Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 7/2015

01-07-2015 | Original Article – Clinical Oncology

FIB-4 index for assessing the prognosis of hepatocellular carcinoma in patients with Child-Pugh class A liver function

Authors: Takanori Ito, Takashi Kumada, Hidenori Toyoda, Toshifumi Tada

Published in: Journal of Cancer Research and Clinical Oncology | Issue 7/2015

Login to get access

Abstract

Purpose

We evaluated the prognosis of hepatocellular carcinoma (HCC) patients with Child-Pugh (C-P) class A based on FIB-4 index, which is a liver fibrosis marker.

Patients and methods

A total of 915 HCC patients with C-P class A were investigated. We assessed the prognosis using FIB-4 index, and factors associated with survival rates were analyzed in these patients.

Results

When patients were categorized according to FIB-4 index as <2.0 (n = 93), ≥2.0 and <4.0 (n = 311), and ≥4.0 (n = 511), survival rates at 5 years were 70.5 % [95 % confidence interval (CI) 59.0–79.9], 56.4 % (95 % CI 50.1–62.5), and 47.1 % (95 % CI 42.2–52.1), respectively. Patients with FIB-4 index <2.0 had a higher survival rate than the other groups (≥4.0 vs ≥2.0 and <4.0, p = 0.010; ≥2.0 and <4.0 vs <2.0, p = 0.028). We were able to predict prognosis in patients with C-P score 5 by FIB-4 index, but survival rate did not significantly differ in patients with C-P score 6. Multivariate analysis identified C-P score, FIB-4 index [≥2.0 and <4.0; hazard ratios (HRs) 1.638 (95 % CI 1.084–2.474); p = 0.019/≥4.0; HR 1.828 (95 % CI 1.217–2.744); p = 0.004], Lens culinaris agglutinin-reactive α-fetoprotein, tumor size, number, vascular invasion, antiviral therapy, and hepatectomy as independent predictive factors for survival.

