Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2015 Feb 17.
Published in final edited form as: Infect Control Hosp Epidemiol. 2009 Oct;30(10):1000–1005. doi: 10.1086/605718

A pilot study of post-exposure prophylaxis for hepatitis C virus in healthcare workers

Kathleen E Corey 1,5, Julie C Servoss 1,5, Deborah R Casson 1,5, Arthur Y Kim 2,5, Gregory K Robbins 2,5, Jean Franzini 3, Katherine Twitchell 3, Susan C Loomis 4, Diane R Abraczinskas 1,5, Adam M Terella 1,5, Jules L Dienstag 1,5, Raymond T Chung 1,5
PMCID: PMC4331129  NIHMSID: NIHMS661993  PMID: 19743901

Abstract

Background and Objective

Hepatitis C transmission occurs in 0.2–10% of accidental needle-stick exposures. However, post-exposure prophylaxis is not currently recommended. We sought to determine the safety, tolerability and acceptance of post-exposure prophylaxis with peginterferon in healthcare workers exposed to blood from hepatitis C-infected patients.

Design

Open label pilot trial of peginterferon for hepatitis C post-exposure prophylaxis.

Setting

Two academic tertiary-referral centers.

Methods

Healthcare workers exposed to blood from hepatitis C infected patients were informed of the availability of post-exposure prophylaxis. Persons who elected post-exposure prophylaxis were given weekly doses of peginterferon alfa-2b for 4 weeks.

Partcipants

Healthcare workers.

Results

Among 2,702 HCWs identified with potential exposures to blood-borne pathogens, 213 (7.9%) were exposed to an anti-HCV-positive source. Of 51 HCWs who enrolled in the study, 44 (86%) elected to undergo post-exposure prophylaxis (Treated Group). Seven subjects elected not to undergo post-exposure prophylaxis (Untreated Group). No cases of hepatitis C virus transmission were observed in either the Treated or Untreated Groups and no cases occurred in the remaining 162 HCWs who did not enroll in this study. No serious adverse events related to PEG-IFN were recorded, but side effects were frequent.

Conclusion

In this pilot study, there was a lower than expected frequency of hepatitis C transmission after accidental occupational exposure. Although peginterferon was safe, because of the lack of hepatitis C transmission in either the Treated or Untreated Groups, there is little evidence to support routine post-exposure prophylaxis against hepatitis C in healthcare workers.

INTRODUCTION

The rate of infection after accidental percutaneous exposure to hepatitis C virus (HCV) is estimated to be 0.2%–10%.(1–5) Several factors can influence the risk of viral transmission. Needlesticks with hollow bore needles are associated with higher rates of HCV transmission when compared to solid bore suture needlesticks, presumably the result of a larger inoculum of virus.(6) In addition, the type of exposure influences infectivity. Percutaneous exposure carries the highest risk of viral transmission, while transmission from mucutanesous exposures is limited to case reports.(7, 8) No case reports of HCV transmission from skin contact with contaminated body fluids have been reported.(6, 9) High levels of HCV RNA have been associated with increased transmission rates in vertical transmission and theoretically could be associated with increased transmission risk in percutaneous exposures although data are lacking.(10) Finally, co-infection of the source patient with HIV infection increases the risk of HCV transmission.(6)

Unlike hepatitis B and human immunodeficiency virus infection, no therapies have been demonstrated to be effective for hepatitis C post-exposure prophylaxis (PEP).(9) Pooled immunoglobulin (IG) was studied for prevention of transfusion-associated HCV infection (11) and had been recommended after accidental exposure; However, studies of IG in both chimpanzees and human found that while IG prolonged the incubation period of hepatitis C infection it was ineffective in preventing infection and is no longer recommended.(12, 13) (14)

Current therapy for chronic hepatitis C has focused on patients with chronic HCV infection. Combination therapy with peginterferon alfa (PEG-IFN) and ribavirin is currently the most effective treatment for chronic hepatitis C, with an overall sustained virological response (SVR) rate of 45–55%.(15, 16)

Peginterferon has also been studied for use in patients with acute HCV infection. Rates of sustained virologic response for acute hepatitis C infection vary widely in the literature from responses as low as 21% to a high of 98%.(16–19) Several studies have suggested that the early initiation of treatment is associated with higher rates of SVR.(16, 20, 21) Other studies suggest that even short-term interferon therapy (e.g., 4 weeks) may be effective in treating acute hepatitis C with response rates of 87%.(22) These studies suggest a benefit for the early initiation of short course treatment. The initiation, then, of a short course of prophylactic treatment following HCV exposure could be hypothesized to be similarly effective in preventing HCV infection.

