https://orcid.org/0009-0009-7432-8723
Figures
Abstract
Background
Chronic hepatitis B virus (HBV) infection is still a major public health problem. In response to the World Health Organization (WHO), Tanzania implemented immunization and treatment to achieve the eradication of HBV infection by 2030. To achieve this goal, frequent updates of demographic data, antiviral therapy eligibility, and uptake are essential. We therefore evaluated demographic data, antiviral therapy eligibility, and uptake among chronically HBV-infected patients attending at Bugando Medical Centre (BMC), Tanzania.
Methods
A cross-sectional study enrolled 196 chronic HBV patients from April 23, 2023, to October 10, 2023, at BMC, where 100 and 96 patients were retrospectively and prospectively enrolled, respectively. Study’s ethical clearance and permission were observed by the Catholic University of Health and Allied Sciences/Bugando Medical Centre research ethics and review committee and the Bugando Medical Centre management respectively. For all patients, socio-demographic data and whole blood samples were obtained. Full blood picture, alanine and aspartate amino transferases, and HBV viral load parameters were determined. Aspartate-Platelet Ratio Index (APRI) and Fibrosis Four (FIB-4) scores were calculated according to their respective formulas. Therapy eligibility and uptake were evaluated according to the 2015 WHO HBV prevention, treatment, and care guidelines. The data were summarized and analysed using STATA version 15.
Results
The median age for all patients was 39 [IQR: 32–47.5] years. Nearly all study patients, 99% (194/196), were older than 20 years old, with significant male dominance (73.5% [144/196] versus 26.5% [52/196]; p<0.0001). Anti-HBV antiviral therapy eligibility was 22.4%, while uptake was 6.8% (3/4), which was significantly lower than the WHO expectation of 80% (p <0.0001).
Citation: Mlewa M, Nyawale HA, Henerico S, Mangowi I, Shangali AR, Manisha AM, et al. (2024) Hepatitis B infection: Evaluation of demographics and treatment of chronic hepatitis B infection in Northern-western Tanzania. PLoS ONE 19(10): e0309314. https://doi.org/10.1371/journal.pone.0309314
Editor: Jason T. Blackard, University of Cincinnati College of Medicine, UNITED STATES OF AMERICA
Received: May 9, 2024; Accepted: August 8, 2024; Published: October 8, 2024
Copyright: © 2024 Mlewa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript.
Funding: The author(s) received no specific funding for this work.
Competing interests: I have read the journal’s policy and the authors of this manuscript have no competing interesrs.
Introduction
Chronic hepatitis infection is still a public concern in Tanzania, with a pooled prevalence of 5.2% (5160) in 100,000 individuals [1]. In Mwanza, North-Western Tanzania, hepatitis B surface antigen (HBsAg) prevalence has been reported to range from 3.0% among pregnant women attending the antenatal clinic (ANC) at Bugando Medical Centre (BMC), Mwanza [2], to 7.0% among health care workers (HCWs) at BMC, Mwanza [3]. Hepatitis B virus (HBV) can cause hepatitis B liver diseases such as liver cirrhosis and hepatocellular carcinoma [4, 5], which have poor treatment outcomes [6]. In 1992, the WHO responded to the threat of HBV infection by summoning every country to integrate HBV vaccination into their universal childhood vaccination programs by 1997 [7]. In response to this summons, Tanzania introduced a free infant and paediatric HBV vaccination in the form of a pentavalent vaccine containing the Diphtheria, Pertussis, Polio, Tetanus, Hepatitis B, and Haemophilus influenzae type b3 (DPT-Heb-Hib3) vaccine in 2003 [8]. HBV vaccination is also available for adults, but not for free, and has mostly been focused on HCWs [9]. In addition to HBV vaccination, the World Health Organization (WHO) introduced the first guidelines for the prevention, treatment, and care of persons living with chronic hepatitis B virus (CHBV) infection in 2015, (Table 1), [10]. Following the release of the WHO guidelines in 2015, several countries have adopted their local HBV prevention, treatment and care guidelines. Among the well-known local guidelines are American Association for the Study of Liver Diseases (AASLD) [11] and European Association for the Study of Liver (EASL) [12]. Tanzania has not yet developed any local guidelines for HBV treatment and therefore it relies on the WHO guidelines for both HBsAg testing and treatment (Fig 1). Although this study was conducted and analysed during the era of 2015 WHO-HBV guidelines, in March 2024, the new 2024 WHO-HBV guidelines were released, which have more eligibility criteria and lower cut-off values [13]. Both of the 2015 and 2024 WHO guidelines criteria are shown in Table 1. In Tanzania, testing for coinfections (HIV, HCV, and HDV) and transient elastography (TE) value estimations are not routinely done. Moreover, some criteria found in the new 2024 guidelines were not assessed at the time of conducting this study. These criteria include family history of liver cancer or cirrhosis, presence of immune suppression, presence of comorbidities and presence of extrahepatic manifestations. Therefore, criteria assessed in this study are based