Hepatitis C

"The mechanisms of HCV transmission among non-injecting drug users are not well understood[3]. This study identified six risk factors for HCV infection. Having a tattoo was associated with HCV infection. Commonly, a tattoo is identified as a risk factor for HCV infection in illicit-drug users[2, 6, 8]. Likely, this reflects the lifestyle of illicit-drug users, which could include greater exposure to HCV. Furthermore, the daily use of drugs, paraphernalia sharing during drug use, and a long history of drug use were also associated with HCV infection in non-injecting drug users. Few studies have reported the presence of HCV-RNA in the nasal secretions of cocaine and crack users, indicating a possible alternative route for the transmission of the virus – the sharing of the paraphernalia used to consume these drugs[4, 30]. One hypothesis to account for these cases involves intranasal transmission of HCV via contaminated implements, requiring two primary virological preconditions: the presence of blood and HCV in the nasal secretions of intranasal drug users, and the transfer of blood and HCV from the nasal cavity onto sniffing implements, which are often shared by intranasal drug users[4, 30]. In Pará, HCV transmission may be associated with and powered by three risk factors: daily use of drugs, paraphernalia sharing during drug use, and a long history of drug use (more than 5 years). To prove this hypothesis, other, more-specific studies will be needed in the future."

"Hepatitis C is associated with more deaths in the United States than 60 other infectious diseases reported to CDC combined. Despite curative hepatitis C virus (HCV) therapies and known preventive measures to interrupt transmission, new HCV infections have increased in recent years (1,2). Injection drug use is the primary risk factor for new HCV infections (2). One potential strategy to decrease the prevalence of HCV is to create and strengthen public health laws and policies aimed specifically at reducing transmission risks among persons who inject drugs."

"Hepatitis A is a vaccine-preventable liver disease caused by the hepatitis A virus (HAV). HAV is usually transmitted person-to-person through the fecal–oral route or through consumption of contaminated food or water. The majority of adults and older children with hepatitis A have symptoms that usually resolve ≤2 months after infection; children aged <6 years usually do not have symptoms, or they have an unrecognized infection. Signs and symptoms associated with hepatitis A can include ≥1 of the following: fever, fatigue, nausea, vomiting, loss of appetite, abdominal pain, dark urine, and clay-colored stools. Hepatitis A is a self-limited disease that does not result in chronic infection. Treatment for HAV infection might include rest, adequate nutrition, and fluids. Hospitalization might be required for more severe cases. The best way to prevent hepatitis A is by being vaccinated(1).

"Hepatitis B is a vaccine-preventable liver disease caused by the hepatitis B virus (HBV). HBV is transmitted when blood, semen, or another body fluid from a person infected with the virus enters the body of someone who is uninfected. This can happen through sexual contact; sharing needles, syringes, or other drug-injection equipment; or from mother to baby at birth. For some persons, hepatitis B is an acute, or short-term, illness; for others, it can become a longterm, chronic infection. Chronic hepatitis B can lead to serious health problems, including cirrhosis, liver cancer, and death. Treatments are available, but no cure exists for hepatitis B. The best way to prevent hepatitis B is by being vaccinated(2,3).

"Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). HCV is a bloodborne virus. Today in the United States, the majority of persons become infected with HCV by sharing needles or other equipment used in injecting drugs(4). For certain persons, hepatitis C is a short-term illness, but for >50% of persons who become infected with the HCV, it becomes a long-term, chronic infection(5). Like chronic hepatitis B, chronic hepatitis C is a serious disease that can result in cirrhosis, liver cancer, and death. Persons might not be aware of their infection because they are not clinically ill. However, since 2013, a highly effective, well-tolerated curative treatment has been available for hepatitis C, but no vaccine for preventing hepatitis C is yet available(6). The best way to prevent hepatitis C is by avoiding behaviors that can spread the disease, especially injecting drugs."

