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Three Part Question

In [a person who has sustained a needlestick injury from a known hepatitis C source] is [post exposure prophylaxis with a combination of ribavirin and interferon or interferon alone] more effective at [reducing hepatitis C virus]

Clinical Scenario

A very distressed nurse came to the emergencgy department with a bleeding injury site following a needlestick injury from a patient who was an intravenous drug user and already known to be hepatitis C positive. We wondered if in the event of her developing hepatitis C, is inteferon monotherapy or inteferon and ribavirin combination therapy more effective at managing hepatitis C.

Search Strategy

Medline 1966-July 2006 using the OVID interface.
[blood exposure.tw or needlestick$.tw or needle?stick.tw or EXP needlestick injuries/] AND [hepatitis C adj treatment$or hepatitis C adj management or ribivirin or inteferon adj ribavirin]

Search Outcome

88 papers found, 12 papers relevant, 1 paper used Cochrane reveiw

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
BrokJ, GluudLL, Gluud C. 2005 USA	Patients with HCV RNA and/or elevated liver transaminases for > 6months, based on previous antiretroviral treatment, patients were classified as naïve (not previously treated), relapsers or non-responders	Systematic review and meta-analysis of randomised-control trials	Sustained loss of HCV and liver-related morbidity plus all-cause mortality	72 randomised trials with 9991 patients were included. Compared with interferon, combination therapy had a significant beneficial effect on sustained virological response Relative risk (RR) 0.73, 95% CI 0.71-0.75 , and in subgroups of naïve patients (RR 0.72, 95% CI 0.68-0.76), relapsers (RR 0.63, 95% CI 0.54-0.73), and non-responders (RR 0.89, 95% CI 0.84-0.94) individually. Combination therapy (CT) significantly reduced morbidity plus mortality (Peto OR 0.46, 95% CI 0.22-0.96), but not in naïve, relapsers, or non-responders individually. CT also had a significant beneficial effect on the histological response. CT however significantly increased anaemia risk (RR 10.48, 95% CI 5.34-20.55), which occurred in 22% of patients on CT. CT increased the risk of dermatological, gastrointestinal, infectious, and miscellaneous (cough, dyspnoea, fatigue) adverse events. Accordingly, CT significantly increased the risk of treatment discontinuation (RR 1.19, 95% CI 1.01-1.39)	The authors state that most trials had low methodological quality however there was no significant influence on quality of the results Variability of included patients and intervention regimens in the review

Comment(s)

Hepatitis C infection is a common cause of liver disease following needlestick injury (up to 10% risk) and it is particularly common in intravenous drug users . This Cochrane review of 72 randomised trials with 9991 patients shows that ribavirin in combination with interferon compared with interferon alone, increases the number of patients who clear the HCV, as well as those who demonstrate improved liver histology. This may reduce the risk of liver-related morbidity and mortality. However, the number needed to treat to prevent one patient developing morbidity or dying has been noted to seem really large. In addition, combination therapy was associated with increased risk of anaemia and several other adverse events Clinical bottom line

Clinical Bottom Line

Compared with interferon alone, ribavirin plus interferon is more effective in clearing HCV and improving liver histology. This may lead to reduced morbidity and mortality. However, combination therapy significantly increased the risk of several adverse events.

References

1. BrokJ, GluudLL, Gluud C. Ribavirin plus interferon versus interferon for chronic hepatitis C. The Cochrane Database of systematic Reviews 2005, Issue 2. Art. No.CD005445