Q4. Safety: Is TAF safe and efficacious in patients with hepatic impairment/decompensation ?

Safety:
Is TAF safe and efficacious in patients with hepatic impairment/decompensation ?

依據 VEMLIDY^® 仿單，對於輕度、中度或重度肝功能不全（Child-Pugh A、B 或 C）的病人，並不須調整 VEMLIDY^® 的劑量 ¹。
According to the VEMLIDY US PI, no dosage adjustment is required in patients with mild hepatic impairment (Child-Pugh A). The safety and efficacy of VEMLIDY in patients with decompensated cirrhosis (Child-Pugh B or C) have not been established; therefore, VEMLIDY is not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment.³
在重度肝功能不全（Child-Pugh C）的病人，TAF 與 tenofovir 的總血漿濃度要比肝功能正常的受試者低。依血漿蛋白結合狀態修正之後，重度肝功能不全與肝功能正常之受試者的未結合（游離） TAF 濃度大致相當 （Figure 1） ^1,2。
According to a pharmacokinetic study in patients with severe hepatic impairment, free TAF exposure was comparable between subjects with severe hepatic impairment and healthy controls.²
- No clinically relevant change in laboratory parameters was observed in either group.
- The authors concluded that severe hepatic impairment does not result in clinically relevant changes in TAF or TFV exposures, and that TAF was generally well tolerated.

試驗 4035 評估了中至重度肝功能不全（Child-Pugh B/C 或曾有 CPT ≥ 7 紀錄）且病毒已受抑制的 CHB 病人，轉換為 TAF 的療效與安全性 ^1,4。
Study 4035 evaluated the efficacy and safety of switching to TAF in virologically suppressed CHB patients with moderate/severe hepatic impairment (CPT ≥ 7).⁵
- 從 TDF 和 / 或其他口服抗病毒藥物轉換為 TAF，在 96 週時仍維持高比例的病毒抑制效果，有更高比例的病人 ALT 恢復正常（Figure 2），而且在 96 週治療期間內，腎臟與骨骼方面的安全性指標均維持穩定（Figure 3）⁴。
  - Switching from TDF and/or other oral antivirals to TAF resulted in the persistence of high rates of viral suppression and improved rates of normal ALT at week 96.
  - Switching from TDF and/or other oral antivirals to TAF resulted in stable renal and bone safety parameters through 48 weeks.
- TAF 的耐受性良好，很少發生第 3 或 4 級不良事件，也沒有發生與治療相關的第 3 或 4 級不良事件和嚴重不良事件 ⁴。
  TAF was well tolerated overall with low occurrences of Grade 3 or 4 AEs. No Grade 3–4 or SAEs were judged to be related study treatment. There were no deaths in this cohort.

AASLD, American Association for the Study of Liver Diseases; AE, adverse event; ALT, alanine aminotransferase; AUC, area under the curve; BMD, bone mineral density; CG, Cockcroft-Gault formula; CHB, chronic hepatitis B; CPT, Child-Pugh-Turcotte score; CrCl, creatinine clearance rate; DNA, deoxynucleic acid; eGFR, estimated glomerular filtration rate; HI, hepatic impairment; hr, hour; IU, international unit; OAV, oral antiviral; PI, prescribing information; PK, pharmacokinetics; Q, quartile; SAE, serious adverse event; SD, standard deviation; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; TFV, tenofovir; US, United States.

References: 1. 韋立得膜衣錠。中文仿單［TWN-NOV20-US-FEB20-（EU-NOV17）］; 2. Custodio JM, et al. EASL 2016, Poster Fri-127; 3. VEMLIDY® [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; August 2020; 4. Lim YS, et al. EASL 2021. #2338; 5. Lim YS, et al. EASL 2020. SAT442.

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