty-five HCV nonviremic candidates received HCV Ab+/NAT- organs; 64% male, median age 59 years (range 36 to 69 years) and median Model for End-Stage Liver Disease score of 22.5. Two recipients were excluded due to death before HCV testing. The HCV disease transmission occurred in 5 recipients (9%). Of these, 4 (80%) underwent anti-HCV treatment with eradication of virus. No patient found to be negative at 3 months seroconverted at 1-year follow-up. No patients who received PHS increased-risk donor HCV Ab-/NAT- organs had viremia develop (0 of 57) and there was no difference in graft and renal function, complications, or survival between HCV Ab+/NAT- recipients and PHS increased-risk donor HCV Ab-/NAT- recipients. CONCLUSIONS: We report the largest experience with LTx from HCV Ab+/NAT- donors into 55 seronegative recipients with a HCV transmission rate of 9% with no late conversions at 1 year and no difference in function or graft loss compared with PHS increased-risk donor HCV Ab-/NAT- recipients. Due to availability of safe and effective HCV therapies, the use of such organs should be strongly considered to increase the donor organ pool.

Hepatitis C transmission from seropositive, nonviremic donors to non-hepatitis C liver transplant recipients.

Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody-positive but serum NAT-negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV PCR test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died 18 days after transplantation from primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow-up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct-acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated postoperative course and did not receive antiviral therapy. CONCLUSION: In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682).

Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria.

BACKGROUND: Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single-center experience with tumor downstaging and its effects on post-orthotopic liver transplantation outcomes. METHODS: All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N = 214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha-fetoprotein >400 ng/mL were categorized as at high risk for tumor recurrence and post-transplant mortality. RESULTS: Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high-risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha-fetoprotein <400 ng/mL before orthotopic liver transplantation, through locoregional therapies. Recurrence of hepatocellular carcinoma was higher but acceptable between downstaged high-risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow-up period of 17 months. Downstaged high-risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log-rank P > .05). CONCLUSIONS: In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post-transplant outcomes. These data support an aggressive downstaging approach for selected patients who would otherwise be deemed ineligible for transplantation.

Successful Simultaneous Liver-Kidney Transplantation in the Presence of Multiple High-Titered Class I and II Antidonor HLA Antibodies.

The results of simultaneous liver-kidney transplants in highly sensitized recipients have been controversial in terms of antibody-mediated rejection and kidney allograft outcomes. This case report provides a detailed and sophisticated documentation of histocompatibility and pathologic data in a simultaneous liver-kidney transplant performed in a recipient with multiple high-titered class I and II antidonor HLA antibodies and a strongly positive cytotoxic crossmatch. Patient received induction with steroids, rituximab, and eculizumab without lymphocyte depleting agents. The kidney transplant was delayed by 6 hours after the liver transplant to allow more time to the liver allograft to "absorb" donor-specific antibodies (DSA). Interestingly, the liver allograft did not prevent immediate antibody-mediated injury to the kidney allograft in this highly sensitized recipient. Anti-HLA single antigen bead analysis of liver and kidney allograft biopsy eluates revealed deposition of both class I and II DSA in both liver and kidney transplants during the first 2 weeks after transplant. Afterward, both liver and kidney allograft functions improved and remained normal after a year with progressive reduction in serum DSA values.