Guidelines issued for management of hepatitis C in people who inject drugs

Guidelines for the management of hepatitis C virus (HCV) infection among people who inject drugs have been published in a supplement to Clinical Infectious Diseases. Developed by an expert panel on behalf of the International Network of Hepatitis in Substance Abuse, the recommendations cover topics including the natural history of HCV, non-invasive methods of assessment, indications for HCV therapy, treatment strategies, adherence and mental health, the management of HIV and/or hepatitis B virus (HBV) co-infection and liver transplant.

The authors believe the guidelines “demonstrate that treatment among PWID [people who inject drugs] is feasible,” and also provide “a framework for HCV assessment, management, and treatment.”

In the developed world, between 50 and 80% of individuals who inject drugs – both current and past injectors – are have HCV. Liver disease is an increasingly importance cause of serious illness and death in this population.

Until recently, guidelines excluded people who inject drugs from HCV therapy. This was due to concerns about adherence, side-effects and re-infection. However, successful outcomes have been observed among current and former drug users. Guidelines therefore now recommend that therapy for this population should be considered on a case-by-case basis.

Nevertheless, few active or former injecting drug users have so far received treatment. An international team of experts therefore developed the present recommendations to enhance the assessment, management and treatment of people who inject drugs.

The recommendations were graded, with the strength reflecting the quality of the supporting evidence. The quality of the research evidence was classified as A (high); B (moderate); or C (low). The grade of recommendation was either 1 (strong) or 2 (weak).

Prevalence of HCV among people with a history of long-term injecting drug use is between 65 and 80%. Incidence of new infections is high at between 2 and 45% each year. Harm reduction programmes including opioid substitution and needle exchange can reduce incidence and modelling studies suggest that increasing HCV treatment rates could also curtail the epidemic.

The panel recommends routine and voluntary HCV RNA and antibody testing for all people who inject drugs every six to twelve months (recommendation strength: B1). Harm reduction programmes should include access to clean injecting equipment and opioid substitution therapy (recommendation strength: B1).

Chronic infection develops in 75% of individuals and there is a 10 to 20% risk of developing liver cirrhosis within 20 to 30 years of infection. Factors associated with accelerated disease progression are heavy alcohol consumption, HIV co-infection, older age, obesity and insulin resistance.

Neither heroin nor methadone have liver toxicities. Heavy alcohol consumption does increase the risk of cirrhosis and smoking cannabis has been shown to accelerate the pace of liver fibrosis. Drinking coffee has benefits for liver function.

The panel makes the following recommendations:

1. Patients should be advised to moderate their alcohol intake or to abstain if there is evidence of advanced liver disease (recommendation strength: A1).
2. Individuals should be counselled to moderate their use of cannabis or to abstain if they have significant liver disease (recommendation strength: B1).
3. Cessation of injecting is not required to limit the progression of HCV disease (recommendation: B2).
4. Healthcare workers should discuss with patients the potential impact of drug use on the liver (recommendation: C2).

Liver biopsy has long been regarded as the “gold standard” test for the assessment of liver fibrosis. However, non-invasive scans and/or use of biomarkers of liver disease can be used to monitor liver disease and have been shown to be highly reliable in the context of cirrhosis.

The following recommendations are made regarding assessment:

1. Non-invasive tests have a lower risk and have greater acceptance among patients than liver biopsy. They may enhance screening rates and should be offered when available (recommendation strength: B1).
2. Combining multiple non-invasive tests is recommended where possible (recommendation strength: B1).

People with HCV who inject drugs often have complex social, medical and psychiatric problems than can complicate decisions about their care. Poor or inaccurate knowledge of HCV are barriers to accessing care.

Recommendations:

1. Pre-therapeutic education should include discussion of HCV transmission, risk factors for the progression of fibrosis, treatment, the risk of re-infection and harm reduction (recommendation strength: B1).
2. Pre-treatment assessment could include an evaluation of social issues, support and function, as well as drug and alcohol use. Patients should be linked to social support and peer support, when available (recommendation strength: A1).

Recommendations:

1. Patients who inject drugs should receive an HCV assessment. Treatment decisions should be individualised and based on an evaluation of social, lifestyle and clinical factors (recommendation strength: B1).
2. Individuals with absolute contraindications for therapy as laid down in standards of care should not receive HCV treatment (recommendation strength: B1).

Standard treatment used to consist of pegylated interferon with ribavirin. Outcomes are improved by the addition of an HCV protease inhibitor and other direct-acting antivirals (DAAs) with favourable efficacy and safety profiles are in development.

Individuals with active drug use have been excluded from DAA studies, but some have included patients on opioid substitution therapy. However, outcomes have not been presented in this subgroup. Drug interaction studies have shown that there are no clinically important interactions between methadone and the currently licensed HCV protease inhibitors.

Recommendations:

1. Evaluation of the safety and efficacy of HCV treatment regimens including the current licensed protease inhibitors is required for people who inject drugs (recommendation strength: C1).
2. The currently available HCV protease inhibitors can be used by people on opioid substitution therapy (recommendation strength: B1).
3. There are no interactions between these protease inhibitors and methadone. However, patients should be monitored for signs of opioid toxicity or withdrawal (recommendation strength: B1).
4. Decisions about the use of the existing DAAs should be made on an individual basis. However, patients with early liver disease should generally be advised to wait for more effective and tolerable therapies (recommendation strength: B1).

