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%.