on age, APRI scores, ALT, HBV DNA levels. According to the 2015 WHO guidelines, criteria used were: i) all chronic HBV-infected patients with an aspartate-platelet ratio index (APRI) of ≥2; ii) all chronic HBV-infected patients older than 30 years old with a hepatitis B viral load of ≥20,000 IU/mL. Eligible patients are required to take antiviral therapy, which can be either interferon-based or nucleoside/nucleotide-based therapy [10]. Treating eligible patients with anti-retroviral therapy is believed to reduce the risk of developing hepatitis B liver diseases [14, 15]. Also, by suppressing HBV viral load [16], treatment reduces the risk of patients’ infectivity [17]. Currently, HBV treatment in Tanzania are available at Bugando Medical Centre since 2009 and Muhimbili National Hospital (MNH) through up-to date ongoing project since 2016 [8]. Although HBV treatment is given for free at MNH to eligible chronically infected patients, patients have to buy their own anti-HBV drugs. This might impose an economical barrier to anti-HBV drug uptake. Moreover, data of chronic hepatitis B infected patients taking anti-HBV drugs are scarce in Tanzania. A recently published study done at Bugando Medical Centre has shown no anti-HBV uptake among the eligible chronic HBV infected patients [18]. Tanzania has no local HBsAg testing, treatment and monitoring algorithm and therefore it relies on the WHO guidelines which is more universal. Tanzania is in line with the WHO-HBV combat efforts through the achievement targets of eliminating HBV infection by 2030 [19]. To achieve this goal, Tanzania needs to be updated frequently on the demographic profile of chronic HBV infected patients as well as anti-HBV antiviral therapy (AVT) eligibility and uptake. It has been almost 20 years since the introduction of the infantile-paediatric HBV vaccination program; however, the distribution of chronic HBV infection among patients younger than and older than 20 years old is not well known in Tanzania. Moreover, the proportion of patients eligible for anti-HBV AVT eligibility and taking anti-HBV AVT according to the 2015 WHO-HBV prevention, treatment, and care guidelines among chronically HBV-infected patients has not been evaluated and known since the introduction of treatment in Tanzania. Therefore, this study provides information on the demographic distribution of chronic HBV infection by age and sex, proportions of anti-HBV AVT eligibility, and uptake according to the 2015 WHO-HBV prevention, treatment, and care guidelines among chronically HBV-infected patients attending the BMC in North-western Tanzania due to the fact that these patients were diagnosed and managed during the era of the 2015 WHO-HBV guidelines.
Patients, materials and methods
Ethical considerations
The study was approved by the joint Catholic University of Health and Allied Sciences/Bugando Medical Centre (CUHAS/BMC) research ethics and review committee (CREC/663/2023). In both prospective and retrospective participants, the need for consent was waived by CUHAS/BMC research and review committee. Permission to use the retrospective data from the Bugando Medical records was granted by to conduct the study at Bugando Medical Centre was given by the Bugando Medical Centre management (AB.286/317/01/PART "M"). All retrospective data were accessed with fully anonymity by using their hospital registration number. After retrieving, the participants were given study identification number. The prospective participants were recruited by using study identification number. These study identification numbers were used in all of their hospital tests related to the study.
Study design, duration and sample size
From 23rd April 2023 to 10th October 2023, we conducted a cross-sectional study at the Bugando Medical Centre, a referral, consultancy, and teaching university hospital. BMC serves a definitive population of about 640 patients with chronic HBV infection annually. The Yamane Taro formula (n = N/1+N(e)2 was used to calculate the minimum sample size. In this formula, n represents the sample size, N represents the total population, e represents the level of significance and 1 (one) represents a constant value. Yamen Taro formula is used for calculating sample size in a definite study population. Since this study was conducted for a duration of six months, the definitive study population was 320. Therefore, in this study, N was 320 and e used was 0.05. On computing these figures on the above formula, a minimum sample size of 178 was obtained. However, in this study 196 patients were enrolled and included in the final analysis. Of these, 100 patients were recruited retrospectively from 23rd April 2023 to 21st May 2023, whereas 96 patients were recruited prospectively from 23rd April 2023 to 7th August 2023.
Participants
Prospective patients.
The study enrolled patients with repeatedly confirmed Hepatitis B surface antigen-positive (HBsAg-positive) for more than six months who came for routine full blood picture (FBP), liver enzymes: alanine amino transferase (ALT) and aspartate amino transferase (AST), as well as HBV deoxyribonucleic acid (DNA) levels at Bugando Medical Centre (BMC).
Prospective sample collection and processing.
