Pak. J. Pharm. Sci., Vol.26, No.6, November 2013, pp.1251-1257 1151 REVIEW The effects and underlying mechanism of interferon therapy on body weight and body composition Ibrar Alam 1 , Niamat Ullah 2 , Iftikhar Alam 3,4 and Ijaz Ali 1 1 Institute of Bio-Technology & Genetics Engineering (IBGE), The University of Agricultural, Peshawar, Pakistan 2 Departments of Human Nutrition, Faculty of Nutrition Sciences, The University of Agricultural, Peshawar, Pakistan 3 Department of Agriculture, Bacha Khan University, Charsadda, KPK, Pakistan 4 Tübingen Ageing and Tumour Immunology Group (TATI), Centre for Medical Research (ZMF), University of Tübingen, Tübingen Germany Abstract: Body weight changes in HCV patients on interferon therapy are well documented. However, the underlying mechanism involved in these changes is poorly understood and rarely reported. The main objectives of this review are to 1) discuss changes in body weight and other compartments of body composition, particularly, body fat, and 2) to discuss the underlying mechanism for these changes. The literature review suggests weight loss (12-29%) as a function of interferon therapy is common, affecting up to 90% of HCV patients. Whilst, loss in weight means proportionate loss in other body compartments (lean body mass and body fat, in particular) data on changes in segmented body composition are fragmentary. The possible mechanisms underlying weight loss or changes in other body composition have been reported and these include suppressed appetite due to induction of TNF by IFN, a decrease in serum leptin level, and importantly mitochondrial damage induced by the therapy. It is, therefore, suggested that close monitoring of chronic HCV patients receiving PEG-IFN and/or ribavirin for side effects of these drugs, particularly those related to weight loss, is vitally important from clinical point of view. Keywords: HCV, interferon, weight loss, body composition, mitochondrial damage. INTRODUCTION Hepatitis C treatment is improved dramatically after the introduction of pegylated interferon (PEG IFN) and/or ribavirin therapy and it reportedly eradicates the virus in 50 % HCV positive patients. However, a number of side effects are associated with the therapy, which may ultimately lead to dose reduction or even discontinuation of therapy on the part of patient or the physician (Alan Francisus et al., 2008). Severe weight loss is a well established side effect associated with interferon therapy and majority of the patients on interferon therapy reportedly suffers from mild to moderate weight loss. In HCV patients, weight loss and tissue wasting are common, and particularly are highly prevalent in the advance stages of the disease. The researchers have reported a number of causes for interferon therapy- associated weight loss, which primarily include malnutrition, anorexia, infection, and perhaps an HCV- induced hypermetabolic state. Loss in weight is considered a strong indicator of poor health and hence a poor prognosis outcome. It is, however, well-established that weight loss is closely and positively related with mortality but not if the individuals have always been lean (Rumpel et al., 1993; cited by Han et al., 2011). Individuals who have been always lean are reportedly to be healthier than those who have the same body weight but who have recently experienced loss in body weight due to conditions that are known to cause weight loss unintentionally. These conditions include but not limited to all types of cancers and a number of chronic heart and lung disease (Seidell and Visscher, 2000). It is a common experience that such unintentional weight loss presents problems when interpreting body weight in clinical and/or research settings. In addition, intentional weight loss through changes and modification in life style or by medical and pharmaceutical intervention results in a wide range of clinical benefits as well as improvement in quality of life. On the contrary, unintentional weight loss is experienced mostly because of illness and usually is not very well-controlled in the sense that it usually undesirably involves loss of lean body mass, which, no doubt, triggers a poor prognosis, even if there is subsequent weight regain which very often involves accumulation of fat mass and/or edema (Seidell and Visscher, 2000; cited by Han et al., 2011). There are many factors contributing to weight loss in HCV patients on interferon therapy. These include but not limited to taste changes, low or even diminished appetite, *Corresponding author: e-mail: niamatullah@aup.edu.pk