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Spectrum of Liver Disease in Hepatitis B Virus (HBV) Patients Co-infected with Human Immunodeficiency Virus (HIV)

Results of the HBV-HIV Cohort Study

Sterling, Richard K., MD, MSc, FACG1; Wahed, Abdus S., PhD2; King, Wendy C., PhD2; Kleiner, David E., MD3; Khalili, Mandana, MD4; Sulkowski, Mark, MD5; Chung, Raymond T., MD6; Jain, Mamta K., MD7; Lisker-Melman, Mauricio, MD8; Wong, David K., MD9; Ghany, Marc G., MD3 the HIV-HBV Cohort Study of the Hepatitis B Research Network

American Journal of Gastroenterology: May 2019 - Volume 114 - Issue 5 - p 746–757
doi: 10.1038/s41395-018-0409-9

BACKGROUND: 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.

1Virginia Commonwealth University, Richmond, VA, USA;

2University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA;

3National Institutes of Health, Bethesda, MD, USA;

4University of California at San Francisco, San Francisco, CA, USA;

5The Johns Hopkins University, Baltimore, MD, USA;

6Massachusetts General Hospital, Boston, MA, USA;

7University of Texas Southwestern, Dallas, TX, USA;

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

9University Health Network, Toronto, ON, Canada.

Correspondence: Richard K. Sterling, MD, MSc, FACG. E-mail:

Received August 06, 2018

Accepted September 13, 2018

© The American College of Gastroenterology 2019. All Rights Reserved.
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