Iatrogenic Hepatitis C Virus Transmission and Safe Injection Practices

Iatrogenic HCV Transmission Risks and Epidemiology

While there is no vaccine for HCV, there are effective treatment options.^3,11 Until 2011, combination treatment with interferon-α and ribavirin was the only available option for patients with HCV infection.¹ Since that time, antivirals and protease inhibitors that are HCV specific and have fewer adverse effects have become first-line treatment for patients with HCV infection, and treatment is based on which of the 7 HCV genotypes is present in a patient.^12-14 The classic genotype found in the United States is genotype 1, which can be treated in 1 of 4 ways determined by further classification of the subtype, nonstructural protein 5A resistance, and a patient's history of cirrhosis. For example, to treat patients with HCV genotype 1A without cirrhosis, a once-per-day combination tablet of sofosbuvir (400 mg) and ledipasvir (90 mg) for 12 weeks is a level-A recommendation.^12,14 The presence of liver cirrhosis and other comorbidities not only indicates the need for aggressive, urgent treatment but can also indicate different treatments for appropriate management.¹⁴ Use of the recommendations by the American Association for the Study of Liver Diseases and the Infectious Disease Society of America to select the most appropriate therapy based on the patient's specific infection genotype, viral resistance, and symptom profile is highly recommended.¹⁴

Identification and treatment does not always occur, however, because significant adverse health effects often take decades to develop, leaving a significant asymptomatic window for disease transmission.^1,4,6,11,15 In 2009, a review article¹⁵ reported that in 25% of HCV-infected persons, the infection progressed to display acute hepatitis with symptoms such as jaundice.

The CDC's screening recommendations for HCV infection try to take advantage of the large asymptomatic window to initiate effective treatment.¹⁵ These recommendations include screening all patients in any of the following categories^4,10:

• ■ Birth between 1945 and 1965

• ■ History of injectable drug use

• ■ Recipient of clotting factor concentrates before 1987

• ■ Recipient of blood transfusions or organ transplants before 1992

• ■ History of long-term dialysis

• ■ Infection with HIV

• ■ Elevation in alanine aminotransferase level

• ■ Known HCV exposure

• ■ Born to HCV-positive mother (screening of these patients must occur at age ≥18 months)

The calculated 130 to 170 million people with HCV infection globally, representing a 2.2% to 3% global prevalence (the CDC's 2014 US estimated prevalence was 2.7-3.9 million people), represents a serious health concern.^4,15,16 The asymptomatic window of HCV infection makes it especially important to understand the potential risk factors that indicate screening and, potentially, treatment. In the case of an HCV outbreak, reporting cases of HCV infection to the CDC to prompt an investigation could help to identify an iatrogenic source patient and others who may be linked to the transmission. Although screening and treatment can be effective for many patients, prevention is of paramount importance in protecting patients from the health risks associated with HCV infection.^1,4 Implementing safe injection practices is an important way medical professionals can take personal responsibility to reduce the risk of iatrogenic HCV transmission.

Historically, iatrogenic HCV infection proliferated through blood transfusions and organ transplantations before 1992, when donations began to be screened in the United States.⁹ Abundant improper use of glass syringes for vaccinations, insulin, and antibiotic injections further contributed to iatrogenic HCV transmission at the end of the 20th century.⁹ Currently, injection drug use has become the major contributor to the epidemic of HCV transmission.^4,9 Similarly, any medical procedure that involves injections during which contaminated equipment could be used poses a risk for HCV transmission.⁴ Iatrogenic HCV transmission has been reported in various outpatient settings, including hospitals and clinics for alternative medicine, cardiology, dialysis, endoscopy, insulin infusion, pain management, oncology, and prolotherapy.^5-7,17-23 The known or suspected mode of transmission includes syringe reuse, fingerstick device reuse, single-dose vial reuse, infection control lapses in medication preparation, drug diversion, and breaches in environmental cleaning and disinfection practices.^17,18 Adherence to injection safety procedures would effectively eliminate this transmission risk.

Iatrogenic HCV Transmission: A Common and Widespread Problem

A report¹⁹ released in 2009 documented 16 HCV outbreaks in the previous decade at a variety of health care facilities, leading to 275 patients acquiring iatrogenic HCV infection. Another review article²⁰ cataloged 35 reports of injection safety violations between 2001 and 2011 that required patient notification related to bloodborne pathogen risk. These 35 reports were from 17 states as well as Washington, DC, and resulted in notification of an estimated 130,198 patients.²⁰ Look-back investigations like these are conducted on a case-by-case basis with CDC guidance (Table 1).^20,21

