BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. It is not well understood, however, which individuals with NAFLD are at highest risk for cardiovascular disease. AIMS To determine the factors associated with incident cardiovascular events in a prospective cohort of individuals with biopsy-proven NAFLD without pre-existing cardiovascular disease. METHODS From 2011 to 2018, adults with biopsy-proven NAFLD without cardiovascular disease were enrolled in a tissue repository and were followed prospectively to the first recorded date of incident cardiovascular disease, death or the end of follow-up (11/1/2018). Competing risks analysis was performed to identify predictors of incident cardiovascular disease. RESULTS After a median follow-up time of 5.2 years, 26/285 (9.1%) individuals experienced an incident cardiovascular event. Advanced fibrosis (stage 3-4) on biopsy was a significant predictor of incident cardiovascular disease, and this persisted on multivariable analysis (SHR 2.86, 95% CI 1.36-6.04) after considering relevant covariates, including cardiovascular risk scores, which were not independent predictors. Of the non-invasive indicators of fibrosis, the NAFLD fibrosis score was the only independent predictor of cardiovascular disease. Other histologic features, including steatohepatitis, were not associated with incident cardiovascular disease. CONCLUSIONS In adults with biopsy-proven NAFLD, advanced fibrosis on biopsy and higher NAFLD fibrosis score were significant and independent predictors of incident cardiovascular disease, even after considering traditional risk factors and cardiovascular risk scores. These findings should be considered when evaluating NAFLD patients for primary prevention of cardiovascular disease, and further evaluation into the link between advanced fibrosis and cardiovascular disease is needed.

中文翻译：

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非酒精性脂肪肝患者的晚期纤维化与心血管疾病有关。

背景技术非酒精性脂肪肝疾病（NAFLD）与心血管疾病的风险增加相关。但是，尚不清楚哪些NAFLD患者患心血管疾病的风险最高。目的确定具有活检证实的NAFLD且未患心血管疾病的个体的预期队列中与心血管事件相关的因素。方法从2011年至2018年，将经活检证实为无心血管疾病的NAFLD的成年人纳入组织库，并对其进行前瞻性随访，以记录心血管事件的首次记录日期，死亡或随访结束（11/1/2018） 。进行竞争风险分析以识别心血管事件的预测因素。结果中位随访时间为5.2年，26/285（9。1％）的个人经历了心血管事件。活检的晚期纤维化（3-4期）是心血管疾病发生的重要预测指标，在考虑了相关的协变量（包括心血管风险评分）后，该变量在多变量分析（SHR 2.86，95％CI 1.36-6.04）中仍然存在预测变量。在纤维化的非侵入性指标中，NAFLD纤维化评分是心血管疾病的唯一独立预测因子。其他组织学特征，包括脂肪性肝炎，均与心血管疾病无关。结论在经活检证实为NAFLD的成人中，活检中的晚期纤维化和较高的NAFLD纤维化评分是心血管事件发生的重要独立指标，即使在考虑了传统的危险因素和心血管疾病风险评分之后。在评估NAFLD患者对心血管疾病的一级预防时应考虑这些发现，并且需要进一步评估晚期纤维化与心血管疾病之间的联系。