NON-ALCOHOLIC FATTY LIVER DISEASE () & NON-ALCOHOLIC STEATOHEPATITIS () ADDRESSING A GROWING SILENT EPIDEMIC
PREVALENCE OF / USA Prevalence in Middle Age Patients San Antonio, Texas (Williams et al., Gastroenterology 2011; 140:124-31) Dallas Heart Study Prevalence Numbers (Browning et al., Hepatology 2004;40:1387-95) 60 58.3% Prevalence (%) 40 20 46% 45% 44.6% 30% 33% 35.1% 24% 12.2% 29.9% 0 Overall Hispanic Caucasian African American Overall among diagnosed Worldwide prevalence of : 20-30% 13-44% in Middle Eastern countries Approx. 20% in Asian countries Approx. 30% in European countries worldwide prevalence unknown (estimate from U.S. study: 6-8%) / Prevalence among Patients with diabetes 80-90% 56-69% ADVANCED FIBROSIS 37-50% / Prevalence among obese Patients Prevalence among bariatric surgery patients 70-90% 25-30%
NON-ALCOHOLIC FATTY LIVER DISEASE () ISOLATED STEATOSIS NON- WITH MILD FIBROSIS CVD WITH ADVANCED FIBROSIS CIRRHOSIS HEPATOCELLULAR CARCINOMA is an umbrella term that encompasses the spectrum of fatty liver disease, from isolated steatosis to cirrhosis and liver cancer with underlying CVD.
NATURAL HISTORY OF ~70-75% Isolated Fatty Liver Fatty Liver with Mild inflammation 1- None to very minimal progression to fibrosis 2- No of death compared with the general population ~20-25% Possible sampling variability with some of progression ~11% over 15 years, but significant variability 1- of death compared with general population 1- Cardiovascular 2- Malignancy 3- Liver-related 2- with fibrosis portends worse prognosis 1- Fibrosis progression a/w DM, severe IR, weight gain>5kg, rising ALT, AST Cirrhosis HCC ~7.2% over 6.5 years Decompensation ~19-45% over 7-10 years Modified from Torres DM et al. Features, diagnosis, and treatment of. Clin Gastro Hepatol 2012;10:837-858 Progression of isolated steatosis to cirrhosis is very rare Fatty liver with inflammation but not may progress but at a slower rate than with fibrosis is at greater for disease progression Patients with and metabolic syndrome are also an enriched population for disease progression / is now the second leading cause for liver transplantation in the U.S. Hierarchy of Histologic Features Associated with disease progression and mortality a - increased mortality or lt Predictors Fibrosis, stage 1 Fibrosis, stage 2 Fibrosis, stage 3 Fibrosis, stage 4 Age (years) Diabetes (yes) Smoking Never Former Current Statins use (yes) Hazard Ratio Decreased 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 Increased B - Increased of liver-related event 95% Cl of HR P value 1.18, 2.81.007 1.20, 3.03.007 1.16, 3.12.01 3.35, 12.04 <.001 1.05, 1.08 <.001 1.11, 2.30.01 0.71, 1.73.640 1.67, 4.10 <.001 0.15, 0.71.005 Predictors Fibrosis, stage 1 Fibrosis, stage 2 Fibrosis, stage 3 Fibrosis, stage 4 Hazard Ratio 95% Cl of HR P value 0.63, 8.91.198 2.26, 24.94.001 4.35, 43.65 <.001 11.94, 188.61 <.001 Decreased 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 Increased c - Major Prognosis Factors Ballooning Portal Fibrosis inflammation
& MORTALITY: TOP 3 CAUSES 1 2 CARDIOVASCULAR DISEASE (CVD) ALL CAUSE MALIGNANCY 3 LIVER-RELATED DEATH CONDITIONS ASSOCIATED WITH CVD OSA Hyperlipidemia Hypothyroidism Hypertension Adenomatous polyps Metabolic Syndrome Vitamin D deficiency PCOS Diabetes Modified from Torres DM et al. Features, diagnosis, and treatment of, Clin Gastro Hepatol 2012; 32:30-38 DIAGNOSIS AASLD practice guidelines require liver biopsy to diagnose Liver enzymes can be normal in up to 60% of patients with No non-invasive test with sufficient sensivity or specificity to rule in or rule out Age Gender Hispanic Hypertension Obesity Red Flags Increasing Probability for When deciding who to biopsy ALT and AST level AST/ALT ratio Insulin level PNPLA3 No lab test or imaging study will be able to predict with 100% accuracy All variables have been shown to predict
TREATMENT Diet, lifestyle modification and exercise remain the top priority. Ultimate goal is to achieve 10% weight loss as this has been shown to improve all histopathologic parameters of. No approved therapies for the treatment of. Diet and exercise are not always satisfactory options, and there is a lack of treatment. To address this unmet need, enrollment in one of the clinical trials underway can be considered. : KEY CONSIDERATIONS is the liver manifestation of metabolic diseases. patients are often obese, have type 2 diabetes, and cardiovascular disease. is the underlying cause of cirrhosis and its complications: treating is the appropriate approach to prevent progression to cirrhosis. Liver biopsy is required to diagnose. How to reverse : stop the disease activity i.e. necroinflammation (ballooning + inflammation) that is the driver leading to liver fibrosis and progressive liver fibrosis. therapies should be efficacious against both the underlying liver disease and comorbid conditions associated with such as insulin resistance, diabetes, and hyperlipidemia. Because is a chronic and silent disease, therapies should be safe and well tolerated. Follow our activities: www.the-nash-education-program.com contact@nash-education-program.com _Education The Education Program Copyright 10 2018 The Education Program. All rights reserved. NEP-1801.