Colchicine delays the development of hepatocellular carcinoma in patients with hepatitis virus-related liver cirrhosis.
BACKGROUND
Hepatocellular carcinoma (HCC) is a malignant neoplasm associated with liver cirrhosis, with an annual incidence of 3% to 9%, which is one of the main causes of death in patients with cirrhosis. Viral hepatitis is associated with an increased risk of HCC, probably due to an inflammatory reaction. Colchicine is an antiinflammatory agent that inhibits the formation of intracellular microtubules, affecting mitosis and fibrogenesis. Diverse clinical studies have failed to demonstrate the benefit of colchicine over the progression of fibrosis in patients with liver cirrhosis; nevertheless, to the authors' knowledge there are no studies that evaluate its effect in the development of HCC.


METHODS
The effect of the administration of colchicine on the development of HCC was evaluated in 186 patients with hepatitis virus-related liver cirrhosis in a retrospective cohort study. The minimum follow-up time was 3 years (median, 84 months +/- 2.8 months). One hundred sixteen patients received treatment with colchicine. The characteristics of both groups were similar.


RESULTS
The percentage of patients who developed HCC was significantly smaller in the colchicine group when compared with the noncolchicine group (9% vs. 29%; P = .001). On multivariate analysis, an alpha-fetoprotein level > or = 5 ng/dL (P = .03), a platelet count < 100,000 at diagnosis (P = .05), alanine aminotransferase > or = 52 IU (P = .006), and a lack of treatment with colchicine (P = .0001) were found to be associated with an earlier development of HCC. The average time for the development of HCC was 222 months +/- 15 months and 150 months +/- 12 months in the patients who received and who did not receive colchicine, respectively.


CONCLUSIONS
The results suggest that treatment with colchicine prevents and delays the development of HCC in patients with hepatitis virus-related cirrhosis. The protective mechanisms of colchicine over the development of HCC could be related to antiinflammatory properties and inhibition of mitosis. Prospective studies to confirm this observation with a greater number of patients and long-term follow-up may be indicated.
Arrieta
Oscar
O
Department of Medical Oncology, Instituto Nacional de Cancerologia, Tlalpan, Mexico. ogar@servidor.unam.mx
Rodriguez-Diaz
Jose Luis
JL
Rosas-Camargo
Vanessa
V
Morales-Espinosa
Daniela
D
Ponce de Leon
Sergio
S
Kershenobich
David
D
Leon-Rodriguez
Eucario
E
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D015331:Cohort Studies; D003078:Colchicine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006525:Hepatitis, Viral, Human / Q000150:complications*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D008113:Liver Neoplasms / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D000893:Anti-Inflammatory Agents; D003078:Colchicine