Conclusions

The FIB-4 index is useful for assessing prognosis in HCC patients with C-P class A, especially those with C-P score 5.
Literature
go back to reference A new prognostic system for hepatocellular carcinoma (1998) A retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 28:751–755 A new prognostic system for hepatocellular carcinoma (1998) A retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 28:751–755
go back to reference Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M et al (2014a) The ION-1 investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 370:1889–1898CrossRefPubMed Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M et al (2014a) The ION-1 investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 370:1889–1898CrossRefPubMed
go back to reference Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E et al (2014b) Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. ION-2 investigators. N Engl J Med 370:1483–1493CrossRefPubMed Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E et al (2014b) Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. ION-2 investigators. N Engl J Med 370:1483–1493CrossRefPubMed
go back to reference Buster EH, Hansen BE, Buti M, Delwaide J, Niederau C, Michielsen PP et al (2007) HBV 99-01 Study Group. Peginterferon alpha-2b is safe and effective in HBeAg-positive chronic hepatitis B patients with advanced fibrosis. Hepatology 46:388–394CrossRefPubMed Buster EH, Hansen BE, Buti M, Delwaide J, Niederau C, Michielsen PP et al (2007) HBV 99-01 Study Group. Peginterferon alpha-2b is safe and effective in HBeAg-positive chronic hepatitis B patients with advanced fibrosis. Hepatology 46:388–394CrossRefPubMed
go back to reference Clinical Practice Guidelines for Hepatocellular Carcinoma (2009) The Japan Society of Hepatology update. Hepatol Res 2010(40):2–144 Clinical Practice Guidelines for Hepatocellular Carcinoma (2009) The Japan Society of Hepatology update. Hepatol Res 2010(40):2–144
go back to reference de Lope CR, Tremosini S, Forner A, Reig M, Bruix J (2012) Management of HCC. J Hepatol 56:75–87CrossRef de Lope CR, Tremosini S, Forner A, Reig M, Bruix J (2012) Management of HCC. J Hepatol 56:75–87CrossRef
go back to reference El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576CrossRefPubMed El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576CrossRefPubMed
go back to reference European Association for the Study of the Liver (2012) European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943CrossRef European Association for the Study of the Liver (2012) European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943CrossRef
go back to reference Fernández-Esparrach G, Sánchez-Fueyo A, Ginès P, Uriz J, Quintó L, Ventura PJ et al (2001) A prognostic model for predicting survival in cirrhosis with ascites. J Hepatol 34:46–52CrossRefPubMed Fernández-Esparrach G, Sánchez-Fueyo A, Ginès P, Uriz J, Quintó L, Ventura PJ et al (2001) A prognostic model for predicting survival in cirrhosis with ascites. J Hepatol 34:46–52CrossRefPubMed
go back to reference Izumi R, Shimizu K, Ii T, Yagi M, Matsui O, Nonomura A et al (1994) Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection. Gastroenterology 106:720–727PubMed Izumi R, Shimizu K, Ii T, Yagi M, Matsui O, Nonomura A et al (1994) Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection. Gastroenterology 106:720–727PubMed
go back to reference Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS et al (2013) POSITRON Study; FUSION Study; Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 368:1867–1877CrossRefPubMed Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS et al (2013) POSITRON Study; FUSION Study; Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 368:1867–1877CrossRefPubMed
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRefPubMed
go back to reference Kudo M, Chung H, Haji S, Osaki Y, Oka H, Seki T et al (2004) Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score. Hepatology 40:1396–1405CrossRefPubMed Kudo M, Chung H, Haji S, Osaki Y, Oka H, Seki T et al (2004) Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score. Hepatology 40:1396–1405CrossRefPubMed
go back to reference Kumada T, Toyoda H, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A et al (2013a) Characteristics of elderly hepatitis C virus-associated hepatocellular carcinoma patients. J Gastroenterol Hepatol 28:357–364CrossRefPubMed Kumada T, Toyoda H, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A et al (2013a) Characteristics of elderly hepatitis C virus-associated hepatocellular carcinoma patients. J Gastroenterol Hepatol 28:357–364CrossRefPubMed
go back to reference Kumada T, Toyoda H, Tada T, Kiriyama S, Tanikawa M, Hisanaga Y et al (2013b) Effect of nucleos(t)ide analogue therapy on hepatocarcinogenesis in chronic hepatitis B patients: a propensity score analysis. J Hepatol 58:427–433CrossRefPubMed Kumada T, Toyoda H, Tada T, Kiriyama S, Tanikawa M, Hisanaga Y et al (2013b) Effect of nucleos(t)ide analogue therapy on hepatocarcinogenesis in chronic hepatitis B patients: a propensity score analysis. J Hepatol 58:427–433CrossRefPubMed
go back to reference Leroy V, Hilleret MN, Sturm N, Trocme C, Renversez JC, Faure P et al (2007) Prospective comparison of six non-invasive scores for the diagnosis of liver fibrosis in chronic hepatitis C. J Hepatol 46:775–782CrossRefPubMed Leroy V, Hilleret MN, Sturm N, Trocme C, Renversez JC, Faure P et al (2007) Prospective comparison of six non-invasive scores for the diagnosis of liver fibrosis in chronic hepatitis C. J Hepatol 46:775–782CrossRefPubMed
go back to reference Llovet JM, Brú C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338CrossRefPubMed Llovet JM, Brú C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338CrossRefPubMed
