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

Tateyama, Masao; Yatsuhashi, Hiroshi; Taura, Naota; Motoyoshi, Yasuhide; Nagaoka, Shinya; Yanagi, Kenji; Abiru, Seigo; Yano, Koji; Komori, Atsumasa; Migita, Kiyoshi; Nakamura, Minoru; Nagahama, Hiroyasu; Sasaki, Yutaka; Miyakawa, Yuzo; Ishibashi, Hiromi

doi:10.1007/s00535-010-0293-6

Cited by 79 publications

(62 citation statements)

References 62 publications

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“…Few early-stage HCC-nonBC cases present with abnormal AFP serum levels. Several reports have shown elevated AFP to be a risk factor for HCC development in HCV and/or HBV patients [24,[30][31][32][33][34][35][36]. However, our results suggest AFP alone to be insufficient for HCC-nonBC surveillance.…”

Section: Discussioncontrasting

confidence: 59%

“…One reason for these differences involves the use of different cut-off values in the various studies (e.g., 40, 60, and 100 mAU/mL for DCP; and 20, 100, and 200 ng/mL for AFP). Other possible reasons include differences in the causes of the underlying liver diseases, and patients with cirrhosis tending to have higher AFP levels than those with chronic hepatitis [36,41]. Another possible reason for these differences might be etiological differences in liver diseases among the patients examined in prior studies.…”

Section: Discussionmentioning

confidence: 99%

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758 Frequency of Elevated Biomarkers in Patients With Cryptogenic Hepatocellular Carcinoma

Taura¹,

Ichikawa²,

Miyaaki³

et al. 2012

Journal of Hepatology

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Background:The incidence of hepatocellular carcinoma (HCC) continues to increase in Japan, but the clinical characteristics of Japanese patients with HCC have not been well described. The aim of this study was to determine the frequencies and utilities of elevated a-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels as biomarkers in cryptogenic HCC. Material/Methods:A total of 2638 patients with HCC diagnosed between 1999 and 2010 in the Nagasaki Association Study of Liver (NASLD) were recruited for this study. The cause of HCC was categorized into 4 groups; HCC-B, HCC-C, HCC-BC, and HCC-nonBC. The significance of factors was examined for HCC-nonBC using logistic regression analysis in all patients. Results:Multivariate analysis identified age, sex, BMI, alcohol consumption, platelet count, AST, ALT, AFP, DCP, and TNM stage as independent and significant risk factors for HCC-nonBC. According to TNM stage, the median AFP levels in HCC-nonBC with TNM stages I, II, and III were significantly lower than in either HCC-B or HCC-C. In TNM stage IV, the median AFP level in HCC-nonBC was significantly lower than in either HCC-B or HCC-BC. The median DCP levels in HCC-nonBC with TNM stages I and II were significantly higher than those in either HCC-B or HCC-C. In TNM stage III, the median DCP level in HCC-nonBC was significantly higher than that in HCC-C. Conclusions:DCP was more sensitive than AFP for the diagnosis of early stage cryptogenic HCC. DCP should be used as the main serum test for cryptogenic HCC detection.

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Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

758 Frequency of Elevated Biomarkers in Patients With Cryptogenic Hepatocellular Carcinoma

Taura¹,

Ichikawa²,

Miyaaki³

et al. 2012

Journal of Hepatology

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“…Recently, Tateyama et al demonstrated that elevated AFP levels are a risk factor for the development of HCC in patients with HCV infection; the 10-year cumulative incidence rates of HCC in the patients with AFP levels of <6, 6-20 and ≥20 ng/ml at entry were 6.0, 24.6 and 47.3%, respectively, and that AFP levels may be used as a non-invasive and predictive marker in place of stage of fibrosis (27). In this study, all 7 BLD patients who developed HCC during the follow-up period exhibited measurable hs-AFP-L3% prior to detection of HCC, and 6 patients exhibited hs-AFP-L3% ≥5%.…”

