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Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Hepatitis B | Research article

Late presentation of hepatitis B among patients with newly diagnosed hepatocellular carcinoma: a national cohort study

Authors: Dong Hyun Sinn, Danbee Kang, Minwoong Kang, Seung Woon Paik, Eliseo Guallar, Juhee Cho, Geum-Youn Gwak

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Recently, the concept of “late presentation with viral hepatitis” was introduced to help quantify the proportion of patients missing timely diagnosis and treatment for viral hepatitis. The clinical implications of late presentation of hepatitis B at the population level, however, are largely unexplored.

Methods

Using newly-diagnosed hepatitis B related hepatocellular carcinoma (HCC) patients (N = 1276) from the Korean National Health Insurance Service-National Sample Cohort, a nationally representative cohort study was conducted between 2002 and 2013. HCC patients were classified into 3 groups: late presentation of hepatitis B (no prior clinic visits for hepatitis B before HCC diagnosis), irregular visits (irregular pattern of outpatient clinic visits), and regular visits (regular pattern of outpatient clinic visits).

Results

The proportion of patients with late presentation decreased from 50.8% in 2003 to 23.1% in 2013. In multivariable analysis compared with patients in the regular visits group, patients with late presentation were more likely to be younger and to be in lower income percentiles. After adjusting for age, sex, year of HCC diagnosis, income percentile, and initial treatment, the hazard ratios (95% confidence intervals) for all-cause mortality comparing the late presentation and irregular visits groups to the regular visits group were 1.76 (1.42–2.18) and 1.31 (1.06–1.61), respectively.