All laboratory procedures were performed in the ISO‐certified Department of Central Pathology Laboratory of Bugando Medical Centre. Aseptic techniques were used to collect whole blood from the 96 prospective patients. Approximately 15 mL of whole blood from each patient were drawn from each patient for analysis of the full blood picture, liver enzymes alanine and aspartate transferase, as well as the hepatitis B viral load. The full blood picture was analysed with whole blood drawn into ethylenediaminetetraacetic acid tubes using the Sysmex XN-1000 hematology analyser, while the alanine and aspartate amino transferases were analysed with whole blood drawn into plain tubes using COBAS integra 400. Plasma for HBVL was prepared by using whole blood drawn into an ethylenediaminetetraacetic acid tube, followed by centrifugation at 1500 revolutions for 10 minutes, and then about 2000 μL of plasma was drawn into well-labelled cryotubes and stored at -80°C while waiting for batch hepatitis viral load testing. During batch HBV DNA levels testing, about 1000μL of plasma per patient were used in a real-time PCR assay using the automatic COBAS® AmpliPrep/COBAS® TaqMan® HBV Test, v2.0, Roche Diagnostics, with a quantification linear range of 20 to 1.7 x 108 IU/mL [20]. PCR amplification of HBV DNA was achieved using the HBV DNA kit with Lot No. J1493600000. Results of HBV DNA batch testing was either target not detected (TND), HBV DNA levels <20 IU/mL, with the linear range of 20 to 1.7 x 108 IU/mL or > 108 IU/mL. The prospective participants were tested according to their routine clinic visits request and payments managed by the patient themselves. Although, HDV test is not available in Tanzania, HIV and HCV tests were not routinely requested. Therefore HDV, HIV and HCV were not included in this study. All the HBV DNA levels, FBP, and liver enzymes (ALT and AST) results were directly entered into a Microsoft Excel sheet version 16.
Retrospective participants.
The study also included all retrospective participants who were confirmed HBsAg-positive patients for more than six months in the BMC HBV medical records with a complete set of demographic and laboratory data, including age, gender, FBP, ALT, AST, and HBV DNA levels. The study excluded HBsAg-positive patients with missing either one of the demographics, FPB, liver enzymes, HBV DNA levels, or all of them.
Retrospective participants’ data extraction and processing.
Data extracted from retrospective participants were demographic data, FBP, Liver enzymes (AST and ALT). Two hematology analysers had been used to analyse FBP; 82 had been performed by Sysmex XN-1000 and 18 by Dymind-DH 76. Among the AST data, 74 of them had been performed by COBAS integra 400 and 26 by Cobas E 601. Eight six (86) ALT data had been performed by Cobas integra 400 and 14 by Cobas E 601. All HBV DNA levels had been analysed by using real-time PCR assay using the automatic COBAS® AmpliPrep/COBAS® TaqMan® HBV Test, v2.0, Roche Diagnostics, with a quantification linear range of 20 to 1.7 x 108 IU/mL [20]. However, the kit Lot numbers used for real-time PCR amplification were not readily identified. HBV DNA levels recorded were either target not detected (TND), HBV DNA levels <20 IU/mL, with the linear range of 20 to 1.7 x 108 IU/mL or > 108 IU/mL. Anti-hepatitis B virus (anti-HBV) antiviral therapy (AVT) uptake data were extracted from the Bugando Medical Centre (BMC) medical record database. Although, HIV and HCV testings are done in Tanzania, most of retrospective participants had not been tested for these parameters. Therefore, these data were no considered for anti-HBV drug eligibility selection. The extracted data were entered directly into an Excel sheet version 16.
Data management and analysis.
Both prospective and retrospective patients’ data (demographics, HBV DNA levels, ALT, and AST laboratory results) were directly entered into a Microsoft Excel sheet version 16. HBV DNA levels of the target not detected; <20IU/mL and >1.7 × 108 IU/mL were treated as 0, 20, and 1.7 × 108 IU/mL respectively, for statistical analysis. Aspartate amino transferase-platelet ratio index (APRI) score [21] and Fibrosis Four score (FIB-4) [22] were calculated according to their respective formula. After cleaning and coding, these data were subsequently transferred to STATA software version 15 for analysis. The percentage was used to summarize categorical variables, which included sex, age groups, and outcome cut off values. The median with Inter Quartile Range [IQR] was used to summarize continuous variables, which included the patients’ age, HBV DNA levels, APRI score, and FIB-4 score. The patients were grouped into two age groups. Group I included patients younger than or equal to 20 years old, and Group II included patients older than 20 years old. The age cut off of 20 years was chosen because the free infantile-paediatric hepatitis B (HBV) vaccination began in January 2003; making a lapse of almost 20 years. Hence, all patients in Group I with age of 20 years old and below were presumed to be from the vaccinated cohort. The anti-hepatitis B antiviral therapy eligibility and uptake were also analysed based on the 2015 WHO-HBV prevention, treatment, and care guidelines. We used a two-sample proportion test to analyse the significance of the difference in proportions of chronic hepatitis B infection between Groups I and II, between males and females, and between the AVT uptake of this index study and that recommended by the WHO.
