Submitted October 31, 2002
Accepted February 25, 2003
Six-month versus 12-month surveillance for hepatocellular carcinoma in 559 hemophiliacs infected with the hepatitis C virus
Elena Santagostino, Massimo Colombo*, Monica Rivi, Maria G Rumi, Angiola Rocino, Silvia Linari, Pier M Mannucci, and Study Group of the Association of Italian Hemophilia Centers
A. Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, University of Milan, Milan, Italy
Division of Hepatology, IRCCS Maggiore Hospital, University of Milan, Milan, Italy
Department of Hematology, Hemophilia Center, Naples, Italy
Department of Hematology, Hemophilia Center, Florence, Italy
* Corresponding author; email: massimo.colombo{at}unimi.it.
Hepatocellular carcinoma (HCC) is an increasingly frequent cause of mortality in hemophiliacs with chronic viral hepatitis. Early diagnosis of the tumor at an initial stage is known to improve the outcome of HCC treatment. Since all HCC cases detected in a previous study based upon annual ultrasound (US) surveillance of hemophiliacs with elevated alanine aminotransferase were multinodular, this study was designed to evaluate if a more intense surveillance with US and alphafetoprotein (AFP) serum levels of all the patients infected with the hepatitis C virus (HCV) improved the identification of single nodule tumors. A multicenter cohort of 559 HCV-infected hemophiliacs was divided into 2 arms, one followed-up at 6-month intervals and one at 12-month intervals depending on the choice and available facilities of each treatment center. During a 6-year surveillance period, HCC was diagnosed in 5/210 (2.4%) patients in the 6-month group and in 3/349 (0.9%) patients in the 12-month group. The overall incidence rate of HCC was 239 per 100,000 per year (397 per 100,000 per year in the 6-month group and 143 per 100,000 per year in the 12-month group) (differences not statistically significant). By multivariate analysis, HCC risk was increased 12.9-fold with alcohol intake greater than 80g/day and 15.2-fold with AFP levels higher than 11ng/ml. Liver-related death occurred in 8 cases (1.4%), including 3 with HCC. Three patients with multinodular tumors treated with repeat chemoembolization followed by orthotopic liver transplantation are still alive and tumor free after 24-34 months from diagnosis. In conclusion, 6-month surveillance with US did not increase the chances of detection of single nodule tumors, but it is reasonable to assume that successful treatment of multinodular tumors based upon debulking with chemoembolization and liver transplantation was facilitated by this approach.
