Effect of antiviral treatment on alfa-fetoprotein levels in HBV-related cirrhotic patients: early detection of hepatocellular carcinoma K. Luo, 1 Z. Liu 1 and P. Karayiannis 2 1 Department of Infectious Diseases and Hepatology Center, Nanfang Hospital, Southern Medical University, Guangzhou, China; and 2 Department of Medicine, Imperial College, London, UK Received April 2009; accepted for publication July 2009 SUMMARY. Alpha-fetoprotein (AFP) is a marker of the pres- ence of hepatocellular carcinoma (HCC), but is also elevated in advanced chronic hepatitis B. The detection and usage of AFP tests need to be improved. A cohort of 101 patients with advanced chronic hepatitis B and elevated AFP values was treated with entecavir (ETV) or peginterferon-a2a. ETV was more effective in reducing AFP levels; mean time to AFP normalization was 11.9 weeks after ETV treatment initiation vs 22.3 weeks in peginterferon treated patients (P = 0.000). An additional cohort of 93 hepatitis B virus (HBV) cirrhotic patients with elevated AFP were treated with ETV prospec- tively and maintained under intensive surveillance. HCC developed in 16 (17.2%) patients in whom the strongest independent predictor was a continued AFP rise in spite of ongoing treatment. In this context, nodules of sizes 10–14 mm and 15–20 mm were detected in 40% of patients each. In conclusion, HBV cirrhotic patients with rising AFP levels were at very high risk of HCC development. Early detection of minute lesions may be possible by monitoring AFP levels, whilst patients are on treatment in conjunction with enhanced computed tomography examination. Keywords: alpha-fetoprotein, antiviral therapy, chronic hepatitis B, cirrhosis, minute hepatocellular carcinoma. INTRODUCTION China is one of the most highly endemic areas of hepatitis B virus (HBV) infection. Unfortunately, chronic hepatitis B is associated with cirrhosis and hepatocellular carcinoma (HCC), and more than half-a-million deaths annually are because of these severe complications [1]. Routine screening for HCC is recommended in patients with chronic hepatitis B, especially in those with evidence of cirrhosis [2]. Alpha-fetoprotein (AFP) is an oncofetal glycoprotein generally used as a screening tool with abdominal ultraso- nography (AUS) for HCC detection in patients with chronic liver disease [2,3]. However, many chronic hepatitis B patients without HCC have elevated AFP values [4,5], and some patients with cirrhosis and concomitant high inflammatory activity have very high AFP levels [6,7]. On the other hand, patients with minute HCC lesions may have AFP levels that may be moderately elevated [8–10]. Simi- larly, there are patients with large HCC masses with negative AFP results [11,12] and whom form a minority in China, and therefore were not included in the present study. Because of the inadequacy in sensitivity and specificity of the AFP test, its diagnostic efficiency for HCC is poor, nev- ertheless still useful in screening [13]. AUS has shortcomings also; it is very operator-dependent and the performance characteristics have not been as well defined in nodular cirrhotic livers [10]. AUS in conjunction with AFP testing improves HCC detection. Hence, AFP remains the onco- marker universally utilized with AUS for monitoring patients with high HCC risk in clinical practice, and scientific socie- tiesÕ guidelines also support its use in this respect [10,11]. In Asian patients in particular, HBV-related HCC is character- ized by higher AFP levels [12]. During the last two decades, newer markers, mainly AFP glycoforms have been exten- sively studied, but only few can be used as supplementary tests and none of them is recommended to replace AFP for clinical routine use [10,14,15]. As the AFP level is closely linked with the characteristics of patient populations [16], both the detection of serum AFP and the usage of the test for HCC surveillance need to be Abbreviation: AFP, alpha-fetoprotein; HCC, hepatocellular carcinoma; HBV, hepatitis B virus; AUS, abdominal ultrasonogra- phy; ETV, entecavir; ALT, alanine aminotransferase; CT, computed tomography; MEIA, microparticle enzyme immunoassay; HAI, histology activity index. Correspondence: Kangxian Luo, North Guangzhou Avenue 1838#, Department of Infectious Diseases and Hepatology Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. E-mail: luokangxian@yahoo.com.cn Journal of Viral Hepatitis, 2010, 17, 511–517 doi:10.1111/j.1365-2893.2009.01208.x Ó 2009 Blackwell Publishing Ltd