From Cell Biology to Tissue Engineering


Hepatocellular carcinoma in non-alcoholic fatty liver disease (NAFLD) - pathological evidence for a predominance of steatohepatitic inflammatory non-proliferative subtype

Priscila B. de Campos1, Claudia P. Oliveira1,2, José T. Stefano2, Sebastião N. Martins-Filho3, Aline L. Chagas4, Paulo Herman4, Luiz C. D'Albuquerque4, Mário R. Alvares-da-Silva5, Adhemar Longatto-Filho3,6,7, Flair J. Carrilho1,2 and Venancio A.F. Alves1,3

1University of São Paulo Medical School, 2Laboratory of Clinical and Experimental Gastroenterology (LIM-07) Department of Gastroenterology and Hepatology, 3Department of Pathology (LIM-14), 4Department of Gastroenterology, Hospital das Clínicas HCFMUSP, School of Medicine, University of São Paulo, São Paulo, SP, 5Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brasil, 6Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga and 7ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal

Offprint requests to: Claudia Pinto Marques de Souza de Oliveira, Laboratório de Gastroenterologia Clínica e Experimental (LIM-07) do Departamento de Gastroenterologia e Hepatologia do Hospital das Clínicas HCFMUSP da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455 3th floor 3115, 01246-903 - Sao Paulo, Brazil. e-mail: cpm@usp.br

Summary. Objectives. This study evaluated clinical and pathological aspects of patients with hepatocellular carcinoma (HCC) secondary to non-alcoholic fatty liver disease (NAFLD) and related these factors to immunohistochemical markers representative of the proliferative class. Methods. We evaluated 35 HCC nodules from 21 patients diagnosed with NAFLD undergoing liver resection (n=12) or liver transplantation (n=8) or both (n=1). Demographic, clinical and biochemical data were compared to histological features and to immunohisto-chemical reactivity for K19 and Ki-67. Results. Cirrhosis was present in 58% of patients. Ages ranged from 50 to 77 years. Sixteen patients (76%) were male and had type 2 diabetes mellitus, 81% had arterial hypertension, and 90% had BMI above 25 kg/m2. Alpha-fetoprotein levels were normal in 62% of patients. Twenty-five (70%) nodules were diagnosed as "steatohepatitic HCC". Only 32% of the nodules presented high levels of Ki-67 (>10%) and/or K19 (>5%), although 63% were poorly differentiated (G.3/G.4) according to Edmondson & Steiner grading system. K19 positivity (>5%) was associated with higher degree of intratumoral inflammation (G.2/G.3), and with fibrosis, both at the center of the tumor and at the tumor front, whereas Ki-67 positivity (>10%) was associated with ballooning of neoplastic cells and occurred in more than 70% in non-cirrhotic patients. Conclusion. NAFLD-related HCC was found in non-cirrhotic patients in 42% of cases, alpha-fetoprotein level was normal in 63% and "steatohepatitic HCC" was the predominant histological type. Immunoexpression of K19 and/or Ki-67 occurred in 32% of the nodules and were associated with intratumoral inflammation and ballooning, suggesting that HCC in MtS may be preferentially "an inflammatory, non-proliferative subtype of HCC". Histol Histopathol 35, 729-740 (2020)

Key words: Hepatocellular carcinoma, Non-alcoholic fatty liver disease, Pathology, Immunohistochemistry

DOI: 10.14670/HH-18-194