RESUMEN
BACKGROUND: In sub-Saharan Africa, less than 1% of treatment-eligible chronic hepatitis B (CHB) patients receive antiviral therapy. Experiences from local CHB programs are needed to inform treatment guidelines and policies on the continent. Here, we present 5-year results from one of the first large-scale CHB treatment programs in sub-Saharan Africa. METHODS: Adults with CHB were enrolled in a pilot treatment program in Addis Ababa, Ethiopia, in 2015. Liver enzymes, viral markers, and transient elastography were assessed at baseline and thereafter at 6-month intervals. Tenofovir disoproxil fumarate was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. Survival analysis was performed using the Kaplan-Meier method. RESULTS: In total, 1303 patients were included in the program, of whom 291 (22.3%) started antiviral therapy within the initial 5 years of follow-up. Among patients on treatment, estimated 5-year hepatocellular carcinoma-free survival was 99.0% in patients without cirrhosis at baseline, compared to 88.8% in patients with compensated cirrhosis, and 54.2% in patients with decompensated cirrhosis (p < 0.001). The risk of death was significantly higher in patients with decompensated cirrhosis at baseline (adjusted hazard ratio 44.6, 95% confidence interval 6.1-328.1) and in patients older than 40 years (adjusted hazard ratio 3.7, 95% confidence interval 1.6-8.5). Liver stiffness declined significantly after treatment initiation; the median change from baseline after 1, 3, and 5 years of treatment was - 4.0 kPa, - 5.2 kPa, and - 5.6 kPa, respectively. CONCLUSIONS: This pilot program demonstrates the long-term benefits of CHB therapy in a resource-limited setting. The high mortality in patients with cirrhosis underscores the need for earlier detection of CHB and timely initiation of antiviral treatment in sub-Saharan Africa. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02344498) on January 26, 2015.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Adulto , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Etiopía/epidemiología , Tenofovir/uso terapéutico , Antivirales/uso terapéutico , Carcinoma Hepatocelular/complicaciones , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/complicacionesRESUMEN
BACKGROUND: Elimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity. METHODS: Through an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR. RESULTS: A total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (ß = 3.749), cost (ß = -2.550), specificity (ß = 1.134), and time-to-result (ß = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%. CONCLUSIONS: African HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs.
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Virus de la Hepatitis B , Mujeres Embarazadas , Lactante , Femenino , Embarazo , Humanos , Virus de la Hepatitis B/genética , Carga Viral , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Sensibilidad y Especificidad , Antivirales , Personal de SaludRESUMEN
Approximately 80 million people live with chronic hepatitis B virus (HBV) infection in the WHO Africa Region. The natural history of HBV infection in this population is poorly characterised, and may differ from patterns observed elsewhere due to differences in prevailing genotypes, environmental exposures, co-infections, and host genetics. Existing research is largely drawn from small, single-centre cohorts, with limited follow-up time. The Hepatitis B in Africa Collaborative Network (HEPSANET) was established in 2022 to harmonise the process of ongoing data collection, analysis, and dissemination from 13 collaborating HBV cohorts in eight African countries. Research priorities for the next 5 years were agreed upon through a modified Delphi survey prior to baseline data analysis being conducted. Baseline data on 4,173 participants with chronic HBV mono-infection were collected, of whom 38.3% were women and the median age was 34 years (interquartile range 28-42). In total, 81.3% of cases were identified through testing of asymptomatic individuals. HBeAg-positivity was seen in 9.6% of participants. Follow-up of HEPSANET participants will generate evidence to improve the diagnosis and management of HBV in this region.
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Hepatitis B Crónica , Hepatitis B , Humanos , Femenino , Adulto , Masculino , Hepatitis B Crónica/epidemiología , Hepatitis B/epidemiología , Virus de la Hepatitis B/genética , África/epidemiología , Antígenos e de la Hepatitis BRESUMEN
BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).
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COVID-19 , Humanos , Adulto , Masculino , Persona de Mediana Edad , Femenino , SARS-CoV-2 , ARN Viral , Tratamiento Farmacológico de COVID-19 , Método Doble CiegoRESUMEN
BACKGROUND: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown. METHODS: Plasma was collected during hospital admission and after 3 months from the NOR-Solidarity trial (n = 181) and analyzed for markers of gut barrier dysfunction and inflammation. At the 3-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene. RESULTS: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal 3 months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 (P/F ratio) <26.6 kPa. LBP levels remained elevated during and after hospitalization and were associated with low-grade inflammation and respiratory dysfunction after 3 months. CONCLUSION: Respiratory dysfunction after COVID-19 is associated with altered gut microbiota and persistently elevated LBP levels. Our results should be regarded as hypothesis generating, pointing to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.
