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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 7
Jul.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(7): 1589-1593

Risk factors for hepatocellular carcinoma in patients with chronic hepatitis B

DOI: 10.3969/j.issn.1001-5256.2021.07.022
  • 1.

    Department of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China

  • 2.

    The First Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100700, China

Research funding:

Capital Health Development Research Project (2018-1-2172);

Beijing Municipal Commission of Science and Technology (Z191100006619033);

National Administration of Traditional Chinese Medicine Clinical Cooperation Pilot Project of Traditional Chinese and Western Medicine for Major and Difficult Diseases (2018-6-4);

Regional TCM Diagnosis and Treatment Center of State Administration of Traditional Chinese Medicine (2019-3-18)

  • Received Date: 2021-01-02
  • Accepted Date: 2021-02-10
  • Published Date: 2021-07-20
    Abstract
  •   Objective  To investigate the risk factors for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).  Methods  A total of 1239 patients who were diagnosed with CHB in Beijing Ditan Hospital from January 2013 to June 2015 and were followed up for more than 3 years were enrolled, among whom 1108 had no liver cirrhosis and 131 had liver cirrhosis. General information and laboratory markers were collected. The chi-square test was used for comparison of categorical data between groups, and the t-test or the Mann-Whitney U test was used for comparison of continuous data between groups. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test for comparison of categorical data between two groups. A multivariate Cox regression analysis was used to identify the independent risk factors for HCC. The area under the ROC curve (AUC) was used to compare the ability of fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) scores to predict the development of HCC, and the DeLong test was used for comparison of AUC. Goodness of fit was used to evaluate the calibration ability of mFIB-4 score. The Kaplan-Meier method was used to analyze the development of HCC, and the log-rank test was used for comparison.  Results  The median follow-up time was 4.6 years, and of all patients, 37 (3.0%) developed HCC. The multivariate Cox regression analysis showed that age (hazard ratio [HR]=1.046, 95% confidence interval [CI]: 1.018-1.074, P=0.001), alanine aminotransferase (ALT) (HR=0.995, 95%CI: 0.992-0.999, P=0.008), aspartate aminotransferase (AST) (HR=0.994, 95%CI: 0.990-0.998, P=0.020), and platelet count (PLT) (HR=0.988, 95%CI: 0.981-0.994, P=0.001) were independent risk factors for HCC in CHB patients. The mFIB-4, FIB-4, and APRI scores had an AUC of 0.771, 0.658, and 0.676, respectively, and mFIB-4 score had a significantly higher AUC than FIB-4 score (Z=5.629, P < 0.000 1) and APRI score (Z=4.243, P < 0.000 1). Compared with the patients with mFIB-4 < 2.68, the patients with mFIB-4 ≥2.68 had a significantly higher risk of HCC (Z=37.840, P < 0.000 1).  Conclusion  Age, ALT, AST, and PLT are independent risk factors for HCC in CHB patients. Compared with FIB-4 and APRI scores, mFIB-4 s core has a higher value in predicting HCC in CHB patients. The patients with mFIB-4 ≥2.68 are the high-risk population of HCC.

     

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    • References(28)
  • [1]
    SINGAL AG, El-SERAG HB. Hepatocellular carcinoma from epidemiology to prevention: Translating knowledge into practice[J]. Clin Gastroenterol Hepatol, 2015, 13(12): 2140-2151. DOI: 10.1016/j.cgh.2015.08.014.
    [2]
    HEIMBACH JK, KULIK LM, FINN RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma[J]. Hepatology, 2018, 67(1): 358-380. DOI: 10.1002/hep.29086.
    [3]
    ARENDS P, SONNEVELD MJ, ZOUTENDIJK R, et al. Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: Limited role for risk scores in Caucasians[J]. Gut, 2015, 64(8): 1289-1295. DOI: 10.1136/gutjnl-2014-307023.
    [4]
    European Association for the Study of the Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection[J]. J Hepatol, 2012, 57(1): 167-185. DOI: 10.1016/j.jhep.2012.02.010.
    [5]
    JUNG KS, KIM SU, SONG K, et al. Validation of hepatitis B virus-related hepatocellular carcinoma prediction models in the era of antiviral therapy[J]. Hepatology, 2015, 62(6): 1757-1766. DOI: 10.1002/hep.28115.
    [6]
    VALLET-PICHARD A, MALLET V, NALPAS B, et al. FIB-4: An inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest[J]. Hepatology, 2007, 46(1): 32-36. DOI: 10.1002/hep.21669.
    [7]
    WAI CT, GREENSON JK, FONTANAL RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C[J]. Hepatology, 2003, 38(2): 518-526. DOI: 10.1053/jhep.2003.50346.
    [8]
    PAIK N, SINN DH, LEE JH, et al. Non-invasive tests for liver disease severity and the hepatocellular carcinoma risk in chronic hepatitis B patients with low level viremia[J]. Liver Int, 2018, 38(1): 68-75. DOI: 10.1111/liv.13489.
    [9]
    WANG HW, PENG CY, LAI HC, et al. New noninvasive index for predicting liver fibrosis in Asian patients with chronic viral hepatitis[J]. Sci Rep, 2017, 7(1): 3259. DOI: 10.1038/s41598-017-03589-w.
    [10]
    Chinese Society of Infectious Diseases and Chinese Society of Hepatology Chinese, Medical Association. The guideline of prevention and treatment for chronic hepatitis B: A 2019 update[J]. J Clin Hepatol, 2019, 35 (12): 2648-2669. DOI: 1001-5256(2019)12-2648-22.

