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•Evidence to support feasibility of elimination of hepatitis C as a public health threat.•High uptake of hepatitis C treatment reflected in reduction in viraemic ...prevalence.•Surveillance and monitoring are required to track progress toward elimination goals.
The World Health Organization (WHO) established targets to eliminate hepatitis C virus (HCV) infection as a public health threat by 2030. Evidence that HCV treatment can lower viraemic prevalence among people who inject drugs (PWID) is limited. Broad accessibility of direct-acting antiviral (DAA) therapy in Australia, since March 2016, provides an opportunity to assess the efficacy of these treatments at a population level in a real-world setting.
Data from Australia’s annual bio-behavioural surveillance examined treatment uptake and estimated viraemic prevalence among PWID attending needle syringe programs nationally between 2015 and 2017. Multivariate logistic regression identified variables independently associated with HCV treatment among those considered eligible (anti-HCV positive excluding HCV RNA negative with no self-reported history of HCV treatment) in 2017.
Annual samples ranged from 1,995–2,380 PWID. Anti-HCV prevalence declined from 57% (2015) to 49% (2017, χ2p trend <0.001), with 40–56% of anti-HCV positive respondents providing sufficient sample for HCV RNA testing. Between 2015 and 2017, treatment uptake among those eligible increased from 10% to 41% (χ2p trend <0.001) and viraemic prevalence among the overall sample declined from 43% to 25% (χ2p trend <0.001). In multivariable analysis, older age (≥50 years adjusted odds ratio aOR 1.82; 95% CI 1.09–3.06;p = 0.023 and 44–49 years aOR 1.75; 95% CI 1.03–3.00;p = 0.038 vs. ≤37 years) and history of opioid substitution therapy (aOR 2.06; 95% CI 1.30–3.26; p = 0.002) were independently associated with treatment.
This study confirms PWID are willing to initiate treatment when HCV DAA therapy is available and provides population-level evidence of a decline in viraemic prevalence among people most at risk of ongoing HCV transmission. Scaled up surveillance and monitoring are required to evaluate progress toward WHO HCV elimination goals.
The World Health Organization’s goal to reduce hepatitis C virus incidence by 80% will be difficult to achieve without widespread scale up and a corresponding reduction in viraemic prevalence among those most at risk of onward transmission. Our results indicate that a population-level reduction in viraemic prevalence is achievable through high levels of treatment and cure among people who inject drugs.
Summary
The next decade will be a crucial period in the public health response to hepatitis C virus (HCV) infection.
The rapid development of direct‐acting antiviral therapy for HCV infection has ...brought considerable optimism to the HCV sector, with the realistic hope that therapeutic intervention will soon be more effective and offer shorter treatment duration.
The initial phase of combination pegylated interferon, ribavirin and a protease inhibitor will be associated with increased toxicity and complexity of therapeutic management but, over the course of the decade, strategies including interferon‐free combination direct‐acting antiviral regimens with enhanced tolerability and simplified dosing schedules and monitoring protocols will emerge.
Hepatitis C Martinello, Marianne; Solomon, Sunil S; Terrault, Norah A ...
The Lancet (British edition),
09/2023, Letnik:
402, Številka:
10407
Journal Article
Recenzirano
Hepatitis C virus (HCV) is a hepatotropic RNA virus that can cause acute and chronic hepatitis, with progressive liver damage resulting in cirrhosis, decompensated liver disease, and hepatocellular ...carcinoma. In 2016, WHO called for the elimination of HCV infection as a public health threat by 2030. Despite some progress, an estimated 57 million people were living with HCV infection in 2020, and 300 000 HCV-related deaths occur per year. The development of direct-acting antiviral therapy has revolutionised clinical care and generated impetus for elimination, but simplified and broadened HCV screening, enhanced linkage to care, and higher coverage of treatment and primary prevention strategies are urgently required.
HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and ...those receiving opioid agonist therapy (OAT).