In studies, a history of injecting drug use did not compromise adherence to HCV therapy or treatment outcomes. However, some research has found lower treatment completion rates in this group. Lower adherence has been observed in people with frequent drug use during therapy. A number of social factors have been associated with adherence and treatment completion rates.

Recommendations:

1. Monitoring of adherence should evaluate both missed doses and treatment discontinuation (recommendation strength: B1).
2. Before starting therapy, patients should be advised of the importance of adherence and its association with treatment outcomes (recommendation strength: A1).
3. HCV therapy can be considered for people who inject drugs, provided they wish to receive treatment and are willing to maintain regular clinic attendance (recommendation strength: A1).
4. A history of injecting drug use and recent injecting are not associated with poorer treatment outcomes. Decisions on when to treat should be made on a case-by-case basis (recommendation strength: B1).
5. Individuals with frequent drug use or psychiatric and social need are at risk of lower adherence and poorer outcomes and should be closely monitored (recommendation strength: B1).

There is a high prevalence of psychiatric co-morbidity among people who inject drugs. However, these have not been associated with lower adherence or treatment completion rates, poorer outcomes or the risk of depression with pegylated interferon/ribavirin.

Major and controlled psychiatric conditions are a contraindication to HCV therapy. Prophylactic antidepressants may reduce the risk of depression for people treated with pegylated interferon/ribavirin. Therapy with antidepressants can be effective should depression occur during treatment.

Recommendations:

1. Pre-treatment assessment should include an evaluation of mental health and engagement with mental health and drug-support services. There should be a discussion of potential treatment options (recommendation strength: A1).
2. If there are psychiatric co-morbidities, decisions about therapy with pegylated interferon/ribavirin should be made on a case-by-case basis (recommendation strength: A1).
3. A pre-treatment psychiatric assessment is recommended for people with major or uncontrolled mental health problems (recommendation strength: C2).
4. Prophylactic antibiotics are recommended for people with depressive symptoms at baseline or a history of interferon-induced depression (recommendation strength: B1).

HCV therapy has been successfully delivered to people who inject drugs in a variety of settings. Key to success is the presence of a multidisciplinary team including clinicians, specialist nurses, drug and alcohol services, psychiatric support, social work and other social support services.

Recommendations:

1. HCV therapy should be considered for patients on an individualised basis and delivered within the context of a multidisciplinary team (recommendation strength: B1).
2. Access to harm reduction programmes, social work and social support should be a component of the clinical management of HCV (recommendation strength: B2).
3. Peer-based support should be evaluated as a means to improve the clinical management of HCV (recommendation strength: B2).

There are concerns that patients will be re-infected via drug use following successful therapy. However, re-infection rates are low, typically between 1 and 5% per year.

Recommendations:

1. People who inject drugs should not be excluded from therapy due to perceived concerns about the risk of re-infection (recommendation strength: B1).
2. Harm reduction education and counselling should be provided in the context of HCV therapy (recommendation strength: B1).
3. Patients should be monitored for re-infection and risky behaviour after successful therapy (recommendation strength: B2).

Approximately a quarter of patients clear HCV during the acute phase. Treatment during the acute phase can achieve good outcomes.

1. Patients should be monitored using HCV RNA tests for 12 to 16 weeks to allow for the potential of spontaneous cure (recommendation strength: A1).
2. Monotherapy with pegylated interferon lasting 24 weeks should be considered in cases of acute infection (recommendation strength: B1).
3. Strategies to optimise adherence should be used in cases of acute infection. Consideration should be given to directly-observed treatment with pegylated interferon (recommendation strength: B2).

There is a high prevalence of HIV/HCV co-infection among people who inject drugs. Liver disease caused by HCV is a leading cause of death in this group. HCV treatment responses may be poorer in people with co-infection.

Recommendations:

1. All patients with HCV who inject drugs should be screened for HIV (recommendation strength: B1).
2. Accelerated HCV disease progression in the context of co-infection should be considered when reaching decisions about HCV therapy (recommendation strength: B2).
3. Potential drug-drug interactions between HIV treatment, HCV therapies and opioid substitution therapy should be considered (recommendation strength: A1).
4. Early HIV therapy should be considered (recommendation strength: B1).

Hepatitis B (HBV) vaccination is effective in people who inject drugs and HCV treatment is successful in the context of HBV co-infection. Hepatitis D virus co-infection is common in people with HBV. The only effective therapy is pegylated interferon.

Recommendations:

1. Patients should be vaccinated against hepatitis A and B.
2. Patients with active HBV/HCV co-infection should be considered for treatment with pegylated interferon/ribavirin.

Selection criteria for transplantation often includes 6 to 24 months abstinence from drug use, controlled psychiatric disease and the presence of stable support networks. Opioid substitution therapy is not a contraindication. There are no data on liver transplant outcomes among people who inject drugs.

Recommendations:

1. Awareness should be raised that liver transplant is an option for those with a history of injecting drug use (recommendation strength: B2).
2. Opioid substitution therapy is not a contraindication and therefore patients should not be advised to reduce or stop treatment (recommendation strength: A1).
3. Psychiatric evaluation and follow-up should be offered to patients undergoing liver transplant (recommendation strength: B1)

The authors stress that “strategies to enhance assessment and treatment” for patients who inject drugs are urgently needed. They call for further research into adherence, and treatment outcomes, especially with the use of new DAAs.