Liu Wen-Yue, Huang Shanshan, Ji Hongsheng, Kim Seung Up, Yip Terry Cheuk-Fung, Wong Grace Lai-Hung, Petta Salvatore, Tsochatzis Emmanuel, Nakajima Atsushi, Bugianesi Elisabetta, Goh Boon-Bee George, Chan Wah-Kheong, Romero-Gomez Manuel, Sanyal Arun J, Boursier Jérôme, Hagström Hannes, Calleja José Luis, de Lédinghen Victor, Newsome Philip Noel, Fan Jian-Gao, Lai Michelle, Castéra Laurent, Lee Hye Won, Pennisi Grazia, Yoneda Masato, Armandi Angelo, Teh Kevin Kim-Jun, Gallego-Durán Rocio, Asgharpour Amon, de Saint-Loup Marc, Shang Ying, Llop Elba, Fournier Céline, Mahgoub Sara, Lara-Romero Carmen, Canivet Clemence M, Chan Mandy Sau-Wai, Lin Huapeng, Chen Li-Li, Targher Giovanni, Byrne Christopher D, Du Mulong, Wai-Sun Wong Vincent, Zheng Ming-Hua
Department of Endocrinology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Wenzhou Key Laboratory of Diabetes Research, Wenzhou, China.
Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Gastroenterology. 2025 Mar 18. doi: 10.1053/j.gastro.2025.02.034.
The absence of hepatic fat in advanced fibrosis has been documented in metabolic dysfunction-associated steatotic liver disease (''burnt-out" MASLD). However, whether hepatic fat loss occurs continuously with fibrosis progression is controversial. We proposed a "burning-out" concept to describe this process and analyze the long-term outcomes of "burnt-out" and "burning-out" MASLD.
We included a MASLD cohort from 16 centers, including 3273 individuals with baseline histology and 5455 with serial vibration-controlled transient elastography measurements during the follow-up. "Burnt-out" MASLD was defined by steatosis grade ≤S1 and fibrosis stage ≥F3. Trajectory analysis identified "burning-out" patients with continuous trends of decreasing controlled attenuation parameter and increasing liver stiffness measurement values.
Of 3273 patients with histologic evaluation included, 435 had "burnt-out" MASLD. Compared with those with pronounced steatosis in advanced fibrosis, patients with "burnt-out" had higher risks of all-cause mortality (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.14-4.02), liver-related events (LREs; HR, 1.77; 95% CI, 1.12-2.78), and hepatic decompensation (HR, 1.83; 95% CI, 1.11-3.01). Of 5455 patients with vibration-controlled transient elastography included for trajectory analysis, 176 were identified as "burning-out" MASLD. The incidence rates of all-cause mortality, LREs, and decompensation were 7.28, 26.47, and 21.92 per 1000 person-years in "burning-out" patients, respectively. The "burning-out" group had higher cumulative incidences of adverse outcomes than patients with consistently high controlled attenuation parameter and moderate/low liver stiffness measurement values (P < .0001).
Continuous hepatic fat loss accompanied by fibrosis progression, referred to as "burning-out," was observed in advanced MASLD and associated with high rates of all-cause mortality, LREs, and hepatic decompensation.
代谢功能障碍相关脂肪性肝病（“耗竭型”MASLD）中已证实晚期纤维化时肝脏脂肪缺失。然而，肝脏脂肪丢失是否随纤维化进展持续发生仍存在争议。我们提出一个“耗竭”概念来描述这一过程，并分析“耗竭型”和“正在耗竭型”MASLD的长期结局。
我们纳入了来自16个中心的MASLD队列，包括3273例有基线组织学检查的个体以及5455例在随访期间进行了连续振动控制瞬时弹性成像测量的个体。“耗竭型”MASLD定义为脂肪变性分级≤S1且纤维化分期≥F3。轨迹分析确定了具有受控衰减参数持续下降和肝脏硬度测量值持续升高趋势的“正在耗竭型”患者。
在纳入组织学评估的3273例患者中，435例为“耗竭型”MASLD。与晚期纤维化伴明显脂肪变性的患者相比，“耗竭型”患者全因死亡风险更高（风险比[HR]，2.14；95%置信区间[CI]，1.14 - 4.02）、肝脏相关事件（LREs；HR，1.77；95% CI，1.12 - 2.78）以及肝失代偿风险更高（HR，1.83；95% CI，1.11 - 3.01）。在纳入轨迹分析的5455例进行振动控制瞬时弹性成像的患者中，176例被确定为“正在耗竭型”MASLD。“正在耗竭型”患者的全因死亡率、LREs发生率和失代偿发生率分别为每1000人年7.28、26.47和21.92。与受控衰减参数持续高且肝脏硬度测量值为中度/低度的患者相比，“正在耗竭型”组不良结局的累积发生率更高（P <.0001）。
在晚期MASLD中观察到肝脏脂肪持续丢失并伴有纤维化进展，即“正在耗竭”，且与全因死亡率、LREs和肝失代偿的高发生率相关。
