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( Sang Hoon Ahn ),( Young-Suk Lim ),( Pietro Lampertico ),( Ho Bae ),( Wan-Long Chuang ),( Jeong Heo ),( Yi-Hsiang Huang ),( Aric Josun Hui ),( Chun-Yen Lin ),( Claire Fournier ),( Chien-Hung Chen ),( 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: TAF, a novel tenofovir (TFV) prodrug, has greater plasma stability, more targeted delivery of TFV to hepatocytes, and reduced circulating levels of TFV compared to TDF. We evaluated efficacy and safety when virally suppressed CHB (Chronic Hepatitis B) patients with hepatic impairment were switched to TAF. Methods: In this Phase 2 study (NCT03180619) CHB patients with a ChildTurcottePugh (CTP) score of ³7 and £12 at screening (or past history of CTP ³7 and any score £12 at screening) who were taking TDF and/or other OAVs for ³48 weeks, with HBV DNA <LLOQ for ³24 weeks and <20 IU/mL at screening were eligible. All patients were switched to TAF 25 mg QD and treated for 96 weeks. The co-primary endpoints were proportion with HBV DNA <20 IU/mL and graded adverse events (AEs)/lab abnormalities at Week 24. Results: 31 patients were enrolled at 18 sites in 7 countries. At baseline, 19 (61%), 9 (29%) and 3 (10%) were CTP Class A, B, or C, respectively. Median age was 57 y (19% ³65 y), 68% male, 81% Asian, 90% HBeAg-negative, median fibrotest score 0.81, and median eGFR<sub>CG</sub> 98 mL/min; up to 48% had low BMD at hip and/or spine, and 68% had prior TDF exposure. Key efficacy/safety results at Week 24 are summarized in the Table. All patients had HBV DNA <20 IU/mL and a high proportion had normal ALT. Switching to TAF resulted in increases in hip/spine BMD, decreases in bone turnover markers, an increase in eGFR<sub>CG</sub> with decreases in tubular markers. TAF was well tolerated with few having Grade 3 or 4 AEs (2 patients) and no discontinuations for and AE. <sup>a</sup>HBV DNA results are missing=failure. <sup>b</sup>ALT normal is the proportion with ALT ≤ULN at Week 48, regardless of baseline ALT level; <sup>c</sup>ULN 35 U/L males, 25 U/L females; <sup>d</sup>Patients with ALT >ULN at baseline; <sup>e</sup>HBeAg-positive at baseline. <sup>f</sup>Serum C-type collagen sequence (bone resorption marker); <sup>g</sup>Serum procollagen type 1 N-terminal propeptide (bone formation marker); <sup>h</sup>Urine retinol binding protein/creatinine (tubular marker); <sup>i</sup>Urine beta-2 microglobulin/creatinine (tubular marker). BMD, bone mineral density by DXA scan; sCr, serum creatinine; PO<sub>4</sub>, serum phosphorus; eGFR<sub>CG</sub>, estimated creatinine clearance (Cockcroft-Gault method) Conclusions: In CHB patients with hepatic impairment switched to TAF from TDF or other OAVs, viral suppression was well maintained and improved bone and renal safety was seen at Week 24.