INTRODUCTION — Chronic infection with the hepatitis C virus (HCV) is one of the most common causes of chronic liver disease. It is prevalent throughout the world; the main route of transmission is through bloodborne exposure.
This topic will review the epidemiology and transmission of HCV infection. Screening for HCV, the approach to patients with acute HCV, and the clinical features, diagnosis, natural history, and management of patients with chronic HCV infection are discussed separately:
●(See "Clinical manifestations, diagnosis, and treatment of acute hepatitis C virus infection in adults".)
●(See "Screening and diagnosis of chronic hepatitis C virus infection".)
●(See "Clinical manifestations and natural history of chronic hepatitis C virus infection".)
●(See "Extrahepatic manifestations of hepatitis C virus infection".)
●(See "Overview of the management of chronic hepatitis C virus infection".)
●(See "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults".)
●(See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults".)
●(See "Hepatitis C virus infection in liver transplant candidates and recipients".)
Global distribution — Precise estimates of the global prevalence of HCV are difficult to establish because of underdiagnosis, underreporting, and a lack of systematic surveillance in most countries. In 2022, the World Health Organization (WHO) estimated that approximately 58 million people had chronic HCV infection, and approximately 1.5 million new infections occurred each year .
The areas with the highest burden of infection were:
●Eastern Mediterranean region (12 million chronic infections)
●European region (12 million chronic infections)
Moderate burden of infection was reported in:
●Southeast Asian region (10 million chronic infections)
●Western Pacific region (10 million chronic infections)
●Africa (9 million chronic infections)
Lower burden of infection was reported in:
●Americas (5 million chronic infections)
Within these regions, there are differences in the prevalence of HCV by country; as examples, prevalence has been higher in Eastern Europe compared with Western Europe and is higher in West Africa compared with East Africa (figure 1) . The four countries with the highest burden of cases are China, Pakistan, India, and Egypt because of high overall population, high prevalence, or both . Egypt has had very high prevalence related to health care-associated transmission . (See 'Breaches in infection control protocols' below.).
Incidence of new infection — In the United States, the incidence of HCV infection has increased over the past decade. The Centers for Disease Control and Prevention (CDC) estimated 66,700 new HCV infections in 2020, which represented a doubling in incidence since 2013 and a fourfold increase since 2005 (figure 2) . The incidence of HCV increased in all adult age groups from 2013 to 2020 but was greatest was among adults aged 20 to 40 years. This estimated incidence is adjusted for case ascertainment and underreporting, although it may still underestimate the actual incidence of acute HCV infection given the difficulties in diagnosis .
Other studies have also reported a substantial increase in HCV infection rates among young adults in the United States [6,7]. In one surveillance study, the incidence of acute HCV infection in young adults rose faster in nonurban than urban counties, and the majority of infected individuals were White (85 percent) with an even sex distribution .
Injection drug use is the most commonly identified risk factor for new HCV infection in the United States . Accordingly, these HCV incidence trends among young individuals in various urban, suburban, and rural settings have mirrored the epidemic of injection prescription opioid and subsequently heroin and fentanyl use in these areas [8-10]. (See 'Injection drug use' below and "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis", section on 'Epidemiology'.)
As the prevalence of HCV in young females of childbearing age increases, an increase in perinatal transmission is expected. (See "Hepatitis C virus infection in children", section on 'Epidemiology'.)
In contrast, transmission through surgery or transfusion in the United States is extremely rare. Specifically, the number of cases of transfusion-associated acute HCV infection decreased significantly after 1985 and has been reduced almost to zero . Thus, health care-associated hepatitis has had little impact on the change in the incidence of HCV infection. (See 'Bloodborne transmission' below.)
Prevalence of chronic infection — An estimated 2 million individuals have chronic HCV infection in the United States [12,13]. Most newly reported chronic infections are among males, and the age distribution is bimodal, with peaks at ages 20 to 39 years and at 55 to 70 years .
