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According to the CDC, there are approximately 180 million hepatitis C antibody-positive individuals worldwide, 4.1 million of which reside in the United States. With 3 to 4 million new cases diagnosed per year, hepatitis C is among the fastest growing illnesses.

There are more than 7 million carriers of the hepatitis C virus (HCV) and 2.7 million chronically infected individuals. Approximately 12,000 people die from hepatitis C every year. The highest prevalence of the disease is among those aged 30 to 54 years.

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Hepatitis C is often not recognized until asymptomatic persons are identified as HCV-positive. Blood testing, first made available in 1992, is the only way to determine that an individual has hepatitis C. The treatment goal is viral eradication. If eradication cannot be accomplished, clinicians must slow disease progression, improve histology, decrease the risk of hepatocelluar carcinoma and improve quality of life.

What is hepatitis C and who is at risk?

Hepatitis C (Flaviviridae hepacivirus) is a small, enveloped, single-stranded RNA virus. This virus mutates rapidly, so changes in the envelope proteins may help it invade the immune system. The virus does not incorporate itself into the host DNA, resulting in the ability to cure the infection indefinitely. 

Acute hepatitis C refers to the first six months after infection. Between 60% and 70% of individuals infected with HCV develop no symptoms during this acute phase. In the minority of patients, acute-phase symptoms may be mild and nonspecific. Approximately 55% to 85% of acute hepatitis C patients will remain infected. Signs and symptoms of acute hepatitis C infection include fatigue, fever, dark urine, clay-colored stools, abdominal pain, loss of appetite, nausea, vomiting, joint pain and jaundice. 

Hepatitis C can also be chronic and cause chronic liver disease that ranges from mild to severe, including cirrhosis and liver cancer. Liver disease associated with chronic hepatitis C is usually insidious and progresses slowly without any signs or symptoms for several decades. 

HCV can be transmitted through a variety of ways, including: 

  • Transfusions and organ transplants before 1992 

  • IV drug use

  • Intranasal cocaine use

  • Sharing personal items with an infected person (e.g., razors, shavers, and toothbrushes)

  • Tattooing and body piercing

  • High-risk sexual activity

  • Clotting factors before 1987

  • Occupational exposures (health-care professionals)

  • Mother-to-infant transmission (rare but still considered a risk). 

Testing and screening

HCV antibody testing is sensitive and inexpensive. Anti-HCV screening assays include the enzyme immunoassay (EIA) or the enhanced chemiluminescence immunoassay (CIA). Positive results are reportable and should be confirmed with a repeat test. The recombinant immnunoblot assay (RIBA), a more specific serologic anti-HCV assay, is no longer used. Once the antibody test is positive, HCV-polymerase chain reaction (PCR) RNA test measures how much HCV is in the bloodstream. 

The American Association for the Study of Liver Disease (AASLD) recommends that all persons be screened for behaviors that place them at risk for hepatitis C infection as part of comprehensive health screening. Universal testing is not required at this time. The groups that are most strongly recommended for testing include:

  • Recent and current injection drug users (even if they have only used once)

  • HIV-infected individuals

  • Hemodialysis recipients

  • Hemophilia patients who received clotting factor concentrates before 1987

  • Patients with unexplained elevated liver abnormalities

  • Recipients of organ transplant or transplantation before July 1992

  • Children born to women infected with hepatitis C

  • Health-care workers who have had a needle exposure 

  • Current sexual partners of individuals with hepatitis C 

  • Persons who have used illicit noninjectible drugs (e.g., intranasal cocaine). 

The CDC has updated its guidelines for testing individuals born between 1945 and 1965. This group accounts for 73% of HCV mortality, and 35% of undiagnosed “baby boomers” have already progressed to advanced stages of liver disease. A one-time test for HCV is recommended without prior ascertainment of risk.

In addition to the viral load measurement or the PCR RNA testing, genotyping should also be performed. Of the six genotypes, genotypes 1, 2 and 3 are the most common in the United States.

Consequences of hepatitis C

Some of the consequences of chronic hepatitis C include hepatic fibrosis, cirrhosis, hepatocellular carcinoma, end-stage liver disease requiring transplantation and various extra-hepatic manifestations.

Hepatitis C causes inflammation of the tissue, resulting in fibrosis, which leads to scarring. This affects liver function, which further progresses the scarring to cirrhosis, eventually leading to liver failure and ultimately transplant. About 30% of those with hepatitis C will experience liver scarring leading to potential cirrhosis. Hepatocellular carcinoma occurs in about 3% of the population infected with hepatitis C. This incidence has increased over the past two decades and is identified through imaging studies or jaundice and in elevated alpha-fetoprotein levels in the blood. Surgical resection or ablative procedures increase the chance for cure.

Extra-hepatic manifestations of hepatitis C include:

  • Hematologic (anemia, and lymphoma)

  • Dermatologic (lichen planus and vasculitis)

  • Renal (glomular nephritis and nephritic syndrome)

  • Endocrine (hypothyroidism and diabetes)

  • Neuropsychiatric disease

  • Ocular (corneal ulcer and uveitis)

  • Vascular (polyarteritis nodosa and necrotizing vasculitis)

  • Neuromuscular (arthralgias and arthritis)

  • Autoimmune (CREST syndrome). 


Avoiding transmission to others is one of the best ways to contain the spread of the infection. Advise individuals with hepatitis C to: avoid sharing toothbrushes, shaving equipment, razors, nail files, and clippers; avoid tattoos and body piercings; do not donate blood, organ tissue or semen; cover bleeding wounds to prevent contact with others; discontinue illicit drug use; do not share needles. Because of the low sexual transmission rate, barrier protection is not needed in monogamous relationships; otherwise, safe sex practices are warranted. 

Alcohol and hepatitis C

The effects in alcohol and hepatitis C are well documented. Alcohol consumption of greater than 50 g per day clearly increases the progression of hepatitis C fibrosis. Daily consumption of less than 50 g appears to increase hepatitis C PCR RNA viral load levels. 

Treatment eligibility

The AASLD recommends that all patients with chronic hepatitis C be considered candidates for treatment. Review all risks and benefits with the patient. Treatment is based on histology, symptoms, probability of viral eradication, and progression of disease — not just the alanine aminotransferase levels. Treatment is contraindicated in patients with:

  • Major uncontrolled depression

  • Solid organ transplant (e.g., renal, heart, or lung)

  • Autoimmune hepatitis and other autoimmune conditions that could be worsened by treatment

  • Undiagnosed and untreated thyroid disease

  • Pregnancy unwillingness to comply with contraception

  • Severe hypertension, congestive heart failure, coronary artery disease, diabetes, and chronic obstructive pulmonary disease that is not well controlled

Hypersensitivity to any of the treatment medications (i.e., peginterferon alfa-2a [Pegasys] and alfa-2b [PEG-Intron], ribavirin [Copegus, Rebetol, RibaTab, Ribasphere], telaprevir [Incivek], Boceprevir [Victrelis]). 


The initial work-up of hepatitis C should include a complete medical, family, and social history; depression scale; and laboratory testing (Table 1). With the advent of the protease inhibitors (PIs), liver biopsy is not required; however, if a patient is considering treatment and unsure whether to proceed, a biopsy can document what liver damage has occurred and determine the grade of inflammation and the stage of liver fibrosis.

Dental work must be completed prior to treatment. Vaccination for hepatitis A and B should be initiated and should not delay the start of treatment.