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COVID-19 , Microbioma Gastrointestinal , COVID-19/complicaciones , Ensayos Clínicos como Asunto , Humanos , Inflamación , ARN Ribosómico 16S/genética , SARS-CoV-2 , Síndrome Post Agudo de COVID-19RESUMEN
BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , COVID-19/virología , Hidroxicloroquina/uso terapéutico , Carga Viral/efectos de los fármacos , Adenosina Monofosfato/uso terapéutico , Alanina/uso terapéutico , Anticuerpos Antivirales/sangre , Biomarcadores/sangre , COVID-19/complicaciones , COVID-19/mortalidad , Causas de Muerte , Femenino , Mortalidad Hospitalaria , Humanos , Inflamación/virología , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Orofaringe/virología , Insuficiencia Respiratoria/virología , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , Nivel de Atención , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: In 2015, the World Health Organization (WHO) issued guidelines for the management of chronic hepatitis B (CHB) in low- and middle-income countries, but little is known about the applicability of the WHO treatment criteria in sub-Saharan Africa. The aim of this study was to evaluate the diagnostic performance of the WHO guidelines in a large CHB cohort in Ethiopia. METHODS: Treatment-naïve adults who attended a public CHB clinic in Addis Ababa were included in this analysis. All patients underwent a standardized evaluation at recruitment, including blood tests and transient elastography (Fibroscan®). A Fibroscan result >7.9â¯kPa was used to define significant fibrosis and >9.9â¯kPa to define cirrhosis. Treatment eligibility was assessed using the most recent guidelines from the European Association for the Study of the Liver (EASL) as the 'gold standard'. RESULTS: Out of 1,190 patients with CHB, 300 (25.2%) were eligible for treatment based on the EASL 2017 guidelines and 182 (15.3%) based on the WHO 2015 guidelines. The sensitivity and specificity of the WHO criteria were 49.0 and 96.1%, respectively. Most patients (94 of 182; 51.6%) who fulfilled the WHO criteria had decompensated cirrhosis and might have a dismal prognosis even with therapy. Only 41 of 115 patients (35.7%) with compensated cirrhosis, who are likely to benefit the most from therapy, were eligible for treatment based on the WHO criteria. CONCLUSIONS: The WHO guidelines for CHB failed to detect half of the patients in need of treatment in Ethiopia, implying the need for a revision of the WHO treatment criteria. LAY SUMMARY: Antiviral therapy prevents disease progression and death in patients with chronic hepatitis B (CHB), but the identification of patients in need of treatment is a challenge in low- and middle-income countries. The World Health Organization (WHO) has suggested treatment eligibility criteria for use in such settings, but in our study the WHO criteria detected less than half of those in need of therapy in a large Ethiopian cohort of 1,190 patients with CHB. Our findings suggest that the WHO criteria might be unsuitable in sub-Saharan Africa. TRIAL REGISTRATION NUMBER: NCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.
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Hepatitis B Crónica/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Adulto , Alanina Transaminasa/sangre , Diagnóstico por Imagen de Elasticidad , Etiopía , Femenino , Hepatitis B Crónica/diagnóstico , Humanos , Masculino , Organización Mundial de la SaludRESUMEN
The chewing of the leaves of Catha edulis (khat) has been implicated in the development of liver disease, but no controlled observations have been undertaken. The objective of the present study was to determine whether khat chewing is associated with development of chronic liver disease (CLD). A case-control study was conducted at two public hospitals in Harar, Ethiopia, between April 2015 and April 2016. A consecutive sample of 150 adult hospital attendees with CLD were included as cases, and 300 adult hospital attendees without clinical or laboratory evidence of CLD were included as controls. Khat consumption was quantified in "khat years"; 1 khat year was defined as daily use of 200 g of fresh khat for 1 year. A logistic regression model was used to control for confounders. There was a significant association between chewing khat and the risk for developing CLD (crude odds ratio, 2.64; 95% confidence interval [CI], 1.56-4.58). In men, this risk, following adjustment for age, alcohol use, and chronic hepatitis B/C infection, increased with increasing khat exposure; thus, compared to never users the adjusted odds ratios were for low khat exposure 3.58 (95% CI 1.05-12.21), moderate khat exposure 5.90 (95% CI 1.79-19.44), and high khat exposure 13.03 (95% CI 3.61-47.02). The findings were robust in a post hoc sensitivity analysis in which individuals with identifiable risk factors for CLD were excluded. CONCLUSION: A significant association was observed between chewing khat and the risk for developing CLD, and in men the association was strong and dose-dependent, suggesting a causal relationship; as the prevalence of khat chewing is increasing worldwide, these findings have major public health implications. (Hepatology 2018;68:248-257).
