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Fatty Liver

Fatty Liver. Shahin Merat, M.D. Associate Professor of Medicine Digestive Disease Research Center, Tehran University of Medical Sciences, 8 th International Congress of Endocrine Disorders Tehran, Oct 2009. Fatty Liver (aka steatosis). Any amount of fat in liver histology

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Fatty Liver

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  1. Fatty Liver Shahin Merat, M.D. Associate Professor of Medicine Digestive Disease Research Center, Tehran University of Medical Sciences, 8th International Congress of Endocrine Disorders Tehran, Oct 2009

  2. Fatty Liver (aka steatosis) • Any amount of fat in liver histology • Mirovesicular or macrovesicular • With or without inflammation • With or without fibrosis • Associated with other disease or not • Alcohol related or not • Alcoholic fatty liver • Non alcoholic fatty liver (NAFL)

  3. Non-Alcoholic Fatty Liver Disease (NAFLD) • Defined as: • Deposition of fat droplets in hepatocytes • AND the absence of significant alcohol intake • Generally defined as less than 20gr ethanol per week • NAFLD is a range of conditions from near normal liver to cirrhosis

  4. Other Terms • Simple non-alcoholic fatty liver disease (NAFLD) • Only deposition of fat in liver • No inflammation or fibrosis • Non-Alcoholic Steatohepatitis (NASH) • NAFLD with inflammation (lobular or portal), hepatocyte ballooning, or fibrosis • Absence of serologic evidence of infection with hepatitis B or hepatitis C, …

  5. NAFLD—Spectrum of Disease Steatosis Steatohepatitis (NASH) NASH with Fibrosis Cirrhosis NAFLD

  6. NAFLD, simple steatosis • Fatty Liver • Only deposition of fat in liver • No inflammation • No fibrosis • Not believed to progress to cirrhosis • Up to 25 % of some populations!

  7. NAFLD—Steatosis Source: Ibdah 2003

  8. NAFLD—NASH (without fibrosis) Source: Ibdah 2003

  9. NAFLD—NASH (with fibrosis) Source: Ibdah 2003

  10. Multiple Hit Theory Normal Liver Hit 1: ? Insulin resistance, endotoxins, …  Fat accumulation Fatty Liver Hit 2: ? Oxidative stress, …  Inflammation Steatohepatitis Hit 3: ? Oxidative stress, …  Fibrosis Cirrhosis May loose fat

  11. NAFLD—Histological Spectrum Cirrhosis Time Progression Fibrosis Lobular Inflammation Macrovesicular Steatosis

  12. Impact • Liver-related death rate: • General population: 9.5/100,000 • NASH: 11% ! • Liver-related deaths were the second most common cause of death in NAFL

  13. Natural History • In various follow-up studies (4-18 years) • Improved: 0-4% • No change: 50-60% • Progession: 40-45% • Fibrosis: 27% • Cirrhosis: 19% • Much better than alcoholic hepatitis • Approximately 38-50% progress to cirrhosis over seven years

  14. NAFLD—Clinical Predictors Patients at risk to develop NASH with fibrosis: A. Age > 45 B. Obesity (BMI > 31-32) C. Diabetes D. AST/ALT > 1

  15. Survival • NASH (Hepatology 2001) • 5-year all-cause survival: 67% • 10-year all-cause survival: 59% • Alcoholic hepatitis • 5-year survival: 38% • 10-year survival: 15% • Hepatitis C with compensated cirrhosis 384 cases (Gastroenterology 1997) • 5-year survival: 91% • 10-year survival: 79%

  16. Hepatitis C (as a comparison) • 222 cases of Hepatitis C and 377 controls after 25 years of follow-up: (Hepatology 2001) • All cause mortality in HCV: 67% • In controls: 65% (not significant) • 917 women with acute HCV due to contaminated anti-D immune globulin (Hepatology 2000) • After 20 yrs: 0.4% cirrhosis • Shiraz liver transplant cases (n=207) (2005): • Cryptogenic cirrhosis: 23% (most common cause) • Hepatitis B: 17% • Hepatitis C: 2%

