Presentation is loading. Please wait.

Presentation is loading. Please wait.

Fatty Liver Disease Jamie Blazek, MPH, APRN, FNP-C Liver Transplant Department Ochsner Health Systems New Orleans, La.

Similar presentations


Presentation on theme: "Fatty Liver Disease Jamie Blazek, MPH, APRN, FNP-C Liver Transplant Department Ochsner Health Systems New Orleans, La."— Presentation transcript:

1 Fatty Liver Disease Jamie Blazek, MPH, APRN, FNP-C Liver Transplant Department Ochsner Health Systems New Orleans, La

2 DisclosuresNone

3 Objectives Identify risk factors for fatty liver disease Identify risk factors for fatty liver disease Order appropriate screening tests Order appropriate screening tests Diagnose and treat Diagnose and treat fatty liver disease fatty liver disease Initiate appropriate referrals Initiate appropriate referrals

4 Terminology ALD: Alcoholic Liver Disease ALD: Alcoholic Liver Disease Significant alcohol consumption* Significant alcohol consumption* > 21 drinks/week for males > 21 drinks/week for males > 14 drinks/weeks for females > 14 drinks/weeks for females NAFLD: Non-Alcoholic Fatty Liver Disease NAFLD: Non-Alcoholic Fatty Liver Disease steatosis without hepatocyte steatosis without hepatocyte injury injury NASH: Non-Alcoholic Steatohepatitis NASH: Non-Alcoholic Steatohepatitis steatosis with inflammation, steatosis with inflammation, hepatocyte injury hepatocyte injury with or without fibrosis with or without fibrosis *Sanyal, et al Hepatology 2011

5 Fatty liver Normal liver

6 Statistics Alcoholic liver disease 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 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

7 By 2020

8 Natural History of FLD fatty liver steatohepatitis steatohepatitis + fibrosis steatohepatitis + cirrhosis cryptogenic cirrhosis

9 Mortality risk: Cirrhotics with NAFLD vs hepatitis C Sanyal,et al Hepatology 2006: Sanyal,et al Hepatology 2006: –NAFLD had lower rate of mortality Yatsuji, et al Gastroenterology and Hepatology 2009: Yatsuji, et al Gastroenterology and Hepatology 2009: –No difference Both showed pts with NAFLD at lower risk for HCC than Hepatitis C pts. Both showed pts with NAFLD at lower risk for HCC than Hepatitis C pts.

10 NAFLD: risk factors Middle age Middle age Female gender Female gender Over-weight or obese Over-weight or obese Viral hepatitis Viral hepatitis Iron overload Iron overload Medications Medications Rapid weight loss Rapid weight loss Starvation/refeeding syndrome Starvation/refeeding syndrome Reye’s syndrome Reye’s syndrome Auto-immune disease Auto-immune disease Malnutrition Malnutrition Abetalipoproteinemia Abetalipoproteinemia Overgrowth of bacteria in small intestines Overgrowth of bacteria in small intestines TPN TPN Acute fatty liver of pregnancy Acute fatty liver of pregnancy HELLP syndrome HELLP syndrome Hispanic ethnicity Hispanic ethnicity Hereditary Hereditary

11 Risk factors: Established association Obesity Obesity Type 2 DM: insulin resistance (IR) Type 2 DM: insulin resistance (IR) Dyslipidemia Dyslipidemia Metabolic syndrome (MS) Metabolic syndrome (MS)

12 Risk factors: Emerging association Polycystic ovary syndrome Polycystic ovary syndrome Hypothyroidism Hypothyroidism Obstructive sleep apnea Obstructive sleep apnea Hypopituitarism Hypopituitarism Hypogonadism Hypogonadism Pancreatic-duodenal resection Pancreatic-duodenal resection

13 Risk factor: Medications Amiodarone Amiodarone Methotrexate Methotrexate Tamoxifen Tamoxifen Corticosteroids Corticosteroids Diltiazem Diltiazem Valproic acid Valproic acid Highly active antiretroviral therapy Highly active antiretroviral therapy

