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非酒精性脂肪性肝病相关肝外疾病的研究进展

朱蕗颖 李雨晨 邓利华 王晶桐

引用本文:
Citation:

非酒精性脂肪性肝病相关肝外疾病的研究进展

DOI: 10.3969/j.issn.1001-5256.2021.09.043
利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:朱蕗颖负责课题设计, 查阅文献, 撰写论文;李雨晨、邓利华参与文献审核、修改论文;王晶桐负责拟定写作思路, 指导撰写文章并最后定稿。
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    通信作者:

    王晶桐,jingtongw@aliyun.com

  • 中图分类号: R575.5

Research advances in extrahepatic diseases associated with nonalcoholic fatty liver disease

  • 摘要: 非酒精性脂肪性肝病(NAFLD)是全球慢病肝病的主要病因,涵盖了从脂肪变性到炎症和纤维化以至发生肝硬化的一系列病理表现。NAFLD与肝外疾病相关,包括代谢综合征、心血管疾病、慢性肾脏疾病、内分泌疾病、阻塞性睡眠呼吸暂停低通气综合征、银屑病、骨骼肌肉改变等。NAFLD的主要死因包括心血管疾病、恶性肿瘤及肝脏相关并发症,提示临床医生应重视NAFLD相关肝外疾病表现。对NAFLD相关肝外疾病研究进展进行综述,旨在为临床评估及治疗提供思路。

     

  • 表  1  NAFLD相关肝外疾病及二者之间的联系

    肝外器官 疾病表现 建立的联系
    代谢综合征 肥胖、2型糖尿病等 NAFLD与代谢功能障碍密切相关, 国际共识建议更名为MAFLD[5-8]
    心血管疾病 动脉粥样硬化、心脏瓣膜病、心律失常、心功能不全等 NAFLD死亡的主要原因是心血管疾病[9-11];NAFLD患者患心脏瓣膜病、心律失常、心脏传导系统缺陷、心功能不全风险显著增加[12-13]
    肝外肿瘤 消化道肿瘤、乳腺癌、前列腺癌、皮肤癌等 肝外肿瘤是NAFLD三大死因之一[9-10];NAFLD患者结直肠癌、结直肠腺瘤、食管癌、胃癌、胰腺癌、乳腺癌、皮肤癌、前列腺癌、甲状腺癌、肺癌等的风险显著升高[14-20]
    肾脏 慢性肾脏病 NAFLD患者中慢性肾脏病风险显著增加[21-22];肝脏病理学改善与肾功能改善独立相关[23]
    内分泌系统 多囊卵巢综合征、甲状腺功能减退症、生长激素缺乏症 肥胖、胰岛素抵抗是NAFLD与多囊卵巢综合征的共同通路, 部分解释了二者的双向联系[24-30];NAFLD患者患甲减的风险显著增加[31-33];生长激素缺乏与NAFLD相关, 激素替代治疗后肝功能改善[34-35]
    骨及肌肉系统 骨质疏松、肌少症 男性NAFLD患者患骨质疏松的风险显著增加[36-38]肌少症与NAFLD呈现双向联系, 相互促进[39-41]
    呼吸系统 OSAHS OSAHS者患NAFLD风险显著升高[42-45], 睡眠呼吸暂停-低通气指数是肝纤维化的独立预测因子
    皮肤 银屑病 银屑病是NAFLD的独立危险因素[46-50]
    血液 血清铁蛋白升高 铁蛋白与NAFLD的组织学表现相关, 是晚期纤维化的独立预测因子[5, 51-53]
    注: MAFLD, 代谢相关脂肪性肝病;OSAHS, 阻塞性睡眠呼吸暂停低通气综合征。
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  • [1] YOUNOSSI ZM, KOENIG AB, ABDELATIF D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology, 2016, 64(1): 73-84. DOI: 10.1002/hep.28431.
    [2] WU TF, LIAO XH, ZHONG BH. Epidemiology of nonalcoholic fatty liver disease in some regions of China[J]. J Clin Hepatol, 2020, 36(6): 1370-1373. DOI: 10.3969/j.issn.1001-5256.2020.06.039.

