The impact of directly acting antivirals on the enzymatic liver function of liver transplant recipients with recurrent hepatitis C

Abstract

Antiviral treatment with DAAs enabled sustained elimination of recurrent HCV in liver transplant recipients and was associated with a significant improvement of the enzymatic liver function.

Impact of direct‐acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients

“…A retrospective cohort study in 52 LT patients treated with DAAs found significant decreases in serum TAC concentrations after achieving SVR . In a study examining the impact of DAAs on the enzymatic liver function of 21 LT recipients, TAC concentration‐to‐dose ratio significantly decreased stepwise from the start of treatment until week 12 of therapy, indicating increased TAC metabolism during and after treatment . Similarly, in a retrospective review of 34 simultaneous liver/kidney transplant recipients with HCV, immunosuppression dosage increases were required in seven patients during DAA treatment and five patients following treatment .…”

“…After week 4, the TAC dose‐normalized concentration stabilized. These results conflict with those of Raschzok et al who found the decrease most notably between week 12 of DAA and post‐week 12. Kugelmas et al saw the greatest decrease in immunosuppression at months 2 and 6 of therapy in patients treated with IFN‐based regimens.…”

“…Because the observed changes in dose‐normalized TAC concentrations were calculated in ratios, we transformed the dose‐normalized TAC concentrations to the logarithmic scale by calculating the natural log of the data. Tacrolimus concentration divided by dose (C/D) is a method used in solid organ transplant literature to determine the rate of tacrolimus metabolism . As the primary outcome was a continuous variable comparing two non‐paired groups, a t test was performed.…”

“…The majority of large randomized controlled trials evaluating HCV DAA therapy post‐LT do not specifically report on immunosuppression management during and following HCV DAA therapy . However, there are a small number of retrospective reports that observed a decline in TAC whole blood concentrations in LT recipients during treatment with DAAs …”

“…[14][15][16][17][18] However, there are a small number of retrospective reports that observed a decline in TAC whole blood concentrations in LT recipients during treatment with DAAs. [19][20][21][22] The hypothesis for this decline in whole blood trough concentrations is that there is repression of drug-metabolizing enzymes from inflammatory and infectious stimuli while patients are actively infected with HCV. 19 As the HCV virus is cleared and there is an increase in liver cell function, CYP3A4/5 activity normalizes and larger TAC doses are necessary to achieve adequate troughs.…”