现代人生活节奏快，饮食结构日益高脂高糖，脂肪肝的发病率也逐年升高，已经成为最主要的慢性非传染性疾病之一。这是一种常见的代谢问题，与饮食、运动习惯、体重密切相关。肝脏细胞脂肪变性比例超过5%的病理状态被称为脂肪肝Wu H, Chen J, Guo S, et al. Advances in the acting mechanism and treatment of gut microbiota in metabolic dysfunction-associated steatotic liver disease. Gut Microbes. 2025;17(1):2500099.。很多人虽在体检中被告知有脂肪肝，却认为没有症状就不用担心，但实际上，肝脏不仅是代谢中心，也是一个重要的免疫器官，其中有丰富的免疫细胞，帮助维持身体健康Pham UNT, Chou KC, Ngo TL, Pan WY, Ruan T, Lin YJ. Targeted immunomodulation with H2-generating nanostructures to mitigate obesity-induced inflammation and metabolic dysfunctions. Biomaterials. 2026;325:123570.。脂肪肝会影响你的免疫系统，让你更易患病，恢复更慢，甚至增加严重疾病的风险。
免疫系统是身体的“防御网络”，它由多种免疫细胞组成，共同抵抗细菌、病毒，并清除体内异常细胞Unagolla JM, Flanagan R, Perera K, et al. A novel Kupffer cell-targeting nanoparticle system to Mitigate alcohol-associated liver disease. Biomaterials. 2026;325:123623.。巨噬细胞负责“吃掉”细菌和代谢废物；NK细胞（自然杀伤细胞）则直接清除被病毒感染或发生异常的细胞；T细胞和B细胞识别并记住“敌人”，进行长期防御Yahoo N, Dudek M, Knolle P, Heikenwälder M. Role of immune responses in the development of NAFLD-associated liver cancer and prospects for therapeutic modulation. J Hepatol. 2023;79(2):538-551.。
脂肪肝对免疫力的影响是一个长期、渐进的过程，主要通过以下三个方面：
1. 脂肪堆积引发慢性炎症，导致免疫过度消耗。肝细胞长期堆积脂肪后，像“仓库被塞满”，导致细胞受损。受损的肝细胞会释放危险信号（如TNF-α、IL-6），吸引中性粒细胞与单核-巨噬细胞浸润，炎症恶性循环开启Hart KM, Fabre T, Sciurba JC, et al. Type 2 immunity is protective in metabolic disease but exacerbates NAFLD collaboratively with TGF-β. Sci Transl Med. 2017;9(396):eaal3694.。如果这种炎症长期存在，就会让免疫细胞持续处于“高负荷状态”，逐渐过度消耗，反而削弱了免疫力Akabane M, Imaoka Y, Kawashima J, Pawlik TM. Advancing precision medicine in hepatocellular carcinoma: current challenges and future directions in liquid biopsy, immune microenvironment, single nucleotide polymorphisms, and conversion therapy. Hepat Oncol. 2025;12(1):2493457.。
2. 关键免疫细胞功能受损。巨噬细胞从清理垃圾的“环卫工”，变成不断释放炎症信号的“警报器”，加剧炎症反应Hammerich L, Tacke F. Hepatic inflammatory responses in liver fibrosis. Nat Rev Gastroenterol Hepatol. 2023;20(10):633-646.。NK细胞数量减少、活性下降，导致身体更容易受到病毒感染，也降低了对癌细胞的监控能力。T细胞进入“耗竭状态”，应对新感染的能力下降。这些免疫细胞功能的下降导致脂肪肝患者易患病，且感染后恢复更慢，甚至出现慢性炎症和肿瘤风险上升Ge Z, Wu Q, Lv C, He Q. The Roles of T Cells in the Development of Metabolic Dysfunction-Associated Steatohepatitis. Immunology. 2025;176(2):145-163.。
3. 脂肪肝常伴随肠道菌群失衡与屏障功能受损，导致LPS等内毒素入血，经门静脉到肝，激活TLR4信号通路，这放大了炎症与免疫失衡。同时，这些有害物质随血液进入肝脏和全身，进一步引发免疫混乱。这就像一道“城墙”出现了漏洞，敌人可以从多个方向进攻Tilg H, Adolph TE, Dudek M, Knolle P. Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity. Nat Metab. 2021;3(12):1596-1607.。
值得注意的是，脂肪肝在早期是可以逆转的，其中生活方式的改变是最有效、最安全的方法。
