Development of a simple score based on HBeAg and ALT for selecting patients for HBV treatment in Africa.

BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, it is essential to scale up antiviral treatment through decentralized services. However, access to the conventional tools to assess treatment eligibility (liver biopsy/Fibroscan®/HBV DNA) is limited and not affordable in resource-limited countries. We developed and validated a simple score to easily identify patients in need of HBV treatment in Africa. METHODS: As a reference, we used treatment eligibility determined by the European Association for the Study of the Liver based on alanine aminotransferase (ALT), liver histology and/or Fibroscan and HBV DNA. We derived a score indicating treatment eligibility by a stepwise logistic regression using a cohort of chronic HBV infection in The Gambia (n = 804). We subsequently validated the score in an external cohort of HBV-infected Africans from Senegal, Burkina Faso, and Europe (n = 327). RESULTS: Out of several parameters, two remained in the final model, namely HBV e antigen (HBeAg) and ALT level, constituting a simple score (treatment eligibility in Africa for the hepatitis B virus: TREAT-B). The score demonstrated a high area under the receiver operating characteristic curve (0.85, 95% CI 0.79-0.91) in the validation set. The score of 2 and above (HBeAg-positive and ALT ≥20 U/L or HBeAg-negative and ALT ≥40 U/L) had a sensitivity and specificity for treatment eligibility of 85% and 77%, respectively. The sensitivity and specificity of the World Health Organization criteria based on the aspartate aminotransferase-to-platelet ratio index (APRI) and ALT were 90% and 40%, respectively. CONCLUSIONS: A simple score based on HBeAg and ALT had a high diagnostic accuracy for the selection of patients for HBV treatment. This score could be useful in African settings. LAY SUMMARY: Limited access to the diagnostic tools used to assess treatment eligibility (liver biopsy/Fibroscan/hepatitis B virus DNA) has been an obstacle to the scale up of hepatitis B treatment programs in low- and middle-income countries. Using the data from African patients with chronic HBV infection, we developed and validated a new simple diagnostic score for treatment eligibility, which only consists of hepatitis B virus e antigen and alanine aminotransferase level. The diagnostic accuracy of the score for selecting patients for HBV treatment was high and could be useful in African settings

The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa.

BACKGROUND: Simple and inexpensive non-invasive fibrosis tests are highly needed but have been poorly studied in sub-Saharan Africa. METHODS: Using liver histology as a gold standard, we developed a novel index using routine laboratory tests to predict significant fibrosis in patients with chronic HBV infection in The Gambia, West Africa. We prospectively assessed the diagnostic accuracy of the novel index, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and Fib-4 in Gambian patients with CHB (training set) and also in French and Senegalese CHB cohorts (validation sets). RESULTS: Of 135 consecutive treatment-naïve patients with CHB who had liver biopsy, 39% had significant fibrosis (Metavir fibrosis stage ≥F2) and 15% had cirrhosis (F4). In multivariable analysis, gamma-glutamyl transpeptidase (GGT) and platelet count were independent predictors of significant fibrosis. Consequently, GGT-to-platelet ratio (GPR) was developed. In The Gambia, the area under the receiver operating characteristic curve (AUROC) of the GPR was significantly higher than that of APRI and Fib-4 to predict ≥F2, ≥F3 and F4. In Senegal, the AUROC of GPR was significantly better than Fib-4 and APRI for ≥F2 (0.73, 95% CI 0.59 to 0.86) and better than Fib-4 and Fibroscan for ≥F3 (0.93, 0.87 to 0.99). In France, the AUROC of GPR to diagnose ≥F2 (0.72, 95% CI 0.59 to 0.85) and F4 (0.87, 0.76 to 0.98) was equivalent to that of APRI and Fib-4. CONCLUSIONS: The GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa

Liver Stiffness Measurement and Biochemical Markers in Senegalese Chronic Hepatitis B Patients with Normal ALT and High Viral Load

Despite the high prevalence of chronic hepatitis B (CHB) in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM) and two biochemical scores (FibroTest®, Fibrometer®) to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log(10) IU/mL and normal alanine aminotransferase (ALT) values.LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB). Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring.225 patients were evaluated (84% male) and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7-13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT), and Fibrometer® (FM) using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis) and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively.In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Inactive hepatitis B carriers: outcomes of patients followed at hôpital principal de Dakar, Senegal

The evolutive profile of inactive HBV carriers is variable. Patients can remain inactive, or may evolve into chronic active hepatitis or hepatocellular carcinoma. Aim: to describe the long-term outcome of chronic hepatitis B inactive carriers followed at Hôpital Principal de Dakar. This is a retrospective study including all inactive HBV carriers, followed since 2001, and with regular monitoring of at least 5 years. Transaminases, viral load and screening for hepatocellular carcinoma were performed every 6 to 12 months. We included 52 patients. The mean follow-up was 76.2 months (60-162), the mean age 36 years (13-62 years) and the sex ratio 0.93 (25 men, 27 women). Four patients (7.7%) had an ALT above the normal. Eleven patients (21.1%) had persistently elevated viral load greater than 2000 IU/ml, while in three cases (5.8%), this increase was transient. Twenty-six patients (50%) had a detectable viral load, but still below 2000 IU/ml. Twelve patients (23.1%) had an undetectable viral load for the duration of monitoring. Eleven patients (21.2%) underwent liver biopsy. The activity or fibrosis were minimal in all cases (A or F = 1) or absent (A or F = 0). Only four patients (7.7%), had HBs seroconversion after a follow-up of six, seven and ten years. There was no focal lesion or cirrhosis detected during the follow-up. After a follow-up of at least 5 years, inactive HBV carriers remain inactive in 92.3% of cases. Their evolutive profile is characterized by an absence of elevated liver enzymes but with fluctuations of the viral load. HBs seroconversion rate is low and the risk of progression to hepatocellular carcinoma almost nil

Box plots of LSM, FibroTest® and Fibrometer® scores according METAVIR stages from Liver Biopsy.

<p>Box plots of LSM, FibroTest® and Fibrometer® scores according METAVIR stages from Liver Biopsy.</p

Results of FT, FM METAVIR scoring stages according to Liver Stiffness Measurement values.

<p>Results of FT, FM METAVIR scoring stages according to Liver Stiffness Measurement values.</p

LSM values for each FibroTest® and Fibrometer® stage of fibrosis.

<p>LSM values for each FibroTest® and Fibrometer® stage of fibrosis.</p

Values of parameters used to scoring FibroTest® and Fibrometer® in the 7 patients with LSM<7 kPa and FibroTest® METAVIR scoring stages ≥F3.

<p><u>Normal values</u>: PT (prothrombin time):>70%, TB (total bilirubin): <20 µmol/L, GGT<73 IU/L, Platelets:>150 Giga/L, HA (Hyaluronic acid) <100 µg/L, Urea: 3.3–8.3 mmol/L, A2M (Alpha-2 macroglobulin): 1.3–3 g/L, Hapto (Haptoglobin): 0.64–1.7 g/L, ApoA1 ( Apolipoprotein A1): 1.04–2.02 g/L, ALT: 72 IU/L, AST: 59 IU/L.</p