Digestive Diseases and Sciences

, Volume 64, Issue 2, pp 358–366 | Cite as

A Comparison Between Community and Academic Practices in the USA in the Management of Chronic Hepatitis B Patients Receiving Entecavir: Results of the ENUMERATE Study

  • Hannah M. LeeEmail author
  • Joseph Ahn
  • W. Ray Kim
  • Joseph K. Lim
  • Mindie Nguyen
  • Calvin Q. Pan
  • Donghee Kim
  • Ajitha Mannalithara
  • Helen Te
  • Huy Trinh
  • Danny Chu
  • Tram Tran
  • Jocelyn Woog
  • Anna S. Lok
Original Article


Background and Aims

The management of chronic hepatitis B patients is not well characterized in real-world practice. We compared baseline characteristics of CHB patients on entecavir, the frequency of on-treatment monitoring, and the effectiveness of ETV treatment between academic and community practices.


Treatment-naïve CHB patients ≥18 years old, treated with ETV for ≥12 months from 2005 to 2013, in 26 community and academic practices throughout the USA were retrospectively evaluated.


Of 841 patients enrolled, 658 (65% male, 83% Asian, median age 47, 9% with cirrhosis) met inclusion criteria. Half of the patients (52%) were from community practices. A lower percentage of patients in community practices had cirrhosis or liver cancer (5 vs. 14%). Community practices more often treated patients with baseline ALT < 2 × ULN. Over a median follow-up of 4 years, community practices were more likely to discontinue ETV with less frequent laboratory monitoring compared to academic practices. The 5-year cumulative probability of ALT normalization was greater among patients treated in community practices (70 vs. 50%, p < 0.001), but the 5-year cumulative probability of undetectable HBV DNA was lower (45 vs. 70%, p < 0.001) than those treated in academic practices.


Academic practices saw CHB patients with more advanced liver disease, more often followed AASLD guidelines, and monitored patients on ETV treatment more frequently than community practices. While patients in community practices were less likely to achieve undetectable HBV DNA and more likely to achieve ALT normalization, the rates of HBeAg loss and seroconversion as well as HBsAg loss were similar.


Chronic HBV Practice management Antiviral therapy HBeAg loss HBsAg loss 



Alanine aminotransferase


Chronic hepatitis




Tenofovir disoproxil fumarate


Hepatitis B e antigen


Hepatitis B e antibody


Hepatitis B virus


Institutional review board






Nonalcoholic fatty liver disease



The authors thank the following ENUMERATE investigators and AHF members for their contributions: Daryl Lau: Beth Israel Deaconess Medical Center; Truong-Sinh Leduc: Leduc Medical Group; Albert Min: Mount Sinai Beth Israel, NYC, NY; Loc Trong Le: Woodholme Gastroenterology Associates; Ho Bae: Asian Pacific Liver Center; San Van Tran: Sang Van Tran PC; Son Do: Digestive Health Associates of Texas, Plano, TX; Hie-Won L. Hann: Jefferson University Hospitals; Clifford Wong: San Francisco, CA; Steve-Huy Han: UCLA; K. Rajender Reddy: University of Pennsylvania, Philadelphia, PA; James Park: New York University; Anjana Pillai: Emory University; Myron Tong: UCLA.

Author’s contribution

Hannah Lee, Joseph Ahn, Joseph Lim, W. Ray Kim, Calvin Pan, Mindie Nguyen, and Anna Lok helped in study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, obtained funding, and study supervision. Donghee Kim and Ajitha Mannalithara contributed to statistical analysis. Huy Trinh, Danny Chu, Tram Tran, Helen Te, and Jocelyn Woog helped in acquisition of data, critical revision of the manuscript for important intellectual content.


This study is supported by an investigator-initiated grant to the Asian Health Foundation by Bristol-Myers Squibb.

Compliance with ethical standards

Conflict of interest

Hannah Lee and Joseph Ahn have no disclosures. Anna S. Lok has research grant support from Bristol-Myers Squibb, Gilead Sciences and NIH Grant U01 DK082863. Mindie Nguyen has research support from BMS, Gilead, Janssen, National Cancer Institute, Pfizer. She is on the Advisory board/consultant for Janssen, Novartis, Gilead, Alnylam, Dynavax, Spring Bank, Intercept. Calvin Pan is a speaker, consultant for Bristol-Myers Squibb. Helen Te has research grant support from Abbvie, Conatus, Bristol-Myers Squibb. She is on the Advisory board for Bristol-Myers Squibb. Danny Chu is on the Advisory board and speaker’s bureau for Gilead Sciences. Tram Tran has Research grant support from Bristol-Myers Squibb and Gilead Sciences. She is on the Advisory board for Bristol-Myers Squibb and Gilead Sciences. There is no other disclosures for all other authors.

Ethical statement

Hannah Lee confirms that this work is original and has not been published elsewhere nor is it currently under consideration for publication elsewhere. Hannah Lee is acting as the submission’s guarantor and takes responsibility for the integrity of the work as a whole, from inception to published article. All authors approved the final version of the article.


