Abstract
Alcohol increases the risk of both hepatocellular carcinoma (HCC) and colorectal neoplasia. In this hospital-based case-control and retrospective cohort study, we sought to determine whether development of colorectal neoplasia increases the risk of HCC in patients with alcoholic liver disease (ALD). In the phase I case-control analysis, the association between history of colorectal cancer (CRC) and HCC development was assessed in patients with ALD by logistic regression modeling (n = 1,659). In the phase II retrospective cohort analysis, the relative risk of HCC development was compared in ALD patients with respect to the history of CRC by a Cox model (n = 1,184). The history of CRC was significantly associated with HCC in the case-control analysis (adjusted odds ratio, 1.82; 95% CI, 1.06–3.15; P < 0.05). ALD patients with CRC had higher risk of developing HCC compared to those without CRC (adjusted hazards ratio [HR], 5.48; 95% CI, 1.63–18.36; P = 0.006) in the cohort analysis. Presence of CRC, liver cirrhosis, elevated baseline alpha-fetoprotein level, and low platelet counts were independent predictors of HCC development in ALD patients. Patients with history of CRC had an increased risk of HCC in both cirrhotic (HR, 3.76; 95% CI, 1.05–13.34, P = 0.041) and non-cirrhotic (HR, 23.46; 95% CI, 2.81–195.83, P = 0.004) ALD patients. In conclusion, ALD patients with CRC are at increased risk of developing HCC.
Highlights
Alcohol-related liver disease is a global health burden that causes 348,000 deaths and 10,997,000 disability-adjusted life years annually[1]
Logistic regression analysis showed that past history of colorectal cancer (CRC) was significantly associated with future development of hepatocellular carcinoma (HCC), along with sex, drinking amount and smoking as additional significant variables associated with HCC development (Table 2)
The association of CRC history with HCC remained significant after adjustment for confounders, indicating possible association between development of CRC and HCC in alcoholic liver disease (ALD)
Summary
Alcohol-related liver disease is a global health burden that causes 348,000 deaths and 10,997,000 disability-adjusted life years annually[1]. Cirrhosis is one of the most important predictors for alcohol-related HCC, along with old age, comorbid chronic viral hepatitis, and the amount of alcohol consumption[8,9,10]. Chronic ethanol consumption usually promotes carcinogenesis by production of toxic acetaldehyde, induction of cytochrome P450 2E1 that causes oxidative stress and procarcinogen activation, and provocation of global DNA hypomethylation[18]. Since these carcinogenic pathways are known to contribute to the development of both colorectal neoplasm and HCC10,19,20, we hypothesized that ALD patients who develop colorectal neoplasm are at risk of further developing HCC.
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