Conclusion

Timely diagnosis and treatment for hepatitis B related HCC was suboptimal at the population level. More intensive strategies to minimize late presentation for hepatitis B are needed, with special attention to younger people and lower income levels.
Literature
1.
go back to reference Global Burden of Disease Liver Cancer Collaboration, Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, Allen C, Al-Raddadi R, Alvis-Guzman N, Amoako Y, et al. The burden of primary liver Cancer and underlying etiologies from 1990 to 2015 at the global, regional, and National Level: results from the global burden of disease study 2015. JAMA Oncol. 2017;3(12):1683–91.CrossRef Global Burden of Disease Liver Cancer Collaboration, Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, Allen C, Al-Raddadi R, Alvis-Guzman N, Amoako Y, et al. The burden of primary liver Cancer and underlying etiologies from 1990 to 2015 at the global, regional, and National Level: results from the global burden of disease study 2015. JAMA Oncol. 2017;3(12):1683–91.CrossRef
2.
go back to reference European Association For the Study of the Liver. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43.CrossRef European Association For the Study of the Liver. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43.CrossRef
3.
go back to reference Kim BH, Park JW. Epidemiology of liver cancer in South Korea. Clin Mol Hepatol. 2018;24(1):1–9.CrossRef Kim BH, Park JW. Epidemiology of liver cancer in South Korea. Clin Mol Hepatol. 2018;24(1):1–9.CrossRef
4.
go back to reference Singal AG, El-Serag HB. Hepatocellular carcinoma from epidemiology to prevention: translating knowledge into practice. Clin Gastroenterol Hepatol. 2015;13(12):2140–51.CrossRef Singal AG, El-Serag HB. Hepatocellular carcinoma from epidemiology to prevention: translating knowledge into practice. Clin Gastroenterol Hepatol. 2015;13(12):2140–51.CrossRef
5.
go back to reference Sinn DH, Kang D, Jang HR, Gu S, Cho SJ, Paik SW, Ryu S, Chang Y, Lazo M, Guallar E, et al. Development of chronic kidney disease in patients with non-alcoholic fatty liver disease: a cohort study. J Hepatol. 2017;67(6):1274–80.CrossRef Sinn DH, Kang D, Jang HR, Gu S, Cho SJ, Paik SW, Ryu S, Chang Y, Lazo M, Guallar E, et al. Development of chronic kidney disease in patients with non-alcoholic fatty liver disease: a cohort study. J Hepatol. 2017;67(6):1274–80.CrossRef
6.
go back to reference Cho EJ, Kim SE, Suk KT, An J, Jeong SW, Chung WJ, Kim YJ. Current status and strategies for hepatitis B control in Korea. Clin Mol Hepatol. 2017;23(3):205–11.CrossRef Cho EJ, Kim SE, Suk KT, An J, Jeong SW, Chung WJ, Kim YJ. Current status and strategies for hepatitis B control in Korea. Clin Mol Hepatol. 2017;23(3):205–11.CrossRef
7.
go back to reference Korean Association for the Study of the Liver. KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol. 2016;22(1):18–75.CrossRef Korean Association for the Study of the Liver. KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol. 2016;22(1):18–75.CrossRef
8.
go back to reference Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013;58(3):593–608.CrossRef Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013;58(3):593–608.CrossRef
9.
go back to reference Samji H, Yu A, Kuo M, Alavi M, Woods R, Alvarez M, Dore GJ, Tyndall M, Krajden M, Janjua NZ, et al. Late hepatitis B and C diagnosis in relation to disease decompensation and hepatocellular carcinoma development. J Hepatol. 2017;67(5):909–17.CrossRef Samji H, Yu A, Kuo M, Alavi M, Woods R, Alvarez M, Dore GJ, Tyndall M, Krajden M, Janjua NZ, et al. Late hepatitis B and C diagnosis in relation to disease decompensation and hepatocellular carcinoma development. J Hepatol. 2017;67(5):909–17.CrossRef
10.
go back to reference Mauss S, Pol S, Buti M, Duffell E, Gore C, Lazarus JV, der Grient HL, Lundgren J, Mozalevskis A, Raben D, et al. Late presentation of chronic viral hepatitis for medical care: a consensus definition. BMC Med. 2017;15(1):92.CrossRef Mauss S, Pol S, Buti M, Duffell E, Gore C, Lazarus JV, der Grient HL, Lundgren J, Mozalevskis A, Raben D, et al. Late presentation of chronic viral hepatitis for medical care: a consensus definition. BMC Med. 2017;15(1):92.CrossRef
11.
go back to reference Weinbaum CM, Mast EE, Ward JW. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. Hepatology. 2009;49(5 Suppl):S35–44.CrossRef Weinbaum CM, Mast EE, Ward JW. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. Hepatology. 2009;49(5 Suppl):S35–44.CrossRef
12.
go back to reference Evlampidou I, Hickman M, Irish C, Young N, Oliver I, Gillett S, Cochrane A. Low hepatitis B testing among migrants: a cross-sectional study in a UK city. Br J Gen Pract. 2016;66(647):e382–91.CrossRef Evlampidou I, Hickman M, Irish C, Young N, Oliver I, Gillett S, Cochrane A. Low hepatitis B testing among migrants: a cross-sectional study in a UK city. Br J Gen Pract. 2016;66(647):e382–91.CrossRef
13.
go back to reference Wendland A, Ehmsen BK, Lenskjold V, Astrup BS, Mohr M, Williams CJ, Cowan SA. Undocumented migrant women in Denmark have inadequate access to pregnancy screening and have a higher prevalence hepatitis B virus infection compared to documented migrants in Denmark: a prevalence study. BMC Public Health. 2016;16:426.CrossRef Wendland A, Ehmsen BK, Lenskjold V, Astrup BS, Mohr M, Williams CJ, Cowan SA. Undocumented migrant women in Denmark have inadequate access to pregnancy screening and have a higher prevalence hepatitis B virus infection compared to documented migrants in Denmark: a prevalence study. BMC Public Health. 2016;16:426.CrossRef
14.
go back to reference Kim DY, Kim HJ, Jeong SE, Kim SG, Kim HJ, Sinn DH, Lee YJ, Jeong WK, Choi KS, Heo NY, et al. The Korean guideline for hepatocellular carcinoma surveillance. J Korean Med Assoc. 2015;58(5):385–97.CrossRef Kim DY, Kim HJ, Jeong SE, Kim SG, Kim HJ, Sinn DH, Lee YJ, Jeong WK, Choi KS, Heo NY, et al. The Korean guideline for hepatocellular carcinoma surveillance. J Korean Med Assoc. 2015;58(5):385–97.CrossRef
15.
