Case 5
An 18-year-old female with CF (F508del/F508del), short bowel secondary to meconium ileus and resection, and history of liver transplant as an infant secondary to biliary atresia and failed Kasai procedure. This patient had no episodes of acute or chronic rejection since the transplant, nor any other post-transplant complications. LFTs were predominantly normal (occasional intermittent elevations), with intermittently low platelets. Liver biopsies showed mild inflammatory changes (plasma cell predominant) with significant fibrosis dating back to 2010. Ultrasound in 2019 demonstrated stable, mild inhomogeneous echotexture of the liver with normal hepatic Doppler. This patient was initiated on full dose elx/tez/iva in March 2020. One week after starting therapy, her tacrolimus concentration tripled from 5.0 to 15.1 ng/mL. During this time, no medication changes had been made, her overall medical condition remained stable, and LFTs remained normal. No adverse outcomes occurred as a result of the elevated tacrolimus concentration. The tacrolimus dose was reduced by 50% to attain her goal trough of 5 ng/mL. Weekly tacrolimus concentrations thereafter showed declining trough levels which allowed for subsequent increases in tacrolimus dose. Within 1 month of starting elx/tez/iva the patient had returned to the tacrolimus dose she was using prior to initiation of elx/tez/iva. LFTs were normal for the first month of therapy, but then became mildly elevated with normal bilirubin. The elx/tez/iva was continued with close monitoring. Her LFTs remained persistently mildly elevated for 7 months. Platelets decreased during this time period and INR was elevated. She underwent liver biopsy with further imaging and consultation. Upon completion of these investigations, it was believed this patient had developed cirrhosis (Child Pugh A) of the graft and chronic active hepatitis. There was no evidence of drug induced liver injury and it was felt the changes were not related to elx/tez/iva. She continued treatment with elx/tez/iva and is being managed by the liver transplant team for the findings of rejection/alloimmune hepatitis with the addition of mycophenolate mofetil. Clinically, the patient responded well to elx/tez/iva with reduced oxygen and BiPAP requirements, improved exercise tolerance, reduced cough, improved appetite, increased energy, and the ability to taper off morphine previously required to manage dyspnea. Her ppFEV1 improved from 27% to 35%. Over 7 months of treatment her BMI percentile improved from 1.9% to 9.1%.