The overall prevalence of chronic HCV infection in the United States has been estimated by analyses of the National Health and Nutrition Examination Survey (NHANES), in which participants, chosen according to an algorithm to produce a representative sample of the noninstitutionalized population of the United States, are tested for antibodies to HCV and viral RNA if positive [12,14]. Between 2013 and 2016, the estimated prevalence of antibodies to HCV was 1.5 percent (reflecting an approximate 3.7 million people with past or current HCV infection), and the estimated prevalence of HCV RNA positivity was 0.9 percent (reflecting approximately 2 million people with current HCV infection) [12,13].
One major limitation of using the NHANES data to extrapolate HCV prevalence is that they do not include individuals who are homeless or incarcerated and thus underestimate the overall prevalence . Based on other surveys, it is estimated that 16 to 41 percent of adult prison inmates have serologic evidence of HCV infection and that 12 to 35 percent have chronic infection [16,17].
Although the peak prevalence of chronic HCV infection had historically been observed among individuals born between 1945 and 1965, prevalence among younger individuals appears to have surpassed that [4,7], consistent with the incidence trends of chronic HCV among younger adults. (See 'Incidence of new infection' above.)
ROUTES OF TRANSMISSION
Bloodborne transmission — Percutaneous exposure to HCV is the most efficient means of transmission. Most patients infected with HCV in the United States and Europe acquired the disease through intravenous drug use or blood transfusion, the latter of which has become rare since routine testing of the blood supply for HCV was begun in 1990 (see 'Blood transfusion' below). Other types of parenteral exposure are important in specific regions of the world .
The outsized importance of the bloodborne route in the transmission of HCV was illustrated by a case-control study of blood donors in the United States, in which HCV exposure (as evidenced by reactive anti-HCV antibody and reported in 2316 individuals) was associated with the following factors :
●Injection drug use – odds ratio (OR) 49.6
●History of blood transfusion in people who did not inject drugs – OR 10.9
●Sex with a person who injected drugs – OR 6.3
●Having been in jail more than three days – OR 2.9
●Religious scarification – OR 2.8
●Having been struck or cut with a bloody object – OR 2.1
●Pierced ears or body parts – OR 2.0
●Immunoglobulin injection – OR 1.6
Injection drug use — Injection drug use with needles or other paraphernalia contaminated with HCV is a primary route of transmission, and in many countries, including the United States, is the most commonly identified source of acute HCV infection (figure 3) .
The efficiency of transmission through injection drug use is reflected by the high rate of anti-HCV antibody detection among people who inject drugs and by outbreaks of HCV infection among such populations. As an example, a 2017 systematic review estimated that, worldwide, the prevalence of anti-HCV antibody reactivity among people who inject drugs was 52 percent; in several countries, the prevalence was estimated to exceed 80 percent . In another systematic review, the mean prevalence of anti-HCV antibody reactivity after one year of injection drug use was 32 percent in resource-rich settings and 59 percent in resource-limited settings . Widespread transmission of HCV can occur rapidly within injection drug communities, as reflected by publicized outbreaks of HCV (and HIV) among opioid injectors in a small rural county in the Midwestern United States and in an urban area in the Northeast [21,22].
Measures to reduce injection drug use and risky injecting behavior, such as needle and syringe exchange programs and medications for opioid use disorder, have been associated with reductions in HCV risk. As an example, in one meta-analysis of predominantly observational studies, opioid agonist therapy was associated with a 50 percent reduction of HCV incidence alone and a 74 percent reduction when combined with high coverage of needle and syringe exchanges . Accordingly, successful opioid agonist therapy has been associated with a reduced risk of HCV reinfection in people who inject drugs with previously treated HCV infection [24,25]. In a meta-analysis of 36 studies with over 6000 person-years of follow-up, the rate of reinfection was lower among those receiving opioid agonist therapy without recent injection drug use (1.4 cases per 100 person-years) compared with those with recent injection drug use, either with or without opioid agonist therapy (5.9 and 6.6 cases per 100 person-years) .
The high risk of HCV infection with injection drug use may be related to the durability of HCV on injection paraphernalia. Viable virus has been recovered from the inside of syringes up to nine weeks after contamination .
