Chapter 3 The health effects of active smoking

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Kalitsis, L|Winnall, WR|Hurley, S|Greenhalgh, EM|Winstanley, MH. 3.5.7 Liver cancer. In Greenhalgh, EM|Scollo, MM|Winstanley, MH [editors]. Tobacco in Australia: Facts and issues. Melbourne : Cancer Council Victoria; 2019. Available from https://www.tobaccoinaustralia.org.au/chapter-3-health-effects/3-5-other-cancers/3-5-7-liver-cancer
Last updated: January 2025

3.5.7 Liver cancer

The liver is an abdominal organ essential for metabolism and detoxification. It has multiple functions including the production of bile for fat digestion, the breakdown of toxic compounds, the regulation and storage of carbohydrates, and the breakdown of aging red blood cells. About 80% of liver cancers are hepatocellular carcinomas, with numerous other types of liver cancer that are less common. Risk factors for liver cancer include cirrhosis from hepatitis infection, alcohol consumption, tobacco use, illicit drug use, unsafe sex, diabetes, and obesity.1

In Australia, liver cancer is considered to be a less common cancer. In 2024, 3,208 people were diagnosed with liver cancer and an estimated 2,595 deaths from the disease.2,3 In Australia, people with liver cancer have a 24% chance of surviving for at least five years, based on data from the period 2016–2020.4 Mortality from liver cancer is relatively high, with it estimated to be the sixth most common cause of cancer death in 2024.5

People with liver cancer experience a range of difficulties, including pain, extreme tiredness, yellow skin (jaundice) and loss of appetite.6

3.5.7.1 Risk associated with smoking

Smoking causes liver cancer.7,8 Results from a meta-analysis from the IARC showed a 51% increased risk of liver cancer for people who currently smoke compared to those who never smoked.9 Similarly, the 2014 US Surgeon General’s report found a 60–70% increased risk of liver cancer among people who currently smoke compared to those who never smoked.8 Australian research has demonstrated that people aged 45 and over have a 4-fold higher risk of liver cancer if they currently smoke, compared to those who have never smoked.10

A large meta-analysis published in 2017 found that compared with people who never smoked, people who currently smoke had 1.55-fold higher odds of hepatocellular carcinoma. Moreover, those who formerly smoked and those who heavily smoke had 1.39 and 1.9-fold higher odds of hepatocellular carcinoma respectively.11

3.5.7.2 How tobacco smoke causes liver cancer

The liver metabolises many circulating carcinogens from tobacco smoke,8 with NNK, other nitrosamines, and furan identified as likely liver carcinogens.12 A number of potential mechanisms have been identified for liver carcinogenesis, including long-term exposure to carcinogens in cigarette smoke increasing the risk of liver cell damage, promoting the development of cancer. Smoking also increases the risk of liver fibrosis, primary biliary cirrhosis, and chronic liver disease, which can progress to liver cancer.8,13

3.5.7.3 Factors affecting risk

Intensity and duration of smoking

A meta-analysis found some evidence of an increase in risk of liver cancer with the number of cigarettes smoked per day, but this effect differed between studies.9

The incidence of liver cancer in Australia has increased almost 4-fold since 1982, despite decreases in smoking rates in this time-period.10 This rise indicates that risk factors other than smoking are making a major contribution to liver cancer.

Alcohol consumption

Alcohol consumption is a risk factor for liver cancer. Since people who smoke are more likely to also consume alcohol, it is difficult to separate the effects of alcohol and smoking on this risk. Some studies have concluded that alcohol and smoking are independent risk factors,14,15 but the potential for an interaction, or synergistic effect of both alcohol and smoking on the risk of liver cancer warrants further research.15

Hepatitis infection

Hepatitis is a cause of cirrhosis and liver cancer. Several studies have investigated the association between smoking, hepatitis, and liver cancer. Among people with hepatitis, smoking is associated with greater levels of cirrhosis, and this association appears to be dose dependent.16,17 Multiple meta-analyses have built on these findings to investigate the effect of smoking on liver cancer among people with hepatitis.18,19 A 2023 meta-analysis found that the combination of hepatitis B and smoking increased the odds of liver cancer by 19.81-fold, and the combination of hepatitis C and smoking increased the odds of liver cancer by 24.86-fold.19 A synergistic effect of hepatitis and smoking on the risk of liver cancer is observed, where the risk of liver cancer from the combination of hepatitis and smoking is greater than the sum of the individual risks.18,19

Smoking cessation

Smoking cessation reduces the risk of liver cancer.20

3.5.7.4 Impact of smoking on prognosis

Smoking adversely affects the prognosis for people diagnosed with liver cancer. A 2015 meta-analysis of 27 studies concluded that people with a history of smoking were more likely to die from liver cancer than people who never smoked.21 A large meta-analysis of 81 studies found that people with hepatocellular carcinoma who currently smoke had a 1.29-fold higher odds of dying from the disease compared to people who never smoked, while people who formerly smoked had a 1.2-fold higher odds of dying.11

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References

1. Australian Institute of Health and Welfare. Cancer in Australia 2019.  Canberra: AIHW. 2019. Available from: https://www.aihw.gov.au/getmedia/8c9fcf52-0055-41a0-96d9-f81b0feb98cf/aihw-can-123.pdf.aspx?inline=true.

