Preventive Treatment for Hepatocelullar Carcinoma

Patients who develop hepatocellular carcinoma (HCC), a type of liver cancer caused by the hepatitis B virus, have up to a 55 percent chance of having the virus reactivated during chemotherapy. The idea of preemptively treating these patients with the antiviral drug lamivudine in order to prevent hepatitis B relapse and it varying complications is promising but has never been investigated in patients with HCC.

Researchers led by Jeong Won Jang of the Department of Internal Medicine at the Catholic University of Korea in Seoul, conducted a prospective randomized study on pretreating HCC patients undergoing chemotherapy with lamivudine between January 2004 and February 2005. The study involved 36 patients with HCC who were given the drug while undergoing transarterial chemo-lipiodolization (TACL) chemotherapy and a control group of 37 patients who underwent the chemotherapy without receiving lamivudine.

The chemotherapy was continued every month without any limit on the number of cycles until the tumors disappeared, while treatment with lamivudine began with the chemotherapy and continued for 12 months following its completion.In total, 43 percent of the patients in the control group developed overall clinical hepatitis during the follow-up period, compared to 17 percent of the patients who took lamivudine.

In addition, there was a significantly higher incidence of severe hepatitis in the control group and the researchers established the level of viral load (>104 copies/ml) that predicted whether a patient would have a relapse of hepatitis B.In addition to demonstrating that treatment with lamivudine significantly reduced hepatitis B reactivation, allowing chemotherapy to continue in these cancer patients, the study suggests that lamivudine therapy decreases the severity of clinical hepatitis if it develops during chemotherapy.

"The beneficial effects of preemptive therapy on the severity of hepatitis most probably result from an elimination of any potential risk arising from viral reactivation," the authors state.

While previous studies have shown a higher viral load as a predictor of hepatitis B reactivation, the lower cutoff in the current study was identified as a better predictor and the authors urge the use of a highly sensitive test to detect and measure viral load in order to identify patients at the greatest risk of hepatitis B reactivation.

In those patients with lower viral loads, it would still be beneficial to closely monitor virological and biochemical changes when they are undergoing repeated courses of chemotherapy, since the study demonstrated that even lower viral loads are associated with an approximately 30 percent risk of viral reactivation.

Although the study did not examine long-term survival in the patients who took lamivudine, the authors conclude: "Given that preemptive antiviral therapy ameliorates the hepatic morbidity seen during transarterial chemotherapy and facilitates further chemotherapy without disruptions in the treatment schedules, the expectation would be for an increased chance of survival with this approach."

(From the February 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). http://www.interscience.wiley.com/journal/hepatology.)