Non-Alcoholic Fatty Liver Disease and Extrahepatic Cancers: A Wolf in Sheep's Clothing?

Abstract

Non-alcoholic fatty liver disease (NAFLD) is now considered the main driver and leading cause of chronic liver disease globally. The umbrella term NAFLD describes a range of liver conditions closely related to insulin resistance, metabolic syndrome, diabetes mellitus, obesity, and dyslipidemia. At the same time, several malignancies, including hepatocellular carcinoma and colorectal cancer, are considered to be common causes of death among patients with NAFLD. At first, our review herein aims to investigate the role of NAFLD in developing colorectal neoplasms and adenomatous polyps based on the current literature. We will also explore the connection and the missing links between NAFLD and extrahepatic cancers. Interestingly, any relationship between NAFLD and extrahepatic malignancies could be attributable to several shared metabolic risk factors. Overall, obesity, insulin resistance, metabolic syndrome, and related disorders may increase the risk of developing cancer. Therefore, early diagnosis of NAFLD is essential for preventing the progression of the disease and avoiding its severe complications. In addition, cancer screening and early detection in these patients may improve survival and reduce any delays in treatment.

Keywords: colorectal adenomas; colorectal cancer; extrahepatic cancers; insulin resistance; metabolic syndrome; non-alcoholic fatty liver disease.

Figure 1

In a bid to raise awareness of the disease, a multidisciplinary group of experts recommended changing the definition and nomenclature of NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD is diagnosed in patients with steatosis and at least one of the three criteria: obesity/overweight, type 2 diabetes mellitus and any evidence of metabolic dysregulation. NAFLD—non-alcoholic fatty liver disease; MAFLD—metabolic dysfunction-associated fatty liver disease.

Figure 2

Non-alcoholic fatty liver: There is fat accumulation within hepatocytes at this stage, a process known as hepatic steatosis. Non-alcoholic steatohepatitis: The accumulation of fat in the hepatocytes is accompanied by liver inflammation and hepatocellular ballooning. Fibrosis: Fibrotic scar tissue starts to form in an inflamed liver. According to the NASH Clinical Research Network (CRN) scoring system, fibrosis staging includes stage 0 (no fibrosis), stage 1A (mild perisinusoidal fibrosis), stage 1B (moderate perisinusoidal fibrosis), stage 1C (portal/periportal fibrosis), stage 2 (perisinusoidal and portal/periportal fibrosis), stage 3 (bridging fibrosis), and stage 4 (cirrhosis). Cirrhosis: End-stage liver disease, in which the formation of fibrotic septa bridges together adjacent portal tracts and central veins. There is an increased risk of hepatocellular carcinoma development. NASH—non-alcoholic steatohepatitis; CRN—Clinical Research Network.

Figure 3

NAFLD is a multisystem disease leading to severe liver-related and extrahepatic complications. NAFLD—non-alcoholic fatty liver disease.

Figure 4

The association between NAFLD and the risk of developing other extrahepatic malignancies besides colorectal cancer remains a subject of ongoing research. Recent studies suggest that NAFLD and metabolic syndrome might be closely related to an increased cancer risk. NAFLD—non-alcoholic fatty liver disease.