Case 3
A 31-year-old male with CF (F508del/F508del) status post living donor
liver transplant April 2019 for CFLD with esophageal varices, ascites,
and cirrhosis was interested in elx/tez/iva therapy. After discussing
with his liver transplantation team, he was switched from full dose
tez/iva to elx/tez/iva in early November 2019, seven months after his
transplantation at full dose. Baseline ppFEV1 was 90%
and baseline LFTs and total bilirubin were within normal limits (WNL) at
baseline and were ordered for two weeks after initiation. Two days after
initiating therapy, the patient presented to the emergency department
with complaints of sudden onset abdominal pain with diffuse tenderness
to palpation acute tenderness to palpation in the left upper quadrant
with positive guarding. On presentation, LFTs and bilirubin were stable
WNL. Full workup was performed with no remarkable imaging findings on
abdominal imaging. At the time of presentation, he was also diagnosed
with a CF pulmonary exacerbation and admitted for intravenous antibiotic
therapy. With all other causes reasonably excluded, the patient’s pain
was classified as a side effect of elx/tez/iva. Upon discharge five days
later to complete his antibiotic course at home, the patient’s abdominal
pain had resolved and LFTs and bilirubin remained WNL. Repeat LFTs and
bilirubin at one-week post discharge remained WNL with plans to continue
to monitor every two weeks. At approximately one month after therapy
initiation, ppFEV1 was 95, but AST rose to 6 times the
ULN, ALT increased to 2 times the ULN, and total bilirubin remained WNL.
Repeat labs were ordered for one week later at which point the patient’s
AST and ALT were 5.7 and 5 times the ULN, respectively with total
bilirubin WNL. At this time, elx/tez/iva therapy was discontinued and
patient underwent testing for hepatic graft rejection. Hepatic graft
rejection was ruled out and pathological evidence of drug induced liver
disease was identified. His transplant team ordered labs for every two
weeks for close monitoring of hepatic markers, which gradually trended
back to WNL over several months. In May 2020, the patient was
re-challenged with elx/tez/iva at reduced dose of one triple combination
pill in the morning and one iva tablet in the evening. Labs were ordered
weekly to monitor. At one week post re-initiation, his ALT and AST rose
to 3.4 and 5.7 times the upper limit of normal respectively with total
bilirubin of 1.4 mg/dL, so therapy was discontinued. Again, liver
function tests (LFTs) trended to WNL within about three months. In
September 2020, he restarted full dose tez/iva by the transplant clinic.
To date, LFTs have remained WNL.