A Decrease in AFP Level Related to Administration of Interferon in Patients with Chronic Hepatitis C and a High Level of AFP

Abstract

It is known that there is a very high incidence of hepatocellular carcinoma (HCC) among patients with type C chronic hepatitis and cirrhosis, and alpha -fetoprotein (AFP) has been widely used as a diagnostic marker for HCC. However, there are some patients showing continuous high AFP values but no evidence of HCC, and some studies have defined such patients as a high-risk group for HCC. In vitro study has shown that interferon (IFN) inhibits cell proliferation and enhances apoptosis as well as specific cytotoxic T lymphocytes against HCC, resulting in direct anticancer actions. In this study, we investigated the effect of IFN on AFP changes in chronic hepatitis C patients. Of 40 patients with chronic hepatitis C in whom diagnostic imaging confirmed the absence of HCC, 24 patients showed high pretreatment AFP values (high AFP group: AFP level > 10 ng/dl; mean +/- SD, 46.3 +/- 41.5 ng/dl) and 16 showed low pretreatment AFP values (low AFP group: pretreatment AFP level < or = 10 ng/dl; mean +/- SD, 5.3 +/- 2.2 ng/dl). Pretreatment clinical parameters were statistically evaluated in relation to the AFP value. In the high AFP group, the platelet count, albumin level, and prothrombin (%) were significantly lower (P = 0.047, P = 0.0002, and P = 0.044, respectively), suggesting that AFP value increases with advancing liver disease. Subsequently 27 patients were administered IFN (IFN group), and the remaining 13 patients were administered Stronger Neo-minophagen C (SNMC), a glycyrrhizin preparation (SNMC group), as a control group receiving liver-protective therapy. Alanine aminotransferase was reduced in both the IFN and the SNMC group (mean, 132.56 to 60.07 mg/ml [P < 0001] and 147.85 to 56.23 mg/ml [P = 0.0240], respectively). AFP was significantly reduced in the IFN group (mean, 30.03 to 12.65 ng/ml; P = 0.0034), but there was no significant change in AFP in the SNMC group (mean, 29.70 to 39.17 ng/ml). AFP is useful for diagnosing HCC; however, some patients show a persistently high AFP level in the absence of HCC, and these patients have been described as a high-risk group for HCC. In this study, we found that IFN therapy but not SNMC universally reduced the AFP baseline. Since AFP is a significant predictor for HCC, therapeutic strategies for hepatitis C, e.g., long-term low-dose IFN treatment, may reduce hepatocarcinogenesis.

Efficacy and safety of 6-month iron reduction therapy in patients with hepatitis C virus-related cirrhosis: a pilot study

“…Until now, it has been recognized that only low-dose long-term interferon injection can improve serum AFP levels 11 . Since a high level of AFP is suggested to be one of the major risk factors of the development of HCC 12,13 , lowering serum AFP levels is important to prevent HCV-related hepatocarcinogenesis.…”

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Liver, Bladder, Cervical, and Gastric Cancers

“…For the high-risk group, ultrasound and tumor-marker measurements are recommended every 6 months. Addition of DCP or AFP-L3 is considered necessary because these are diagnostic markers whereas AFP is a marker of risk (129,130 ). Detection of a nodular lesion by ultrasound and/or a continuous rise in AFP (Ͼ200 g/L), DCP [in arbitrary units (AU) with 1 AU ϭ 1 g prothrombin] (Ͼ40 mAU/mL), or AFP-L3 (Ͼ15%) requires further evaluation by dynamic CT or MRI (127,128 ).…”

Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus

“…In addition, there are case reports that IFN therapy reduced AFP levels in virological nonresponders [49]. Murashima et al [50] showed that IFN therapy, but not Strong NeoMinophagen C (SNMC) (Glycyrrhizin, Tokyo, Japan), universally reduced basic AFP levels. In an in vitro study of the effects of IFN on an HCC cell line, IFN exhibited antitumor effects [51].…”