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Nuclear factor-κB inhibition and non-alcoholic steatohepatitis: inflammation as a target for therapy
  1. Fabio Marra
  1. Dipartimento di Medicina Interna, University of Florence, Italy
  1. Dr Fabio Marra, Dipartimento di Medicina Interna, University of Florence, Viale Morgagni, 85, I-50134 Florence, Italy; f.marra{at}dmi.unifi.it

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Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, a cluster of closely related clinical features linked to visceral obesity, and characterised by insulin resistance, dyslipidaemia and hypertension.1 The prevalence of the metabolic syndrome in the general population is increasing at an alarming pace, and NAFLD has become the most common cause of liver disease in Western countries.2 Population studies indicate that NAFLD may be found in approximately one-quarter to one-third of the general adult population in Western Europe. In a subset of these patients, fatty infiltration of the hepatocytes is accompanied by hepatocellular injury, inflammation and fibrosis, and these histopathological changes characterise the picture of non-alcoholic steatohepatitis (NASH). A number of studies have underscored the danger associated with a diagnosis of NASH, because these patients may progress to advanced cirrhosis and to the development of its complications, including hepatocellular carcinoma.3 ,4 It has also been suggested that NAFLD or NASH increase the risk of developing cardiovascular diseases, which are likely to occur in this population due to the presence of the metabolic syndrome.3 ,5 Nonetheless, the factors leading from NAFLD to NASH are still largely unknown, and basic research has started to elucidate the pivotal mechanisms implicated in these entities. The need to understand the molecular basis of NASH and its progression to cirrhosis is particularly critical, because at this time no pharmacological therapies have been approved for the treatment of the non-alcoholic steatosis syndromes. It is widely accepted that weight loss and an increase in physical activity are beneficial for these conditions, but a long-term reduction in body weight and lifestyle changes are extremely difficult to achieve and may require a multidisciplinary effort.6

Inflammation is an aspect of NASH that has received considerable attention as a possible …

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