Colchicine therapy prevents or delays the development of hepatocellular carcinoma in patients who have cirrhosis related to viral hepatitis, reported Dr. Oscar Arrieta of the National Cancer Institute, Mexico City, and his associates.
Until now, no treatment had been found effective in preventing hepatocellular carcinoma (HCC) from developing in patients with cirrhosis of any etiology.
The alkaloid and antimitotic agent colchicine has shown mixed effects on the progression of fibrosis, ascites, esophageal varices, portal vein pressure, functional status, and mortality in cirrhosis patients, but no studies had assessed its effect against HCC, the investigators said.
They evaluated colchicine in a retrospective cohort study involving 186 patients with hepatitis virus-related cirrhosis who were treated between 1980 and 2000 and who were followed every 3–6 months for a minimum of 3 years. A total of 116 of these subjects (62%) received 1 mg colchicine 5 days per week for a mean of 63 months (range 6–168 months). Almost all of these subjects (96%) were treated for at least 1 year. None discontinued the drug because of adverse effects.
Of the subjects who took colchicine, 9% developed HCC compared with 29% of the subjects who did not take the drug, a significant difference, Dr. Arrieta and his associates said (Cancer 2006 Sept. 11 [Epub doi:10.1002/cncr.22198]).
Moreover, among subjects who did develop HCC, the cancer-free interval was significantly longer in those treated with colchicine (222 months) than in those who did not take the drug (150 months).
The exact oncogenic mechanism of viral-related HCC is not known, but virus-induced inflammation is thought to lead to hepatocyte destruction and liver fibrosis. Colchicine may decrease inflammation and may also have antimitotic properties that reduce cellular proliferation, “thereby interrupting the hyperplasia-dysplasia-metaplasia sequence of HCC and preventing mutations leading to HCC,” the researchers said.
In this study, as in previous studies, colchicine showed no direct beneficial effect on the progression of cirrhosis. With colchicine, 9% of patients showed improvement on their Child-Turcotte-Pugh score during follow-up, 35% showed no change, and 56% showed disease progression. The corresponding numbers in the subjects who didn't take colchicine were 2.5%, 37%, and 60%—progression rates that were not significantly different.
The study findings indicate that colchicine prevents or delays the development of HCC independent of factors such as age, platelet count, alpha fetoprotein levels, and transaminase levels.