14 Risk factor: Bacteria overgrowth Grieco, et al. Hepatology 2009 Grieco, et al. Hepatology 2009 –35 pts with NAFLD bx confirmed –27 pts with celiac disease –24 healthy individuals –Those with FLD had increased intestinal permeability and increased small bowel bacterial overgrowth Compare, et al Nutrition Metabolism & Cardiovascular Disease Feb 2012 Compare, et al Nutrition Metabolism & Cardiovascular Disease Feb 2012 –Liver is 1 st line of defense against gut-derived antigens –Levels of bacterial lipopolysaccharide (component of GN bacteria) are increased in the circulation in several types of chronic liver disease –Can modulation of gut microbia represent a new way to treat/prevent NAFLD???? treat/prevent NAFLD????

15 Screening Considerations AASLD rec’s Liver biochemistries can be normal Liver biochemistries can be normal Ultrasounds are expensive Ultrasounds are expensive General population screening not recommended General population screening not recommended Undergoing surgical procedure? Undergoing surgical procedure? Planned pregnancy with obese mother? Planned pregnancy with obese mother? Systematic screening of family members: not recommended at this time Systematic screening of family members: not recommended at this time

16 Further work-up indicated Incidental finding on imaging for some other reason Incidental finding on imaging for some other reason Abnormal liver enzymes Abnormal liver enzymes Symptoms of liver disease Symptoms of liver disease Rule out other causes: alcohol, medications, hepatitis, etc. Rule out other causes: alcohol, medications, hepatitis, etc.

17 NAFLD fibrosis score AgeBMIHyperglycemia Platelet count AlbuminASTALT

18 NAFLD fibrosis score < : predictor of absence of significant fibrosis (F0-F2 fibrosis) < : predictor of absence of significant fibrosis (F0-F2 fibrosis) ≤ to ≤ 0.675: indeterminate score ≤ to ≤ 0.675: indeterminate score > 0.675: predictor of presence of significant fibrosis (F3-F4 fibrosis) > 0.675: predictor of presence of significant fibrosis (F3-F4 fibrosis)

19 Algorithm for evaluating NAFLD* *taken from AGA position paper 2002 Accidental discovery Screen those with risk factors Accidental discovery Screen those with risk factors AST or AST AST or AST Symptomatic liver disease Symptomatic liver disease elevated normal elevated normal r/o other causes of liver disease monitor monitor ongoing alcohol ongoing alcohol yes no yes no Abstain Imaging study Abstain Imaging study Echogenic US or fat on CT Echogenic US or fat on CT May need biopsy May need biopsy

20 Liver biopsy AASLD rec’s Incidental finding on imagery with normal enzymes: no biopsy indicated, monitor. Incidental finding on imagery with normal enzymes: no biopsy indicated, monitor. Presence of metabolic syndrome and persistently elevated biochemistries may benefit from liver biopsy 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 Patients with biopsy proven NASH cirrhosis should be screened routinely for esophageal varices and HCC

21 Assessment Symptoms Symptoms –Malaise, fatigue, RUQ discomfort –Snores, disturbed sleep, wakes up tired –Chronic pain disorders, achy muscles Physical exam Physical exam –Abdominal obesity –Enlarged liver –RUQ tenderness on palpation Labs Labs –Consistent with metabolic syndrome –Elevated bilirubin, AST, ALT, AP, GGT

22 Management: Lifestyle Interventions

23 Lifestyle Interventions Weight loss by lower caloric intake and increased physical exercise * led to improvement in biopsy. 9.3% weight loss: improvement in steatosis, necrosis, and inflammation; not fibrosis 3-5% weight loss improves steatosis but more is needed to improve inflammation 3-5% weight loss improves steatosis but more is needed to improve inflammation Alcohol consumption: Alcohol consumption: –heavy intake should be avoided –light intake (<1/day) may have benefits**, may not*** * Promrat, et al. Hepatology 2010 * Promrat, et al. Hepatology 2010 ** Dunn, et al. Hepatology 2008 ** 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

