Gibril Ndow

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.

Natural history of chronic HBV infection in West Africa: a longitudinal population-based study from The Gambia

Background The natural history of chronic HBV infection in sub-Saharan Africa is unknown. Data are required to inform WHO guidelines that are currently based on studies in Europe and Asia. Methods Between 1974 and 2008, serosurveys were repeated in two Gambian villages, and an open cohort of treatment-naive chronic HBV carriers was recruited. Participants were followed to estimate the rates of hepatitis B e (HBeAg) and surface antigen (HBsAg) clearance and incidence of hepatocellular carcinoma (HCC). In 2012–2013, a comprehensive liver assessment was conducted to estimate the prevalence of severe liver disease. Results 405 chronic carriers (95% genotype E), recruited at a median age of 10.8 years, were followed for a median length of 28.4 years. Annually, 7.4% (95% CI 6.3% to 8.8%) cleared HBeAg and 1.0% (0.8% to 1.2%) cleared HBsAg. The incidence of HCC was 55.5/100 000 carrier-years (95% CI 24.9 to 123.5). In the 2012–2013 survey (n=301), 5.5% (95% CI 3.4% to 9.0%) had significant liver fibrosis. HBV genotype A (versus E), chronic aflatoxin B1 exposure and an HBsAg-positive mother, a proxy for mother-to-infant transmission, were risk factors for liver fibrosis. A small proportion (16.0%) of chronic carriers were infected via mother-to-infant transmission; however, this population represented a large proportion (63.0%) of the cases requiring antiviral therapy. Conclusions The incidence of HCC among chronic HBV carriers in West Africa was higher than that in Europe but lower than rates in East Asia. High risk of severe liver disease among the few who are infected by their mothers underlines the importance of interrupting perinatal transmission in sub-Saharan Africa.

Validation of Rapid Point-of-Care (POC) Tests for Detection of Hepatitis B Surface Antigen in Field and Laboratory Settings in the Gambia, Western Africa

ABSTRACT Hepatitis B virus (HBV) infection is a leading cause of death in sub-Saharan Africa (SSA). Point-of-care tests for hepatitis B surface antigen (HBsAg) could be an ideal tool for a large-scale HBV screening/treatment program in SSA. Using data from the PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa) program, we conducted a cross-sectional study to assess the diagnostic accuracy of three point-of-care tests (Determine, Vikia, and Espline) for the detection of HBsAg in the field or a laboratory setting in the Gambia. In the field, we used finger-prick whole blood for the Determine and Vikia tests and dried blood spots for the reference standard test (AxSYM HBsAg enzyme-linked immunosorbent assay [ELISA]). In the laboratory we used serum for the Determine, Espline, and reference test (Architect chemiluminescent microparticle immunoassay). Of 773 participants recruited at the community and 227 known chronic HBV carriers (1,000 subjects in total), 293 were positive for HBsAg. The sensitivity and specificity of the Determine test were 88.5% and 100% in the field and 95.3% and 93.3% in the laboratory setting, respectively. The sensitivity and specificity were 90.0% and 99.8% for the Vikia test (in the field) and 93.9% and 94.7% for the Espline test (in the laboratory). There was no evidence that one kit was better than another. Most of the patients with false-negative results (18/19) were classified as inactive chronic carriers. In summary, the three point-of-care tests had acceptable ranges of diagnostic accuracy. These tests may represent accurate, rapid, and inexpensive alternatives to serology testing for the screening of HBV infection at field level in SSA.

Acceptability and feasibility of a screen-and-treat programme for hepatitis B virus infection in The Gambia: the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) study

BACKGROUND Despite the introduction of immunisation for hepatitis B virus (HBV) in the 1990s, HBV-related morbidity and mortality remain high in sub-Saharan Africa. Identification and treatment of asymptomatic people with chronic HBV infection should reduce the disease burden. We therefore assessed the feasibility of a screen-and-treat programme for HBV infection in The Gambia, west Africa, and estimated the proportion of HBV-infected people who had significant liver disease in need of treatment. METHODS Between Dec 7, 2011, and Jan 24, 2014, individuals living in randomly selected communities in western Gambia were offered hepatitis B surface antigen (HBsAg) screening via a point-of-care test. The test was also offered to potential blood donors attending the central hospital in the capital, Banjul. HBsAg-positive individuals were invited for a comprehensive liver assessment and were offered treatment according to international guidelines. We defined linkage to care as visiting the liver clinic at least once. Eligibility for treatment was judged in accordance with the 2012 European Association for the Study of the Liver guidelines. FINDINGS HBsAg screening was accepted by 5980 (weighted estimate 68·9%, 95% CI 65·0-72·4) of 8170 adults from 27 rural and 27 urban communities and 5559 (81·4%, 80·4-82·3) of 6832 blood donors. HBsAg was detected in 495 (8·8%, 7·9-9·7) individuals in communities and 721 (13·0%, 12·1-13·9) blood donors. Prevalence was higher in men (239 [10·5%, 8·9-12·1] of 2328 men vs 256 [7·6%, 6·5-8·7] of 3652 women; p=0·004) and middle-aged participants. Linkage to care was high in the communities, with 402 (81·3%) of 495 HBsAg-positive individuals attending the clinic. However, only 300 (41·6%) of 721 HBsAg-positive people screened at the blood bank linked into care. Of those who attended the clinic, 18 (4·4%, 2·5-7·7) patients from the communities and 29 (9·7%, 6·8-13·6) from the blood bank were eligible for treatment. Male sex was strongly associated with treatment eligibility (odds ratio 4·35, 1·50-12·58; p=0·007). INTERPRETATION HBV infection remains highly prevalent in The Gambia. The high coverage of community-based screening, good linkage into care, and the small proportion of HBsAg carriers who need treatment suggest that large-scale screening and treatment programmes are feasible in sub-Saharan Africa. FUNDING European Commission (FP7).

Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case-control study in The Gambia.

Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity.

The prevalence and burden of symptoms in patients with chronic liver diseases in The Gambia, West Africa

In The Gambia, the smallest country in the African continent with a population of 1.73 million, hepatocellular carcinoma (HCC) is the most frequent type of cancer. Curative treatment is often unavailable because of late presentation to hospital and limited health infrastructure. Palliative care has been provided by a single non-governmental organisation (NGO) since 2004, but its coverage is limited. To date, there is no published data on the symptom burden of cancer patients in The Gambia. This cross-sectional study aimed to determine the symptom prevalence and burden among patients with HCC in The Gambia. In addition, the prevalence and burden of symptoms in patients with other non-malignant chronic liver diseases were estimated and compared with those of HCC patients.

Implementation of an in-house quantitative real-time polymerase chain reaction method for Hepatitis B virus quantification in West African countries

Hepatitis B virus (HBV) is a major cause of chronic liver disease worldwide. HBV infection is diagnosed by serological tests, while real‐time polymerase chain reaction (qRT‐PCR) assays are used to quantify viral load, which is a crucial parameter to determine viral replication and to monitor antiviral treatments. However, measuring viral load in resource‐limited countries remains nonsystematic, due to the high cost of commercial kits. Here, we describe the development, validation and implementation of a low‐cost, in‐house qRT‐PCR assay to monitor HBV viral load in chronic carriers enrolled in the PROLIFICA programme in the Gambia and Senegal. Over 1500 HBsAg‐positive patients, including 210 chronically infected HBV patients, who were given antiviral treatment (tenofovir), were monitored by qRT‐PCR using the SYBR Green‐ and HBV‐specific primers. Twenty‐four tenofovir‐treated patients were followed up and their viral load was tested every 3 months over the 12‐month experimental time course. Compared to commercial assays, our in‐house assay was shown to be (i) highly reliable, with good intra‐ and interassay reproducibility over a wide range (45–4.5 × 108 copies mL−1), (ii) very similar in the viral loads detected (R2 = .90), (iii) highly sensitive, as it detected loads as low as 30 copies mL−1 (~5 IU mL−1), (iv) cheaper (2‐ to 3‐fold), (v) easier to implement and (vi) more rapid. Based on our experience, we recommend this assay as a reliable alternative to commercial assays, for monitoring HBV viraemia in resource‐limited, highly endemic countries to reduce the cost and technical obstacles associated with commercial kits.

Hepatitis E virus infection and acute‐on‐chronic liver failure in West Africa: a case–control study from The Gambia

In sub‐Saharan Africa, it is unknown whether hepatitis E virus (HEV) infection is a common precipitating event of acute‐on‐chronic liver failure (ACLF).

Ebola: is the response justified?

Ebola virus disease is a viral hemorrhagic fever, first discovered in 1976 in Sudan, where the outbreak infected over 284 people with a 53% case fatality ratio. There have been 34 further epidemics, the current major incident in West Africa having recorded more cases and deaths than all previous outbreaks combined. To date there have been over 27, 000 confirmed, probable and suspected cases and 11,000 reported deaths in Liberia, Guinea and Sierra Leone. With total funding and pledges to help control the outbreak amounting to more than US

Hepatitis B testing and treatment in HIV patients in The Gambia—Compliance with international guidelines and clinical outcomes

2.4billion, many question how the disease has continued to spread in Sierra Leone and Guinea Conakry, and whether the response to the outbreak has been justified. This article aims to analyze the effectiveness of the responses to the outbreak in terms of economic, social, cultural and, to an extent, political impact. We argue that the response has been justified due to the awareness raised, the infrastructure and staffing improvements, the success in receiving financial aid and the minimal spread to other countries outside the main transmission zone. Despite this, some failures in communication and a slow early response were noted.