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Risk For Hepatitis C Transmission in Hospital/Clinic Setting:
use of multidose medication vials- HCV transmission risk and management of acute HCV in hospital settings

 
 
  At the recent ICAAC science conference a research group reported on potential risks for transmission of hepatitis C that had not previously been identified. The large study was conducted in France and the potential risks they identified included hospitization of medical procedures in the hospital setting such as IM & IV injections, and surgery. Here is the link to the full report:
 
http://www.natap.org/2002/ICAAC/day4.htm
 
As well, 2 recent newswire reports alerted us to reports of hepatitis C outbreaks in clinics in Oklahoma and Nebraska where the use of multidose medication vials and reuse of syringes without changing syringes were suspected as the source for transmission.
 
Here is link to these articles:
 
Nebraska Clinic-www.natap.org/2002/Oct/101702_1.htm
 
Oklahoma Pain Clinic- www.natap.org/2002/Oct/101102_1.htm
 
In the current issue (October 2002) of Hepatology, Larghi et al. describe their investigation of an outbreak of nosocomially acquired hepatitis C virus (HCV) infection.1 The report is an important one, for it serves as a reminder of our duty to protect patients from accidental HCV transmission, while raising interesting questions concerning HCV biology. Fifteen healthy volunteers with acute HCV infection acquired while participating in two pharmacokinetics studies are described. Although the investigators are cautious to point out that infection was probably transmitted via blood-contaminated heparin multidose vials (used to maintain intravenous catheters for repeated phlebotomy in the studies), the evidence they present is convincing. There is little doubt that this was actually what occurred. The investigators point out that this is not the first description of common-use items' implication in nosocomial HCV infection. For instance, Widell et al. came to a similar conclusion, implicating multiuse vials in an HCV outbreak on a pediatric oncology unit,2 and improper use of spring-loaded finger-stick devices for blood glucose monitoring has been implicated in other disease clusters.3 An extensive review of hospital- and clinic-based outbreaks of HCV with their mechanisms of transmission has recently been published and, not surprisingly, inadvertent exposure to trace amounts of blood is the common theme.4
 
We can take a lesson from the risk-reduction behaviorists who study virus transmission among intravenous drug users. In several studies, investigators have documented a reduction in human immunodeficiency virus transmission through needle exchange programs (although not in all cases) while, surprisingly, HCV transmission was minimally affected.5,6 Further investigation revealed ongoing sharing of "cookers," cotton filters, and syringes used for drug preparation, even as shared use of needles for injection was diminished.7 The investigators concluded that the risk of exposure to accessory paraphernalia must be simultaneously addressed in programs designed to decrease needle sharing. From the hospital and clinic perspective, we can reach a similar conclusion. Although the primary risk factor for iatrogenic HCV transmission has been rigorously addressed (contamination of blood and blood products with HCV), it is time now to consider anew the risks associated with our accessory paraphernalia. Multidose medication vials belong at the top of this list, and policies restricting their use to individual patients should be considered.
 
In the present acute infection cohort, it is quite interesting that 56% of patients achieved spontaneous virus clearance without treatment. An emerging theme in the literature is reinforced: earlier studies describing older patient populations that acquired HCV through blood transfusion overestimate somewhat the chronicity rate for HCV infection, at least with regard to current and generally younger at-risk groups.8 Why do some patients clear acute HCV infection without therapy, while others do not? Immunologic studies of acute HCV infection indicate that robust and polyclonal CD4 proliferative responses to HCV antigens are a prerequisite for viral clearance, but not all patients generating such responses achieve a spontaneous cure, and over time, the responses wane.9-11 HCV-specific CD8+ T-lymphocyte responses in acute infection may also be dysfunctional, with diminished or absent interferon gamma (IFN-) expression by cells identified as HCV specific in tetramer assays.9,12 Simultaneous with the elaboration of the host humoral and cellular immune response, the infecting virus itself undergoes dynamic replication and substantial change with emergence of new quasispecies. One view holds that the virus may simply outstrip the host's ability to contain it, with evolution of viral sequence mutations that anergize, antagonize, or abrogate host CTL and humoral responses. One conclusion is clear though; it appears that an individual has their best shot at achieving spontaneous viral clearance in the early stage of infection, before host "accomodation" (waning of cellular immune responses) and virus adaptation ("escape mutations" of various types) become established.
 