24 Management Medications

25 Insulin sensitizing agents Metformin * Metformin * –reduction in IR and enzymes, –no improvement in histology Thiazolidinediones Thiazolidinediones –Rosiglitazone**: improved enzymes and steatosis, but not inflammation –Pioglitazone:***+weight gain, but improvement in hepatocellular injury * Uygun, et al Aliment Pharm Ther 2004 * Uygun, et al Aliment Pharm Ther 2004 *Nair, et al Aliment Pharm Ther 2004 *Nair, et al Aliment Pharm Ther 2004 **Ratziu, et al Gastroenterology 2008 **Ratziu, et al Gastroenterology 2008 ***Sanyal, et al NE J Med 2010 ***Sanyal, et al NE J Med 2010

26 PIVENS Study Pioglitazone, Vitamin E, placebo Pioglitazone, Vitamin E, placebo 96 weeks 96 weeks Adults Adults –with NASH –without DM, cirrhosis, Hep C, heart failure –limited alcohol intake over previous 5 years Randomized trial Randomized trial –Pio group: 80 –Vit E group: 84 –Placebo: 83 Sanyal et al, New England J of Medicine 2010 Sanyal et al, New England J of Medicine 2010

27 Primary outcome Vitamin E vs placebo Vitamin E vs placebo 43% improvement vs 19%: significant (Steatosis, lobular inflammation, hepatocellular ballooning and fibrosis) (Steatosis, lobular inflammation, hepatocellular ballooning and fibrosis) Pio vs placebo Pio vs placebo 34% improvement vs 19%: not significant Sanyal et al, New England J of Medicine 2010

28 Secondary outcome Vitamin E vs placebo Vitamin E vs placebo –Also reduction in SGOT/SGPT Pio vs placebo Pio vs placebo –Reduction in SGOT/SGPT –Reduction in steatosis, lobular inflammation –Improvement in IR –Increase in weight that did not resolve after discontinuance of Pio Sanyal et al, New EngJ of Med 2010

29 PIVEN Conclusions Vitamin E was superior to placebo in adults with NASH and without DM Vitamin E was superior to placebo in adults with NASH and without DM Pioglitazone may have a role in treating patients with biopsy-proven NASH, however long term safety and efficacy has not been established Pioglitazone may have a role in treating patients with biopsy-proven NASH, however long term safety and efficacy has not been established Sanyal et al, New EnglJ of Med 2010 Sanyal et al, New EnglJ of Med 2010

30 AASLD recommendations: Pio can be used to treat certain patients with biopsy-proven NASH who do not have DM but long term safety and efficacy has not been established Pio can be used to treat certain patients with biopsy-proven NASH who do not have DM but long term safety and efficacy has not been established Vitamin E 800 IU/day improves liver histology in NASH pts Vitamin E 800 IU/day improves liver histology in NASH pts –Not recommended to treat NASH in those with other chronic liver diseases, diabetics, those with NASH cirrhosis or cryptogenic cirrhosis, NAFLD without biopsy

31 Vitamin E: other concerns Meta-analysis* including 136,000 participants found taking Vitamin E supplements > 400 IU/day had a higher risk of all cause mortality 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 Vitamin E** > 400 IU/day increases risk of prostate cancer in relatively healthy men *Miller et al Annals of Internal Medicine 2005 *Miller et al Annals of Internal Medicine 2005 ** Klein, et al, JAMA 2011 ** Klein, et al, JAMA 2011

32 Other meds for NASH Ursodeoxycholic acid* Ursodeoxycholic acid* –no histologic benefit Omega-3 fatty acids** 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 *Lindor, et al. Hepatology 2004 **Capanni, et al. Alimen Pharm Ther 2006 **Capanni, et al. Alimen Pharm Ther 2006