"During 2019, a total of 4,136 acute hepatitis C cases were reported to CDC, corresponding to 57,500 estimated infections (95% CI: 45,500–196,000) after adjusting for case underascertainment and underreporting (see Technical Notes)(9). The reported acute hepatitis C case count corresponds to a rate of 1.3 cases per 100,000 population, a 63% increase from the reported rate of 0.8 cases per 100,000 population during 2015. Approximately 63% of acute hepatitis C cases reported to CDC during 2019 were among persons aged 20–39 years. The rate of acute hepatitis C was highest among American Indian/Alaska Native persons (3.6 cases per 100,000 population), compared with other racial/ethnicity groups. Among the 1,952 (47%) reported acute cases that included risk information for injection drug use, 1,302 (67%) reported injection drug use. A total of 1,041 patients with acute hepatitis C were hospitalized (48% hospitalization rate among 2,156 cases with hospitalization information available).

"A total of 123,312 new cases of chronic hepatitis C were reported to CDC during 2019, corresponding to a rate of 56.7 cases per 100,000 population. The rate of newly reported chronic hepatitis C was highest among persons aged 30–39 years (109.1 cases per 100,000 population), followed by persons aged 50–59 years (79.6 cases per 100,000 population), compared with other age categories. These rates are consistent with the previously reported bimodal distribution of newly reported chronic hepatitis C affecting multiple generations(11). The rate of newly reported chronic hepatitis C cases was highest among American Indian/Alaska Native persons (86.7 cases per 100,000 population), compared with other racial/ethnicity categories."

"Among the 4,136 case reports of acute hepatitis C received by CDC for 2019, data regarding risk behaviors or exposures were missing for 1,873 (45.3%) cases. At least one risk behavior or exposure was reported for 1,626 (39.3%) cases during the 6 weeks to 6 months before illness onset. More than one risk can be reported for each case.

"Among risk behaviors and exposures identified, injection drug use was most commonly reported (67% of the 1,952 cases for which injection drug use information was available). Hepatitis C virus transmission associated with surgery, dialysis, or transfusion is extremely rare in the United States; thus, the reporting of these exposures might represent a history of recent exposure to these health care procedures."

"In conclusion, although the incidence of HCV was very low in this study among never-injecting DU, the prevalence was much higher than in the general population. In the methadone outposts of the Amsterdam Health Service, HCV screening is offered every year irrespective of recent injecting drug use. Although, we could not distinguish whether the increased risk of HCV infection in never-injecting DU was related to underreporting of injection or to household or sexual transmission, HCV strains of never-injecting DU cluster with those found among injecting DU. HCV treatment has improved substantially since 2000 and is effective in up to 80–90% of patients [3]. Therefore, whatever the route of transmission, it is clear that routine HCV testing and treatment should be extended to both never-injecting and injecting DU."

"Modeled Hepatitis C prevalence estimates varied meaningfully by demographic characteristics, within and across U.S. jurisdictions. In most jurisdictions, we estimated higher disease prevalence among males compared with females, persons born during 1945 to 1969 compared with older or younger persons, and non-Hispanic black persons compared with persons of other race/ethnicities. Reducing the overall number of HCV infections with a focus on disparities requires an understanding of both hepatitis C prevalence and number of infections in high-risk populations.

"HCV infections are increasing among young, mostly white persons in rural areas who inject drugs,1, 24, 25 but our analysis suggests that non-Hispanic blacks continue to have larger proportions of prevalent infections in most jurisdictions. Nationally, an estimated 72% of prevalent HCV infections occurred among persons born during 1945 to 1969, and even in states like West Virginia and Kentucky with higher than average percentages of infections among young people, more than 50% of all infections were still among persons born during 1945 to 1969 based on these estimates. Jurisdictions with future growth in hepatitis C burden, however, may be those with the highest prevalence of opioid-use disorder and associated injection drug use. This pattern begins to emerge to some extent in our results, in which many jurisdictions with higher than average overall prevalence are also those with larger percentages of infections among the youngest age group (e.g., New Mexico, West Virginia, Kentucky, Ohio).