    中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 1001-5256(2019) 12-2648-22.
    [11]
    Chinese Society of Infectious Diseases Chinese, Medical Association. Chinese guidelines on the management of liver cirrhosis[J]. J Clin Hepatol, 2019, 35(11): 2408-2425. DOI: 1001-5256(2019)11-2408-18.

    中华医学会肝病学分会. 肝硬化诊治指南[J]. 临床肝胆病杂志, 2019, 35 (11): 2408-2425. DOI: 1001-5256(2019) 11-2408-18.
    [12]
    OMATA M, CHENG AL, KOKUDO N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma, a 2017 update[J]. Hepatol Int, 2017, 11(4): 317-370. DOI: 10.1007/s12072-017-9799-9.
    [13]
    CHAN SL, WONG VW, QIN S, et al. Infection and cancer: The case of hepatitis B[J]. J Clin Oncol, 2016, 34(1): 83-90. DOI: 10.1200/JCO.2015.61.5724.
    [14]
    CHAN HLY. Okuda lecture: Challenges of hepatitis B in the era of antiviral therapy[J]. J Gastroenterol Hepatol, 2019, 34(3): 501-506. DOI: 10.1111/jgh.14534.
    [15]
    PAPATHEODORIDIS GV, IDILMAN R, DALEKOS GN, et al. The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B[J]. Hepatology, 2017, 66(5): 1444-1453. DOI: 10.1002/hep.29320.
    [16]
    PAPATHEODORIDIS GV, MANOLAKOPOULOS S, TOULOUMI G, et al. Hepatocellular carcinoma risk in HBeAg-negative chronic hepatitis B patients with or without cirrhosis treated with entecavir: HepNet. Greece cohort[J]. J Viral Hepat, 2015, 22(2): 120-127. DOI: 10.1111/jvh.12283.
    [17]
    CHEN CF, LEE WC, YANG HI, et al. Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma[J]. Gastroenterology, 2011, 141(4): 1240-1248, 1248. e1-e2. DOI: 10.1053/j.gastro.2011.06.036.
    [18]
    TSENG TC. Risk factors of liver cancer progression in patients with chronic hepatitis B virus infection[J/CD]. Chin J Exp Clin Infect Dis (Electronic Edition), 2019, 13(5): 440. DOI: 10.3877/cma.j.issn.1674-1358.2019.05.017.

    TSENG TC. 慢性乙型肝炎病毒感染者进展为肝癌的危险因素[J/CD]. 中华实验和临床感染病杂志(电子版), 2019, 13(5): 440. DOI: 10.3877/cma.j.issn.1674-1358.2019.05.017.
    [19]
    KIM JH, KIM YD, LEE M, et al. Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy[J]. J Hepatol, 2018, 69(5): 1066-1073. DOI: 10.1016/j.jhep.2018.07.018.
    [20]
    BERZIGOTTI A, SEIJO S, ARENA U, et al. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis[J]. Gastroenterology, 2013, 144(1): 102-111. e101. DOI: 10.1053/j.gastro.2012.10.001.
    [21]
    THOMOPOULOS KC, LABROPOULOU-KARATZA C, MIMIDIS KP, et al. Non-invasive predictors of the presence of large oesophageal varices in patients with cirrhosis[J]. Dig Liver Dis, 2003, 35(7): 473-478. DOI: 10.1016/s1590-8658(03)00219-6.
    [22]
    TANDON P, GARCIA-TSAO G. Portal hypertension and hepatocellular carcinoma: Prognosis and beyond[J]. Clin Gastroenterol Hepatol, 2006, 4(11): 1318-1319. DOI: 10.1016/j.cgh.2006.09.009.
    [23]
    SUH B, PARK S, SHIN DW, et al. High liver fibrosis index FIB-4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers[J]. Hepatology, 2015, 61(4): 1261-1268. DOI: 10.1002/hep.27654.
    [24]
    KIM MN, KIM SU, KIM BK, et al. Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with transient elastography-defined subclinical cirrhosis[J]. Hepatology, 2015, 61(6): 1851-1859. DOI: 10.1002/hep.27735.
    [25]
    BAGLIERI J, BRENNER DA, KISSELEVA T. The role of fibrosis and liver-associated fibroblasts in the pathogenesis of hepatocellular carcinoma[J]. Int J Mol Sci, 2019, 20(7): 1723. DOI: 10.3390/ijms20071723.
    [26]
    GABELE E, BRENNER DA, RIPPE RA. Liver fibrosis: Signals leading to the amplification of the fibrogenic hepatic stellate cell[J]. Front Biosci, 2003, 8: d69-d77. DOI: 10.2741/887.
    [27]
    SAKURAI T, HE G, MATSUZAWA A, et al. Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis[J]. Cancer Cell, 2008, 14(2): 156-165. DOI: 10.1016/j.ccr.2008.06.016.
    [28]
    FARAZI PA, DEPINHO RA. Hepatocellular carcinoma pathogenesis: From genes to environment[J]. Nat Rev Cancer, 2006, 6(9): 674-87. DOI: 10.1038/nrc1934.
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