Sparse data exists regarding the use of interferon as post-exposure prophylaxis. Chung et al studied the use of peginterferon in 885 health care workers who suffered HCV antibody positive needlesticks.(1) Two hundred and seventy-nine patients underwent treatment with interferon for a median duration of 1 day (range 1–3 days). Only one patient in the treated and one patient in the untreated group developed acute HCV, resulting transmission rates of 0.3% and 0.2%. However, this study was significantly limited by the lack of documented viremia in the source subjects and may not adequately reflect transmission risks associated with active viral infection.

Given the results of these recent studies, peginterferon is an effective agent for treating acute and chronic hepatitis C. However, its role as PEP remains uncertain. We describe a pilot study of PEP using peginterferon.

Methods

Selection of patients

From July 2001 until September 2006, healthcare workers (HCW) who presented to the Occupational Health Services at Massachusetts General Hospital (MGH) or Brigham and Women’s Hospital (BWH) after percutaneous or mucus membrane exposure to bodily fluids from patients infected with HCV (anti-HCV (+) and/or HCV RNA (+)) were offered entry into this study. Participants were informed of the Centers for Disease Control guidelines that currently do not recommend PEP for HCV.

Exclusion criteria included (1) pregnancy; (2) neutrophil count, < 1,500 per cubic millimeter; (3) platelet count, <90,000 per cubic millimeter; (4) psychiatric disorder not controlled by medications; (5) positive hepatitis B surface antigen; (6) positive HIV antibody, determined by enzyme immunoassay; (7) severe rheumatologic disorder; (8) baseline evidence of hepatitis C infection (assessed by anti-HCV); (9) malignancy; or (10) other conditions for which, in the opinion of the investigators, peginterferon is contraindicated. Concomitant exposure to HIV or hepatitis B virus (HBV) was not an exclusion criterion, and those who underwent HIV PEP were not excluded. After determination of eligibility, written informed consent was obtained.

Study Design

After determination of eligibility and informed consent, we administered a questionnaire to elicit the type of exposure/injury. High-risk exposure was defined as percutaneous injury with a hollow-bore needle containing blood or scalpel laceration with visible blood.(23) The determination of high or low risk exposure was made on this basis by the study investigators and documented as “high-risk” or “low risk”.

Study drug was offered to subjects who were exposed to potentially HCV-infected blood after percutaneous injury or blood exposure on mucus membrane (conjunctival or oral mucosa). Blood on intact skin was considered low-risk, and, therefore, treatment was not recommended. Other unusual injuries/exposures were included on an individual basis by study physicians.

Enrolled HCW were offered PEP with PEGIFN-alfa-2b 1.0 mcg/kg SQ weekly, the FDA-approved dose for HCV monotherapy, for 4 weeks within a 7-day period after exposure. A four week duration of therapy was chosen as it was felt to be the shortest effective duration as demonstrated by Nomura et al that would also minimize the duration of exposure to interferon and its side effects.(22) Ribavirin was not included in the study protocol because of concerns about the high number of women of childbearing age in this cohort. HCV PEP was available only through this study protocol. Those electing treatment had injection technique reviewed by the study nurse. HCW were also counseled about the transmission risk, availability of successful antiviral treatment for acute infection, and the potentially self-limited nature of acute infection. HCW who declined PEP entered the routine follow-up algorithm offered by the Partners Occupational Health Services, which included serial laboratory testing for evidence of HCV infection and quality-of-life assessments, as detailed below.

In addition to the usual laboratory tests obtained by Occupational Health (anti-HCV antibody at week 0, HCV RNA at weeks 0, 4 and 12), urine beta-HCG and complete blood count with differential were measured prior to consideration of study medication treatment. HCV RNA was assessed by Roche Amplicor qualitative RT-PCR (lower limit of detection 60 IU/mL).

