**8. Imaging tecnology in NAFLD**

The Adult Treatment Panel III clinical definition of the metabolic syndrome: - Requires the presence of three or more of the following features:

Triglyceride level 150mg/dl or greater.

172 Liver Biopsy – Indications, Procedures, Results

treat obesity.

cases [39].

vere disease [40].

Fasting plasma glucose level 110 mg/dl or greater.

**Table 7.** Definition of the metabolic syndrome [31].

Waist circumference greater than 102 cm in men or greater than 88 cm in women.

Systolic blood pressure 130 mmHg or greater or diastolic pressure 85 mmHg or greater.

fibrosis (65,5%) and for complete resolution of NASH was 69,5%.

High-density lipoprotein (HDL) cholesterol level less than 40 mg/dl in men and less than 50 mg/dl in women.

**NAFLD after bariatric surgery.** Improvements of major histological features of disease ac‐ tivity, grade of steatohepatitis and rarely fibrosis following therapy (dietary, medicines or surgery) have been reported [34]. After surgical intervention liver histology improve in these features: lobular steatosis, necroinflammatory changes and fibrosis, against no im‐ prove in portal abnormalities [35]. Recent meta-analysis [36] shows that patients after bariat‐ ric surgery have improvement or resolution in steatosis (91,6%), in steatohepatitis (81,3%), in

In the near future, we will have to get used to new types of treatment, for example, "meta‐ bolic surgery", which might be performed to non-morbid obese patients with diabetes, and to the new changes in hepatic parenchyma following endoscopic procedures performed to

**NAFLD in children.** Pediatric NAFLD can have a different histologic presentation than adult NAFLD. In the first large biopsy series of pediatric NAFLD [37], two different histo‐ logic patterns were described with differences in race and gender. Type 1 NASH: similar to adults, more common in Caucasian children. Histologic characteristics are: steatosis, bal‐ looning degeneration and perisinusoidal fibrosis. On the other hand, Type 2 NASH was more common in Asian, Native American and Hispanics. Typical features in the liver biopsy are: steatosis with lymphocytic portal inflammation and portal fibrosis. Children with type 2 were younger and had a greater severity of obesity, and advanced fibrosis. This kind of pat‐ tern was described in adult morbid obese patients undergoing bariatric surgery, these pa‐ tients mean age were slightly lower [33]. Overlap cases with characteristic of both histological types may also be observed in pediatric NASH. A multicentre retrospective co‐ hort study reviewed 130 liver biopsies of children according to these criteria of pediatric NAFLD [38]. The majority of the biopsies presented an overlapping pattern (82%). Ad‐

vanced fibrosis was associated with the presence of lobular and portal inflammation.

Portal fibrosis is common in pediatric NAFLD and may evolve to periportal fibrosis and bridging fibrosis in some patients, whereas progression to cirrhosis is observed in rare

It is not clear, that Type 2 NASH, described as pediatric NASH, is an entity by itself or it is another stage of the spectrum of NASH which could be a predictor of those who have a se‐

Ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) can identi‐ fy liver steatosis but not steatohepatitis, nevertheless they provide anatomical and morpholog‐ ical information. The sensitivity of these imaging methods is optimal for steatosis over 33%. When advance liver disease, radiology techniques can provide indirect signs of cirrhosis, such as portal hypertension, or may be useful for the screening and diagnosis of hepatocellular carci‐ noma (HCC)[41]. Imaging technique may help to differentiate diffuse from focal form of steato‐ sis. Hepatic fatty infiltration can present as focal steatosis (a focal area of steatosis in an otherwise normal liver) or as focal fatty sparing (fatty change with sparing of certain areas) [42].

**Abdominal US** is the most commonly used imaging technique to clinically evaluate the pres‐ ence of liver steatosis. Advantages include low cost, lack of radiation exposure and wide availa‐ bility. The brightness of the liver echo is compared with the kidney, the attenuation of the sound beam by the fat results in relatively hypoechoic kidney. For detailed description of sono‐ graphic features for staging fatty liver see table 8. This US feature is not characteristic of NAFLD because it can be present in other diffuse parenchymal liver disease. The US can be accurate de‐ tecting hepatic steatosis when there is a moderate to severe infiltration [43]. Overall sensitivity and specificity are 60-94% and 66-95%, respectively, however the sensitivity is lower when BMI (body mass index) is over 35 Kg/m2 . Although this acceptable level of sensitivity it does not pro‐ vide reproducible quantitative information. US scoring system for fatty liver is based on hyper‐ echogenic liver tissue, the increased discrepancy of echo amplitude between liver and kidney and the loss of echoes from the walls of the portal system [44]. US cannot differentiate between steatosis and fibrosis, but with advance degrees of fibrosis an increase in coarse echoes without posterior beam attenuation can be seen.


