A 25-Year Study of the Clinical and Histologic Outcomes of Hepatitis C Virus Infection and Its Modes of Transmission in a Cohort of Initially Asymptomatic Blood Donors

Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 06/2012; 206(5):654-61. DOI: 10.1093/infdis/jis410
Source: PubMed


A total of 738 volunteer blood donors who were positive for anti-hepatitis C virus (HCV) were assessed for risk factors and outcomes for up to 15 years within the study and up to 54 years from the estimated onset of infection.
A third-generation recombinant immunoblot assay (RIBA) was performed to distinguish true from false anti-HCV reactivity. Findings of HCV polymerase chain reaction classified subjects as having chronic HCV infection or as having recovered. Liver biopsy specimens were staged by Ishak fibrosis score and graded by histologic activity index.
Of 738 anti-HCV-positive subjects, 469 (64%) had positive RIBA results, 217 (29%) had negative results, and 52 (7%) had indeterminate results. Primary independent risk factors were injection drug use (odds ratio [OR], 35.0; P < .0001), blood transfusion (OR, 9.9; P < .0001), and intranasal cocaine use, including 79 "snorters" who repeatedly denied injection drug use or blood transfusion (OR, 8.5; P < .0001). Classification and regression tree and random forest analyses confirmed these risk factors. A total of 384 RIBA-positive donors (82%) were HCV RNA positive; of these, liver biopsy specimens from 185 (48%) showed no fibrosis in 33%, mild fibrosis in 52%, bridging fibrosis in 12%, and cirrhosis in 2% a mean duration of 25 years after infection. Analysis of 63 repeat biopsy specimens showed that 8% progressed ≥2 Ishak stages over 5 years (mean progression, 0.06 Ishak stages/year).
Injection drug use and blood transfusion before 1990 are dominant risk factors for HCV acquisition; intranasal cocaine use may be a surreptitious route of parenteral spread. After a mean of 25 years of HCV infection, histologic outcomes were relatively mild: 85% had no or mild fibrosis, and only 2% had cirrhosis. Nearly one-fifth spontaneously recovered.

Download full-text


Available from: Robert D. Allison, Mar 26, 2015
  • Source
    • "The prevalence of HCV infection in illicit drug users varies from 10% to 95%, reflecting the presence or absence of specific risk factors, such as the history of drug use, sharing of drug paraphernalia (needles, syringes, pipes, cans, and so on), the number of partners present during shared use, detention and the use of drugs in jail or prison, and the type of consumption: inhaled or injected [2,3]. A number of studies have shown that the sharing of drug paraphernalia is responsible for the spread of HCV among both injecting drug users and non-injecting drug users [2,4-6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Currently, sharing of drug paraphernalia is the main form of HCV transmission worldwide. In South America, consistent findings indicate that shared sniffing equipment is an important factor in the spread of HCV among non-injecting drug users. Epidemiological data on the status of HCV infection in illicit drug users in the Amazon region are scarce, although reports of clinical cases of hepatitis or pathologies associated with HCV infection in other population groups are numerous. Thereby, this study investigated the prevalence, genotype frequency, and epidemiological factors associated with HCV infection in non-injecting drug users in the state of Para, eastern Amazon. During 2008-2011, 300 non-injecting drug users attending drug-treatment centers participated in this study. Most non-injecting drug users were male (63.7%). The mean age was 32.5 years. The non-injecting drugs most consumed were: cannabis (15.6%), cocaine paste (21.3%), and oxi cocaine (25.7%). Tobacco (60.9%) and alcohol (79.4%) were also commonly consumed. One hundred six (35.1%; CI 95%: 29.8 - 41.1) non-injecting drug users presented anti-HCV antibodies by EIA. The HCV-RNA prevalence was 28.0% (95% CI: 20.6 - 35.8). Genotypes 1 (76.9%) and 3 (23.1%) of HCV have been identified. A multivariate analysis demonstrated that HCV infection was independently associated with the following factors: "age (>= 35 years)", "tattoos", "use of a needle or syringe sterilized at home", "shared use of drug paraphernalia", "uses drugs for more than 5 years", and "use of drugs everyday". This study revealed a high prevalence of HCV infection in non-injecting drug users, and most infections are occasioned by genotype 1. Likely, HCV transmission is associated with the tattoos, the use of needle or syringe sterilized at home by people over the age of 35 years, and sharing, time and frequency of use of non-injecting drugs. These findings should serve as an incentive for the establishment of a program of Hepatitis C prevention and control by the local public-health authorities in order to develop effective policies and strategies for contain the spread of HCV infection.
    Virology Journal 02/2014; 11(1):38. DOI:10.1186/1743-422X-11-38 · 2.18 Impact Factor
  • Source
    • "- Non-intravenous recreational drug exposure. Increasing evidence is accumulating that HCV may also cross the nasal mucosa and infect subjects chronically using inhalatory recreational drugs, such as cocaine, by the sharing of inhalatory instrumentation, favored by the frequent bleeding of the nasal mucosa occurring in these individuals [4]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis C virus (HCV), first recognized as a cause of transfusion-associated acute and chronic hepatitis in 1989, plays a major role as a cause of chronic liver injury, with potential for neoplastic degeneration. It is mainly transmitted by the parenteral route. However, although with lower efficiency, it may be also transmitted by sexual intercourses and by the mother-to-child route. Epidemiological evidence shows that a wave of infection occurred in the 1945-65 period (baby boomers) in western countries. After acute infection, as many as 50-85% of the patients fail to clear the virus resulting in chronic liver infection and/or disease. It is estimated that, on a global scale, about 170 million people are chronically infected with HCV, leading to about 350.000 deaths yearly. Among western countries southern Europe, and particularly Italy, is among the most affected areas. The impact on the public health systems is noteworthy, with high number of hospitalizations due to chronic liver disease, cirrhosis or hepatocellular carcinoma. While waiting for a safe and effective vaccine to be made available, new promising direct-acting antiviral (DAA) drugs offer a better therapeutic scenario than in the past even for the poor responder genotypes 1 and 4, provided that effective screening and care is offered. However, the long and aspecific prodromic period before clinical symptoms develop is a major obstacle to early detection and treatment. Effective screening strategies may target at-risk groups or age specific groups, as recently recommended by the CDC.
    BMC Infectious Diseases 11/2012; 12 Suppl 2(Suppl 2):S2. DOI:10.1186/1471-2334-12-S2-S2 · 2.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, the prevalence, genotype frequency, and risk factors for HCV infection in 384 cocaine users were determined. One hundred twenty-four (32.3 %) cocaine users had anti-HCV antibodies and 120 (31.3 %) had HCV-RNA. Genotyping results indicated the predominance of genotypes 1 (73.3 %) and 3 (26.7 %). Multivariate analysis showed an association of HCV infection with tattoos, shared use of paraphernalia, daily cocaine use, and a long history of cocaine use. The epidemiological aspects of HCV infection among cocaine users presented here should serve as an incentive for the establishment of a program of hepatitis C prevention and control by the local public-health authorities in the Amazon.
    Archives of Virology 02/2013; 158(7). DOI:10.1007/s00705-013-1627-5 · 2.39 Impact Factor
Show more