How Should We Manage Patients with NAFLD in 2007

Henry LY Chan, MD, FRCP

Professor

Department of Medicine and Therapeutics

The Chinese University of Hong Kong

Diagnosis of Fatty Liver

USG; CT if US not informative

Imaging can detect > 33% fat on liver biopsy Saadeh S et al., Gastroenterology 2002

Cannot differentiate steatosis from steatohepatitis

• Liver biopsy is usually not needed to

diagnose fatty liver disease

AFLD vs NAFLD

Alcohol consumption to define NAFLD (g/wk)

0 40 140

Ludwig (1980) Powell (1996) Bacon (1994)

Diehl (1988) Angulo (1999) Teli (1995)

Lee (1989) George (1998)

Bonkovsky (1999)

Metteoni (1999)

Faick-Ytter et al., Semin Liver Dis 2001

Exclude other Liver Disease

HBV – HBsAg, (HBV DNA)

HCV – anti-HCV, (HCV RNA)

Autoimmune hepatitis – ANA

Alfa-1 anti-trypsin deficiency

Wilson’s disease

Hepatic malignancy

Hepatic infection

Biliary disease

Liver biopsy

N Cirrhosis Liver-related death

Simple steatosis 59 3.3% 1.7%

Steatohepatitis 73 24.6% 10.9%

Steatohepatitis = fat accumulation + ballooning degeneration ± Mallory hyaline or fibrosis

Recommendation for liver biopsy 1. Diagnostic uncertainty2. High risk of advanced fibrosis3. Clinical trial4. With laparoscopic procedure/surgery

Matteoni CA, et al. Gastroenterology 1999

Advanced NAFLD

Clinical factors– Advanced age– Diabetes mellitus– Obesity

0 4 8 12 16

0.25

0.20

0.15

0.10

0.05

0

El-Serag and Everharts, Gastroenterology, 2004

DM

No DM

% HCC

Serum biomarker

• AST/ALT ratio• Serum hyaluronic acid• HOMA score• Plasma homocysteine• Triglyceride• Adiponectin• Steatotest• Fibrotest

Accuracy was seldom above

75-80%

Cannot substitute liver

biopsy

Guha et al, Gut 2006 Sebastian et al, WJG 2006

Metabolic Syndrome

ATP III 2001 IDF 2005

3 of the following Central obesity plus any 2 of the following

Central obesity

Hypertriglyceridaemia TG ≥ 1.7 mmol/l

Hypertriglyceridaemia TG ≥ 1.7 mmol/l or medication

Low HDL-C < 1.03 mmol/l (M), < 1.29 mmol/l (F)

Low HDL-C < 1.03 mmol/l (M), < 1.29 mmol/l (F) or medication

High BP ≥ 130/85 mmHg High BP ≥ 130/85 mmHg or medication

High fasting glucose ≥ 6.1 mmol/l High fasting glucose ≥ 6.1 mmol/l or pervious diagnosed type 2 diabetes

50%

40%

30%

20%

10%

36%

12% 14%2%

IGT DM

50%

40%

30%

20%

10%

33%

14%23%

7%

IGT DM

High fasting blood glucose alone

High fasting glucose +/- 2-hr post-prandial glucose

NAFLD

Control Wong VW et al., Aliment Pharmacol Ther 2006

OGTT recommended in patients without known DM and normal fasting glucose

Diet

No association between total caloric or protein vs severity of NAFLD

Soiga et al, Dig Dis Sci 2004

Low carbohydrate and low fat diet– Weight loss– Lower BMI– Lower insulin resistance– ? Some benefit in NAFLD

Huang et al., Am J Gastroenterol 2005

Daubioul et al. Eur J Clin Nutr 2005

Physical Activity

Aerobic exercise with dietary restriction can improve insulin resistance and liver disease in NAFLD in human

Cinar et al., JGH 2006

Nobili et al., Hepatology 2006Kugelmas et al., Hepatol 2003Ueno et al., J Hepatol 1997Suzuki et al, J Hepatol 1005Hicknam et al, Gut 2004Screenivasa et al, JGH 2006

Randomized controlled studies lacking

Pharmacological Treatment

Controversial or Preliminary No Benefit

Metformin Ursodeoxycholic acid

Thiazolidinediones Vitamin C or E

Betaine

Angiotensin II inhibitor

Pentoxifyline

Probucol

Statins

Adams and Angulo, Postgrad Med J 2006

Pharmacological treatment for NAFLD remains investigational

Use of Statins in NAFLD

Statins are safe in NAFLD

Recommended if clinically indicated for treatment of metabolic syndrome

Frequent monitoring of liver enzymes is not required

Chalasani et al., Hepatology 2005

Bariatric surgery

Bariatric surgery can induce weight loss and improve steatosis and ALT in patients with NAFLD

Effect on inflammation and fibrosis variable

Recommended for morbidly obese patients, particularly for those failed dietary restriction and exercise

Dixon et al, Hepatology 2004Kral et al., Surgery 2004Luyckx et al, Int J Oes Ralat Metab Disord 199

8Silverman et al, Am J Clin Pathol 1995

Proposal 5 Exclude secondary causes of fatty liver

Assess for severity of NAFLD

Screen and treat metabolic risk factors

Lifestyle modification (+/- some weight reduction) to reduce insulin resistance

Bariatric surgery for morbidly obese who fails lifestyle measures

Pharmacological treatment is not recommended as routine practice