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Position Statement on the Use of Tenofovir Alafenamide for the Treatment of Chronic Hepatitis B Virus Infection in Africa

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Position Statement on the Use of Tenofovir Alafenamide for the Treatment of Chronic Hepatitis B Virus Infection in Africa Gastroenterology & Hepatology: Open Access Research Article Open Access Position statement on the use of Tenofovir Alafenamide for the treatment of chronic Hepatitis B Virus infection in Africa Abstract Volume 11 Issue 2 - 2020 The prevalence and morbidity of hepatitis B virus (HBV) infection is high in Africa. Scale-up Edward John Gane,1 Allah Kouadio Emile,2 of treatment with the use of nucleos(t)ide analogs (NAs) with high barrier to resistance such Onyekwere Charles Asabamaka,3 A Mongo as entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) 4 5 may help curtail the disease burden in sub-Saharan Africa. However, limited accessibility Onkouo, Oudou Njoya, Okon Anassi Jean 6 7 to these NAs and limitations of ETV (development of resistance in lamivudine-exposed Baptiste, SOMDA Küssome Paulin, Sombie patients), and TDF (decline in renal function and bone mineral density with long-term use) Arsene Roger,8 Tadesse T Mekonen9 act as barriers to optimization of HBV treatment in this region. Therefore, a panel of 9 1Professor, Liver Unit, University of Auckland, New Zealand (nine) hepatology experts from Africa convened, reviewed the literature, and developed 2Department of Hepato-Gastroenterology, CHU Cocody, Côte the current position statement for use of TAF in resource-limited African settings. This d’Ivoire 3 article presents an overview of the efficacy and safety of TAF versus TDF in both HBeAg- Department of Internal Medicine, Lagos State University negative and HBeAg-positive chronic HBV patients. Studies have revealed non-inferiority College of Medicine, Nigeria 4Assistant Head of Clinic, Congo for the proportion of patients who had HBV DNA <29IU/mL; higher rate of normalization 5Department of Hepatology, The Yaoundé University Hospital of alanine aminotransferase levels; and better bone/renal safety, with TAF vs. TDF up to Center, Cameroon 144weeks. Tenofovir alafenamide has better renal/bone safety compared to TDF, due to 6Lecturer-Researcher, Université Alassane Ouattara, Côte its less systemic exposure of tenofovir and greater exposure of tenofovir diphosphate to d’Ivoire target cells. In view of these benefits of TAF, the expert panel proposed indications for 7Public health doctor, option planning and management of health scale-up of the use of TAF, specifically in patients with renal/bone health issues, in Africa. programs and services, Burkina Faso Optimization of use of TAF in the proposed patient population may help in lowering the 8Practitioner, Center Hospitalier Universitaire Yalgado prevalence and morbidity from HBV in Africa. Ouédraogo, Burkina Faso 9Clinical Director at Avacare Health, Namibia Keywords: hepatitis B virus, nucleoside analogs, tenofovir alafenamide, Africa Correspondence: Prof Edward John Gane, Professor, Liver Unit, University of Auckland, Auckland, 1010, New Zealand, Tel +6421548371; Email Received: February 06, 2020 | Published: March 04, 2020 Abbreviations: HBV, hepatitis B virus; NAs, nucleos(t) In 2015, the birth dose vaccination coverage in Africa was only 10%.1 ide analogs; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil As a result of the low neonatal vaccination rates, the prevalence of fumarate; ETV, entecavir; WHO, world health organization; HBsAg, HBsAg infection in children aged five years has been reported to be hepatitis B surface antigen; HBIG, hepatitis B immunoglobulin the highest in Africa (3.4%; over a million HBsAg-positive children G; ALT, alanine aminotransferase; AASLD, american association aged five years in 2016), which represents a significant barrier to for the study of liver diseases; ULN, upper limit of normal; LAM, achieving the WHO HBV elimination targets.2 lamivudine; YMDD, tyrosine-methionine-aspartate-aspartate In addition to the high prevalence, the morbidity from HBV infection is also high in Africa. Chronic HBV infection has been Introduction reported to be the leading cause of hepatocellular carcinoma (HCC) in According to the latest World Health Organization (WHO) several regions of Africa,3 and about 50% of liver cancer cases in sub- estimates, globally, hepatitis B virus (HBV) infection was prevalent Saharan Africa have been noted to be caused by HBV infection.4 The in about 257million individuals (3.5%) in 2015, with Africa having mortality from chronic HBV infection is also high, both globally and the second highest disease prevalence (60million HBV-infected in Africa. Globally, about 1.34million deaths were attributed to viral individuals [6.1%]).1The Polaris Observatory Collaborators, in a hepatitis in 2015, of which 66% were due to chronic HBV infection, modeling study that involved 120 countries, reported hepatitis B surface with Africa recording the third highest number of deaths (136,000).1 antigen (HBsAg) positivity to be 12.2, 22.2, 6.8, and 39.1million Scale-up of treatment and care is therefore, crucial