1 / 50

Dr Jonathan Stenner

Dr Jonathan Stenner. Alcoholic fatty liver Non Alcoholic fatty liver Primary Associated with metabolic syndrome Secondary Drugs – Steroids, Amiodarone, Tamoxifen Metabolic/ Genetic – Lipodystrophies Nutritional – TPN, Rapid weight loss Small bowel disease- IBD, Bacterial overgrowth

vicki
Download Presentation

Dr Jonathan Stenner

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Dr Jonathan Stenner

  2. Alcoholic fatty liver • Non Alcoholic fatty liver • Primary • Associated with metabolic syndrome • Secondary • Drugs – Steroids, Amiodarone, Tamoxifen • Metabolic/ Genetic – Lipodystrophies • Nutritional – TPN, Rapid weight loss • Small bowel disease- IBD, Bacterial overgrowth • Environmental - petrochemicals

  3. What is fatty liver? • Histopathological • Accumulation of fat in the liver > 5-10% of total liver weight • In clinical practice • Abnormal LFTS • Fatty liver on USS (not present if steatosis < 33%) • What does Non- alcoholic mean? • Daily alcohol consumption of < 20g/day • 1 unit alcohol = 8g

  4. Largely benign • Few good studies • Largest study of paired liver biopsies (n=103 mean follow up 3.2 ±3 years) • 37% progressed fibrosis stage • 34% remained stable • 29% regressed • Mean rate of fibrosis progression 0.09 stages/year Adams et al J. Hep 2005 Fibrosis progression rate was highly variable

  5. Extrapolation of data in autopsy and liver biopsy studies • 20-30 % of general public have NAFLD • Of whom 10-25% may have NASH • 2-10% of these patients may be at risk of progressive liver fibrosis, cirrhosis and HCC

  6. Data from Mediplus practices

  7. Prevalence of NAFLD is similar in adults with (25%) and WITHOUT abnormalities of liver enzymes) • 50% of NAFLD cases will be missed if abnormal LFTS are considered as a selection criteria Bedogni et al Hepatology 2005

  8. Obese (36-78%) • Diabetes Mellitus (43-62%) • Patients with hyperlipidaemia (50%) • Hypertension (30%) • Metabolic Syndrome (50-83%) • Insulin Resistance (80%)

  9. Suspect the diagnosis • Diabetic • Metabolic syndrome • BMI > 30 • Incidental finding of “bright liver on USS” • > 33% steatosis • Abnormal LFTs • Mildly elevated ALT • GGT often isolated elevation

  10. Patients at risk to develop NASH with fibrosis: A. Age > 45 B. Obesity (BMI > 31-32) C. Diabetes • Angulo et al. Independent predictors of liver fibrosis in patients with NASH. Hepatology. 2000; 30: 1356-1362.

  11. Risk factors for advanced fibrosis at baseline • ALT > 100 IU/ml • AST:ALT ratio > 1.0 • Platelet count < 150 x 109/ml Faster progression to advanced fibrosis • BMI > 30 • Type 2 Diabetes Mellitus Matteoni et al 1999

  12. Peripheral stigmata of chronic liver disease • Splenomegaly • Cytopaenia • Abnormal iron studies • Diabetes and/or significant obesity in an individual over the age of 45

  13. Argo CK, J Hepatol 2009

  14. Abn LFTs Suspicion of NAFLD Fatty liver on USS LIVER OPD 1 History and exam Bloods USS LIVER OPD 2 Diagnosis NAFLD Risk Factor assessed ? Screening bloods and USS organised prior to referral HIGH RISK OF FIBROSIS Age>45 DM or Obese AST:ALT > 1 Platelets < 150 LOW RISK OF FIBROSIS No risk factors Age < 45 BMI <30 With AST:ALT < 1 PRIMARY CARE Management of BP Rx Hyperlipidaemia Yearly screening AST/ALT ALT>100 Ferritin > 400 2 occasions 3 months apart Platelets Abnormal LIVER BIOPSY NASH Mild fibrosis Cirrhosis Bridging fibrosis Bland Steatosis Standard Follow up Secondary Care HCC screening varices follow up etc

  15. How to Treat? Antioxidants Insulin Sensitizers Cytoprotectants Antihyperlipidemics Second Hit First Hit Steatosis NASH Insulin resistance ↑ Fatty acids Lipid peroxidation Weight Loss Diet/Exercise

  16. 348 male subjects with abn ALT (other causes excluded) Followed for 1 year after health advice re exercise and weight loss Patients who normalised ALT were followed for a further 2 years Weight loss of 5% improved ALT with OR 3.6 for ALT normalisation Maintainance of weight loss OR 4.6 for ALT normalisation Suzuki et al 2005

  17. Palmer et al. Gastroenterology 1990 --39 obese patients, no primary liver disease --Retrospective analysis after weight loss --Lower ALT seen in patients with >10% weight loss Anderson et al. Journal Hepatology 1991 --41 obese patients with biopsy-proven NAFLD --Low calorie diet (~400 kcal/d) --Most improved, but 24% worse fibrosis/inflammation --Histological worsening associated with rapid weight loss

  18. Can lead to sustained improvement in liver enzymes, histology, serum insulin levels, and quality of life. • Improvement in steatosis following bariatric surgery • Should not exceed approximately 1.6 kg per week in adults .