Results
Participants’ social demographic and clinical data
A total of 196 chronically HBV-infected patients were enrolled in the study. The median age of patients was 39 [IQR: 32–47.5] years old. Nearly all study patients, 99% (194/196), were older than 20 years old (Group I), with a significant male predominance (73.5% [144/196] versus 26.5% [52/196]; p <0.0001). The patients analyzed were from 11 regions of Tanzania, and almost half of the patients (44.4%) were from the Mwanza region (Table 1).
Study participants had HBV DNA levels with a median of 979 [185.5–8457.5] IU/mL, and the majority, 160/196 (81.6%) of the patients, had HBVL below 20,000 IU/mL. The median ALT was 26.0 [18.6–39.4] IU/L, and the majority of them, 76.5% (150/196), had ALT values ≤ 41 IU/L. The median of AST values was 25.8 [IQR: 21.6–39.6] IU/L, and the majority of them, 75.5% (148/196), had AST values ≤40 IU/L. The median platelet counts were 198 [IQR: 154.5–241] cells/μL, and most of them, 79.6% (156/196), had values within the normal range of between 150 cells/μL and 500 cells/μL. These patients had a median APRI score of 0.34 [IQR: 0.25–0.68], while their median FIB-4 score was 1.1 [IQR: 0.8–1.8] (Tables 1 and 2).
Anti-HBV ARV eligibility and uptake status.
Out of 196 patients, a minority of 22.4% (44/196) were eligible for anti-hepatitis B virus (anti-HBV) antiretroviral therapy (AVT) according to the 2015 World Health Organization (WHO) hepatitis B virus (HBV) prevention, treatment, and care guidelines. Among the eligible patients, 77.3% (34/44) were eligible due to having a HBV DNA levels > 20,000 IU/mL and an age above 30 years, while 22.7% (10/44) were eligible due to having an aspartate amino transferase-platelet ratio index (APRI) ≥2 score. No eligible patient was due to HBV co-infection with either HDV, HIV or HCV as these data were not available or not tested as explained the methodology section. Among the eligible patients, AVT uptake was 6.8% (3/44) which was significantly lower than the WHO expectation of 80% towards elimination of hepatitis B infection by 2030, p<0.0001. However, the eligibility proportion was 30.6% based on the new 2024 guidelines with AVT uptake of 3.3%. The eligible participants with age ≥12 years and APRI score of ≥0.5 regardless of HBV-DNA and ALT levels were 95% (57/60) and with age ≥12 years and HBV DNA >2,000 IU/mL and an ALT level above the upper limit of normal (ULN) were 5% (3/60). All participants aged ≥12 years and with APRI score of >1 regardless of HBV-DNA and ALT levels were also found to be a group of participants with age ≥12 years and APRI score of ≥0.5 regardless of HBV-DNA and ALT levels. Persistently abnormal ALT levels (defined as two ALT values above the ULN at unspecified intervals during a 6- to 12-month period) was not assed due to the nature of the study. Also, the overall antiviral therapy uptake which included eligible and non-eligible antiviral uptake was 6.1% (12/196) and among these, majority, 75% (9/12) uptake was non-eligible (Table 3). Among the eligible patients on antiviral therapy, two patients were on Tenofovir Disoproxil Fumarate, and one patient was on Tenofovir Alafenamide Fumarate. In the non-eligible group of patients who were on antiviral therapy, five of them were on Tenofovir Disoproxil Fumarate; three of them were on a fixed drug combination antiretroviral drug with Emtricitabine and Tenofovir Disoproxil Fumarate (TRUVADA); and one patient was on a fixed drug combination antiretroviral drug with Tenofovir Disoproxil Fumarate, Lamivudine, and Dolutegravir (Table 4). Furthermore, among the eligible patients with high HBV DNA levels above 20,000 IU/mL, the majority of them, 91.12% (31/34) were not on anti-HBV antiretroviral therapy (Table 5).
Discussion
We believe that this is the first study to report on evaluation of demographic data and treatment of chronic hepatitis B (CHBV) infection since the introduction of the national infantile-paediatric HBV vaccination program and HBV treatment in Tanzania. Our results have shown that, nearly all chronic hepatitis B-infected patients were older than 20 years. This might be due to the effect of the national infantile-pediatric HBV vaccination program that started about 20 years ago. On the other hand, the study showed remarkably lower anti-HBV antiviral therapy uptake than the expectation of the WHO towards the elimination of HBV by 2030 among the eligible patients.
