Smoking reduces survival after liver cancer diagnosis for people with viral hepatitis

People with viral hepatitis who smoked were three times more likely to die after being diagnosed with liver cancer (hepatocellular carcinoma, HCC), according to a study of Swiss patients published in Liver International.

Whereas non-smokers lived for a median of 3.2 years after diagnosis, smokers died after a median of 18 months. Smoking had a similar impact on survival in those who did not receive curative treatment in the form of liver resection (surgery), liver transplantation or ablation (use of heat to destroy tumours in the liver).

Smoking has been found to increase the risk of developing liver cancer in some, but not all studies, and to increase the risk of liver cancer in some studies of people with viral hepatitis.

Glossary

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

fibrosis

Scarring of the liver – the development of hard, fibrous tissue. See also ‘cirrhosis’, which is more severe scarring.

compliance

An alternative term for ‘adherence’.

Child-Pugh score

A classification system used to measure liver function, especially in people with chronic liver disease. The score includes 5 clinical measures of liver disease, including ascites, encephalopathy, serum bilirubin level, serum albumin level, and prothrombin time.

To look at the effect of continuing to smoke after a diagnosis of primary liver cancer (HCC) Swiss researchers analysed survival in 238 people with at least 12 months of follow-up after diagnosis of HCC. Sixty-four reported smoking at the time of inclusion in the cohort study. Smokers were followed for a median of 489 days and non-smokers for 1170 (p = 0.002), the difference reflecting the poorer survival in smokers.

HCC developed at a younger age in smokers (59 vs 66 years, p < 0.001).

There was no significant difference between smokers and non-smokers in the stage of liver cancer whether measured by Child-Pugh grade or BCLC (Barcelona Clinic Liver Cancer) system, nor in any markers of liver damage with the exception of platelet counts and INR (international normalised ratio) scores. Smokers showed some evidence of greater liver injury. They had lower platelet counts and slightly higher INR scores. (Smokers usually have higher platelet counts than non-smokers.)

There was no difference between smokers and non-smokers in the type of treatment they received.

HCC attributable to viral hepatitis (B or C) or alcohol was more common in smokers.

A multivariate analysis which controlled for other risk factors showed that smoking increased the risk of death in people with viral hepatitis diagnosed with HCC (HR 2.41, 95% CI 1.28-4.41, p = 0.007) but not in people with liver cancer attributable to other causes. A more advanced stage of HCC at diagnosis also increased the risk of death (HR 2.73, 95% CI 1.93-3.85, p < 0.001).

Smoking is known to increase liver fibrosis in people with hepatitis C and might also directly influence HCC progression after diagnosis. Poorer fitness or less compliance with medical treatment or advice might also affect survival, the investigators suggest. They say that it is not possible to tell from their cohort whether the effect of smoking was a consequence of smoking intensity – how many cigarettes a day – or duration (persistence in smoking after diagnosis).

“Based on these findings, smoking cessation should be considered for incorporation into the disease management for patients with HBV or HCV [with HCC],” the authors conclude. They point out that around 80% of HCC cases worldwide are probably attributable to viral hepatitis.

References

Kolly P et al. Effect of smoking on survival of patients with hepatocellular carcinoma. Liver International 37: 1682-1687, 2017.