    吴挺丰, 廖献花, 钟碧慧. 中国部分地区非酒精性脂肪肝病的流行情况[J]. 临床肝胆病杂志, 2020, 36(6): 1370-1373. DOI: 10.3969/j.issn.1001-5256.2020.06.039.
    [3] ZHOU F, ZHOU J, WANG W, et al. Unexpected rapid Increase in the burden of NAFLD in China from 2008 to 2018: A systematic review and Meta-analysis[J]. Hepatology, 2019, 70(4): 1119-1133. DOI: 10.1002/hep.30702.
    [4] ESTES C, ANSTEE QM, ARIAS-LOSTE MT, et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030[J]. J Hepatol, 2018, 69(4): 896-904. DOI: 10.1016/j.jhep.2018.05.036.
    [5] NAKAMURA A, YONEDA M, SUMIDA Y, et al. Modification of a simple clinical scoring system as a diagnostic screening tool for non-alcoholic steatohepatitis in Japanese patients with non-alcoholic fatty liver disease[J]. J Diabetes Investig, 2013, 4(6): 651-658. DOI: 10.1111/jdi.12101.
    [6] ESLAM M, NEWSOME PN, SARIN SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement[J]. J Hepatol, 2020, 73(1): 202-209. DOI: 10.1016/j.jhep.2020.03.039.
    [7] ESLAM M, SARIN SK, WONG VW, et al. The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease[J]. Hepatol Int, 2020, 14(6): 889-919. DOI: 10.1007/s12072-020-10094-2.
    [8] MENDEZ-SANCHEZ N, ARRESE M, GADANO A, et al. The Latin American Association for the Study of the Liver (ALEH) position statement on the redefinition of fatty liver disease[J]. Lancet Gastroenterol Hepatol, 2021, 6(1): 65-72. DOI: 10.1016/S2468-1253(20)30340-X.
    [9] ADAMS LA, LYMP JF, ST SAUVER J, et al. The natural history of nonalcoholic fatty liver disease: A population-based cohort study[J]. Gastroenterology, 2005, 129(1): 113-121. DOI: 10.1053/j.gastro.2005.04.014.
    [10] ONG JP, PITTS A, YOUNOSSI ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease[J]. J Hepatol, 2008, 49(4): 608-612. DOI: 10.1016/j.jhep.2008.06.018.
    [11] TARGHER G, BYRNE CD, LONARDO A, et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis[J]. J Hepatol, 2016, 65(3): 589-600. DOI: 10.1016/j.jhep.2016.05.013.
    [12] MANTOVANI A, DAURIZ M, SANDRI D, et al. Association between non-alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta-analysis[J]. Liver Int, 2019, 39(4): 758-769. DOI: 10.1111/liv.14044.
    [13] ANSTEE QM, MANTOVANI A, TILG H, et al. Risk of cardiomyopathy and cardiac arrhythmias in patients with nonalcoholic fatty liver disease[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(7): 425-439. DOI: 10.1038/s41575-018-0010-0.
    [14] KIM GA, LEE HC, CHOE J, et al. Association between non-alcoholic fatty liver disease and cancer incidence rate[J]. J Hepatol, 2017, 68(1): 140-146. DOI: 10.1016/j.jhep.2017.09.012.
    [15] HAMAGUCHI M, HASHIMOTO Y, OBORA A, et al. Non-alcoholic fatty liver disease with obesity as an independent predictor for incident gastric and colorectal cancer: A population-based longitudinal study[J]. BMJ Open Gastroenterol, 2019, 6(1): e000295. DOI: 10.1136/bmjgast-2019-000295.
    [16] MANTOVANI A, DAURIZ M, BYRNE CD, et al. Association between nonalcoholic fatty liver disease and colorectal tumours in asymptomatic adults undergoing screening colonoscopy: A systematic review and meta-analysis[J]. Metabolism, 2018, 87: 1-12. DOI: 10.1016/j.metabol.2018.06.004.
    [17] HUBER Y, LABENZ C, MICHEL M, et al. Tumor incidence in patients with non-alcoholic fatty liver disease[J]. Dtsch Arztebl Int, 2020, 117(43): 719-724. DOI: 10.3238/arztebl.2020.0719.
    [18] LEE JM, PARK YM, YUN JS, et al. The association between nonalcoholic fatty liver disease and esophageal, stomach, or colorectal cancer: National population-based cohort study[J]. PLoS One, 2020, 15(1): e0226351. DOI: 10.1371/journal.pone.0226351.
    [19] LIU SS, MA XF, ZHAO J, et al. Association between nonalcoholic fatty liver disease and extrahepatic cancers: A systematic review and meta-analysis[J]. Lipids Health Dis, 2020, 19(1): 118. DOI: 10.1186/s12944-020-01288-6.
    [20] WANG Z, ZHAO X, CHEN S, et al. Associations between nonalcoholic fatty liver disease and cancers in a large cohort in China[J]. Clin Gastroenterol Hepatol, 2021, 19(4): 788-796. e4. DOI: 10.1016/j.cgh.2020.05.009.
