Altern Ther Health Med. 2024 Sep;30(9):146-151.
Long-term antiviral treatment is necessary for chronic hepatitis B (CHB) patients, and treatment safety is imperative for these patients. Previous studies showed tenofovir alafenamide (TAF) has shown efficacy non-inferior to that of tenofovir disoproxil fumarate (TDF) with improved renal and bone safety. However, there is still a lack of a rapid and convenient method to identify CHB patients at high risk of osteoporosis before initiating antiviral treatment. The International Osteoporosis Foundation (IOF) recommended a one-minute osteoporosis risk test to identify early high-risk patients. Our aim was to evaluate the feasibility of the one-minute osteoporosis risk test, along with evaluating the effectiveness and safety for virologically suppressed CHB patients switching to TAF.
In this multicenter, prospective study, patients with chronic HBV infection who had been receiving TDF or Entecavir (ETV) for 48 weeks or more with HBV DNA less than 20 IU/mL for longer than 6 months were screened by one-minute osteoporosis risk test. Patients with a high risk of osteoporosis and then diagnosed with osteopenia or osteoporosis by dual-energy X-ray absorptiometry (DEXA) were enrolled. Safety in bone and bone turnover markers and antiviral efficacy of TAF were assessed respectively at 24 and 48 weeks.
84.95% (175/206) CHB patients screened by one-minute osteoporosis risk test were at risk of osteoporosis.85.71% (150/175) were diagnosed with osteopenia by DEXA. The analysis included a total of 138 patients, of whom 92(62.3%) were male and 46 (37.7%) were female, with a mean age of 45 years old. HBV DNA was suppressed at 48 weeks at 88% (35/40) in the prior ETV group and 90% (88/98) at 48 weeks group in the prior TDF group. Bone mineral density (BMD) of the lumbar spine (L1-L4) from TDF switching to TAF was improved at 24 weeks (1.03±0.11 vs. 0.97±0.12, P = .001) than baseline. Propeptides of type I procollagen (PINP) and beta-C-terminal telopeptides of type 1 collagen (CTX) in serum at 24 weeks after switching from TDF to TAF declined compared with baseline (50.35±18.90 vs. 63.65±19.17, P = .016 and 0.21±0.13 vs. 0.32±0.10, P = .017). BMD, PINP, and CTX in ETV to TAF group remained stable during treatment.
Attention should be paid to osteoporosis risk during lone-term nucleot(s)ide analogue treatment. One minute test of osteoporosis risk could rapidly identify most CHB patients at risk of osteoporosis. Given its convenience, we recommend using this test for early screening in CHB patients prior to initiating antiviral treatment. Our results further demonstrated that an improvement in bone safety after switching to TAF in virologically suppressed CHB patients with osteoporosis.
慢性乙型肝炎（CHB）患者需要长期进行抗病毒治疗，因此治疗安全性对这些患者至关重要。先前的研究表明，替诺福韦艾拉酚胺（TAF）在疗效不劣于富马酸替诺福韦二吡呋酯（TDF）的基础上，改善了肾脏和骨骼安全性。然而，目前仍然缺乏一种快速便捷的方法，在开始抗病毒治疗之前识别出有发生骨质疏松症高风险的 CHB 患者。国际骨质疏松基金会（IOF）建议采用一分钟骨质疏松风险测试来识别早期高风险患者。我们的目的是评估一分钟骨质疏松风险测试的可行性，同时评估病毒学抑制的 CHB 患者转换为 TAF 的有效性和安全性。
在这项多中心、前瞻性研究中，筛选出接受 TDF 或恩替卡韦（ETV）治疗 48 周或以上且 HBV DNA 持续 6 个月以上小于 20 IU/mL 的慢性 HBV 感染患者，采用一分钟骨质疏松风险测试进行筛查。通过双能 X 线吸收法（DEXA）对骨质疏松风险高且随后被诊断为骨量减少或骨质疏松症的患者进行评估。分别在 24 周和 48 周评估 TAF 的骨骼和骨转换标志物安全性以及抗病毒疗效。
84.95%（175/206）接受一分钟骨质疏松风险测试的 CHB 患者存在骨质疏松风险。85.71%（150/175）通过 DEXA 诊断为骨量减少。共有 138 例患者纳入分析，其中 92 例（62.3%）为男性，46 例（37.7%）为女性，平均年龄为 45 岁。在先前接受 ETV 治疗的 40 例患者中，有 88%（35/40）在 48 周时 HBV DNA 得到抑制，在先前接受 TDF 治疗的 98 例患者中，有 90%（88/98）在 48 周时 HBV DNA 得到抑制。从 TDF 转换为 TAF 后，腰椎（L1-L4）的骨密度（BMD）在 24 周时改善（1.03±0.11 比基线时的 0.97±0.12，P=.001）。从 TDF 转换为 TAF 后 24 周时，血清Ⅰ型前胶原氨基端肽（PINP）和Ⅰ型胶原 C 端肽（CTX）β分别下降（50.35±18.90 比基线时的 63.65±19.17，P=.016 和 0.21±0.13 比基线时的 0.32±0.10，P=.017）。ETV 转换为 TAF 组在治疗期间 BMD、PINP 和 CTX 保持稳定。
在长期核苷（酸）类似物治疗期间应注意骨质疏松症风险。一分钟骨质疏松症风险测试可以快速识别大多数存在骨质疏松症风险的 CHB 患者。鉴于其便利性，我们建议在开始抗病毒治疗前，对 CHB 患者使用该测试进行早期筛查。我们的研究结果进一步证实，在病毒学抑制的骨质疏松 CHB 患者中，转换为 TAF 后骨骼安全性得到改善。
