A potential clinical based score in hepatitis C virus cirrhotic patients to exclude small hepatocellular carcinoma

Abstract

Aim: Hepatitis C virus (HCV) cirrhosis is an important cause of hepatocellular carcinoma (HCC). This study aimed to identify factors of HCC presence among HCV cirrhotic patients with and without small diameter HCC (≤ 3 cm).

Methods: A case control transversal study between 1998 and 2003 including 93 patients: 31 with small diameter HCC and 62 without HCC. Groups were matched by age and gender. Multiple logistic regression analysis using Akaike Information Criteria to estimate the probability of HCC was performed. A model score was generated and bootstrap analysis was performed for internal validation.

Results: Three significant laboratorial variables for HCC presence were found: alanine aminotransferase > 37 U/L [odds ratio (OR): 7.43 (1.61-34.19), P = 0.01], alpha-fetoprotein > 20 ng/mL [OR: 16.2 (4.17-63.01), P < 0.001] and platelet count < 100,000/mm³ [OR: 3.62 (1.43-9.14), P = 0.007]. A model score with an area under curve of 0.79 (95% CI: 0.7-0.89) was built based on these variables. The negative predictive value of those classified as at low risk of HCC was 99.1%.

Conclusion: An easy and practical model score was generated. It may be an auxiliary tool for identification of HCV patients with low probability of small diameter HCC at initial evaluation composed of three serum examinations used in routine outpatient clinical practice.

Keywords

Clinical score / hepatocellular carcinoma / hepatitis C

References

[1] Llovet JM,Bruix J.Hepatocellular carcinoma..Lancet2003;362:1907-17

[2] Yang JD.Hepatocellular carcinoma: a global view..Nat Rev Gastroenterol Hepatol2010;7:448-58 PMCID:PMC3926946

[3] Venook AP,Furuse J.The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective..Oncologist2010;15:5-13

[4] Ahmed F,Kwong S,Friedman C.National trends and disparities in the incidence of hepatocellular carcinoma, 1998-2003..Prev Chronic Dis2008;5:A74 PMCID:PMC2483571

[5] Parkin DM,Ferlay J.Global cancer statistics, 2002..CA Cancer J Clin2005;55:74-108

[6] Bosch FX,Díaz M.Primary liver cancer: worldwide incidence and trends..Gastroenterology2004;127:S5-16

[7] El-Serag HB.Hepatocellular carcinoma: epidemiology and molecular carcinogenesis..Gastroenterology2007;132:2557-76

[8] Fattovich G,Degos F,Diodati G,Nevens F,Mura D,Thomas H,Casarin C,Fuschi P,Tocco A,Galassini R,Schalm SW.Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients..Gastroenterology1997;112:463-72

[9] Liang TJ.Pathogenesis of hepatitis C-associated hepatocellular carcinoma..Gastroenterology2004;127:S62-71

[10] El-Serag HB,Chen GJ,Richardson PA.Effectiveness of AFP and ultrasound tests on hepatocellular carcinoma mortality in HCV-infected patients in the USA..Gut2011;60:992-7

[11] Mittal S,Ying J,Sada YH,Davila JA.Effectiveness of surveillance for hepatocellular carcinoma in clinical practice: a United States cohort..J Hepatol2016;65:1148-54 PMCID:PMC5322857

[12] European Organisation for Research and Treatment of Cancer.EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma..J Hepatol2012;56:908-43

[13] Heimbach JK,Finn RS,Abecassis MM,Zhu AX,Marrero JA.AASLD guidelines for the treatment of hepatocellular carcinoma..Hepatology2018;67:358-80

[14] Omata M,Kokudo N,Lee JM,Tateishi R,Chawla YK,Jafri W,Ohki T,Chen PJ,Lesmana LA,Obi S,Sarin SK.Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update..Hepatol Int2017;11:317-70 PMCID:PMC5491694

[15] Singal A,Waljee A,Higgins P,Marrero JA.Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis..Aliment Pharmacol Ther2009;30:37-47

[16] Carrilho FJ,Branco F,Mattos AA.Clinical and epidemiological aspects of hepatocellular carcinoma in Brazil..Clinics (Sao Paulo)2010;65:1285-90 PMCID:PMC3020338

[17] Paranaguá-Vezozzo DC,Alvarado-Mora MV,Cunha-Silva M,Alves VA,Carrilho FJ.Epidemiology of HCC in Brazil: incidence and risk factors in a ten-year cohort..Ann Hepatol2014;13:386-93

[18] Paranagua-Vezozzo DC,Chagas AL,Mello ES,Ono-Nita SK.Incidence of hepatocellular carcinoma in cirrhotic patients in Sao Paulo, Brazil..Hepatology2006;44:A504-5

[19] van Meer S,Coenraad MJ,van Nieuwkerk KM,Jansen PL,van Oijen MG,van Erpecum KJ.Surveillance for hepatocellular carcinoma is associated with increased survival: results from a large cohort in the Netherlands..J Hepatol2015;63:1156-63

[20] Goldberg DS,Serper M,Dieperink E,Baytarian M,Hunt K,Pocha C,Kaplan DE.Identifying barriers to hepatocellular carcinoma surveillance in a national sample of patients with cirrhosis..Hepatology2017;65:864-74

[21] von Elm E,Egger M,Gøtzsche PC,STROBE Initiative.The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies..Lancet2007;370:1453-7