    [21] MUSSO G, GAMBINO R, TABIBIAN JH, et al. Association of non-alcoholic fatty liver disease with chronic kidney disease: A systematic review and meta-analysis[J]. PLoS Med, 2014, 11(7): e1001680. DOI: 10.1371/journal.pmed.1001680.
    [22] MANTOVANI A, ZAZA G, BYRNE CD, et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis[J]. Metabolism, 2018, 79: 64-76. DOI: 10.1016/j.metabol.2017.11.003.
    [23] VILAR-GOMEZ E, CALZADILLA-BERTOT L, FRIEDMAN SL, et al. Improvement in liver histology due to lifestyle modification is independently associated with improved kidney function in patients with non-alcoholic steatohepatitis[J]. Aliment Pharmacol Ther, 2017, 45(2): 332-344. DOI: 10.1111/apt.13860.
    [24] BRZOZOWSKA MM, OSTAPOWICZ G, WELTMAN MD. An association between non-alcoholic fatty liver disease and polycystic ovarian syndrome[J]. J Gastroenterol Hepatol, 2009, 24(2): 243-247. DOI: 10.1111/j.1440-1746.2008.05740.x.
    [25] HOSSAIN N, STEPANOVA M, AFENDY A, et al. Non-alcoholic steatohepatitis (NASH) in patients with polycystic ovarian syndrome (PCOS)[J]. Scand J Gastroenterol, 2011, 46(4): 479-484. DOI: 10.3109/00365521.2010.539251.
    [26] ASFARI MM, SARMINI MT, BAIDOUN F, et al. Association of non-alcoholic fatty liver disease and polycystic ovarian syndrome[J]. BMJ Open Gastroenterol, 2020, 7(1): e000352. DOI: 10.1136/bmjgast-2019-000352.
    [27] SALVA-PASTOR N, LÓPEZ-SÁNCHEZ GN, CHÁVEZ-TAPIA NC, et al. Polycystic ovary syndrome with feasible equivalence to overweight as a risk factor for non-alcoholic fatty liver disease development and severity in Mexican population[J]. Ann Hepatol, 2020, 19(3): 251-257. DOI: 10.1016/j.aohep.2020.01.004.
    [28] CAI J, WU CH, ZHANG Y, et al. High-free androgen index is associated with increased risk of non-alcoholic fatty liver disease in women with polycystic ovary syndrome, independent of obesity and insulin resistance[J]. Int J Obes (Lond), 2017, 41(9): 1341-1347. DOI: 10.1038/ijo.2017.116.
    [29] MACUT D, TZIOMALOS K, BOŽIĆ-ANTIĆ I, et al. Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome[J]. Hum Reprod, 2016, 31(6): 1347-1353. DOI: 10.1093/humrep/dew076.
    [30] TARANTO D, GUIMARÃES T, COUTO CA, et al. Nonalcoholic fatty liver disease in women with polycystic ovary syndrome: Associated factors and noninvasive fibrosis staging in a single Brazilian center[J]. Arch Endocrinol Metab, 2020, 64(3): 235-242. DOI: 10.20945/2359-3997000000242.
    [31] PAGADALA MR, ZEIN CO, DASARATHY S, et al. Prevalence of hypothyroidism in nonalcoholic fatty liver disease[J]. Dig Dis Sci, 2012, 57(2): 528-534. DOI: 10.1007/s10620-011-2006-2.
    [32] ESHRAGHIAN A, HAMIDIAN JAHROMI A. Non-alcoholic fatty liver disease and thyroid dysfunction: A systematic review[J]. World J Gastroenterol, 2014, 20(25): 8102-8109. DOI: 10.3748/wjg.v20.i25.8102.
    [33] CHUNG GE, KIM D, KIM W, et al. Non-alcoholic fatty liver disease across the spectrum of hypothyroidism[J]. J Hepatol, 2012, 57(1): 150-156. DOI: 10.1016/j.jhep.2012.02.027.
    [34] TAKAHASHI Y. The role of growth hormone and insulin-like growth factor-I in the liver[J]. Int J Mol Sci, 2017, 18(7): 1447. DOI: 10.3390/ijms18071447.
    [35] NISHIZAWA H, IGUCHI G, MURAWAKI A, et al. Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy[J]. Eur J Endocrinol, 2012, 167(1): 67-74. DOI: 10.1530/EJE-12-0252.
    [36] LI M, XU Y, XU M, et al. Association between nonalcoholic fatty liver disease (NAFLD) and osteoporotic fracture in middle-aged and elderly Chinese[J]. J Clin Endocrinol Metab, 2012, 97(6): 2033-2038. DOI: 10.1210/jc.2011-3010.
    [37] UPALA S, JARUVONGVANICH V, WIJARNPREECHA K, et al. Nonalcoholic fatty liver disease and osteoporosis: A systematic review and meta-analysis[J]. J Bone Miner Metab, 2017, 35(6): 685-693. DOI: 10.1007/s00774-016-0807-2.