The reduction of proportion of chronic HBV infection in patients older than 20 years old is probably due to the effect of the national infantile-pediatric HBV vaccination, which started in 2003 in Tanzania [8]. This reduction in HBV infection in the population with an age equal to an age of the HBV vaccination program has also been reported in Iran [23]. In this this current study, majority of the study participants 73.5% (144/196) were sexually active male with median age of 39 [31–47.5] years old. These findings are comparable with several other global reports on sexual activeness and male dominance in chronic HBV infection [1]. Taken together, these findings of less chronic HBV infection in paediatrics and young adults and more middle-aged, sexually active patients with chronic HBV infection indicate that the main mode of HBV transmission in the country is the horizontal route, particularly through sexual activities, rather than the vertical (intrauterine and perinatal) transmission route, as previously thought in endemic countries, including Tanzania [24]. The sexual transmission route can also be supported by the predominance of genotypes A, D, and E in Tanzania [25], which are more transmitted by the horizontal route than by the vertical route [26]. Moreover, HBV vaccination prevents HBV infection rather than clearing infection. Infantile-pediatric HBV vaccination is given after birth and not intrauterine [8]. Therefore, from this study, we speculate that there could be more horizontal sexual transmission that is contributed more by male individuals in our local setting, which might signify a need to target this sexually active group in preventive measures such as HBV vaccination.
An anti-HBV antiviral therapy eligibility of 22.5% and 30.6% according to 2015 and 2024 WHO guidelines were observed in this study. This eligibility proportion was higher than the 4·4% and 9.7% reported in the Gambian study, which was conducted among community and blood donors using the 2015 WHO guideline, respectively. Community and blood donors have more individuals in the early stages of HBV infection and hence are unlikely to be eligible for antiviral therapy (AVT) compared to the clinical population. The eligibility proportion in this study was also higher than the 10.2% which was previously reported in a largely community (62.9%) composed study population in Zambia conducted according to the 2015 WHO guidelines [27]. Another study using the TREAT-B algorithm guidelines reported an eligibility rate of 56.8% [28], which is higher than that observed in the present study; the difference lies in the criteria used. TREAT-B algorithm guidelines have high sensitivity for identifying patients eligible for anti-HBV antiretroviral therapy [29] compared to the 2015 WHO-HBV guidelines. Moreover, the TREAT-B algorithm guidelines are designed to overcome the limited access to HBV infection diagnostic and evaluation tools in Africa [30]. However, the eligibility proportion of this index study was in accordance with other previous study report (23%) conducted according to the 2015 WHO guidelines [31]. Eligibility proportion of this index study by using the 2024 WHO guidelines [13] was 30.6% which reflects the increase in number of eligibility criteria compared to the old 2015 WHO guidelines.
In our study, anti-HBV antiretroviral therapy uptake observed in this study was 6.8% as per the 2015 WHO-HBV prevention, treatment, and care guidelines. This anti-HBV antiretroviral therapy uptake in the present study was far below the WHO-HBV achievement target of treating 80% of all anti-HBV antiretroviral therapy-eligible patients [19]. The anti-HBV antiviral therapy uptake observed in our study was also far lower than 62.8%, which was reported in a previous study in London [31] which is one of the first world countries. In contrast Tanzanians, citizens in London are likely to be economically capable and feasible of accessing these anti-HBV antiviral drugs. A previous study in Botswana involving HIV/HBV coinfection reported a higher uptake of AVT of 84%, however, the treatment uptake was primarily due to HIV infection [32]. The overall percentage of patients with anti-HBV antiretroviral therapy uptake in the whole population of 196 patients was 6.1%, with an eligible uptake rate of 25%. With respect to non-eligible patients, most of them used different antiretroviral drugs, probably indicating a different and non-formal source of anti-HBV antiretroviral drugs, which was not easily identified in our study population. This low anti-HBV antiretroviral therapy uptake could be due to the antiretroviral drug cost barrier. Most drugs used for HBV infection treatment are the same as those used for HIV infection treatment. However, in the case of HIV infection, these drugs are offered for free but have to be bought for HBV infection treatment, except at MNH [8]. Anti-HBV antiretroviral drug costs have been a major barrier to drug uptake in both low- and high-income countries [33]. WHO has recommended strategies to encourage countries to develop actions that can control HBV infection and diseases, including ensuring the availability and accessibility of anti-HBV drugs [34]. China in its pilot study, it reduced the cost barrier and resulted into increase of uptake of TDF and ETV [35]. Although Tanzania is among the low- and middle-income countries, with many of its citizens having low to moderate economic capacity [36], it should join the global strategies of controlling hepatitis B infection and disease by ensuring ease availability and accessibility of anti-HBV drugs [34]. The anti-HBV antiviral uptake was much lower (3.3%) than that obtained from by using the old 2015 WHO guideline. This might be to increase in eligibility criteria while uptake remains constant in this index study.
