title: Association of early age at establishment of chronic hepatitis B infection with persistent viral replication, liver cirrhosis and hepatocellular carcinoma: a systematic review.
abstract: Age at infection with hepatitis B virus (HBV) is a known risk factor for chronic HBV infection. However, in addition, there is some evidence that early age at infection further increases the risk of primary liver cancer beyond its association with increased risk of chronic infection. This systematic review of observational studies assesses the association between age at initiation of chronic HBV infection and liver cirrhosis, hepatocellular carcinoma, and their predictors including indicators of ongoing viral replication and hepatic damage. The review includes birth order and maternal HBV serology as proxies for age at infection. Electronic searches in two English-language (Medline and Embase, until Jan 2012) and two Chinese-language (CNKI and SinoMed, until Sep 2012) databases without language restriction and manual search through reference lists identified 7,077 papers, of which 19 studies of 21 outcomes (8 primary liver cancer, 1 liver cirrhosis, 10 viral replication and 2 liver inflammation) are included. One study directly examined the age at infection in a longitudinal cohort, 12 assessed maternal sero-status and 6 investigated birth order. The direction of associations in all studies was in accordance with our hypothesis that earlier age at infection is associated with worse outcomes in addition to its effect of increasing the probability of chronic HBV infection. This has implications for the control of hepatitis B.
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom. yusuke.shimakawa@lshtm.ac.uk
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shimakawa
authors.forename: Hong-Jing
authors.initials: HJ
authors.lastname: Yan
authors.forename: Naho
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Christian
authors.initials: C
authors.lastname: Bottomley
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hall
mesh_terms: D000367:Age Factors; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology*; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D018811:Maternal Exposure; D016017:Odds Ratio; D017594:Publication Bias; D013997:Time Factors; D014779:Virus Replication
references.citation: Proc Biol Sci. 1993 Aug 23;253(1337):197-201
references.pmid: 8397416
references.citation: Lancet. 2009 Feb 14;373(9663):582-92
references.pmid: 19217993
references.citation: J Viral Hepat. 2007 Mar;14(3):147-52
references.pmid: 17305879
references.citation: N Engl J Med. 2002 Jul 18;347(3):168-74
references.pmid: 12124405
references.citation: Am J Epidemiol. 1992 Nov 1;136(9):1115-21
references.pmid: 1334366
references.citation: Virol J. 2008 Apr 16;5:49
references.pmid: 18416832
references.citation: Am J Trop Med Hyg. 1999 Nov;61(5):716-9
references.pmid: 10586900
references.citation: Cancer. 1989 Dec 1;64(11):2377-80
references.pmid: 2553245
references.citation: J Gastroenterol Hepatol. 2003 Mar;18(3):246-52
references.pmid: 12603523
references.citation: Zhonghua Liu Xing Bing Xue Za Zhi. 2003 Jan;24(1):22-5
references.pmid: 12678957
references.citation: Epidemiol Infect. 1996 Oct;117(2):313-25
references.pmid: 8870629
references.citation: Ann Eugen. 1948 Apr;14(2):117-24
references.pmid: 18863975
references.citation: Liver Int. 2011 Oct;31(9):1373-80
references.pmid: 21745315
references.citation: J Viral Hepat. 2002 Jul;9(4):272-9
references.pmid: 12081604
references.citation: Hepatology. 2010 Feb;51(2):435-44
references.pmid: 19918971
references.citation: Hepatology. 1988 Mar-Apr;8(2):378-82
references.pmid: 3356420
references.citation: Hepatology. 2009 May;49(5 Suppl):S85-95
references.pmid: 19399797
references.citation: Gastroenterology. 2007 Nov;133(5):1452-7
references.pmid: 17920063
references.citation: Epidemiology. 2000 Nov;11(6):680-3
references.pmid: 11055629
references.citation: N Engl J Med. 1976 Apr 1;294(14):746-9
references.pmid: 943694
references.citation: J Viral Hepat. 2004 Mar;11(2):97-107
references.pmid: 14996343
references.citation: J Med Virol. 2005 Apr;75(4):513-21
references.pmid: 15714494
references.citation: J Hepatol. 2011 Jul;55(1):183-91
references.pmid: 21238520
references.citation: Ann Intern Med. 2001 Nov 6;135(9):759-68
references.pmid: 11694101
references.citation: J Pediatr Gastroenterol Nutr. 2002 Oct;35(4):487-94
references.pmid: 12394372
references.citation: JAMA. 2006 Jan 4;295(1):65-73
references.pmid: 16391218
references.citation: J Clin Epidemiol. 2009 Oct;62(10):e1-34
references.pmid: 19631507
references.citation: N Z Med J. 2000 Apr 14;113(1107):114-6
references.pmid: 10834277
references.citation: J Hepatol. 1989 Mar;8(2):226-31
references.pmid: 2715622
references.citation: Int J Cancer. 2006 Aug 1;119(3):687-94
references.pmid: 16496403
references.citation: J Pediatr. 1989 Sep;115(3):385-90
references.pmid: 2769497
references.citation: Vaccine. 2010 Jan 8;28(3):589-90
references.pmid: 19896455
references.citation: Nihon Shokakibyo Gakkai Zasshi. 1991 Aug;88(8):1545-53
references.pmid: 1942609
references.citation: Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):369-76
references.pmid: 11927497
references.citation: Hepatology. 2011 Feb;53(2):429-36
references.pmid: 21274864
references.citation: Cancer Epidemiol Biomarkers Prev. 1998 Jul;7(7):559-65
references.pmid: 9681522