The natural history of hepatitis C infection acquired through injection drug use: Meta-analysis and meta-regression

Background & Aims

Our aim was to estimate the rate of progression to cirrhosis for those infected with hepatitis C virus (HCV) through injection drug use.

Methods

We searched the published literature for articles assessing cirrhosis in this population and abstracted data on cirrhosis prevalence, mean duration of infection, mean age, mean alanine aminotransferase (ALT) enzyme levels, proportion of males, proportion HIV co-infected, proportion consuming excessive alcohol, and study setting. Summary progression rates were estimated using weighted averages and random effects Poisson meta-regression. The impact of co-variates was assessed by estimating the posterior probability that the relative risk (RR) of progression exceeded 1.0.

Results

A total of 47 published articles were identified. After adjusting for covariates in 44 studies representing 6457 patients, the estimated rate of progression to cirrhosis, was 8.1 per 1000 person-years (95% credible region (CR), 3.9–14.7). This corresponds to a 20-year cirrhosis prevalence of 14.8% (95% CR, 7.5–25.5). A 5% increase in the proportion of male participants and a 5% increase in the proportion consuming excessive alcohol were associated with faster progression (probability RR >1 = 0.97 and 0.92, respectively). A 5% increase in the proportion of HIV co-infected, an increase in ALT of 5 IU/L and studies in settings with a high risk of referral bias were not associated with faster progression (probability RR >1 = 0.42, 0.65, and 0.43, respectively).

Conclusions

Analysis of aggregate level data suggests that for patients who contracted HCV through injection drug use prognosis is poor in populations with many male patients and high levels of alcohol consumption.

Introduction

Hepatitis C is a blood-borne viral illness responsible for significant morbidity and mortality throughout the world. Seroprevalence data indicate that approximately 3.2 million persons are chronically infected in the United States [3]. The screening of the blood supply has virtually eliminated blood products as a source of infection. International estimates of the incidence of HCV among IDUs range from 11 to 42 per 100 person-years [7], [9], [19], [22], [33]. The prevalence of HCV infection among injection drug users (IDUs) has been shown to be as high as 88% [29].

Chronic infection with HCV can result in end-stage liver disease such as cirrhosis, liver failure, and/or hepatocellular carcinoma (HCC) [12], [13]. Many studies demonstrate that treatment of active or recent drug users with antiviral therapies can be successful, especially in the context of addiction therapy [18], [25]. However, very few active or recent drug users receive treatment with antiviral therapies [2], [16]. Due to the large clinical and economic burden associated with end-stage liver disease, and the disproportionate burden of disease in injection drug users, information on the natural history of chronic HCV infection acquired through injection drug use is important for individual counseling and health care policy.

The rate of progression to cirrhosis is perhaps the most important factor in HCV natural history. Cirrhosis is associated with a significant risk of liver failure and hepatocellular carcinoma. Individuals with a history of injection drug use may have a high prevalence of co-infection with HIV and a high prevalence of alcohol abuse. It is important to understand the impact of these characteristics on the natural history of HCV infection and understand the interactions among risk factors that may be unique to this population. We estimated the rate of progression to cirrhosis and the impact of risk factors for patients who acquired HCV infection through injection drug use, using a systematic review of the literature and meta-analysis of relevant studies. The association between risk factors and fibrosis progression rates was assessed at the aggregate level, as we did not have access to individual patient level data. The resulting estimates are most useful for understanding the morbidity of chronic HCV infection for populations of patients. This information will be useful to clinicians and policy-makers considering ways to expand access to antiviral therapy and improve uptake of antiviral therapy for patients who acquired infection through injection drug use. Individual-level associations between risk factors and fibrosis progression rates suggested by the results of the analysis should be interpreted with caution.