We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies.
Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1–8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3–9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5–5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1–9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5–5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8–2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0–8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4–12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio aRR per year increase in mean/median follow-up 0.77; 95% CI 0.69–0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62–7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82–8.59) had higher reinfection rates.
HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment.
Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population – reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment.
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•We assessed the rate of HCV reinfection after treatment among people who recently used drugs and those receiving opioid agonist therapy.•The rate of reinfection was lowest among people receiving opioid agonist therapy with no recent drug use.•The rate of HCV reinfection was comparable after interferon therapy or direct-acting antiviral therapy.•A higher rate of HCV reinfection was observed in studies with shorter follow-up.
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We determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating ...treatment of people who inject drugs (PWID).
A dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12weeks at £3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years (QALYs) gained using a £20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment.
The most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment £60,640/£23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -£3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage.
Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high.
•The burden of hepatitis C virus infection is growing among people who inject drugs (PWID).•HCV eradication is feasible, given therapy is effective in PWID.•Harm reduction and HCV treatment as ...prevention provide a basis for eradication.•HCV eradication requires broad expansion of effective, tolerable HCV therapy.•Although eradication should be strived for, elimination is more feasible.
People who inject drugs (PWID) represent the core of the hepatitis C virus (HCV) epidemic in many countries and HCV-related disease burden continues to rise. There are compelling data demonstrating that with the appropriate programs, treatment for HCV infection among PWID is successful, with responses to therapy similar those observed in large randomized controlled trials in non-PWID. However, assessment and treatment for HCV infection lags far behind the numbers who could benefit from therapy, related to systems-, provider- and patient-related barriers to care. The approaching era of interferon-free directly acting antiviral therapy has the potential to provide one of the great advances in clinical medicine. Simple, tolerable and highly effective therapy will likely address many of these barriers, thereby enhancing the numbers of PWID cured of HCV infection. This commentary will consider why we should strive for the eradication of HCV infection among PWID, whether eradication of HCV infection among PWID is feasible, components that would be needed to achieve eradication of HCV infection in PWID, potential settings and strategies required to establish programs targeted towards eradicating HCV infection among PWID and the feasibility of eradication versus elimination of HCV infection among PWID. This article forms part of a symposium in Antiviral Research on “Hepatitis C: next steps toward global eradication.”
Published estimates of liver fibrosis progression in individuals with chronic hepatitis C virus (HCV) infection are heterogeneous. We aimed to estimate stage‐specific fibrosis progression rates and ...their determinants in these individuals. A systematic review of published prognostic studies was undertaken. Study inclusion criteria were as follows: (1) presence of HCV infection determined by serological assays; (2) available information about age at assessment of liver disease or HCV acquisition; (3) duration of HCV infection; and (4) histological and/or clinical diagnosis of cirrhosis. Annual stage‐specific transition probabilities (F0→F1, … , F3→F4) were derived using the Markov maximum likelihood estimation method and a meta‐analysis was performed. The impact of potential covariates was evaluated using meta‐regression. A total of 111 studies of individuals with chronic HCV infection (n = 33,121) were included. Based on the random effects model, the estimated annual mean (95% confidence interval) stage‐specific transition probabilities were: F0→F1 0.117 (0.104–0.130); F1→F2 0.085 (0.075–0.096); F2→F3 0.120 (0.109–0.133); and F3→F4 0.116 (0.104–0.129). The estimated prevalence of cirrhosis at 20 years after the infection was 16% (14%–19%) for all studies, 18% (15%–21%) for cross‐sectional/retrospective studies, 7% (4%–14%) for retrospective‐prospective studies, 18% (16%–21%) for studies conducted in clinical settings, and 7% (4%–12%) for studies conducted in nonclinical settings. Duration of infection was the most consistent factor significantly associated with progression of fibrosis. Conclusion: Our large systematic review provides increased precision in estimating fibrosis progression in chronic HCV infection and supports nonlinear disease progression. Estimates of progression to cirrhosis from studies conducted in clinical settings were lower than previous estimates. (HEPATOLOGY 2008.)
