Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Eur J Clin Pharmacol. 2024 Mar;80(3):335-354. doi: 10.1007/s00228-023-03616-y. Epub 2024 Jan 10.
Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy.
To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis.
Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95% confidence intervals (CI) were calculated using RevMan 5.4 and Stata 16.0 software, and network meta-analysis was based on a frequentist framework.
A total of 4194 patients were included in the study, including patients with CHB treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), as well as patients not receiving antiviral therapy [patients with inactive CHB who were not receiving antiviral therapy (referred as inactive CHB patients) and non-HBV-infected patients]. TDF reduced TC levels compared to the non-antiviral group (TDF vs. inactive CHB patients: MD = - 17.27, 95% CI (- 30.03, - 4.47); TDF vs. non-HBV-infected individuals: MD = - 17.10, 95% CI (- 20.13, - 14.07)). TC changes in the TAF and ETV groups were not statistically different from the non-antiviral group (TAF vs. inactive CHB patients: MD = - 2.69, 95% CI (- 14.42, 9.04); TAF vs. non-HBV-infected individuals: MD = - 2.52, 95% CI (- 8.47, 3.43); ETV vs. inactive CHB patients: MD = - 4.24, 95% CI (- 17.12, 8.64); ETV vs. non-HBV-infected individuals: MD = - 4.07, 95% CI (- 9.90, 1.75)). The ranking of the effects for lowering TC is as follows: CHB patients treated with nucleotide analogues [with varying efficacy: TDF (SUCRA = 99.9) > ETV (SUCRA = 59.3) > TAF (SUCRA = 43.6)] > inactive CHB patients (SUCRA = 27.3) > non-HBV-infected individuals (SUCRA = 19.9). As for secondary outcomes, among the three antiviral drugs, TDF had the most significant effect on lowering TG, LDL-C, and HDL-C, but none of the three drugs was statistically different from the non-antiviral group. Subgroup analysis showed that the lipid-lowering effect of TDF was more pronounced in the elderly (≥ 50 years).
TDF was effective in lipid reduction, particularly pronounced in the older population. TAF and ETV had a neutral effect to TC, TG, LDL-C, and HDL-C. Despite a relative increase in lipids observed in patients transitioning from TDF to TAF or ETV, these changes remained within acceptable limits.
最近的研究发现，慢性乙型肝炎（CHB）患者在抗病毒治疗期间血脂水平可能会发生变化。
使用网络荟萃分析评估一线核苷（酸）类似物（NAs）对 CHB 患者血脂谱的影响。
截至 2023 年 8 月 1 日，我们在 7 个电子数据库（PubMed、Embase、Cochrane 图书馆和 4 个中文数据库）中搜索了关于 NAs 对 CHB 患者血脂影响的队列研究。血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）的变化被视为结局。使用 RevMan 5.4 和 Stata 16.0 软件计算连续变量的均数差（MD）和 95%置信区间（CI），并基于似然框架进行网络荟萃分析。
共有 4194 名患者纳入研究，包括接受恩替卡韦（ETV）、替诺福韦酯富马酸二异丙酯（TDF）和替诺福韦艾拉酚胺（TAF）治疗的 CHB 患者，以及未接受抗病毒治疗的患者[未接受抗病毒治疗的慢性乙型肝炎不活动患者（简称慢性乙型肝炎不活动患者）和非乙型肝炎病毒感染患者]。与非抗病毒组相比，TDF 降低了 TC 水平（TDF 与慢性乙型肝炎不活动患者相比：MD = -17.27，95%CI [-30.03，-4.47]；TDF 与非乙型肝炎病毒感染个体相比：MD = -17.10，95%CI [-20.13，-14.07]）。TAF 和 ETV 组的 TC 变化与非抗病毒组无统计学差异（TAF 与慢性乙型肝炎不活动患者相比：MD = -2.69，95%CI [-14.42，9.04]；TAF 与非乙型肝炎病毒感染个体相比：MD = -2.52，95%CI [-8.47，3.43]；ETV 与慢性乙型肝炎不活动患者相比：MD = -4.24，95%CI [-17.12，8.64]；ETV 与非乙型肝炎病毒感染个体相比：MD = -4.07，95%CI [-9.90，1.75]）。降低 TC 的效果排名如下：接受核苷酸类似物治疗的 CHB 患者[疗效不同：TDF（SUCRA = 99.9）> ETV（SUCRA = 59.3）> TAF（SUCRA = 43.6）]>慢性乙型肝炎不活动患者（SUCRA = 27.3）>非乙型肝炎病毒感染个体（SUCRA = 19.9）。对于次要结局，在三种抗病毒药物中，TDF 对降低 TG、LDL-C 和 HDL-C 的作用最为显著，但与非抗病毒组相比，三种药物均无统计学差异。亚组分析表明，TDF 的降脂效果在老年人（≥50 岁）中更为明显。
TDF 对降低血脂有效，在老年人群中效果更为显著。TAF 和 ETV 对 TC、TG、LDL-C 和 HDL-C 无明显影响。尽管从 TDF 转为 TAF 或 ETV 后患者的血脂有相对升高，但这些变化仍在可接受范围内。