go back to reference Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R, Reindollar R, Rustgi V, McPhee F, Wind-Rotolo M, Persson A, Zhu K, Dimitrova DI, Eley T, Guo T, Grasela DM, Pasquinelli C et al (2012) Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med 366:216–224CrossRefPubMed Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R, Reindollar R, Rustgi V, McPhee F, Wind-Rotolo M, Persson A, Zhu K, Dimitrova DI, Eley T, Guo T, Grasela DM, Pasquinelli C et al (2012) Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med 366:216–224CrossRefPubMed
go back to reference Merkel C, Bolognesi M, Sacerdoti D, Bombonato G, Bellini B, Bighin R et al (2000) The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 32:930–934CrossRefPubMed Merkel C, Bolognesi M, Sacerdoti D, Bombonato G, Bellini B, Bighin R et al (2000) The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 32:930–934CrossRefPubMed
go back to reference Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60:646–649CrossRefPubMed Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60:646–649CrossRefPubMed
go back to reference Schiff E, Simsek H, Lee WM, Chao YC, Sette H Jr, Janssen HL et al (2008) Efficacy and safety of entecavir in patients with chronic hepatitis B and advanced hepatic fibrosis or cirrhosis. Am J Gastroenterol 103:2776–2783CrossRefPubMed Schiff E, Simsek H, Lee WM, Chao YC, Sette H Jr, Janssen HL et al (2008) Efficacy and safety of entecavir in patients with chronic hepatitis B and advanced hepatic fibrosis or cirrhosis. Am J Gastroenterol 103:2776–2783CrossRefPubMed
go back to reference Sebastiani G, Vario A, Guido M, Noventa F, Plebani M, Pistis R et al (2006) Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C. J Hepatol 44:686–693CrossRefPubMed Sebastiani G, Vario A, Guido M, Noventa F, Plebani M, Pistis R et al (2006) Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C. J Hepatol 44:686–693CrossRefPubMed
go back to reference Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ (2009) Nash Clinical Research Network. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 7:1104–1112CrossRefPubMedCentralPubMed Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ (2009) Nash Clinical Research Network. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 7:1104–1112CrossRefPubMedCentralPubMed
go back to reference Shim JH, Lee HC, Kim KM, Lim YS, Chung YH, Lee YS et al (2010) Efficacy of entecavir in treatment-naïve patients with hepatitis B virus-related decompensated cirrhosis. J Hepatol 52:176–182CrossRefPubMed Shim JH, Lee HC, Kim KM, Lim YS, Chung YH, Lee YS et al (2010) Efficacy of entecavir in treatment-naïve patients with hepatitis B virus-related decompensated cirrhosis. J Hepatol 52:176–182CrossRefPubMed
go back to reference Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J et al (2006) APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 43:1317–1725CrossRefPubMed Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J et al (2006) APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 43:1317–1725CrossRefPubMed
go back to reference Tamaki N, Kurosaki M, Matsuda S, Muraoka M, Yasui Y, Suzuki S et al (2013) Non-invasive prediction of hepatocellular carcinoma development using serum fibrosis marker in chronic hepatitis C patients. J Gastroenterol. doi:10.1007/s00535-013-0914-y Tamaki N, Kurosaki M, Matsuda S, Muraoka M, Yasui Y, Suzuki S et al (2013) Non-invasive prediction of hepatocellular carcinoma development using serum fibrosis marker in chronic hepatitis C patients. J Gastroenterol. doi:10.​1007/​s00535-013-0914-y
go back to reference Toyoda H, Kumada T, Tada T, Sone Y, Kaneoka Y, Maeda A (2011) Characteristics and prognosis of patients with hepatocellular carcinoma after the year 2000 in Japan. J Gastroenterol Hepatol 26:1765–1771CrossRefPubMed Toyoda H, Kumada T, Tada T, Sone Y, Kaneoka Y, Maeda A (2011) Characteristics and prognosis of patients with hepatocellular carcinoma after the year 2000 in Japan. J Gastroenterol Hepatol 26:1765–1771CrossRefPubMed
go back to reference Umemura T, Ichijo T, Yoshizawa K, Tanaka E, Kiyosawa K (2009) Epidemiology of hepatocellular carcinoma in Japan. J Gastroenterol 44:102–107CrossRefPubMed Umemura T, Ichijo T, Yoshizawa K, Tanaka E, Kiyosawa K (2009) Epidemiology of hepatocellular carcinoma in Japan. J Gastroenterol 44:102–107CrossRefPubMed
go back to reference Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V et al (2007) FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology 46:32–36CrossRefPubMed Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V et al (2007) FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology 46:32–36CrossRefPubMed
go back to reference Vergniol J, Boursier J, Coutzac C, Bertrais S, Foucher J, Angel C et al (2014) The evolution of non-invasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C. Hepatology 60:65–76CrossRefPubMed Vergniol J, Boursier J, Coutzac C, Bertrais S, Foucher J, Angel C et al (2014) The evolution of non-invasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C. Hepatology 60:65–76CrossRefPubMed
go back to reference Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS et al (2003) A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic heparins C. Hepatology 38:518–526CrossRefPubMed Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS et al (2003) A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic heparins C. Hepatology 38:518–526CrossRefPubMed
Metadata
Title
FIB-4 index for assessing the prognosis of hepatocellular carcinoma in patients with Child-Pugh class A liver function
Authors
Takanori Ito
Takashi Kumada
Hidenori Toyoda
Toshifumi Tada
Publication date
01-07-2015
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 7/2015
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-015-1922-5

Other articles of this Issue 7/2015

Journal of Cancer Research and Clinical Oncology 7/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.