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A global view of hepatocellular carcinoma: trends, risk, prevention and management

Abstract

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C, alcohol addiction, metabolic liver disease (particularly nonalcoholic fatty liver disease) and exposure to dietary toxins such as aflatoxins and aristolochic acid. All these risk factors are potentially preventable, highlighting the considerable potential of risk prevention for decreasing the global burden of HCC. HCC surveillance and early detection increase the chance of potentially curative treatment; however, HCC surveillance is substantially underutilized, even in countries with sufficient medical resources. Early-stage HCC can be treated curatively by local ablation, surgical resection or liver transplantation. Treatment selection depends on tumour characteristics, the severity of underlying liver dysfunction, age, other medical comorbidities, and available medical resources and local expertise. Catheter-based locoregional treatment is used in patients with intermediate-stage cancer. Kinase and immune checkpoint inhibitors have been shown to be effective treatment options in patients with advanced-stage HCC. Together, rational deployment of prevention, attainment of global goals for viral hepatitis eradication, and improvements in HCC surveillance and therapy hold promise for achieving a substantial reduction in the worldwide HCC burden within the next few decades.

Key points

  • Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide; >80% of HCC cases occur in low-resource and middle-resource countries, particularly in Eastern Asia and sub-Saharan Africa, where medical and social care resources are often constrained.

  • Prevention and treatment of viral hepatitis and mitigation of exposure to aflatoxin and aristolochic acid, the main risk factors in high-incidence regions, are critical for decreasing the global burden of HCC.

  • HCC surveillance enables early detection and increases the chance of potentially curative treatment; therefore, broad implementation of HCC surveillance in high-risk patients is essential to reduce the high mortality from HCC.

  • Early-stage HCC is amenable to potentially curative treatment, which includes local ablation, surgical resection and liver transplantation.

  • Catheter-based locoregional treatment is indicated in patients with intermediate-stage disease; kinase and immune checkpoint inhibitors have been shown to be effective treatment options in patients with advanced-stage HCC.

  • Global reduction of HCC burden can be achieved by universal HBV vaccination, control of chronic viral hepatitis, avoiding environmental and lifestyle risk factors, and improving early detection and management.

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Fig. 1: Global disease burden of primary liver cancer.
Fig. 2: Global variation in the overall survival of patients with HCC.
Fig. 3: Strategy for HCC treatment in countries with different resource levels.

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Acknowledgements

The authors are supported by grant numbers T32 DK07198 from the National Institute of Diabetes and Digestive and Kidney Diseases (J.D.Y.), CA165076, CA186566, CA 221205 and CA 210964 from the National Cancer Institute (L.R.R.) and the French National Research Agency ‘Investissements d’avenir’ program (ANR-15-IDEX-02) (P.H.). The contents of this Review are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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Glossary

Years of life lost

An estimate of the average years a person would have lived if he or she had not died prematurely.

Age-standardized incidence rate

(ASIR). The incidence rate after accounting for the differences in the age structure of the populations.

Sociodemographic index

A summary measure of geographical sociodemographic development, determined based on average income per person, educational attainment and total fertility rate.

Surveillance, Epidemiology, and End Results (SEER)

A National Cancer Institute programme that provides information on the incidence of cancer and survival from cancer in the USA.

Adjusted odds ratio (AOR)

The ratio of the odds of the presence of an antecedent in those with a positive outcome to the odds in those with a negative outcome after adjusting for other factors that can affect the outcome.

Population-attributable fraction

The proportion of incidents in the population that are attributable to the risk factor.

Relative risk

The ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group.

Absolute risk

The risk of developing the outcome of interest.

Direct-acting antiviral (DAA)

A new class of medication that acts directly to target specific steps in the HCV life-cycle.

Sustained virologic response (SVR)

An undetectable viral titre at least 12 weeks after completing treatment.

Primary prevention

Preventive interventions that are applied before there is any evidence of disease or injury.

Hepatitis B immunoglobulin

A human immunoglobulin that is used to prevent the transmission of HBV infection.

Enterosorbents

An adsorbent for binding toxic substances in the gastrointestinal tract.

Secondary prevention

Preventive interventions that try to detect a disease early and prevent it from getting worse.

Child–Pugh score

A classification system for the severity of cirrhosis.

Up-to-seven criterion

The sum of the largest tumour size in centimetres and the number of tumours ≤7.

Eastern Cooperative Oncology Group performance status

A performance status score used to assess the ability of a patient to tolerate cancer treatment.

MELD

A scoring system for assessing the severity of chronic liver disease which is now used by the United Network for Organ Sharing and Eurotransplant for prioritizing allocation of liver transplants.

Embolization

A treatment that blocks blood vessels to prevent blood flow to the tumour.

Heat sink effect

The cooling effect of blood flow leading to incomplete thermal ablation of liver tumours near large blood vessels.

Bridge therapy

Hepatocellular carcinoma treatment during the waiting time prior to transplantation to prevent tumour progression.

Lobar ablation

Delivery of high-dose radiation to one lobe of the liver, causing hypotrophy of the treated lobe of the liver.

Brachytherapy

A form of radiotherapy where a sealed radiation source is placed inside or next to the area requiring treatment.

Stereotactic body radiation therapy

A focused radiation treatment using several beams of various intensities aimed at different angles to precisely target the tumour.

Objective response rate

The proportion of patients with a reduction in tumour burden of a predefined amount.

Immune checkpoint inhibitors

A form of immunotherapy that works by releasing a natural brake on the immune system so that T cells can recognize and attack tumours.

Sustainable Development Goals

A collection of 17 global goals set by the United Nations General Assembly in 2015 for the year 2030 to end poverty, protect the planet and ensure that all people enjoy peace and prosperity.

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Yang, J.D., Hainaut, P., Gores, G.J. et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 16, 589–604 (2019). https://doi.org/10.1038/s41575-019-0186-y

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