Rastogi Archana, Shasthry Saggere Muralikrishna, Agarwal Ayushi, Bihari Chhagan, Jain Priyanka, Jindal Ankur, Sarin Shiv
Department of Pathology, Institute of Liver & Biliary Sciences, Delhi, India.
Department of Hepatology, Institute of Liver & Biliary Sciences, Delhi, India.
APMIS. 2017 Nov;125(11):962-973. doi: 10.1111/apm.12742.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver disease. Till date, liver biopsy remains the gold standard for identification and quantification of the wide histological spectra of NAFLD. Histological scorings are very useful and widely applied for the diagnosis and management in clinical trials and follow-up studies of non-alcoholic steatohepatitis (NASH). However, in view of scarce published literature, there is a need to evaluate them in large cohort of NAFLD. This study was aimed to evaluate the two histological scoring systems (NAS-CRN, SAF) in the diagnosis of NAFLD and to assess the role of histological characteristics as injury markers in NAFLD. Retrospective histological study of liver biopsies of 1000 patients diagnosed as NAFLD, between 2010 and 2016, was conducted. Histopathologic evaluation and semiquantiative scoring based on NAS-CRN and SAF algorithm and their correlation with serum aminotransferase and fibrosis were performed. Liver biopsies were classified according to the NAS-CRN scoring, as NAS <3 (not NASH) in 72 (7.2%), NAS 3-4 (borderline NASH) in 310 (31%), and NAS ≥5 (definite NASH) in 618 (61.8%), and SAF classified 117 (11.7%) not NASH and 883 (88.3%) definite NASH. There was excellent concordance for definite NASH and not NASH; however, 88.06% of borderline NASH was classified as NASH by SAF. 76.39% by NAS and 78.63% by SAF algorithm who were diagnosed as not NASH showed the presence of fibrosis; however, higher stages of fibrosis were significantly more prevalent in definite NASH, excluding burnt-out cirrhosis. Serum ALT was significantly associated with increasing stages of fibrosis (p < 0.001) and the three categories (not NASH, borderline NASH, and definite NASH) when classified as with/without fibrosis (p < 0.001). Steatosis of higher grades, more ballooned cells, and more foci of Lobular Inflammation were found in significantly higher proportion of patients with NASH (p < 0.001), with higher fibrosis stages (p < 0.001) and higher serum ALT levels (p < 0.001). NAFLD classifications based on histological scoring NAS-CRN and SAF algorithm are concordant for the category of definite NASH and not NASH, while borderline NASH shows discrepant interpretation. There was highly significant correlation between the NAS and SAF categories with high grades of histological characteristics, with serum ALT and with higher stages of fibrosis. Exclusion of fibrosis is a limitation with both scores.
非酒精性脂肪性肝病（NAFLD）是慢性肝病日益常见的病因。迄今为止，肝活检仍是识别和量化NAFLD广泛组织学谱的金标准。组织学评分非常有用，广泛应用于非酒精性脂肪性肝炎（NASH）的临床试验和随访研究的诊断与管理。然而，鉴于已发表的文献稀缺，有必要在大量NAFLD队列中对其进行评估。本研究旨在评估两种组织学评分系统（NAS-CRN、SAF）在NAFLD诊断中的作用，并评估组织学特征作为NAFLD损伤标志物的作用。对2010年至2016年间诊断为NAFLD的1000例患者的肝活检进行回顾性组织学研究。基于NAS-CRN和SAF算法进行组织病理学评估和半定量评分，并分析它们与血清转氨酶和纤维化的相关性。根据NAS-CRN评分，肝活检分类如下：NAS<3（非NASH）72例（7.2%），NAS 3-4（临界NASH）310例（31%），NAS≥5（确诊NASH）618例（61.8%）；SAF分类为非NASH 117例（11.7%），确诊NASH 883例（88.3%）。确诊NASH和非NASH的一致性极佳；然而，88.06%的临界NASH被SAF分类为NASH。被诊断为非NASH的患者中，76.39%按NAS分类、78.63%按SAF算法分类显示存在纤维化；然而，排除终末期肝硬化后，确诊NASH中更高阶段的纤维化明显更为普遍。血清ALT与纤维化阶段增加（p<0.001）以及按有无纤维化分类的三类（非NASH、临界NASH和确诊NASH）显著相关（p<0.001）。在NASH患者中，更高等级的脂肪变性、更多的气球样细胞和更多的小叶炎症灶比例显著更高（p<0.001），纤维化阶段更高（p<0.001），血清ALT水平更高（p<0.001）。基于组织学评分NAS-CRN和SAF算法的NAFLD分类在确诊NASH和非NASH类别上是一致的，而临界NASH显示出不同的解读。NAS和SAF类别与高等级组织学特征、血清ALT以及更高阶段的纤维化之间存在高度显著的相关性。两种评分都存在排除纤维化这一局限性。
