Background. We aimed to determine if an association exists between uncomplicated hepatitis C virus (HCV) infection and depression or fatigue.

Method. A review of the literature was undertaken.

Results. There is an association between HCV infection and either depression or fatigue in certain circumstances – those who are aware they are HCV positive, those with advanced liver disease and those seen in specialist referral centres. All these studies are subject to important biases. There are only a few studies in which knowledge of HCV status and assessment of fatigue or depression is independent. These studies do not suggest an association. There is no association between conventional markers of liver disease and depression or fatigue.

Conclusions. Despite anecdotal evidence to the contrary, at the moment there is no evidence that HCV infection per se is associated with fatigue or depression, and there is a suggestion that it is not. The same risk factors that exist for fatigue in other physical illnesses, such as metabolic disorder, mood disorder, demographics and lack of exercise, certainly exist for HCV. Although there are elegant theoretical mechanisms, there is no compelling epidemiological evidence for an additional HCV specific fatigue or depression factor.