Early experiences from one of the first treatment programs for chronic hepatitis B in sub-Saharan Africa

Hanna Aberra, Hailemichael Desalegn, Nega Berhe, Girmay Medhin, Kathrine Stene-Johansen, Svein Gunnar Gundersen, Asgeir Johannessen, Hanna Aberra, Hailemichael Desalegn, Nega Berhe, Girmay Medhin, Kathrine Stene-Johansen, Svein Gunnar Gundersen, Asgeir Johannessen

Abstract

Background: Treatment for chronic hepatitis B (CHB) is virtually absent in sub-Saharan Africa. Here we present early experiences from a pilot program for treatment of CHB in Ethiopia.

Methods: Adults (≥18 years) with CHB were included in a cohort study at St. Paul's Hospital Millennium Medical College, Addis Ababa, from February 2015. The baseline assessment included liver function tests, viral markers and transient elastography (Fibroscan 402, Echosense, France). Logistic regression models were used to identify predictors of fibrosis. Tenofovir disoproxil fumarate (TDF) was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. The initial 300 patients underwent a more comprehensive evaluation and are presented here.

Results: One-hundred-and-thirty-eight patients (46.0%) were women and median age was 30 years (interquartile range 26-40). Co-infections were rare: four patients (1.3%) were anti-HCV positive, 11 (3.7%) were anti-HDV positive, whereas 5 (1.7%) had HIV-infection. The majority were hepatitis B e-antigen (HBeAg) negative (n = 262; 90.7%) and had a normal (≤40 U/L) alanine aminotransferase (ALT) (n = 245; 83.1%). Of 268 patients with a valid Fibroscan result, 79 (29.5%) had significant fibrosis (>7.9 kPa). Independent predictors of fibrosis were male sex, age > 35 years and viral load >20,000 IU/ml. In total, 74 patients (24.7%) started TDF therapy, of whom 46 (62.2%) had cirrhosis.

Conclusions: The majority were HBeAg negative and had normal ALT. However, one quarter of the patients were in need of antiviral treatment, underscoring the need to scale up CHB treatment on the African continent.

Trial registration: NCT02344498 ( ClinicalTrials.gov identifier). Registered 16 January 2015.

Keywords: Africa; Antiviral therapy; Hepatitis B virus; Resource-limited settings.

Figures

Fig. 1
Fig. 1
Liver fibrosis as a function of a sex, b age, c ALT and d HBV viral load in a cohort of patients with chronic hepatitis B in Ethiopia. Patients with invalid/missing Fibroscan results or ALT elevated more than 5 times the upper limit of normal were excluded from this analysis

