Biomarkers of chronic liver disease and their determinants in northern Ethiopia: Evaluating the synergistic impact of HBV and Schistosoma mansoni and the contribution of metabolic and lifestyle factors to liver injury

Abstract

Background Liver diseases are a major global health concern, affecting over 1.5 billion people and ranking among the leading causes of death. Sub-Saharan Africa carries a high burden, yet the underlying etiology of chronic liver disease is poorly described. The aim of this study was to assess biomarkers of chronic liver disease and their determinants in Northern Ethiopia. Methods A community-based cross-sectional study was conducted between December 2019 and June 2020 among randomly selected participants aged 5 years or older in Alamata district of Tigray region. Socio-demographic, behavioral, and clinical factors were collected via structured questionnaires; blood was tested for liver function biomarkers and Hepatitis B Virus (HBV) and stool samples for S.mansoni infection. Liver function biomarkers’ abnormalities were defined based on age and sex-specific thresholds. Multivariable hierarchical logistic regression analysis was performed to identify predictors of abnormal alanine aminotransferase (ALT) and adjusted odds ratios (AOR) with 95% confidence intervals (CI) were reported. Results A total of 767 participants were included, with a median age of 27 years (5–80 years); 53.1% were female and 67.5% resided in rural areas. The prevalence of HBV and S.mansoni infection was 5.9%, and 26.6%, respectively. Overall, 23.5% of participants had abnormal liver function biomarker with 7.3%, 14.2%, 9,4%, and 8.0% had elevated aspartate aminotransferase(AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin levels, respectively. Besides, the De Ritis, aspartate to alanine (AAR) ratio revealed a median of 0.96(IQR:0.62–1.74), with 51% (79/155) of the participants presented with an AAR < 1.0, and 21.3% of participants exhibited an AAR > 2.0. Moreover, the R value depicted the patterns of liver injury with 90(52.0%) participants exhibited R-value below 2(cholestatic injury), whereas 44(22.43%), and 39(22.54%) of the participants were found to have R-values between 2 and 5(mixed injury), and R > 5(hepatocellular injury), respectively. The hierarchical modeling depicted that the infectious domain accounted for the largest portion of model variance (change in Nagelkerke R-squared (ΔR 2 ) =0.157, p < .001). Accordingly, the model demonstrated that several determinants of hepatocellular injury led by significant synergistic interaction between HBV and S. mansoni co-infection conferred a 19.7-fold increase in the odds of elevated ALT (aOR:19.7; 95%CI:5.50, 70.6; p < .001), significantly higher than mono-infections of HBV (aOR:13.7; 95%CI: 5.82, 32.04; p < .001) or S. mansoni (aOR:3.4;95% CI:2.5; 5.51, p < .001). Beyond the infectious synergy, khat chewing (aOR:4.1, 95%CI:2.21, 7.58), and diabetes mellitus (aOR:4.01, 95%CI:1.55–10.36); p = .004) were confirmed as significant independent predictors, each associated with a four-fold increase in likelihood of having elevated ALT. Conclusion Liver function biomarkers’ abnormalities were common in northern Ethiopia driven by infectious, metabolic and lifestyle factors. The significant synergy between HBV and S.mansoni creates a compounded risk that far exceeds the impact of mono-infections, diabetes, or khat chewing. The findings emphasize the need for integrated public health strategies that address both infectious and non-infectious determinants simultaneously to effectively reduce the burden of chronic liver disease in the region.