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Catha/toxicidad , Hepatopatías/epidemiología , Adulto , Estudios de Casos y Controles , Enfermedad Crónica/epidemiología , Etiopía/epidemiología , Femenino , Humanos , Hepatopatías/etiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Antiviral treatment for chronic hepatitis B (CHB) is largely unavailable in sub-Saharan Africa; hence, little is known about the prognosis after initiating treatment in African CHB patients. In this study we aimed to assess predictors of mortality in one of the largest CHB cohorts in sub-Saharan Africa. METHODS: Two-hundred-and-seventy-six CHB patients who started treatment with tenofovir disoproxil fumarate at a public hospital in Ethiopia between March 18, 2015, and August 1, 2017, were included in this analysis. Patients were followed up until October 1, 2017, and deaths were ascertained through hospital records and telephone interview with relatives. Decompensated cirrhosis was defined as current or past evidence of ascites, either by clinical examination or by ultrasonography. Cox proportional hazard models were used to identify independent predictors of mortality. RESULTS: Thirty-five patients (12.7%) died during follow-up, 33 of whom had decompensated cirrhosis at recruitment. The median duration from start of treatment to death was 110 days (interquartile range 26-276). The estimated survival was 90.3, 88.2 and 86.3% at 6, 12 and 24 months of follow-up, respectively. Independent predictors of mortality were decompensated cirrhosis (adjusted hazard ratio [AHR] 23.68; 95% CI 3.23-173.48; p = 0.002), body mass index < 18.5 kg/m2 (AHR 3.65; 95% CI 1.73-7.72; p = 0.001) and older age (per 1-year increment; AHR 1.06; 95% CI 1.02-1.10; p = 0.007). CONCLUSIONS: Decompensated cirrhosis, low body mass index and older age were independent predictors of mortality. Improved access to antiviral treatment and earlier initiation of therapy could improve the survival of African CHB patients. TRIAL REGISTRATION: NCT02344498 ( ClinicalTrials.gov identifier). Registered 16 January 2015.
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Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/mortalidad , Tenofovir/uso terapéutico , Adolescente , Adulto , Factores de Edad , Índice de Masa Corporal , Etiopía/epidemiología , Femenino , Hepatitis B Crónica/complicaciones , Humanos , Cirrosis Hepática/fisiopatología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenAsunto(s)
Hepatitis B , Humanos , Hepatitis B/diagnóstico , Hepatitis C/diagnóstico , Tamizaje Masivo/normasRESUMEN
BACKGROUND: The World Health Organization has set an ambitious goal of eliminating viral hepatitis as a major public health threat by 2030. However, in sub-Saharan Africa, antiviral treatment of chronic hepatitis B (CHB) is virtually unavailable. Herein, we present the 1-year results of a pilot CHB treatment program in Ethiopia. METHODS: At a public hospital in Addis Ababa, CHB patients were treated with tenofovir disoproxil fumarate based on simplified eligibility criteria. Baseline assessment included liver function tests, viral markers, and transient elastography (Fibroscan). Changes in laboratory markers were analyzed using Wilcoxon signed-rank tests. Adherence to therapy was measured by pharmacy refill data. RESULTS: Out of 1303 patients, 328 (25.2%) fulfilled the treatment criteria and 254 (19.5%) had started tenofovir disoproxil fumarate therapy prior to September 1, 2016. Of the patients who started therapy, 30 (11.8%) died within the first year of follow-up (28 of whom had decompensated cirrhosis), 9 (3.5%) self-stopped treatment, 7 (2.8%) were lost to follow-up, and 4 (1.6%) were transferred out. In patients who completed 12 months of treatment, the median Fibroscan value declined from 12.8 to 10.4 kPa (p < 0.001), 172 of 202 (85.1%) patients with available pharmacy refill data had taken ≥ 95% of their tablets, and 161 of 189 (85.2%) patients with viral load results had suppressed viremia. Virologic failure (≥ 69 IU/mL) at 12 months was associated with high baseline HBV viral load (> 1,000,000 IU/mL; adjusted OR 2.41; 95% CI 1.04-5.55) and suboptimal adherence (< 95%; adjusted OR 3.43, 95% CI 1.33-8.88). CONCLUSIONS: This pilot program demonstrated that antiviral therapy of CHB can be realized in Ethiopia with good clinical and virologic response. Early mortality was high in patients with decompensated cirrhosis, underscoring the need for earlier detection of hepatitis B virus infection and timely initiation of treatment, prior to the development of irreversible complications, in sub-Saharan Africa. TRIAL REGISTRATION: NCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.