Additionally, the present study has observed that 18.4% of patients had a high hepatitis B virus DNA level of ≥20,000 IU/mL. The proportion in our index study was higher than 9.8%, from a study conducted in HBV/HDV coinfected population in Mauritania [37]. Contrast to this current study, HBV/HDV is associated with low HBV replication [38]. A previous study conducted in HIV/HBV co-infected patients who were starting anti-HIV antiretroviral therapy involving Mozambique and Zambia reported a higher proportion of 49.4% [39] than in this current study. HIV has been reported to suppress the immune system, allowing for high replication of HBV [40]. This justifies the high proportion of patient with HBV DNA levels os >20,000IU/mL observed in that previous study involving Mozambique and Zambia. In the present study, the HIV statuses of the patients were not known. Contrast to this current study, a France national surveillance study with most participants likely to be in their early stage of HBV infection with high viral replication reported a high proportion of patients with HBV DNA levels ≥20,000 IU/mL [41]. Among the patients with high HBVL >20,000 IU/mL in our study, only 8.8% (3/34) were on anti-HBV antiviral drugs. It has been hypothesized that high HBV DNA levels above 20,000 IU/mL could be associated with a high risk of developing HBV liver-related diseases such as liver cirrhosis and hepatocellular carcinoma [42, 43]. Therefore, the majority of the eligible patients with high HBV DNA levels above 20,000 IU/mL in this current study, (91.2%) are at high risk of developing hepatitis B liver-related diseases such as liver cirrhosis and hepatocellular carcinoma as they are not taking anti-HBV antiretroviral therapy.
Moreover, this current study has observed a significant number of patients, 20.4%, with platelets below 150 cells/μL. This was lower than what has been reported previously, 6.5% in Taiwan [44]. The difference could be due to the platelet cut off value used: a platelet cut off value of ≤100 or ≤50 cells/μL versus ≤150 cells/μL in the Taiwan study versus this index study, respectively. It was almost similar to a previous study done in Iran, which reported a proportion of 28.3% [45]. The similarity could be due to similar platelet cut off values used of ≤150 cells/μL.
In this current study, some limitations were observed. First, the classification of chronic hepatitis B infection was based on records of repeated HBsAg positive results for more than six months in the BMC HBV infection database rather than the presence of HBsAg-IgG antibodies and the absence of HBsAg-IgM. HBsAg-IgM and HBsAg-IgG are not routinely done at Bugando Medical Centre (BMC). This could have excluded many potential patients, whom might have resulted in different results in the study analysis. Secondly, HIV/HDV/HCV infection testing and transient elastography (TE) value estimation in HBV infected patients are not routinely done at BMC. This might have resulted into missing of more eligible patients. Thirdly, the sample size used was calculated based on six months of the study duration. This might be lower than what is required to characterize the definitive population served annually at BMC. This might have given lower or higher estimates of anti-HBV therapy eligibility and uptake. Lastly, at the time of designing and planning this current study, the new 2024 WHO guidelines were not yet released. This made this study to be more centred on the 2015 WHO guidelines.
In conclusion, almost all chronically hepatitis B-infected patients attending at BMC were older than 20 years old and were significantly dominated by males. The reduction of proportion of chronic HBV infection in participants younger than 20 years old might be due to the effect of infantile-paediatric HBV vaccination program. This could be indicating that the Ministry of Health of Tanzania should sustain the infantile-paediatric HBV vaccination program and expand it to the non-paediatric population. Antiviral therapy uptake was remarkably lower than what is expected by the WHO to combat HBV by 2030. This alarms the country to devise and implement strategies that can increase the availability, ease of accessibility, and usage of anti-HBV antiviral drugs among chronically HBV-infected patients. We also call upon the follow-up study on anti-HBV antiviral therapy eligibility and uptake that addresses the limitations observed in this study but also follows the new 2024 WHO guidelines.
Acknowledgments
The authors would like to acknowledge the funding support provided by Mwanza University for this work as part of the master thesis. The authors would also like to acknowledge Mr. Teonas A. Nyalu and Barnaba Sospeter from the department of medical records at Bugando Medical Centre for their support during data extraction.
References
- 1. Kafeero HM, Ndagire D, Ocama P, Kudamba A, Walusansa A, Sendagire H: Prevalence and predictors of hepatitis B virus (HBV) infection in east Africa: evidence from a systematic review and meta-analysis of epidemiological studies published from 2005 to 2020. Archives of Public Health 2021, 79:1–19.
- 2. Geffert K, Maponga TG, Henerico S, Preiser W, Mongella S, Stich A, et al: Prevalence of chronic HBV infection in pregnant woman attending antenatal care in a tertiary hospital in Mwanza, Tanzania: a cross-sectional study. BMC infectious diseases 2020, 20:1–10.
- 3. Mueller A, Stoetter L, Kalluvya S, Stich A, Majinge C, Weissbrich B, et al: Prevalence of hepatitis B virus infection among health care workers in a tertiary hospital in Tanzania. BMC infectious diseases 2015, 15:1–9.
