腎臟移植受贈者使用 Maribavir 誘發胰臟炎：病例報告

黃鈺翔、王大民、林國仁、林志德、潘柏諺、陳思遠、林晏頎、楊聿寬、王敘涵

林口長庚紀念醫院 外科部 泌尿外科

Maribavir induced pancreatitis in renal transplant recipient: A Case Report

Yu-Hsiang Huang, Ta-Min Wang, Kuo-Jen Lin, Chih-Te Lin, Pai-Yen Pan, Sy-Yuan Chen, Yen-Chi Lin, Yu-Kuan Yang, Hsu-Han Wang

Division of Urology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan

Background

Cytomegalovirus (CMV) is a widespread pathogen that infects more than half of the global population.[1] In immunocompetent individuals, primary CMV infection typically presents as a mild and self-limited illness, after which the virus establishes lifelong latency. However, either primary CMV infection or reactivation of latent virus may occur during periods of significant immunosuppression such as in solid organ transplant (SOT) recipients, leading to a broad clinical spectrum ranging from asymptomatic infection to severe and potentially life-threatening disease. Given the detrimental impact of CMV on transplant outcomes, effective prevention remains a critical aspect of post-transplant care. Prevention strategies rely on either universal antiviral prophylaxis or preemptive therapy for asymptomatic viral replication.[2] Ganciclovir has served as the primary antiviral agent for CMV for more than three decades. Ganciclovir is available as an intravenous formulation, while valganciclovir serves as its oral prodrug.[3]

Ganciclovir has been extensively validated as an effective agent for both prevention and treatment of CMV in SOT recipients.[4] However, its use is often complicated by hematologic toxicities—especially leukopenia and neutropenia. Dose adjustments are further challenged by the fluctuating renal function commonly seen in transplant patients. Failure to appropriately adjust dosing may result in subtherapeutic levels, which can promote the emergence of drug-resistant CMV strains. Resistance occurs most often through UL97 mutations that impair ganciclovir phosphorylation.[5]

In cases of ganciclovir resistance, alternative treatments such as foscarnet or cidofovir may be used, although both carry significant nephrotoxicity risks. Like ganciclovir, these agents inhibit CMV DNA synthesis by targeting UL54-encoded DNA polymerase. Nonetheless, CMV may also develop UL54 mutations that confer resistance to DNA polymerase inhibitors (ganciclovir, cidofovir, and foscarnet), resulting in severely limited therapeutic options.[2] This underscores the need for newer antiviral therapies that offer improved safety and efficacy.

Another alternative medication which is called maribavir is an orally administered benzimidazole L-riboside with strong and selective multimodal activity against CMV. Its primary mechanism of action involves inhibition of the UL97 kinase, where it competitively blocks adenosine triphosphate (ATP) binding to pUL97. This viral kinase is responsible for phosphorylating multiple downstream viral proteins that are essential for CMV replication.[4] By preventing ATP binding, maribavir disrupts the phosphorylation processes required for CMV DNA synthesis, viral encapsidation, and nuclear egress of viral capsids.[6]

Maribavir is considered a promising option for managing ganciclovir-resistant CMV disease due to its distinct mechanism of action and is now approved for the treatment of refractory or resistant CMV infection. However, there is still some adverse reactions such as taste disturbance (dysgeusia), which is described as bitter, metallic, or altered taste. Other common adverse effects include nausea, diarrhea, vomiting, headache, rashes, and fatigue. However, the incidence of gastrointestinal adverse events—such as nausea, vomiting, and diarrhea was comparable between patients treated with maribavir and those receiving ganciclovir, valganciclovir, foscarnet or cidofovir. No significant hematologic, hepatic, or renal toxicities were observed.[7] Aside from the adverse events mentioned above, here we present a case as a kidney transplant recipient under maribavir use who encounted acute pancreatitis.

Case Presentation

This is a 41-year-old female with a history of systemic lupus erythematosus (SLE) diagnosed in 2009. Her initial presentation included proteinuria with positive ANA and anti-Sm antibodies, complicated by lupus nephritis. As her renal function progressively declined to end-stage renal disease, she began regular hemodialysis in 2009. She underwent cadaveric kidney transplantation on March 21, 2025. Postoperatively, she developed persistent hydronephrosis of the graft kidney, attributed to a ureterovesical junction stricture. Consequently, a transureteroureterostomy, connecting the graft ureter to the right native ureter, was performed on July 11, 2025. Despite this intervention, hydronephrosis of the graft kidney persisted over subsequent months. She was therefore admitted for graft ureter antegrade augmentation and stent placement on September 1, 2025. On September 2, 2025, percutaneous placement of a ureteral stent into the graft kidney was successfully performed.

Because of her immunosuppressed status, valganciclovir had been administered for CMV prophylaxis from the time of kidney transplantation until June 7, 2025, when it was discontinued due to leukocytosis and replaced with maribavir at a dosage of 200 mg twice daily. During admission, the patient reported no fever, dysuria, flank pain, abdominal pain, or hematuria. Physical examination revealed a soft, non-tender abdomen.

On hospital day 4, however, markedly elevated amylase (1663 U/L) and lipase (2107 U/L) levels were detected. Maribavir was temporarily discontinued due to suspicion of drug-induced pancreatitis. Two days after withholding maribavir, both amylase and lipase returned to normal ranges. A non-contrast abdominal CT scan showed mild pancreatic swelling with surrounding inflammatory changes and moderate ascites. Although the pancreatitis improved, the patient required antibiotic treatment for recurrent urinary tract infection, and no further elevations in amylase or lipase were observed. She was discharged in stable condition after resolution of the urinary tract infection two weeks later.

Discussion

Despite progress in preventive strategies, CMV infection continues to pose a major challenge in solid organ transplantation (SOT), contributing to adverse patient and graft outcomes, particularly in cases of refractory or resistant CMV disease.[8] Ganciclovir-resistant CMV is being identified with increasing frequency in the solid organ transplant population, and although it remains relatively uncommon, it is associated with substantial morbidity.[9] Advances in diagnostic testing and the introduction of new antiviral agents have improved CMV management; however, the optimal prevention and treatment strategies remain unclear. Assessment of CMV-specific cell-mediated immunity may enable more individualized approaches in the future.

Reference

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