At week 4, all enrolled patients underwent qualitative HCV RNA testing (regardless of whether they elected treatment). If HCV RNA was detectable, subjects were referred to Hepatology for consideration of intensified antiviral therapy; if HCV RNA was negative for patients in the treatment arm, then peginterferon was discontinued.

At week 12 and 24, qualitative HCV RNA was repeated in all subjects. If positive, the subject was referred for intensified antiviral therapy. Week 24 HCV RNA testing was obtained to exclude the possibility that early prophylaxis with PEGIFN delayed, rather than prevented, the onset of HCV infection.

The presence of leukopenia, thrombocytopenia, and alterations in thyroid stimulating hormone (TSH) were assessed by testing complete blood count (CBC) and TSH at baseline and weeks 1, 2, and 4.

Adverse events were recorded. Study nurses attempted to contact subjects by phone after each dose of PEGIFN, and study participants were encouraged to call Occupational Health Services or the study nurses if adverse events occurred. In addition, all who elected PEP were assessed at weeks 1, 2, and 4, for adverse events. A serious adverse event was defined using the Food and Drug Administration guidelines and included death, life threatening event, hospitalization, persistent or permanent disability, congenital anomaly, or requirement for intervention to prevent permanent impairment.

Baseline quality-of-life (QOL) measurements were obtained with a modified SF-36 instrument. These questionnaires were administered to consenting subjects irrespective of PEP election status at weeks 0, 4, 12, and 24.

Statistical Analysis

The primary endpoints of the trial were (1) election rate of PEP for all HCW exposed to HCV; (2) safety and tolerability of PEG IFN; and (3) quality-of-life measures at week 0, 4, 12, and 24 weeks.

This trial was not designed nor powered to demonstrate efficacy of PEG-IFN for post-exposure prophylaxis. The trial was performed by an intention to treat analysis.

This study was approved by the Partners Human Research Committee.

RESULTS

Characteristics of Exposed Healthcare Workers

During implementation of the HCV PEP protocol from July 2001 to September 2006, 2,702 HCW were identified with potential exposures to blood-borne pathogens at MGH and BWH Among these, 213 (7.9%) were exposed to an HCV-positive source; of these, 77 (36%) were considered high-risk exposures. The proportions of HCV-positive exposures during the treatment phase are comparable to those during the pre-HCV PEP period.

Of the 213 HCW informed by Occupational Health Services of the availability of post-exposure prophylaxis, 51 (24%) contacted us electively for possible participation in the study protocol. All 51 evaluated subjects met eligibility criteria for study participation; 25 (49%) had high-risk and 26 (51%) had low-risk exposures (Figure 1). In contrast, of the remaining known HCV-positive exposures, 38/162 (23%) were considered high-risk exposures (p=0.001;). Forty-four of the 51 who enrolled in the study elected to receive post-exposure prophylaxis; including 21/25 (84%) with high-risk exposures and 23/2 (88%) with low-risk exposures. All patients had percutaneous exposure to blood; no other infectious fluid exposures were reported. Based on the definition of “high risk” noted above, once enrolled, patients were documented as having “high risk” or “low risk” exposures. Details of the exposures were available for 41 subjects. Five subjects suffered scalp lacerations with visible blood, 17 had hollow bore needle sticks, and 1 was lacerated with a Bovie tip with visible blood, all considered high risk. Eighteen subjects had solid bore needle exposures from suture needles, all considered low risk. The majority of the 44 who elected to receive PEP were physicians, 60.7%, followed by registered nurses 28.6%, and medical students or nursing assistants10.7%. Twenty-one of 44 (47%) subjects who received peginterferon were administered concomitant PEP for human immunodeficiency virus (HIV). Administration of HIV PEP was discontinued, per Occupational Health Services protocol, when source-patient anti-HIV testing was negative.

Figure 1.

Figure 1

Open in a new tab

Schema of HCW Exposed to an HCV Positive Source

Characteristics of Source Patients

The mean HCV RNA for source patients was 460,649 IU/mL (SD 299470). Genotype was available for 10 patients; 5 patients had genotype 1, three patients had genotype 2 and two patients had genotype 3. No patients were receiving hepatitis C therapy at the time of the needlestick exposure. One source patient was infected with HIV and receiving antiretroviral therapy. Two patients were hepatitis B surface antigen positive, only one of whom had detectable hepatitis B DNA. Neither were undergoing hepatitis B treatment.