  17. NASH, Epidemiology (world) • The most common cause of elevated enzyme levels among asymptomatic patients • Only 10% of NAFLD have NASH • Among patients who have had liver biopsies, NASH is seen in approximately 7-9% in Western countries

  18. Epidemiology • There are many indications that a large number of patients labeled as cryptogenic cirrhosis have been cases of NASH who have lost indications of NASH. • There is evidence that the increased rate of cirrhosis and liver-related death in many conditions such as diabetics and malabsorbtion states (eg celiac disease) is due to NASH

  19. NASH, Prevalence in Iran • NASH is considered as the hepatic manifestation of the metabolic syndrome (syndrome X). • In a large scale study on 10,368 subjects in Tehran, the prevalence of the metabolic syndrome was found to be 30.1% (Azizi et al.) • This study did not look to the liver tests or its ultrasonographic appearance, but it can be considered a good estimation of the at-risk population in Iran.

  20. NASH, Prevalence in Iran • An autopsy series on 895 consecutive deaths from non-medical causes (Sotoudehmanesh et al) • 283 (31.6%) had steatosis • 19 (2.1%) had steatohepatitis • 6.7% of cases of steatosis had steatohepatitis • Non had alcohol consumption or diabetes • Post-mortem changes ?

  21. NASH, Prevalence in Iran • 1959 blood donors • Subjects with abnormal liver enzymes were invided • Further studies performed • Viral studies • Ultrasonography • 2.35% NASH

  22. NASH, Prevalence in Iran • Only 2.2% of these cases had a BMI of less than 25 • Limitations: • The population studied was 75.1% male. • No histologic confirmation • Cases studied were among volunteer blood donors • obese subjects are more likely to donate blood • high risk subjects are screened out. • Nevertheless, this is currently the only published study addressing the prevalence of NASH in Iran’s general population. • Another study on 6,000 randomly selected subjects from the general population is on the way

  23. NASH, Diagnosis • Poorly studied • Many doctors do not even believe in NASH! • Benign compared to other hepatitis • One of the most common ways by which NAFLD comes to medical attention is its incidental report during abdominal ultrasonography. • Unfortunately some ultrasonographists don’t believe in NAFLD too!

  24. NASH, Diagnosis • Most patients are asymptomatic. • Hepatomegaly is the most common physical finding. • ALT / AST > 1, usually not so high • Ultrasound will demonstrate a fatty or “bright liver.” • In CT, the liver is darker than the spleen • Liver biopsy is required

  25. Diagnosis, Ultrasonography • Unfortunately many radiologists in Iran do not report mild steatosis • Technically unsuitable equipment ? • Simple negligence ? • They don’t believe in it!

  26. Diagnosis, Ultrasonography • Increased echogenecity of the liver parenchyma, white liver • Not the same as coarse echogenicity which is a sign of fibrosis • Can be staged to grade I, II, and III according to vascular blurring or visibility of the diaphragm

  27. Diagnosis, CT • The liver and spleen usually have equal, or near-equal, density • In hepatic steatosis the liver is hypodense when compared to the spleen • You may see liver angiogram even without contrast injection

  28. Summary (1/2) • It appears that about 30% of the adult population in Iran is at risk for NAFLD • The overweight, obese, and diabetic is more prone. • About 10% of these subjects, almost 2-3% of the general adult population, already have NASH. • In may be roughly estimated that 10% of NASH cases will progress to cirrhosis.

  29. Summary (2/2) • The prevalence of NASH (2-3%) is comparable to the prevalence of hepatitis B, and much larger than the prevalence of hepatitis C • Since hepatitis B is being vaccinated for, we will be seeing less of this disease in the future • But obesity is on the rise. (as is hepatitis C) • It can be concluded that in the near future, NASH and hepatitis C will be the major liver diseases we will be facing in Iran

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