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Hepatitis C

Hepatitis C

Hepatitis C is a liver infection caused by the hepatitis C virus (HCV). Hepatitis C is spread through contact with blood from an infected person. Today, most people become infected with the hepatitis C virus by sharing needles or other equipment used to prepare and inject drugs. For some people, hepatitis C is a short-term illness, but for more than half of people who become infected with the hepatitis C virus, it becomes a long-term, chronic infection. Chronic hepatitis C can result in serious, even life-threatening health problems like cirrhosis and liver cancer. People with chronic hepatitis C can often have no symptoms and don’t feel sick. When symptoms appear, they often are a sign of advanced liver disease. There is no vaccine for hepatitis C. The best way to prevent hepatitis C is by avoiding behaviors that can spread the disease, especially injecting drugs. Getting tested for hepatitis C is important, because treatments can cure most people with hepatitis C in 8 to 12 weeks.

Who is at risk for hepatitis C infection?

The following people are at increased risk for hepatitis C:

  1. People with HIV infection
  2. Current or former people who use injection drugs (PWID), including those who injected only once many years ago
  3. People with selected medical conditions, including those who ever received maintenance hemodialysis
  4. Health care, emergency medical, and public safety personnel after needle sticks, sharps, or mucosal exposures to HCV-positive blood
  5. Children born to mothers with HCV infection

Is it possible for someone to become infected with HCV and then spontaneously clear the infection?

Yes. Recent data reveal that up to approximately half of people who test anti-HCV positive do not have current chronic infection, indicating they may have experienced spontaneous clearance after acute infection. Only those with current infection as evidenced by a positive HCV RNA test need treatment. Factors that are predictive of spontaneous clearance of HCV include having jaundice, elevated ALT level, and hepatitis B virus surface antigen (HBsAg) positivity; younger age, being female; being infected with HCV genotype 1; and having certain host genetic polymorphisms, most notably those near the IL28B gene.

What is the likelihood of HCV infection becoming chronic?

More than half of people who become infected with HCV will develop chronic infection.

Why do most people remain chronically infected with HCV?

A person infected with HCV mounts an immune response to the virus, but replication of the virus during infection can result in changes that evade the immune response. This may explain how the virus establishes and maintains chronicity.

What are the chances of someone with HCV infection developing cirrhosis or liver cancer?

Of every 100 people infected with HCV, approximately 5–25 will develop cirrhosis within 10–20 years. Patients who develop cirrhosis have a 1%–4% annual risk of developing hepatocellular carcinoma and a 3%–6% annual risk of hepatic decompensation; for the latter patients, the risk of death in the following year is 15%–20%.

Who is more likely to develop cirrhosis after becoming infected with HCV?

Rates of progression to cirrhosis are increased in the presence of a variety of factors, including

  1. Being male
  2. Being age >50 years
  3. Consuming alcohol
  4. Having nonalcoholic fatty liver disease, hepatitis B, or HIV coinfection
  5. Receiving immunosuppressive therapy

How many different genotypes of HCV exist?

Seven HCV genotypes and 67 subtypes have been identified.

Can superinfection with more than one HCV genotype occur?

Superinfection is possible if risk behaviors for HCV infection (e.g., injection-drug use) continue; however, superinfection does not appear to complicate decisions regarding treatment, because HCV antivirals with pan-genotypic activity are available.

Can people become infected with a different strain of HCV after they have cleared the initial infection?

Yes. Prior infection with HCV does not protect against later infection with the same or different genotypes of the virus. This is because people infected with HCV typically have an ineffective immune response due to changes in the virus during infection.

Is hepatitis C a common cause for liver transplantation?

Yes. Chronic liver disease and liver cancer caused by chronic HCV infection are a common reason for liver transplants in the United States.

Is there a hepatitis C vaccine?

Development of a vaccine for hepatitis C has been challenging, because the virus has multiple genotypes and subtypes and mutates rapidly, allowing it to evade the immune system. However, novel vaccine candidates based on advanced molecular technology have been explored. 

 

How is HCV transmitted?

HCV is transmitted primarily through parenteral exposures to infectious blood or body fluids that contain blood. Possible exposures include

  1. Injection-drug use
  2. Birth to an HCV-infected mother

Although less frequent, HCV can also be spread through:

  1. Sex with an HCV-infected person (an inefficient means of transmission, although HIV-infected men who have sex with men [MSM] have increased risk of sexual transmission)
  2. Sharing personal items contaminated with infectious blood, such as razors or toothbrushes
  3. Other health-care procedures that involve invasive procedures, such as injections (usually recognized in the context of outbreaks)
  4. Unregulated tattooing
  5. Receipt of donated blood, blood products, and organs (rare since blood screening became available)
  6. Needlestick injuries in health-care settings

Can hepatitis C be spread within a household?

