Article | Published:

Spectrum of Liver Disease in Hepatitis B Virus (HBV) Patients Co-infected with Human Immunodeficiency Virus (HIV): Results of the HBV-HIV Cohort Study

The American Journal of Gastroenterology (2018) | Download Citation

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Abstract

Background/Aims

Because most HBV/HIV co-infected patients on combination antiretroviral therapy (cART) have suppressed HBV DNA and normal liver enzymes, the histologic spectrum of liver disease in HBV/HIV coinfection is poorly defined. To address this gap in knowledge, we conducted a prospective study to comprehensively characterize liver disease severity assessed by liver biopsy in a well-defined cohort of HBV/HIV patients in North America receiving cART.

Methods

Adult HIV/HBsAg positive patients on stable cART were recruited. Demographic, clinical, serological, and virological data were collected. Liver histology was assessed by a central pathology committee. The association of demographic, clinical, serologic, and virologic characteristics with liver histology was assessed using logistic regression.

Results

In this cross-sectional analysis, the mean age of the cohort (N = 139) was 49 years; 92% were male, 51% were non-Hispanic black, 7% had at-risk alcohol use with a median duration of infections of 14 years. The median ALT was 28 IU/L and CD4 count was 568 cells/mm3. Almost all (99%) were on cART. Three-fourths (75%) had undetectable HIV RNA (<20 copies/mL). HBeAg was positive in 62%, HBV DNA was below the limit of quantification (<20 IU/mL) in 57% and <1000 IU/mL in 80%; 7% had incomplete viral suppression (HBV DNA  ≥1000 IU/mL and HIV RNA <20 copies/mL). Liver histology (available in n = 114) showed significant periportal, lobular, and portal inflammation (scores ≥2) in 14%, 31%, and 22% respectively. Over a third (37%) had significant fibrosis (Ishak stage ≥2); 24% had advanced fibrosis (Ishak stage ≥3). Higher ALT (adjusted OR 1.19 per 10 IU/L; 95% CI [1.01, 1.41]; p = 0.03) and lower platelet count (adjusted OR 0.81 per 20,000 mm3; 95% CI [0.67–0.97]; p = 0.02) but not HBV DNA were independently associated with advanced fibrosis.

Conclusions

In this cohort of patients with HBV/HIV coinfection receiving long-term cART with viral suppression, we observed significant fibrosis in more than one-third of patients.

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Acknowledgements

We would like to thank our patients for their participation, the HBRN Steering Committee for their guidance, Roche Diagnostics and Roche Molecular for supplying test kits, and NIDDK for funding this R01. This research was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute. In addition to the authors, the HBV–HIV Cohort Study of the HBRN would like to acknowledge the contributions of the following: Massachusetts General Hospital: Nifasha Rusibamayila, BA, Cara Foley, BA, Jenna Gustafson, MS, Atul Bhan, MD (Boston, MA); Johns Hopkins University: Kathleen Ward, MSPH, CHES (Baltimore, MD); Washington University School of Medicine: Rachel Presti, MD, PhD, Lisa Kessels, RN, BSN, Warren Seyfried, PhD, Michael K. Klebert, Ph.D, R.N, ANP-BC (St. Louis, MO); University Health Network: Bryan Boyachuk, RN, CCRP (Toronto, Ontario); University of California at San Francisco: Norah Terrault, MD, Annie Luetkemeyer, MD, Rageshree Ramachandran, MD, PhD, Anna Trujillo, BS, Claudia Ayala, MS, Ivy Lau, BS, Ashley Shobe, MS (San Francisco, CA); University of Texas Southwestern: Minerva Santos, Kranthi Vysyaraju, MS, Tianna Petersen, MS (Dallas, TX); Virginia Commonwealth University: Paula Smith, RN, BSN, Charlotte Hofmann, RN, Michael Idowu, MD (Richmond, VA); Liver Diseases Branch, NIDDK, NIH: Vanessa Haynes-Williams, RN, PhD, Nancy E. Fryzek, BSN, MBA, Elenita Rivera, BSN, Wen-Chun A. Huang, BS, BSN, Nevitt Morris, BS, BSN, Varun Takyar, MD, Chunwei W. Lai, MD, PhD (Bethesda, MD); Liver Disease Research Branch, NIDDK, NIH: Jay H. Hoofnagle, MD, Averell H. Sherker, MD, Edward Doo, MD (Bethesda, MD); University of Pittsburgh Graduate School of Public Health Data Coordinating Center: Steven Belle, PhD, MScHyg, Michelle Danielson, PhD, Tamara Haller, Stephanie Kelley, MS, Sharon Lawlor, MBA, Melissa Weiner, MPH (Pittsburgh, PA).