33 Statins CVD common cause of death for NAFLD and NASH CVD common cause of death for NAFLD and NASH Stratify risks and treat accordingly Stratify risks and treat accordingly Several studies show NAFLD and NASH pts are not at increased risk of liver injury over general population* Several studies show NAFLD and NASH pts are not at increased risk of liver injury over general population* No RCTs with histological end points using statins to treat NASH No RCTs with histological end points using statins to treat NASH *Chalasani, et al. Am J Gastro 2012 *Chalasani, et al. Am J Gastro 2012

34 GREACE study* Concluded statins significantly improve liver biochemistries and CV outcomes in pts with elevated enzymes likely due to NASH Concluded statins significantly improve liver biochemistries and CV outcomes in pts with elevated enzymes likely due to NASH Athyros et al Lancet 2010 Athyros et al Lancet 2010

35 AASLD Recommendation on 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.”

36 Bariatric surgery No RCTs No RCTs Cochrane review 2010: lack of RCTs prevents definitive assessment of risks/benefits Cochrane review 2010: lack of RCTs prevents definitive assessment of risks/benefits Prospective study* Prospective study* –381 adults with severe obesity, fibrosis score<3 –Clinical, metabolic, liver biopsy comparisons at 1 year and 5 years –Significant improvement in steatosis, ballooning, resolution of probable/definite NASH at 1 and 5 years –Small but significant increase of fibrosis score at 5 years (96% had improvement) *Mathurin et al Gastroenterology 2009 *Mathurin et al Gastroenterology 2009

37 AASLD Recommendation on Bariatric Surgery Premature to consider foregut surgery as an option to specifically treat NASH 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 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 For those with cirrhosis: type, safety and efficacy of foregut surgery is not established

38 Transplant Considerations

39 MS & Immunosuppression Steroids Steroids – BP induce IR –lipid metabolism weight gain – gluconeogenesis peripheral glucose utilization CNIs : pancreatic beta cell toxicity CNIs : pancreatic beta cell toxicity –Nephrotoxicity –TAC - glucose intolerance and de novo DM –CSA - HTN and hyperlipdemia mTOR inhibitors mTOR inhibitors –hyperlipidemia

40 Metabolic Syndrome in Kidney Transplant* Metabolic syndrome (MS) may play a role in allograft loss and poor function Metabolic syndrome (MS) may play a role in allograft loss and poor function Pathophysiology of MS is altered by immunosuppression Pathophysiology of MS is altered by immunosuppression * Hricik, Clin J of ASN 2011 * Hricik, Clin J of ASN 2011

41 Metabolic Syndrome in Kidney Transplant Prevalence of MS post KTx Prevalence of MS post KTx –22.6% at 1 year* –37.7% at 18 months* –63% at a median of 6 years** * Porrini et al, Amer J of Kid Dis 2006 ** de Vries et al, Amer J of Trans 2004

42 Metabolic Syndrome in Kidney Transplant MS lowered creatinine clearance by 5mL/min after 7 years MS lowered creatinine clearance by 5mL/min after 7 years Systolic BP and hypertriglyceridemia had most negative impact Systolic BP and hypertriglyceridemia had most negative impact *de Vries et al, Amer J of Trans 2004

43 Metabolic Syndrome in Kidney Transplant: Blood Pressure Choice of antihypertensive post KTx: Cochrane Group Review blood-pressure-medication-for-kidney- transplant-recipients blood-pressure-medication-for-kidney- transplant-recipients

44 Metabolic Syndrome in Kidney Transplant: Hyperlipdemia ALERT trial* ALERT trial* –Randomized, double blind, placebo control (N=1100) –Fluvastatin was superior to placebo in significantly lowering total and LDL cholesterol in renal transplant pts and in lowering rates of cardiac death and MI Hypertriglyceridemia: anecdotal use of fenofibric acid, fish oils, ezetimibe Hypertriglyceridemia: anecdotal use of fenofibric acid, fish oils, ezetimibe *Fellstrom et al Kid Internat 2004

