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Other metabolic factors
Obesity is just one component of MetS. Hyperglycemia, dyslipidemia and hypertension are also
associated with NAFLD (Table 4) [2]. In particular, cirrhosis is uncommon in NAFLD patients with
normal glucose regulation. Moreover, insulin resistance is almost universal in NAFLD patients even
when plasma glucose is within the normal range. In a large retrospective study in Korea, non-obese
patients with NAFLD had higher prevalence ratios for other MetS components than obese patients [4].
Diagnostic workup
The purposes of investigations in the management of NAFLD in lean patients are three-fold: establishing
the diagnosis of NAFLD, screening for concomitant metabolic disorders and CVD, and assessing the
severity of liver disease.
Establish the diagnosis
The diagnosis of NAFLD is usually straightforward. For practical purposes, abdominal ultrasonography
is the test to detect fatty liver in most clinical settings. Fatty liver has bright echotexture, vascular blurring
and deep attenuation of ultrasound signal. NAFLD can be diagnosed when fatty liver is detected and
there is no evidence of an alternative liver disease.This would involve exclusion of excessive alcohol intake
and consumption of drugs that may lead to fatty liver (e.g. systemic corticosteroids and tamoxifen).
Further investigations to exclude other liver diseases would depend on whether the liver biochemistry
is abnormal as well as the local epidemiology. For example, HCV infection, particularly genotype 3, is
often associated with hepatic steatosis.
Table 4. Definition of metabolic syndrome by the International Diabetes Federation and joint
societies (2009).
Measure Categorical cut points
Elevated waist circumference Ethnic specific definitions
Elevated triglycerides or on drug treatment ≥150 mg/dl (1.7 mmol/l)
Reduced high density lipoprotein-cholesterol Male: <40 mg/dl (1.0 mmol/l)
or on drug treatment Female: <50 mg/dl (1.3 mmol/l)
Elevated blood pressure or on drug treatment ≥130/85 mmHg
Elevated fasting glucose or on drug treatment ≥100 mg/dl (5.6 mmol/l)
However, if a patient has fatty liver together with features of advanced disease but is lean and has low
metabolic burden, an alternative diagnosis should be suspected. Apart from other chronic liver diseases,
hypothyroidism, hypopituitarism, hypogonadism and lipodystrophy may be considered.
Concomitant metabolic disorders and CVD
NAFLD is often referred to as the hepatic manifestation of MetS. A patient with NAFLD should
therefore be screened for diabetes, hypertension and dyslipidemia. Several studies have reported a
high incidence of postprandial hyperglycemia in NAFLD patients. A formal oral glucose tolerance test
should be considered, especially if the fasting plasma glucose is borderline. Regardless, NAFLD is
associated with increased risk of CVD; therefore, patients with cardiovascular symptoms should be
promptly investigated and managed.
Disease severity
Since the pre-test probability of NASH and advanced fibrosis is lower in lean patients, liver biopsy cannot
be justified unless an alternative diagnosis is suspected. Non-invasive tests are therefore preferred.These
have been covered in another part of this course, so only specific points relevant to lean patients will be
covered here.
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 39
Obesity is just one component of MetS. Hyperglycemia, dyslipidemia and hypertension are also
associated with NAFLD (Table 4) [2]. In particular, cirrhosis is uncommon in NAFLD patients with
normal glucose regulation. Moreover, insulin resistance is almost universal in NAFLD patients even
when plasma glucose is within the normal range. In a large retrospective study in Korea, non-obese
patients with NAFLD had higher prevalence ratios for other MetS components than obese patients [4].
Diagnostic workup
The purposes of investigations in the management of NAFLD in lean patients are three-fold: establishing
the diagnosis of NAFLD, screening for concomitant metabolic disorders and CVD, and assessing the
severity of liver disease.
Establish the diagnosis
The diagnosis of NAFLD is usually straightforward. For practical purposes, abdominal ultrasonography
is the test to detect fatty liver in most clinical settings. Fatty liver has bright echotexture, vascular blurring
and deep attenuation of ultrasound signal. NAFLD can be diagnosed when fatty liver is detected and
there is no evidence of an alternative liver disease.This would involve exclusion of excessive alcohol intake
and consumption of drugs that may lead to fatty liver (e.g. systemic corticosteroids and tamoxifen).
Further investigations to exclude other liver diseases would depend on whether the liver biochemistry
is abnormal as well as the local epidemiology. For example, HCV infection, particularly genotype 3, is
often associated with hepatic steatosis.
Table 4. Definition of metabolic syndrome by the International Diabetes Federation and joint
societies (2009).
Measure Categorical cut points
Elevated waist circumference Ethnic specific definitions
Elevated triglycerides or on drug treatment ≥150 mg/dl (1.7 mmol/l)
Reduced high density lipoprotein-cholesterol Male: <40 mg/dl (1.0 mmol/l)
or on drug treatment Female: <50 mg/dl (1.3 mmol/l)
Elevated blood pressure or on drug treatment ≥130/85 mmHg
Elevated fasting glucose or on drug treatment ≥100 mg/dl (5.6 mmol/l)
However, if a patient has fatty liver together with features of advanced disease but is lean and has low
metabolic burden, an alternative diagnosis should be suspected. Apart from other chronic liver diseases,
hypothyroidism, hypopituitarism, hypogonadism and lipodystrophy may be considered.
Concomitant metabolic disorders and CVD
NAFLD is often referred to as the hepatic manifestation of MetS. A patient with NAFLD should
therefore be screened for diabetes, hypertension and dyslipidemia. Several studies have reported a
high incidence of postprandial hyperglycemia in NAFLD patients. A formal oral glucose tolerance test
should be considered, especially if the fasting plasma glucose is borderline. Regardless, NAFLD is
associated with increased risk of CVD; therefore, patients with cardiovascular symptoms should be
promptly investigated and managed.
Disease severity
Since the pre-test probability of NASH and advanced fibrosis is lower in lean patients, liver biopsy cannot
be justified unless an alternative diagnosis is suspected. Non-invasive tests are therefore preferred.These
have been covered in another part of this course, so only specific points relevant to lean patients will be
covered here.
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 39
