Non alcoholic fatty liver disease (NAFL) consists in the accumulation of fat vacuoles in the cytoplasm of hepatocytes and is characterized by the presentation of hepatic lesions similar to those made by alcohol in subjects without significant alcohol consumption. This term was introduced by Ludwig J in 1980 [1
] and covers a wide spectrum of hepatic lesions including simple fatty liver, steatohepatitis with necroinflammatory changes and a variable degree of fibrosis which may finally progress to liver cirrhosis and, even hepatocarcinoma. However, there is little information on the clinical relevance of this disorder as a healthcare problem in the general population, since the studies published generally include a limited number of patients and the diagnosis is established on the basis of clear biochemical alterations and liver biopsy [2
Many etiologic factors are associated with NAFL and are classified as primary, related to factors that cause an increase in insulin resistance (obesity, diabetes, dyslipemia), and the metabolic syndrome (obesity, type 2 diabetes, dyslipemia and arterial hypertension) and secondary to consumption of medications (amiodarone, tamoxifen, corticoids, estrogenos, nifedipine) to metabolic congenital or acquired alterations, nutrition, surgical procedures, and other toxics [3
]. In clinical practice most patients with NAFL have obesity, type 2 diabetes or dyslipemia as the etiologic factor, with the association of several of these factors being frequent [8
NAFL is possibly the most common cause of an elevation in transaminases in adults [9
] and is considered the hepatic component of the metabolic syndrome [3
]. The importance to detect patients with NAFL is to intervene in the associated factors and avoid evolution to more severe forms of the disease.
Fatty liver is an ever more prevalent disease involving 17 to 33% of the general population according to the different series and is increasing with the higher incidence of obesity [10
]. A currently ongoing study in our reference area has found a prevalence of NAFL about 23% – 25% correlated with components of the metabolic syndrome, similar to other series [11
]. In this study, the most important risk factor for NAFL is obesity, with 70% of overweight or obese patients presenting this disease.
Most patients with NAFL are asymptomatic. Diagnosis is made by presentation of increased transaminases, especially ALT, found during a health check up or during the study of some other manifestation of the metabolic syndrome. Diagnosis may also be suspected by accidental discovery of hepatomegaly or a radiological test carried out for another reason showing suggestive changes of fatty liver [8
], although the final diagnosis should be confirmed by liver biopsy.
As we have seen the main risk factor for the development of NAFL is, therefore, obesity. It is well known that the increase in the number of obese persons within the general population has progressed up to the point that the healthcare authorities consider obesity to be one of the main healthcare problems for the near future and it has been made one of the priorities for intervention and investigation. In addition, patients with NAFL who are overweight/or obese are more to likely to develop steatohepatitis, with a percentage of these patients evolving to more severe forms of liver disease. We therefore believe that it is important to determine several indexes with the aim to establish which patients may evolve to more severe forms. These indexes are the HAIR score established by Dixon [12
], the Mayo Clinic index (NAFLD fibrosis score) [13
], among others. The HAIR score includes: insulin resistance defined as: type 2 diabetes with baseline glycaemia values greater than 110 mg/dl and less than 126 mg/dl and two of the following factors: arterial hypertension, triglycerides above 150 mg/dl and/or HDLc < 35 in males and < 39 in females, a waist/hip index > 0.90 in males and 0.85 in females and/or body mass index >30 kg/m2, and ALT levels > 40. Patients with a HAIR score ≥ 2 are considered to have a high probability of developing non alcoholic steatohepatitis.
The NAFLD fibrosis score combines: age, hyperglycaemia, body mass index, platelet count, albumin values and the AST/ALT ratio. The regression formula (risk score) for prediction of severity of fibrosis based on these 6 variables is: NAFL fibrosis score = -1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m2) +1.13 × IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio – 0.013 × platelet (×109/l) – 0.66 × albumin (g/dl). Using the area under the ROC curve, 2 cutoff points were selected to identify the presence (greater than 0.676) and absence (lower than – 1.455) of significant fibrosis.
In addition to knowing the risk factors associated with the presence of NAFL, it is important to know the relationship between NAFL and the metabolic syndrome. The presence of the metabolic syndrome is increasing in the last years and is constituted by the presence of several factors in a same subject such as obesity, arterial hypertension, dyslipemia and glycaemia intolerance. Some criteria define the metabolic syndrome with the most commonly used being those of the World Health Organization (WHO) [14
] modified by the European Group for the Study of Insulin Resistance (EGIR) [15
], the criteria of the Adult Treatment Panel III (ATP-III) of the National Cholesterol Education Program (NCEP) [16
], and those of the International Federation Diabetes [17
]. These criteria include a combination of clinical and analytical parameters, mainly abdominal perimeter. Other parameters are the body mass index, insulin levels, arterial hypertension, glycaemia, HDL, triglycerides and microalbuminuria. So, the criteria of the WHO require the presentation of some alteration in carbohydrate metabolism, whether diabetes, abnormal glucose tolerance or resistance to insulin and two of the following criteria must also be taken into account: arterial hypertension > 140/90 mmHg, obesity (BMI = 30 kg/m2
), hypertriglyceridemia ≥ 150 mg/dL or cHDL values < 35 in males and < 40 in females and microalbuminuria ≥ 20 μg/min. The EGIR has proposed several changes in the definition of the WHO, such as the presence of obesity (waist perimeter ≥ 94 cm in males and ≥ 80 cm in females), fasting plasma insulin determination and altered fasting glycaemia. The criteria of ATP-III of the NCEP are based on the presence of abdominal obesity (≥ 102 cm in males and ≥ 88 cm in females), hypertriclyceridemia (≥ 150 mg/dL), cHDL values < 40 mg/dl in males and < 50 mg/dl in females, arterial hypertension (≥ 130/85 mmHg) and altered fasting glycaemia (≥ 110 mg/dL). Finally, the criteria of the International Federation of Diabetes are based on the presence of abdominal obesity (≥ 94 cm in males and ≥ 80 cm in females), arterial hypertension (≥ 130/85 mmHg), altered fasting glycaemia (≥ 100 mg/dL), cHDL values (<40 mg/dl in males and <50 mg/dl in females), and hypertriclyceridemia (≥ 150 mg/dL). Given the importance of the metabolic syndrome we will analyse these three types of criteria in all the study subjects to determine which criteria identify the metabolic syndrome best.