1. 饮食调整：不是“少吃”，而是“吃对”，整体降低“饮食炎症指数”，减糖、减油、补充优质营养。减少高糖饮料、奶茶、甜品。少吃油炸食物、加工肉制品。增加优质蛋白质：鱼、鸡胸肉、鸡蛋、豆制品。多吃蔬菜和全谷类食物，增加膳食纤维。
2. 规律运动：动起来就是最好的药。每周至少150分钟中等强度运动，例如快走、游泳、骑车。配合力量训练，帮助增加肌肉，提高基础代谢率。
3. 体重管理：适度减重，大大获益。如果能减掉7%-10%的体重，肝脏脂肪就会明显减少，免疫力也会得到改善。
4. 避免酒精和不必要的药物：酒精会加重肝脏损伤，最好完全戒酒或尽量减少摄入。不擅自服用“保肝药”或保健品，应先咨询医生Hao X, Song H, Su X, et al. Prophylactic effects of nutrition, dietary strategies, exercise, lifestyle and environment on nonalcoholic fatty liver disease. Ann Med. 2025;57(1):2464223.。
脂肪肝作为现代生活方式的“信号灯”，提醒我们身体已经出现代谢失衡。它不仅伤害肝脏，更会让免疫系统长期疲劳，降低对疾病的抵抗力。不过通过合理饮食、规律运动、科学管理体重，脂肪肝是可以逆转的，免疫力也会逐渐恢复。给肝脏“减负”，就是给免疫力“加分”。
图1 脂肪肝通过炎症级联反应削弱机体免疫防御能力
参考文献
Wu H, Chen J, Guo S, et al. Advances in the acting mechanism and treatment of gut microbiota in metabolic dysfunction-associated steatotic liver disease. Gut Microbes. 2025;17(1):2500099.
Pham UNT, Chou KC, Ngo TL, Pan WY, Ruan T, Lin YJ. Targeted immunomodulation with H2-generating nanostructures to mitigate obesity-induced inflammation and metabolic dysfunctions. Biomaterials. 2026;325:123570.
Unagolla JM, Flanagan R, Perera K, et al. A novel Kupffer cell-targeting nanoparticle system to Mitigate alcohol-associated liver disease. Biomaterials. 2026;325:123623.
Yahoo N, Dudek M, Knolle P, Heikenwälder M. Role of immune responses in the development of NAFLD-associated liver cancer and prospects for therapeutic modulation. J Hepatol. 2023;79(2):538-551.
Hart KM, Fabre T, Sciurba JC, et al. Type 2 immunity is protective in metabolic disease but exacerbates NAFLD collaboratively with TGF-β. Sci Transl Med. 2017;9(396):eaal3694.
Akabane M, Imaoka Y, Kawashima J, Pawlik TM. Advancing precision medicine in hepatocellular carcinoma: current challenges and future directions in liquid biopsy, immune microenvironment, single nucleotide polymorphisms, and conversion therapy. Hepat Oncol. 2025;12(1):2493457.
Hammerich L, Tacke F. Hepatic inflammatory responses in liver fibrosis. Nat Rev Gastroenterol Hepatol. 2023;20(10):633-646.
Ge Z, Wu Q, Lv C, He Q. The Roles of T Cells in the Development of Metabolic Dysfunction-Associated Steatohepatitis. Immunology. 2025;176(2):145-163.
Tilg H, Adolph TE, Dudek M, Knolle P. Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity. Nat Metab. 2021;3(12):1596-1607.
Hao X, Song H, Su X, et al. Prophylactic effects of nutrition, dietary strategies, exercise, lifestyle and environment on nonalcoholic fatty liver disease. Ann Med. 2025;57(1):2464223.