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Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Tenofovir/uso terapéutico , Adolescente , Adulto , Biomarcadores , Etiopía , Femenino , Estudios de Seguimiento , Hepatitis B Crónica/complicaciones , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Cumplimiento y Adherencia al Tratamiento , Resultado del Tratamiento , Carga Viral/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND & AIMS: Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. METHODS: In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA-positive samples by nucleotide sequencing followed by phylogenetic analyses. Demographical, clinical and biological data from patients were recorded and compared based on HDV RNA results. RESULTS: Most patients (n = 748, 59.0%) were men, and the median age was 31 years (interquartile range 26-40). Anti-HDV antibodies were detected in 19 individuals (1.5%), 12 of whom were HDV RNA-positive with a viral load ranging from <2 to >8 log 10 IU/mL. All strains were genotype 1. HDV RNA-positive patients were more likely to have significant liver fibrosis (63.6% vs 24.7%, P = .007) and cirrhosis (45.5% vs 16.4%, P = .024). CONCLUSIONS: HDV infection is rare in Ethiopia but is associated with more advanced liver fibrosis.
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Coinfección/virología , Hepatitis B Crónica/complicaciones , Hepatitis D/epidemiología , Virus de la Hepatitis Delta/genética , Cirrosis Hepática/virología , Adolescente , Adulto , Estudios de Cohortes , Coinfección/mortalidad , Ensayo de Inmunoadsorción Enzimática , Etiopía/epidemiología , Femenino , Anticuerpos Antihepatitis/sangre , Hepatitis D/mortalidad , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Filogenia , Reacción en Cadena en Tiempo Real de la Polimerasa , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development. METHODS: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia. The study population comprised of consenting adults with clinical and radiological evidence of chronic liver disease. The baseline evaluation included: (i) a semi-structured interview designed to obtain information about the ingestion of alcohol, herbal medicines and local recreational drugs such as khat (Catha edulis); (ii) clinical examination; (iii) extensive laboratory testing; and, (iv) abdominal ultrasonography. RESULTS: One-hundred-and-fifty patients with CLD (men 72.0%; median age 30 [interquartile range 25-40] years) were included. CLD was attributed to chronic HBV infection in 55 (36.7%) individuals; other aetiological agents were identified in a further 12 (8.0%). No aetiological factors were identified in the remaining 83 (55.3%) patients. The overall prevalence of daily khat use was 78.0%, while alcohol abuse, defined as > 20 g/day in women and > 30 g/day in men, was rare (2.0%). Histological features of toxic liver injury were observed in a subset of patients with unexplained liver injury who underwent liver biopsy. CONCLUSION: The aetiology of CLD in eastern Ethiopia is largely unexplained. The widespread use of khat in the region, together with histopathological findings indicating toxic liver injury, suggests an association which warrants further investigation.