Post-Exposure Prophylaxis Completion

Twenty-nine of 44 (66%) who elected PEP completed all 4 weeks of PEG IFN. All surveillance HCV RNA assays, among both those who elected and who declined post-exposure prophylaxis, at weeks 0 and 4, (including those who received < 4 weeks of treatment) were negative. One patient received one dose of PEGIFN but was lost to follow-up after one week and had no lab work done. Four patients completed treatment but had only partial post-treatment follow-up (4, 7, 9 and 13 weeks after treatment completion). All HCV RNAs were negative at these time points. The remaining patients had HCV RNAs done 24 weeks after the completion of therapy. Of the 18 (38%) who chose PEP but did not complete 4 weeks of treatment, reasons for discontinuation included side effects that interfered with work (fatigue, n=1); insomnia (n=1), chest pain (n=1), pre-existing flu-like symptoms (n=2); rash (n=1); nausea and vomiting (n=1) a subject’s plan at the time of enrollment to take only 2 weeks of PEP (n=3); and undetectable HCV RNA in the source patient (n=2). Six patients did not give reasons why they discontinued treatment.

Anti-HCV seroconversion or acquisition of hepatitis C viremia

None of the 44 subjects in the Treated Group who received post-exposure prophylaxis experienced hepatitis C viremia or anti-HCV seroconversion at the end of treatment or at 4 weeks following treatment. Additionally none of the 40 study subjects in the Treated Group who completed 24 weeks of follow-up developed hepatitis C viremia or ant-HCV seroconversion. Similarly, over the same time period, none of the seven subjects in the Untreated Group who did not receive PEP experienced hepatitis C viremia or anti-HCV seroconversion. Notably, none of the remaining 162 HCWs exposed to known anti-HCV positive source patients acquired HCV. Thus, there was no transmission of HCV in any exposed HCWs during our study period.

Adverse events

The 44 subjects who received PEP had side-effect profiles completed at week 4. Flu-like symptoms were the most common complaint occurring in 41 subjects (93%). Flu-like symptoms prevented work in 10 (23%) subjects, who missed an average of 1.8 days of work. Headache and injection site irritation occurred in 31 (70%) and 26 (59%) subjects, respectively. Depressed mood occurred only in 3 subjects. A rash developed in two subjects; one discontinued treatment, after which the rash resolved, while the other was able to complete treatment. One subject developed chest pain after his first dose and was diagnosed with likely esophageal spasm, after which he discontinued treatment. The average duration of symptoms was 2 weeks.

Thrombocytopenia did not occur. Two subjects had an elevated baseline TSH that was followed by an endocrinologist. Leukopenia occurred in 15 (34%) subjects during treatment. Four subjects had a WBC nadir below 3,000 cells/mm3, all of whom improved despite continuation of therapy. No subjects required peginterferon dose adjustments and no serious adverse events occurred. (moved this to Methods)

Quality-of-life measurements

Forty-five subjects completed the QOL measurements through the 24-week follow-up period. Of the 45 who completed these questionnaires, 3 had declined post-exposure prophylaxis.

The majority of screened subjects (86%) elected post-exposure prophylaxis, which limited our ability to compare QOL measurements between screened subjects who elected and declined post-exposure prophylaxis. In addition, because the decision to accept treatment was left to the subject, the QOL comparison between treated and untreated subjects may have been confounded by subject self-selection. Still, we observed that, among the 45 subjects who completed questionnaires through week 24, 39 (86%), 5 (11%), and 1 (2%) reported that their health had an impact on their ability to perform work none, some, and all of the time, respectively; 38 (84%) reported that treatment side effects had no or minimal impact on their social activities, and only 6 (13%) reported “feeling blue a good bit of time,” one of whom declined post-exposure prophylaxis.

DISCUSSION

There are two major findings of this pilot study. First, over a two-year period we observed no HCV transmission events among 213 HCWs exposed to anti-HCV positive source patients. While 44 of these HCWs did receive peginterferon, the remaining 163 did not. Thus, it appears in our two institutions that the frequency of HCV transmission is lower than cited in most reports and appears to be closer to the lower figures cited by Chung et al.(1). Thus, any potential benefit of peginterferon as a PEP agent could not be discerned.