References

    1. World Health Organization . Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. Geneva: WHO; 2015.
    1. European Association for the Study of the Liver EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57(1):167–185. doi: 10.1016/j.jhep.2012.02.010.
    1. World Health Organization. Global health sector strategy on viral hepatitis. Towards ending viral hepatitis. Geneva: WHO; 2016.
    1. 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(6):377–386. doi: 10.1111/j.1365-2893.2012.01602.x.
    1. Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468–475. doi: 10.1016/S0140-6736(12)61425-1.
    1. Kim WR, Loomba R, Berg T, et al. Impact of long-term tenofovir disoproxil fumarate on incidence of hepatocellular carcinoma in patients with chronic hepatitis B. Cancer. 2015;121(20):3631–3638. doi: 10.1002/cncr.29537.
    1. Terrault NA, Bzowej NH, Chang KM, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261–283. doi: 10.1002/hep.28156.
    1. Su TH, Hu TH, Chen CY, et al. Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients. Liver Int. 2016;36(12):1755–1764. doi: 10.1111/liv.13253.
    1. Lok AS, Trinh H, Carosi G, et al. Efficacy of entecavir with or without tenofovir disoproxil fumarate for nucleos(t)ide-naive patients with chronic hepatitis B. Gastroenterology. 2012;143(3):619–628. doi: 10.1053/j.gastro.2012.05.037.
    1. Nwokediuko SC. Chronic hepatitis B: management challenges in resource-poor countries. Hepat Mon. 2011;11(10):786–793.
    1. World Health Organization . Global hepatitis report, 2017. Geneva: WHO; 2017.
    1. World Health Organization. Ethiopia. Factsheets of health statistics. Regional office for Africa: WHO; 2016: . Accessed 5 April 2017.
    1. Belyhun Y, Maier M, Mulu A, Diro E, Liebert UG. Hepatitis viruses in Ethiopia: a systematic review and meta-analysis. BMC Infect Dis. 2016;16(1):761. doi: 10.1186/s12879-016-2090-1.
    1. Ministry of Health . National guideline for prevention and control of viral hepatitis in Ethiopia. Addis Ababa: Ethiopian Ministry of Health; 2016.
    1. Schiff E, Sorrell M, Maddrey W. Schiff's diseases of the liver. tenth. Philadelphia: Lippincott Williams and Wilkins; 2007.
    1. Chon YE, Choi EH, Song KJ, et al. Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis. PLoS One. 2012;7(9) doi: 10.1371/journal.pone.0044930.
    1. Lemoine M, Shimakawa Y, Nayagam S, et al. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa. Gut. 2016;65(8):1369–1376. doi: 10.1136/gutjnl-2015-309260.
    1. Chan HL, Wong GL, Choi PC, et al. Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B. J Viral Hepat. 2009;16(1):36–44. doi: 10.1111/j.1365-2893.2008.01037.x.
    1. European Association for the Study of the Liver. EASL 2017 Clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 2017; doi:10.1016/j.jhep.2017.03.021.
    1. Johannessen A, Naman E, Ngowi BJ, et al. Predictors of mortality in HIV-infected patients starting antiretroviral therapy in a rural hospital in Tanzania. BMC Infect Dis. 2008;8:52. doi: 10.1186/1471-2334-8-52.
    1. Kiire CF. The epidemiology and prophylaxis of hepatitis B in sub-Saharan Africa: a view from tropical and subtropical Africa. Gut. 1996;38(Suppl 2):S5–12. doi: 10.1136/gut.38.Suppl_2.S5.
    1. Kramvis A. The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics. Rev Med Virol. 2016;26(4):285–303. doi: 10.1002/rmv.1885.
    1. Alexopoulou A, Karayiannis P. HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection. World J Gastroenterol. 2014;20(24):7644–7652. doi: 10.3748/wjg.v20.i24.7644.
    1. Buti M, Fung S, Gane E, et al. Long-term clinical outcomes in cirrhotic chronic hepatitis B patients treated with tenofovir disoproxil fumarate for up to 5 years. Hepatol Int. 2015;9(2):243–250. doi: 10.1007/s12072-015-9614-4.
    1. Liu Y, Corsa AC, Buti M, et al. No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg- patients with chronic hepatitis B after 8 years of treatment. J Viral Hepat. 2017;24(1):68–74. doi: 10.1111/jvh.12613.
    1. Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130(3):678–686. doi: 10.1053/j.gastro.2005.11.016.
    1. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65–73. doi: 10.1001/jama.295.1.65.
    1. Sharma SK, Saini N, Chwla Y. Hepatitis B virus: inactive carriers. Virol J. 2005;2:82. doi: 10.1186/1743-422X-2-82.
    1. Matthews PC, Geretti AM, Goulder PJ, Klenerman P. Epidemiology and impact of HIV coinfection with hepatitis B and hepatitis C viruses in sub-Saharan Africa. J Clin Virol. 2014;61(1):20–33. doi: 10.1016/j.jcv.2014.05.018.
    1. Lemoine M, Shimakawa Y, Njie R, et al. Acceptability and feasibility of a screen-and-treat programme for hepatitis B virus infection in the Gambia: the prevention of liver fibrosis and cancer in Africa (PROLIFICA) study. Lancet Glob Health. 2016;4(8):e559–e567. doi: 10.1016/S2214-109X(16)30130-9.
    1. Kim WR. Epidemiology of hepatitis B in the United States. Hepatology. 2009;49(5 Suppl):S28–S34. doi: 10.1002/hep.22975.
    1. Hundie GB, Raj VS, GebreMichael D, Haagmans BL. Seroepidemiology of hepatitis B and C virus infections among blood donors in Ethiopia. J Med Virol. 2017;89(7):1300–1303. doi: 10.1002/jmv.24770.
    1. Winter A, Letang E, Vedastus Kalinjuma A, et al. Absence of hepatitis delta infection in a large rural HIV cohort in Tanzania. Int J Infect Dis. 2016;46:8–10. doi: 10.1016/j.ijid.2016.03.011.
    1. Fung J, Lai CL, But D, Wong D, Cheung TK, Yuen MF. Prevalence of fibrosis and cirrhosis in chronic hepatitis B: implications for treatment and management. Am J Gastroenterol. 2008;103(6):1421–1426. doi: 10.1111/j.1572-0241.2007.01751.x.
    1. Shimakawa Y, Lemoine M, Njai HF, et al. Natural history of chronic HBV infection in West Africa: a longitudinal population-based study from the Gambia. Gut. 2016;65:2007–16.

Source: PubMed

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