Federico Tanno, Mario Tanno

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a term that includes a number of conditions ranging from benign simple steatosis to nonalcoholic steatohepatitis (NASH).. In recent years there have been a large number of publications that recognize it as a potentially serious condition, which can progress to cirrhosis, liver failure and hepatocarcinoma. This entity, of worldwide distribution, presents a clinical spectrum of variable severity. Several mechanisms appear to be involved in the accumulation of fat in the liver: de novo synthesis of triglycerides, altered secretion of lipoproteins, and increased supply of fatty acids. These abnormalities correlate with central obesity and sedentary lifestyle. The important role of insulin resistance in this disease is the physiopathological rationale for its production. It is recognized today as the involvement of the liver in patients with the so-called metabolic syndrome (diabetes, obesity, dyslipidemia and arterial hypertension).

Epidemiology and prevalence of high-risk groups.

It can affect any age and has been described in almost all ethnic groups. The exact prevalence is unknown, but it is estimated to be around 10-24% of the general population. This is higher in obese patients, in patients with type 2 diabetes and in dyslipidemic patients.

Pathogeny

The “double impact” theory is the most widely accepted to explain the pathogenesis of nonalcoholic steatohepatitis, with insulin resistance being a key factor in its production. In the "first hit" the increased influx of fatty acids into the hepatocyte, combined with decreased triglyceride clearance and decreased fatty acid oxidation, produces steatosis. This is not always quiescent, since the accumulated fatty acids are susceptible to a "second impact", in which the following would intervene: a) oxidative stress, with increased production of oxygen free radicals that facilitate the formation of cytokines;

Clinical and laboratory findings.

It is presumed in the patient to be a carrier of central obesity, arterial hypertension, type 2 diabetes and dyslipidaemia. In this context, an increase in transaminases in the absence of another cause that justifies them, added to a liver ultrasound that shows an increase in echoes, compatible with steatosis, is enough to suspect it. However, the relationship between diagnosis and prognosis are not linear. One of the great problems of this entity is the poor differentiation between the most benign spectrum (simple steatosis) of NAFLD with the most aggressive spectrum of steatohepatitis (NASH).

Different studies with serial biopsy have established the possible progression of NASH to a cirrhotic stage with loss of the typical characterization of NAFLD, suggesting that many cases of cryptogenetic cirrhosis are actually a consequence of the progression of non-alcoholic steatohepatitis.

Signs and symptoms.

The majority of NASH patients are asymptomatic. However, according to different series, they become symptomatic in up to 48% of patients. The symptoms described are fatigue and pain in the right upper quadrant presenting hepatomegaly due to fatty infiltration. Acanthosis nigricans has been reported in children. The presence of a hepatic palm and stellar nevi suggests a liver disease in a more advanced stage, which may correspond to a cirrhotic state. Findings associated with metabolic syndrome such as obesity, type 2 diabetes, hyperlipidemia, arterial hypertension (HT), hyperuricemia, insulin resistance, as well as gallstones are common in these patients.

With respect to the laboratory variants, a large percentage present only with altered liver function tests (ASAT and ALAT), found in routine examinations or during the study of a patient with overweight or metabolic syndrome. The ALAT is twice the normal value. There is no good correlation between laboratory alteration and histological severity, since patients with a totally normal laboratory with severe histological activity and even cirrhosis have been described. Elevations of gamma-glutamyl and alkaline phosphatase may be present.

Diagnosis

The gold standard is still liver biopsy, both to confirm the diagnosis and to stage the extent of the injury and evaluate the activity. However, the biopsy is often postponed, taking a more conservative attitude, prescribing diet and exercise as the initial step. The use of surrogate tests such as fibrosis markers are promising options for the near future, but to date they have not shown effectiveness to replace biopsy.

Imaging diagnosis : Ultrasound reveals fatty infiltration by an increase in diffuse echogenicity of the liver compared to the kidneys. It has a relatively high sensitivity and specificity to detect it. Magnetic resonance imaging with spectroscopy allows a precise diagnosis with quantitative determination of fat.

Natural History.

Although patients with NAFLD frequently have comorbidities that may influence survival, progressive liver disease frequently becomes a dominant problem. Nonalcoholic steatohepatitis has a variable histological course, with one third of patients having progression to fibrosis. Histological damage correlates with higher levels of transaminases, but not with other clinical factors. Steatosis can progress to steatohepatitis with fibrosis. There is also a smaller group of patients who can progress to hepatocarcinoma (HCC).