Tobacco is a Leading Risk Factor for Liver and Extrahepatic Cancers in Patients With Liver Cirrhosis: A Prospective Cohort Study

Abstract

Background & aims

This study aims to assess the incidence and characteristics of all cancers, hepatocellular carcinoma (HCC), and extrahepatic cancers in patients with cirrhosis of various etiologies.

Methods

Prospective cohort study in patients with cirrhosis but no cancer, followed every 6–9 months through the HCC early detection program. Cancer incidence was compared with Spanish population data to calculate standardized incidence ratios (SIR), and cumulative incidence was calculated separately for cancer and competing events. Longitudinal outcomes were assessed with multivariate Fine-Gray and Cox regression models.

Results

A total of 215 patients (68.4% male, median age 61 years) were included. Cirrhotic etiology was alcohol (38%), hepatitis B or C virus infection (36%), alcohol plus hepatitis B or C virus infection (9%), and other causes (17%). Sixty percent were current or former smokers. Thirty-nine cancers were observed (56% liver cancer), while 3.3 were expected (SIR 11.7; 95% confidence interval [CI] 8.6–16.1). Ten (4.6%) patients were censored for liver transplantation and 34 (15.8%) for death, constituting relevant competing risks. Smoking was significantly associated with overall cancer incidence (smokers: subdistribution hazard ratio [SHR] 3.14, 95% CI 1.33–7.38; former smokers: SHR 2.54, 95% CI 1.08–5.98). In the multivariable regression analysis, viral etiology, Child-Pugh score (B or C versus A), and smoking were associated with liver cancer, and smoking with extrahepatic cancer.

Conclusions

Patients with cirrhosis have an 11-fold risk of cancer compared to the general population. Risk is increased in liver and non-liver cancers. Active surveillance of any type of cancer and smoking cessation interventions are needed in these patients.