Incidence of Hepatocellular Carcinoma in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis

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Abstract

Background

The risk and determinants of HCC in patients with primary biliary cholangitis (PBC) are unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and risk factors associated with HCC risk among patients with PBC.

Methods

We searched PubMed, EMBASE, MEDLINE, Cochrane databases and reference lists from relevant articles to identify cohort studies that examined incidence of HCC in patients with PBC from inception through November 2019.

Results

A total of 29 studies including 22,615 patients met the eligibility criteria. The median cohort size was 292 patients followed for an average of 76 months. The pooled incidence rate for patients with PBC was 4.17 per 1000 patient-years (95% CI 3.17–5.47). On subgroup analysis, the incidence of HCC in patients with PBC cirrhosis was 15.7 per 1000 patient-years (95% CI 8.73–28.24). The HCC incidence rate was 9.82 per 1000 person-years (95% CI 5.92–16.28) in men and 3.82 per 1000 person-years (95% CI 2.85–5.11) in women.

Conclusions

Cirrhosis is the strongest risk factor for HCC in patients with PBC. Male gender was also a risk factor. Our meta-analysis supports current recommendations of HCC surveillance in patients with PBC cirrhosis. Further studies are needed to evaluate risk factors in this population.

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Change history

  • 29 September 2020

    The original version of the article unfortunately contained an error in the first name and the surname of the third author.

Abbreviations

PBC:

Primary biliary cirrhosis

HCC:

Hepatocellular carcinoma

CI:

Confidence interval

OR:

ODDS ratio

HR:

Hazard ratio

PH:

Proportional hazards

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Funding

This research was not funded. Dr Kanwal receives funding from in part by the U.S. Department of Veterans Affairs, and the Houston Veterans Affairs Health Services Research Center of Innovations (CIN13-413).

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YN is the guarantor of the article, collaborated in study design, screened articles, collected and analyzed the data and wrote the manuscript. AT collaborated in study design, screened articles, collected and analyzed the data and wrote the manuscript. PP screened articles and collected data. KE screened articles and collected data. RS collaborated in study design, screened articles and collected data. ZQ collaborated in study design, screened articles and collected data. HBES collaborated in study design and wrote the manuscript. APT analyzed data and wrote the manuscript. FK collaborated in study design, analyzed the data and wrote the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Yamini Natarajan.

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The authors declare no conflict of interest. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the National Institute of Diabetes Digestive and Kidney Diseases.

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Appendix 1

Appendix 1

Search Strategy

  1. 1.

    “liver cirrhosis, biliary”[mesh: noexp]

  2. 2.

    “primary biliary cirrhosis” [TIAB]

  3. 3.

    “primary biliary cholangitis” [TIAB]

  4. 4.

    #1 OR #2 OR #3

  5. 5.

    (liver[TIAB] OR hepatocellular[TIAB])

  6. 6.

    (carcinoma[TIAB] OR cancer*[TIAB] OR neoplasm*[TIAB] OR malignancy[tiab])

  7. 7.

    #5 AND #6

  8. 8.

    liver neoplasms [mesh: noexp]

  9. 9.

    #7 OR #8

  10. 10.

    #4 AND #9

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Natarajan, Y., Tansel, A., Patel, P. et al. Incidence of Hepatocellular Carcinoma in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis. Dig Dis Sci (2020). https://doi.org/10.1007/s10620-020-06498-7

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Keywords

  • Epidemiology
  • Hepatology
  • Hepatocellular carcinoma
  • Primary biliary cirrhosis
  • Risk factor
  • Natural history
  • Mortality
  • Systematic review