Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Seville, Spain.
SeLiver Group, Instituto de Biomedicina de Sevilla, Seville, Spain.
Liver Int. 2021 Sep;41(9):2076-2086. doi: 10.1111/liv.14898. Epub 2021 May 7.
Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD).
Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years).
Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these.
The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.
组织学评分系统可能无法充分捕捉到非酒精性脂肪性肝炎（NASH）的基本特征，这是非酒精性脂肪性肝病（NAFLD）临床试验中筛选失败的主要原因之一。我们评估了 NASH 在纤维化各阶段的分布及其各组成部分，并研究其对预后的影响，以及与代谢相关脂肪性肝病（MAFLD）概念的关系。
这是一项来自西班牙的多中心研究，纳入了来自 HEPAmet 登记处的 1893 例经活检证实的非酒精性脂肪性肝病（NAFLD）患者。采用 NAS 评分≥4（包括脂肪变性、气球样变和肝小叶炎症）诊断 NASH，采用 Kleiner 评分诊断纤维化。确定 MAFLD 的存在。在随访期间（4.7±3.8 年）收集肝硬化进展、首次失代偿性肝硬化发作和死亡的情况。
纤维化程度为 F0 34.3%（649/1893），F1 27%（511/1893），F2 16.5%（312/1893），F3 15%（284/1893）和 F4 7.2%（137/1893）。NASH 的诊断率为 51.9%（982/1893），其各个组成部分（严重脂肪变性、气球样变和肝小叶炎症）从 F0（33.6%）增加到 F2（68.6%），在 F4 患者中显著下降（51.8%）（P=.0001）。超过 70%的非 NASH 患者表现出一定的炎症活动（气球样变或肝小叶炎症），其 MAFLD 发生率与 NASH 相似（96.2%[945/982]比 95.2%[535/562]），明显高于非酒精性脂肪肝（NAFL）患者（89.1%[311/349]）（P<.0001）。NASH（9.5%[51/539]）和不确定型 NASH（7.9%[25/316]）的肝硬化进展率相似，均高于单纯脂肪变性（5%[14/263]）（对数秩检验 8.417；P=.015）。这些患者的死亡率和失代偿性肝硬化的发生率相似。
在晚期肝病中，肝炎的患病率下降。然而，大多数这些患者在组织学上表现出一定的炎症活动，且存在代谢紊乱。这些发现应在临床试验中考虑，临床试验的主要目的是预防肝硬化进展和并发症、肝移植和死亡。
