Risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) infection: a systematic review and meta‐analysis

Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is a leading cause of death in individuals with chronic hepatitis B virus (HBV) infection. It is uncertain how the presence of other metabolic factors and comorbidities influences HCC risk in HBV. The...

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Published inJournal of viral hepatitis Vol. 28; no. 3; pp. 493 - 507
Main Authors Campbell, Cori, Wang, Tingyan, McNaughton, Anna L., Barnes, Eleanor, Matthews, Philippa C.
Format Journal Article
LanguageEnglish
Published England Wiley Subscription Services, Inc 01.03.2021
John Wiley and Sons Inc
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Abstract Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is a leading cause of death in individuals with chronic hepatitis B virus (HBV) infection. It is uncertain how the presence of other metabolic factors and comorbidities influences HCC risk in HBV. Therefore, we performed a systematic literature review and meta‐analysis to seek evidence for significant associations. MEDLINE, EMBASE and Web of Science databases were searched from 1 January 2000 to 24 June 2020 for studies investigating associations of metabolic factors and comorbidities with HCC risk in individuals with chronic HBV infection, written in English. We extracted data for meta‐analysis and generated pooled effect estimates from a fixed‐effects model. Pooled estimates from a random‐effects model were also generated if significant heterogeneity was present. We identified 40 observational studies reporting on associations of diabetes mellitus (DM), hypertension, dyslipidaemia and obesity with HCC risk. Only DM had a sufficient number of studies for meta‐analysis. DM was associated with >25% increase in hazards of HCC (fixed‐effects hazards ratio [HR] 1.26, 95% confidence interval (CI) 1.20–1.32, random‐effects HR 1.36, 95% CI 1.23–1.49). This association was attenuated towards the null in a sensitivity analysis restricted to studies adjusted for metformin use. In conclusion, in adults with chronic HBV infection, DM is a significant risk factor for HCC, but further investigation of the influence of antidiabetic drug use and glycaemic control on this association is needed. Enhanced screening of individuals with HBV and diabetes may be warranted.
AbstractList Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is a leading cause of death in individuals with chronic hepatitis B virus (HBV) infection. It is uncertain how the presence of other metabolic factors and comorbidities influences HCC risk in HBV. Therefore, we performed a systematic literature review and meta‐analysis to seek evidence for significant associations. MEDLINE, EMBASE and Web of Science databases were searched from 1 January 2000 to 24 June 2020 for studies investigating associations of metabolic factors and comorbidities with HCC risk in individuals with chronic HBV infection, written in English. We extracted data for meta‐analysis and generated pooled effect estimates from a fixed‐effects model. Pooled estimates from a random‐effects model were also generated if significant heterogeneity was present. We identified 40 observational studies reporting on associations of diabetes mellitus (DM), hypertension, dyslipidaemia and obesity with HCC risk. Only DM had a sufficient number of studies for meta‐analysis. DM was associated with >25% increase in hazards of HCC (fixed‐effects hazards ratio [HR] 1.26, 95% confidence interval (CI) 1.20–1.32, random‐effects HR 1.36, 95% CI 1.23–1.49). This association was attenuated towards the null in a sensitivity analysis restricted to studies adjusted for metformin use. In conclusion, in adults with chronic HBV infection, DM is a significant risk factor for HCC, but further investigation of the influence of antidiabetic drug use and glycaemic control on this association is needed. Enhanced screening of individuals with HBV and diabetes may be warranted.
Author Barnes, Eleanor
Matthews, Philippa C.
Campbell, Cori
McNaughton, Anna L.
Wang, Tingyan
AuthorAffiliation 2 Department of Hepatology Oxford University NHS Foundation Trust John Radcliffe Hospital Oxford UK
4 NIHR BRC John Radcliffe Hospital Oxford UK
3 Department of Infectious Diseases and Microbiology Oxford University Hospitals NHS Foundation Trust John Radcliffe Hospital Oxford UK
1 Nuffield Department of Medicine University of Oxford Oxford UK
AuthorAffiliation_xml – name: 2 Department of Hepatology Oxford University NHS Foundation Trust John Radcliffe Hospital Oxford UK
– name: 4 NIHR BRC John Radcliffe Hospital Oxford UK
– name: 1 Nuffield Department of Medicine University of Oxford Oxford UK
– name: 3 Department of Infectious Diseases and Microbiology Oxford University Hospitals NHS Foundation Trust John Radcliffe Hospital Oxford UK
Author_xml – sequence: 1
  givenname: Cori
  orcidid: 0000-0001-5890-7105
  surname: Campbell
  fullname: Campbell, Cori
  organization: University of Oxford
– sequence: 2
  givenname: Tingyan
  orcidid: 0000-0002-8351-9494
  surname: Wang
  fullname: Wang, Tingyan
  organization: University of Oxford
– sequence: 3
  givenname: Anna L.
  orcidid: 0000-0002-7436-8727
  surname: McNaughton
  fullname: McNaughton, Anna L.
  organization: University of Oxford
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  surname: Barnes
  fullname: Barnes, Eleanor
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  givenname: Philippa C.
  orcidid: 0000-0002-4036-4269
  surname: Matthews
  fullname: Matthews, Philippa C.
  email: philippa.matthews@ndm.ox.ac.uk
  organization: John Radcliffe Hospital
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33305479$$D View this record in MEDLINE/PubMed
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Copyright 2020 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.
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2020 The Authors. published by John Wiley & Sons Ltd.
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– notice: 2020. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2020 The Authors. published by John Wiley & Sons Ltd.
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Issue 3
Keywords HCC
Hepatitis B virus
comorbidities
diabetes
hepatocellular carcinoma
Language English
License Attribution
2020 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.
This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Snippet Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is a leading cause of death in individuals with chronic...
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SubjectTerms Antidiabetics
Chronic infection
comorbidities
Diabetes
Diabetes mellitus
Dyslipidemia
HCC
Hepatitis
Hepatitis B
Hepatitis B virus
Hepatocellular carcinoma
Infections
Literature reviews
Liver cancer
Meta-analysis
Metabolism
Metformin
Original
Risk factors
Sensitivity analysis
Title Risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) infection: a systematic review and meta‐analysis
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fjvh.13452
https://www.ncbi.nlm.nih.gov/pubmed/33305479
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https://pubmed.ncbi.nlm.nih.gov/PMC8581992
Volume 28
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