What Can the US and Japan Learn From Each Other on Liver Cancer Prevention?

As the leading causes of hepatocellular carcinoma (HCC) shift from viral hepatitis to metabolic dysfunction, clinicians in Japan and the US face the challenge of preventing liver cancer in a far larger and more heterogeneous population.

At The Liver Meeting® 2026, CancerNetwork® spoke with Ryosuke Tateishi, MD, PhD, FAASLD, of The University of Tokyo, about his presentation on physical and dietary interventions to prevent liver cancer from metabolic causes in Japan, part of a joint session of the American Association for the Study of Liver Diseases (AASLD) and the Japan Society of Hepatology (JSH).

Tateishi began by outlining the causal chain from an unhealthy lifestyle to metabolic dysfunction–associated steatotic liver disease (MASLD) and HCC and explained why evidence linking lifestyle changes to cancer prevention remains limited. He then discussed why surveillance should currently focus on patients with cirrhosis and what the US and Japan can learn from each other. He also described the role of the multidisciplinary team in prevention and the emerging drugs that may address multiple obesity-related disorders at once.

CancerNetwork: Your talk at The Liver Meeting covered physical and dietary interventions to prevent liver cancer from metabolic causes in Japan. What does the evidence show so far, and which lifestyle changes are most strongly linked to lower liver cancer rates?

Tateishi: As you may know, the causes of liver cancer are shifting worldwide from viral hepatitis to metabolic dysfunction–related diseases. Before answering, it is important to understand the causal chain. An unhealthy lifestyle leads to obesity or overweight, which causes insulin resistance, which may cause steatotic liver disease. MASLD may then progress to MASH [metabolic dysfunction–associated steatohepatitis], MASH may progress to liver cirrhosis, and then cancer develops. There is a long distance from the cause to the final outcome of liver cancer. With viral hepatitis, on the other hand, the effect on liver cancer is quite clear. We have worked to eliminate viral hepatitis over the past 2 or 3 decades, and in Japan we have almost eliminated hepatitis C. Now we are facing a new era of MASLD.

The evidence linking lifestyle intervention to liver cancer prevention is very limited, so we need to collect evidence for each step. For example, lifestyle intervention may decrease body weight, which may improve steatotic liver disease. Once you observe improvement in steatotic liver disease or MASH, you may expect fibrosis regression, according to some clinical trials using drugs or bariatric surgery. Once fibrosis regresses, there may be a chance of decreased liver cancer risk. However, this last piece has only been proven by evidence from viral hepatitis, so we extrapolate our previous experience and knowledge to the new era of MASLD.

Many patients with MASLD-related HCC do not have cirrhosis, so they often fall outside standard surveillance protocols. How should clinicians decide which of these patients need screening?

As we learned from viral hepatitis, we need to extrapolate some of our experience to the new era of MASLD-related HCC. First, I agree that approximately 50% of patients with MASLD-related HCC do not have cirrhosis.¹ However, among patients with MASLD who do not have cirrhosis, the proportion who develop HCC is extremely small, so it is not a good idea to build a surveillance program for those without cirrhosis at this moment. We need other biomarkers or tests to narrow down the high-risk population without cirrhosis, but we do not yet have such a tool. For now, we need to focus on patients with cirrhosis in the MASLD population.

Your session compares liver cancer prevention in Japan and the US, 2 fairly distinct patient populations. What could US practice learn from Japan’s approach to surveillance and early detection, and what could Japan learn from the US?

Regarding hepatitis C, the spread of the virus in Japan was perhaps 20 to 30 years ahead of that in the US, so the US may learn from Japan. Regarding obesity and obesity-related disorders, however, the US is a great teacher for us, and we need to learn from it.

When you look at the prevalence of MASLD according to body weight or body mass index, Asians are more susceptible to fatty liver disease than people of European ancestry, so we may need a somewhat different approach to lifestyle intervention to reduce cancer risk. However, the mechanism linking overeating or a sedentary lifestyle to cancer development is quite similar in the US and Japan, so we may extrapolate evidence from the US to Japan, or from Japan to the US.

Patients who exercise and eat well may tolerate treatment better and have better outcomes. How should dietitians, exercise specialists, and other supportive care staff fit into the multidisciplinary team, both for prevention and after a diagnosis?

MASLD is part of metabolic dysfunction, or metabolic syndrome, so reducing body weight may reduce liver cancer risk as well as the risk of cardiovascular disease and even renal dysfunction related to diabetes. In the prevention of liver cancer in patients with MASLD, a multidisciplinary team is much preferred, and we also need to look at the risk of cardiovascular disease and other comorbidities related to obesity and lifestyle disorders.

Looking at this meeting as a whole, what new data or themes in liver cancer prevention, detection, or treatment should multidisciplinary oncology teams watch most closely over the next year?

We are still far from the final goal in preventing liver cancer related to unhealthy lifestyles. However, evidence is accumulating that some drugs may reduce both liver disease and cardiovascular disease, and that 1 drug may simultaneously reduce many types of disorders related to obesity. Eventually, we may find that this kind of intervention also reduces liver cancer.

Reference

Mi K, Ye T, Zhu L, Pan CQ. Risk-stratified hepatocellular carcinoma surveillance in non-cirrhotic patients with MASLD. Gastroenterol Rep (Oxf). 2025;13:goaf018. doi:10.1093/gastro/goaf018