Yes; however, transmission between household members does not occur very often. If hepatitis C is spread within a household, it is most likely a result of direct (i.e., parenteral or percutaneous) exposure to the blood of an infected household member.

What are the signs and symptoms of acute HCV infection?

People with newly acquired HCV infection usually are asymptomatic or have mild symptoms that are unlikely to prompt a visit to a health-care professional. When symptoms do occur, they can include:

  1. Fever
  2. Fatigue
  3. Dark urine
  4. Clay-colored stool
  5. Abdominal pain
  6. Loss of appetite
  7. Nausea
  8. Vomiting
  9. Joint pain
  10. Jaundice

How soon after exposure to HCV do symptoms appear?

In those people who do develop symptoms, the average period from exposure to symptom onset is 2–12 weeks (range: 2–26 weeks).

What are the signs and symptoms of chronic HCV infection?

Most people with chronic HCV infection are asymptomatic or have non-specific symptoms such as chronic fatigue and depression. Many eventually develop chronic liver disease, which can range from mild to severe, including cirrhosis and liver cancer. Chronic liver disease in HCV-infected people is usually insidious, progressing slowly without any signs or symptoms for several decades. In fact, HCV infection is often not recognized until asymptomatic people are identified as HCV-positive when screened for blood donation or when elevated alanine aminotransferase (ALT, a liver enzyme) levels are detected during routine examinations.

What are the extrahepatic manifestations of chronic HCV infection?

Some people with chronic HCV infection develop medical conditions due to hepatitis C that are not limited to the liver. Such conditions can include:

  1. Diabetes mellitus
  2. Glomerulonephritis
  3. Essential mixed cryoglobulinemia
  4. Porphyria cutanea tarda
  5. Non-Hodgkin’s lymphoma

 

Who should be tested for HCV infection?

We recommends universal hepatitis C screening for all adults and all pregnant women during every pregnancy, except in settings where the prevalence of HCV infection is <0.1%. This includes

  1. All adults aged 18 years and older
  2. All pregnant women during each pregnancy
  3. People who ever injected drugs and shared needles, syringes, or other drug preparation equipment, including those who injected once or a few times many years ago
  4. People with HIV
  5. People who have ever received maintenance hemodialysis
  6. People with persistently abnormal ALT levels
  7. People who were notified that they received blood from a donor who later tested positive for HCV infection
  8. Health care, emergency medical, and public safety personnel after needle sticks, sharps, or mucosal exposures to HCV‑positive blood 
  9. Children born to mothers with HCV infection
  10. Any person who requests hepatitis C testing

Who should be tested for HCV on a routine basis?

Routine periodic testing is recommended for people with ongoing risk factors, while risk factors persist, including those who currently inject drugs and share needles, syringes, or other drug preparation equipment, along with people who have certain medical conditions (e.g., people who ever received maintenance hemodialysis). Testing of people at risk should occur regardless of setting prevalence.

What blood tests are used to detect HCV infection?

Several blood tests can detect HCV infection, including:

  1. Screening tests for antibody to HCV (anti-HCV)
    1. enzyme immunoassay (EIA)
    2. enhanced chemiluminescence immunoassay (CLIA)
    3. Chemiluminescence microparticle immunoassay (CMIA)
    4. Microparticle immunoassay (MEIA)
    5. Electrochemiluminescence immunoassay (ECLIA)
    6. Immunochromatographic assay (rapid test)
  2. Qualitative nucleic acid tests to detect presence HCV RNA
  3. Quantitative nucleic acid tests to detect levels of HCV RNA

How soon after exposure to HCV can HCV antibodies be detected?

Anti-HCV seroconversion occurs an average of 8–11 weeks after exposure, although cases of delayed seroconversion have been documented in people who are immunosuppressed (e.g., those with HIV infection).

How soon after exposure to HCV can HCV RNA be detected?

People with recently acquired acute infection typically have detectable HCV RNA levels as early as 1–2 weeks after exposure to the virus.

Is an HCV antibody (anti-HCV) test sufficient to diagnose current HCV infection?

No. The anti-HCV test only provides information about past exposure to HCV. A negative anti-HCV result indicates that a patient has never been exposed to the virus, and therefore the anti-HCV test is only used to rule out HCV infection. If a person tests positive for HCV antibodies, hepatitis C testing is not considered complete unless the initial positive anti-HCV test is followed by a test for HCV RNA. A positive test for HCV RNA is needed before a patient can be diagnosed with current HCV and begin receiving treatment. Ideally, positive antibody tests are “reflexed” to an HCV RNA test automatically from the same blood sample. However, reflex testing is not possible in every laboratory or clinical setting.

