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The number of new cases and deaths from
liver cancer could rise by >55% by 2040.
Global burden of primary liver cancer in 2020 and predictions to 2040
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Although HBV and HCV infections constitute the most important exogenous risk factors for primary liver cancer, excessive alcohol consumption and the related conditions of metabolic syndrome, type 2 diabetes, obesity, and non-alcoholic fatty liver disease have also become prominent causes of primary liver cancer.[4],[5]
Further exogenous risk factors include cigarette smoking, ingestion of aflatoxin-contaminated food, and liver fluke infestation.[5] Recent studies suggest that approximately 56% of liver cancer is related to HBV and 20% is related to HCV [6] A further 18% of liver cancer burden may be related to tobacco smoking,[7] and an estimated 17% could be attributable to alcohol drinking globally,[8] with the possibility of multiple risk factors being attributed to the same cases or deaths.
An updated evaluation of the global burden of liver cancer incidence and mortality is warranted due to the disparities in burden across populations and the availability of more recent estimates. In this analysis, we describe where liver cancer ranks amongst all cancer types for cancer diagnoses and deaths in nations across the world. We also present predictions of the future liver cancer burden to 2040.
studies in three US states further disaggregated the ethnic groups and found the highest liver cancer incidence rates in California were among Vietnamese, Cambodian and Laotian groups,[30] and the most elevated liver cancer mortality rates in California, Florida, and New York were among Vietnamese, Chinese and Korean groups.[31]
It is estimated that hepatocellular carcinoma makes up 80% of liver cancer diagnoses globally; thus, addressing risk factors for hepatocellular carcinoma in regions with increasing rates would have the biggest impact on liver cancer burden.
[47]
In summary, while the burden of liver cancer varies greatly, it is among the top three causes of cancer death in 46 countries, and among the top five causes of cancer death in 90 countries worldwide. Furthermore, the number of cases and deaths from liver cancer is predicted to increase by more than 50% over the next 20 years if global rates do not change, and will increase unless a 3% or greater annual decrease in rates is achieved. Liver cancer due to some major risk factors is preventable if control efforts are prioritised. While the impact of HBV and HCV elimination efforts is only beginning to be reflected in the burden of liver cancer today, increasing prevalence of other risk factors might drive future changes in liver cancer incidence. Considering these changes, public health officials must prepare for an increase in demand for resources to manage the care of patients with liver cancer throughout the cancer pathway.
Cases, deaths, and ASRs of primary liver cancer are presented by country, by 19 world regions based on UN definitions,[10] and by the UN’s four-tier Human Development Index (HDI) in 2020,[13] the latter being a means to assess the burden, the strength of health systems, and the ability to report primary liver cancer cases and deaths at varying levels of development (low, medium, high and very high HDI).
Risk factors for liver cancer include older age and sex (higher risk among males than females), and there are some differences in risk by ethnicity.[4]
For example, in multi-ethnic populations such as the US, American Indians/Alaskan Natives, Hispanic persons, non-Hispanic Black persons and Asians/Pacific Islanders have higher rates than non-Hispanic White persons.[4]
Although HBV and HCV infections constitute the most important exogenous risk factors for primary liver cancer, excessive alcohol consumption and the related conditions of metabolic syndrome, type 2 diabetes, obesity, and non-alcoholic fatty liver disease have also become prominent causes of primary liver cancer.[4],[5]
Further exogenous risk factors include cigarette smoking, ingestion of aflatoxin-contaminated food, and liver fluke infestation.[5] Recent studies suggest that approximately 56% of liver cancer is related to HBV and 20% is related to HCV [6] A further 18% of liver cancer burden may be related to tobacco smoking,[7] and an estimated 17% could be attributable to alcohol drinking globally,[8] with the possibility of multiple risk factors being attributed to the same cases or deaths.
Another major risk factor for liver cancer is chronic HCV infection which causes approximately 20% of liver cancer cases globally, and more than 50% of liver cancer cases are attributable to HCV in the most affected countries including Egypt, the US, and Pakistan[6] (Fig. S1B). There is no vaccine for HCV, but cure of chronic infection can be achieved with direct-acting antivirals (DAAs), and strategies to reduce HCV transmission can be applied worldwide.[22]
A prospective study of patients with HCV infection and cirrhosis in France observed a 70% reduction in risk of liver cancer incidence after a sustained virologic response, and suggested that DAA therapy will have a substantial effect on liver cancer rates in the future.[23]
This was further supported by a modelling study on patients with chronic HCV in England, which predicted an increase in liver cancer incidence unless there was a 115% increase in the number of eligible patients treated for HCV by 2018, which would have reduced the number of HCV-related liver cancer cases by 50% by 2020.[24]
In response to these trends, in 2016, the World Health Organization (WHO) set a goal of reducing HBV infections by 90% and reducing HBV- and HCV-related deaths by 65% by 2030; universal health coverage, with access to HBV immunisation and affordable DAAs, is essential to achieving this goal.[25],[26]
Predicted number and percentage increase of cases and deaths from liver cancer
The number of new cases of liver cancer is predicted to increase by 55.0% between 2020 and 2040, with 1.4 million new diagnoses forecast for 2040 (Fig. 3). An estimated 1.3 million deaths are predicted to occur in 2040, an increase of 56.4%. By HDI group, the highest absolute increase in cases and deaths could occur in high HDI countries, with 55.7% more cases (306,000 additional cases) and 57.6% more deaths (302,000 additional deaths) per year by 2040, reflecting the already elevated rates in the high HDI group and its large population which is predicted to continue to grow. However, the largest relative increases in cases and deaths are predicted to occur in low HDI countries (99.9% and 101.0% increases, respectively) and medium HDI countries (69.2% and 68.8% increases, respectively), due to the predicted growth and aging of the population.
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