Polyunsaturated Fatty Acid (Pufa) Omega 3 in the Reduction of the Inflammatory Component of the Nonalcoholic Steatohepatitis (Nash):Randomized Placebo Controlled Study

Nonalcoholic fatty liver disease (NAFLD) is a clinical and pathological condition, whose spectrum can range from steatosis to steatohepatitis and cirrhosis, in patients without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), the severe form of (NAFLD), has emerged as a clinically important type of chronic liver disease in industrialized countries and is characterized pathologically by hepatocellular ballooning, Mallory's hyaline, scattered inflammation and perisinusoidal fibrosis. NASH associated with cirrhosis can decompensate into subacute liver failure, progress to hepatocellular cancer and reoccur post transplantation.

The 'two-hit' hypothesis has been proposed to explain the pathogenesis of NASH, with an initial metabolic disturbance (insulin resistance) causing steatosis and a second pathogenic stimulus promoting oxidative stress, increased generation of reactive oxygen species (ROS), lipid peroxidation, and resultant NASH . Insulin resistance plays a major role in hepatic fat accumulation through increased influx of free fatty acids (FFA) from peripheral fat stores due to enhanced lipolysis, increased de novo hepatocyte triglyceride synthesis from glucose and reduced apo B production, which diminishes fat export from the liver.

In the absence of established treatment, therapy is generally directed to treatment of risk factors for metabolic syndrome. Recently, some studies have been demonstrated that Polyunsaturated fatty acids (PUFAs), omega3 type, could reduced TNFalfa, IL6, aminotransferases, insulin resistance and steatosis verified by ultrasound. Nevertheless, this is the first study that evaluate liver histology after six months of PUFA (omega3) in the treatment of patients with NASH.

Based on these aspects, the aim of this prospective investigation, is evaluate the effectiveness of PUFA (omega3) in the treatment of patients with NASH.

METHODS Population This study will be developed in the center of study of DHGNA/NASH in the Central Institute of the Hospital of the Clinics in São Paulo, Brazil. This study comprised 60 patients diagnosed with NASH based on liver biopsy findings. In addition, all of the patients will have elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels on at least two occasions over 6 months prior to enrollment. Other causes of liver disease included a hepatobiliary system ultrasound, viral serology, autoantibody titers, serum iron, ferritin and transferrin saturation, ceruloplasmin and copper levels and alpha1-antitrypsin will be exclude. Patients who have a > 100 g/week alcohol intake determined by a detailed personal history, questioning of family members, and investigation of previous medical records, will be excluded. Patients with steatohepatitis accompanying other liver diseases, or systemic diseases other than obesity, hyperlipidemia, and diabetes or with intake of hepatotoxic drugs or lipid-lowering agents were excluded. Specific informed consent was obtained for the study and the protocol was approved by the Internal Review Board of University of São Paulo. Diagnosis of diabetes type II, hypertension, dyslipidemia were based on the criteria of the American Diabetes Association (fasting glucose above 100mg/dl; Triglyceride > 150mg/dl; HDL < 40mg/dl in man or < 50mg/dl in woman; > 130mmHg systolic or > 85mmHg diastolic)28. Overweight corresponded to body mass index (BMI) ≥ 25 kg/m2 and obesity to BMI ≥ 30 kg/m2.