to help control individuals in the Central, East, Southern, and West regions of sub- the high prevalence, morbidity, and mortality due to HBV infection, Saharan Africa, respectively.2 The reasons for the high prevalence of both globally and in Africa.5 HBV infection in sub-Saharan Africa may be due to the high mother- to–child transmission rate of the disease, which in the case of HBsAg- Current guideline recommendations on positive and hepatitis B e-antigen (HBeAg)-positive mothers is about 40% in Africa.1 The high mother-to–child transmission rate of HBV treatment of chronic HBV infection infection in Africa may be due to the lack of access to antiviral therapy The American Association for the Study of Liver Diseases in pregnant women with high viral load, along with low uptake of (AASLD) 2018 guidelines recommend the nucleos(t)ide analogs birth dose vaccination and hepatitis B immunoglobulin G (HBIG).1,2 Submit Manuscript | http://medcraveonline.com Gastroenterol Hepatol Open Access. 2020;11(2):57‒63. 57 ©2020 Gane et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Copyright: Position statement on the use of Tenofovir Alafenamide for the treatment of chronic Hepatitis B Virus 58 infection in Africa ©2020 Gane et al. (NAs), entecavir (ETV), tenofovir disoproxil fumarate (TDF), or DNA replication.5 However, accessibility issues may limit the use of tenofovir alafenamide (TAF) as the preferred first-line option for NAs for the treatment of HBV monoinfection in sub-Saharan Africa.5,8 the treatment of adults with immune-active, chronic HBV infection, Further, there are several limitations to the use of ETV and TDF for to decrease the risk of liver-associated complications. Tenofovir the treatment of chronic HBV infection. alafenamide or ETV is recommended as a preferable option in patients with or at risk of renal dysfunction or bone disease. In immune- Limitations of ETV tolerant, chronic HBV-infected patients, the American guidelines Although ETV is a NA analog with a high barrier to HBV recommend antiviral therapy only in select adults aged >40 years, resistance, and only 1%–2% resistance reported in NA-naïve patients with normal alanine aminotransferase (ALT) levels, but elevated receiving long-term ETV monotherapy (over five years),9,10 the HBV DNA (1,000,000IU/mL) and presence of liver-associated incidence of ETV resistance has been found to be high in patients 6 complications such as necroinflammation or fibrosis. with lamivudine (LAM) resistance. The probability of ETV resistance The European Association for the Study of the Liver (EASL) 2017 through 5 years of treatment in LAM-refractory patients has been guidelines recommend NAs with a high barrier to HBV resistance, such found to be 43% and 51%, with and without virological breakthrough, 10 as ETV, TDF, or TAF as the preferred first-line antiviral monotherapy respectively. The resistance rate with ETV therapy has also been in all adults with chronic HBV infection, with the below-mentioned noted to be higher in LAM-exposed patients, with no detectable LAM recommendations for initiation of therapy:7 resistance when compared to NA-naïve patients, thus indicating the need for monitoring during ETV monotherapy in LAM-exposed a. All HBeAg-positive or -negative chronic HBV-infected patients, regardless of the presence or absence of LAM resistance.9 patients, defined by HBV DNA >2000IU/mL, ALT greater than the upper limit of normal (ULN) and/or at least moderate Resistance to prolonged LAM monotherapy is due to the liver necroinflammation or fibrosis, should be treated. substitution of methionine in the tyrosine-methionine-aspartate- aspartate (YMDD) motif at amino acid position 204 in the C domain b. Patients with compensated or decompensated cirrhosis and of the HBV DNA polymerase enzyme gene, with valine or isoleucine. detectable HBV DNA should be treated, regardless of ALT These changes are labeled as rtM204V/I, and are often associated levels. with other compensatory mutations, such as rtL180M, rtV173L, and rtL80V/I, which enhance viral replication.11 Resistance to LAM c. Treatment should be initiated in patients with HBV DNA increases with increased treatment duration and has been noted to >20,000IU/mL and ALT >2xULN, regardless of the degree of be about 70% at five years of LAM therapy.12 Furthermore, LAM fibrosis. resistance may also be noted in chronic HBV-infected patients with d. Patients with HBeAg-positive chronic HBV infection, defined no history of antiviral therapy (NA-naïve patients or inactive HBsAg by persistently normal ALT and high HBV DNA levels, may carriers), owing to spontaneous structural changes in the viral DNA be treated if they are older than 30 years, regardless of the polymerase enzyme.13,14 The pooled incidence of YMDD-motif severity of liver histological lesions. mutations in LAM-untreated patients from eight countries across Asia and Europe has been found to be 12.21%.14 This finding, therefore, e. Patients with HBeAg-positive or -negative chronic HBV highlights the need for monitoring long-term ETV therapy, even in infection and family history of HCC or cirrhosis and LAM-untreated or NA-naïve patients.
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