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Hepatopatías/epidemiología , Hepatopatías/etiología , Lesión Pulmonar Aguda/patología , Adulto , Alcoholismo/complicaciones , Biopsia , Catha , Enfermedad Crónica , Estudios Transversales , Etiopía/epidemiología , Femenino , Humanos , Hígado/patología , Hepatopatías/diagnóstico , Hepatopatías/patología , Masculino , Prevalencia , Factores de Riesgo , Trastornos Relacionados con Sustancias/complicacionesRESUMEN
BACKGROUND: In the absence of liver biopsy, the World Health Organization recommends non-invasive tests, such as aspartate aminotransferase to platelet ratio index and FIB-4, to assess liver fibrosis in patients with chronic hepatitis B. However, these tests are not well validated in sub-Saharan Africa. Recently, a new marker, gamma-glutamyl transpeptidase to platelet ratio, was found to be more accurate in an African setting, but this needs confirmation in other cohorts. METHODS: A treatment program for chronic hepatitis B was initiated in Addis Ababa, Ethiopia, in 2015. Non-invasive tests were compared with transient elastography (Fibroscan 402, Echosense, France) using the following thresholds: no fibrosis (≤7.9 kPa), significant fibrosis (>7.9 kPa) and cirrhosis (>11.7 kPa). The diagnostic accuracy was estimated by calculating the area under the receiver operating characteristics curve. RESULTS: Of 582 treatment-naïve patients, 141 (24.2%) had significant fibrosis and 90 (15.5%) had cirrhosis. The area under the receiver operating characteristics curve of aspartate aminotransferase to platelet ratio index, FIB-4 and gamma-glutamyl transpeptidase to platelet ratio was high both to diagnose significant fibrosis (0.79 [95% CI 0.75-0.84], 0.79 [95% CI 0.75-0.84], 0.80 [95% CI 0.75-0.85]) and cirrhosis (0.86 [95% CI 0.81-0.91], 0.86 [95% CI 0.81-0.91], 0.87 [95% CI 0.82-0.91]). The specificity was high for all tests (94%-100%); however, the sensitivity was poor both to detect fibrosis (10%-45%) and cirrhosis (10%-36%). CONCLUSIONS: Aspartate aminotransferase to platelet ratio index, FIB-4 and gamma-glutamyl transpeptidase to platelet ratio had good diagnostic properties to detect liver fibrosis and cirrhosis in patients with chronic hepatitis B in East Africa. However, the sensitivity was low, and only 10% of patients with cirrhosis were detected using aspartate aminotransferase to platelet ratio index at the World Health Organization recommended threshold.
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Aspartato Aminotransferasas/sangre , Plaquetas , Pruebas Enzimáticas Clínicas , Hepatitis B Crónica/diagnóstico , Cirrosis Hepática/diagnóstico , gamma-Glutamiltransferasa/sangre , Adulto , Área Bajo la Curva , Biomarcadores/sangre , Diagnóstico por Imagen de Elasticidad , Etiopía , Femenino , Hepatitis B Crónica/sangre , Hepatitis B Crónica/virología , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/virología , Masculino , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
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.
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Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/virología , Adulto , Alanina Transaminasa/sangre , Biomarcadores , Estudios de Cohortes , Coinfección/tratamiento farmacológico , Etiopía , Femenino , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/sangre , Hepatitis B Crónica/complicaciones , Humanos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Tenofovir/uso terapéutico , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Unhealthy lifestyle factors such as smoking, obesity, inactivity and type 2 diabetes are endemic in the Middle East. The public health consequences might be detrimental; however, local studies on risk factors for coronary artery disease (CAD) are scarce. METHODS: Patients referred for coronary angiography at a tertiary hospital in Amman, Jordan, between January and December 2015, were included in this study. Risk factors for CAD were assessed in a multivariate logistic regression model, and presented as odds ratio (OR) with 95% confidence interval (CI). RESULTS: Among 557 participants, 356 (63.9%) had CAD and 201 (36.1%) had a normal cardiogram. The majority (n = 395, 70.9%) were male, and median age was 55 years (interquartile range 47-64). Two-hundred-and-fifteen (38.6%) individuals reported previous diabetes, and 287 (51.5%) were current or previous smokers. In multivariate analysis, male gender (OR 3.7, 95% CI 2.3-6.0), age (45-54 years: OR 4.8, 95% CI 2.7-8.5; 55-64 years: OR 6.0, 95% CI 3.2-11.4; ≥65 years: OR 15.7, 95% CI 7.8-31.3), previous diabetes (OR 2.6, 95% CI 1.7-4.1) and current/previous smoking (OR 2.1, 95% CI 1.3-3.4) were significant predictors of CAD. CONCLUSIONS: Age, gender, diabetes and smoking were strong and significant risk factors for CAD in Jordan. Public health interventions to reduce the prevalence of smoking and diabetes are urgently needed.
