NAFLD/NASH in Sub- Saharan Africa

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NAFLD/NASH in Sub- Saharan Africa Corné Kruger Gastroenterologist Durbanville Mediclinic Cape Town Liver Interest group meeting: Cape Town 2015

Introduction NAFLD is the most common liver disease disease in the world today. NAFLD/NASH is closely associated with diabetes and obesity. Both diabetes and obesity have reached epidemic proportions worldwide. There are at least 2.1 billion obese adults worldwide. Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 2014.

Introduction NAFLD/ NASH is not as common in Sub-Saharan Africa as in the rest of the World? There is almost no data available for the prevalence of NAFLD in Sub-Saharan Africa? NAFLD/NASH only presents with complications later in life and as the life expectancy in Africa is lower than the rest of the world, therefore NAFLD/NASH is uncommon?

Overweight and obesity in males

Overweight and obesity in females.

South Africa is the third fattest nation in the world. 4 out of 10 males are overweight and 7 out of 10 females are overweight. Marie et al. Lancet 2014, No figures available for prevalence of NAFLD in South Africa. Mixed race population of the Western Cape similar prevalence to Caucasian population studied. Kruger et al. SAMJ 2010

NAFLD/NASH in Sub-Saharan Africa 1 Published study from Nigeria 150 Nigerian obese patients attending an endocrinology clinic at teaching hospital in Lagos. Diabetics versus non-diabetic patients. Diagnosed with abdominal ultrasound. The prevalence was 8.7% Only 1 subject had raised transaminase levels.? Not severe disease Onyekwere et al. Annals of Hepatology 2011

NAFLD in children In a landmark study that examined the incidence of NAFLD in 742 autopsy specimens of children who had died of an accident found that 17.3% of the children aged 15 to 19 years had the disease. NAFLD was more common in children of Asian descent (10.2%) and Hispanic (mostly Mexican) descent (11.8%), with the lowest rate in African Americans (1.5%), findings that have been confirmed in other studies. Schwimmer JB et al. Pediatrics. 2006

NAFLD/NASH in African Americans

Ethnicity and NAFLD in USA In a community study the distribution of hepatic triglyceride content (HTGC) in 2,287 subjects from a multiethnic, population-based sample (32.1% white, 48.3% black, and 17.5% Hispanic) using proton magnetic resonance spectroscopy was compared. Ethnicity Hispanic 45 White 33 Black 24 % Hepatic steatosis The lower frequency of hepatic steatosis in blacks was not explained by ethnic differences in body mass index, insulin resistance, ethanol ingestion, or medication use Browning et al. Hepatology 2004

The histological spectrum of liver disease of African American, Non Hispanic white and Hispanics Study of patients undergoing bariatric surgery Morbidly obese African American patients had a lower rate of NAFLD, NASH and less fibrosis than non- Hispanic whites and Hispanics Kallwitz et al. Am J Gastroenterology 2009

Mechanisms for racial/ethnic differences Lifestyle IR Distribution of adiposity Genetics

Steatopygia

PNPLA and Steatosis

PNPLA risk factor for NASH, fibrosis and HCC Findings from at least two recent meta-analyses have also confirmed the clinical relevance of PNPLA3 rs738409 as a potent genetic risk factor for NASH, severe hepatic fibrosis and hepatocellular carcinoma Sookoian S, Pirola CJ. Hepatology 2011, Singal et al. Am J Gastroenterology 2014,

PNPLA and ethnicity In the Dallas Heart Study, the frequencies of the G allele in patatin-like phospholipase domaincontaining 3 (PNPLA3) gene were highest in Hispanics (0.49), with lower frequencies observed in European Americans (0.23) and African Americans (0.17). Romeo et al. Nat Genet 2008

PNPLA in South African patients In a group of South African patients referred for participation in a chronic disease screening program, the frequency of the minor G-allele noted for controls (0.24) was comparable to what is reported in the HapMap database (0.23), while that noted for NAFLD patients (0.46) was within the range reported in previous similar studies (~0.43-0.51) Lückhoff et al. 2013

Summary Due to a paucity of studies the true prevalence of NAFLD in Africa not known. Extrapolate from ethnic population studies of USA. NAFLD not only less prevalent but also less severe in African Americans. There is good genetic evidence to explain these ethnic differences.