Objectives

Individuals infected with hepatitis C virus (HCV) can develop extrahepatic conditions which may have a significant impact on life expectancy and quality of life. We conducted a systematic review to assess the causal relationship between HCV and extrahepatic conditions and the impact of HCV upon health-related quality of life of people in the UK.

Methods

HCV advocacy groups identified conditions that they thought most important to research, and the perspectives of various stakeholders informed the scope of the review. A comprehensive literature search of a range of electronic databases and websites was undertaken. Screening, quality assessment and data extraction were conducted using specialist software. The key criterion for inclusion in a synthesis was a study’s testing of the association between HCV and either quality of life or conditions specified as important by advocacy groups: depression, anxiety or painful conditions. Other criteria relating to study populations, measures and matching of study groups were also applied. Two reviewers assessed included studies, with disagreements resolved by a third reviewer where necessary. Studies were assessed for methodological quality using standardised appraisal tools. Meta-analyses were performed. Based on the consistency and sufficiency of research evidence, the findings were graded as strong, promising, tentative or inconclusive.

Results

71 studies were included in the review’s syntheses. All studies were judged to be at a moderate or high risk of bias. Only two UK studies met our inclusion criteria.

Quality of life

Evidence from 22 studies indicates that people with HCV have worse quality of life than ‘general’ or ‘healthy’ populations; meta-analysis of nine studies indicated that the physical (PCS) and mental health (MCS) domains of quality of life on the Health-Related Quality of Life Scale were both statistically and clinically worse among HCV-infected people (PCS: MD 5.54, 95% CI 3.73-7.35, MCS: MD 3.81, 95% CI 1.97-5.64). Evidence from seven included studies suggests that people co-infected with HCV and HIV have worse quality of life than individuals with HIV only; meta-analysis of five studies indicated that both the physical and mental health domains of quality of life were significantly worse among people who were co-infected (PCS: MD 2.57, 95% CI 1.08-4.06, MCS: MD 1.88, 95% CI 0.06-3.69).

Depression and anxiety

Evidence from 22 studies indicates that depression and anxiety are more severe, and depression is more common among people with HCV compared to those without it. Meta-analysis of 12 studies identified the severity of depression in people with HCV to be significantly greater than in those without HCV (Mean difference 0.98, 95% CI 0.43-1.53). Meta-analysis of nine studies identified the severity of clinical anxiety to be significantly greater among people with HCV (Mean difference 0.47, 95% CI 0.09-0.86). Meta-analysis of seven studies identified participants with HCV to be approximately three times more likely to be depressed compared to those without HCV (OR 2.77, 95% CI 1.62-4.74). No statistically significant evidence that anxiety is more common among people with HCV was found.

Pain

Evidence was appraised from 26 studies on painful conditions. A meta-analysis of four studies indicates that people with HCV are 17% more likely to suffer from arthralgia than those without HCV (RR 1.17, 95% CI 1.04-1.31). A meta-analysis of five studies suggested that people with HCV are significantly more likely to suffer from fibromyalgia; key differences across the studies in terms of the health status (co-morbidities) of HCV patients and comparison groups mean it is not possible to quantify the increased risk attributable to HCV. Other studies, including those on arthritis, were not amenable to meta-analysis.

Conclusions

Evidence suggests an association between HCV infection and depression, anxiety, fibromyalgia, arthralgia and health-related quality of life. However, the evidence was graded as ‘promising’ or ‘tentative’ rather than ‘strong’. More high-quality research on the association between HCV and these conditions is needed.