2. Australian Institute of Health and Welfare. Cancer data in Australia. Data tables: CDIA 2024: Book 1a – Cancer incidence (age-standardised rates and 5-year age groups) Canberra: AIHW. 2024. Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/data.

3. Australian Institute of Health and Welfare. Cancer data in Australia. Data tables: CDIA 2024: Book 2a – Cancer mortality (age-standardised rates and 5-year age groups) Canberra: AIHW. 2024. Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/data.

4. Australian Institute of Health and Welfare. Cancer data in Australia. Data tables: CDIA 2024: Book 3a – Cancer survival summary (observed, relative and conditional estimates) Canberra: AIHW. 2024. Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/data.

5. Australian Institute of Health and Welfare. Cancer data in Australia.  Canberra: AIHW. 2024. Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia.

6. Cancer Council Australia. Understanding liver cancer, Cancer Council Australia, Editor 2024: Sydney, Australia. Available from: https://www.cancer.org.au/assets/pdf/understanding-liver-cancer-booklet.

7. International Agency for Research on Cancer Working Group on the Evaluation of Carcinogenic Risks to Humans. Tobacco smoke and involuntary smoking.  IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Volume 83.  Lyon: International Agency for Research on Cancer. 2004. Available from: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Tobacco-Smoke-And-Involuntary-Smoking-2004.

8. US Department of Health and Human Services. The health consequences of smoking: 50 years of progress. A report of the Surgeon General.  Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2014. Available from: https://www.ncbi.nlm.nih.gov/books/NBK179276/pdf/Bookshelf_NBK179276.pdf.

9. Lee YC, Cohet C, Yang YC, Stayner L, Hashibe M, et al. Meta-analysis of epidemiologic studies on cigarette smoking and liver cancer. International Journal of Epidemiology, 2009; 38(6):1497-511. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19720726

10. Weber MF, Sarich PEA, Vaneckova P, Wade S, Egger S, et al. Cancer incidence and cancer death in relation to tobacco smoking in a population-based Australian cohort study. International Journal of Cancer, 2021; 149(5):1076-88. Available from: https://www.ncbi.nlm.nih.gov/pubmed/34015143

11. Abdel-Rahman O, Helbling D, Schob O, Eltobgy M, Mohamed H, et al. Cigarette smoking as a risk factor for the development of and mortality from hepatocellular carcinoma: An updated systematic review of 81 epidemiological studies. Journal of Evidence Based Medicine, 2017; 10(4):245-54. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28891275

12. US Department of Health and Human Services. How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease. A report of the US Surgeon General Atlanta, Georgia: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2010. Available from: https://www.ncbi.nlm.nih.gov/books/NBK53017/.

13. Jain D, Chaudhary P, Varshney N, Bin Razzak KS, Verma D, et al. Tobacco smoking and liver cancer risk: Potential avenues for carcinogenesis. Journal of Oncology, 2021; 2021:5905357. Available from: https://www.ncbi.nlm.nih.gov/pubmed/34925509

14. Pelucchi C, Gallus S, Garavello W, Bosetti C, and La Vecchia C. Cancer risk associated with alcohol and tobacco use: focus on upper aero-digestive tract and liver. Alcohol Research and Health, 2006; 29(3):193-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17373408

15. Bui TT, Park E, Kang HY, and Oh JK. Combined effects of smoking and alcohol consumption on the risk of liver cancer according to metabolic syndrome: A nested case-control study in South Korea. International Journal of Cancer, 2024; 155(4):654-65. Available from: https://www.ncbi.nlm.nih.gov/pubmed/38533737

16. Yu MW, Hsu FC, Sheen IS, Chu CM, Lin DY, et al. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. American Journal of Epidemiology, 1997; 145(11):1039-47. Available from: https://www.ncbi.nlm.nih.gov/pubmed/9169913

17. Hezode C, Lonjon I, Roudot-Thoraval F, Mavier JP, Pawlotsky JM, et al. Impact of smoking on histological liver lesions in chronic hepatitis C. Gut, 2003; 52(1):126-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12477773

18. Chuang SC, Lee YC, Hashibe M, Dai M, Zheng T, et al. Interaction between cigarette smoking and hepatitis B and C virus infection on the risk of liver cancer: a meta-analysis. Cancer Epidemiology, Biomarkers and Prevention, 2010; 19(5):1261-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20447919

19. Shadi Y, Heshmati B, and Poorolajal J. Interaction between hepatitis B, hepatitis C and smoking in the development of hepatocellular carcinoma: a systematic review and meta-analysis. Journal of Public Health, 2024; 46(1):51-60. Available from: https://www.ncbi.nlm.nih.gov/pubmed/37934962

20. US Department of Health and Human Services. Smoking cessation. A report of the Surgeon General.  Atlanta, GA U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Centre for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health  2020. Available from: https://www.cdc.gov/tobacco-surgeon-general-reports/reports/2020-smoking-cessation/.

21. Pang Q, Qu K, Zhang J, Xu X, Liu S, et al. Cigarette smoking increases the risk of mortality from liver cancer: A clinical-based cohort and meta-analysis. Journal of Gastroenterology and Hepatology, 2015; 30(10):1450-60. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25967392

Intro
Chapter 2