September 14, 2012

What to do with a positive hep C test

Lynn Rapsilber, MSN, ANP-BC, APRN

September 13, 2012

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.

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.

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).

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 or 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.

Predictors of treatment response include age (younger individuals have greater likelihood of response), sex (both males and females are at the same rate of treatment response), race (blacks respond less favorably to treatment than whites), and weight (higher BMI, insulin resistance, and fatty liver can hinder the ability to process medications that can help treatment response). Severe depression and anxiety and continued drug and alcohol use will impact the ability of the medications to be effective in cure. HIV-positive individuals who are co-infected with hepatitis C respond less favorably to treatment.

Treatment response

Treatment response for hepatitis C is measured by viral response. Rapid viral responders have no measurable virus at four weeks. Early viral responders have a >2 log drop at four weeks and no measureable virus at 12 weeks. Slow viral responders are not negative at week 12 but turn negative at week 24. Null responders have <2 log drop in viral load. Sustained viral response is no measurable virus six months after treatment and is considered a cure.

Genotype used to be a factor in treatment response, but with the development of the new PIs, genotype 1 responses are equal to or comparable to genotype 2 and 3. The higher the viral load the greater the virus to be killed, which can impede response.

Adherence to treatment is favorable when there is a good patient/provider relationship; adequate support systems in place; compliance with follow-up instructions, appointments, and lab draws; belief on the part of the patient that treatment will be beneficial; completion of the treatment; and a thorough explanation of the costs associated with treatment (i.e., insurance co-payments, medications, prior authorization).

Treatment recommendations

The current treatment recommendations for hepatitis C are based on genotype. Individuals with genotype 2 HCV receive peginterferon and ribavirin. Peginterferon helps fight the virus in two ways: (1) it helps healthy cells defend themselves against the virus; and (2) it strengthens the immune response, which helps the T and B cells fight off the virus. Peginterferon alfa-2a and alfa-2b are administered as subcutaneous weekly injections.

Side effects of treatment include flulike symptoms, fatigue, headache, arthralgias and myalgias, fever and chills. Other potential symptoms include anemia, diarrhea, nausea, worsening depression, mood instability, injection-site reaction, weight change, alopecia and increased susceptibility to infections and insomnia.

Ribavirin is an antiviral that interferes with RNA metabolism and slows the growth of the virus when used together with peginterferon. Ribavirin is administered orally b.i.d. Side effects include nausea; hemolytic anemia; MI with anemia; and such pulmonary symptoms as dyspnea, infiltrate and pneumonitis. Ribavirin is teratogenic and can cause birth defects or death of an unborn child. Female partners and female partners of individuals being treated with ribavirin should not become pregnant during treatment or for six months after treatment has stopped.

Protease inhibitors

PIs represent the new class of hepatitis C treatment and give new hope for individuals infected with genotype 1 HCV. Eligibility includes those who are treatment-naïve, partial responders, relapsers and null responders. PIs are given in conjunction with peginterferon and ribavirin. The response rates are quite phenomenal: 80% in treatment-naïve individuals; 75%-85% in relapsers; 50% in partial responders; and even 30% in null responders. There are two PIs available at this time.

Boceprevir. This medication is given orally 800 mg (four 200-mg tablets) t.i.d., every eight hours with food. Treatment is initiated with a four-week lead-in period of peginterferon and ribavirin alone; the triple therapy with boceprivir begins at week 5.

Duration of boceprevir for treatment-naïve individuals depends on response. If a negative HCV PCR RNA is achieved at week 4, week 8, and week 12, treatments can cease at 28 weeks. Response-guided treatment (RGT) continues depending on whether the patient is below 100 IUs of viral load measurement at specific intervals. A treatment-naive patient detected at eight weeks and negative at 12 weeks will complete boceprivir at week 36 but continue the peginterferon and ribavirin for a total of 48 weeks.

Previous partial responders and relapsers get the four-week lead in of peginterferon and ribavirin, followed by triple therapy for at least 36 weeks if negative viral-load measurements are found at four, eight, 12, 24 and 36 weeks. A patient who had measurable viral load at week 8 but was below 100 IU/mL would continue treatment for a total of 36 weeks and then dual therapy with peginterferon and ribavirin for 48 weeks.

