背景:非酒精性脂肪性肝病是慢性肝病的最常见原因之一,甚至发生在体重指数(BMI)正常或低的瘦个体中。关键的问题是了解临床,与肥胖患者相比,病理生物学和代谢特征。很少有研究比较瘦和肥胖的临床病理特征。发表的文献通常是在一小部分患者中,很少包括超重作为单独的类别,大多数情况下,BMI标准的使用不规范,结论不一致.关于肝活检证实的队列和来自亚洲的文献非常稀少;此外,没有人探索过星状细胞等介质的作用,祖细胞和巨噬细胞。
目的:在组织学证实的NAFLD的大型队列中,评估瘦肉患者NAFLD的患病率,与超重和肥胖相比,探讨瘦NAFLD的临床病理谱。此外,研究肝星状细胞的作用,巨噬细胞极化及其与肝祖细胞的关系,特别是与纤维化和不同BMI类别的关系。
方法:对2011年至2021年期间诊断的所有连续NAFLD患者的11年回顾性横断面数据进行前瞻性分析。所有符合纳入和排除标准的组织学证实的NAFLD病例根据基于亚洲标准的BMI分为三组。人口统计,实验室,新陈代谢,对瘦和超重肥胖患者进行组织学比较。通过NAS-CRN评分对NAFLD组分进行组织学分级和分期。基于免疫组织化学和图像分析的星状细胞评估和定量,祖细胞,并进行巨噬细胞极化。采用了适当的统计方法,研究得到了机构伦理委员会的批准。
结果:经活检证实的精益患者占总NAFLD(n=1273)的21%(n=267)。其他组是超重患者(232;18.2%),最高的是肥胖患者(774;60.8%)。13.9%的NAFLD患者体重不足,BMI<18.5kg/m2。与其他组相比,瘦患者的BMI和腰围明显较低,空腹血糖水平也较低。其余的代谢参数几乎相似。精益患者显示较高的血清ALT水平,与其他组相比,肝细胞膨胀和脂肪变性等组织学特征也更为明显。小叶炎症和晚期纤维化在患有NASH相关肝硬化的瘦患者中仅20.9%的患者中明显不常见。免疫表型研究揭示了HPCs的相互关系,HSC,巨噬细胞受纤维化阶段的影响,而不受BMI的影响。
结论:在组织学证实的患者队列中,瘦个体中NAFLD的患病率为21%。(n=267/1273)。这项研究的主要优势是来自单个中心的大量精瘦个体,仅包括组织学证实的病例,亚洲特定的BMI标准使用情况,比较临床,新陈代谢,基于免疫形态学和图像分析的表征,除肥胖患者外,还包括超重,并调查主要病理生理标志物的串扰。
BACKGROUND: Non-alcoholic fatty liver disease is one of the most common causes of chronic liver diseases and occurs even in
lean individuals having normal or low body mass index (BMI). Crucial issue is understanding the clinical, pathobiologic and metabolic characteristics in comparison to obese patients. Very few studies have compared clinicopathological characteristics between
lean and obese. Published literature is generally in a small cohort of patients, rarely included over-weight as separate category, and most often had non-standardized use of BMI criteria with discordant conclusions. There is very sparse published literature on liver biopsy-confirmed cohort and that to from Asia; also, none had explored the role of mediators such as stellate cells, progenitor cells and macrophages.
OBJECTIVE: To evaluate the prevalence of NAFLD in lean patients in a large cohort of histology-confirmed NAFLD, and explore clinico-pathological spectrum of
lean NAFLD in comparison to over-weight and obese. Also, to investigate role of hepatic stellate cells, macrophage polarization and their relation to hepatic progenitor cells, in particular the relation to fibrosis and to different BMI categories.
METHODS: Prospective analysis of eleven-year retrospective cross-sectional data of all consecutive patients of NAFLD diagnosed in the period between the year 2011 and 2021. All histologically confirmed cases of NAFLD fulfilling inclusion and exclusion criteria were stratified to three groups according to BMI based on Asian criteria. Demographic, lab, metabolic, and histological comparisons between lean and overweight-obese patients were performed. Histological grading and staging of NAFLD components were performed by NAS-CRN score. Immunohistochemical and image analysis-based assessment and quantification of stellate cells, progenitor cells, and macrophage polarization was performed. Appropriate statistical methods were applied, and
study was approved by the Institutional ethics committee.
RESULTS: Lean patients with biopsy-proven diagnosis constituted 21 % (n = 267) of total NAFLD (n = 1273). Other groups were-over-weight patients (232;18.2 %), and the highest were obese patients (774; 60.8 %). 13.9 % of the lean patients with NAFLD were under-weight with BMI<18.5 kg/m2. Lean patients had significantly lower BMI and waist circumference along with lesser fasting glucose levels in comparison to the other groups. Rest of the metabolic parameters were nearly similar. Lean patients showed higher serum ALT levels, and histological characteristics such as ballooning of hepatocytes and steatosis were also more marked in comparison to other groups. Lobular inflammation and advanced fibrosis were significantly less common in lean patients with NASH related cirrhosis found in only 20.9 % of them. Immunophenotypic studies revealed the inter-relationship of HPCs, HSCs, and macrophages was influenced by the stage of fibrosis and not by the BMI.
CONCLUSIONS: Prevalence of NAFLD in lean individuals in a histological-confirmed patient cohort was 21 %. (n = 267/1273). Major strengths of this
study are large cohort of
lean individuals from a single center, inclusion of only histology-confirmed cases, Asia specific BMI criteria usage, comparative clinical, metabolic, immune-morphologic and image analysis-based characterization, inclusion of over-weight in addition to obese patients, and investigating cross-talk of principal patho-physiologic markers.