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Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Adulto , Factores de Edad , Anciano , Distribución de Chi-Cuadrado , Comorbilidad , Enfermedad de la Arteria Coronaria/epidemiología , Estudios Transversales , Diabetes Mellitus/epidemiología , Femenino , Humanos , Jordania , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Fumar/efectos adversos , Fumar/epidemiología , Centros de Atención TerciariaRESUMEN
OBJECTIVES: In resource-limited settings, it is a challenge to get quality clinical specimens due to poor infrastructure for their collection, transportation, processing and storage. Using dried blood spots (DBS) might be an alternative to plasma for HIV-1 drug resistance testing in this setting. The objectives of this study were to determine mutations associated with antiretroviral resistance among children <18 months old born to HIV-1-infected mothers enrolled in prevention of mother-to-child transmission services in northern Tanzania. PATIENTS AND METHODS: Kilimanjaro Christian Medical Center (KCMC) Clinical Laboratory is the zonal centre for early infant diagnosis using DBS in northern Tanzania. DBS were collected from January 2011 to December 2012. Mothers were kept on triple therapy and single-dose nevirapine before pregnancy and during labour, respectively. Infants were given single-dose nevirapine and most of them were breastfed. Genotypic resistance was determined in those with a viral load of >400 copies/mL. RESULTS: Genotypic resistance mutations were detected in 13 of 46 children (28%). HIV-1 genotypes were A1 (nâ=â27), C (nâ=â10), A/D (nâ=â4), D (nâ=â3) and CRF10_CD (nâ=â2). The median age was 12 weeks (IQR 6-28). The mean log10 viral load was 3.87 copies/mL (SD 0.995). All major mutations were detected in the reverse transcriptase gene and none in the protease gene region. The most frequent mutations were Y181C (nâ=â8) and K103N (nâ=â4), conferring resistance to non-nucleoside reverse transcriptase inhibitors. CONCLUSIONS: One-third of infants newly diagnosed with HIV in northern Tanzania harboured major drug resistance mutations to currently used antiretroviral regimens. These mutations were detected from DBS collected from the field and stored at room temperature. Surveillance of drug resistance among this population in resource-limited settings is warranted.
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Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/genética , Mutación Missense , Fármacos Anti-VIH/uso terapéutico , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , VIH-1/aislamiento & purificación , Humanos , Lactante , Masculino , Datos de Secuencia Molecular , Embarazo , Análisis de Secuencia de ADN , TanzaníaRESUMEN
BACKGROUND: Chronic hepatitis B (CHB) virus infection is a major cause of liver-associated morbidity and mortality, particularly in low-income countries. A better understanding of the epidemiological, clinical, and virological characteristics of CHB will guide appropriate treatment strategies and improve the control and management of CHB in Ethiopia. AIM: To investigate the characteristics of CHB in Eastern Ethiopia and assess the efficacy and safety of antiviral treatment. METHODS: This cohort study included 193 adults who were human immunodeficiency virus-negative with CHB between June 2016 and December 2019. Baseline assessments included chemistry, serologic, and viral markers. χ 2 tests, Mann-Whitney U tests, and logistic regression analyses were used to identify the determinants of cirrhosis. Tenofovir disoproxil fumarate (TDF) was initiated using treatment criteria from the Ethiopian CHB pilot program. RESULTS: A total of 132 patients (68.4%) were men, with a median age of 30 years [interquartile range (IQR): 24-38]. At enrollment, 60 (31.1%) patients had cirrhosis, of whom 35 (58.3%) had decompensated cirrhosis. Khat use, hepatitis B envelope antigen positivity, and a high viral load were independently associated with cirrhosis. Additionally, 66 patients (33.4%) fulfilled the treatment criteria and 59 (30.6%) started TDF. Among 29 patients who completed 24 months of treatment, the median aspartate aminotransferase to platelet ratio index declined from 1.54 (IQR: 0.66-2.91) to 1.10 (IQR: 0.75-2.53) (P = 0.002), and viral suppression was achieved in 80.9% and 100% of patients after 12 months and 24 months of treatment, respectively. Among the treated patients, 12 (20.3%) died within the first 6 months of treatment, of whom 8 had decompensated cirrhosis. CONCLUSION: This study highlights the high prevalence of cirrhosis, initial mortality, and the efficacy of TDF treatment. Scaling up measures to prevent and control CHB infections in Ethiopia is crucial.