  1. 1.
    Schweitzer A, Horn J, Mikolajczyk RT, et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546–1555.CrossRefGoogle Scholar
  2. 2.
    Kowdley KV, Wang CC, Welch S, et al. Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology. 2012;56:422–433.CrossRefGoogle Scholar
  3. 3.
    Weinbaum M, Williams I, Mast E, et al. MMWR Recomm Rep. 2008;57 (RR-8):1–20.Google Scholar
  4. 4.
    Terrault NA, Lok AS, McMahon BJ, et al. Update on prevention, diagnosis, and treatment and of chronic hepatitis B: AASLD 2018 Hepatitis B Guidance.
  5. 5.
    Sarkar M, Scvachko VA, Ready JB, et al. Characteristics and management of patients with chronic hepatitis B in an integrated care setting. Dig Dis Sci. 2014;59:2100–2108. CrossRefGoogle Scholar
  6. 6.
    Giannini EG, Marenco S, Boni S, et al. Therapeutic management of chronic hepatitis B in clinical practice: a region-wide survey. J Clin Gastroenterol. 2015;49:228–234.CrossRefGoogle Scholar
  7. 7.
    Arama V, Leblebicioglu H, Simon K, et al. Chronic Hepatitis B monitoring and treatment patterns in five European countries with different access and reimbursement policies. Antivir Ther. 2014;19:245–257.CrossRefGoogle Scholar
  8. 8.
    Zhang S, Ristau J, Trinh H, et al. Undertreatment of Asian chronic hepatitis B patients on the basis of standard guidelines: a community–based study. Dig Dis Sci. 2012;57:1373–1383. CrossRefGoogle Scholar
  9. 9.
    Ahn J, Lee HM, Lim JK, et al. Entecavir safety and effectiveness in a national cohort of treatment- naïve chronic hepatitis B patients in the US- the ENUMERATE study. Aliment Pharmacol Ther. 2015;43:134–144.CrossRefGoogle Scholar
  10. 10.
    Lok AS, McMahon BJ. Chronic Hepatitis B: Update 2009. Hepatology. 2009;50:1–36.Google Scholar
  11. 11.
    Keefe EB, Dietrich DT, Han SH, et al. A treatment of algorithm for the management of chronic hepatitis B infection in the United States. Clin Gastroenterol Hepatol. 2004;2:87–106.CrossRefGoogle Scholar
  12. 12.
    Keefe EB, Dietrich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315–1341.CrossRefGoogle Scholar
  13. 13.
    Tong MJ, Pan CQ, Hann HW, et al. The management of chronic hepatitis B in Asian Americans. Dig Dis Sci. 2011;56:3143–3162.CrossRefGoogle Scholar
  14. 14.
    Tong MJ, Hsu L, Chang PW, et al. Evaluation of current treatment recommendations for chronic hepatitis B: a 2011 update. J Gastroenterol Hepatol. 2011;26:829–835.CrossRefGoogle Scholar
  15. 15.
    European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol. 2009;50:227–242.CrossRefGoogle Scholar
  16. 16.
    Lai M, Hyatt BJ, Nasser I, et al. The clinical significance of persistently normal ALT in chronic hepatitis B infection. J Hepatol. 2007;47:760–767.CrossRefGoogle Scholar
  17. 17.
    Jang JW, Choi JY, Kim YS, et al. Long- term effect of antiviral therapy on disease course after decompensation in patients with hepatitis B virus-related cirrhosis. Hepatology. 2015;61:1809–1820.CrossRefGoogle Scholar
  18. 18.
    Sinn DH, Lee J, Goo J, et al. Hepatocellular carcinoma risk in chronic hepatitis B virus-infected compensated cirrhosis patients with low viral load. Hepatology. 2015;62:694–701.CrossRefGoogle Scholar
  19. 19.
    Ha NB, Trinh HN, Nguyen HA, et al. Response to higher dose of entecavir 1.0 mg daily in patients with partial response to entecavir 0.5 mg daily. J Clin Gastroenterol. 2013;47:461–465.CrossRefGoogle Scholar
  20. 20.
    Chang TT, Lai CL, Kew Yoon S, et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen- positive chronic hepatitis B. Hepatology. 2010;51:422–430.CrossRefGoogle Scholar
  21. 21.
    Pol S, Lampertico P. First-line treatment of chronic hepatitis B with entecavir or tenofovir in ‘real-life’ settings: from clinical trials to clinical practice. J Viral Hepat. 2012;19:377–386.CrossRefGoogle Scholar
  22. 22.
    Ku K, Li J, Ha NB, et al. Chronic hepatitis B management based on standard guidelines in community primary care and specialty clinics. Dig Dis Sci. 2013;58:3626–3633. Scholar
  23. 23.
    Kim LH, Nguyen VG, Trinh HN, et al. Gender disparity and real-life practice setting differences in actual treatment rates of patients with chronic hepatitis B. Dig Dis Sci. 2014;59:2091–2099.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hannah M. Lee
    • 1
    Email author
  • Joseph Ahn
    • 2
  • W. Ray Kim
    • 3
  • Joseph K. Lim
    • 4
  • Mindie Nguyen
    • 3
  • Calvin Q. Pan
    • 5
  • Donghee Kim
    • 3
  • Ajitha Mannalithara
    • 3
  • Helen Te
    • 6
  • Huy Trinh
    • 7
  • Danny Chu
    • 8
  • Tram Tran
    • 9
  • Jocelyn Woog
    • 10
  • Anna S. Lok
    • 11
  1. 1.Division of Gastroenterology, Hepatology and NutritionVirginia Commonwealth University Medical CenterRichmondUSA
  2. 2.Division of Gastroenterology and HepatologyOregon Health and Science UniversityPortlandUSA
  3. 3.Division of Gastroenterology and HepatologyStanford UniversityStanfordUSA
  4. 4.Yale UniversityNew HavenUSA
  5. 5.Division of Gastroenterology and HepatologyNYU Langone Health, NYU School of MedicineNew YorkUSA
  6. 6.Digestive Disease CenterUniversity of ChicagoChicagoUSA
  7. 7.San Jose GastroenterologySan JoseUSA
  8. 8.Albert Einstein College of MedicineNew YorkUSA
  9. 9.Department of MedicineCedars Sinai Medical CenterLos AngelesUSA
  10. 10.Asian Health FoundationRochesterUSA
  11. 11.Division of Gastroenterology and HepatologyUniversity of MichiganAnn ArborUSA

Personalised recommendations