Differential role of chronic liver diseases on the incidence of cancer: a longitudinal analysis among 248,224 outpatients in Germany

BACKGROUND: Chronic liver diseases, especially chronic hepatitis, are a known risk factor for the development of liver cancer. However, the risk of total cancer development and malignant potential from these diseases is largely unknown. Systematic data on the risk of cancer development from these diseases are missing. Therefore, the goal of this study is to analyze the risk of total cancer development in chronic liver diseases. METHODS: A cohort of 15,706 patients with chronic hepatitis and 15,706 patients without hepatitis were matched by propensity scoring from outpatient practices in Germany over a period of 15 years. Cox regression models were conducted to study the association between alcoholic hepatitis, autoimmune hepatitis, hepatitis B, hepatitis C and cancer incidence, including liver, other digestive organs, skin, prostate, breast and lymphoid and hematopoietic tissue cancer. RESULTS: Within 10 years of the index date, 19.3% of patients with alcoholic hepatitis and 13.4% of non-hepatitis individuals were diagnosed with cancer (log-rank p = 0.035). These proportions were 15.0 vs. 9.9% (p = 0.078) for autoimmune hepatitis, 8.7 vs. 7.1% (p = 0.015) for hepatitis B, and 12.7 vs. 7.6% (p < 0.001) for hepatitis C. In regression analyses, only alcoholic hepatitis (HR: 1.84, 95% CI 1.32–2.54) and hepatitis C (HR: 2.10, 95% CI 1.77–2.50) were significantly associated with increased risk of cancer. There was a very strong positive association between hepatitis C and liver cancer (HR: 78.2 (95% CI 10.9–560.7). Furthermore, hepatitis C was associated with an increased risk of respiratory organ cancer (HR: 2.59, 95% CI 1.42–4.73). CONCLUSION: This study confirms the strong association between chronic hepatitis and liver cancer, but also with an overall elevated cancer risk, and especially of cancer in the respiratory tract in patients with chronic hepatitis C.