Null responders and all cirrhotic patients get a four-week lead-in, followed by triple therapy with boceprivir, peginterferon and ribavirin for a total of 44 weeks. Any time the viral load measurement is above 100 IU/mL, the treatment is discontinued.

Telaprevir. This medication is given orally 750 mg (two 375-mg tablets) t.i.d. every eight hours with a high-fat 20-gram snack. RGT for telaprevir includes starting with triple therapy. Therapy for treatment-naïve and previous relapsers includes all three medications up front (telaprevir, peginterferon and ribavirin) for a period of 12 weeks. Depending on response, the treatment can end as early as 24 weeks or may continue for up to 36 weeks. Patients with cirrhosis may benefit from a full 48-week course.

For a previous partial responder or null responder, prescribe triple therapy (telaprevir, peginterferon and ribavirin) for 12 weeks, followed by 36 weeks of peginterferon and ribavirin alone. If viral load is nondetected at week 4 and week 12, discontinue the telaprevir and continue the peginterferon and ribavirin for a total response-week duration of 24 weeks. If the viral load is detectable but below 1,000 IU/mL at week 4 and week 12, continue the treatment to week 12, and then order an additional 36 weeks of dual therapy with peginterferon and ribavirin for a total treatment duration of 48 weeks. If at any time the viral load measurement goes above 1,000 IU/mL, at week 4, week 12, or detectable at week 24, the therapy is discontinued.

Managing side effects

Educate patients on the importance of adequate hydration and maximizing nutrition and energy-conservation strategies. If possible, clinicians should work with patient's employer to see about decreasing 12-hour shifts to eight hours to maximize energy conservation.

It is imperative that patients undergoing treatment for hepatitis C be able to continue to work, as this provide a distraction from the side effects of the medication. Counseling, patient support groups, or referral for professional help should also be considered.

Advise patients to use moisturizer to prevent rashes and dry skin. Alopecia can be minimized through less-frequent hair manipulation. Antiemetics for nausea, hematologic support for anemia and premedication with nonsteroidal anti-inflammatory drugs and alternating with acetaminophen for flulike symptoms is recommended.

During treatment monitoring, have patient visit every other week for side-effect management, counseling, and review of lab data. Viral load measurements throughout the course of treatment as described by the PI treatment algorithms are recommended and should be adhered to for the futility rules.

Above all, no PI should be stopped once it is started. The chance of developing resistance to these medications rapidly increases with the omission of even one dose. It is essential that all patients take peginterferon and ribavirin with these medications as well, and they are not interchangeable. Always stop the PI if the viral load measurement continues to increase.

Patient selection for antiviral therapy

For successful outcomes, it is imperative that clinicians spend the time up front to counsel and teach the patients and their families or supportive others. Explain that commitment requires the full duration of the treatment. Have patients sign a consent form agreeing to frequent blood testing, scheduled office visits, pregnancy prevention, and abstention from alcohol and drug use.

There is significant risk for medication reactions with PIs. A throughout medication review must be obtained before starting these drugs. Several medications are contraindicated, including simvastatin (Zocor), St. John's wort, and sildenafil (Viagra). Other medications require cautious use, including amlodipine (Norvasc), clarithromycin (Biaxin), methadone and zolpidem (Ambien). Please see the Victrelis and Incivek pagackage inserts for a complete list of potential drug interactions.

The goal with any of the treatments described is to support the patient through the process, foster a partnership in this unique opportunity to cure, and provide congratulations on the successes along the way.

Lynn Rapsilber, MSN, ANP-BC, APRN, is a nurse practitioner with Litchfield County Gastroenterology in Torrington, Conn.


  1. Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335-1374.
  2. Strader DB, Wright T, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004;39:1147-1171.
  3. Victrelis (boceprevir) Package Insert. Merck & Co., Inc.; 2011.
  4. Incivek (telaprevir) Package Insert. Vertex Pharmaceuticals; 2011.

    All electronic documents accessed September 13, 2012.


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