How to prevent 3 in 5 liver cancer cases worldwide

Liver cancer affects one of the body's largest and most vital organs. Primary liver cancer, which originates in the liver itself, is categorized into several types based on the cells from which the cancer develops. The most prevalent form is hepatocellular carcinoma (HCC), which begins in the main liver cells called hepatocytes and accounts for about 75% of all liver cancers. Another significant type is intrahepatic cholangiocarcinoma (iCCA, ~10 to 15%), which forms in the bile ducts that carry bile from the liver. Rarer forms of primary liver cancer include angiosarcoma, which starts in the liver's blood vessels, and hepatoblastoma, a type that primarily affects children.

Globally, liver cancer is a major cause of cancer-related death (third among all cancers). The prognosis is often poor as the cancer is frequently diagnosed at an advanced stage. The American Cancer Society estimates that for 2025 in the United States, approximately 42,240 new cases of primary liver cancer and bile duct cancer will be diagnosed, leading to an estimated 30,090 deaths. Worldwide, the incidence and death rates from liver cancer have been on an upward trend over the past few decades. They are highest in parts of East Asia and sub-Saharan Africa, reflecting differences in hepatitis B and C prevalence, alcohol use, metabolic disease, and access to vaccination, antiviral therapy, and surveillance programs.

Symptoms of liver cancer often do not appear until later stages and can include abdominal pain or a lump in the upper right side, unexplained weight loss, loss of appetite, a feeling of fullness, weakness, nausea, jaundice (yellowing of the skin and eyes), and swelling in the abdomen or legs. Diagnosis begins with a physical exam and blood tests to check liver function and levels of the tumor marker alpha-fetoprotein (AFP). If these results are abnormal, doctors will use imaging tests such as an ultrasound, CT scan, or MRI to visualize the liver and identify any tumors. In many cases, the appearance of a tumor on these scans is sufficient for a diagnosis, but sometimes a liver biopsy is performed for a definitive confirmation.

The treatment and prognosis for liver cancer depend heavily on the stage at diagnosis and the patient's overall liver health. For localized cancer confined to the liver, treatments include surgical options like tumor removal (hepatectomy) or a full liver transplant, as well as less invasive procedures like ablation (using heat or cold to destroy tumors), embolization (blocking the tumor's blood supply), and targeted radiation therapy. For advanced cancer that has spread, systemic treatments such as targeted therapy and immunotherapy are used to control the disease. The prognosis is often challenging due to late-stage diagnosis; the 5-year relative survival rate is about 37.6% for localized cancer, but drops to 13.2% if it has spread regionally, and 3.5% for distant metastasis. However, outcomes can be significantly better for patients eligible for early-stage interventions like surgery or a transplant.

Liver cancer is primarily caused by chronic liver damage, most often stemming from long-term hepatitis B (HBV) or hepatitis C (HCV) infections, heavy alcohol consumption, and nonalcoholic fatty liver disease (MASLD caused by fat build up in liver) linked to obesity and diabetes, all of which can lead to cirrhosis (liver scarring). Consequently, prevention is centered on mitigating these risks. Key strategies include receiving the hepatitis B vaccine, seeking antiviral treatment for hepatitis C, limiting alcohol intake, and maintaining a healthy weight through diet and exercise to prevent MAFLD. For individuals with established high-risk conditions like cirrhosis, regular cancer surveillance through ultrasound can aid in early detection and improve outcomes.

With this backdrop, one can ask what are the practical preventive public health measures that would reduce the worldwide toll from liver cancer. A recent Lancet Commission review addresses this question, but first raises the alarm by projecting new HCC cases to nearly double from ~0.87M (2022) to ~1.52M (2050) with deaths increasing from ~0.76M to ~1.37M driven by aging and population growth. The review also notes that >40% of global cases are in China (largely HBV-driven), and that there are wide survival disparities (5-year survival often ~5–30%), but overall the survival numbers are not terribly encouraging, underscoring the importance of prevention and early detection.

The article predicts some shift in the causes of liver cancer, but hepatitis will remain the dominant etiological agent (Figure 1). The MASH (more advanced stage of MASLD) share of HCC is projected to grow from ~8% (2022) to ~11% (2050), and alcohol-attributable HCC is expected to increase from ~19% to ~21% by 2050. Meanwhile, HBV/HCV proportions will decline modestly (HBV ~39% to 37%, HCV ~29% to 26%) thanks to vaccination and treatment scale-up.

Thus, the primary prevention strategy is universal HBV vaccination and HCV testing with curative treatment access (there is no HCV vaccine). In addition, alcohol minimum unit pricing, curbs on marketing, and obesity/MASLD policies (sugar taxes, front-of-pack labels) would be implemented. Secondary measures would focus on early detection with risk-stratified surveillance of cirrhosis/MASLD populations, non-invasive fibrosis tests, and improved referral pathways.

Focusing on China for a moment, because of viral hepatitis dominance, eliminating HBV and HCV could avert the majority of liver cancer deaths. Modeling estimates HBV elimination prevents ~66% (57–74%) and HCV elimination prevents ~28% (25–32%) of liver cancer deaths, respectively. Thus, one can envision the following comprehensive control scenario: Combining HBV vaccination + HBV treatment scale-up, HCV testing/treatment, and lifestyle risk reduction (alcohol, metabolic risk/obesity) would yield >80% of liver cancer deaths prevented in China by 2050 in the most ambitious scenario. These numbers would roughly translate from China to the worldwide liver cancer statistics.

The Lancet review proposes that three in five (60%) liver cancer (HCC) cases are preventable by targeting modifiable risks -- viral hepatitis (HBV/HCV), alcohol use, and metabolic dysfunction–associated steatotic liver disease (MASLD/MASH). More realistically, the Commission sets a global target of 2–5% annual reductions in incidence through integrated prevention and early detection. Meeting the Commission’s 2–5% yearly reduction goal could prevent up to ~17M new cases and up to ~15M deaths by 2050.

In summary, the combination of vaccination, screening, pricing/tax policies, lifestyle interventions, and earlier detection could substantially bend the mortality curve for a cancer that is otherwise difficult to treat once advanced.

Figure 1. Projections of hepatocellular carcinoma (HCC) liver cancer case distribution by etiology for 2022, 2035, and 2050. Hepatitis B and C fractions will decline slightly from 2022 to 2050 but remain the dominant cause. Data from Global Burden of Disease and World Population Prospects. HBV=hepatitis B virus. HCV=hepatitis C virus. MASH=metabolic dysfunction-associated steatohepatitis (fatty liver disease). Reproduced from Fig. 4 of Chan et al. Lancet, 2025.