    [38] MANTOVANI A, DAURIZ M, GATTI D, et al. Systematic review with meta-analysis: Non-alcoholic fatty liver disease is associated with a history of osteoporotic fractures but not with low bone mineral density[J]. Aliment Pharmacol Ther, 2019, 49(4): 375-388. DOI: 10.1111/apt.15087.
    [39] FERNÁNDEZ-MINCONE T, CONTRERAS-BRICEÑO F, ESPINOSA-RAMÍREZ M, et al. Nonalcoholic fatty liver disease and sarcopenia: Pathophysiological connections and therapeutic implications[J]. Expert Rev Gastroenterol Hepatol, 2020, 14(12): 1141-1157. DOI: 10.1080/17474124.2020.1810563.
    [40] KIM G, LEE SE, LEE YB, et al. Relationship between relative skeletal muscle mass and nonalcoholic fatty liver disease: A 7-year longitudinal study[J]. Hepatology, 2018, 68(5): 1755-1768. DOI: 10.1002/hep.30049.
    [41] CAI C, SONG X, CHEN Y, et al. Relationship between relative skeletal muscle mass and nonalcoholic fatty liver disease: A systematic review and meta-analysis[J]. Hepatol Int, 2020, 14(1): 115-126. DOI: 10.1007/s12072-019-09964-1.
    [42] MESARWI OA, LOOMBA R, MALHOTRA A. Obstructive sleep apnea, hypoxia, and nonalcoholic fatty liver disease[J]. Am J Respir Crit Care Med, 2019, 199(7): 830-841. DOI: 10.1164/rccm.201806-1109TR.
    [43] MUSSO G, CASSADER M, OLIVETTI C, et al. Association of obstructive sleep apnoea with the presence and severity of non-alcoholic fatty liver disease. A systematic review and meta-analysis[J]. Obes Rev, 2013, 14(5): 417-431. DOI: 10.1111/obr.12020.
    [44] CHEN LD, CHEN MX, CHEN GP, et al. Association between obstructive sleep apnea and non-alcoholic fatty liver disease in pediatric patients: A meta-analysis[J]. Pediatr Obes, 2021, 16(3): e12718. DOI: 10.1111/ijpo.12718.
    [45] AGRAWAL S, DUSEJA A, AGGARWAL A, et al. Obstructive sleep apnea is an important predictor of hepatic fibrosis in patients with nonalcoholic fatty liver disease in a tertiary care center[J]. Hepatol Int, 2015, 9(2): 283-291. DOI: 10.1007/s12072-015-9615-3.
    [46] DAUDEN E, BLASCO AJ, BONANAD C, et al. Position statement for the management of comorbidities in psoriasis[J]. J Eur Acad Dermatol Venereol, 2018, 32(12): 2058-2073. DOI: 10.1111/jdv.15177.
    [47] NARAYANASAMY K, SANMARKAN AD, RAJENDRAN K, et al. Relationship between psoriasis and non-alcoholic fatty liver disease[J]. Prz Gastroenterol, 2016, 11(4): 263-269. DOI: 10.5114/pg.2015.53376.
    [48] GISONDI P, BARBA E, GIROLOMONI G. Non-alcoholic fatty liver disease fibrosis score in patients with psoriasis[J]. J Eur Acad Dermatol Venereol, 2016, 30(2): 282-287. DOI: 10.1111/jdv.13456.
    [49] ABEDINI R, SALEHI M, LAJEVARDI V, et al. Patients with psoriasis are at a higher risk of developing nonalcoholic fatty liver disease[J]. Clin Exp Dermatol, 2015, 40(7): 722-727. DOI: 10.1111/ced.12672.
    [50] van der VOORT EA, KOEHLER EM, DOWLATSHAHI EA, et al. Psoriasis is independently associated with nonalcoholic fatty liver disease in patients 55 years old or older: Results from a population-based study[J]. J Am Acad Dermatol, 2014, 70(3): 517-524. DOI: 10.1016/j.jaad.2013.10.044.
    [51] KOWDLEY KV, BELT P, WILSON LA, et al. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease[J]. Hepatology, 2012, 55(1): 77-85. DOI: 10.1002/hep.24706.
    [52] NELSON JE, WILSON L, BRUNT EM, et al. Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease[J]. Hepatology, 2011, 53(2): 448-457. DOI: 10.1002/hep.24038.
    [53] SUMIDA Y, YONEDA M, HYOGO H, et al. A simple clinical scoring system using ferritin, fasting insulin, and type Ⅳ collagen 7S for predicting steatohepatitis in nonalcoholic fatty liver disease[J]. J Gastroenterol, 2011, 46(2): 257-268. DOI: 10.1007/s00535-010-0305-6.
    [54] BUGIANESI E, MCCULLOUGH AJ, MARCHESINI G. Insulin resistance: A metabolic pathway to chronic liver disease[J]. Hepatology, 2005, 42(5): 987-1000. DOI: 10.1002/hep.20920.
    [55] GUO L, TANG QQ. Research progress of the mechanism and therapy of non-alcoholic fatty liver disease[J]. Chin Bull Life Sci, 2018, 30(11): 1165-1172. DOI: 10.13376/j.cbls/2018141.

