Liver function tests and fibrosis scores in a rural population in Africa: estimation of the burden of disease and associated risk factors

Abstract

ABSTRACT Introduction Liver disease is a major cause of morbidity and mortality in sub-Saharan Africa. However, its prevalence, distribution and aetiology have not been well characterised. We examined liver function tests (LFTs) and calculated liver fibrosis scores in a rural population in Uganda. Methodology A cross-sectional survey of LFTs was undertaken in 2011 in a rural population cohort in South-Western Uganda. We classified abnormal LFTs based on reference ranges set in America and in Africa. We derived fibrosis scores (AST to Platelet Ratio Index, fibrosis-4, GGT to platelet ratio, red cell distribution width to platelet ratio, and S-index) to evaluate the potential prevalence of liver disease. We collected information about alcohol intake, and infection with HIV, HBV and HCV, to determine the contribution made by these factors to liver inflammation or fibrosis. Results Data were available for 8,099 participants (median age 30 years; 56% female). The prevalence of HBV, HCV and HIV infection were 3%, 0.2% and 8%, respectively. The prevalence of abnormal LFTs was higher based on the American reference range compared to the African reference range (e.g. for AST 13% vs 3%, respectively). The prevalence of AST/ALT ratio >2 was 11%, suggestive of alcoholic hepatitis. The highest prevalence of fibrosis was suggested by the GPR score, with 24% of the population falling above the threshold for fibrosis. By multivariate analysis, elevated LFTs and fibrosis scores were most consistently associated with older age, male sex, being under-weight, infection with HIV or HBV, and alcohol consumption. Based on population attributable risk, the highest proportion of elevated fibrosis scores was associated with alcohol use (e.g. 64% of elevated S-index scores). Conclusion Further work is required to determine normal reference ranges for LFTs in this setting, to evaluate the specificity and sensitivity of fibrosis scores, and to determine aetiology of liver disease. KEY FINDINGS What is already known? Liver disease is not well characterised in many parts of sSA despite the high prevalence of chronic viral infections (HIV, HBV and HCV), and potential exposure to hepatotoxins including alcohol, aflatoxins and traditional herbal medicine. Non-invasive blood tests for markers of fibrosis are relatively simple and offer a safe route to assess for liver fibrosis, however, their diagnostic accuracy is not well established in sSA. Appropriate reference ranges for LFTs are crucial for optimising the sensitivity and specificity of the detection of underlying liver disease. What are the new findings? There is a disparity in the prevalence of abnormal LFTs in our study cohort when comparing two references ranges (American vs. local reference ranges). Based on GPR score, there is a high prevalence of liver fibrosis (almost 1 in 4 of this population) and elevated GPR score is associated with older age, male sex, being under-weight, infection with HIV or HBV, and alcohol consumption. Alcohol consumption accounted for 64% of abnormal S-index scores, 32% of elevated FIB-4 scores, and 19% of GPR abnormalities. What do the new findings imply? Appropriate reference ranges for LFTs are necessary to contribute to an understanding of the burden and aetiology of liver disease. Alcohol, HIV and HBV are risk factors for deranged LFTs and liver fibrosis, with alcohol making the most significant and striking contribution. Further investigation is needed to determine other factors that contribute to liver disease in this setting.