Treatment of patients with non-alcoholic fatty liver disease: current views and perspectives.

Non-alcoholic fatty liver disease is considered a component of the metabolic syndrome associated with obesity. Problems still exist concerning non-alcoholic fatty liver disease patients in clinical practice, for example: (a) how to diagnose non-alcoholic fatty liver disease and its type; (b) how to select patients candidate to treatment; (c) how to treat selected patients. Non-alcoholic fatty liver disease includes steatosis and non-alcoholic steatohepatitis, but only non-alcoholic steatohepatitis evolves into cirrhosis and the absolute risk of mortality for non-alcoholic fatty liver disease is low. As yet, no tools, other than liver biopsy, are available to differentiate the various types of non-alcoholic fatty liver disease. Many drugs are, currently, under study to treat non-alcoholic fatty liver disease, even if well-performed trials are until necessary to define the best treatment. At the moment, the entity of the problem and the characteristics of patients frequently put the physician, in clinical practice, to choose the therapeutic approach arbitrarily which is considered more effective for each individual patient. Probably the future will consider the possibility of treating non-alcoholic fatty liver disease with more than one drug, by considering the various aspects and degree of this syndrome. Actually each physician should select the individual treatment on the basis of his/her knowledge and experience, by never forgetting the old saying 'primum non nocere'. However, the epidemiological entity of the problem, the characteristics of the patients, generally young, the frequent lack of clinical evidence of involvement of the liver, are all the factors that require vast well-performed clinical trials in order to define the best therapeutic approach for each individual patient.

The treatment of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is becoming an increasing cause of chronic liver damage. The decision of start a medical treatment is based on the documented risk of progression to cirrhosis and liver cancer, when steatohepatitis (NASH) occurs. The therapy of this syndrome requires, as obviously, some considerations on the natural history of the condition, on the efficacy and safety of various therapeutic options, as well as on the costs. Treatment of patients with NAFLD has typically been focused on the management of associated conditions such as obesity, diabetes mellitus and hyperlipemia. Weight loss improves insulin sensitivity, and NASH may resolve with weight reduction. Insulin resistance seems to be the common denominator in many cases of NAFLD. Two classes of drugs have been shown to correct insulin resistance: biguanides (e.g., metformin) and thiazolidinediones (e.g., rosiglitazone and pioglitazone). The last two decades have witnessed a considerable progress in the understanding of the mechanisms respon-sible for the fibrogenic progression of chronic liver diseases. Several drugs believed to be hepatoprotective or antifibrotic agent as UDCA, betaine, vitamin E, lecithin, beta-carotene and selenium have been used in patients with NASH. Silybin is the main component of silymarin that is absorbed when linked whith a phytosome. This substance reduces in rats the lipid-peroxidation and the activaction of hepatic stellate cells. In humans, some non controlled data show that silybin is able to reduce insulin resistance, liver steatosis and plasma markers of liver fibrosis.

[Effects of a new pharmacological complex (silybin + vitamin-E + phospholipids) on some markers of the metabolic syndrome and of liver fibrosis in patients with hepatic steatosis. Preliminary study]. / Effeto di un nuovo complesso farmacologico (sillibina vitamina E+ fosfolipidi) su alcuni indicatori di sindrome metabolica e di fibrosi epatica in pazienti con epatopatia steatosica. Studio pilota.

AIM: This open preliminary pilot study was aimed to evaluate the effect of a new pharmaceutical complex (silybin+vitamin E+phospholipids - RealSIL-IBI-Lorenzini Pharmaceutical, Italy) on some parameters of metabolic syndrome and of liver fibrosis in patients with non alcoholic fatty liver disease (NAFLD) with or without the contemporaneous presence of hepatitis C virus (HCV)-related chronic hepatitis. METHODS: Eighty five patients were consecutively enrolled in the study and divided in 2 groups; the first group was represented by 59 patients affected by NAFLD, negative for other known causes of chronic liver damage (M/F= 39/20; median age and range: 44 years, 22-76, group A); the second group was represented by 26 patients (M/F=19/7; median age and range 51 years, 20-75, group B) with HCV-related chronic hepatitis associated to NAFLD. Adverse events and drop-outs were absent in all group and compliance at the study was absolute. RESULTS: This open preliminary study shows that the new compound silybin+vitamin E+ phospholipids is active, in vivo, and produces some therapeutic effects in patients with different forms of chronic liver damage. In particular, it improves insulin resistance and plasma levels of markers of liver fibrosis in patients in whom these parameters are particularly altered. CONCLUSIONS: Our data have a role of suggestion to further evaluate, through a controlled trial, a possible therapeutic use of this new compound in the management of patients with NAFLD.