Epidemiology, Natural History, and Diagnosis of Hepatitis C

Receipt of Infected Blood or Blood Products

In the United States, before heat treatment of plasma products became a routine practice in 1987 and universal screening of blood donors for HCV was implemented in 1992, these products were the source of many HCV infections. Recipients of multiple transfusions of blood and blood products from unscreened donations have prevalence rates reaching 95%. This route of transmission accounts for a considerable share of the infection among the aging population of persons born from 1945 to 1965 (i.e., “baby boomers”), who comprise the largest percentage of the almost three million Americans who are estimated to be currently living with HCV infection. This same epidemiologic pattern is seen in most developed countries. However, in countries where blood donations are not routinely screened for HCV, transfusion is still an important mode of transmission. The most recently reported data from the World Health Organization's (WHO's) blood safety survey of 164 countries in 2008 revealed that blood donations in 39 countries were not routinely tested for transfusion-transmissible infections (TTIs), including HCV.

Moreover, the median prevalence rate of TTIs in blood donations was much higher in resource-constrained areas (middle- and low-income countries) than in developed (high-income) countries. The survey also found that compared with previous years, of the 23 countries reporting a greater than 10% decrease in voluntary unpaid blood donations (a practice that can reduce the risk of infection from TTIs in contrast to family/replacement and paid donations), all were resource-constrained. Use of particular testing assays with lower sensitivity and poor quality control procedures, as can occur when appropriate equipment and reagents for HCV screening are unavailable, can also impact the ability to detect HCV and is more of a concern in resource-constrained areas.

Occupational Transmission Among Healthcare Workers

Occupational transmission of HCV among healthcare workers is uncommon. Cases of HCV seroconversion, typically from accidental needle sticks, have been documented in developed countries, although the reported seroprevalence is low with estimates ranging from 1% to 2%. A recent U.K. study examining 1997 to 2007 surveillance data to determine factors associated with HCV transmission among healthcare workers demonstrated a seroconversion rate of 1.8% to 2.2%. Similar to a prior study in Europe, the researchers found that the depth of the puncture injury to the healthcare worker was a relevant factor in transmission; when the injury was deep, it was significantly and independently associated with HCV seroconversion.

Healthcare Settings

Transmission of HCV in healthcare settings is common in many resource-constrained countries, and unsafe injections in these settings are a leading cause of HCV transmission worldwide. Egypt is notable for one of the largest epidemics of HCV infection in the world, widely attributed to the reuse of syringes during a program in the 1960s and 1970s to eradicate schistosomiasis. In developed countries, where infection control and safe injections are generally practiced in healthcare settings, nosocomial HCV transmission is infrequent. However, even in developed countries, lapses in infection control and safe-injection practices can occur, particularly in nonhospital healthcare settings; several outbreaks have been identified in such settings throughout the world. Hemodialysis centers have historically been important settings for HCV transmission in many countries. Estimates of HCV infection among hemodialysis patients vary, ranging from 9% to 31% in recently published studies, with the highest prevalence reported from developing countries. In 2002, HCV prevalence among hemodialysis patients in the United States was 7.8% ; more recent survey data are lacking. Of 16 U.S. outbreaks resulting in transmission of HCV identified by CDC between 1998 and 2008, six occurred in hemodialysis centers; the remainder involved other healthcare settings, such as private physician offices and endoscopy and pain remediation clinics. The U.S. outbreaks were ascribed to lapses in infection control, as investigations revealed the practice of syringe reuse (which resulted in the contamination of vials later used for other patients) and preparation of injections in a contaminated environment. From 2008 to 2014, an additional 22 outbreaks of HCV infection were identified and investigated by CDC, 11 of which were in hemodialysis settings. Similar to previous outbreaks, most involved reuse of syringes, although two of the outbreaks were attributed to drug diversion by HCV-infected healthcare providers, the largest of which involved transmission to dozens of patients from 16 facilities across eight states.

Injection Drug Use

Drug injection can efficiently transmit HCV. The virus spreads quickly once it has been introduced into a network of drug injectors through sharing contaminated needles or syringes or other injection-related equipment, such as cookers, cotton, and rinse water. Not unexpectedly, the higher the prevalence of HCV infection within a drug-injection network, the greater the risk of transmission.

