Abstract
Hepatocellular carcinoma (HCC) is on the rise globally, causing more than 800 thousand deaths annually, with an estimated annual percent change of 0.51 for causes other than viral hepatitis, including nonalcoholic fatty liver disease (NAFLD). The incidence of NAFLD-related HCC is peaking in several Far East regions (6-12% vs. 2-3% in Western Europe and USA), HCC risk being mainly driven by the epidemic of obesity and diabetes, both favored by an unhealthy diet and sedentary lifestyle. Under inherited susceptibility outlined by such genetic markers as variants in PNPLA3, TM6SF2 and MBOAT7, neoplastic transformation of NAFLD is driven by sublethal lipotoxicity consequent to hepatocyte lipid overload, whereas a myriad of factors spanning from subverted circadian homeostasis and gut dysbiosis to alcohol abuse and tobacco may interact as risk modifiers. At variance with viral HCC, NAFLD-HCC shows a frequent association with cardiovascular co-morbidities, absence of cirrhosis in up to half of patients and an association with persistently normal transaminase values. All these misleading features of NAFLD-related HCC account for the low uptake of surveillance and linkage to curative treatments that has been reported in patients with this cancer, a downside that could be attenuated when scores for cost-effective risk stratification become available.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a large spectrum of abnormalities resulting from hepatic fat deposition, most frequently caused by overnutrition and sedentary lifestyle
The large fraction of hepatocellular carcinoma (HCC) arising in patients without cirrhosis affects the interpretation of data provided by the retrospective calculation of HCC incidence in NAFLD patient subgroups, that were likely to be biased by the heterogeneous source of data and modalities of diagnosis and accurate staging of NAFLD/non-alcoholic steatohepatitis (NASH), and the lack of a structured surveillance program in some reports under scrutiny
Owing to the strict correlation that exists between NAFLD and HCC, the current strategies aimed at reducing mortality from liver cancer are affected in parallel
Summary
Non-alcoholic fatty liver disease (NAFLD) is a large spectrum of abnormalities resulting from hepatic fat deposition, most frequently caused by overnutrition and sedentary lifestyle. This condition affects about a quarter of the world’s adult population, thereby posing a major health and economic burden to all societies [1]. Liver complications of NAFLD tend to evolve slowly and silently in a majority of individuals, including patients with persistently normal transaminase levels and those with a nonfibrotic liver. This both impairs the development of screening pro-. Liver trajectory of NAFLD with respect to the evolution towards cardiovascular complications [6,7]
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