45 Risk factors for NASH after liver transplant* Post transplant obesity Post transplant obesity TAC based regimen TAC based regimen DM DM Hyperglycemia Hyperglycemia HTN HTN ETOH as primary cause for transplant ETOH as primary cause for transplant Pre-transplant allograft biopsy showing steatosis Pre-transplant allograft biopsy showing steatosis *Dumortier, et al Am J of Gastro March 2010

46 MS Post Liver Transplant 44-58% of pts > 6months post OLT 44-58% of pts > 6months post OLT BMI increase of 10% increases risk of post OLT NAFLD BMI increase of 10% increases risk of post OLT NAFLD Associated with increased cardiovascular and cerebrovascular events Associated with increased cardiovascular and cerebrovascular events CVD causes 19-42% non-liver related deaths CVD causes 19-42% non-liver related deaths Diabetes, HTN, IR add 2-fold increased mortality risk Diabetes, HTN, IR add 2-fold increased mortality risk Watt & Charlton J Hepatology 2010 Watt & Charlton J Hepatology 2010

47 MS Post Liver Transplant Obesity Obesity –Between 1990 and 2002 the % of obese OLT recipients increased from 15% to 25% and average increase of 1kg/year* –Orlistat (tetrahydrolipstatin)** Limited efficacy  May interfere with drug absorption –Post transplant bariatric surgery: few reported cases***  May interfere with drug absorption * Everhart et al, Liver Transpl Surg 1998 * Richards et al, Transpl Int 2005 ** Cassiman et al, Transpl Int 2006 ***Takata et al, Surg Obes Relat Dis 2008 *** Butte et al, Obes Surg 2007 *** Campsen et al, Obes Surg 2008

48 MS Post Liver Transplant* Diabetes post OLT Diabetes post OLT –5 year occurrence of advanced fibrosis is increased in patients treated for DM (49%) when compared to those with normal insulin sensitivity (20%) –Treatment goals same as general population * Watt & Charlton J Hepatology 2010 * Watt & Charlton J Hepatology 2010

49 MS Post Liver Transplant* Dyslipidemia post OLT: 45-69% Dyslipidemia post OLT: 45-69% –Changing immunosuppression: CsA to TAC, Rapa to TAC, steroid free –High cholesterol: Statins:  pravastatin most studied; does not require P450 enzyme system  With other statins: reduction in TAC/CsA dose???  Mediterranean diet –High Triglycerides:  fish oils  Fenofibric acids derivatives: reduction in TAC/CsA dose???  ezetimide * Watt & Charlton J Hepatology 2010 * Watt & Charlton J Hepatology 2010

50 MS and Heart Transplant* 48% of heart transplant recipients Long term survival better without MS Differences observed in MS group Differences observed in MS group –Median age older –Pre-tx creatinine higher –Pre-tx HTN higher –BMI higher –Dyslipidemia higher rate No difference MS vs nonMS No difference MS vs nonMS –Gender –Underlying etiology –Smoking –DM history pre-tx –Immunosuppression *Sanchez-Lazaro et al Transplantation Proc 2011

51 MS and Lung Transplant

52 Impact of FLD on Donors Deaths due to CVA and CVD result in atherosclerotic Deaths due to CVA and CVD result in atherosclerotic vessels vessels –Poorer quality organs –Fewer organs  Discarded livers with>30% steatosis

53 Special Considerations

54 NASH and Hepatocellular Carcinoma Retrospective study* 6,508 pts with NAFLD by US Retrospective study* 6,508 pts with NAFLD by US F/up 5.6 years F/up 5.6 years Primary end point: onset of HCC Primary end point: onset of HCC 16 new cases of HCC (0.25%) 16 new cases of HCC (0.25%) Cumulative rates of NAFLD-related HCC: Cumulative rates of NAFLD-related HCC: –0.02% at year 4 –0.19% at year 8 –0.51% at year 12 * Kawamura et al, Am J Gastroenterology 2011