Secondly, among those receiving peginterferon, the regimen was safe. However, it did affect quality of life, and resulted in premature discontinuation in 30% of HCWs. One difference between the group of HCW entering our study and the group that did not enter our study were the rates of high risk exposures. The group contacting our study for possible PEP had significantly more high risk exposures than the overall group of HCW undergoing exposures. This increased likely reflects a volunteer bias with patients with higher risk exposures having a predisposition to enroll in a PEP study. Despite the higher risk exposures of our patients, no transmission of HCV was seen. While it is possible that a transmission was averted in the group receiving PEG because it was higher risk, this can not be proven in a small, uncontrolled sample.

Based on these findings, given the low frequency of transmission, the high adverse event rate and impaired quality of life, and the effectiveness of peginterferon for acute HCV infection, we do not recommend routine PEP with peginterferon for occupational exposures. Careful surveillance in the immediate post exposure period will be important to detect and optimally manage the rare case of occupational transmission of HCV.

Finally, despite the arguments for watchful waiting, the relatively high rate of election of an unproven agent, PEGIFN, on the part of HCWs, indicates the strength of the desire on the part of HCWs to seek PEP against HCV. The development of targeted antiviral drugs against HCV such as polymerase or protease inhibitors will be an important advance not only for management of chronic infection, but will also provide considerably more rational agents for post-exposure prophylaxis. It would therefore appear to be a reasonable recommendation to defer routine PEP regimens with peginterferon until these agents are available.

Footnotes

Potential Conflicts of Interest: Schering-Plough provided partial support as well as peginterferon for this trial. RTC has received grant support from Schering-Plough and from Roche Laboratories. KEC has received funding from Bristol-Myers Squibb. JCS has received funding from Bristol-Myers Squibb and from the AASLD/Schering Advanced Hepatology Fellowship Program. JLD has received research support from Vertex, served as an ad hoc consultant for Achillion Pharmaceuticals, scientific advisory board for Metabasis Therapeutics, the clinical advisory board for Nucleonics, the adjudication committee for Schering-Plough Research Institute, the safety monitoring board for Human Genome Sciences and the ad hoc hepatitis advisory board for Abbott Molecular and Boehringer-Ingelheim.

All remaining authors have no conflicts of interest to report.