"We also observed that model-based hepatitis C prevalence was more than twice as prevalent among non-Hispanic black persons than among persons of other race/ethnicities, and in 15 jurisdictions, was at least 3 times as high. This disparity has been shown previously,18 and these estimates suggest racial disparities in hepatitis C have not declined since 2010. Higher prevalence among non-Hispanic blacks compared with persons of other race/ethnicities likely stems from a combination of factors including lower rates of acute hepatitis C clearance,26-28 higher rates of incarceration,29-33 and less access to effective treatment services.34-36 Clinical evidence suggested that interferon-based therapies were less effective for treating genotype 1 HCV infection among non-Hispanic black versus persons of other race/ethnicities, but newer direct-acting antiviral medications provide equally effective treatment across racial groups.37 Efforts are urgently needed to reduce racial disparities in hepatitis C burden by increasing treatment rates among non-Hispanic black Americans through improved health coverage and development of culturally appropriate care and treatment interventions.37, 38"

"Several studies have demonstrated that non-injection drug users have a higher anti-HCV prevalence than the general population, with estimates ranging from 5 to 29%.^6–8 Two studies have found an association between intranasal use of cocaine and anti-HCV,^9,10 and researchers have isolated HCV RNA in nasal secretions and implements used for drug inhalation.¹¹ Blood-contaminated non-injection implements such as straws could transmit infection via damaged nasal mucosa.¹² Similarly, other research demonstrated low viral titers of HCV in saliva,¹³ lending plausibility to shared oral drug utensils such as crack pipes as a route of transmission. While some studies have shown an association with sharing non-injection implements or non-injection drug use and HCV infection,^1,9,13 others have not shown a significant association.^7,14,15"

"After receiving reports of cases of acute hepatitis C ranging from 781-877 during the years 2006–2010, reported cases of acute HCV infection increased more than 2.5 times from 2010–2014. Cases of acute HCV infection rose annually, from 850 in 2010 to 1,232 in 2011, 1,778 in 2012, 2,138 in 2013, and 2,194 in 2014. The increase from 2010–2014 is thought to reflect both true increases in incidence and, to a lesser extent, improved case ascertainment. Based on new epidemiologic studies, at least 4.6 million persons are HCV-antibody positive and approximately 3.5 million are currently infected with HCV (13). New cases of HCV infection are predominately among young persons who are white, live in non-urban areas (particularly in Eastern and Midwestern states), have a history of injection-drug use, and previously used opioid agonists such as oxycodone (14). Improved case ascertainment by Florida, Massachusetts, and New York, which were funded by CDC to conduct enhanced surveillance, partially explains the increased incidence of acute HCV infection in these states. In other locations where the number of cases has increased markedly (e.g., Kentucky, Tennessee, Virginia, and West Virginia), increases have occurred without any federal support for investigation or follow-up, reflecting overall increases in incidence (15, 16). After adjusting for under-ascertainment and under-reporting (2), an estimated 30,500 new HCV infections occurred in 2014.

"Mortality among HCV-infected persons — primarily adults aged 55–64 years — is increasing (17, 18). For the first time in the United States (17), in 2007 the number of HCV-related deaths (n=15,106) exceeded the number of HIV/AIDS-related deaths (n=12,734) (17) and has since continued to increase. The number of HCV-related deaths rose to 19,659 in 2014 and more than one-half of deaths occurred among persons aged 55-64 years. A key public health challenge is to increase the proportion of persons tested, and of those who are currently infected, increase the proportion referred for care and treatment (10, 11). To address this challenge the USPSTF joined with CDC in 2013 to recommend one-time testing for HCV infection among adults born during 1945–1965 (19)."

"Crack users often use and share pipes made of various makeshift materials, including broken glass pipes, metal tubing, aluminum cans, car antennas, or glass ginseng bottles, all of which can cause cuts, sores, burns, and blisters in and around the user’s mouth (Faruque et al., 1996; Porter & Bonilla, 1993; Porter, Bonilla, & Drucker, 1997; Shannon, Kerr et al., 2008). A number of recent studies point to nonIDU equipment sharing as possible routes of infectious disease transmission (Fischer, Powis, Firestone-Cruz, Rudzinski, & Rehm, 2008; Macias et al., 2008; McMahon & Tortu, 2003; Roy et al., 2001; Shannon, Rusch et al. 2008: Tortu, Neaigus, McMahon, & Hagen, 2001). In a study of drug users with no history of drug injection, Tortu et al. (2004) found noninjection drug use equipment sharing to be a risk factor for HCV infection, suggesting that HCV transmission may occur through noninjection routes such as oral and intranasal drug use methods. This is particularly concerning given that HCV is almost 30 times more infective that HIV through blood contact (Sulkowski & Thomas, 2003)."