55 Acute Fatty Liver & Pregnancy Presents at weeks Presents at weeks Mitochondrial dysfunction preventing oxidation of FFA which accumulate in liver Mitochondrial dysfunction preventing oxidation of FFA which accumulate in liver Presents with malaise, N/V in 3 rd trimester, RUQ pain, UGI bleed, ARF, FHF, confusion, HTN, jaundice, hypoglycemia Presents with malaise, N/V in 3 rd trimester, RUQ pain, UGI bleed, ARF, FHF, confusion, HTN, jaundice, hypoglycemia Mortality: maternal %, infant 7-66% Mortality: maternal %, infant 7-66% Postpartum: may resolve or proceed to needing a transplant Postpartum: may resolve or proceed to needing a transplant

56 Pediatric Issues NAFLD reported as early as 2 y/o NAFLD reported as early as 2 y/o NASH-related cirrhosis as early as 8 y/o NASH-related cirrhosis as early as 8 y/o Independent predictors of FLD in adolescence Independent predictors of FLD in adolescence Obesity Obesity Older age Older age Male gender Male gender Dyslipidemia Dyslipidemia Hispanic ethnicity Hispanic ethnicity HTN HTN IR IR Schwimmer, et al. Pediatrics 2006 Schwimmer, et al. Hepatology 2005 Schwimmer, et al. Gastroenterology 2009

57 Pediatric Issues Children very young or not overweight who have NAFLD should be worked up for other causes of liver disease Children very young or not overweight who have NAFLD should be worked up for other causes of liver disease –Alcohol –Inborn errors of metabolism –Storage disorders –Wilson’s disease –Auto-immune hepatitis –Cystic fibrosis –Viral hepatitis

58 Pediatric Issues: screening Expert panel recommendations: Biannual AST/ALT starting at age 10 in obese children and those whose BMI >85% percentile with other risk factors* Expert panel recommendations: Biannual AST/ALT starting at age 10 in obese children and those whose BMI >85% percentile with other risk factors* AASLD has no recommendations AASLD has no recommendations * Barlow et al. Pediatrics 2007

59 Pediatric Issues: treatment Prospective: Intensive lifestyle behavior modification improves ALT and steatosis by ultrasound* Prospective: Intensive lifestyle behavior modification improves ALT and steatosis by ultrasound* –>20% body weight reduction –94% were able to lose weight by calorie reduction and exercise * Nobili, et al. Hepatology 2006

60 Pediatric Issues: treatment RCT: Antioxidant therapy* RCT: Antioxidant therapy* –Groups  Lifestyle modification alone  Lifestyle modification with Vitamin E (600IU/d) and Vitamin C (500mg/d) –Both groups improved ALT, steatosis, inflammation, ballooning equally –Concluded: no advantage to adding Vitamins E & C to lifestyle modifications * Nobili, et al. Hepatology 2008 * Nobili, et al. Hepatology 2008

61 Pediatric Issues: treatment TONIC study* vitamin E (800IU/d) or metformin (500mg BID) vs placebo TONIC study* vitamin E (800IU/d) or metformin (500mg BID) vs placebo 8 to 17 y/o’s with NAFLD 8 to 17 y/o’s with NAFLD Primary outcome: sustained reduction of ALT not achieved in either group Primary outcome: sustained reduction of ALT not achieved in either group Statistically significant improvement in resolution of NASH in Vitamin E group over placebo Statistically significant improvement in resolution of NASH in Vitamin E group over placebo Metformin offered no benefit over placebo Metformin offered no benefit over placebo *Lavine, et al JAMA 2011 *Lavine, et al JAMA 2011

62 AASLD Pediatric Recommendations Intensive lifestyle behavior modification, including dietitian consultation, is first line treatment Intensive lifestyle behavior modification, including dietitian consultation, is first line treatment Metformin 500mg BID offers no benefit 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. Vitamin E 800 IU/d offers histological benefit but confirmatory studies are needed before it can be recommended in clinical use.

63


Download ppt "Fatty Liver Disease Jamie Blazek, MPH, APRN, FNP-C Liver Transplant Department Ochsner Health Systems New Orleans, La."

Similar presentations


Ads by Google