Non-alcoholic fatty liver disease, NAFLD, is associated with several health risks. According to a new registry study led by researchers at Karolinska Institutet in Sweden, NAFLD is linked to a 17-fold increased risk of liver cancer. The findings, published in Hepatology, underscore the need for improved follow-up of NAFLD patients with the goal of reducing the risk of cancer.

“In this study with detailed liver histology data, we were able to quantify the increased risk of cancer associated with NAFLD, particularly hepatocellular carcinoma,” says first author, Tracey G. Simon, researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and hepatologist at Massachusetts General Hospital and Harvard Medical School. “We also found that all stages of NAFLD were associated with excess cancer risk, even early stages of the disease.”

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Europe and the United States, affecting more than 100 million adults. A large proportion of patients progress to nonalcoholic steatohepatitis (NASH) with fibrosis, which in turn can lead to cirrhosis.

There is relatively little research on cancer development with NAFLD, and prior research has some limitations that make it difficult to draw far-reaching conclusions. Hence, there is a need for more information on links between cancer risk and NAFLD, and for improved monitoring strategies for high-risk patients with NAFLD.

17-fold increased risk of liver cancer

In this study, researchers at Karolinska Institutet, in collaboration with researchers at Harvard University and Columbia University, examined the risk of cancer in people with NAFLD. The registry study included 8,892 Swedish patients with biopsy-confirmed NAFLD and 39,907 healthy controls.

Data on cancer were retrieved through the nationwide Swedish Cancer Register. Patients with NAFLD were identified through the ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden) cohort.

Individuals with NAFLD were at a 27% increased risk of any cancer. This risk was to a large extent driven by the 17-fold increased risk of hepatocellular carcinoma (HCC). Furthermore, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma, but no other cancers.  

More targeted intervention

“These findings should be used to develop more targeted interventions designed to reduce cancer risk in patients with NAFLD,” says corresponding author Jonas F. Ludvigsson, pediatrician at Örebro University Hospital and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “They also highlight the need for more personalized strategies to screen for HCC in certain high-risk patients, such as those with NAFLD fibrosis and type 2 diabetes.”

This project was supported by grants from NIH, Harvard University, Region Stockholm, Crohn’s and Colitis Foundation and Karolinska Institutet.

Jonas F. Ludvigsson coordinates a study on behalf of the Swedish IBD quality register (SWIBREG). That study has received funding from the Janssen corporation. Tracy G. Simon has previously served as a consultant to Aetion, for work unrelated to this project. Hannes Hagström's department has received research grants from AstraZeneca, Intercept and Gilead, and he has been an advisory board member of Bristol Myers Squibb and Gilead.