Incidence and predictors of non-hepatic cancers in biopsy-proven alcohol-related liver disease.

Objective: Alcohol-related liver disease (ALD) is a known contributor to non-hepatic cancers (NHC). We aimed to describe the incidence and predictors of NHC in patients with ALD.

Methods: The WALDO study is a multicenter cohort study of patients with histologically characterized ALD. Participants are followed from the time of liver biopsy and outcomes are captured from health records. The primary outcome was the incidence of the first NHC. Risk factors for NHC were presented as unadjusted and adjusted sub-distribution hazards (SDH) based on competing risk analysis. Statistical analyses were done in R.

Results: 691 patients were included. The median age was 51 years (IQR 43- 59), 427 (62 %) patients were male and 406 (59 %) had cirrhosis on biopsy. During a median follow-up of 4.7 years (IQR 1.2-9.5 years), 76 patients (11 %) with ALD developed NHC. The cumulative incidence of NHC in ALD was 2.4 % (1.4-3.9 %) over five years. The most common NHC was respiratory (18 cases, 23 % of NHC) followed by digestive tract (17 cases, 22 %) and cancers of the head and neck (13 cases, 17 %). On multivariable analysis, increasing age (SDH 1.04; CI 1.01-1.06; p = 0.011), previous smoking (SDH 3.65, CI 1.44-9.65; p = 0.006) and current smoking (SDH 3.14; CI 1.27-7.74; p = 0.013) were associated with a higher risk of NHC.

Conclusions: NHC is common and frequently fatal. However, NHC is an infrequent cause of morbidity or mortality in ALD compared to liver-related outcomes.