**Diagnosis and Characterization of Non-Alcoholic Fatty Liver Disease Liver Disease**

**Diagnosis and Characterization of Non-Alcoholic Fatty** 

DOI: 10.5772/intechopen.72668

Paula Iruzubieta, Marta González, Joaquín Cabezas, María Teresa Arias-Loste and Javier Crespo María Teresa Arias-Loste and Javier Crespo Additional information is available at the end of the chapter

Paula Iruzubieta, Marta González, Joaquín Cabezas,

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.72668

#### **Abstract**

Non-alcoholic fatty liver disease (NAFLD) can develop cirrhosis and even hepatocellular carcinoma, resulting in a high liver-related morbidity and mortality, being important to know those risk factors for disease progression, among which the presence of diabetes stands out. In addition, it is a disease with multisystemic behavior, becoming an independent risk factor for cardiovascular disease and extrahepatic tumors. Hence, early diagnosis and multidisciplinary management of NAFLD are really important. In this chapter, we will expose the different diagnostic and follow-up tools available for this disease, and with them we will make an algorithm according to the recommendations and the current evidence.

**Keywords:** NAFLD, biomarkers, transient elastography, multisystemic disease

#### **1. Introduction**

Non-alcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver damage whose distinctive feature is the accumulation of intrahepatic fat, especially triglycerides, which cannot be attributed to secondary causes such as alcohol and certain drugs. NAFLD is nowadays considered to be the most common cause of chronic liver disease in western countries, showing a prevalence of around 30% in the general population [1]. Within NAFLD, two histological subtypes can be distinguished: (a) non-alcoholic fatty liver (NAFL), which includes patients with simple steatosis with or without mild inflammation and (b) non-alcoholic steatohepatitis (NASH), characterized by the presence of hepatic inflammation and hepatocyte injury (ballooning) with or without fibrosis [2, 3]. NAFL is a generally benign condition, and NASH is the progressive subtype that can lead to cirrhosis and hepatocellular carcinoma

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

(HCC) [4]. However, several studies with paired liver biopsies have demonstrated that both patients with NASH and those with NAFL have the potential to develop a progressive hepatic disease, and in this risk of progression there are some key factors such as diabetes mellitus [5, 6]. In general, patients with NAFLD have a higher long-term mortality than the general population, cardiovascular disease (CVD) being the principal cause of death, followed by different types of cancer [7–9] and liver-related complications, as well as the cardiovascular risk caused by the different factors of the metabolic syndrome, very frequent in this type of subjects; NAFLD is itself an independent risk factor for CVD [10]. Liver-related mortality is increased up to 10-fold in patients with NAFLD. In this sense, it should be emphasized that cirrhosis and HCC are the fifth most prevalent cause of mortality in the world. Therefore, given the hepatic and cardiovascular morbi-mortality generated by NAFLD, the early identification of these patients is important to provide suitable management that can lower the mortality for all causes.

enzymes [25]. To attempt to answer this question, valid cost-utility studies are necessary in screening programmes. There is no discussion, however, about the need to act when faced with a patient suspected of having NAFLD and not to underestimate its discovery due to the limited clinical and analytical repercussion manifested at first. In our opinion, patients with NAFLD and suspected to have advanced disease must be evaluated in specialist units for

Diagnosis and Characterization of Non-Alcoholic Fatty Liver Disease

http://dx.doi.org/10.5772/intechopen.72668

5

A diagnosis of NAFLD is very often reached through a casual analytical discovery during a health examination after an alteration in tests of liver function, or an alteration in hepatic morphology detected through an image study done with another objective, given that it is generally an asymptomatic disease. In the cases in which the patient reports symptoms, they are usually mild and unspecific, asthenia and abdominal problems being frequent, especially in the right hypochondria. The physical exploration may be normal or detect a soft, painless hepatomegaly, although occasionally it is difficult to evaluate as these patients very often present with central-type obesity, and in the patients with advanced fibrosis and cirrhosis, we

their correct characterization in case of a prompt availability of specific treatment.

may find signs of portal hypertension such as ascites, splenomegaly or jaundice [26].

Analytically, most of the patients present tests with normal or discretely altered liver function, with a predominance of ALT (alanine aminotransferase) compared to AST (aspartate aminotransferase). On specific occasions, a discrete elevation can be appreciated in the markers of cholestasis, especially GGT (gamma-glutamyl transpeptidase), which has been related to obesity and IR [27]. Another frequent analytical discovery is the elevation of the levels of ferritin in blood and of the transferrin saturation index without having demonstrated a corresponding increase in the deposits of hepatic iron [28]. Something similar occurs with the presence of elevated autoantibodies, which appear quite frequently in NAFLD and are con-

Hepatic steatosis is defined histologically as the deposit of fat ≥5% of the hepatocytes and is classified in four grades depending on the percentage of hepatocytes with steatotic vacuoles. The normal liver (S0) contains fat in less than 5% of the hepatocytes while grade 1 steatosis (S1) corresponds to less than 33% of the steatotic hepatocytes. In grade 2 and 3 steatosis, fat is

The presence of risk factors such as DM2, metabolic syndrome and obesity with the elevation of the hepatic enzymes, especially ALT, increases the possibility of fatty liver presenting. Nevertheless, although the ALT is a useful test, it is not valid for predicting the presence of this disease, or even the risk of progression, given that it can occur with normal hepatic enzymes [30]. In fact, in patients with DM2 and normal levels of ALT, a high prevalence of

In clinical practice, ultrasound scan is a first-rate image technique if NAFLD is suspected due to its wide availability, low cost and safety [32]. The sensitivity of this technique is 93%

**2.1. Clinical and analytical manifestations**

sidered an epiphenomenon [29].

NAFL and NASH has been reported [31].

present in at least 33 or 66% of the hepatocytes, respectively.

**2.2. Diagnosis of steatosis**
