1. Nonalcoholic Fatty Liver Disease / Nonalcoholic Steatohepatitis 소화기내과 R3 신아리 1

2. Nonalcoholic fatty liver disease (NAFLD) - 1950’ 1st described : fatty liver in obese patients - Characterized by excessive fat accumulation (steatosis) ; from simple steatosis to nonalcoholic steatohepatitis (NASH) with progressive fibrosis, cirrhosis and liver failure Nonalcoholic steatohepatitis (NASH) - 1980’ described, Ludwig and colleagues at the Mayo Clinic - Subgroup of NAFLD where steatosis coexists with liver-cell injury and inflammation (steatohepatitis) 2 Introduction Harrison 18th Ch14, page 2604-2605

3. Epidemiology 3 Prevalence - NAFLD : 10~30% of general population in U.S - NASH : 3~6% of the general population in U.S Risk factor : obesity, diabetes mellitus, hypertension hyperlipidemia, insulin resistance (metabolic syndrome) - With progressive epidemics of obesity and diabetes mellitus NAFLD and its associated complications is expected to increase Hepatology (2010) 53, 372-384

4. 4 Epidemiology J Gastroenterology and Hepatology (2011) 26, 163-172

5. Natural history of NAFLD 5 Hepatology (2010) 51, 1820-1832

6. Natural Course 6 SCIENCE (2011) 332, 1519-1523

7. 7 Pathogenesis of NASH AJR (2008) 190, 993-1002

8. 8 Clinical Features of NAFLD SymptomsP/ELabImaging Asymptomatic (majority) Fatigue RUQ abdomen discomfort Hepatomegaly (common) Splenomegaly (25%) AST, ALT (<X4 ULN) ALP, GGT (uncommon) Abd sono - Large liver c increased echogenicity Not able to distinguish simple steatosis from NASH NASH is by definition clinicohistologic entity, histology is requied to confirm the diagnosis !! Clinical Gastroenterology And Hepatology (2004) 2, 1048-1058

9. 9 Diagnosis General - Exclusion of other causes of liver disease and daily alcohol consumption <20g in women & <30g in men, showing that alcohol-induced steatosis Aminotransferase Serological markers Imaging techniques : Sono, CT, MRI : Fibroscan (transient elastography, MR elastography) Liver biopsy

10. Association with Other Conditions World J Gastroenterol (2008) 14, 2474-2486

11. 11 Diagnosis Aminotransferase - AST, ALT < x4 ULN - AST/ALT > 1 : most common cases AST/ALT < 1 : suspected progressive fibrosis or cirrhosis Hepatology (2008) 48, 792-798 Risk of severe liver disease in NAFLD with normal aminotrasferase levels 62% of patients who reported normal ALT diagnosis NASH In subjects with normal ALT should also be considered in the selection of NAFLD cases for histological assessment of disease severity and progression

12. 12 World J Gastroenterol (2010) 16, 4784-4791

13. 13 Diagnosis Imaging techniques - Ultrasonography : detect hepatic steatosis (sensitivity 60~94%, specificity 84~95%) - CT scan, MRI - Fibroscan : Transient elastography, MR elastography Various radiologic methods can detect fat in the liver, But, no imaging modality is able to distinguish simple steatosis from steato-hepatitis with progressive fibrosis

14. Liver biopsy - In the absence of definitive clinical or laboratory evidence, the only way to confirm or exclude the diagnosis of NAFLD Diagnosis Arguments (+) Arguments (-) 1) Exclude other causes of liver disease 2) Distinguish steatosis versus NASH 3) Permit determination of disease severity 4) Provide insight into prognosis 1) Generally, NAFLD has good prognosis 2) Lack of effective therapy 3) Risk of complication (<0.5%), associated with biopsy

15. Liver biopsy in NAFLD Hepatology (2005) 41, 1313-1321

16. Recommendations J Hepatology (2010) 53, 372-384

17. Recommendations 2010 대한간학회 추계학술대회 Symposium 순천향대학교 의과대학 내과학교실 김영석

18. 18 Suspected NAFLD : NL~Abnl LFT & Steatosis in sono : Exclusion of other chronic liver disease improved Not improved Consider liver biopsy But, if there is no meaningful fibrosis In non-invasive test, avoid liver biopsy (Fibroscan, Serum serologic marker) If suggest progressive liver fibrosis, consider liver biopsy early KMC Protocol : Evaluation and Management of NAFLD Monitor liver enzyme (serology marker) and sono every 4-6 months Assess risk factors and treat accordingly Obesity : diet/exercise bariatric surgery Diabetes : insulin or OHA Insulin resistance : thiazolidinedione agent Hyperlipidemia : statin agent Drug/Toxin : discontinue agents Continue to monitor every 4-6 months

19. Treatment Oncologic, Endocine & Metabolic (2005) 10, 661-670

20. Treatment J Hepatology (2010) 53, 372-384 - A position statement on NAFLD/NASH based on the EASL 2009 special conference

21. 21 NAFLD Evaluation Package History taking 및 P/Ex - P/Ex : BMI, Waist circumference, BP - PHx : Alcohol consumption Hx - FHx : 1 st degree relatives of individuals with obesity and/or diabetes Serum marker - CBC/PT INR, TB/AST/ALT, ALP/GGT, Prot/Alb, if needed AFP - Viral marker (HbsAg/Ab, Anti-HCV) - Lipid Profile : Total-Chol, LDL-Chol, HDL-Chol, TG, ApoA1, ApoB - Fasting Glc, HbA1c - hsCRP, Ferritin (increased with NASH compared with NAFLD) Image - Abdominal sono, if needed Liver CT or MRI - IMT (Intima-media thickness)