Non-alcoholic fatty liver disease: Prognosis and Treatment

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1 Non-alcoholic fatty liver disease: Prognosis and Treatment Zachary Henry, M.D. Assistant Professor UVA Gastroenterology & Hepatology October 28, 2015 Overview Case Presentation Prognosis Effects of fibrosis Outcomes on the liver and other organs Affect of other metabolic risk factors Case Revisited Treatment Insulin sensitizing agents Vitamin E, fish oil, etc. New Horizons The old staple - Lifestyle modification 1

2 Case Presentation 53 yo female presenting with RUQ pain noted to have diabetes, HTN, HLD, and steatosis on US. Pain resolved on its own Liver biopsy revealed simple steatosis with no fibosis and little to no inflammation ALT = 22 AST = 22 Plt = 358 Bili = 0.3 Albumin = 4.8 Trig = 195 HDL = 43 Total Chol = 175 Hgb A1C = 6.9 BMI = 37.4 Case Presentation Recommendations: Lose weight Monitor enzymes Did not follow up with hepatology Follow up 3 years later (age 56) and now has elevated liver enzymes, worse lipids and DM Started on fish oil Reinforced weight loss Reinforced good DM control 2

3 Case Presentation Follow up still intermittent but returned to clinic one year later for IBS symptoms Liver enzymes normal again, BMI down to range Again lost to follow up Follow up two years later, now 59 years old: ALT = 64 AST = 70 Plt = 223 Bili = 0.4 Albumin = 3.7 Trig = 160 HDL = 44 Total Chol = 163 Hgb A1C = 13.0 BMI = 31.5 Case Presentation Recommendations: Advised diet and exercise Continued management of diabetes (had been on metformin for years, also on insulin now) Continued management of other metabolic risk factors (HTN and HLD pretty well controlled medically) 3

4 Case Presentation One year later (age 60) ALT improved, AST still elevated LIVER, NEEDLE BIOPSY: MILDLY-ACTIVE CIRRHOSIS CONSISTENT WITH END-STAGE NON-ALCOHOLIC STEATOHEPATITIS. What Happened? How could we predict this? She had NO fibrosis seven years ago Prognosis of NAFLD General Dogma surrounding progression of NAFLD Simple Steatosis NAFLD NASH Addition of inflammation signs of cell death (balloong,fibrosis) Argo, et al. Chapter 39 Nonacloholic fatty liver disease. Schiff s diseases of the liver. 4

5 Prognosis of NAFLD NAFLD NASH Anstee et al. Journal of Hepatology 2015 vol. 62 j % of patients who progressed had T2DM compared to only 25% of patients that did not progress 30% 55% 42% 35% Prognosis of NAFLD 129 total patients NASH = 71 followed for 13 years NAFLD = 58 CV related Death = 15.5% Liver related Death = 2.8% CV related Death = 8.6% Liver related Death = 0% General Population CV related Death = 7.5% 5.4% of patients w/ early fibrosis developed ESLD Ekstedt M, et al. Hepatology Oct;44(4): General Population CV related Death = 7.5% 17/36 patients developed fibrosis 5

6 Prognosis of NAFLD tied to Metabolic Syndrome NASH Year 1 Year 2 Year 3 Year Worsening Obesity Worsening DM Worsening NASH Back to our Patient NAFLD simple steatosis CAD NONE Worsening Diabetes OSA Diagnosis CAD silent disease Prior to her biopsy diagnosis of NASH cirrhosis she had been diagnosed with a TIA (90 s) as well as OSA Prior to her biopsy diagnosis of NASH cirrhosis she is diagnosed with small vessel CAD and found to have an old infarct INCREASED RISK OF CAD DEATH IN PATIENTS WITH NASH NASH cirrhosis by biopsy 6

7 Treatment- Insulin sensitizing agents Metformin: Many studies but all with small numbers of patients and most without overt diabetes Some benefit to reducing ALT/AST and possibly reduction in inflammation on liver biopsy but unclear how relates to long term outcomes with NASH Pioglitazone: PIVENS trial NEJM 2012 reduces inflammation and actually reverses NASH in about 1/2 of people all non-diabetic patients Treatment- Insulin sensitizing agents (Pioglitazone) Sanyal, et al. N Engl J Med May 6;362(18): Reversal of NASH with Pioglitazone was 47% in this study!!! 7

8 Treatment Vitamin E Sanyal, et al. N Engl J Med May 6;362(18): Improvement in histologic features of NASH with some increased rates of reversal, but not significant WARNING: Risk of CAD?, Risk of prostate CA? Fish Oil Argo, et al. J Hepatol Jan;62(1): Can improve lipid profile (triglycerides) May improve fat in liver Does not improve NASH significantly Treatment The Horizon Obeticholic Acid Neuschwander-Tetri, et al. Lancet Mar 14;385(9972): Bile acid derivative that works well to reduce fibrosis on rodent livers Single large human trial Some improvement in fibrosis Some reversal of NASH (though minimal) Significantly INCREASED LDL Is this something to avoid in patients at increased risk of CAD? Significantly increased Pruritus 8

9 Our Patient and Others Our patient had worsening metabolic syndrome and progressive liver and coronary disease Alternatively: 56 yo lady with increased liver enzymes and steatosis, lost 24 pounds over 6 months and everything normalized 38 yo man with DM, NASH and stage 3 fibrosis started on metformin, lost weight, 2 years later biopsy showed stage 1 fibrosis Stopped metformin, gained weight and 2 years later was back at stage 2-3 The only treatment proven time and time again Lifestyle Modification Pomrat, et al. Hepatology Jan;51(1): Losing 7 10 % body weight significantly reduces liver fat and inflammation Also reduces fibrosis but not significant in studies Long term studies needed 9

10 The only treatment proven time and time again Lifestyle Modification EXERCISE: Dose Responsive Oh, et al. Hepatology Apr;61(4): Previously recommended 150 minutes of aerobic exercise per week Newer studies show that 250 minutes or more per week improves insulin sensitivity and fat parameters even more Resistance training Bacchi, et al. Hepatology Oct;58(4): Likely equally effective to aerobic exercise Ideally a combination of aerobic and resistance exercises will improve outcomes Take Home Points NASH (fatty liver with notable cell damage and/or fibrosis) Can progress to end stage liver disease Has high risk of coronary artery disease NAFLD (fatty liver without cellular destruction) ~40% can develop and progress fibrosis (develop NASH) Even without developing NASH have increased risk fof CAD Treatment should focus on lifestyle modification 10

11 Treatment Algorithm Steatosis on US +/- elevated liver enzymes Rule out Alcoholism and Viral hepatitis Begin lifestyle modification Consider Referal to Specialist UVA Clinic for Metabolic Liver Disease Our Support Team (the really important people) Location: UVA Medical Park Northridge Phone (scheduling/referrals): Anne Hedelt NP Mary Lou Perry RD Laura Dick Nurse Coordinator ***If making a referral for NAFLD please inform the schedulers that the appointment is for Dr. Henry 11