7th Call - Dr. Bartholomew Dzudzor
Project Title: Association between Serum 25-hydroxyvitamin D Level and its Common Genetic Determinants in Patients with Chronic Liver Disease (CLD) at Different Stages and Correlation with the Degree of Liver Fibrosis at Korle Bu Teaching Hospital, Accra, Ghana
Principal Investigator: Dr. Bartholomew Dzudzor (Department of Medical Biochemistry, UGMS)
Email Address: bdzudzor@ug.edu.gh
Award Amount: GHC 24,999.00
Project Status: On-going
Summary:
Liver fibrosis leading to severe complications in chronic liver diseases is a major cause of morbidity, mortality and expensive health-care cost globally. World report on the burden of liver diseases attributable to hepatitis B and C and alcoholism is increasing annually with cirrhosis and hepatitis alone being the 9th leading cause of death globally. Indeed nearly 45% of all deaths in the developed countries are attributable to some type of chronic fibroproliferative diseases. In Ghana, published data on severity of liver fibrosis is unavailable, however, records from the Gastroenterology clinic at Korle Bu Teaching hospital (KBTH) indicated that on the average ten new cases of liver disease associated to chronic hepatitis B infection are recorded every week. Furthermore, ten liver biopsies are taken on the average per month for staging and further analysis. This high liver disease burden from KBTH records is not entirely surprising because the main causes of liver fibrosis including heavy long-term alcohol consumption, chronic infections with hepatitis viruses, nonalcoholic steatohepatitis and consumption of junk food containing high fats and fructose corn syrup are highly prevalent in Ghana.Currently, organ transplant which is the only means of reversing liver cirrhosis is highly unaffordable to the average Ghanaian. It will therefore be useful to generate baseline data in Ghana to understand the trend for effective and efficient clinical management of liver fibrosis and its complications through non-invasive and cost-effective means. Recent studies in other populations have associated histologically proven severity of hepatic fibrosis to low serum 25 (OH) D levels. Its deficiency or insufficiency has been associated with autoimmune disorders, various cancers as well as certain infectious diseases. Therefore it has been a target for research to help ameliorate these conditions elsewhere but no data is available in Africa. Additionally, genetic determinants can influence the biosynthesis and/or bioavailability of 25(OH) D. It is therefore necessary to genotype genes related to vitamin D metabolism to determine their association or predisposition to vitamin D deficiency/insufficiency among liver fibrotic patients in Ghana.The present proposal seeks to determine 25 (OH) D levels in the serum of CLD patients and the healthy controls as well as to genotype three genes related to vitamin D metabolism in the patients to help associate genetic determinants of 25 (OH) D deficiency/insufficiency to the severity of liver fibrosis.
Liver biopsies of the CLD patients shall be staged to determine the level of fibrosis. Degree of fibrosis will then be correlated with both 25-hydroxyvitamin D levels and SNPs determined from the three genes.
The results from this study could lead to further studies of vitamin D supplementation to find the best dose and verify eventual beneficial effects in managing CLD cases by healthcare providers both in Ghana and sub-Saharan Africa. This non-invasive method shall be more cost-effective than organ transplant which is the only current means of reversing liver cirrhosis.
Justification/ Relevance of the study
Complications of chronic liver diseases including fibrosis and cirrhosis are a worldwide problem that affect and kill millions of people annually, as there is no specific treatment for liver fibrosis yet. Knowing the serum level of 25 hydroxyvitamin D in Ghanaian CLD patients in relations to the level and severity of fibrosis should shed more light as to whether this condition might be aggravated by deficiency or insufficiency of vitamin D. The study will also provide an insight into genetic contribution to predisposition to active vitamin D levels and liver fibrosis in Ghana. The data generated in this study should serve as the basis for future translational research on vitamin D supplementation in treating or preventing the progression of hepatic fibrosis not only in Ghanaians but for all those leaving in sub-Saharan Africa. The study could also lead to future clinical trials that will define the correct dosage of vitamin D supplementation in correlation with the severity of the condition and also any eventual adverse side effects.