Nonalcoholic fatty liver disease is specifically related to the risk of hepatocellular cancer but not extrahepatic malignancies

Abstract

ObjectiveWe performed a matched cohort study among individuals with and without nonalcoholic fatty liver disease (NAFLD) to determine: 1) the incidence of cancers (extrahepatic and liver) and their spectrum and 2) if NAFLD increases the risk of extrahepatic cancers.MethodsThe NAFLD and non-NAFLD (control) cohorts were identified from electronic medical records via International Classification of Diseases (ICD) codes from a single center and followed from 2010 to 2019. Cohorts were matched 1:2 for age, sex, race, body mass index (BMI), and type 2 diabetes.ResultsA total of 1,412 subjects were included in the analyses. There were 477 individuals with NAFLD and 935 controls (median age, 52 years; women, 54%; white vs. black: 59% vs. 38%; median BMI, 30.4 kg/m2; type 2 diabetes, 34%). The cancer incidence (per 100,000 person-years) was 535 vs. 1,513 (NAFLD vs. control). Liver cancer incidence (per 100,000 person-years) was 89 in the NAFLD group vs. 0 in the control group, whereas the incidence of malignancy was higher across other types of cancer in the control group vs. in the NAFLD group.ConclusionsThe overall extrahepatic cancer risk in NAFLD is not increased above and beyond the risk from background risk factors such as age, race, sex, BMI, and type 2 diabetes.

Australians with metabolic dysfunction‐associated steatotic liver disease have a twofold increase in the incidence of cancer

“…Among participants in the UK Biobank (2006–2019), individuals at high risk for MASLD had a 1.23‐fold increased risk of non‐liver gastrointestinal cancers compared with individuals at low risk for MASLD 3 . In contrast, a smaller matched cohort study from a single US center (1412 subjects, 34% with MASLD) did not show an increased risk for EHC after matching major risk factors including age, sex, race, BMI, and diabetes status 4 . As MASLD is a multisystem disorder, it remains difficult to investigate its contribution to EHC independently of obesity and metabolic dysfunction 12 …”

“…3 In contrast, a smaller matched cohort study from a single US center (1412 subjects, 34% with MASLD) did not show an increased risk for EHC after matching major risk factors including age, sex, race, BMI, and diabetes status. 4 As MASLD is a multisystem disorder, it remains difficult to investigate its contribution to EHC independently of obesity and metabolic dysfunction. 12 In our study, the ASI of cancer (all cancers) was not influenced by the presence of T2D at index admission.…”

“…Although the association of metabolic dysfunction‐associated steatotic liver disease (MASLD) with primary liver cancer is well established, extrahepatic cancer (EHC) is far more common. It is the second leading cause of death in people with MASLD (after cardiovascular disease), 1 and some, 2 , 3 but not all studies, 4 report a higher risk (or incidence) of EHC in this patient population. In a meta‐analysis including over 180 000 individuals (one‐quarter with MASLD, mostly from Asian countries), MASLD was associated with a 1.5‐ to 2‐fold increased risk of developing gastrointestinal cancers (e.g.…”

Diabetes mellitus and the progression of non‐alcoholic fatty liver disease to decompensated cirrhosis: a retrospective cohort study

“…Despite the risk of progressive liver disease, the leading causes of death for people with NAFLD are cardiovascular disease and extrahepatic malignancy. Several 18 but not all 19 studies have reported risks of major adverse cardiovascular events and extrahepatic cancers, particularly colorectal cancer, in people with NAFLD, but these associations may be confounded by shared metabolic dysfunction related to obesity and diabetes mellitus driving systemic inflammation and changes in the gut microbiota and secondary bile acid levels 20 . Nevertheless, our finding of relationships between several medical conditions and the risk of NAFLD progression to decompensation indicates the multisystem nature of metabolic dysregulation and the need for a holistic approach to management.…”

Immunotherapy for NAFLD and NAFLD-related hepatocellular carcinoma

“…It involves a spectrum of diseases, including hepatic steatosis and non-alcoholic steatohepatitis (NASH) (2). NAFLD may lead to lifethreatening hepatic diseases, such as liver cirrhosis and hepatocellular carcinoma (HCC), and extrahepatic diseases, such as cardiovascular disease and dementia (3)(4)(5)(6). Along with advances in retrospective operational definitions, such as fatty liver index and Korea National Health and Nutrition Examination Survey-NAFLD score, and non-invasive diagnostic approaches for NAFLD, prevention, management, and treatment of NAFLD are being actively investigated (7)(8)(9).…”