Globally, three in five liver cancer cases may be due to preventable risk factors, and obesity-linked cases of the disease are on the rise, according to findings from The Lancet Commission on hepatocellular carcinoma. The majority of liver cancer cases could be prevented by reducing levels of viral hepatitis, alcohol consumption, and metabolic dysfunction–associated steatotic liver disease (MASLD; previously called nonalcoholic fatty liver disease), reported investigators. The Commission also highlights several ways to reduce these risk factors, including increasing the coverage of the hepatitis B vaccine and public health policies targeting obesity and alcohol consumption. 

Previous analyses have predicted that the number of new liver cancer cases will nearly double from 870,000 in 2022 to 1.52 million in 2050, primarily due to population growth and aging populations, with the largest increases in incidence expected in Africa. The number of deaths from liver cancer are predicted to grow from 760,000 in 2022 to 1.37 million in 2050. Globally, liver cancer is already the sixth most common cancer and the third leading cause of death from cancer. More than 40% of global liver cancer cases occur in China, mostly due to relatively high rates of hepatitis B infections in the country.  

Chair of the Commission Jian Zhou, MD, PhD, of Fudan University in Shanghai, said, “Liver cancer is a growing health issue around the world. It is one of the most challenging cancers to treat, with 5-year survival rates ranging from approximately 5% to 30%. We risk seeing close to a doubling of cases and deaths from liver cancer over the next quarter of a century without urgent action to reverse this trend.” 

First author Stephen Lam Chan, MD, of the Chinese University of Hong Kong, added, “As three in five cases of liver cancer are linked to preventable risk factors, mostly viral hepatitis, alcohol [use], and obesity, there is a huge opportunity for countries to target these risk factors, prevent cases of liver cancer, and save lives.” 

Changes in the Causes of Liver Cancer 

In a novel analysis, the Commission estimated that at least 60% of liver cancers are preventable via control of modifiable risk factors, including hepatitis B virus (HBV), hepatitis C virus (HCV), MASLD, and alcohol use.  

Approximately one-third of the global population are estimated to have MASLD. However, only 20% to 30% of patients with MASLD develop the more severe form of the condition with liver inflammation and damage, called metabolic dysfunction–associated steatohepatitis (MASH).

MASH is the fastest-growing cause of liver cancer globally, followed by alcohol use. The Commission projects that the proportion of liver cancer cases associated with MASH are projected to increase from 8% in 2022 to 11% in 2050, and liver cancer cases associated with alcohol are projected to increase from 19% in 2022 to 21% in 2050 

In contrast, the proportion of liver cancer cases linked to HBV is expected to decrease from 39% in 2022 to 37% in 2050, while HCV-related cases are projected to drop from 29% to 26% over the same period.

Additionally, the rate of MASLD-linked liver cancer is expected to rise over the next decade, particularly in the United States, Europe, and Asia, due to increasing rates of obesity. In the United States, MASLD prevalence continues to climb in parallel with the obesity epidemic; by 2040, over 55% of U.S. adults could have MASLD, the authors estimated.

Commission author Hashem B. El-Serag, MD, MPH, of Baylor College of Medicine, commented, “Liver cancer was once thought to occur mainly in patients with viral hepatitis or alcohol-related liver disease. However, today, rising rates of obesity are an increasing risk factor for liver cancer, primarily due to the increase in cases of excess fat around the liver.” 

“One approach to identify patients at high risk of liver cancer would be to introduce screening for liver damage into routine health-care practice for patients at high risk of MASLD, such as individuals living with obesity, diabetes, and cardiovascular disease,” he continued. “Health-care professionals should also integrate lifestyle counseling into routine care to support patients to transition to a healthy diet and regular physical activity. Furthermore, policymakers must promote healthy food environments via policies such as sugar taxes and clear labeling on products with high fat, salt, and/or sugar.”

Global Targets and Recommendations 

The Commission estimates that if countries can reduce the incidence of liver cancer cases by 2% to 5% each year by 2050, it could prevent 9 to 17 million new cases of liver cancer and save 8 to 15 million lives. 

As more patients live with liver cancer than ever before, in addition to prevention efforts, there is an urgent need for increased research and attention for these patients to improve their quality of life.  

The Commission suggested several strategies for reducing the global burden of liver cancer, including:

• Governments should intensify efforts to increase HBV vaccination—such as vaccine mandates in high-prevalence countries—and implement universal HBV screening for adults aged 18 years and older, alongside targeted HCV screening in high-risk areas based on cost-effectiveness.
• Policymakers should enact minimum alcohol unit pricing, warning labels, and advertisement restrictions for alcoholic beverages.
• National health authorities and cancer control programs should prioritize investments in public awareness campaigns and deployment of early detection resources.
• Professional organizations and the pharmaceutical industry should work together to reduce differences between Eastern and Western regions of the world in the clinical management of liver cancer.
• Hospitals and professional organizations should provide palliative care training, with the aim of integrating palliative care in the early phases for patients in need.

Commission author Valérie Paradis, MD, PhD, of Beaujon Hospital, France, concluded, “There is an urgent need to raise awareness within society about the severity of the growing health issue of rising liver cancer cases. Compared with other cancers, liver cancer is very hard to treat but has more distinct risk factors, which help define specific prevention strategies. With joint and continuous efforts, we believe many liver cancer cases can be prevented and both the survival and quality of patients with liver cancer will be considerably improved.” 

Disclosure: This Commission was supported by grants from the Natural Science Foundation of China, Noncommunicable Chronic Diseases-National Science and Technology Major Project, and Shanghai Municipal Science and Technology Major Project. For full disclosures of the study authors, visit thelancet.com.