Non-Alcoholic Fatty Liver Disease

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1 Non-Alcoholic Fatty Liver Disease None Disclosures Arslan Kahloon M.D Chief, Division of Gastroenterology and Hepatology University of Tennessee College of Medicine Chattanooga Objectives Understand the terminology Identify risk factors for fatty liver disease Appropriate screening Diagnosis and treatment Statistics Alcoholic liver disease 15 million people abuse/overuse ETOH in USA 90% of those will develop fatty livers Moderate use with another risk factor Non-alcoholic liver disease Most common chronic liver disease in USA 4 th most common reason for liver transplant Projected to be the most common in 10-20yrs Up to 20-40% adults 6 million children Prevalence Overall global prevalence of NAFLD diagnosed by imaging is around 25.24% The highest prevalence of NAFLD is reported from: Middle East 31.79% South America 30.45% Whereas the lowest prevalence rate is reported from Africa 13.48% The prevalence of NASH in the general population ranges between 1.5% and 6.45% By

2 Spectrum of fatty liver fatty liver steatohepatitis steatohepatitis + fibrosis steatohepatitis + cirrhosis cryptogenic cirrhosis Terminology Risk Factors Screening Considerations Routine Screening for NAFLD in high-risk groups attending primary care, diabetes, or obesity clinics: Not advised at this time Systematic screening of family members: Not recommended at this time Further work-up indicated Incidental finding on imaging for some other reason Abnormal liver enzymes Symptoms of liver disease Rule out other causes: alcohol, medications, hepatitis, etc. 2

3 Age BMI Hyperglycemia Platelet count Albumin AST ALT NAFLD fibrosis score < : predictor of absence of significant fibrosis (F0-F2 fibrosis) to 0.675: indeterminate score > 0.675: predictor of presence of significant fibrosis (F3-F4 fibrosis) Algorithm for evaluating NAFLD* Accidental discovery AST or Symptomatic liver disease r/o other causes of liver disease yes Abstain ongoing alcohol *taken from AGA position paper 2002 no Imaging study Echogenic US or fat on CT Screen those with risk factors elevated May need biopsy AST normal monitor Liver biopsy Incidental finding on imagery with normal enzymes: no biopsy indicated, monitor Presence of metabolic syndrome and persistently elevated biochemistries may benefit from liver biopsy Patients with biopsy proven NASH cirrhosis should be screened routinely for esophageal varices and HCC Lifestyle Interventions Diet, exercise, and weight loss >10% weight loss was associated with improvement in all features of NASH 7% body weight reduction was associated with NAS improvement 3-5% weight loss improves steatosis but more is needed to improve inflammation Promrat, et al. Hepatology 2010, Dunn, et al. Hepatology 2008, Gunji. et al. Am J Gastro 2009, Moriya, et al. Alim Pharm Ther 2011, Ruhl, et al. Clin Gastro Hepatol 2005 Insulin sensitizing agents Metformin: Metformin is not recommended for treating NASH in adult patients reduction in IR and enzymes, Pioglitazone: improves liver histology in NASH patients Risks and benefits should be discussed Vitamin E Vitamin E administered at a daily dose of 800 IU/day improves liver histology in nondiabetic adults with biopsy-proven NASH and therefore may be considered for this patient population Vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis 3

4 Vitamin E: Concerns Meta-analysis including 136,000 participants found taking Vitamin E supplements > 400 IU/day had a higher risk of all cause mortality Vitamin E > 400 IU/day increases risk of prostate cancer in relatively healthy men Miller et al Annals of Internal Medicine 2005, Klein, et al, JAMA 2011 Other meds for NASH Ursodeoxycholic acid* no histologic benefit Omega-3 fatty acids** Effective in treating hypertriglyceridemia in pts with NAFLD Evidence for treatment of NASH inconclusive to date Large multi-center trial on-going now *Lindor, et al. Hepatology 2004 **Capanni, et al. Alimen Pharm Ther 2006 Statins Given lack of evidence that patients with NAFLD and NASH are at increased risk for serious drug-induced liver injury from statins, they can be used to treat dyslipidemia in patients with NAFLD and NASH. AASLD Recommendation on Bariatric Surgery Premature to consider foregut surgery as an option to specifically treat NASH Foregut surgery is not contra-indicated in otherwise eligible pts with NASH or NAFLD WITHOUT cirrhosis For those with cirrhosis: type, safety and efficacy of foregut surgery is not established MS Post Liver Transplant 44-58% of pts > 6months post OLT BMI increase of 10% increases risk of post OLT NAFLD Associated with increased cardiovascular and cerebrovascular events CVD causes 19-42% non-liver related deaths Diabetes, HTN, IR add 2-fold increased mortality risk Watt & Charlton J Hepatology 2010 Impact of Fatty Liver on Donors Deaths due to CVA and CVD result in atherosclerotic vessels Poorer quality organs Fewer organs Discarded livers with>30% steatosis 4

5 NASH and Hepatocellular Carcinoma Retrospective study 6,508 pts with NAFLD by US F/up 5.6 years Primary end point: onset of HCC 16 new cases of HCC (0.25%) Cumulative rates of NAFLD-related HCC: 0.02% at year % at year % at year 12 *Kawamura et al, Am J Gastroenterology 2011 Pediatric Issues NAFLD reported as early as 2 y/o NASH-related cirrhosis as early as 8 y/o Independent predictors of FLD in adolescence Obesity Older age Male gender Dyslipidemia Hispanic ethnicity HTN Insulin Resistance Schwimmer, et al. Pediatrics 2006 Schwimmer, et al. Hepatology 2005 Schwimmer, et al. Gastroenterology 2009 AASLD Pediatric Recommendations Intensive lifestyle behavior modification, including dietitian consultation, is first line treatment Thanks Metformin 500mg BID offers no benefit Vitamin E 800 IU/d offers histological benefit but confirmatory studies are needed before it can be recommended in clinical use. 5