The present study characterized health status and health-related quality of life (HRQoL) levels of a large sample of previous opiate users (POUs) at the beginning of an antiviral treatment for hepatitis C in routine settings. POUs were predominantly males, with a median age of 47 years. About half of them were employed at the time of enrolment. Significant minorities showed psychiatric diseases and alcohol use disorder, and the vast majority were smokers. Compared with patients who had never used opiates (NOU), the POU group was markedly younger, with a higher proportion of males, and a lower proportion of individuals with migrant background. Compared with OAT patients, POUs were similar with regard to these characteristics. In contrast, employment rates for POUs were similar to NOU, and much higher than for OAT patients. It must be taken into account, though, that 90% of POUs were younger than 60 years, the typical working age, while this proportion was only 66% in the NOU group; therefore, it can be assumed that, in the NOU group, a considerable proportion of patients without employment had already retired, while in the POU group, they were in fact unemployed.

In the POU group, rates for cannabis use and for mental disorders were higher than in NOU, but lower than in OAT patients. However, alcohol abuse was markedly higher in the POU group (17.4%) than in the OAT group (12.1%) and in the NOU group (2.9%).

Regarding the domains of the SF-36, a large proportion and often the majority of POUs showed limited or poor health-related quality of life, except physical pain. The HRQoL profile of POUs was very similar to OAT and NOU groups, but the level of impairment was between these two comparison groups. In addition, POUs’ mean aggregate score for mental HRQoL was much lower than for the general population; the aggregate physical health score, in contrast, was not markedly different from the general population. Moreover, POUs showed significantly lower mental health scores than the NOU patients, but higher and statistically significant mental and physical health scores than OAT patients.

Health-related quality of life (HRQoL) is a multidimensional concept assessing how physical, mental, emotional, and social health affects an individual’s daily functioning and well-being. It captures a patient’s own perspective on how health conditions, treatments, or diseases impact their life, covering aspects like mobility, pain, and psychological state [29]. A number of factors influence HRQoL in individuals with HCV and in those with present or past opiate use.

Regarding physical factors, patients with chronic hepatitis C experience a variety of symptoms including fatigue, muscle aches, pruritis, swelling, sexual dysfunction, and nausea, all of which negatively affect HRQoL [30]. Moreover, the severity of the disease itself might directly influence HRQoL, although evidence is inconclusive [31]. Of particular concern here is the impact of chronic liver diseases on brain function via the liver-brain axis: Possible mechanisms are neuroinflammation due to hepatitis C as a chronic systemic inflammation with increased levels of peripheral cytokines, and gut dysbiosis leading to dysfunction of the intestinal barrier, which in turn results in systemic inflammation with increased cytokine levels and activated immune cells. In addition, there may be a malfunction of the afferent vagal nerve [32,33]. These mechanisms could lead to depressive symptoms, fatigue, and cognitive slowing [32]. Physical determinants based on a chronic hepatitis C infection affect all three groups included in the present study and contribute to their decreased physical and mental HRQoL, compared with the general population. Moreover, the knowledge of HCV positive status impacts HRQoL in addition to actually being infected with the virus. It is commonly reported that the HCV diagnosis elicits depressive symptoms; however, in active opiate users, this reaction is weak [34].

Regarding mental health factors, substance users in general show substantially increased rates of psychiatric disorders [2], which in turn decrease HRQoL. In the present study, the rate for depression and psychosis was markedly higher in the OAT group, and also in the POU group, than in the NOU group (which itself showed a rate twice as high as in the adult population in Germany [35]). Some mental health problems not associated with HCV could have persisted after chronic opiate use. This would contribute to the decreased mental component score in POUs compared with NOU patients.

Behavioural factors such as smoking and regular alcohol consumption were here more prevalent in OAT patients and POUs than in NOU patients. In general, active substance users show lower HRQoL than population norms, irrespective of their HCV status [34]. Finally, social factors such as discrimination, stigma, isolation are common among individuals with HCV [36], and even more so in active opiate users and those in OAT [37]. This might contribute to the decreased HRQoL in all groups and particularly in the OAT group. As indicated by the employment rate, the POU group appears less affected by social instability than the OAT group.

The high mental and somatic health burden of opiate dependent patients may remain even after years in OAT [38]. Chronic HCV infection, in particular, impairs the HRQoL of affected individuals through manifestations of the disease or certain symptoms such as fatigue, weakness and nausea and due to the substantial psychological impact of the infection [39]. The present findings, referring to a natural sample of OAT patients, are in line with observations from patients entering clinical trials of HCV treatment, where HRQoL scores of OAT patients were significantly lower than scores for the general population and lower than scores reported for other HCV patients [40]. The novel finding here relates to previous opiate users, who showed compromised HRQoL in nearly all domains considered, and who roughly fell between OAT patients and patients without an opiate use history.

The implications of this pattern of results are not immediately clear. In terms of mental health, the self-reported impairments in the POU group may reflect a combination of factors: pre-existing vulnerabilities associated with the initiation and maintenance of opiate dependence, the effects of previous opiate use itself, and the impact of hepatitis C infection. Previous research on the health of POUs has focused primarily on psychological variables and psychopathology. Compared with controls without a history of opiate use or with normative population values, POUs exhibit an increased mental health burden, particularly related to depression and anxiety [41,42,43]. There were also here some indications of high rates of chronic pain [16], and/or physical disability, both interfering with finding a job [9], and of alcohol/tobacco consumption [9,42]. Finally, POUs exhibited signs of premature ageing across various biological indicators of ageing [42].

DAA treatment in previous or current drug users, whether or not they are receiving opiate agonist therapy, can achieve sustained virological response rates comparable to those observed in patients without a history of drug use [44]. DAA treatment can also substantially improve patients’ quality of life, starting from the initial phases [39,45]. Regarding HRQoL, several studies indicate that DAA treatment leads to improvements [46,47], although improvements might only be modest [48,49] and may not be persistent in the long-term [50]. In a previous study with patients from the DHC-R, roughly half of all patients did not achieve a clinically important improvement (e.g., 2.5 points) in MCS and PCS. Low MCS and PCS scores were identified as predictors of achieving clinically meaningful improvement, with patients who have lower baseline HRQoL appearing to benefit the most from modern therapeutic options [20]. Both POUs and OAT patients were here clearly identified as those patient groups more in need of improving their HRQoL, hence most possibly taking advantage from antiviral treatment in this respect.

In particular, the POU group showed issues regarding mental health, cannabis and alcohol use. Besides the high risk of a relapse into a dependent opiate use condition, these problems may well need to be therapeutically addressed in order to increase the quality of life of POUs. However, there is concern that this group may face difficulties in accessing adequate treatment, as the standard approach for opiate-dependent individuals is OAT. The problem burden of the POU group fell between that of the NOU and OAT groups, suggesting that a minority of opiate-dependent individuals may achieve abstinence, which could in turn improve their quality of life, for example through better professional integration. Conversely, individuals with opiate dependence who have a lower level of associated problems than the average OAT patient may find it easier to achieve and maintain abstinence.