Association of early age at establishment of chronic hepatitis B infection with persistent viral replication, liver cirrhosis and hepatocellular carcinoma: a systematic review

Yusuke Shimakawa, Hong-Jing Yan, Naho Tsuchiya, Christian Bottomley, Andrew J Hall, Yusuke Shimakawa, Hong-Jing Yan, Naho Tsuchiya, Christian Bottomley, Andrew J Hall

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow diagram of study selection.
Figure 1. Flow diagram of study selection.
Abbreviations: CHB, chronic hepatitis B; HBV, hepatitis B virus.
Figure 2. Effect measures and 95% CIs…
Figure 2. Effect measures and 95% CIs for the association between maternal HBV sero-status and HBV-related outcomes.
Odds ratios for case-control or cross-sectional studies –, – and risk ratios for cohort studies – are presented. Except the study by Wheeley which assessed maternal HBeAg, all studies examined maternal HBsAg.
Figure 3. Funnel plot for studies investigating…
Figure 3. Funnel plot for studies investigating the relation between maternal sero-marker and the persistence/presence of HBeAg.
Dashed line represents pseudo 95% confidence limits.

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