go back to reference Park SH, Heo NY, Park JH, Kim TO, Yang SY, Kim HK, Moon YS, Kim CH, Suk KT, Kim DJ, et al. Hepatocellular carcinoma screening in a hepatitis B virus-infected Korean population. Dig Dis Sci. 2012;57(12):3258–64.CrossRef Park SH, Heo NY, Park JH, Kim TO, Yang SY, Kim HK, Moon YS, Kim CH, Suk KT, Kim DJ, et al. Hepatocellular carcinoma screening in a hepatitis B virus-infected Korean population. Dig Dis Sci. 2012;57(12):3258–64.CrossRef
16.
go back to reference Shin A, Cho ER, Kim J, Sung J, Park KW, Lim MK, Shin HR. Factors associated with awareness of infection status among chronic hepatitis B and C carriers in Korea. Cancer Epidemiol Biomark Prev. 2009;18(6):1894–8.CrossRef Shin A, Cho ER, Kim J, Sung J, Park KW, Lim MK, Shin HR. Factors associated with awareness of infection status among chronic hepatitis B and C carriers in Korea. Cancer Epidemiol Biomark Prev. 2009;18(6):1894–8.CrossRef
17.
go back to reference Lee J, Lee JS, Park SH, Shin SA, Kim K. Cohort profile: the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Int J Epidemiol. 2017;46(2):e15.PubMed Lee J, Lee JS, Park SH, Shin SA, Kim K. Cohort profile: the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Int J Epidemiol. 2017;46(2):e15.PubMed
18.
go back to reference Chun CB, Kim SY, Lee JY, Lee SY. Republic of Korea. Health system review. Health Syst Transit. 2009;11(7):1–184. Chun CB, Kim SY, Lee JY, Lee SY. Republic of Korea. Health system review. Health Syst Transit. 2009;11(7):1–184.
19.
go back to reference Shin DW, Cho B, Guallar E. Korean national health insurance database. JAMA Intern Med. 2016;176(1):138.CrossRef Shin DW, Cho B, Guallar E. Korean national health insurance database. JAMA Intern Med. 2016;176(1):138.CrossRef
20.
go back to reference Deeks A, Lombard C, Michelmore J, Teede H. The effects of gender and age on health related behaviors. BMC Public Health. 2009;9:213.CrossRef Deeks A, Lombard C, Michelmore J, Teede H. The effects of gender and age on health related behaviors. BMC Public Health. 2009;9:213.CrossRef
21.
go back to reference Sinn DH, Gwak GY, Cho J, Paik SW, Yoo BC. Comparison of clinical manifestations and outcomes between hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma: analysis of a nationwide cohort. PLoS One. 2014;9(11):e112184.CrossRef Sinn DH, Gwak GY, Cho J, Paik SW, Yoo BC. Comparison of clinical manifestations and outcomes between hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma: analysis of a nationwide cohort. PLoS One. 2014;9(11):e112184.CrossRef
22.
go back to reference Chang PE, Ong WC, Lui HF, Tan CK. Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome. J Gastroenterol. 2008;43(11):881–8.CrossRef Chang PE, Ong WC, Lui HF, Tan CK. Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome. J Gastroenterol. 2008;43(11):881–8.CrossRef
23.
go back to reference Davila JA, Morgan RO, Richardson PA, Du XL, McGlynn KA, El-Serag HB. Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States. Hepatology. 2010;52(1):132–41.CrossRef Davila JA, Morgan RO, Richardson PA, Du XL, McGlynn KA, El-Serag HB. Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States. Hepatology. 2010;52(1):132–41.CrossRef
24.
go back to reference Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28(9):1067–77.CrossRef Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28(9):1067–77.CrossRef
25.
go back to reference Kim JH, Sinn DH, Kim K, Kim H, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Lamivudine versus Entecavir for newly diagnosed hepatitis B virus-related hepatocellular carcinoma. Gut Liver. 2016;10(6):939–47.CrossRef Kim JH, Sinn DH, Kim K, Kim H, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Lamivudine versus Entecavir for newly diagnosed hepatitis B virus-related hepatocellular carcinoma. Gut Liver. 2016;10(6):939–47.CrossRef
26.
go back to reference Sohn W, Kang TW, Choi SK, Jung SH, Lee MW, Lim HK, Cho JY, Shim SG, Sinn DH, Gwak GY, et al. Effect of oral antiviral treatment on long-term outcomes of radiofrequency ablation therapy for hepatitis B virus-related hepatocellular carcinoma. Oncotarget. 2016;7(30):47794–807.CrossRef Sohn W, Kang TW, Choi SK, Jung SH, Lee MW, Lim HK, Cho JY, Shim SG, Sinn DH, Gwak GY, et al. Effect of oral antiviral treatment on long-term outcomes of radiofrequency ablation therapy for hepatitis B virus-related hepatocellular carcinoma. Oncotarget. 2016;7(30):47794–807.CrossRef
27.
go back to reference Wu CY, Hsu YC, Ho HJ, Chen YJ, Lee TY, Lin JT. Association between ultrasonography screening and mortality in patients with hepatocellular carcinoma: a nationwide cohort study. Gut. 2016;65(4):693–701.CrossRef Wu CY, Hsu YC, Ho HJ, Chen YJ, Lee TY, Lin JT. Association between ultrasonography screening and mortality in patients with hepatocellular carcinoma: a nationwide cohort study. Gut. 2016;65(4):693–701.CrossRef
28.
go back to reference Kansagara D, Papak J, Pasha AS, O'Neil M, Freeman M, Relevo R, Quinones A, Motu'apuaka M, Jou JH. Screening for hepatocellular carcinoma in chronic liver disease: a systematic review. Ann Intern Med. 2014;161(4):261–9.CrossRef Kansagara D, Papak J, Pasha AS, O'Neil M, Freeman M, Relevo R, Quinones A, Motu'apuaka M, Jou JH. Screening for hepatocellular carcinoma in chronic liver disease: a systematic review. Ann Intern Med. 2014;161(4):261–9.CrossRef
29.
go back to reference Cucchetti A, Trevisani F, Pecorelli A, Erroi V, Farinati F, Ciccarese F, Rapaccini GL, Di Marco M, Caturelli E, Giannini EG, et al. Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma. J Hepatol. 2014;61(2):333–41.CrossRef Cucchetti A, Trevisani F, Pecorelli A, Erroi V, Farinati F, Ciccarese F, Rapaccini GL, Di Marco M, Caturelli E, Giannini EG, et al. Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma. J Hepatol. 2014;61(2):333–41.CrossRef
Metadata
Title
Late presentation of hepatitis B among patients with newly diagnosed hepatocellular carcinoma: a national cohort study
Authors
Dong Hyun Sinn
Danbee Kang
Minwoong Kang
Seung Woon Paik
Eliseo Guallar
Juhee Cho
Geum-Youn Gwak
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5508-5

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