HCV infection also has been associated with a history of intranasal drug use, presumably due to blood on shared straws [27,28].
Health care-associated transmission
Blood transfusion — Although blood transfusion was historically a major risk factor for acute HCV infection in the past, donor screening for HCV has nearly eliminated the risk of post-transfusion HCV infection in resource-rich settings. In the United States, the estimated risk of HCV is less than one in a million per unit transfused . However, in certain resource-limited settings, the World Health Organization (WHO) has estimated that up to 25 percent of blood donations do not undergo screening . Blood donor screening is discussed in detail elsewhere. (See "Blood donor screening: Laboratory testing", section on 'Hepatitis C virus'.)
Individuals who received multiple transfusions, such as those with hemophilia or thalassemia, had been at particularly high risk of HCV infection. The prevalence of anti-HCV patients with hemophilia who regularly received concentrates of clotting factors before adequate procedures were used to inactivate viruses was 84 to 100 percent . Following the use of treated or recombinant clotting factors becoming routine, new cases of HCV infection have become uncommon in these patients; the prevalence of anti-HCV antibody reactivity in this population is due to past exposure [31,32].
Organ transplantation — Transplant recipients who receive organs from donors with chronic HCV infection have a high risk of acute HCV infection [33-35]. The use of donor organs from individuals with HCV had previously been avoided in HCV-naïve recipients to avoid this risk of infection. However, with the availability of highly effective antiviral regimens that can preempt or treat HCV infection acquired through organ receipt, the practice is becoming more common among transplant centers to expand the donor pool and reduce time on organ waiting lists. This is discussed in detail elsewhere. (See "Kidney transplantation in adults: Hepatitis C virus infection in kidney donors", section on 'Approach to the use of kidneys from donors with HCV infection' and "Hepatitis C virus infection in liver transplant candidates and recipients", section on 'Use of grafts from HCV-viremic donors'.)
Breaches in infection control protocols — In locations where there are stringent infection control protocols to prevent exposure to bloodborne pathogens, particularly through unsafe medication injection practices, health care-associated transmission has generally been associated with breaches in protocol.
Rare sources of transmission of HCV include contaminated equipment used during the performance of procedures and other breakdowns of infection control procedures or aseptic techniques leading to person-to-person transmission [36-45]. As an example, an outbreak of acute HCV was identified in three hospitalized patients who received saline flushes from a multidose saline vial . Another outbreak of six cases of HCV (along with six cases of hepatitis B virus infection) was linked to inappropriate reuse of syringes and single-patient-use vials of propofol by a single anesthesiologist . Other cases of health care-associated transmission or outbreaks are associated with health care personnel tampering with (diverting, self-injecting, and substituting) injectable opioids intended for medical use . In one outbreak, 32 HCV infections were linked to drug diversion by a technician in a cardiac catheterization laboratory .
In locations where standard precaution and infection control protocols are more lax or not enforced, HCV transmission may be more common [48-50]. In one study from Spain that evaluated 109 cases of acute HCV infection diagnosed at 18 hospitals between 1998 and 2005, health care exposure was believed to account for 67 percent of cases, which were associated with surgical procedures or other interventions and admission to a medical emergency unit ; the proportion of acute HCV infections associated with health care exposures in Spain has subsequently decreased .
Other percutaneous exposures — Other procedures or behaviors associated with exposure to blood, such as procedures involved in folk medicine (eg, scarification, cupping), tattooing, body piercing, and commercial barbering, may also transmit HCV on rare occasions. The risk of transmission to household contacts of individuals with HCV infection is very low, although potential routes of nonsexual transmission in such cases is mucosal exposure to infectious blood or to body fluids containing blood, or percutaneous exposure through personal hygiene items (eg, shared razors or toothbrushes) [52-54].