Is someone with a positive anti-HCV test still at risk for hepatitis C?

Yes. A person with a positive anti-HCV test is susceptible to future HCV infections. People with ongoing risk factors, such as those who currently inject drugs and those who have previously tested anti-HCV positive and HCV RNA negative, should receive periodic HCV RNA testing.

Under what circumstances might a false-negative HCV antibody (anti-HCV) test result occur, even when a person has been exposed to HCV?

People who have been very recently infected with HCV might not yet have developed antibody levels high enough to be detected by the anti-HCV test. The window period for acute HCV infection before the detection of antibodies averages 8 to 11 weeks, with a reported range of 2 weeks to 6 months. In addition, some people might lack the immune response necessary to develop detectable antibodies within this time range. In these people, virologic testing (e.g., PCR for HCV RNA) can be considered.

Can a patient have a normal liver enzyme (e.g., ALT) level and still have chronic hepatitis C?

Yes. It is common for patients with chronic hepatitis C to have fluctuating liver enzyme levels, with periodic returns to normal or near normal levels. Liver enzyme levels can remain normal for over a year despite chronic liver disease.

 

What should a provider do for a patient with confirmed HCV infection?

We recommend that people who are diagnosed with hepatitis C be provided

  1. medical evaluation (by either a primary-care clinician or specialist [e.g., in hepatology, gastroenterology, or infectious disease]) for chronic liver disease, including treatment and monitoring;
  2. hepatitis A and hepatitis B vaccination;
  3. screening and brief intervention for alcohol consumption; and
  4. HIV risk assessment and testing.

What advice and messages should be given to patients diagnosed with hepatitis C?

Providers should talk to their patients about

  1. the effectiveness and benefits of direct acting antivirals (DAAs);
  2. the importance of avoiding alcohol, because alcohol consumption can accelerate cirrhosis and end-stage liver disease;
  3. the need to follow a healthy diet and stay physically active, especially for patients who are overweight (i.e., those with body mass index [BMI] ≥25kg/m2) or obese (BMI ≥30kg/m2); and
  4. the importance of checking with a health professional before taking any new prescription pills, over-the counter drugs (such as non-aspirin pain relievers), or supplements, as these can potentially damage the liver.
  5. the need to avoid or stop donating blood, tissue, or semen;
  6. the low but present risk for transmission to sex partners and when sharing personal items that might have blood on them, such as toothbrushes, dental appliances, razors, nail clippers, glucose meters, and lancet devices;
  7. ways that hepatitis C is not spread (e.g., sneezing, hugging, holding hands, coughing, sharing eating utensils, or drinking glasses or through food or water); and
  8. the need to cover cuts and sores on the skin to keep from spreading infectious blood or secretions.

Which types of health-care providers can effectively manage patients with hepatitis C?

Given that hepatitis C treatment has been simplified, many types of providers can effectively manage HCV-infected patients, including internal medicine and family practice physicians, nurse practitioners, physician assistants, and pharmacists. Specialists (e.g., infectious-disease physicians, gastroenterologists, pediatricians, and hepatologists) may be more appropriate when managing children with hepatitis C and patients who have certain HCV-related sequelae or advanced disease, including those requiring a liver transplant.

Is routine HCV genotyping required when managing a person with hepatitis C?

Not usually. With the advent of hepatitis C therapies that are effective against many genotypes, genotyping is no longer required prior to treatment initiation. However, pre-treatment genotyping continues to be recommended for patients with evidence of cirrhosis and/or past unsuccessful hepatitis C treatment, because this knowledge can help tailor treatment regimens and improve patient outcomes.

Should people with hepatitis C be restricted from working in certain occupations or settings?

No one should be excluded from work, school, play, child-care, or other settings on the basis of their infection status. There is no evidence that hepatitis C can be transmitted from food handlers, teachers, or other service providers in the absence of blood-to-blood contact.

Should patients with acute hepatitis C receive treatment?

With the exception of pregnant women and children under 3 years of age, people with acute hepatitis C (i.e., those with measurable HCV RNA) should be treated for their infection. There is no need to wait for potential spontaneous viral resolution.

What is the treatment for chronic hepatitis C?

Over 90% of people infected with hepatitis C virus (HCV) can be cured of their infection, regardless of HCV genotype, with 8–12 weeks of oral therapy.

Are patients undergoing treatment for hepatitis C at risk for reactivation of an existing hepatitis B virus (HBV) infection? How are these patients managed?

Yes. HBV reactivation has recently been reported in co-infected patients receiving direct acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection. Therefore, all patients initiating HCV DAA therapy should be tested for HBV with HBsAg, anti-HBs, and anti-HBc. People testing positive for HBsAg and/or anti-HBc should be monitored while receiving HCV treatment.