Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Solid-organ Transplant Recipients on Continuous Veno-venous Hemodialysis.

BACKGROUND: Optimal valganciclovir dosing for cytomegalovirus (CMV) prophylaxis in solid-organ transplant (SOT) patients on continuous veno-venous hemodialysis (CVVHD) is not known. Ganciclovir trough concentrations ≥0.60 µg/mL have been suggested for CMV prophylaxis. This study was conducted to determine if valganciclovir 450 mg enterally every 24 hours achieves ganciclovir trough concentrations ≥0.60 µg/mL in patients on CVVHD. METHODS: This single-center, prospective, open-label, pharmacokinetic study included adult SOT patients admitted to an intensive care unit from March 2018 to June 2019 on CVVHD. All patients were receiving valganciclovir 450 mg enterally every 24 hours for CMV prophylaxis prior to enrollment. Each patient had a peak and trough sample drawn at steady state. RESULTS: Ten SOT patients were included in the study (6 liver, 1 simultaneous liver-kidney, 2 bilateral lung, 1 heart). The mean ± SD age was 51.8 ± 14.0 years, and average body mass index was 27 ± 6.9 kg/m2. Ganciclovir trough concentrations ranged from 0.31 to 3.16 µg/mL, and 80% of participants have trough concentrations ≥0.60 µg/mL. No patients had documented neutropenia while on valganciclovir and CVVHD; 60% of patients had significant thrombocytopenia. CONCLUSIONS: Valganciclovir 450 mg enterally every 24 hours achieved ganciclovir trough concentrations ≥0.60 µg/mL in most patients on CVVHD, similar to those reported with intravenous ganciclovir for prophylaxis in this population. Based on these data, valganciclovir may require dosing every 24 hours to achieve concentrations equivalent to ganciclovir. Neutropenia did not occur in the study period. Thrombocytopenia was common and likely multifactorial.

Steroid-sparing maintenance immunosuppression is safe and effective after simultaneous liver-kidney transplantation.

Optimization of maintenance immunosuppression (mIS) regimens in the transplant recipient requires a balance between sufficient potency to prevent rejection and avoidance of excessive immunosuppression to prevent toxicities and complications. The optimal regimen after simultaneous liver-kidney (SLK) transplantation remains unclear, but small single-center reports have shown success with steroid-sparing regimens. We studied 4184 adult SLK recipients using the Scientific Registry of Transplant Recipients, from March 1, 2002, to February 28, 2017, on tacrolimus-based regimens at 1 year post-transplant. We determined the association between mIS regimen and mortality and graft failure using Cox proportional hazard models. The use of steroid-sparing regimens increased post-transplant, from 16.1% at discharge to 88.0% at 5 years. Using multi-level logistic regression modeling, we found center-level variation to be the major contributor to choice of mIS regimen (ICC 44.5%; 95% CI: 36.2%-53.0%). In multivariate analysis, use of a steroid-sparing regimen at 1 year was associated with a 21% decreased risk of mortality compared to steroid-containing regimens (aHR 0.79, P = .01) and 20% decreased risk of liver graft failure (aHR 0.80, P = .01), without differences in kidney graft loss risk (aHR 0.92, P = .6). Among SLK recipients, the use of a steroid-sparing regimen appears to be safe and effective without adverse effects on patient or graft survival.

Hepatitis C-positive donor liver transplantation for hepatitis C seronegative recipients.

BACKGROUND: The opioid crisis has led to an increase in hepatitis C virus-positive donors in the past decade. Whereas historically hepatitis C seropositive organs were routinely discarded, the advent of direct-acting antiviral agents has notably expanded the utilization of organs from donors with hepatitis C. There has been growing experience with liver transplantation (LT) from hepatitis C seropositive donors to hepatitis C seropositive recipients. However, data remain limited on LT from hepatitis C seropositive or hepatitis C ribonucleic acid positive donors to hepatitis C seronegative recipients. METHODS: We performed a retrospective study of 26 hepatitis C seronegative recipients who received hepatitis C seropositive donor livers followed by preemptive antiviral therapy with direct-acting antiviral treatment at the Johns Hopkins Hospital Comprehensive Transplant Center from January 1, 2017, to August 31, 2019. RESULTS: Twenty-five of the 26 recipients are alive with proper graft function; 20 of them received livers from hepatitis C nucleic acid testing positive donors. All 12 recipients who completed their direct-acting antiviral courses and have reached sufficient follow-up for sustained virologic response have achieved sustained virologic response. Nine of our recipients have either completed direct-acting antiviral treatment without sufficient follow-up time for sustained virologic response or are undergoing direct-acting antiviral treatment. One patient is awaiting antiviral treatment initiation pending insurance approval. Of note, 11 of 12 patients with sustained virologic response received a hepatitis C nucleic acid testing positive donor liver. CONCLUSION: Hepatitis C seronegative patients who receive a hepatitis C seropositive or hepatitis C nucleic acid testing positive liver allograft can enjoy good short-term outcomes with hepatitis C cure following direct-acting antiviral treatment.