The landmark study of the German Acute Hepatitis C Therapy Group, in which cure was achieved for 98% of patients with acute symptomatic infection who were treated with IFN- for 24 weeks, should be considered in this context.13 The 43 patients cured of their infection in that study included 27 (61%) with genotype 1a/1b virus, and among the entire group, an average estimated duration of infection prior to onset of therapy of 89 days (range, 30-112 days). The observed clearance rate of 98% for this cohort was a spectacular success in light of the predicted clearance rates for chronic infection were it treated with IFN-2b alone. Therapy administered while the host immune response is still largely intact is certainly more effective, and is clearly indicated. The question then becomes, at what point should one intervene in acute infection? In the cohort studied by Larghi et al., 56% of patients cleared their infection without therapy.1 This was a cohort of patients with HCV genotype 2 infection, and chronicity rates appear to be lower for non­genotype 1a/1b infections.14 It is striking that viremia was still detectable at 8, 13, and 24 months, respectively, in 3 of their patients who nonetheless went on to achieve spontaneous viral clearance. Although it is unlikely that anyone would recommend a prolonged period of observation prior to initiation of therapy given the German Acute Hepatitis C Therapy Group observations, some period of observation in hope of spontaneous viral clearance is probably reasonable. Uncertainty will of course remain over just how long one can delay therapy hoping for spontaneous cure, before a reduction in sustained virologic response rate ensues. The above data suggest that 3 months (from time of infection) is clearly reasonable, and up to 6 months is justifiable on a case-by-case basis. Doctors and patients will have to continue grappling with this difficult issue, and should make the decision jointly.
 
In summary, another unique cohort with acute HCV infection has been described. Interesting observations have already been made, and we can hope that further studies will dissect host and viral factors that mediated viral clearance or persistence in these patients. Finally, and most importantly, while we can learn broad lessons from medical mishaps, we must also prevent their recurrence.
 
David Oldach, M.D., University of Maryland School of Medicine, and Institute of Human Virology, UMBI, Baltimore, MD
 
References
 
1. Larghi A, Zuin M, Crosignani A, Ribero ML, Pipia C, Battezzati PM, Binelli G, et al. Outcome of an outbreak of acute hepatitis C among healthy volunteers participating in pharmacokinetics studies. Hepatology 2002;36:993-1000.
 
2. Widell A, Christensson B, Wiebe T, et al. Epidemiologic and molecular investigation of outbreaks of Hepatitis C Virus infection on a pediatric oncology service. Ann Int Med 1999;130:130-135.
 
3. Desenclos J-C, Bourdiol-Razes M, Rolin B, et al. Hepatitis C in a ward for cystic fibrosis and diabetic patients: possible transmission by spring-loaded finger-stick devices for self-monitoring of capillary blood glucose. Infect Control Hosp Epidemiol 2001;22:701-707.
 
4. Knoll A, Helmig M, Peters O, et al. Hepatitis C Virus transmission in a pediatric oncology ward: analysis of an outbreak and review of the literature. Lab Invest 2001;81:251-262.
 
5. Strathdee SA, Patrick DM, Currie S, et al. Needle exchange is not enough: lessons from the Vancouver injection drug use study. AIDS 1997;11:F59-F65.
 
6. Hagan H, McGough JP, Thiede H, et al. Syringe exchange and risk of hepatitis B and C viruses. Am J Epidemiol 1999;149:23-213.
 
7. Hagan H, Thiede H. Changes in injection risk behavior associated with participation in the Seattle needle-exchange program. J Urban Health 2000;77:369-382.
 
8. Seeff LB. Why is there such difficulty in defining the natural history of hepatitis C? Transfusion 2000;40:1161-1164.
 
9. Thimme R, Oldach D, Chang KM, et al. Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med 2001;194:1395-1406.
 
10. Lechner F, Wong DK, Dunbar R, et al. Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 2000;191:1499-1512.
 
11. Gerlach JT, Diepolder HM, Jung MC, et al. Recurrence of hepatitis C virus after loss of virus-specific CD4+ T-cell response in acute hepatitis C. Gastroenterology 1999;117:933-941.
 
12. Gruener NH, Lechner F, Jung MC, et al. Sustained dysfunction of anti-viral CD8+ T lymphoyctes after infection with hepatitis C virus. J Virol 2001;75:5550-5558.
 
13. Jaeckel E, Cornberg M, Wedemeyer H, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med 2001;345:1452-1457.
 
14. Amoroso P, Rapicetta M, Tosti MEMA, et al. Correlation between virus genotypes and chronicity rate in acute hepatitis C. J Hepatol 1998;28:939-944.
 
 
 
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