Author information

Affiliations

  1. Virginia Commonwealth University, Richmond, VA, 23284, USA

    • Richard K. Sterling MD, MSc, FACG
  2. University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, 15261, USA

    • Abdus S. Wahed Phd
    •  & Wendy C. King Phd
  3. National Institutes of Health, Bethesda, PA, 15261, USA

    • David E. Kleiner MD
    •  & Marc G. Ghany MD
  4. University of California at San Francisco, San Francisco, CA, USA

    • Mandana Khalili MD
  5. Johns Hopkins University, Baltimore, MD, 21218, USA

    • Mark Sulkowski MD
  6. Massachusetts General Hospital, Boston, USA

    • Raymond T. Chung MD
  7. University of Texas Southwestern, Dallas, TX, 75390, USA

    • Mamta K. Jain MD
  8. Washington University School of Medicine, St. Louis, MO, 63110, USA

    • Mauricio Lisker-Melman MD
  9. University Health Network, Toronto, ON, Canada

    • David K. Wong MD

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Consortia

  1. and the HIV-HBV Cohort Study of the Hepatitis B Research Network

    Guarantor of the article

    Dr. Richard K. Sterling, MD, MSc, FACG.

    Specific author contributions

    Richard K. Sterling: planning, collecting data, interpretation of data, drafting the manuscript, and approved final draft submitted. Abdus S. Wahed: planning, interpretation of data, drafting the manuscript, and approved final draft. Wendy C King: planning, interpretation of data, drafting the manuscript, and approved final draft submitted. David K. Kleiner: planning, interpretation of data, drafting the manuscript, and approved final draft submitted. Mandana Khalili: planning, collecting data, interpretation of data, drafting the manuscript, and approved final draft submitted. Mark Sulkowski: planning, collecting data, interpretation of data, drafting the manuscript, and approved final draft submitted. Raymond T. Chung: planning, collecting data, interpretation of data, drafting the manuscript, and approved final draft submitted. Mamta Jain: planning, collecting data, interpretation of data, drafting the manuscript, and approved final draft submitted. Mauricio Lisker-Melman: planning, collecting data, interpretation of data, drafting the manuscript, and approved final draft submitted. David K. Wong: planning, collecting data, interpretation of data, drafting the manuscript, and approved final draft submitted. Marc Ghany: planning, collecting data, interpretation of data, drafting the manuscript, and approved final draft submitted.

    Conflict of interest

    Richard K. Sterling: Gilead, AbbVie, Merck, Roche, Pfizer, and Baxter. Abdus S. Wahed: none. Wendy C King: none. David K. Kleiner: none. Mandana Khalili: Gilead, Intercept Pharmaceuticals, and AbbVie. Mark Sulkowski: Gilead (consultant, research support). Raymond T. Chung: Gilead, BMS, Janssen, AbbVie, Boehringer, and Merck. Mamta Jain: Gilead, Janssen, Merck, and GSK. Mauricio Lisker-Melman: Abbvie, Gilead, Merck, and Simply Speaking. David K. Wong: Gilead, BMS, Vertex, and Boehringer. Marc Ghany: none

    Financial support

    This study was funded by NIDDK (R01-DK94818) as an ancillary study of the Hepatitis B Research Network to Dr. Richard K. Sterling.

    Corresponding author

    Correspondence to Richard K. Sterling MD, MSc, FACG.

    Appendix: Inclusion and exclusion criteria

    Inclusion criteria

    • ≥18 years of age;

    • serologic evidence of HIV infection by HIV antibody positivity or history of positive HIV-RNA prior to screening;

    • serologic evidence of chronic hepatitis B infection by HBsAg positivity;

    • currently receiving any type of antiretroviral therapy for HBV or HIV; and

    • willingness to provide informed consent.

    Exclusion criteria

    • estimated life expectancy of <1 year based on clinical judgment of the investigator;

    • history of hepatic decompensation based on clinical or laboratory criteria;

    • hepatocellular carcinoma (HCC);

    • HCV RNA positive within 6 months prior to the baseline biopsy;

    • history of solid organ or bone marrow transplantation;

    • pregnant women;

    • medical or social condition which, in the opinion of the study physician, would make the patient unsuitable for the study or interfere with or prevent follow-up per protocol;

    • unable or unwilling to return for follow-up visits;

    • contraindications to liver biopsy.

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    DOI

    https://doi.org/10.1038/s41395-018-0409-9