Iatrogenic HCV outbreaks can be avoided by adherence to the CDC's safe injection practices.²⁴ Despite the best efforts of those involved in these lookback investigations or notification events, including state regulatory medical boards, often with help from the CDC, cases of potential infection with HCV and other bloodborne pathogens sometimes remain undetected. Investigations that show a difference between the number of patients notified and the number of patients screened demonstrate the presence of unscreened patients who may be infected with HCV. These patients are not only at risk for the adverse effects of the virus, they present a risk to the community because of possible further viral transmission.^8,19-20,23

Guidelines for Safe Injection Practices: Preventing Iatrogenic HCV Transmission

A list of evidence-based guidelines for safe injection practices that were established by the CDC in 2007 and reaffirmed in 2012 is presented in Table 2.^24,26,27 These guidelines have been promoted by the Safe Injection Practices Coalition,^2,27,28 started in 2009, with the associated One & Only Campaign, which recommends using 1 needle and 1 syringe for only 1 patient.²⁹

Physicians can evaluate their procedures using the CDC injection safety checklist at https://www.cdc.gov/injectionsafety/pdf/sipc_checklist.pdf.³⁰ These guidelines have an accord with the World Health Organization's (WHO) guidelines for safe injection practice published in 2010.¹¹ The WHO guidelines place particular emphasis on the use of an aseptic technique, including hand hygiene, disinfecting the skin at the site of venipuncture, and glove use (1 pair of gloves per procedure or patient). The WHO guidelines also reinforce the CDC's injection safety guidelines in the following areas: the advisement of 1 sharp³¹ used per procedure, with immediate disposal of the used sharp in a designated sharps container with a tamperproof lid; encouragement to assume that damaged or opened medical equipment has been used and cannot be used again; and recommendation to avoid the use of multiuse vials and, if used, to discard contaminated vials immediately.¹¹ Some notable additions in the WHO guidelines are the recommendation to use 1-handed methods whenever possible, to avoid unneeded injections, such as oral or rectal routes of medication administration, and to report accidents immediately.¹¹ For most bloodborne pathogens, it is recommended to start postexposure prophylaxis within 72 hours. However, HCV is unique because, as the WHO guidelines point out, there is no postexposure prophylaxis or vaccine for HCV; the only response to exposure is to perform baseline testing for antibodies to HCV and alanine aminotransferase levels so that appropriate treatment can begin.¹¹

Analysis of a 2014 iatrogenic HCV outbreak in Tennessee showed how the Tennessee Department of Health properly used the CDC guidelines to evaluate the dialysis facility where the suspected source patient was identified.³² The facility was found to have no visible blood; sinks were available for hand hygiene, glove use was observed; dialysis stations were properly disinfected between patients; medications were observed to be prepared for specific patients away from patient areas; and multidose vials were not allowed in treatment areas and were only used in a separate clean room to maintain sterility. Although 2 cases of iatrogenic HCV spread were identified as linked to treatment at this dialysis center, no violation of the CDC's injection safety guidelines was detected.³²

During a 2007 New York State HCV infection outbreak investigation, 2 distinct groups of iatrogenic HCV-infected patients were identified.³³ This investigation was initiated after a patient from the first group reported having acute symptoms, which started the process of notification and screening for bloodborne pathogens.^20,33 Most patients with chronic HCV infection are asymptomatic, as were all of the patients in the second group discovered during this investigation.^6,19 This second group of patients would likely not have been identified if a concurrent local investigation had not been initiated.^20,33 Therefore, a reasonable medical professional cannot rely solely on using injection safety guidelines for documented HCV infection.^4,5,19

Step 3 in the Figure shows that replacement of just the needle does not remove the HCV infection risk from the contaminated syringe.^20,24,28 This concept also applies to the use of IV bags, tubing, and connectors, which must also be changed between every patient in addition to replacement of the needle that punctured the skin.⁵ Research has shown that check valves and needle exchanges do not reduce the risk of contamination back to IV bags and tubing.⁵ Single-dose vials also cannot be used more than once, as shown in step 4 in the Figure.^24,28 These vials lack preservatives and are an environment in which bacteria or viruses have a high potential to multiply and compromise the vial,^2,26 leading to iatrogenic infection if that vile is used for another patient.^24,28

Figure.

Iatrogenic hepatitis C virus infection through contamination and multiple uses of a single-use vile. Replacing the needle does not remove the risk of iatrogenic spread owing to contamination of the vial from the contaminated syringe.³⁴ Source: Centers for Disease Control and Prevention. Acute hepatitis C virus infections attributed to unsafe injection practices at an endoscopy clinic--Nevada, 2007. MMWRMorb Mortal Wkly Rep. 2008;57(19):513-517.

