Abstract
Background
Concomitant chronic hepatitis B infection (CHB) and non-alcoholic fatty liver disease (NAFLD) is common, but the implications of NAFLD on clinical outcomes of CHB, including hepatocellular carcinoma (HCC), are not well-investigated.
Methods
CHB patients were recruited for transient elastography assessment for liver stiffness (LS), and controlled attenuation parameter (CAP), a non-invasive quantification of hepatic steatosis, and were prospectively followed up for development of HCC. Steatosis and severe steatosis were diagnosed by CAP ≥ 248 dB/m and ≥ 280 dB/m respectively, and advanced fibrosis/cirrhosis was diagnosed by LS ≥ 9 kPa. The independent effect of hepatic steatosis on HCC was examined via propensity score matching (PSM) of LS and other significant clinical variables.
Results
Forty-eight patients developed HCC among 2403 CHB patients (55.6% male, median age 55.6 years, 57.1% antiviral-treated, median ALT 26 U/L) during a median follow-up of 46.4 months. Multivariate Cox regression analysis showed age (HR 1.063), male (HR 2.032), Albumin-Bilirubin score (HR 2.393) and CAP (HR 0.993) were associated with HCC development. The cumulative probability of HCC was 2.88%, 1.56% and 0.71%, respectively for patients with no steatosis, mild-to-moderate steatosis, and severe steatosis, respectively (p = 0.01). The risk of HCC increased from 1.56 to 8.89% in patients without severe steatosis if advanced fibrosis/cirrhosis was present (p < 0.001). PSM yielded 957 pairs of CHB patients and hepatic steatosis was independently associated with HCC (HR 0.41).
Conclusion
Reduced hepatic steatosis was significantly associated with a higher risk of incident HCC in CHB infection. Routine CAP and LS measurements are important for risk stratification.
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Data availability
Data available within the article or its supplementary materials.
Abbreviations
- CHB:
-
Chronic hepatitis B
- NAFLD:
-
Non-alcoholic fatty liver disease
- HCC:
-
Hepatocellular carcinoma
- HCV:
-
Hepatitis C virus
- HBV:
-
Hepatitis B virus
- HBsAg:
-
Hepatitis B surface antigen
- NA:
-
Nucleos(t)ide analogue
- CAP:
-
Controlled attenuation parameter
- HbA1c:
-
Glycated hemoglobin
- FG:
-
Fasting glucose
- TG:
-
Triglyceride
- LDL:
-
Low density lipoprotein
- HDL:
-
High density lipoprotein
- ALT:
-
Alanine aminotransferase
- AST:
-
Aspartate aminotransferase
- HBeAg:
-
Hepatitis B e antigen
- LS:
-
Liver stiffness
- F0/F1:
-
No/minimal fibrosis
- F3:
-
Advanced fibrosis
- F4:
-
Cirrhosis
- dB/m:
-
Decibel/ meter
- IQR:
-
Interquartile range
- HR:
-
Hazard ratio
- CI:
-
Confidence interval
- NASH:
-
Non-alcoholic steatohepatitis
- HBcAg:
-
Hepatitis B core antigen
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Acknowledgements
The interim results of this study was presented in the Digital Liver Meeting 2020 as a poster (Hepatology 2020; volume 72, issue number 1 supplementary, P.658A; poster number 1084). The authors would like to thank Ms. Carmen Chan, Ms. Carol Chu and Mr. Justin Ma for the logistical arrangement of patients.
Funding
This study was supported by the General Research Fund, Research Grants Council, The Government of the Hong Kong Special Administrative Region (ref no: 17125916); Innovative Research Fund of the State Key Laboratory of Liver Research, The University of Hong Kong (Ref no: SKLLR/IRF/2018/08); and the Outstanding Young Researcher Award, The University of Hong Kong.
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The authors declare they have participated in the preparation of the manuscript and have seen and approved the final version. LYM was involved in data acquisition, data analysis and interpretation, and drafting of manuscript. RWHH and KSC were involved in data acquisition and analysis. FL and DKHW were involved in data acquisition. BL was responsible for analysis of data. JF and MFY was involved in critical revision of manuscript. WKS was involved in study concept and design, analysis and interpretation of data, critical revision of manuscript and overall study supervision.
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J Fung has been a consultant for Gilead Sciences. MF Yuen received speaker fees and received research funding from Bristol-Myers Squibb and Gilead Sciences. WKS received speaker fees from Mylan and is an advisory board member, received speaker fees and research funding from Gilead Sciences. All other authors: none to declare.
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The present study was approved by the Institutional Review Board/Ethics Committee of the University of Hong Kong and the Hong Kong West Cluster of Hospital Authority.
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Mak, LY., Hui, R.WH., Fung, J. et al. Reduced hepatic steatosis is associated with higher risk of hepatocellular carcinoma in chronic hepatitis B infection. Hepatol Int 15, 901–911 (2021). https://doi.org/10.1007/s12072-021-10218-2
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DOI: https://doi.org/10.1007/s12072-021-10218-2