Background & Aims There are conflicting data regarding the epidemiology of hepatocellular carcinoma (HCC) arising in the context of non-alcoholic and metabolic-associated fatty liver disease (NAFLD and MAFLD). We aimed to examine the changing contribution of NAFLD and MAFLD, stratified by sex, in a well-defined geographical area and highly characterised HCC population between 1990 and 2014. Methods We identified all patients with HCC resident in the canton of Geneva, Switzerland, diagnosed between 1990 and 2014 from the prospective Geneva Cancer Registry and assessed aetiology-specific age-standardised incidence. NAFLD-HCC was diagnosed when other causes of liver disease were excluded in cases with type 2 diabetes, metabolic syndrome, or obesity. Criteria for MAFLD included one or more of the following criteria: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. Results A total of 76/920 (8.3%) of patients were diagnosed with NAFLD-HCC in the canton of Geneva between 1990 and 2014. Between the time periods 1990–1994 and 2010–2014, there was a significant increase in HCC incidence in women (standardised incidence ratio [SIR] 1.83, 95% CI 1.08–3.13, p = 0.026) but not in men (SIR 1.10, 95% CI 0.85–1.43, p = 0.468). In the same timeframe, the proportion of NAFLD-HCC increased more in women (0–29%, p = 0.037) than in men (2–12%, p = 0.010) while the proportion of MAFLD increased from 21% to 68% in both sexes and from 7% to 67% in women ( p <0.001). From 2000–2004 to 2010–2014, the SIR of NAFLD-HCC increased to 1.92 (95% CI 0.77–5.08) for men and 12.7 (95% CI 1.63–545) in women, whereas it decreased or remained stable for other major aetiologies of HCC. Conclusions In a populational cohort spanning 25 years, the burden of NAFLD and MAFLD associated HCCs increased significantly, driving an increase in HCC incidence, particularly in women. Lay summary Hepatocellular carcinoma (HCC) is the most common type of liver cancer, increasingly arising in patients with liver disease caused by metabolic syndrome, termed non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD). We assessed all patients with HCC between 1990 and 2014 in the canton of Geneva (western Switzerland) and found an increase in all HCC cases in this timeframe, particularly in women. In addition, we found that HCC caused by NAFLD or MAFLD significantly increased over the years, particularly in women, possibly driving the increase in overall HCC cases.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. In recent years, the metabolic syndrome epidemic is changing the etiological landscape of HCC, with metabolic liver disease comprising an exponentially increasing proportion of HCC cases. In this review, we discuss HCC in the context of metabolic syndrome, including its epidemiology, its unique clinical and pathological characteristics, and its multifactorial pathogenesis. We also discuss HCC prevention and management as relates to these patients.

Résumé La stéatopathie dysmétabolique (NAFLD) est une maladie hépatique à évolution lente qui comprend un spectre allant de la stéatose hépatique non alcoolique, à la stéatohépatite non alcoolique (NASH) et dans les cas graves, la cirrhose. La NAFLD est la pathologie hépatique la plus répandue dans les pays occidentaux industrialisés, dont la Suisse, avec une prévalence en croissance rapide reflétant celle de l’obésité et du diabète de type 2. Un panel d’experts a récemment proposé l’utilisation d’une nomenclature alternative, la stéatose hépatique associée à un dysfonctionnement métabolique (MAFLD) dont l’utilisation reste discutée. Bien qu’il existe un pipeline de développement de médicaments très actif et que de nombreux médicaments sont actuellement en essai clinique de phase II et III, aucun traitement pharmacologique n’a encore été approuvé pour la NASH. Dans certains cas une chirurgie bariatrique pourra être discutée. Néanmoins, à l’heure actuelle, la prise en charge reste centrée sur les mesures hygiéno-diététiques et le suivi par le médecin de premier recours ou le spécialiste en fonction du stade d’hépatopathie et des comorbidités.

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