Patient-to-patient transmission in the health care environment is the major concern of the CDC guidelines, the One & Only Campaign, and the WHO guidelines, but preventing transmission to patients from clinicians is another way to reduce the iatrogenic spread of HCV. The Society for Health Care Epidemiology of America (SHEA) compiled a list of evidence-based guidelines to reduce the risk of clinician-to-patient transmission of bloodborne pathogens.^3,35 Although SHEA states that infected clinicians pose almost no risk to patients, it also states that this low risk applies to noninvasive procedures or an infected clinician whose infection is well controlled.^3,35 The SHEA guidelines recommend that if a clinician's viral load is greater than or equal to ×10⁴ GE/mL, he or she should wear 2 pairs of gloves and should not perform category-3 procedures, during which there is a high transmission risk.^3,35 Category-3 procedures include general surgery, general oral surgery, cardiothoracic surgery, open extensive head and neck surgery, neurosurgery, emergency surgery, obstetrics and gynecology, orthopedic surgery, transplantation, plastic surgery, trauma intervention, and any open surgical procedure longer than 3 hours, as well as situations in which there is a risk of a patient biting a clinician.^3,35

Clinicians who know that they have a bloodborne pathogen such as HCV are ethically obligated to monitor their own viral load and submit to twice-per-year testing.^3,35 It is also recommended that infected clinicians have the results analyzed by a physician who can initiate proper viral load-reducing treatment and report the results to a review panel to regulate the infected clinician's practice scope.^3,35 A lookback study can be initiated if proactive reporting identifies a clinician who may have a viral load that could put patients at risk,^3,35 if there is a suspected or recorded clinician-to-patient transmission event, if a clinician's viral infection is linked to a viral burden beyond the stated limits, or if recommended screening determines that a clinician was involved in category-3 procedures while having a viral load beyond the stated limits.^3,35 Prevention of iatrogenic clinician-to-patient HCV transmission additionally involves identifying clinicians who are impaired owing to the use of injectable drugs in or outside the workplace.^18,20 A total of 13,162 patients were notified of bloodborne pathogen risk in notification events associated with clinician drug diversion of fentanyl in 2004, 2009, and 2010.^18,20 Policies that prevent diversion include locking medications in schedule II through V categories securely in accordance with the Comprehensive Drug Abuse Prevention and Control Act of 1970,¹⁸ using tamper-resistant syringes, testing wasted drugs to confirm whether they are narcotics, and labeling prefilled syringes with patient identification.¹⁸ Drug diversion by clinicians must be reported to regulatory agencies, and the clinicians need to be referred to the State Medical Licensing Board's physician health program for rehabilitation.^18,20

Legal and Regulatory Ramifications of Iatrogenic HCV Infection

Clinician-focused laws require clinicians, independent or within medical institutions, to follow CDC infection prevention procedures, such as the 2007 guidelines for safe injection practices.^2,24,25,36 These guidelines are part of the standard of care defined legally as the actions consistent with what “a reasonable provider would (execute) under the same circumstances.”³⁶ There is a duty to report violations of the CDC's infection control guidelines.³⁶ Proactive reporting is important to limit the negative effects of specific violations of infection control guidelines. The notification events mentioned previously could have been reduced in scope if the unsafe practices were stopped earlier through proactive reporting. One review article reported that 63% of iatrogenic HCV infection cases were discovered after identifying an acute case of HCV infection, and 37% were discovered by direct observation and proactive reporting.²⁰ Administrators of health care facilities need to be aware that legal regulations define health care facilities as accountable to establish and maintain programs for patient safety.³⁶ When there is a violation of safe injection practices, the clinicians involved need to be reported to their state licensing board, and they are subjected to 3 types of legal ramifications: state law, criminal law, and tort law.³⁶

State law establishes the responsibility for practicing health care and averting preventable harm,³⁶ primarily through establishing requirements for licensure, such as completion of accredited medical training and continuing medical education requirements.^32,36 Facilities can be subjected to inspection to promote safe clinical settings for medical practice.³⁶ Patient files may also be accessed to investigate violations of the standard of care because of the public health exception in the Health Insurance Portability and Accountability Act of 1996.³⁶ Medical license regulation was implemented after a 2007 investigation of iatrogenic HCV spread at a New York outpatient endoscopy clinic.^32,36 An anesthesiologist misused single-use medication to treat several patients and reused the syringes, leading to patient notifications and bloodborne pathogen screenings.³² This anesthesiologist's license was suspended and then revoked in accordance with state laws, which can be implemented if violations of the standard of care produce preventable harm.^25,36 In addition, the New York State Department of Health updated its licensure requirements to include required continuing medical education on the prevention of bloodborne pathogen transmission and developed new accreditation requirements for outpatient clinics that use anesthesia.³² The anesthesiologist filed for bankruptcy during the progression of this case.³⁶