- 4. Yang H-I, Lu S-N, Liaw Y-F, You S-L, Sun C-A, Wang L-Y, et al: Hepatitis B e antigen and the risk of hepatocellular carcinoma. New England Journal of Medicine 2002, 347(3):168–174. pmid:12124405
- 5. Chen YC, Chu CM, Liaw YF: Age‐specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B. Hepatology 2010, 51(2):435–444. pmid:19918971
- 6. Desalegn H, Orlien SMS, Aberra H, Mamo E, Grude S, Hommersand K, et al: Five-year results of a treatment program for chronic hepatitis B in Ethiopia. BMC medicine 2023, 21(1):373. pmid:37775742
- 7. McGregor A: WHO: World Health Assembly. The Lancet 1992, 339(8804):1287–1287. pmid:1349679
- 8. TANZANIA MINISTRY OF HEALTH CD G, ELDERLY AND CHILDREN: NATIONAL STRATEGIC PLAN FOR THE CONTROL OF VIRAL HEPATITIS. 2023.
- 9. Ndunguru B, Wilfred D, Kapesa A, Kilonzo SD, Mirambo M, Hyera F, et al: Low uptake of hepatitis B vaccination among healthcare workers in primary health facilities in Mwanza region, North-Western Tanzania. Frontiers in Public Health 2023, 11:1152193. pmid:37333557
- 10. ORGANIZATION WH: Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. 2015.
- 11. Koh C, Zhao X, Samala N, Sakiani S, Liang TJ, Talwalkar JA: AASLD clinical practice guidelines: a critical review of scientific evidence and evolving recommendations. Hepatology 2013, 58(6):2142–2152. pmid:23775835
- 12. Agarwal K, Berg T, Buti M, Janssen H, Lampertico P, Papatheodoridis G, et al: EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. Journal of hepatology 2017, 67(2):370–398. pmid:28427875
- 13. Organization WH: 2021 WHO Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection. 2024.
- 14. Lok AS, McMahon BJ, Brown RS Jr, Wong JB, Ahmed AT, Farah W, et al: Antiviral therapy for chronic hepatitis B viral infection in adults: a systematic review and meta‐analysis. Hepatology 2016, 63(1):284–306. pmid:26566246
- 15. Papatheodoridis GV, Sypsa V, Dalekos G, Yurdaydin C, van Boemmel F, Buti M, et al: Eight-year survival in chronic hepatitis B patients under long-term entecavir or tenofovir therapy is similar to the general population. Journal of hepatology 2018, 68(6):1129–1136. pmid:29427727
- 16. Wang T, Smith DA, Campbell C, Mokaya J, Freeman O, Salih H, et al: Hepatitis B virus (HBV) viral load, liver and renal function in adults treated with tenofovir disoproxil fumarate (TDF) vs. untreated: a retrospective longitudinal UK cohort study. BMC infectious diseases 2021, 21(1):610. pmid:34174833
- 17. Gerlich WH: Reduction of infectivity in chronic hepatitis B virus carriers among healthcare providers and pregnant women by antiviral therapy. Intervirology 2014, 57(3–4):202–211. pmid:25034489
- 18. Kilonzo SB, Nkandala I, Jaka H, Marmo L: Antiviral Therapy Eligibility and Low Treatment Coverage among Hepatitis B Virus Infected Patients in Tanzania. Open Journal of Gastroenterology 2023, 13(10):299–312.
- 19. ORGANIZATION WH: Elimination of viral hepatitis by 2030. 2016.
- 20. Shin K-H, Lee H-J, Chang CL, Kim H-H: Performance of the cobas Hepatitis B virus (HBV) test using the cobas 4800 system and comparison of HBV DNA quantification ability between the COBAS AmpliPrep/COBAS TaqMan HBV test version 2.0 and cobas HBV test. Journal of Clinical Virology 2018, 101:47–51. pmid:29414188
- 21. Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cárdenas E, Sánchez-Avila F, Vargas-Vorácková F: AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Annals of hepatology 2008, 7(4):350–357. pmid:19034235
- 22. Ahmad W, Ijaz B, Javed FT, Gull S, Kausar H, Sarwar MT, et al: A comparison of four fibrosis indexes in chronic HCV: development of new fibrosis-cirrhosis index (FCI). BMC gastroenterology 2011, 11:1–10.
- 23. Moghadami M, Dadashpour N, Mokhtari AM, Ebrahimi M, Mirahmadizadeh A: The effectiveness of the national hepatitis B vaccination program 25 years after its introduction in Iran: a historical cohort study. Brazilian Journal of Infectious Diseases 2020, 23:419–426.
