Division of Gastroenterology & Hepatology, Department of Medicine, The Pennsylvania State University - Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA.
Department of Public Health Sciences, The Pennsylvania State University - Milton S. Hershey Medical Center, Hershey, PA, USA.
Dig Dis Sci. 2023 Jun;68(6):2695-2703. doi: 10.1007/s10620-022-07809-w. Epub 2023 Jan 24.
BACKGROUND & AIMS: Cardiorespiratory fitness and liver fibrosis are independently associated with poor outcomes in patients with nonalcoholic steatohepatitis (NASH), however, conflicting reports exist about their relationship. We aimed to better characterize the relationship between cardiorespiratory fitness and liver histology in a cross-sectional study of patients with biopsy-proven NASH.
Participants aged 18-75 years completed VO fitness assessment using symptom-limited graded exercise testing. Participants were compared by liver fibrosis stage and NAFLD Activity Score (NAS). Multivariable models were constructed to assess factors related to relative VO, including liver fibrosis and NAS.
Thirty-five participants with mean age 48 ± 12 years and body mass index 33.5 ± 7.6 kg/m were enrolled. Seventy-four percent of participants were female and 49% had diabetes. A dose-dependent relationship was found between relative VO and liver fibrosis. Relative VO was significantly lower in participants with advanced fibrosis (F3 disease- 15.7 ± 5.3 vs. ≤ F2 disease- 20.7 ± 5.9 mL/kg/min, p = 0.027). NAS > 5 was also associated with lower relative VO (22.6 ± 5.7 vs. 16.5 ± 5.1 mL/kg/min, p = 0.012) compared to NAS ≤ 5. With multivariable modeling, advanced fibrosis remained independently predictive of relative VO while NAS trended towards significance.
Advanced liver fibrosis is independently associated with cardiorespiratory fitness in patients with NASH. This may explain the incremental increase in mortality as liver fibrosis stage increases. Further research is needed to determine if exercise training can improve cardiorespiratory fitness across multiple stages of liver fibrosis and directly reduce morbidity and mortality in patients with NASH.
心肺适能和肝纤维化与非酒精性脂肪性肝炎（NASH）患者的不良结局独立相关，但它们之间的关系存在相互矛盾的报告。我们旨在通过对经活检证实的 NASH 患者进行横断面研究，更好地描述心肺适能与肝组织学之间的关系。
年龄在 18-75 岁之间的参与者使用症状限制分级运动测试完成 VO 适应性评估。根据肝纤维化分期和 NAFLD 活动评分（NAS）对参与者进行比较。构建多变量模型来评估与相对 VO 相关的因素，包括肝纤维化和 NAS。
共有 35 名参与者，平均年龄 48±12 岁，体重指数 33.5±7.6kg/m2。74%的参与者为女性，49%患有糖尿病。相对 VO 与肝纤维化之间存在剂量依赖性关系。纤维化程度较高（F3 期疾病-15.7±5.3 vs. ≤F2 期疾病-20.7±5.9mL/kg/min，p=0.027）的参与者相对 VO 显著降低。与 NAS≤5 相比，NAS>5 也与相对 VO 降低相关（22.6±5.7 vs. 16.5±5.1mL/kg/min，p=0.012）。在多变量模型中，肝纤维化的严重程度仍然是相对 VO 的独立预测因素，而 NAS 则呈趋势性。
晚期肝纤维化与 NASH 患者的心肺适能独立相关。这可能解释了随着肝纤维化分期的增加，死亡率逐渐增加的原因。需要进一步的研究来确定运动训练是否可以改善多个肝纤维化阶段的心肺适能，并直接降低 NASH 患者的发病率和死亡率。
