Assessment and management of NAFLD in the Asia-Pacific region

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Assessment and management of NAFLD in the
Asia-Pacific region

• Shiv Chitturi, Geoff Farrell, George Lau, Toshiji
  Saibara
• for writing team 1

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• How do we define NAFLD
• (and NASH)?

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Simple steatosis
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Steatohepatitis
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Proposal 1An operational definition of NAFLD

• For research studies and clinical practice
  settings, an operational definition of NAFLD is
  required because pathological definition is often
  not possible
• 1A Fatty liver can be defined by the presence of
  at least 2 of 3 abnormal findings on abdominal
  ultrasonography (Yajima et al. Tohoku J Exp Med
  198313943-50)
• Diffusely increased echogenicity (bright
  liver), with liver echogenicity greater than
  kidney
• Blurring of hepatic vessels
• Deep attenuation of the ultrasound signal

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Proposal 1An operational definition of NAFLD

• 1A Fatty liver can be defined by the presence of
  at least 2 of 3 abnormal findings on abdominal
  ultrasonography (Yajima et al. Tohoku J Exp Med
  198313943-50)
• Diffusely increased echogenicity (bright
  liver), with liver echogenicity greater than
  kidney
• Blurring of hepatic vessels
• Deep attenuation of the ultrasound signal
• NAFLD is highly likely provided other causes of
  liver disease are excluded (Proposal 2),
  particularly significant alcohol intake and
  medication use

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Operational definitionProposal 1B

• In patients with otherwise unexplained ALT
  elevation, NAFLD is highly likely to be the cause
  
• if hepatic imaging results are compatible with
  fatty liver (see Proposal 1A),
• and metabolic risk factors are present

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Exclusion criteriaProposal 2.1

• Excess alcohol intake (gt 50 g/day or 350 g/week)
  regard as having fatty liver consistent with
  alcoholic liver disease
• Intake levels of 2 standard drinks (20 g ethanol)
  /day (140 g/week) in men, and 1 standard
  drink/day (70 g/week) in women are endorsed as
  thresholds to define non-alcoholic
• Intake between that defined as excessive versus
  consistent with non-alcoholic disease regard as
  indeterminate
• individual patient management should consider
  potential roles of both alcohol and metabolic
  factors

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Exclusion criteriaProposals 2.2, 2.3

• History of systemic illness known to cause fatty
  liver
• Recently received drugs (including herbal
  medicines) known to cause ALT and GGT elevation
  or fatty liver
• All common (HBV, HCV) and less common liver
  diseases (autoimmune, Wilsons, a1-antitrypsin
  deficiency)
• Hepatic malignancies, infections, biliary tract
  disease
• In HBsAg-pos pts with serum HBV DNA lt104 IU/ mL,
  raised ALT may be due to fatty liver if metabolic
  risk factors present

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Initial assessmentProposal 3

• NAFLD should be suspected in those with metabolic
  risk factors (central obesity, diabetes,
  dyslipidaemia, metabolic syndrome),
• and sought by determining LFTs and hepatic
  ultrasonography
• In pts with raised ALT and/or hepatic imaging
  consistent with fatty liver, examination and
  baseline tests should be performed
• to allow definition of NAFLD (Proposal 1),
• to identify the underlying metabolic factors,
• to exclude other disorders (Proposal 2), and
• to assess the likely severity of NAFLD/NASH

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Proposal 3 (continued)

• These tests encompass biochemical and
  haematological indices, serology, anthropometry,
  blood pressure measurement, hepatic imaging, and
  determination of insulin sensitivity

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Minimal assessment - 1

• Biochemistry
• Bilirubin, ALT, (AST), GGT, albumin, globulin,
  fasting ser lipids
• Haematology
• Complete blood count (platelets)
• Serology
• Anti-HCV, HBsAg, anti-nuclear antibody
• Anthropometry
• Body mass index (BMI) kg/(height in metres)2
  waist circum-ference (Asia-Pacific reference
  standards of IDF, Lancet 2005)

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International Diabetes Federation definitions of
central obesityAlberti KG, et al. Metabolic
syndrome - new worldwide definition. Lancet
20053661059-62.
Group by race and gender Waist circumference (cm)
Europid men 94 (102)
Europid women 80 (88 cm)
Asian men 90
Asian women 80
measured standing midpoint between lower border
of rib cage and iliac crest compare with USA
(NHANES)
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Minimal assessment - 2

• Measure the blood pressure
• Determine insulin sensitivity
• Fasting blood glucose (FBG)
• If FBG 5.6 mmol/L, 75G oral glucose tolerance
  test (OGTT) (in patients without known history of
  diabetes) IDF recommendation, Lancet 2005
• Hepatobiliary imaging
• Abdominal ultrasonography, assessed by defining
  criteria of Proposal 1

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Assessment Proposal 3 (contd)

• Once the diagnosis of NAFLD is established,
• optional tests include
• Abdominal CT, if properly conducted ultrasound is
  not informative
• Liver biopsy is NOT usually required
• to diagnose NAFLD

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Proposal 3 (contd)Liver biopsy

• Consider in
• Cases where there is diagnostic uncertainty
• Patients at high risk of hepatic fibrosis (in the
  absence of clinical or imaging evidence of
  cirrhosis)
• Clinical trials (informed consent)
• Because of reduced risk, greater convenience at
  laparoscopy for another purpose (cholecystectomy,
  gastric banding)

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Proposal 3 (contd)Other tests

• Insulin sensitivity
• In those with normal FBG, 75G OGTT
• Fasting and post-prandial (e.g., 120 min of
  OGGT) serum insulin
• C-peptide
• Tests relevant only to research studies
• Hepatic triglyceride quantification by magnetic
  resonance spectroscopy
• Body fat distribution by DEXA scan or abdominal
  CT
• Biomarkers to distinguish NASH from steatosis,
  estimate fibrotic severity

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Proposal 4 Liver biopsy assessment

• The NIH NASH Clinical Research Network (CRN)
  Pathology Working Party guidelines (Kleiner D et
  al. Hepatology 2005) should be adopted for
  initial diagnosis and for use in therapeutic
  trials.
• Use of the NAFLD Activity Score (NAS) should be
  encouraged in routine reporting, as well as the
  fibrosis stage

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Cryptogenic cirrhosis
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Proposal 4Liver biopsy assessment (contd)

• Caution should be applied to ascribing
  cryptogenic cirrhosis to NAFLD/NASH in the
  absence of histological characteristics of
  steatohepatitis, even with metabolic risk factors
  (diabetes, obesity, metabolic syndrome).
• A rigorous search for secondary disorders,
  including viral hepatitis and surreptitious
  alcohol use should be made in such cases.