- 24. di Filippo Villa D, Navas M-C: Vertical Transmission of Hepatitis B Virus—An Update. Microorganisms 2023, 11(5):1140. pmid:37317114
- 25. Forbi JC, Dillon M, Purdy MA, Drammeh BS, Tejada-Strop A, McGovern D, et al: Molecular epidemiology of hepatitis B virus infection in Tanzania. Journal of General Virology 2017, 98(5):1048–1057. pmid:28537543
- 26. Lin CL, Kao JH: The clinical implications of hepatitis B virus genotype: Recent advances. Journal of gastroenterology and hepatology 2011, 26:123–130. pmid:21199523
- 27. Vinikoor MJ, Sinkala E, Kanunga A, Muchimba M, Zanolini A, Saag M, et al: Eligibility for hepatitis B antiviral therapy among adults in the general population in Zambia. PLoS One 2020, 15(1): e0227041. pmid:31929556
- 28. Kafeero HM, Ndagire D, Ocama P, Kato CD, Wampande E, Kajumbula H, et al: TREAT-B algorithm for treatment eligibility among chronically infected Hepatitis B virus persons in a low and a high endemic region: a potential strategy towards virus elimination by 2030. Frontiers in virology 2022, 2:754711.
- 29. Thanapirom K, Suksawatamnuay S, Thaimai P, Treeprasertsuk S, Komolmit P, Tangkijvanich P: Assessment and validation of the TREAT-B score to assess the treatment eligibility of patients with chronic hepatitis B virus infection. Frontiers in Medicine 2022, 9:995857. pmid:36330056
- 30. McMahon BJ, Dusheiko G: Predicting treatment eligibility for hepatitis B in low income regions: Can treatment scores without HBV DNA testing serve the purpose? Journal of Hepatology 2018, 69(4):765–766. pmid:30007507
- 31. Jachs M, Sauberer R, Stiegler A, Dechêne A, Tazreiter R, Hartl L, et al: Eligibility for antiviral therapy and treatment uptake in chronic hepatitis B patients referred to a European tertiary care center. United European Gastroenterology Journal 2023, 11(3):293–304. pmid:36965148
- 32.
Phinius BB, Anderson M, Gobe I, Mokomane M, Choga WT, Mutenga SR, et al: High prevalence of hepatitis B virus infection among people with HIV in rural and periurban communities in Botswana. In: Open Forum Infectious Diseases: 2023: Oxford University Press US; 2023: ofac707.
- 33. Hill A, Gotham D, Cooke G, Bhagani S, Andrieux-Meyer I, Cohn J, et al: Analysis of minimum target prices for production of entecavir to treat hepatitis B in high-and low-income countries. Journal of virus eradication 2015, 1(2):103–110. pmid:27482399
- 34. Locarnini S, Hatzakis A, Chen D-S, Lok A: Strategies to control hepatitis B: Public policy, epidemiology, vaccine and drugs. Journal of hepatology 2015, 62(1): S76–S86. pmid:25920093
- 35. Yuan J, Lu ZK, Xiong X, Lee T-Y, Huang H, Jiang B: Impact of National Volume-Based Procurement on the procurement volumes and spending for antiviral medications of hepatitis B virus. Frontiers in Pharmacology 2022, 13:842944. pmid:35734415
- 36. Turuka FM: Tanzania middle income country status and implications for future economic growth strategies. Tanzania Journal of Agricultural Sciences 2022, 21(1):335–343.
- 37. Mansour W, Bollahi M-A, Hamed C-T, Brichler S, Le Gal F, Ducancelle A, et al: Virological and epidemiological features of hepatitis delta infection among blood donors in Nouakchott, Mauritania. Journal of Clinical Virology 2012, 55(1):12–16. pmid:22704272
- 38. Shirvani-Dastgerdi E, Tacke F: Molecular interactions between hepatitis B virus and delta virus. World Journal of Virology 2015, 4(2):36. pmid:25964870
- 39. Wandeler G, Musukuma K, Zürcher S, Vinikoor MJ, Llenas-García J, Aly MM, et al: Hepatitis B infection, viral load and resistance in HIV-infected patients in Mozambique and Zambia. PloS one 2016, 11(3): e0152043. pmid:27032097
- 40. Khaitan A, Unutmaz D: Revisiting immune exhaustion during HIV infection. Current HIV/AIDS Reports 2011, 8:4–11. pmid:21188556
- 41. Chevaliez S, Roudot-Thoraval F, Brouard C, Gordien E, Zoulim F, Brichler S, et al: Clinical and virological features of chronic hepatitis B in the French national surveillance program, 2008–2012: A cross-sectional study. JHEP Reports 2022, 4(12):100593. pmid:36313185
- 42. Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ: Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006, 130(3):678–686. pmid:16530509
- 43. Chen C-J, Yang H-I, Su J, Jen C-L, You S-L, Lu S-N, et al: Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. Jama 2006, 295(1):65–73. pmid:16391218
- 44. Huang C-E, Chang J-J, Wu Y-Y, Huang S-H, Chen W-M, Hsu C-C, et al: Different impacts of common risk factors associated with thrombocytopenia in patients with hepatitis B virus and hepatitis C virus infection. biomedical journal 2022, 45(5):788–797. pmid:34508913
- 45. Behnava B, Alavian S-M, AHMADZADASL M: The prevalence of thrombocytopenia in patients with chronic hepatitis B and C. 2006.