"HCV infection in IDUs [intravenous drug users] is acquired primarily through injecting with an infected needle and syringe, which has been used by someone else who is infected with HCV or possibly has become contaminated through contact with other contaminated injecting paraphernalia. The probability of becoming infected after using an infected syringe ranges from 1.5 to 5 per cent for HCV, in contrast to 0.34 to 1.4 per cent for HIV (Vickerman et al., in press)."

"HCV is transmitted primarily through percutaneous (parenteral) exposure that can result from injection-drug use, needle stick injuries, and inadequate infection control in health-care settings. Much less often, HCV transmission occurs among HIV-positive persons, especially MSM, as a result of sexual contact with an HCV-infected partner (30, 31), among persons who receive tattoos in unregulated settings (31), and among infants born to HCV-infected mothers (32). After adjustment for populations not sampled in the NHANES household surveys, such as incarcerated and homeless populations, an estimated 3.5 million persons are living with HCV infection in the United States (28).

"A single positive anti-HCV result cannot distinguish between acute and chronic HCV infection or between current or resolved (cleared) HCV infection. Approximately 75%–85% of newly infected adults and adolescents develop chronic HCV infection (33)."

"Of the estimated 585,000 deaths attributed to drug use in 2017, half are attributed to liver cancer, cirrhosis and other chronic liver diseases related to hepatitis C, which remains mostly untreated among PWID. Deaths attributed to drug use disorders (167,000) account for 28 per cent of all deaths resulting from drug use; 110,000 or 66 per cent of those deaths are attributable to opioids. Over the past decade, the total number of deaths attributed to drug use has increased by a quarter, with a major increase in deaths caused by opioid use disorders (71 per cent increase), followed by cirrhosis and other chronic liver diseases (55 per cent increase) and liver cancer (46 per cent) resulting from hepatitis C.

"The comparison of deaths attributed to drug use among men and women over the past decade shows that the number of deaths attributed to drug use disorders, in particular opioid use disorders, has increased disproportionately among women, with a 92 per cent increase in deaths attributed to opioid use disorders among women compared with a 63 per cent increase among men."

"The potential for blood-borne viral transmission via injection equipment other than syringes was reported in an earlier study of equipment collected in a Miami shooting gallery, where HIV-1 DNA was detected in rinses from cottons and cookers and in water used to clean paraphernalia and to dissolve drugs. A sterile syringe may become contaminated when the tip of the needle is inserted into a contaminated cooker or when the drug is drawn up through contaminated filtration cotton. This type of injection risk behavior appears to be quite common, and fewer injection drug users may recognize the hazard of sharing drug preparation equipment than recognize the hazard of sharing syringes. The present study suggests that HCV may be transmitted via the shared use of drug cookers and filtration cotton even without injection with a contaminated syringe."

"PWID [People Who Inject Drugs] are a key population affected by hepatitis C. Global estimates suggest that 71 million people worldwide were chronically infected with hepatitis C in 2017 and that 23 per cent of new hepatitis C infections and one in three hepatitis C-related deaths are attributable to injecting drug use.¹³⁰ Hepatitis C-related morbidity and mortality continue to rise, mainly as a result of cirrhosis, hepatocellular carcinoma and death in cases of untreated hepatitis C.¹³¹

"UNODC, WHO, UNAIDS and the World Bank jointly estimated the prevalence of hepatitis C among PWID worldwide in 2018 to be 48.5 per cent, or 5.5 million (range: 4 million to 7.8 million) people aged 15–64. This estimate is based on estimates in 108 countries, covering 94 per cent of the estimated global number of PWID. Data on hepatitis C prevalence were available for all estimated PWID in Eastern Europe, South-Eastern Europe, North America, South-West Asia, South Asia, Central Asia and Transcaucasia, but for none in Central America, and for only 31 and 32 per cent, respectively, of all PWID in the Caribbean and West and Central Africa. Overall, reports from 69 per cent of countries (74 out of 108 countries) could be graded as “class A methodology” (seroprevalence study),¹³² and new or updated estimates for hepatitis C among PWID were available for 35 countries in total in 2018."