Tattooing and body piercing have the potential to transmit HCV. However, the extent to which they contribute to the disease burden of HCV is uncertain. In a case-control study that assessed risk factors for infection with questionnaires, having one or more tattoos was more common among 1930 individuals with HCV infection than among 1941 individuals without (35 versus 13 percent) . A history of tattoo receipt was associated with HCV infection even after adjustment for age, race, sex, and other behaviors associated with transmission (OR 3.7, 95% CI 3.0-4.7) and after exclusion of patients with a history of injection drug use or transfusion (OR 3.8, 95% CI 3.0-4.9). It remains unknown whether the transmission risk is from the tattooing itself or from some other associated risk not otherwise accounted for.
Sexual transmission — Sexual transmission of HCV can occur, but the risk appears to be low in general [56-59]. The risk of sexual transmission is higher among men who have sex with men (MSM), particularly among those who also have HIV infection.
●Transmission between MSM – The prevalence of HCV among MSM is higher than that in the general population, and multiple outbreaks of acute HCV among MSM have been reported worldwide, suggesting a meaningful risk of sexual transmission in this population . Among MSM, the prevalence is highest among those with HIV, although the incidence has been increasing among those without HIV.
As an example, in a systematic review of 194 epidemiologic studies, the pooled global prevalence of HCV was 1.5 percent among MSM without HIV and 6.3 percent in MSM with HIV (1.6 and 6.2 times the general population prevalence, respectively) . However, the incidence of HCV was higher among those using pre-exposure prophylaxis (PrEP) to prevent HIV than among those with HIV. In another study of 350 MSM participating in a PrEP program in Amsterdam, 8 primary HCV infections and 7 reinfections were detected (incidence rates 1.27 and 27.8 per 100 person-years, respectively) . There may be regional differences in HCV risk among MSM who use PrEP, however, as other clinics have reported low prevalence rates, especially in areas where HCV treatment uptake rates are high [63-65].
The risk of sexual transmission of HCV may be higher among MSM than the general population because anal sex may be associated with a higher risk of blood exposure than vaginal sex. In a study of 5310 MSM followed for a median of seven years, unprotected receptive anal sex with more than one partner was independently associated with incident HCV infection among participants with and without HIV; unprotected insertive anal sex with multiple partners was not . Risk factors for transmission also include other traumatic sex practices, such as group sex, fisting, and “chem sex” (use of recreational drugs such as methamphetamine or gamma hydroxy butyrate during sex), and genital ulcer disease (lymphogranuloma venereum, syphilis, or herpes simplex virus 2 [HSV-2]) [67-73]. These risk factors highlight the importance of mucosal damage as a risk factor for HCV acquisition. Studies have also reported detectable HCV RNA in rectal and seminal fluids, suggesting that these, in addition to blood from mucosal trauma, may be a route of HCV sexual transmission [74,75].
●Transmission between heterosexual partners – The prevalence of anti-HCV antibodies is increased among heterosexual individuals with multiple partners [59,66,74]. Although the precise risk of transmission of HCV infection between monogamous heterosexual partners has been difficult to assess, it is overall low (a fraction of 1 percent per year).
In one study, the rate of anti-HCV antibody positivity was 4 percent among 500 monogamous, heterosexual partners of patients with HCV infection following a median of 15 years of sexual contact, most of which did not involve regular condom use . However, 40 percent of the 20 partners with positive anti-HCV antibody had discordant genotypes/serotypes from their partners, suggesting that they had acquired HCV through other routes of transmission. In addition, of those with concordant genotypes, phylogenetic evaluation found that the viral isolates from both members of the couple were highly related (and thus consistent with intra-couple transmission) in only three of the couples (0.6 percent of the total population studied). The overall incidence of HCV transmission by sex was an estimated 0.07 percent per year. Another prospective study that followed 895 monogamous heterosexual, HCV-discordant couples for 10 years failed to confirm intra-couple sexual transmission . Other, retrospective studies estimate the likelihood of transmission under these circumstances to be approximately 0.1 percent annually . In many situations, it is difficult to rule out the possibility that transmission resulted from common exposure to risk factors other than sexual exposure .
The risk of sexual transmission of HCV may be higher if the index case also has HIV infection. Several studies have observed a higher prevalence of anti-HCV antibodies in partners of individuals with HCV and HIV coinfection than in partners of individuals with HCV monoinfection [77-79].
