**6. Histologic scoring systems**

NAFLD histologic criteria requires an accumulation of more than 5% of fat deposition, mainly in form of triglycerides. NAFLD was first described by Ludwig and colleagues [28], and since then several systems for grading and staging NAFLD have been proposed.

In 1999, Matteoni and colleagues characterized histologic subtypes that correlate with clini‐ cal outcomes [16] – table 4. In 2005, NASH Clinical Research Network developed NAFLD activity score (NAS) [8]. This score comprises four features evaluated semi-quantitatively: steatosis, lobular inflammation, hepatocellular ballooning and fibrosis. Fibrosis was classi‐ fied separately – table 5. When NAS is >5 sensitivity and specificity for definite NASH were 0,75 and 0,83, respectively. Finally, a recent classification for NAFLD has been proposed by Younossi and colleagues [15]. This classification includes the evaluation of these histologic features: steatosis with centrilobular ballooning, and/or Mallory-Denk bodies of fibrosis – see table 6.

**CLASSIFICATION OF NAFLD BY SUBTYPE**

with NAFLD [15].

nusoidal [19].

**Pathology Clinicopathologic**

Simple steatosis alone No NASH

Steatosis + lobular inflammation only No NASH

Steatosis with centrilobular ballooning and/or Mallory-Denk bodies NASH

Any steatosis with centrilobularpericellular/perisinusoidal or briding fibrosis NASH

The most important difference between NAS and subtype classifications is that the latters include fibrosis and this provides a better prediction of liver-related mortality in patients

**Patients with insulin resistance.** Insulin resistance can be estimated using the homeostasis model for assessing of insulin resistance (HOMA-IR), calculated as the product of fasting in‐ sulin level (mUI/ml) and plasma glucose level (mmol/ml), divides by 22,5 [29]. Portal fibro‐ sis has been linked to the ductular reaction (ductularproliferation at the portal tract interface arising from progenitor cells in the periportal area and accompanied by neutrophils and stromal changes). These findings correlate the insulin resistance with advanced stages of fib‐

In some cases in a study with a few number of patients treated with an insulin sensitizer, histologic evaluation of post-treatment liver biopsy showed that increased portal inflamma‐ tion is a feature related to resolution of NASH, and it is associated to a change in the quality

**NAFLD in bariatric surgery patients.** Patients undergoing bariatric surgery for weight loss are at a risk of NAFLD. They often have comorbidities such as: severe obesity, diabe‐ tes, hypertension, sleep apnea or coronary artery disease. And high percentage will have metabolic syndrome [31] (see table 7). The prevalence of steatosis and steatohepatitis in these patients undergoing liver biopsy when surgery is performed, is 91% and 37%, re‐ spectively [32]. At least a third of morbidity obese patients have portal inflammation, and this is related to the presence of fibrosis [20, 33]. In early stage, localization of fibrosis dif‐ fers from those nonbariatric populations, in bariatric is portal and in nonbariatric is perisi‐

**Table 6.** Classification of NAFLD proposed by Younossi and colleagues [15].

rosis and provide a pathway for fibrosis progression [30].

of zone 3 perisinusoidal fibrosis from dense to delicate [19].

**7. NAFLD in special populations**

**correlation**

Nonalcoholic Fatty Liver Disease: A Pathological View

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

171


**Table 4.** Classification of NAFLD by subtype [16].

#### **CLASSIFICATION OF NONALCOHLIC FATTY LIVER DISEASE BY NAFLD CLINICAL RESEASCH NETWORK**


**Table 5.** Classification of NAFLD by NAFLD CRN [8].

#### **CLASSIFICATION OF NAFLD BY SUBTYPE**

Younossi and colleagues [15]. This classification includes the evaluation of these histologic

features: steatosis with centrilobular ballooning, and/or Mallory-Denk bodies of fibrosis –

**CLASSIFICATION OF NONALCOHOLIC LIVER FATTY LIVER DISESASE (NAFLD) BY SUBTYPE NAFLD subtype Pathology Clinicopathologic correlation**

Type 1 Simple steatosis alone No NASH

Type 2 Statosis + lobular inflammation only No NASH

**Table 4.** Classification of NAFLD by subtype [16].

Perisinusoidal zone 3

NASH requires a score of ≥ 4 with at least 1 point o ballooning injury.

**Table 5.** Classification of NAFLD by NAFLD CRN [8].

Type 3 Steatosis + hepatocellular ballooning NASH without fibrosis

**CLASSIFICATION OF NONALCOHLIC FATTY LIVER DISEASE BY NAFLD CLINICAL RESEASCH NETWORK**

Histologic finding Score

Steatosis 0-3

Lobular inflammation 0-3

Hepatocellular ballooning 0-2

Fibrosis type Score

None 0

Mild 1A

Moderate 1B

Portal/periportal 1C

Persinusoidal and portal/periportal 2

Bridging 3

Cirrhosis 4

Type 4 Steatosis, ballooning, Mallory bodies or fibrosis NASH with fibrosis

see table 6.

170 Liver Biopsy – Indications, Procedures, Results


**Table 6.** Classification of NAFLD proposed by Younossi and colleagues [15].

The most important difference between NAS and subtype classifications is that the latters include fibrosis and this provides a better prediction of liver-related mortality in patients with NAFLD [15].
