ABSTRACT
BACKGROUND: Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies. OBJECTIVE: The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min. METHODS: This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant. RESULTS: Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease. CONCLUSION AND RELEVANCE: Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.
ABSTRACT
PURPOSE: Direct-acting antivirals (DAAs) allow for successful transplantation of livers from hepatitis C nucleic acid test (NAT)-positive donors to negative recipients. However, limited data exist to support crushing DAAs in patients with multiple absorption concerns or significant drug interactions. SUMMARY: Crushed sofosbuvir/velpatasvir has been successfully used in nontransplant patients with dysphagia, but data in transplant patients with absorption concerns are limited. A 31-year-old hepatitis C-negative female underwent liver transplantation from a hepatitis C NAT-positive donor. Her postoperative course was complicated by a mucormycosis infection, gastrointestinal bleed, and necrotizing pancreatitis requiring treatment with liposomal amphotericin B and pantoprazole 80 mg twice daily. Surgical interventions included an above-the-knee amputation and ileostomy. Hepatitis C treatment was initially delayed because of concern for reduced absorption with crushed DAA administration through the nasogastric (NG) tube, high ileostomy output, gastrointestinal bleed, pancreatitis, and a known drug interaction with pantoprazole. One month after transplantation, the patient's bilirubin level remained elevated and hepatitis C treatment was initiated with sofosbuvir/velpatasvir. Crushed sofosbuvir/velpatasvir was mixed with 30 mL of water and administered through the NG tube daily. Hepatitis C viral loads were obtained weekly during treatment to monitor efficacy. Although the patient died before evaluation of sustained virological response at 12 weeks, hepatitis C viral clearance was observed within 4 weeks of initiating treatment. CONCLUSION: A liver transplant patient exhibited viral clearance of hepatitis C following administration of crushed sofosbuvir/velpatasvir in the setting of multiple absorption concerns.