●Transmission between women who have sex with women – This is thought to be negligible in the absence of other risk factors for transmission.
Perinatal transmission — Perinatal transmission of HCV occurs in about 5 to 6 percent of infants born to mothers with HCV infection, and the risk is approximately twofold higher among infants born to women with HCV and HIV coinfection . The risk of perinatal HCV infection is discussed in detail elsewhere. (See "Vertical transmission of hepatitis C virus".)
SELECTED POPULATIONS AT RISK
People who use drugs — Injection drug use is the most common risk factor for HCV infection overall. Studies have estimated that 50 to 90 percent of people who inject drugs have serologic evidence of HCV infection. The epidemiology of HCV associated with injection drug use is discussed in detail above. (See 'Injection drug use' above.)
People with self-reported intranasal but not injection drug use also have higher prevalence rates of HCV infection [81-83]. Other risky drug-related activities include combining of sex with nonprescription drug use (also known as “chem sex”). (See 'Sexual transmission' above.)
Incarcerated or unstably housed populations — Higher-than-average rates of HCV infection have also been reported in incarcerated or unstably housed populations [84,85]. This is likely related to the prevalence past or current injection drug use among these populations. (See 'Injection drug use' above.)
People with HIV — Coinfection with HIV and HCV is common since both infections share similar routes of transmission. In a meta-analysis of over 780 studies evaluating populations with HIV worldwide, the overall prevalence of HCV coinfection was estimated to be approximately 6 percent . However, there was substantial geographic variation, with Eastern Europe and Central Asia estimated to account for 27 percent of the global population of individuals with coinfection. In the United States and Western Europe, studies have suggested that up to 30 percent of patients with HIV also have HCV infection [87,88].
Because the relative efficiency of HCV transmission differs by route, the prevalence of coinfection varies markedly across risk groups, with much higher rates in people who inject drugs than in those whose HIV exposure was through heterosexual sex. The sequence of infections also depends on transmission route. For example, people who inject drugs usually acquire HCV before HIV infection, while men who have sex with men (MSM) typically acquire HIV before HCV infection [89,90].
●Percutaneous exposure – Globally, an estimated 80 percent of individuals with HIV and a history of injection drug use have evidence of HCV coinfection . The ongoing opioid epidemic in the United States and elsewhere has been associated with increasing rates of HIV and HCV coinfection, with several reported outbreaks in both rural and urban areas [21,22]. As an example, in a cluster of 129 HIV cases in Massachusetts reported in 2019, 88 percent reported injection drug use as a risk factor and 90 percent had evidence of HCV coinfection . (See 'Injection drug use' above.)
●Sexual exposure (see 'Sexual transmission' above):
•Among MSM, the global prevalence of HCV and HIV coinfection is estimated to be 6.4 percent, but this varies by geographic region . The seroprevalence of HCV in MSM with HIV in the United States ranges from about 4 to 8 percent [91,92]. HCV is not as common among MSM without HIV. As an example, in a large cohort of MSM in the United States, HIV infection was associated with a sixfold increase in HCV incidence . Similarly, in a study of 689 MSM from the Netherlands, HCV prevalence was 0.4 percent among MSM without HIV and 18 percent among MSM with HIV . HCV is associated with combining sex with the use of nonprescription drugs or “chemsex.”
•Among heterosexual partners, HIV is much more easily transmissible than HCV via intercourse [93,94]. Globally, the prevalence of HCV coinfection is approximately 4 percent among individuals whose main HIV exposure risk was through heterosexual sex .
●Perinatal transmission – Vertical transmission of HCV appears to be facilitated by HIV coinfection; the risk of HCV transmission to an infant is approximately doubled if the mother also has HIV infection . This is discussed in detail elsewhere. (See "Vertical transmission of hepatitis C virus", section on 'HIV coinfection'.)