Criminal law ramifications were brought against a physician who reused syringes to save money and was responsible for 9 iatrogenic HCV infections at a Nevada outpatient endoscopy clinic, resulting in the death of multiple patients.³⁷ Second-degree murder was one of the charges brought against this physician, and a jury found him guilty of this and 26 other criminal charges.³⁷ This physician was imprisoned for life, with parole eligibility after 18 years.³⁷ Other possible criminal law repercussions include fines, arrest, or facility closure, with the magnitude of repercussions based on established gravity and intent of the criminal act.³⁶ Charges can focus on the medical professional who committed the crime, but charges can also be brought against any other health care professionals involved.³⁶ In the Nevada case, charges were also brought against the assistant, which resulted in a prison sentence for this person.^36,37 Medical institutions that allow or encourage a crime can also be the focus of criminal charges.³⁶

Tort law works to provide recompense to victims for the adverse effects of standard of care violations.³⁶ A prosecutor must prove all 4 criteria—duty, breach, causation, and damages—to receive compensation under tort law.^36,38 Duty refers to the standard of care; breach establishes that a different action was taken compared with the duty established; causation defines that the defendant caused or is responsible for the breach; and damages outline or quantify the grievances the prosecutor endures because of the defendant's causation.^26,38 Similar to criminal law, clinicians or facilities can be the focus of charges related to tort law.³⁶ Duty can be based on clinical practice-based guidelines, such as the CDC's guidelines for safe injection practices. Clinical practice-based guidelines themselves cannot be entered as evidence if the author of the guidelines is not available to be cross-examined; they would be thrown out as hearsay.^39,40 The document can, however, enter as a statement from an expert witness that asserts the validity of the guidelines as a learned treatise that can then be evaluated by a jury.^39,40 Tort law repercussions for standard of care violations are either compensatory, meaning equal to the damages established, or punitive, meaning increased beyond the current damages already established.³⁶ Preventable harm is thus mitigated by this compensation.

Historically, causation might be difficult to establish, and a tort law case could be dropped for lack of causation; however, genetic analysis has objectified the process of establishing causation.^4,9,19,36 Diagnosis of HCV currently includes an algorithm of screening with serologic antibody testing followed by HCV RNA detection using reverse-transcription polymerase chain reaction (PCR) analysis.^4,6 Genetic analysis of the conserved nonstructural protein 5B RNA nucleotide region using PCR not only acts as a confirmatory diagnostic test but is also used to establish the HCV genetic subtype.^4,6,7 Investigation of an HCV outbreak in 2002 at a hematology and oncology clinic in Nebraska used PCR to show that 95 patients had been infected with HCV genotype 3a.²² This genotype is geographically associated with Russia because of an unsafe measles vaccination program in Russia.⁹ Genotype analysis of a 2015 outbreak at an acute-care general hospital in Texas identified HCV transmission linkage between 2 patients with iatrogenic HCV infections—both with genotype 4a.²¹ This genotype accounts for 1% of the HCV infections in the United States and is geographically associated with Egypt because of a local antischistosomal therapy campaign.^21,41,42 Confirming the genotype not only guides medical management but also serves as evidence to support causation for harms associated with iatrogenic HCV transmission, as well as prompts further investigation.^4,9,19

Polymerase chain reaction can further and more definitively establish genetic similarity when it is implemented to analyze HCV RNA hypervariable regions, such as region E1, also called hypervariable region 1.^{4,6,7,19,23,41} To investigate the HCV iatrogenic outbreak at the Nevada endoscopy clinic, PCR was used to show 98.6% similarity between the E1 region of 1 patient iatrogenically infected and a suspected source patient. The assay also revealed 98.3% to 100% similarity between E1 and 6 other patients, as well as a different suspected source patient.⁶ In North Carolina, PCR was used to investigate iatrogenic HCV infection at an outpatient cardiology clinic, showing similarities of 97.6% to 99.3% among 3 iatrogenically infected patients and the suspected source patient.⁷ Genetic similarity in the hypervariable regions of HCV, as shown in these examples, objectively established that iatrogenic HCV infection was related to a common source patient and a common mechanism of iatrogenic spread, legally establishing a causality link.^4,6,7,19,23

Physician Responsibility for Infection Prevention

The fact that HCV outbreaks related to failure to implement safe injection practices have persisted despite continued efforts to increase patient safety in the clinical environment shows the critical importance of this issue. Iatrogenic HCV transmission is an example of a preventable harm resulting in adverse clinical outcomes for patients, as well as licensure and legal ramifications for the clinicians involved.^{1,2,4-7,32,36} It is the physician's responsibility to “preserve the health and the life of [their] patients” and to “pursue lifelong learning to better care for the sick and to prevent illness.”^42,43 The CDC's One & Only Campaign continues to promote the use of 1 needle, 1 syringe, only 1 time.³⁴ Health care professionals would do well to evaluate their procedures using the CDC injection safety checklist,³⁰ especially in outpatient settings in which a dedicated infection prevention professional may not be available.