Updating AFP Level in Chronic Hepatitis B to Evaluate the Risk of Hepatocellular Carcinoma Occurrence
Abstract
Background: Hepatocellular carcinoma (HCC) is a cancer with poor prognosis. Indonesia is a country with high prevalence of chronic hepatitis B infection. The performance of alpha fetoprotein (AFP) as a tumor marker in HCC surveillance is primarily influenced by the etiology of the underlying liver disease. We aimed to determine the best cut-off value of AFP biomarker examination for HCC surveillance in patients with chronic hepatitis B infection. Methods: The study collected medical record data of the Hepatobiliary Division of Dr. Cipto Mangunkusumo Hospital from the period of 2017 to 2023. A total of 506 subjects with chronic hepatitis B of all spectrums (hepatitis B without cirrhosis, liver cirrhosis, and early-stage HCC, BCLC 0 and A) were included by total sampling that was performed from 26 July 2023 to 31 August 2023. Determination of the AFP cut-off value was carried out using the receiver operating characteristics (ROC) method. Results: For HCC surveillance caused by hepatitis B virus, ROC curve analysis resulted in an area under the curve (AUC) of 0.792 (95% CI, 0.719-0.866), and the cut-off value with the highest Youden index was 8.7 ng/ml, with 58% sensitivity, 94% specificity, positive predictive value (PPV) 56.14%, negative predictive value (NPV) 94.43%, positive likelihood ratio (LR+) 10.08, and negative likelihood ratio (LR-) 0.46. Conclusion: The cut-off value of AFP in HCC surveillance on hepatitis B specific etiology is lower than the cut-off value of AFP in previous HCC surveillance which was not etiologically specific. The cut-off value of 8.7 ng/ml produces the best sensitivity and specificity for the cut-off value for HCC surveillance with hepatitis B etiology.
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References
Omata M, Cheng AL, Kokudo N, et al. Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11(4):317–70.
Kementerian Kesehatan. Riset Kesehatan Dasar. Kementerian Kesehatan, editor. Jakarta; 2013.
Chun S, Rhie SY, Ki CS, Kim JE, Park HD. Evaluation of alpha-fetoprotein as a screening marker for hepatocellular carcinoma in hepatitis prevalent areas. Ann Hepatol. 2015;14(6):881–7.
Sanai FM, Sobki S, Bzeizi KI, et al. Assessment of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma in Middle Eastern patients. Dig Dis Sci. 2010;55(12):3568–75.
Biselli M, Conti F, Gramenzi A, et al. A new approach to the use of α-fetoprotein as surveillance test for hepatocellular carcinoma in patients with cirrhosis. Br J Cancer. 2015;112(1):69–76.
Marrero JA, Feng Z, Wang Y, et al. α-fetoprotein, Des-γ carboxyprothrombin, and lectin-bound α-fetoprotein in early hepatocellular carcinoma. Gastroenterology. 2009;137(1):110–8.
Tai WC, Hu TH, Wang JH, et al. Clinical implications of alpha-fetoprotein in chronic hepatitis C. Journal of the Formosan Medical Association [Internet]. 2009;108(3):210–8. Available from: http://dx.doi.org/10.1016/S0929-6646(09)60054-1
Chan SL, Mo F, Johnson PJ, et al. Performance of serum α-fetoprotein levels in the diagnosis of hepatocellular carcinoma in patients with a hepatic mass. Hpb [Internet]. 2014;16(4):366–72. Available from: http://dx.doi.org/10.1111/hpb.12146
Paul SB, Gulati MS, Sreenivas V, et al. Evaluating patients with cirrhosis for hepatocellular carcinoma: Value of clinical symptomatology, imaging and alpha-fetoprotein. Oncology. 2007;72(Supp. 1):117–23.
Indonesian Liver Cancer Study. Konsensus Nasional Penatalaksanaan Karsinoma Sel Hati. 2017;
Trevisani F, D’Intino PE, Morselli-Labate AM, et al. Serum α-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol. 2001;34(4):570–5.
Nguyen MH, Garcia RT, Simpson PW, Wright TL, Keeffe EB. Racial differences in effectiveness of α-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis. Hepatology. 2002;36(2):410–7.
Kim KA, Lee JS, Jung ES, et al. Usefulness of serum alpha-fetoprotein (AFP) as a marker for hepatocellular carcinoma (HCC) in hepatitis C virus related cirrhosis: analysis of the factors influencing AFP elevation without HCC development. Korean J Gastroenterol. 2006;48(5):321–6.
Jasirwan COM, Fahira A, Siregar L, Loho I. The alpha-fetoprotein serum is still reliable as a biomarker for the surveillance of hepatocellular carcinoma in Indonesia. BMC Gastroenterol. 2020;20(1):1–8.
Park J, Chen M, Colombo M, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE study. Liver International. 2015;35(9):2155–66.
Petrick J, Florio A, Ruggieri D, et al. International trends in hepatocellular carcinoma incidence. Int J Cancer. 2019.
Zhu R, Seto W, Lai C, Yuen M. Epidemiology of hepatocellular carcinoma in the Asia-Pacific region. Gut Liver. 2016;10(3):332–9.
Oemanti R, Rahajeng E, Kristanto A. Prevalensi tumor dan beberapa faktor yang mempengaruhinya di Indonesia. Balai Penelitian dan Pengembangan Kesehatan. 2011;190–204.
Yi S, Choi J, Yi J, Lee Y, Han K. Risk factors for hepatocellular carcinoma by age, sex, and liver disorder status: A prospective cohort study in Korea. Cancer. 2018;124(13):2748–57.
Grebely J, Page K, Sacks-Davis R, et al. The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology. 2014;59(1):109–20.
Zheng B, Zhu YJ, Wang HY, Chen L. Gender disparity in hepatocellular carcinoma (HCC): multiple underlying mechanisms. Sci China Life Sci. 2017;60(6):575–84.
Wu EM, Wong LL, Hernandez BY, et al. Gender differences in hepatocellular cancer: disparities in nonalcoholic fatty liver disease/steatohepatitis and liver transplantation. Hepatoma Res. 2018;4(10):66.
McGlynn KA, Petrick JL, El‐Serag HB. Epidemiology of hepatocellular carcinoma. Hepatology. 2021;73(S1):4–13.
Zhang C, Cheng Y, Zhang S, Fan J, Gao Q. Changing epidemiology of hepatocellular carcinoma in Asia. Liver International. 2022;42(9):2029–41.
Kew MC. Hepatocellular carcinoma in developing countries: Prevention, diagnosis and treatment. World J Hepatol. 2012;4(3):99.
Katsuta E, Tanaka S, Mogushi K, et al. Age-related clinicopathologic and molecular features of patients receiving curative hepatectomy for hepatocellular carcinoma. American J Surg. 2014;208(3):450–6.
Unggul B. Karsinoma hati. Buku Ajar Ilmu Penyakit Dalam. 6th ed. Jakarta: Interna Publishing; 2015. p. 3040–6.
Patil M, Sheth K, Adarsh C. Elevated alpha fetoprotein, no hepatocellular carcinoma. J Clin Exp Hepatol. 2013;3(2):162–4.
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