There are generally three criteria that must be achieved before establishing a causal relationship between two conditions such as infection with the hepatitis C virus (HCV) and the subsequent development of cognitive impairment: (1) there must be evidence of temporal precedence, where the ‘cause’ happened before the ‘effect’; (2) there should be covariation between the conditions, demonstrated as a relationship response between the presence or absence of either factor; and (3) the absence of other plausible alternatives to explain the relationship.

The report by Abrantes et al1 presents us with an opportunity to take stock and consider the evidence in favour of a direct association between infection with HCV and the subsequent development of cognitive impairment. Although the neurological features of hepatic encephalopathy are well described in patients with viral liver cirrhosis, recent reports have highlighted changes in cognitive performance in HCV-infected patients that emerge long before any evidence of significant hepatic dysfunction.2 These cognitive symptoms appear ‘specific’ to HCV infection and are not as evident in patients infected with hepatitis B virus.3 In a recent review on the topic by Senzolo et al,4 the majority of reports supported an increased prevalence of cognitive impairment in patients with HCV infection which …