Systematic review and individual-patient-data meta-analysis of non-invasive fibrosis markers for chronic hepatitis B in Africa

Abstract

In sub-Saharan Africa, simple biomarkers of liver fibrosis are needed to scale-up hepatitis B treatment. We conducted an individual participant data meta-analysis of 3,548 chronic hepatitis B patients living in eight sub-Saharan African countries to assess the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index and two other fibrosis biomarkers using a Bayesian bivariate model. Transient elastography was used as a reference test with liver stiffness measurement thresholds at 7.9 and 12.2kPa indicating significant fibrosis and cirrhosis, respectively. At the World Health Organization-recommended cirrhosis threshold (>2.0), aspartate aminotransferase-to-platelet ratio index had sensitivity (95% credible interval) of only 16.5% (12.5–20.5). We identified an optimised aspartate aminotransferase-to-platelet ratio index rule-in threshold (>0.65) for liver stiffness measurement >12.2kPa with sensitivity and specificity of 56.2% (50.5–62.2) and 90.0% (89.0–91.0), and an optimised rule-out threshold (<0.36) with sensitivity and specificity of 80.6% (76.1–85.1) and 64.3% (62.8–65.8). Here we show that the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index threshold is inappropriately high in sub-Saharan Africa; improved rule-in and rule-out thresholds can optimise treatment recommendations in this setting.

Real-world experience with nucleos (t) ide analogue therapy and patient survival rates in chronic viral hepatitis B Treatment Centers in Asmara, Eritrea: A multicenter retrospective observational cohort study

“…The excess mortality in males is another recurring feature in HBV literature (29). In a study conducted in Ethiopia, the likelihood of advanced liver disease (ALD) was higher in men (29).These outcome, experts agree; are largely driven by the asymptomatic nature of HBV -only presenting when advanced-stage sequelae emerge (30). Importantly, the higher likelihood of ALD in males is potentially linked to differential exposure to hepatotoxins (hazardous alcohol consumption, a atoxins (a toxin from Aspergillus avus and Aspergillus parasiticus in locally brewed alcoholic drinks, and tobacco use, among others) or other high-risk behavior (25).…”

Hepatitis B in Africa Collaborative Network: cohort profile and analysis of baseline data

“…HEPSANET’s second priority, to develop simplified HBV treatment eligibility criteria for Africa, is being addressed through several current analyses. In one recent publication, a new threshold for the AST-to-platelet ratio index was proposed based on HEPSANET data [ 25 ]. Defining best practices for HBV testing and linkage to care is represented in several top-10 priorities.…”

“…East African data came from Ethiopia, while Southern African data covered Malawi, South Africa, and Zambia. Patients diagnosed on clinical suspicion of HBV infection were excluded as we previously found that they are enriched for cirrhosis and elevated markers of HBV replication [25]. Among participants not currently on anti-HBV treatment and who learnt of their HBV status through asymptomatic testing were assessed by comparing markers of HBV replication (HBV DNA and HBeAg) and of possible liver disease (ALT and A c c e p t e d M a n u s c r i p t https://doi.org/10.1017/S095026882300050X Published online by Cambridge University Press median liver stiffness measurement [LSM]; based on elastography).…”

Hepatitis B viral replication markers and hepatic fibrosis in untreated chronic hepatitis B virus infection with and without HIV coinfection in Zambia

“…or when presenting with signs/symptoms of hepatitis. As HBV viral and liver markers differ between those diagnosed via routine versus clinically driven testing [6], we excluded the later from analysis.…”