References

  • 1.Chung H, Kudo M, Kumada T, et al. Risk of HCV transmission after needlestick injury, and the efficacy of short-duration interferon administration to prevent HCV transmission to medical personnel. J Gastroenterol. 2003;38(9):877–9. doi: 10.1007/s00535-003-1156-1. [DOI] [PubMed] [Google Scholar]
  • 2.Jagger J, Puro V, De Carli G. Occupational transmission of hepatitis C virus. Jama. 2002;288(12):1469. doi: 10.1001/jama.288.12.1469. author reply 1469–71. [DOI] [PubMed] [Google Scholar]
  • 3.Yen T, Keeffe EB, Ahmed A. The epidemiology of hepatitis C virus infection. J Clin Gastroenterol. 2003;36(1):47–53. doi: 10.1097/00004836-200301000-00015. [DOI] [PubMed] [Google Scholar]
  • 4.Takagi H, Uehara M, Kakizaki S, et al. Accidental transmission of HCV and treatment with interferon. J Gastroenterol Hepatol. 1998;13(3):238–43. doi: 10.1111/j.1440-1746.1998.01564.x. [DOI] [PubMed] [Google Scholar]
  • 5.Mitsui T, Iwano K, Masuko K, et al. Hepatitis C virus infection in medical personnel after needlestick accident. Hepatology. 1992;16(5):1109–14. [PubMed] [Google Scholar]
  • 6.Puro V, Petrosillo N, Ippolito G. Risk of hepatitis C seroconversion after occupational exposures in health care workers. Italian Study Group on Occupational Risk of HIV and Other Bloodborne Infections. Am J Infect Control. 1995;23(5):273–7. doi: 10.1016/0196-6553(95)90056-x. [DOI] [PubMed] [Google Scholar]
  • 7.Sartori M, La Terra G, Aglietta M, Manzin A, Navino C, Verzetti G. Transmission of hepatitis C via blood splash into conjunctiva. Scand J Infect Dis. 1993;25(2):270–1. doi: 10.3109/00365549309008497. [DOI] [PubMed] [Google Scholar]
  • 8.Ippolito G, Puro V, Petrosillo N, De Carli G, Micheloni G, Magliano E. Simultaneous infection with HIV and hepatitis C virus following occupational conjunctival blood exposure. Jama. 1998;280(1):28. doi: 10.1001/jama.280.1.28. [DOI] [PubMed] [Google Scholar]
  • 9.Updated U S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm Rep. 2001;50(RR-11):1–52. [PubMed] [Google Scholar]
  • 10.Dore GJ, Kaldor JM, McCaughan GW. Systematic review of role of polymerase chain reaction in defining infectiousness among people infected with hepatitis C virus. Bmj. 1997;315(7104):333–7. doi: 10.1136/bmj.315.7104.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Beltrami EM, Williams IT, Shapiro CN, Chamberland ME. Risk and management of blood-borne infections in health care workers. Clin Microbiol Rev. 2000;13(3):385–407. doi: 10.1128/cmr.13.3.385-407.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Krawczynski K, Alter MJ, Tankersley DL, et al. Effect of immune globulin on the prevention of experimental hepatitis C virus infection. J Infect Dis. 1996;173(4):822–8. doi: 10.1093/infdis/173.4.822. [DOI] [PubMed] [Google Scholar]
  • 13.Sanchez-Quijano A, Pineda JA, Lissen E, et al. Prevention of post-transfusion non-A, non-B hepatitis by non-specific immunoglobulin in heart surgery patients. Lancet. 1988;1(8597):1245–9. doi: 10.1016/s0140-6736(88)92071-5. [DOI] [PubMed] [Google Scholar]
  • 14.Alter MJ. Occupational exposure to hepatitis C virus: a dilemma. Infect Control Hosp Epidemiol. 1994;15(12):742–4. doi: 10.1086/646850. [DOI] [PubMed] [Google Scholar]
  • 15.Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347(13):975–82. doi: 10.1056/NEJMoa020047. [DOI] [PubMed] [Google Scholar]
  • 16.Jaeckel E, Cornberg M, Wedemeyer H, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med. 2001;345(20):1452–7. doi: 10.1056/NEJMoa011232. [DOI] [PubMed] [Google Scholar]
  • 17.Hwang SJ, Lee SD, Lu RH, et al. Hepatitis C viral genotype influences the clinical outcome of patients with acute posttransfusion hepatitis C. J Med Virol. 2001;65(3):505–9. [PubMed] [Google Scholar]
  • 18.Corey KE, Ross AS, Wurcel A, et al. Outcomes and treatment of acute hepatitis C virus infection in a United States population. Clin Gastroenterol Hepatol. 2006;4(10):1278–82. doi: 10.1016/j.cgh.2006.06.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Gerlach JT, Diepolder HM, Zachoval R, et al. Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology. 2003;125(1):80–8. doi: 10.1016/s0016-5085(03)00668-1. [DOI] [PubMed] [Google Scholar]
  • 20.Delwaide J, Bourgeois N, Gerard C, et al. Treatment of acute hepatitis C with interferon alpha-2b: early initiation of treatment is the most effective predictive factor of sustained viral response. Aliment Pharmacol Ther. 2004;20(1):15–22. doi: 10.1111/j.1365-2036.2004.02023.x. [DOI] [PubMed] [Google Scholar]
  • 21.Hofer H, Watkins-Riedel T, Janata O, et al. Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load. Hepatology. 2003;37(1):60–4. doi: 10.1053/jhep.2003.50019. [DOI] [PubMed] [Google Scholar]
  • 22.Nomura H, Sou S, Tanimoto H, et al. Short-term interferon-alfa therapy for acute hepatitis C: a randomized controlled trial. Hepatology. 2004;39(5):1213–9. doi: 10.1002/hep.20196. [DOI] [PubMed] [Google Scholar]
  • 23.Sulkowski MS, Ray SC, Thomas DL. Needlestick transmission of hepatitis C. Jama. 2002;287(18):2406–13. doi: 10.1001/jama.287.18.2406. [DOI] [PubMed] [Google Scholar]

RESOURCES