Among people with HIV, the risk of HCV reinfection after successful treatment also depends on the exposure risk. In a meta-analysis of 41 studies including over 9000 individuals with HIV who had been cured of HCV, the estimated rate of HCV reinfection was 6 per 100 person-years among MSM and 3.3 per 100 person-years among people who injected drugs .
Men who have sex with men — The prevalence of HCV among men who have sex with men (MSM) is higher than in the general population, and they are a key population for HCV screening, prevention, and treatment efforts. The epidemiology and sexual transmission of HCV among MSM are discussed in detail elsewhere. (See 'Sexual transmission' above.)
Dialysis — HCV infection is more common among patients on dialysis than in the general population. Although the incidence of HCV infection has been declining among dialysis patients, the relatively high incidence of anti-HCV seropositivity in this population remains a concern, and intermittent outbreaks in dialysis units continue to occur . HCV infection among patients on dialysis is discussed in detail elsewhere. (See "Hepatitis C virus infection in patients on maintenance dialysis".)
Health care providers — Among health care providers, the main occupational risk for HCV infection is a percutaneous sharps injury with a contaminated object. This is discussed in detail elsewhere. (See "Prevention of hepatitis B virus and hepatitis C virus infection among health care providers", section on 'Epidemiology of bloodborne exposures'.)
Individuals with alcohol use disorder — Unexpectedly high rates of HCV infection (approximately 30 percent) have been detected in patients with alcohol use disorder, even in the absence of other risk factors for infection [98-100]. HCV may accelerate the liver injury in patients who drink heavily  and patients with alcohol- and HCV-induced liver injury have a greater risk for hepatocellular carcinoma [102,103]. (See "Hepatitis C and alcohol".)
Perinatally exposed children — The epidemiology of HCV in children is discussed in detail elsewhere. (See "Hepatitis C virus infection in children", section on 'Epidemiology'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hepatitis C virus infection".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Hepatitis C (The Basics)")
●Beyond the Basics topic (see "Patient education: Hepatitis C (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Global burden – Worldwide, approximately 58 million people have chronic HCV infection and 1.5 million new infections occur each year. Areas with particularly high prevalence include the Eastern Mediterranean region and Eastern Europe (figure 1). (See 'Global distribution' above.)
●Epidemiology in the United States – Approximately 2 million individuals have chronic HCV in the United States, with peaks in prevalence among adults 20 to 39 years and 55 to 70 years old. The incidence of acute infection has increased, particularly among younger adults. Injection drug use is the most commonly identified risk factor for new HCV infection, and HCV incidence trends have mirrored the epidemic of injection opioid use in the country. (See 'United States' above.)
●Bloodborne transmission – Percutaneous exposure to HCV is the most efficient means of transmission.
•Injection drug use – Use of needles or other drug paraphernalia contaminated with HCV is the primary route of transmission in most parts of the world. In some locations, up to 90 percent of people who inject drugs have evidence of prior or chronic HCV infection. (See 'Injection drug use' above.)
•Health care-associated – In resource-rich settings, where blood donor screening has essentially eliminated the risk of post-transfusion HCV infection, health care-associated transmission generally occurs only in rare cases of breaches in infection control or aseptic techniques. (See 'Health care-associated transmission' above.)
•Other percutaneous exposures – Procedures or behaviors associated with exposure to blood, such as those involved in folk medicine (eg, scarification, cupping), tattooing, body piercing, and commercial barbering, may also transmit HCV on rare occasions. (See 'Other percutaneous exposures' above.)
●Sexual transmission – Sexual transmission of HCV can occur, but the risk of transmission between monogamous sexual partners is extremely low. The risk of sexual transmission is higher among men who have sex with men (MSM), particularly among those who also have HIV infection. (See 'Sexual transmission' above and 'People with HIV' above.)
●Perinatal transmission – HCV infection occurs in approximately 5 to 6 percent of infants born to mothers with HCV infection, and the risk is approximately twofold higher among infants born to women with HCV and HIV coinfection. (See "Vertical transmission of hepatitis C virus".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Sanjiv Chopra, MD, MACP, who contributed to an earlier version of this topic review.
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