NAFLD and MAFLD as emerging causes of HCC: A populational study

Abstract

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.

Impact of MAFLD on HBV-Related Stage 0/A Hepatocellular Carcinoma after Curative Resection

“…Therefore, this unsynergistic result was unexpected. In fact, assessment of a large population cohort over 25 years revealed an increasing number of patients with HCC develop liver metabolic disorders, including NAFLD or MAFLD [ 29 ], and these diseases are emerging as new precancerous conditions in addition to the traditional well-characterized risk factor, viral-induced cirrhosis. Theoretically, we assumed patients with HBV-MAFLD-HCC would have poorer RFS and OS due to the ‘double-risk’ condition.…”

Trends in indications and outcomes of liver transplantation in Canada: A multicenter retrospective study

“…According to different indicators in the United States, this is expected to increase in the years to come [31]. In addition, as a result of the obesity epidemic, HCC associated with nonalcoholic fatty liver disease and NASH will likely contribute to this increase [32–34]. The proportion of patients transplanted for ALD in Canada remained relatively stable at approximately 15%.…”

MAFLD-Epidemiology, Natural History, Outcomes and Prevention

“…According to a recent cohort study, the incidence of diabetic patients requiring liver transplant for decompensated cirrhosis due to NAFLD was 305/100,000 person years [54]. Contrary to the common belief that HCC is not very common in fatty liver disease, recent data reported a surge in the burden of HCC secondary to MAFLD [55]. HCC essentially contributes to death as demonstrated by a substantial rise in HCC-related mortality rate for NAFLD (19.1%) [56].…”