Section: Discussionmentioning

confidence: 99%

Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease

Ido

2011

Oncol Rep

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Abstract. The fucosylated fraction of α-fetoprotein (AFP-L3) is a specific marker for hepatocellular carcinoma (HCC). However, conventional AFP-L3% (c-AFP-L3%) has not always been reliable in cases with low serum α-fetoprotein (AFP) levels. In this study, we evaluated the clinical utility of a newly developed assay, highly sensitive AFP-L3% (hs-AFP-L3%). Subjects included 74 patients with benign liver disease (BLD), including chronic hepatitis and cirrhosis, and 94 with HCC. Serum hs-AFP-L3% was significantly higher than c-AFP-L3% in patients with early-stage HCC (solitary or <20 mm in diameter). Additionally, hs-AFP-L3% was significantly increased in patients with well-differentiated HCC. In patients with serum AFP <20 ng/ml, the sensitivities of c-AFP-L3% and hs-AFP-L3% were 12.5 and 44.6%, respectively, at a cut-off value of 5%. In 59 BLD patients with serum AFP <20 ng/ml, the HCC-positive rate in patients with hs-AFP-L3% ≥5% was significantly higher compared to those with hs-AFP-L3% <5% during the follow-up period (median, 35 months; range, 5-48 months). Importantly, none of the BLD patients with both serum AFP <20 ng/ml and hs-AFP-L3% <5% developed HCC. These results indicated that hs-AFP-L3% is useful for early detection of HCC in BLD patients, even for those with serum AFP <20 ng/ml. Furthermore, since hs-AFP-L3% increases before HCC is detectable by various advanced imaging modalities, this assay may help identify BLD patients with a higher risk of HCC. IntroductionHepatocellular carcinoma (HCC) is the sixth most common cancer in the world, and the third most common cause of cancer-related death (1). Although it is more common in Asia and Africa, its incidence in the United States has increased over the past two decades, largely due to the spread of hepatitis C (HCV) infection, which is an underlying risk factor (2). Early detection of HCC increases the potential for curative treatment and improves prognosis. Several methods developed for the diagnosis of HCC, including evaluation of serum markers, ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI), have been tested clinically. α-fetoprotein (AFP) and des-γ carboxy prothrombin (DCP), serum proteins that are elevated in HCC, are the most widely used markers. Although routine screening offers the best chance for early tumor detection, the reported sensitivities and specificities of elevated serum AFP and DCP levels vary significantly (3-8). Furthermore, serum AFP levels increase in only 30-40% of patients with HCC, especially early in the disease process (5). Additionally, an increase in serum AFP is also seen in patients with non-cancerous conditions, including cirrhosis or exacerbation of chronic hepatitis (9). AFP-L3, the lectin lens culinaris agglutinin-bound fraction, is one of the three glycoforms of AFP, and is the major glycoform elevated in the serum of HCC patients. The reported sensitivities of AFP-L3 as a method of detecting HCC range from 75-97% with specificities of 90-92% (10,11). In cases of HCC, however, h...

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“…Patients who underwent a liver biopsy and a 75-g oral glucose tolerance test (OGTT) were included in the analysis, while patients taking antidiabetic drugs were excluded. We set the cutoff value for AFP as 10.0 ng/mL because an even slightly elevated AFP level is a risk factor for HCC (6,9). We analyzed factors associated with elevated AFP levels (!…”

Section: Patientsmentioning

confidence: 99%

“…The serum α-fetoprotein (AFP) level is an important predictor of the clinical course in patients with chronic hepatitis C (CHC), as elevated serum AFP levels are associated with a low viral response rate to interferon [IFN (4)], advanced fibrosis (5-7) and a high frequency of HCC (6,(8)(9)(10). Although IFN can lead to biochemical improvement and eradi-cation of HCV, which reduces the risk of HCC (11), the clinical impact of HCV eradication on HCC prevention is less significant in older patients than in younger patients (8).…”

Section: Introductionmentioning

confidence: 99%

Whole-body Insulin Resistance is Associated with Elevated Serum α-fetoprotein Levels in Patients with Chronic Hepatitis C

et al. 2013

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Objective Little is known about the relationship between elevated serum α-fetoprotein (AFP) levels and insulin resistance, which adversely influence the clinical course of chronic hepatitis C (CHC). Therefore, we investigated the association between serum AFP and insulin resistance in patients with CHC. Methods We retrospectively investigated 300 patients with CHC without hepatoma who underwent liver biopsies and oral glucose tolerance tests. Patients taking antidiabetic drugs were excluded. We analyzed factors associated with elevated AFP levels (! 10.0 ng/mL) in 265 eligible patients. Twenty patients with a homeostasis model assessment for insulin resistance value of ! 2.0 and a whole-body insulin sensitivity index of <5.0 received prospective lifestyle intervention. Results A univariate analysis showed that the body mass index, platelet count, levels of albumin, aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase, glucose metabolism, hepatic inflammation, fibrosis and steatosis were associated with elevated AFP levels. In a multivariate analysis, a platelet count of <15×10 4 /μL, aspartate aminotransferase level of ! 50 IU/L, γ-glutamyl transpeptidase level of ! 35 IU/L, whole-body insulin sensitivity index of <5.0 and stage 3-4 fibrosis were independently associated with an elevated AFP level. A Bayesian Network analysis showed that the aspartate aminotransferase level, whole-body insulin sensitivity index and hepatic fibrosis were directly associated with an elevated AFP level. The lifestyle intervention significantly improved the serum AFP level, homeostasis model assessment for insulin resistance and whole-body insulin sensitivity index. Conclusion Whole-body insulin resistance is associated with an elevated serum AFP level in patients with CHC. Lifestyle interventions targeting insulin resistance can reduce the serum AFP level and may ameliorate the clinical course of CHC.

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

Cited by 79 publications

References 62 publications

758 Frequency of Elevated Biomarkers in Patients With Cryptogenic Hepatocellular Carcinoma

758 Frequency of Elevated Biomarkers in Patients With Cryptogenic Hepatocellular Carcinoma

Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease

Whole-body Insulin Resistance is Associated with Elevated Serum α-fetoprotein Levels in Patients with Chronic Hepatitis C

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