Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Università Cattolica del Sacro Cuore, Rome, Italy.
Clin Nutr. 2024 Dec;43(12):101-108. doi: 10.1016/j.clnu.2024.10.007. Epub 2024 Oct 8.
BACKGROUND & AIMS: The available literature on the effect of apolipoprotein C-III (ApoC-III) inhibition in MASLD reveals inconsistencies. The aim of the present work was to examine levels of ApoC-III in the entire spectrum of metabolic-dysfunction associated steatotic liver disease (MASLD).
This is a multicenter study involving patients enrolled in two gastroenterology-hepatology clinics (Greece and Australia) and in a bariatric-metabolic surgery clinic (Italy), with liver biopsy before and after bariatric surgery or lifestyle modification.
Comparing simple MASL to steatohepatitis (MASH) with fibrosis stage F ≥ 2 (at-risk MASH), revealed a marginally significant trend for decreased ApoC-III levels in the latter group (p = 0.07). Multi-adjusted analysis revealed an inverse association between ApoC-III and at-risk MASH (Odds Ratio = 0.91, 95 % Confidence Interval (0.83, 0.99)). ApoC-III interacted with triglycerides in predicting at-risk MASH (p-for-interaction = 0.002). Participants with ApoC-III > median (∼3.75 mg/dL) and normal triglycerides (triglyceridese≤150 mg/dL) had the lowest likelihood to present at-risk MASH (31.8 %) in contrast with participants with ApoC-III < median and hypertriglyceridemia among whom at-risk MASH was recorded in 57.1 %. In multi-adjusted analysis participants with normal triglycerides and high ApoC-III had 64 % lower odds of at-risk MASH compared with their counterparts with ApoC-III < median (OR = 0.36, 95%CI (0.14, 0.86)). Among participants with hypertriglyceridemia, those with ApoC-III < median had less prevalent at-risk MASH compared with those with ApoC-III ≥ median (OR = 0.54, 95%CI (0.32, 0.98)); however in all cases significance was lost when liver enzymes were taken into account.
In advanced disease stages, ApoC-III levels seem to be decreased and advanced organ damage may be a potential explanation. Mendelian randomization studies are needed to confirm or refute this hypothesis.
目前关于载脂蛋白 C-III（ApoC-III）抑制对 MASLD 影响的文献存在不一致性。本研究旨在检查代谢功能障碍相关脂肪性肝病（MASLD）整个谱中 ApoC-III 的水平。
这是一项多中心研究，纳入了在两个胃肠病学-肝病学诊所（希腊和澳大利亚）和一个减肥代谢手术诊所（意大利）登记的患者，在减肥手术或生活方式改变前后进行肝活检。
将单纯 MASL 与纤维化分期 F≥2（有风险的 MASL）的脂肪性肝炎（MASH）进行比较，后者组的 ApoC-III 水平呈显著下降趋势（p=0.07）。多因素分析显示 ApoC-III 与有风险的 MASL 呈负相关（比值比=0.91，95%置信区间（0.83，0.99））。ApoC-III 与甘油三酯在预测有风险的 MASL 方面存在交互作用（p-交互作用=0.002）。ApoC-III ＞中位数（约 3.75mg/dL）且甘油三酯正常（甘油三酯≤150mg/dL）的参与者发生有风险的 MASL 的可能性最低（31.8%），而 ApoC-III＜中位数且甘油三酯升高的参与者中，有风险的 MASL 发生率为 57.1%。在多因素分析中，与 ApoC-III＜中位数的参与者相比，甘油三酯正常且 ApoC-III 升高的参与者发生有风险的 MASL 的几率降低 64%（OR=0.36，95%CI（0.14，0.86））。在甘油三酯升高的参与者中，ApoC-III＜中位数的参与者发生有风险的 MASL 的比例低于 ApoC-III≥中位数的参与者（OR=0.54，95%CI（0.32，0.98））；然而，当考虑到肝酶时，所有情况下的显著性均丧失。
在疾病晚期阶段，ApoC-III 水平似乎降低，而晚期器官损伤可能是潜在的解释。需要进行孟德尔随机化研究来证实或反驳这一假设。