Globally, an estimated 67% of PWIDs, or 10 million persons, have been infected with HCV. In the United States and other developed countries, injection drug use is the predominant mode of transmission, accounting for most new HCV infections. In developing countries, injection drug use is also a major mode of HCV transmission, particularly among countries with economies in transition. Data from a study of countries in the WHO European Region, but outside the European Union/European Free Trade Association, showed an average HCV antibody (anti-HCV) prevalence of 46% among PWIDs. Another study of data from 77 countries revealed an estimated anti-HCV prevalence among PWIDs of 60% to 80% in 26 countries and greater than 80% in 12 countries. Along with the United States, China and Russia had the largest populations of PWIDs; anti-HCV prevalence among these populations was estimated to be 73.4%, 67.0%, and 72.5%, respectively. A more recent systematic review found that among all HCV-related risk factors examined, injection drug use exhibited the strongest association with HCV infection globally. A further study that undertook an assessment of the global burden of disease attributable to illicit drug use found that as a risk factor for hepatitis C, injection drug use accounted for an estimated 502,000 disability-adjusted life years (DALYs).

Sexual Transmission

Sexual contact has been considered a potential route of HCV transmission, although the evidence for the magnitude of this risk has been mixed and varies by study design and populations studied. The epidemiology of HCV infection among the general population does not support sexual contact as a major route of transmission. In a review of articles published during 1995 to 2009, researchers found no evidence to support sexual transmission among heterosexual couples in regular relationships, but did find an increased risk among persons with multiple sex partners (although this risk could not be distinguished from possible coincidental injection drug use), as well as an increased risk among women coinfected with HIV or other sexually transmittable diseases (STDs) and HIV-infected men who have sex with men (MSM). More recent findings support the very low estimated risk of sexual transmission of HCV among monogamous heterosexual couples. The risk of sexual transmission has been explored most extensively among MSM who have been shown to be at highest risk. These studies have found that sexual transmission of HCV is most likely to occur among HIV-infected MSM who engage in high-risk sexual behaviors, concurrently use noninjection recreational drugs, have multiple sex partners, or have concomitant ulcerative STDs. These findings support the role of mucous membrane exposure in HCV transmission, as having multiple sex partners, engaging in rough sex, and having ulcerative STDs can cause mucosal injury and, in the absence of injection drug use, facilitate sexual transmission of HCV.

Vertical Transmission

Vertical transmission of HCV from an infected mother to her newborn has received considerable study and is the most common source of exposure to infants (and children) in developed countries. Certain factors increase the risk of mother to child transmission of HCV. The most recent systematic review and meta-analysis of data from 109 studies found that the risk of HCV transmission from mother to infant was 5.8% among HCV antibody-positive and HCV-RNA positive women who were HIV-negative; maternal coinfection with HIV increased this risk to 10.8%. Mother's level of viremia also is associated with risk of HCV infection: vertical transmission rarely occurs among infants of HCV-RNA-negative mothers, whereas infants born to mothers with a viral load of approximately 5 log IU/mL or greater have a 14% risk of infection. Other factors have been found to be associated with risk of vertical transmission, including rupture of amniotic membranes during childbirth. A systematic literature review yielded one high-quality study reporting a ninefold increase in HCV transmission after prolonged rupture (≥6 hours) of the amniotic membranes during labor. Risks also are posed by internal fetal monitoring, although neither breastfeeding nor mode of delivery (i.e., vaginal vs. cesarean) has been associated with increased risk.

Other Exposures

Both tattooing and body piercing have been investigated as practices that could transmit HCV. Because instruments used for tattooing and piercing can come into contact with potentially contaminated blood, blood-borne infections such as HCV can be transmitted in the absence of disposable instruments or proper sterilization and maintenance of multiple-use instruments. A global systematic review and meta-analysis found an association between tattooing and HCV infection ; an even stronger association was observed among the subgroup of non-PWIDs. Although a study carried out in the Netherlands showed no relationship between persons with multiple tattoos and/or piercings and HCV-antibody positivity, the prevalence of HCV infection in the total population was low. A more recent global literature review was conducted to evaluate the risk of HCV transmission from tattooing and piercing in which risk of HCV infection from tattooing was examined separately for populations with varying levels of overall HCV infection risk (i.e., the general population, blood donors, prisoners, and veterans). The data were also analyzed by whether tattooing or piercing was performed in a professional setting (licensed and regulated by health authorities) or a nonprofessional setting (unlicensed and potentially nonsterile; by friends, at home, or in prison). The researchers found no association between tattooing and risk of HCV transmission when these procedures were performed in professional settings, but an increased risk was demonstrated when tattoos were applied in nonprofessional, unregulated settings (e.g., in prisons or by friends), particularly among high-risk groups.