Role of lower dose hepatitis B immune globulin prophylaxis in liver transplantation: A single center perspective.

Background and Aim: Prevention of hepatitis B virus (HBV) reinfection is important for long-term outcomes following liver transplantation (LT). Hepatitis B immunoglobulin (HBIG) is used among recipients who have (i) native HBV disease, (ii) hepatitis B core antibody positivity (HBcAb positivity), or (iii) received HBcAb positive organs. Nucleos(t)ide analogue (NA) monotherapy is emerging for treating patients in this setting. There is no generalized consensus on the ideal dosage of HBIG. The aim of this study was to evaluate the efficacy of low-dose HBIG (1560 international unit [IU]) for post-LT HBV prevention. Materials and Methods: HBcAb positive patients who received either HBcAb positive or hepatitis B core antibody negative (HBcAb negative) organs and HBcAb negative patients who received HBcAb positive organs between January 2016 and December 2020 were reviewed. Pre-LT HBV serologies were collected. HBV-prophylaxis strategy included NA with/without HBIG. HBV recurrence was defined as HBV deoxyribonucleic acid (DNA) positivity during the 1-year, post-LT follow-up. No HBV surface antibody titers were followed. Results: A total of 103 patients with a median age of 60 years participated in the study. Hepatitis C virus was the most common etiology. Thirty-seven HBcAb negative recipients and 11 HBcAb positive recipients with undetectable HBV DNA received HBcAb positive organs and underwent prophylaxis with 4 doses of low-dose HBIG and NA. None of the recipients in our cohort had a recurrence of HBV at 1 year. Conclusion: Low-dose HBIG (1560 IU) × 4 days and NA, for HBcAb positive recipients and HBcAb positive donors, appear to be effective in preventing HBV reinfection during the post-LT period. Further trials are needed to confirm this observation.

Access to direct-acting antivirals for hepatitis C-negative transplant recipients receiving organs from hepatitis C-viremic donors.

PURPOSE: A barrier to using organs from hepatitis C virus (HCV)-viremic donors is the high cost of direct-acting antivirals (DAAs) and concerns about access for recipients after transplantation. The purpose of this study was to evaluate access, cost, and timing for HCV DAAs following transplantation. METHODS: This was a single-center, retrospective study of HCV-negative adult transplant recipients from June 2017 to December 2019 who received grafts from HCV-viremic and/or HCV-seropositive individuals and became HCV viremic after transplantation. RESULTS: Between June 2017 and December 2019, there were 60 HCV-negative transplant recipients who became viremic after receiving grafts from HCV-viremic or HCV-seropositive donors. Thirty-eight patients met the inclusion criteria (n = 25 with liver transplants, n = 6 with lung transplants, n = 4 with simultaneous liver and kidney transplants, and n = 3 with kidney transplants). Of these patients, 23 had commercial insurance, 13 had Medicare, and 2 had Medicaid. All patients ultimately received insurance coverage for treatment; however, 36 (95%) required prior authorization and 9 (24%) required appeals to obtain insurance coverage. The median time from DAA prescription to insurance approval was 6 days. The median time from transplantation to start of treatment was 29 days (range, 0-84 days). Patients with Medicaid insurance had a significantly longer time to insurance approval (31.5 vs 6 days, P = 0.007). The average out-of-pocket cost to patients was less than $10 a month after patient assistance. All patients who completed treatment and 12-week follow-up after treatment achieved a sustained virologic response (n = 36). CONCLUSION: In this study, all HCV-negative recipients who developed HCV following transplantation had access to DAA therapy, with the majority starting treatment in the first month after transplantation.

Hepatitis B Virus/Hepatitis D Virus-Coinfected Liver Transplant Candidate Receiving Hepatitis B Virus-Deoxyribonucleic Acid-Positive Allograft and Treated With High-Dose Hepatitis B Immune Globulin.

Liver transplantation (LT) for patients with hepatitis D virus (HDV) and hepatitis B virus (HBV) coinfection is uncommon in the United States. Previous case reports described poor outcomes when hepatitis B surface antigen (HBsAg)-positive grafts are transplanted in HBV/HDV-coinfected recipients. However, LT from an HBsAg-negative/HBV-deoxyribonucleic acid-positive donor in an HBV/HDV-coinfected recipient has not been reported. We describe the clinical course and management of an HBV/HDV-coinfected recipient who had LT from an HBsAg-negative/HBV-deoxyribonucleic acid-positive deceased donor and was treated with high-dose hepatitis B immune globulin in combination with an oral tenofovir alafenamide.