  19. Metformin Marchesini et al. Lancet 2001 --20 patients, biopsy-proven NASH --14 metformin (500 tid) x 4 months; 6 controls --ALT & OGTT improved in metformin Nair et al. AP& T 2004 --22 patients, biopsy-proven NASH --Received metformin 20 mg/kg/d x 12 months --Improvement in ALT & insulin sensitivity --No improvement in liver histology

  20. Non significant improvement in inflammatory markers • No improvement in histological scoring • ?transient in effect.

  21. Rosiglitazone (FLIRT-1 and FLIRT-2) • 1 year RCT • 47% in Rosi group improved steatosis, 16% placebo • 38% normalised ALT in Rosi group vs 7% placebo • Concerns about long term effects especilaly weight gain

  22. Laurin et al. Hepatology 1996- Clofibrate -No significant improvement in ALT or histology Basaranoglu et al. J.Heptol 1999- Gemfibrozil --74% patients in gemfibrozil group had lower ALT --30% patients no treatment group had lower ALT Naserimoghadam SSO - J Hepatol 2003 Probucol was associated with a significant reduction in serum aminotransferases No conclusive evidence of benefit

  23. Statins

  24. BASELINE ALT POSTBASELINE ALT (week 12) <ULN >x1 >x2 <Upper limit normal 56 58 6 8 1 1 P=0.78 >x1 14 12 33 38 9 7 >x2 1 1 9 9 5 9 Patients with Pravastatin Patients with Placebo No differences in baseline ALT values between groups Lewis 2007

  25. Moderate elevation Severe elevation 1.9% 0.2% Cohort 2 (normal LFT + statins) P=0.002 NS Cohort 1 (elevated baseline LFT + statins) 4.7% 0.6% NS NS Cohort 3 (elevated LFT without statins) 6.4% 0.4% In summary, individuals with elevated LFT do not appear to have increased susceptibility to hepatotoxicity from statins.

  26. Measure baseline ALT/AST • Start statin if AST/ALT < 3 xULN • Monitor AST/ALT at 6 and 12 weeks • If AST/ALT < 3 x ULN continue or dose advance • If AST/ALT > 3 x ULN recheck in 1 week if still elevated then dose reduce or stop • If AST/ALT return to baseline then continue lower dose • If stopped then rechallenge with lower dose of another statin

  27. How to Treat? Antioxidants Insulin Sensitizers Cytoprotectants Antihyperlipidemics Second Hit First Hit Steatosis NASH Insulin resistance ↑ Fatty acids Lipid peroxidation Weight Loss Diet/Exercise

  28. Laurin et al. Hepatology 1996 --63% had improved ALT and steatosis --No significant improvement in inflammation/fibrosis Lindor et al. Hepatology 2004 --Randomized controlled double-blind study --168 patients with biopsy-proven NASH --No significant improvement in ALT or histology

  29. Betaine • Losartan • Pentoxifylline • Orlistat

  30. Vitamin E Hasegawa et al. Aliment Pharmacol Ther 2001 --22 patients, 10 steatosis and 12 biopsy-proven NASH --6/12 standard diet followed by Vitamin E 100 IU tid x 12/12 --Steatosis group showed improvement in ALT after diet --Improvement in ALT after Vitamin E --40% NASH patients had histological improvement Kugelmas et al. Hepatology 2003 --16 patients with biopsy-proven NASH followed for 3 mo --9 received diet/exercise and Vitamin E 800 IU qd --7 diet/exercise only --Vitamin E conferred no significant improvement in ALT

  31. 247 non diabetic patients RCT for 96 weeks • 80 Pioglitazone 30 mg daily • 84 Vitamin E 800 IU daily • 83 Placebo • No difference in adverse events amongst groups Sanyal et al NEJM 2010

  32. Sanyal et al NEJM 2010

  33. Sanyal et al NEJM 2010

  34. NAFLD is common, may be clinically silent, and is likely to increase • NAFLD is a marker of metabolic syndrome and increased risk of CV disease • Weight loss / exercise are the only proven treatments-?role of bariatric surgery • Emerging evidence for antioxidants • Other causes must be excluded!!!

  35. Alcohol-use disorders: preventing harmful drinking Workshop on putting NICE guidance into practice June 2010 NICE public health guidance 24

  36. Background • Alcohol is attributable for: • 14,982 deaths in England (2005) • 500,000 recorded crimes (England) • up to 35% of attendances at hospital emergency departments (2003) • 24% of adults drink a hazardous or harmful amount

  37. Screening AUDIT – CFor people aged 16 years and over • Scoring:A total of 5+ indicates increasing or higher risk drinking.

  38. Summary • Addresses recognising alcohol dependency • Advice on “brief intervention” • Criteria for specialist referral • show signs of moderate or severe alcohol-dependence • have failed to benefit from structured brief advice and an extended brief intervention and still want help • show signs of severe alcohol-related impairment or have a related co-morbid condition

  39. Alcohol-use disorders: physical complications Implementing NICE guidance June 2010 NICE clinical guideline 100

  40. Acute alcohol withdrawal: 1 For people in acute alcohol withdrawal with, or who are assessed to be at high risk of developing, alcohol withdrawal seizures or delirium tremens, offer admission to hospital for medically assisted alcohol withdrawal.

  41. Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence Implementing NICE guidance February 2011 NICE clinical guideline 115

  42. Epidemiology Weekly alcohol consumption of more than 50 units (men) or more than 35 units (women) by age (years) and gender – Great Britain, 2009 Source: General Lifestyle Survey, Office for National Statistics

  43. Background • Current practice and service provision across the country is varied • Only 6% per year of people aged 16–65 years who are alcohol dependent receive treatment • Comorbid mental and physical disorders are common.

  44. Assisted alcohol withdrawal Person who drinks > 15 units alcohol per day or scores > 20 on AUDIT • Assessment • Consider offering: • – assessment for and delivery of a community-based assisted withdrawal, or • – assessment and management in specialist alcohol services if there are safety concerns about a community-based assisted withdrawal. Community base assisted withdrawal Inpatient and residential withdrawal Intensive community programmes after assisted withdrawal for severe or mild to moderate dependence with complex needs

  45. Thank you

More Related