"Viral hepatitis accounts for a significant global disease burden and high mortality from liver cancer and cirrhosis. In 2019, 296 million people were living with chronic hepatitis B virus infection and 58 million people with chronic hepatitis C virus infection worldwide. New estimates show that about 1.5 million people newly acquire hepatitis B infection each year, despite the availability of a highly efficacious vaccine. About 1.5 million people newly acquire hepatitis C virus infection. Viral hepatitis caused 1.1 million deaths in 2019, 96% of which were caused by hepatitis B and C virus (5). Most of these deaths result from chronic liver disease and liver cancer. The greatest burden of hepatitis B and C infection is concentrated by geography and population, with 80% of the global burden of hepatitis C infection in the 10 most severely affected countries. People from economically disadvantaged regions, displaced people and migrants, and rural populations are more severely affected. Further, injecting drug use is a major contributor to the hepatitis C epidemic globally (6). Other affected population groups include health-care workers exposed through needle-stick injuries, people in prisons and closed settings, and gay men and other men who have sex with men."

"HBV/HIV and HCV/HIV coinfections are an increasing problem in countries with HIV epidemics and among injecting drug users. For co-infected persons being treated with HIV antiretroviral medicines, underlying viral hepatitis is becoming a major cause of death."

"• Infection control precautions in health care and community settings can prevent transmission of viral hepatitis as well as many other diseases.
"• Safe injection practices can protect against HBV and HCV transmission.
"• Safer sex practices, including minimizing the number of partners and using barrier protective measures (condoms), protect against HBV and possibly against HCV transmission.
"• Harm reduction practices for injecting drug users prevent HAV, HBV and HCV transmission."

"Antiviral agents against HBV and HCV exist. However, drugs active against HBV or HCV are not widely accessible. Currently, three antiretrovirals (TDF, 3TC, FTC) are effective for treatment of both HIV and HBV, so co-infected patients can take fewer drugs to treat the two diseases.

"Although HCV can be treated, access to treatment remains an issue in many countries. Therapeutic advances and intense research have led to the development of many new oral antiviral drugs for HCV infection. A number of HCV-specific oral drugs are in the late stage of development and some have been recently registered."

"No laboratory distinction can be made between acute and chronic (past or present) HCV infection. Diagnosis of chronic infection is made on the basis of anti-HCV positive results upon repeat testing. Approximately 75%-85% of newly infected persons develop chronic infection (14).

"Because of the high burden of chronic HCV infection in the United States and because no vaccine is available for preventing infection, national recommendations (15) emphasize other primary prevention activities, including screening and testing blood donors, inactivating HCV in plasma-derived products, testing persons at risk for HCV infection and providing them with risk-reduction counseling, and consistently implementing and practicing infection control in health-care settings."

"Chronic HCV infection can lead to severe liver disease, liver cancer and death. Rates of progression, though initially slow, increase over time. For example, after 20 to 40 years approximately 20 per cent of those infected will develop cirrhosis of whom approximately three per cent annually will die from decompensated cirrhosis or liver cancer. Chronic HCV can be successfully cleared in at least half of patients that are treated (Department of Health, 2002; Irving, presentation to ACMD, 2008)."

"In the United States, chronic HCV infection accounts for 8,000 to 10,000 related deaths annually.^1,3 It has become the leading cause of liver transplantation, accounting for 30% of all liver transplants. The Centers for Disease Control and Prevention (CDC) conservatively estimates expenditures devoted to HCV to be more than $600 million annually."

"Hepatitis C is the most common blood-borne pathogen in humans and the most common cause of liver failure and reason for liver transplantation in the United States.¹ In a large population-based study, 1.8% (3.9 million) of a large household-based sample was positive for anti-hepatitis C virus antibody.² Of these, 74% (2.7 million) had viremia, an indicator of chronic infection. As many as half of these persons were unaware they were infected.^3,4"

"Recommendation 1. Local service planners need to review local needle and syringe services (and be supported in this work) in order to take steps to increase access and availability to sterile injecting equipment and to increase the proportion of injectors who receive 100 per cent coverage of sterile injecting equipment in relation to their injecting frequency."

"Short-term use of smoked cannabis did not affect viral load in 15 HIV-positive patients and also is associated with adherence to therapy and reduced viral loads in 16 patients with hepatitis C infections."