A clinical epidemiological study on end-stage liver disease in Ghana

Abstract: End-stage liver disease (ESLD), including advanced liver cirrhosis and hepatocellular carcinoma (HCC), is the final stage of long-standing injury to the liver due to risk factors such as chronic viral hepatitis and alcoholic liver disease. There is a high disease burden and mortality globally, especially in sub-Saharan African (SSA) countries such as Ghana, where the primary cause of HCC and cirrhosis is infection with hepatitis B virus (HBV). To overcome the problem of ESLD in Ghana and SSA, epidemiological data on patient characteristics, challenges with diagnosis and management and mortality estimates are necessary so that well-directed and appropriate policies can be developed. This thesis, therefore, aimed to determine the clinical epidemiological profile of liver cirrhosis and HCC patients in Ghana and to explore diagnostic and management practices associated with the care of patients. In Study I, we described the clinical characteristics of ESLD from liver cirrhosis and HCC in Ghana and evaluated the performance of the aspartate aminotransferase (AST) - platelet ratio index (APRI) score and alpha fetoprotein (AFP) in a cross-sectional study involving 141 HCC, 216 cirrhosis and 218 chronic HBV patients. We found a median age at diagnosis of 44 years, with most patients presenting at an advanced stage of disease. APRI cut-off of 2 had sensitivity of 45.4% and specificity of 95% in the diagnosis of cirrhosis, whilst a cut-off of 1 had sensitivity of 75.9% and specificity of 89%. The AUC of AFP of 0.88 indicated the utility of this test in the surveillance of HCC in Ghana. Study II evaluated the in-hospital testing of HBV infection and burden of disease in Ghana by reviewing hospital-based data from 136,068 laboratory register entries, 165,213 blood bank register entries, and 83,920 delivery register entries in 22 healthcare institutions. We found that HBsAg RDT testing was widely available in government hospitals, however, HBV serological profile and DNA testing were mostly limited to teaching hospitals. The crude national seroprevalence was 8.40% ((95% CI 8.25-8.57%), whilst the pooled estimate was 11.39% (95% CI 10.43-12.35). Seroprevalence in children <5 years was 1.87% (95% CI 1.07-3.27). Our study indicated that Ghana remains a country with high endemicity and limitations in the full complement of testing for HBV infection. In Study III, we explored the opinions and practices of cirrhosis patients and health workers on the nutritional management of cirrhosis through a qualitative study. We found that patients and health workers felt dietary recommendations for patients were frequently addressed but could be significantly improved. Additionally, we found that local guidelines were not available for nutritional assessment and management in the opinion of study participants. Participants believed these to be important and necessary in managing cirrhosis patients in Ghana. Study IV assessed the proportion of liver-related deaths from liver cirrhosis and HCC, and their known risk factors in Ghana, and determined clinical factors associated with mortality. We found that 8.8% of deaths between 2018 -2020 in adults aged 18 years and above were due to liver-related causes. The proportion of liver-related deaths associated with HBV infection was 48.76%, HCV infection was 10.0%, and alcohol was 7.01%. Predictors of in-patient mortality in cirrhotic patients were elevated WBC (OR = 1.14 95% CI: 1.00 -1.30) and the revised model for end-stage liver disease with incorporation of sodium (MELD-Na) score (OR = 1.24 95% CI: 1.01-1.54). For HCC patients, female sex (OR=3.74 95% CI: 1.09-12.81) and hepatic encephalopathy (grade 1) were associated with higher mortality (OR = 5.66 95% CI: 1.10-29.2). In conclusion, this thesis presented the current landscape of end-stage liver disease, clinical epidemiology, diagnosis, and management in Ghana. It enhanced knowledge of the burden of viral hepatitis-related to liver cirrhosis and liver cancer. Finally, it shed light on factors associated with in-hospital mortality in Ghana.