Summary Background Although the addition of the HCV NS3/4A protease inhibitors boceprevir and telaprevir to pegylated interferon (peginterferon) alfa plus ribavirin has improved sustained virological ...response (SVR) in treatment-naive and treatment-experienced patients infected with hepatitis C virus (HCV) genotype 1, the regimens have a high pill burden and are associated with increased rates and severity of adverse events, such as anaemia and rash. The efficacy and safety of the combination of simeprevir, a one pill, once-daily, oral HCV NS3/4A protease inhibitor, plus peginterferon alfa 2a plus ribavirin were assessed in treatment-naive patients with HCV genotype 1 infection. Methods In QUEST-1, a phase 3, randomised, double-blind multicentre trial undertaken in 13 countries (Australia, Europe, North America, Puerto Rico, and New Zealand), 394 patients (aged ≥18 years) with chronic HCV genotype 1 infection and no history of HCV treatment, stratified by HCV subtype and host IL28B genotype, were randomly assigned in a 2:1 ratio with a computer-generated allocation sequence to receive simeprevir (150 mg once daily, orally) plus peginterferon alfa 2a plus ribavirin for 12 weeks, followed by peginterferon alfa 2a plus ribavirin (simeprevir group), or placebo orally plus peginterferon alfa 2a plus ribavirin for 12 weeks, followed by peginterferon alfa 2a plus ribavirin (placebo group). Treatment duration was 24 weeks or 48 weeks in the simeprevir group according to criteria for response-guided therapy (ie, HCV RNA <25 IU/mL undetectable or detectable at week 4 and <25 IU/mL undetectable at week 12) and 48 weeks in the placebo group. Patients, study personnel, and the sponsor were masked to the treatment group assignment. The primary efficacy endpoint was sustained virological response 12 weeks after the planned end of treatment (SVR12) and was assessed with an intention-to-treat analysis. The results of the primary analysis (week 60) are presented for safety and SVR12. This trial is registered with ClinicalTrials.gov , number NCT01289782. Findings Treatment with simeprevir, peginterferon alfa 2a, and ribavirin was superior to placebo, peginterferon alfa 2a, and ribavirin (SVR12 in 210 80% patients of 264 vs 65 50% of 130, respectively, adjusted difference 29·3% 95% CI 20·1–38·6; p<0·0001). Adverse events in the first 12 weeks of treatment led to discontinuation of simeprevir in two (<1%) patients and discontinuation of placebo in one patient (<1%); fatigue (106 40% vs 49 38% patients, respectively) and headache (81 31% vs 48 37%, respectively) were the most common adverse events. The prevalences of anaemia (42 16% vs 14 11%, respectively) and rash (72 27% vs 33 25%) were similar in the simeprevir and placebo groups. Addition of simeprevir did not increase severity of patient-reported fatigue and functioning limitations, but shortened their duration. Interpretation Simeprevir once daily with peginterferon alfa 2a and ribavirin shortens therapy in treatment-naive patients with HCV genotype 1 infection without worsening the adverse event profiles associated with peginterferon alfa 2a plus ribavirin. Funding Janssen Infectious Diseases–Diagnostics.
The majority of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection occurs among persons who inject drugs. Rapid improvements in responses to HCV therapy have been observed, ...but liver-related morbidity rates remain high, given notoriously low uptake of HCV treatment. Advances in HCV therapy will have a limited impact on the burden of HCV-related disease at the population-level unless barriers to HCV education, screening, evaluation, and treatment are addressed and treatment uptake increases. This review will outline barriers to HCV care in HCV/HIV coinfection, with a particular emphasis on persons who inject drugs, proposing strategies to enhance HCV treatment uptake and outcomes.
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