ReviewHepatitis C virus (HCV) disease progression in people who inject drugs (PWID): A systematic review and meta-analysis
Introduction
Hepatitis C virus (HCV) infection is a chronic blood-borne viral infection that is of global importance (Averhoff et al., 2012, Nelson et al., 2011). Approximately 160 million people, or 2–3% of the world's population, have chronic HCV; chronic HCV accounts for one-quarter of cases of cirrhosis and hepatocellular carcinoma (HCC) (Averhoff et al., 2012, Lavanchy, 2011, Nelson et al., 2011, World Health Organization, 2014). The vast majority of incident and prevalent HCV infections in the world are related to unsafe medical and illicit drug injections (Colvin & Mitchell, 2010). In most high-income countries, the primary route of HCV transmission is due to drug injection. HCV is concentrated in people who inject drugs (PWID) in these countries (Aceijas and Rhodes, 2007, Nelson et al., 2011), and approximately 50–80% of PWID are chronically infected (Nelson et al., 2011, Wiessing et al., 2014).
Viral and host factors hinder the detection, diagnosis and treatment of HCV in PWID (Hagan, 2011). Acute infection is typically asymptomatic and chronically infected individuals may not develop significant sequelae for decades after initial infection (Grebely et al., 2012). If left untreated, chronic liver disease will occur in 60–70%, cirrhosis in 5–20%, and 1–5% will die from decompensated cirrhosis or HCC (Rein et al., 2011). It has been estimated that fewer than 5% of PWID have received treatment for chronic HCV (Adeyemi et al., 2004, Grebely et al., 2009).
New HCV treatments feature shorter drug regimens with manageable side effects, and are highly likely to result in cure (Kohli, Shaffer, Sherman, & Kottilil, 2014). However these options are expensive and treatment eligibility guidelines may explicitly exclude active drug users (Fralick, 2014, Harris and Rhodes, 2013Robaeys et al., 2013, World Health Organization, 2014). Many US states’ public insurance programs (e.g., Medicaid) have restricted coverage of these new treatments to those with more advanced disease, i.e., METAVIR fibrosis stages 3 or 4, which may delay treatment for years; this restriction will disproportionately affect PWID and other low-income patients (Viohl & Associates, 2014). These restrictions also are in conflict with new HCV treatment guidelines from the American Association for the Study of Liver Disease (2015), which state explicitly that active injection drug users should be prioritized for treatment in part because of the risk of transmission to susceptible injection partners.
Understanding HCV disease progression rates among PWID is important to setting policy to expand access to detection, diagnosis and treatment, and in forecasting the burden of disease. In this paper we synthesize existing data on the natural history of HCV among PWID, including fibrosis progression rates and the incidence of compensated cirrhosis (CC), decompensated cirrhosis (DC), and HCC. Prior systematic reviews of HCV disease progression in PWID did not explicitly exclude studies of HIV-HCV co-infected patients. Because the majority of PWID with HCV are mono-infected, it is important to characterize this group separately. Estimates from the analysis will be used to inform simulations of the impact and cost-effectiveness of HCV management among PWID. This systematic review and meta-analysis and related simulations are conducted as part of the HCV Synthesis Project (see Hagan et al., 2014, Jordan et al., 2014), which is funded to develop guidance and recommendations for HCV control strategies for the US.
Section snippets
Search strategy
A combination of manual and electronic searches for published literature, including scientific conference websites and abstract books, were conducted within the databases of Ovid, Proquest, PubMed, and Web of Science. Variations of the search string consisted of keywords such as “HCV,” “hepatitis C,” “PWID,” “injection drug use,” “intravenous drug use,” “natural history,” “disease progression,” “survival,” “fibrosis,” “cirrhosis,” “hepatocellular carcinoma,” and “end stage liver disease.” The
Overview of included reports
As presented in Fig. 1, 21 unique reports were included in this review. Table 1, Table 2 present the pooled estimates and characteristics of the included reports for each of the four main outcomes of interest: FPR (10 reports), CC (15 reports), DC (4 reports), and HCC (5 reports). The geographic scope of the data focused largely on Europe where 11 reports (52%) originated; a smaller percentage represented data from the United States (5; 24%) and Australia (5; 24%). A total of 8502 unique PWID
Discussion
This systematic review synthesized the available data on the progression of fibrosis and the incidence of severe hepatic sequelae in PWID with chronic HCV infection. Random-effects estimation generated a stage-constant FPR of 0.117 and stage-specific FPRs of 0.128 (F0 → F1), 0.059 (F1 → F2), 0.078 (F2 → F3), and 0.116 (F3 → F4). The stage-constant rate (0.117) is within the range (and near the midpoint) of other stage-constant estimates from samples of HIV-negative patients with HCV infection due to
Acknowledgements
We would like to gratefully acknowledge Dr. Jason Fletcher for his statistical assistance. This study is supported by the National Institutes of Health, grant numbers R01DA034637 and P30 DA011041.
Conflict of interest: The authors have no conflicts of interest to disclose.
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