New diagnostic and treatment approaches in non-alcoholic fatty liver disease (NAFLD)

Figures & data

Table I.  Clinical characteristics that increase the risk of developing NASH.

• Type 2 diabetes

• Central obesity

• Hypertension

• Metabolic syndrome

• Family history of NASH

• Hispanic ethnicity

• Severe elevation of liver transaminases, 2–3-fold ULN

• Older age, long-standing steatosis

• Hepatitis C infection

NASH = non-alcoholic steatohepatitis; ULN = upper limit of normal.

Table II.  Diagnostic considerations in NASH.

• Clinical and laboratory findings:

Few symptoms (i.e. right upper quadrant discomfort)

Most frequently ↑ALT > AST (except if advanced disease)

However, ~2/3 of patients have normal liver ALT/AST

• Imaging:

Ultrasound—CT scan: useful but poor sensitivity in obese patients

Magnetic resonance imaging (MRS): gold-standard for diagnosing steatosis, but not widely available

• Liver biopsy:

Needed for definitive diagnosis

Allows staging of the disease and monitoring of treatment

Table III.  Causes of fatty liver (other than NAFLD).

• Hepatitis C genotype 3

• Autoimmune hepatitis

• Primary biliary cirrhosis

• Alpha-1 antitrypsin deficiency

• Hepatitis B infection

• Wilson's disease

• HIV infection

• Acute fatty liver of pregnancy

• Drugs: corticosteroids, tamoxifen, diltiazem, amiodarone, methotrexate, valproic acid, anti-retroviral therapy

Figure 1.  Effect of diet plus pioglitazone compared to diet alone (plus placebo) on liver transaminases. Note that during the run-in, dietary advice rapidly lowers AST and ALT. However, pioglitazone compared to modest weight reduction has a much more significant impact in improving AST and ALT levels, normalizing both enzymes with 6 months of treatment. Shaded area represents pioglitazone or placebo administration period.

Figure 2.  Mean scores for inflammation, ballooning necrosis, steatosis, and fibrosis in liver biopsy specimens before and after treatment with a hypocaloric diet (-500 kcal per day) plus pioglitazone, or a hypocaloric diet plus placebo, in 55 patients with impaired glucose tolerance or T2DM and liver biopsy-confirmed NASH. Between-group differences were compared by means of the Wilcoxon rank-sum test. Within-group differences (before versus after treatment) were compared by means of the Wilcoxon signed-rank test. Reproduced, with permission, from Belfort R et al. [39].

Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006; 355: 2297–307

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