Institute for Advanced Biosciences, INSERM U1209/CNRS UMR, Grenoble Alpes University, Grenoble, France.
Hepatology, gastro-enterology and digestive oncology, Grenoble Alpes University Hospital, La Tronche, France.
Liver Int. 2022 Jul;42(7):1638-1647. doi: 10.1111/liv.15256. Epub 2022 May 11.
Alcohol-associated hepatocellular carcinoma (AL-HCC) poor prognosis has been attributed to diagnosis at a later stage. However, host factors and specific health trajectories have been associated with severe outcomes in alcohol-related liver disease. We hypothesize AL-HCC is not a homogeneous condition but encompasses subgroups yielding different outcomes.
Our aim was to provide a first attempt at a clinical phenotyping of AL-HCC.
We analysed data for the calendar years 2007-2013 from the French nationwide administrative hospital database. We selected patients with AL-HCC only. Clustering of AL-HCC phenotypes was performed by latent class analysis (LCA).
The study included 11 363 patients with AL-HCC, mainly male (89.6%), median age 67 years [IQR: 61; 74] of which 71.2% had at least one metabolic comorbidity. Five phenotypes were identified. Phenotype 1 (41.4%) displayed high rates of unrecognized cirrhosis prior to HCC diagnosis (81%), low rates of metabolic comorbidities (diabetes 13%), and mostly compensated liver disease at HCC diagnosis while the four other phenotypes displayed high rates of metabolic comorbidities (diabetes up to 100%), various patterns of liver disease trajectories and overall 42% unrecognized cirrhosis. In adjusted survival analysis, compared to phenotype 1, risk of death after HCC diagnosis was significantly different for all phenotypes.
LCA uncovers AL-HCC is a heterogeneous condition with distinct phenotypes yielding specific survival outcomes. Frequent unrecognized cirrhosis prior to HCC underlines the urgent need for implementing strategies to identify the underlying liver disease prior to HCC onset in patients with documented alcohol use disorders and metabolic comorbidities.
酒精相关性肝细胞癌(AL-HCC)预后较差,这归因于其在晚期被诊断出来。然而,宿主因素和特定的健康轨迹与酒精性肝病的严重后果有关。我们假设 AL-HCC 不是一种同质的疾病,而是包含不同结局的亚组。
我们旨在首次尝试对 AL-HCC 进行临床表型分析。
我们分析了法国全国性医院数据库中 2007-2013 年的日历年度数据。我们仅选择了患有 AL-HCC 的患者。采用潜在类别分析(LCA)对 AL-HCC 表型进行聚类。
该研究纳入了 11363 例 AL-HCC 患者,主要为男性(89.6%),中位年龄 67 岁[IQR:61;74],其中 71.2%至少有一种代谢合并症。确定了 5 种表型。表型 1(41.4%)在 HCC 诊断前肝硬化未被识别的比例较高(81%),代谢合并症(糖尿病 13%)比例较低,且 HCC 诊断时大多为代偿性肝病,而其他 4 种表型则代谢合并症(糖尿病高达 100%)比例较高,肝脏疾病轨迹多样,整体未被识别的肝硬化比例为 42%。在调整后的生存分析中,与表型 1 相比,所有表型的 HCC 诊断后死亡风险均显著不同。
LCA 揭示 AL-HCC 是一种异质性疾病,具有不同的表型,产生特定的生存结局。在 HCC 发生之前,在有明确酒精使用障碍和代谢合并症的患者中,未被识别的肝硬化较为常见,这突显了迫切需要制定策略,在 HCC 发生之前识别潜在的肝脏疾病。