[22] Youden WJ.Index for rating diagnostic tests..Cancer1950;3:32-5

[23] Burnham KP.Model selection and multi-model inference: a practical information-theoretic approach..2002;New YorkSpringer-Verlag

[24] Fattovich G,Zagni I.Hepatocellular carcinoma in cirrhosis: incidence and risk factors..Gastroenterology2004;127:S35-50

[25] Efron B.Estimating the error rate of a prediction rule: improvement on cross-validation..J Am Statist Assoc1983;78:316-31

[26] Velázquez RF,Navascués CA,Pérez R,Martínez I.Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis..Hepatology2003;37:520-7

[27] Lok AS,Morgan TR,Sterling RK,Everson GT,Lee WM,Dienstag JL,Morishima C.Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease..Gastroenterology2009;136:138-48 PMCID:PMC3749922

[28] Bruix J.HCC surveillance: who is the target population?.Hepatology2003;37:507-9

[29] Bolondi L,Siringo S,Casali A,Piscaglia F,Zanetti M.Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis..Gut2001;48:251-9 PMCID:PMC1728189

[30] Messori A,Trippoli S.Achieving sustained virological response in hepatitis C reduces the long-term risk of hepatocellular carcinoma: an updated meta-analysis employing relative and absolute outcome measures..Clin Drug Investig2015;35:843-50

[31] Gupta S,Kohlwes J.Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. A systematic review and critical analysis..Ann Intern Med2003;139:46-50

[32] Tong MJ,Kao VW.Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America..J Gastroenterol Hepatol2001;16:553-9

[33] Bruix J.Management of hepatocellular carcinoma: an update..Hepatology2011;53:1020-2 PMCID:PMC3084991

[34] El-Serag HB,Davila JA,Richardson P.A new laboratory-based algorithm to predict development of hepatocellular carcinoma in patients with hepatitis C and cirrhosis..Gastroenterology2014;146:1249-55 PMCID:PMC3992177

[35] Richardson P,Kramer J,Tyson GL.Determinants of serum alpha-fetoprotein levels in hepatitis C-infected patients..Clin Gastroenterol Hepatol2012;10:428-33 PMCID:PMC3311729

[36] Bird TG,Turner RM,Cusack P,Blunsum A,Sturgeon C,Bird SM.Alpha-fetoprotein detection of hepatocellular carcinoma leads to a standardized analysis of dynamic AFP to improve screening based detection..PLoS One2016;11:e0156801 PMCID:PMC4911090

[37] Lu CY,Tien MT,Uen YH.Frequent DNA methylation of MiR-129-2 and its potential clinical implication in hepatocellular carcinoma..Genes Chromosomes Cancer2013;52:636-43

[38] Amr KS,Elhosary YA,Fahim HH.The potential role of miRNAs 21 and 199-a in early diagnosis of hepatocellular carcinoma..Gene2016;575:66-70

[39] Zeng J,Zhou L,Hu C,Niu J,Lin X.Metabolomics identifies biomarker pattern for early diagnosis of hepatocellular carcinoma: from diethylnitrosamine treated rats to patients..Sci Rep2015;5:16101 PMCID:PMC4630653

[40] Qian EN,Ding SZ.Expression and diagnostic value of CCT3 and IQGAP3 in hepatocellular carcinoma..Cancer Cell Int2016;16:55 PMCID:PMC4936258

[41] Attallah AM,Abdelrazek MA,Attallah AA,Elkenawy HM.Combined use of nuclear phosphoprotein c-Myc and cellular phosphoprotein p53 for hepatocellular carcinoma detection in high-risk chronic hepatitis C patients..Br J Biomed Sci2017;74:170-5

[42] Sato T,Yoshida H,Masuzaki R,Goto T,Obi S,Shiina S,Omata M.Ultrasound surveillance for early detection of hepatocellular carcinoma among patients with chronic hepatitis C..Hepatol Int2009;3:544-50 PMCID:PMC2790585

[43] Masuzaki R,Yoshida H,Sato T,Imamura J,Kanai F,Ikeda H,Kawabe T.Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography..Hepatology2009;49:1954-61

[44] Ganne-Carrié N,Bourcier V,Marcellin P,Pol S,de Lédinghen V,Zoulim F,Tran A,Zarski JP,Calès P,Alric L,Mathurin P,Abergel A,Mallat A,Attali P,Wartelle C,Benhamou Y,Silvain C,Capron D,Zucman D,Trinchet JC,Roudot-Thoraval F.Nomogram for individualized prediction of hepatocellular carcinoma occurrence in hepatitis C virus cirrhosis (ANRS CO12 CirVir)..Hepatology2016;64:1136-47

[45] Noh R,Kwon BW,Kim SB.Clinical impact of viral load on the development of hepatocellular carcinoma and liver-related mortality in patients with hepatitis C virus infection..Gastroenterol Res Pract2016;2016:7476231 PMCID:PMC5021494

[46] Flemming JA,Vittinghoff E,Terrault NA.Risk prediction of hepatocellular carcinoma in patients with cirrhosis: the ADRESS-HCC risk model..Cancer2014;120:3485-93 PMCID:PMC4553222

[47] Attallah AM,Attallah AA,Farid K,El-Dosoky I.HCC-ART score, a simple, highly sensitive and specific test for early diagnosis of hepatocellular carcinoma: a large-scale, multicentre study..Br J Cancer2013;109:1657-65 PMCID:PMC3776991