Background and Aims. To examine the changes in serum alpha-fetoprotein (AFP) levels after iron reduction by therapeutic phlebotomy in chronic hepatitis C patients. Methods. This retrospective study included 26 chronic hepatitis C patients. The patients were developed iron depletion by repeated therapeutic phlebotomies. Results. Iron reduction therapy significantly reduced the median level of serum AFP from 13 to 7？ng/mL, ALT from 96 to 50？IU/L, gamma-glutamyl transpeptidase (GGT) from 55 to 28？IU/L, and ferritin from 191 to 10？ng/mL ( for each). The rate of decline in the AFP level correlated positively only with that in GGT , although a spurious correlation was observed between the rates of decline for AFP and ALT. The AFP level normalized (<10？ng/mL) posttreatment in eight (50%) of 16 patients who had elevated pretreatment AFP levels. Normalized post-treatment ALT and GGT levels were seen in 12% (3 of 26) and 39% (7 of 18) of the patients, respectively. Multivariate analysis identified a post-treatment GGT level of <30？IU/L as an independent factor associated with post-treatment AFP normalization (odds ratio, 21; 95% confidence interval, 1.5–293; ). Conclusions. Iron reduction by therapeutic phlebotomy can reduce serum AFP and GGT levels in chronic hepatitis C patients. 1. Introduction Estimated 170 million people worldwide are chronically infected with hepatitis C virus (HCV) [1], which is a leading cause of hepatocellular carcinoma (HCC) [2, 3]. Routine HCC screening is recommended for HCV patients, and alpha-fetoprotein (AFP) has been used widely to screen for HCC in these patients [4, 5]. However, elevated serum AFP levels are found in some patients with HCV but without HCC [6–9]; these patients are recognized as a high-risk group for HCC [10, 11]. Eradication of HCV with interferon (IFN)-based therapy, including peginterferon alpha combined with ribavirin and telaprevir or boceprevir, is the most promising therapeutic intervention for preventing the progression to HCC in HCV patients [12]. Recently, IFN-based therapy was shown to decrease serum AFP levels in HCV patients with elevated pretreatment AFP, even in IFN nonresponders [8, 13–17]. However, especially for those patients who do not respond to or are unsuitable for antiviral therapy, other therapeutic options capable of preventing the progression to HCC are urgently needed. Iron reduction by therapeutic phlebotomy was recently shown to reduce the risk for progression to HCC and improve biochemical and histological outcomes in chronic HCV patients [18, 19]. The effect of iron reduction
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