Hepatitis C overview

Hepatitis C is the most commonly reported bloodborne infection in the United States.

Hepatitis C is transmitted primarily through parenteral [non-oral] exposures to infectious blood or body fluids that contain blood, most commonly through injection drug use.

No vaccine against HCV exists, and no effective pre- or postexposure prophylaxis [PEP or PrEP] is available.

More than half of persons who contract HCV will develop chronic infection.

… more recent data suggest that spontaneous clearance might be as high as 46%, varying by age at the time of infection.

Spontaneous clearance is lower among persons co-infected with HIV. [See the rec-ommendations for factors associated with spontaneous clearance.]

HCV antibodies (anti-HCV) can be detected 4–10 weeks after infection and are present in approximately 97% of persons by 6 months after exposure. HCV RNA can be detected as early as 1–2 weeks after exposure.

The course of chronic liver disease is usually insidious, progressing slowly without symptoms or physical signs in most persons during the first 20 years or more following infection.

Approximately 5%–25% of persons with chronic HCV will develop cirrhosis over 10–20 years.

Those with cirrhosis experience a 1%–4% annual risk for hepatocellular carcinoma.

Persons who are male, aged 50 years or older, use alcohol, have nonalcoholic fatty liver disease, have hepatitis B virus (HBV) or HIV co-infection, and who are undergo-ing immunosuppressive therapy have increased rates of progression to cirrhosis.

Direct-acting antiviral treatment can result in a virologic cure in most persons with 8–12 weeks of all oral medication regimens.

Hepatitis C treatment

Treatment for HCV infection has evolved substantially since the introduction of DAA [direct-acting antiviral] agents in 2011.

DAA therapy is better tolerated, of shorter duration, and more effective than interferon-based regimens used in the past.

Antivirals for hepatitis C treatment include next-generation DAAs, categorized as either protease inhibitors, nucleoside analog polymerase inhibitors, or nonstructural (NS5A) protein inhibitors. 

Many agents are pangenotypic, meaning they have antiviral activity against all genotypes.

A sustained virologic response (SVR) is a cure and is defined as the absence of detectable HCV RNA [aka “viral load”] 12 weeks after completion of treatment.

Approximately 90% [other experts, including the World Health Organization, put the percentage above 95%] of HCV-infected persons can be cured with 8–12 weeks of therapy, regardless of HCV genotype, prior treatment experience, fibrosis level, or presence of cirrhosis.

Hepatitis C epidemiology

National surveillance data revealed an increase in reported cases of acute HCV infection every year from 2009 through 2017.

The highest rates of acute infection are among persons aged 20–39 years.

Surveys conducted during 2013–2016 indicated an estimated 2.4 million persons (1.0%) in the nation were living with hepatitis C.

As new HCV infections have increased among reproductive aged adults, rates of HCV infection nearly doubled during 2009–2014 among women with live births.

In 2017, 3,216 cases (1.0 per 100,000 population) of acute HCV infection were reported to CDC. The reported number of cases in any given year likely represents less than 10% of the actual number of cases because of underascertainment and underreporting. An estimated 44,700 new cases of HCV infection occurred in 2017.

Increased incidence of hepatitis C: 364%

During 2006–2012, the combined incidence of acute HCV infection in four states (Kentucky, Tennessee, Virginia, and West Virginia) increased 364% among persons aged 30 years or younger. Among cases in these states with identified risk information, IDU (injection drug use) was most commonly reported (73%). People who had HCV were primarily non-Hispanic white persons from nonurban areas.

Concerns during pregnancy and childhood

Because of the increasing incidence of HCV infection among women of childbearing age, perinatal transmission (intrauterine or intrapartum) has become an increasingly important mode of HCV transmission. Among pregnant women from 2011 to 2016, hepatitis C virus testing increased by 135% (from 5.7% to 13.4%), and positivity increased by 39% (from 2.6% to 3.6%). The risk for perinatal transmission is informed by a systematic review and meta-analysis of studies conducted in multiple countries and is 5.8% for infants born to mothers who have HCV but not with HIV and doubles for infants born to mothers co-infected with HCV and HIV. Perinatal HCV transmission is almost always confined to infants born to mothers with detectable HCV RNA. Only approximately 20% of infants with perinatally acquired hepatitis C clear the infection, 50% have chronic asymptomatic infection, and 30% have chronic active infection. HCV-related liver disease rarely causes complications during childhood. Because fibrosis increases with disease duration, perinatally infected persons might develop severe disease as young adults.

The CDC’s 2012 guidelines recommended that pregnant women be tested for hepatitis C only if they have known risk factors. However, in 2018, universal hepatitis C screening during pregnancy was recommended by the American Association for the Study of Liver Diseases and IDSA. This report expands hepatitis C screening for all pregnant women during each pregnancy, except in settings where the prevalence of HCV infection is <0.1%.

Despite their favorable safety profile, DAAs (direct-acting antivirals) are not yet approved for use during pregnancy. Safety data during pregnancy are preliminary and larger studies are required. A small study of seven pregnant women treated with ledipasvir/sofosbuvir [Harvoni] identified no safety concerns. Until DAAs become available for use during pregnancy, testing women during pregnancy for HCV infection still has benefits to both the mother and the infant. Many women only have access to health care during pregnancy and the immediate postpartum period. In 2017, 12.4% of women aged 19–44 years were not covered by public or private health insurance. Pregnancy is an opportune time for women to receive a hepatitis C test while simultaneously receiving other prenatal pathogen testing such as for HIV or hepatitis B. The post-partum period might represent a unique time to transition women who have had HCV infection diagnosed during pregnancy to treatment with DAAs. Treatment during the interconception (interpregnancy) period reduces the transmission risk for subsequent pregnancies. Identification of HCV infection during pregnancy can also inform pregnancy and delivery management issues that might reduce the likelihood of HCV transmission to the infant. The Society for Maternal-Fetal Medicine recommends a preference for amniocentesis over chorionic villus sampling when needed, and for avoiding internal fetal monitoring, prolonged rupture of the membranes, and episiotomy among HCV-infected women, unless it is unavoidable.

Testing during pregnancy allows for simultaneous identification of infected mothers and infants who should receive testing at a pediatric visit. Testing of infants consists of HCV RNA testing at or after age 2 months or anti-HCV testing at or after age 18 months. Although DAA treatment is not approved for children aged less than 3 years, infected children aged over 3 years should be monitored. In 2017, [Harvoni] became the first DAA approved for use in persons aged 12–17 years. In 2019 glecaprevir/pibrentasvir [Mavyret] became approved for use in children up to age 12, and [Harvoni] became approved for use in children up to age 3.

Editor’s Note: Read an article on HCV and perinatal syphilis from Hepatitis Editor Andrew Reynolds at positivelyaware.com/articles/twin-epidemics.