Patients receiving opioid maintenance treatment in primary care: successful chronic hepatitis C care in a real world setting

Chronic hepatitis C infection (CHC) is a major cause of end-stage liver disease (ESLD). Injection drug users (IDUs) are a major risk group for HCV infection [1] thus they significantly contribute to the patient group with ESLD in the future [2]. In recent years treatment efficacy of CHC has been steadily increased and a successful virus eradication can be achieved in up to 80% of patients with genotype 2 and 3 and in about 50% of patients chronically infected with genotype 1 [3–5]. However data suggest that about 70% of patients with confirmed CHC go untreated [6–8] therefore reducing therapeutic effectiveness of an anti-HCV therapy.

Increasing evidence suggests similar treatment efficacy of a pegylated interferon-based (pegIFN) combination therapy with ribavirin on HCV clearance in patients with substance abuse compared to patients without drug dependency [9–13]. Despite the revised NIH consensus on medical management of HCV infection that recommended a treatment decision on an individual basis [14] current clinical practice suggests that CHC patients with a history of IDU have a lower chance of getting antiviral therapy compared to other patient groups [7, 15]. This further emphasize that the true therapeutic impact of an anti-CHC therapy is rather an issue of access to treatment than of drug efficacy.

In IDUs concomitant illicit drug use, problem drinking, comorbid medical (e.g. HIV) and psychiatric conditions are prevalent representing common barriers to antiviral treatment. On the other hand opioid maintenance treatment (OMT) is established in the therapy of substance abuse [16] and has been shown to be an effective framework for adherence and virological success in HIV treatment [17, 18]. In addition we previously demonstrated the beneficial role of a substitution treatment as a therapeutic framework for a successful CHC case finding [19]. We hypothesized that a general practitioner (GP) providing an integrated chronic care approach including an OMT can achieve similar CHC treatment rates and viral eradication rates compared to patients without drug dependency. In addition we aimed to assess patient characteristics including duration of OMT which were associated with CHC treatment initiation in a primary care setting.

This study examined CHC treatment and success rates in unselected patients appearing “difficult to treat” in a single-handed general practice in Switzerland. Although a substantial proportion of the study population suffered from psychiatric comorbidities, reported excessive alcohol consumption and current drug misuse including injection drug use, treatment could be started in 41.2% and resulted in an overall sustained virological response rate of 71%. The duration of OMT was associated independently and positively with the start of a CHC treatment.

The observed treatment rate compares favourably with previous studies although comparisons have to be interpreted with caution as patient populations differ greatly across studies. In a UK population of CHC patients, Irving et al. [22] reported an overall treatment rate of 10.2% with a wide range varying according to the source of original HCV screening test with the highest rate of 21.4% in patients referred from GPs and a treatment rate of only 1.6% in patients originally screened for HCV by specialist units for drug and alcohol. Butt and colleagues [23] found a treatment rate of 11.8% in unselected veterans who were older (median age 50 years) compared to our study sample but comparable with regard to the prevalence of comorbidities such as psychiatric disorders and drug and alcohol dependence. The cumulative chance of starting CHC treatment in a 5 year period has been estimated to 33% in a representative Danish CHC cohort study [24]. Among patients attending the specialist consultations of the Swiss Hepatitis C Cohort Study (SDDS) [25] a history of CHC related treatment has been reported in 31% of the whole cohort and in 51% in the subgroup of cirrhotics. We found an independent and positive association between treatment initiation and the duration of OMT. Thus a patient spending 37 months (i.e. the median duration of OMT in our study population) on opioid substitution has doubled the chance ( i.e. OR 1.02^{37 months} =2.0) of getting started CHC treatment compared to a patient simply fulfilling the inclusion criteria of minimum 3 months on substitution. This beneficial effect of OMT has already been shown to increase adherence and virological success in HIV treatment [16, 18] and is in line with the finding that an ongoing OMT significantly increased the chance of a successful CHC case finding [19]. We are not aware of a study that has assessed the specific role of an OMT programme in the context of CHC treatment initiation. Our results further strengthened OMT as a favourable therapeutic setting, expanding its role for HCV-related care.

We achieved a viral eradication rate similar compared to randomized controlled efficacy trials reporting a sustained virological response up to 80% of patients with genotype 2 and 3 and in about 50% of patients chronically infected with genotype 1 [3–5]. The selection criteria for the aforementioned multicenter registration trials however excluded IDUs thus although internal validity of these studies is high illicit drug users constitute the largest proportion of CHC patients and the results do not represent treatment effectiveness in a “real world setting”. Our response rate is in line with a recent meta-analysis suggesting similar treatment efficacy of an antiviral therapy on HCV clearance in patients receiving OMT compared to patients without drug dependency [9]. However in only 3 out of the 16 studies included in the aforementioned meta-analysis active ongoing illicit drug use was not an exclusion criteria thus our results provided further evidence that successful viral eradication is feasible in a population normally excluded from clinical trials and judged “difficult to treat”.

We are aware that the analysis of our study does not address the CHC treatment effectiveness of a primary care setting in comparison to a specialized medical care setting due to the lack of a randomised controlled intervention. The current standard of care for the treatment of chronic HCV infection which is also recommended for patients with substance abuse was applied by the attending GP with a high level of commitment and a special interest in addiction medicine. Providing chronic care (i.e. substitution, psychiatric comorbidities) in combination with acute somatic care is a main feature of a primary care setting. Our treatment rate is in line with a recent randomized controlled study evaluating the impact of an integrated care approach among CHC patients originally deferred from CHC therapy due to mental health and substance abuse comorbidities [26]. In this study patients receiving an integrated care intervention reached a treatment eligibility of 42% compared to the standard care group with a significant lower eligibility rate of 18%. In our population the level of homelessness and unemployment was relatively low but similar when compared to GP patients in other OMT programmes in Switzerland, which probably reflects the low-threshold management of drug addicts in Switzerland [27]. Furthermore it is important to note that an OMT durationof fewer than 3 months was an exclusion criteria thus a selection of our population probably related to a high level of integration in the social framework has to be considered when compared to other settings.

From a clinical perspective the development of new direct acting antiviral agents such as the protease inhibitors boceprevir and telaprevir are long-awaited and their implementation to clinical practice in the near future have the potential for a new standard of care for the treatment of chronic hepatitis C [28]. Although these new antiviral agents showed superior cure rates compared to the current standard of care the public health impact of these new and better medications will remain limited unless more patients are diagnosed and treatment is initiated [29, 30]. To control chronic hepatitis C an increase in treatment uptake is crucial especially in the population of (former) IDUs as these patients have by far the highest prevalence of hepatitis C. On the other hand barriers to HCV-related care are most likely in this “hard to reach” population. An easy to access antiviral treatment linked to OMT has the potential to optimize treatment and cure rates in this “hard to reach” population. We provided a successful example of a low-threshold HCV-related care in a Swiss primary care setting.

We conclude that a high rate of CHC eradication in unselected patients on OMT is feasible in a primary care setting in Switzerland. The independent association between OMT duration and treatment initiation highlights the important role of opioid substitution as a therapeutic framework to optimize CHC care in a patient group that significantly contributes to the global burden of liver diseases caused by HCV infection.