    郭亮, 汤其群. 非酒精性脂肪肝发病机制和治疗的研究进展[J]. 生命科学, 2018, 30(11): 1165-1172. DOI: 10.13376/j.cbls/2018141.
    [56] ESLAM M, SANYAL AJ, GEORGE J. Toward more accurate nomenclature for fatty liver diseases[J]. Gastroenterology, 2019, 157(3): 590-593. DOI: 10.1053/j.gastro.2019.05.064.
    [57] TARGHER G, BYRNE CD, TILG H. NAFLD and increased risk of cardiovascular disease: Clinical associations, pathophysiological mechanisms and pharmacological implications[J]. Gut, 2020, 69(9): 1691-1705. DOI: 10.1136/gutjnl-2020-320622.
    [58] JULLIAN-DESAYES I, TAMISIER R, ZARSKI JP, et al. Impact of effective versus sham continuous positive airway pressure on liver injury in obstructive sleep apnoea: Data from randomized trials[J]. Respirology, 2016, 21(2): 378-385. DOI: 10.1111/resp.12672.
    [59] CHIN K, NAKAMURA T, TAKAHASHI K, et al. Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients[J]. Am J Med, 2003, 114(5): 370-376. DOI: 10.1016/s0002-9343(02)01570-x.
    [60] GANZETTI G, CAMPANATI A, OFFIDANI A. Non-alcoholic fatty liver disease and psoriasis: So far, so near[J]. World J Hepatol, 2015, 7(3): 315-326. DOI: 10.4254/wjh.v7.i3.315.
    [61] CHEN LK, WOO J, ASSANTACHAI P, et al. Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment[J]. J Am Med Dir Assoc, 2020, 21(3): 300-307. e2. DOI: 10.1016/j.jamda.2019.12.012.
    [62] PENG TC, WU LW, CHEN WL, et al. Nonalcoholic fatty liver disease and sarcopenia in a Western population (NHANES Ⅲ): The importance of sarcopenia definition[J]. Clin Nutr, 2019, 38(1): 422-428. DOI: 10.1016/j.clnu.2017.11.021.
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