**Table 8.** Ultrasonographic grading system for diagnosis of fatty liver, adapted from [41].

**Computer Tomography** provides an accurate and a reliable visualization of whole liver, so that not only diffuse but also focal fatty infiltration of the liver parenchyma can be accurately diagnosed. CT enables the evaluation of absolute measurement of attenuation values which are given in Hounsfield units, the difference of attenuation between liver and spleen as well as the calculation of the liver-to-spleen attenuation ratio, those correlate with steatosis degree. Liver density as measured by CT attenuation units has been shown to have an inverse correla‐ tion to the degree of fatty infiltration. Non-enhanced CT provides a high performance in quali‐ tative diagnosis of hepatic steatosis when fatty infiltration is over 30%, obtaining 82% of sensitivity and 100% specificity using histologic analysis of biopsies of liver donors as the refer‐ ence standard [45], however is not sensitive in detecting mild-to-moderate amounts of steato‐ sis between 5% and 30% [43]. New CT scanning techniques are developing, such as dualsource/dual energy scanners, but their evaluation needs further studies. A drawback of this technique is the liver iron overload because it increases the attenuation. This method is associ‐ ated with radiation exposure which limits its use in children.

imaging and a new software will be able to stage fibrosis and to distinguish NASH from no-

Liver biopsy remains a useful tool to confirm the diagnosis and exclude other disease or helps to discover concomitant chronic liver disease. It provides prognostic information by staging and grading this disease. At present non-invasive diagnostic markers could provide a new tool for differentiating fatty liver from NASH as well as for grading /staging NAFLD.

The investigation of these new diagnostic methods comes from the well known drawbacks of liver biopsy. These include sampling error, inadequate biopsy size, variability in patholo‐ gist interpretation, cost and associated morbidity (complications 0,3%, mortality rate 0,01%).

An ideal non-invasive test should be simple, reproducible, readily available, less expensive than liver biopsy, able to predict the full spectrum of liver fibrosis stages, and reflect

Some reviews provide an overview of the role of non-invasive test in NAFLD [48, 50, 51]. We will try to present many of these scores through a table (number 10) to summarize their characteristics. AUROC is a numerical data that assess the performance of a scoring system. AUROC value greater than 0,8 indicate good diagnostic performance. The closer the value

**SCORE [Reference] Variables Cutoff AUROC Sens. (%) Spec. (%) PPV (%) NPV (%)**

0,79-0,86 85 88 46

≥3 0,763 73,7 65,7 68,2 71,4

0,85 87 86

250 U/l 0,83 75 81

63

Nonalcoholic Fatty Liver Disease: A Pathological View

http://dx.doi.org/10.5772/52622

175

93 79

0,3 0,7

<30 >70

NASH. Professor Romero-Gomez conducts this study and it will be soon published.

Table 9 summarizes advantages and disadvantages of these radiologic methods.

**9. Non-invasive assesment in NAFLD**

changes occurring with therapy [48].

NONINVASIVE DIAGNOSIS OF STEATOSIS

NONINVASIVE ASSESSMENT IN NASH

Fatty liver Index (FLI)

[53]

SteatoTest [52] 6 components of FibroTest-

Palekar [54] HA >55 mcg/l, age >50 years,

AAR >80.

CK-18 [17] CK-18 plasma (apoptosis marker)

to 1, the better performing the scoring system.

ActiTest, BMI, cholesterol, triglycerides, glucose

BMI, waist circumference, triglycerides, GGT

female gender, AST >45 UI/ml,

Magnetic Resonance can detect steatosis by exploiting the difference of resonance frequen‐ cies between water and fat proton signals. The sensitivity and specificity of MRI in detecting as low as 5% of liver fat infiltration are 85% and 100%, respectively [46]. The detection of the fatty liver can be seen in "white/bright" when applying in-phase T1 images and "black" when applying out-of-phase images, compared to the signal intensity of the spleen and par‐ aespinal muscles. Another technic of MR imaging with fat saturation may quantify more ac‐ curately liver fat infiltration, especially in patients who have fibrosis.

MR spectroscopy can reliably quantify even minimal steatosis, as low as 0,5% [47]. In has been based on the ubiquitous protons hydrogen and phosphorus [48], and more than 5% of fat content on MR spectroscopy indicates presence of steatosis [49]. Its routine application is limited by cost and lack of availability, and it remains a research tool.


**Table 9.** Pro's and con's of radiologic modalities for the study of NAFLD. S: sensitivity; s: specificity. Adapted from [41].

US, CT and MR are insensitive in differentiating hepatic steatosis from NASH, and they can‐ not be used to stage fibrosis [43, 48]. But in the near future, a novel method based on MRI imaging and a new software will be able to stage fibrosis and to distinguish NASH from no-NASH. Professor Romero-Gomez conducts this study and it will be soon published.

Table 9 summarizes advantages and disadvantages of these radiologic methods.
