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Performance of Serum-Based Scores for Identification of Mild Hepatic Steatosis in HBV Mono-infected and HBV–HIV Co-infected Adults

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Abstract

Background

There are limited data on noninvasive methods to identify hepatic steatosis in coexisting hepatitis B virus (HBV) infection.

Aims

To evaluate the diagnostic performance of noninvasive serum-based scores to detect steatosis using two distinct chronic HBV cohorts with liver histology evaluation.

Methods

Chronic HBV cohorts with untreated HBV mono-infection (N = 302) and with treated HBV–HIV (N = 92) were included. Liver histology was scored centrally. Four serum-based scores were calculated: hepatic steatosis index (HSI), nonalcoholic fatty liver disease Liver Fat Score (NAFLD-LFS), visceral adiposity index (VAI), and triglyceride glucose (TyG) index. Optimal cutoffs (highest sensitivity + specificity) to detect ≥ 5% HS, stratified by cohort, were evaluated.

Results

HBV–HIV (vs. HBV mono-infected) patients were older (median 50 vs. 43 years), and a higher proportion were male (92% vs. 60%), were black (51% vs. 8%), had the metabolic syndrome (41% vs. 25%), and suppressed HBV DNA (< 1000 IU/mL; 82% vs. 9%). Applying optimal cutoffs, the area under the receiver operator curve for detecting ≥ 5% steatosis in HBV-only and HBV–HIV, respectively, was 0.69 and 0.61 for HSI, 0.70 and 0.76 for NAFLD-LFS, 0.68 and 0.64 for TyG, and 0.68 and 0.69 for VAI. The accuracy of optimal cutoffs ranged from 61% (NAFLD-LFS) to 67% (TyG) among HBV-only and 56% (HSI) to 76% (NAFLD-LFS) among HBV–HIV. Negative predictive values were higher than positive predictive values for all scores in both groups.

Conclusion

The relative utility of scores to identify steatosis in chronic HBV differs by co-infection/anti-HBV medication status. However, even with population-specific cutoffs, several common serum-based scores have only moderate utility. ClinicalTrials.gov NCT01924455.

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Abbreviations

HBV:

Hepatitis B virus

HIV:

Human immunodeficiency virus

cART:

Combination antiretroviral therapy

AIDS:

Acquired immunodeficiency syndrome

TDF:

Tenofovir disoproxil fumarate

FTC:

Emtricitabine

3TC:

Lamivudine

HBRN:

Hepatitis B Research Network

NIH:

National Institutes of Health

NIDDK:

National Institute of Diabetes and Digestive and Kidney Diseases

HBsAg:

Hepatitis B surface antigen

HBsAb:

Anti-hepatitis B surface antibody

HBeAg:

Hepatitis B envelop antigen

HBeAb:

Anti-hepatitis B envelop antibody

DNA:

Deoxyribonucleic acid

HDV:

Hepatitis delta virus

HCV:

Hepatitis C virus

RNA:

Ribonucleic acid

BMI:

Body mass index

HAI:

Histologic activity index

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

ALP:

Alkaline phosphatase

NASH:

Nonalcoholic steatohepatitis

IQR:

Interquartile range

NAFLD-LFS:

Nonalcoholic fatty liver disease Liver Fat Score

VAI:

Visceral adiposity index

TyG:

Triglyceride glucose index

HDL:

High-density lipoprotein

LDL:

Low-density lipoprotein

CAP:

Continuous attenuated parameter

VCTE:

Vibration-controlled transient elastography

NRTI:

Nucleoside reverse transcriptase inhibitor

PI:

Protease inhibitor

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Funding

Funding

This study was funded by NIDDK (R01-DK94818) as an ancillary study (NCT01924455) of the Hepatitis B Research Network to Dr. Richard K. Sterling. Dr. Sulkowski was partially supported by K24DA034621. Dr. Khalili was partially supported by K24AA022523

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Authors and Affiliations

  1. Section of Hepatology, Virginia Commonwealth University, 1200 E Broad Street, West Hospital, Rm 1478, Richmond, VA, 23298-0341, USA

    Richard K. Sterling

  2. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA

    Wendy C. King & Amanda S. Hinerman

  3. University of California San Francisco, San Francisco, USA

    Mandana Khalili

  4. National Institutes of Health, Bethesda, USA

    David E. Kleiner & Marc G. Ghany

  5. Johns Hopkins University, Baltimore, USA

    Mark Sulkowski

  6. Massachusetts General Hospital, Boston, USA

    Raymond T. Chung

  7. UT Southwestern Medical Center, Dallas, USA

    Mamta K. Jain

  8. Washington University School of Medicine, St. Louis, USA

    M auricio Lisker-Melman

  9. University Health Network, Toronto, Canada

    David K. Wong

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The HBV-HIV Cohort Study of the Hepatitis B Research Network

Corresponding author

Correspondence to Richard K. Sterling.

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Conflict of interest

Richard Sterling has received research grant from Abbott, AbbVie, Gilead, and Roche and serves on the data safety and monitoring board for Pfizer and Baxter. Mandana Khalili is a recipient of research grant (to her institution) from Gilead Sciences Inc. and Intercept Pharmaceuticals, and she has served as consultant for Gilead Sciences Inc. Raymond Chung has research grants (to institution) from Gilead, AbbVie, BMS, Merck, Boehringer, Roche, and Janssen. Mauricio Lisker-Melman serves on the speaker bureau for AbbVie, Gilead Sciences Inc., and SimplySpeaking. Mamta K. Jain has received research funding from Gilead Sciences, Janssen Pharmaceuticals, Merck, and GlaxoSmithKline. She has served on the scientific advisory board for Gilead Sciences. David Wong, Wendy King, Marc Ghany, and David Kleiner do not have any disclosures relevant to this project.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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The studies have been approved by the appropriate institutional and/or national research ethics committee and have been performed in accordance with the ethical standards as laid down in the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Flowchart of HBRN HBV mono-infected and HBV–HIV co-infected participants.

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Sterling, R.K., King, W.C., Khalili, M. et al. Performance of Serum-Based Scores for Identification of Mild Hepatic Steatosis in HBV Mono-infected and HBV–HIV Co-infected Adults. Dig Dis Sci 67, 676–688 (2022). https://doi.org/10.1007/s10620-021-06860-3

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