Hepatitis C – Current Knowledge

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Objectives

1.         Discuss the potential clinical impact of Hepatitis C infections and how patients are diagnosed and followed-up.

2.         Describe the different ways in which the Hepatitis C virus can be transmitted between adults and to children through perinatal transmission and breastfeeding.

3.         Discuss the potential treatment options for Hepatitis C infected individuals, the limitations of treatment, and the potential for an effective future vaccine or immunoglobulin.

Article

Update on Hepatitis C

                                                  Hepatitis C – Current Knowledge

Authors: Tamerou Asrat, M.D. F.A.C.O.G.

Objectives: Upon the completion of this CNE article, the reader will be able to:

1.         Discuss the potential clinical impact of Hepatitis C infections and how patients are diagnosed and followed-up.

2.         Describe the different ways in which the Hepatitis C virus can be transmitted between adults and to children through perinatal transmission and breastfeeding.

3.         Discuss the potential treatment options for Hepatitis C infected individuals, the limitations of treatment, and the potential for an effective future vaccine or immunoglobulin.

Background and Healthcare Impact:

            Many different viruses can lead to injury of liver cells producing hepatitis. Some of these are considered primary hepatitis viruses whereas others may produce hepatitis as part of their overall infection. For the primary hepatitis viruses, for years only two were distinctly known and were called Hepatitis A and Hepatitis B. Everything else was labeled non-A non-B hepatitis. In 1989, Choo and Kuo identified an RNA viral strand that was felt to be the cause of non-A non-B hepatitis. This RNA virus was soon labeled Hepatitis C (HCV). Since the discovery of the Hepatitis C virus, several distinct genetic variants have been identified based on different nucleic acid sequences. 

Currently, 7 major genotypes exist and most of these have numerous subtypes, which are labeled progressively “a”, “b”, “c”, etc. There are currently over 225 subtypes identified to date. Some studies have reported genotypes 8 through 11, but most authorities list these as primarily variants of genotypes 3 and 6. The most common genotypes in the United States, Western Europe, and Japan are 1a, 1b, 2a, 2b, 3a, 4a, and 6a. The most resistant to treatment is genotype 1. The hepatitis C virus has been classified as a separate genus to the flavivirus family. This RNA virus is approximately 9379 to 9481 nucleotides long and is 30 to 38 nanometers in diameter.

As more information is obtained on the Hepatitis C virus, the potential clinical impact of this disease is becoming apparent. Research showed that the majority of post-transfusion hepatitis was caused by Hepatitis C. The Centers for Disease Control estimates that more than 150,000 new cases occur per year in the United States alone (mostly now related to substance abuse). Based on current information, it is estimated that there are over 200 million carriers worldwide, with approximately 4 million in the United States. Of acute infections, only 20% have symptoms (meaning 80% or 4 out of 5 have no symptoms and do not realize they were infected). Once infected, about 80% become chronic carriers and again they are usually asymptomatic. Of these chronically infected HCV carriers, 75% will have elevated liver function tests, which means that 25% have normal tests but are still carriers. Chronic hepatitis C is slowly progressive, and it is estimated that 10% to 30% progress to cirrhosis after 20 years. Of those with cirrhosis, the risk of developing hepatocellular carcinoma is 2% to 5% per year.  Therefore, the potential impact on healthcare in the United States and worldwide is enormous. 

Furthermore, another difficulty that occurs in evaluating patients infected with this virus is that a viral marker antigen that denotes infectivity has not been identified. If one looks at hepatitis B, the presence of the hepatitis B surface antigen (HBsAg) denotes the possibility that a person is infectious. A similar antigen marker for hepatitis C does not currently exist. Infectivity is usually based on a positive HCV-RNA viral load.

 

Diagnosis:

In 2005, cell culture of hepatitis C became reality by 3 different research groups (Lindenbach et al, Wakita et al, and Zhong et al). This allowed every step of the viral lifecycle to be studied including viral entry into the body, replication, assembly of the virus, and release. What has made studying hepatitis C difficult is that there are essentially no animal hosts other than humans. There has been an attempt to develop a non-human primate host to study this, but research is primarily left to humans. 

The structure of the virus is basically 11 proteins. There are 3 structural proteins, which are the core protein and 2 envelope proteins designated E1 and E2. There are 8 nonstructural proteins, which are primarily different enzymes. Most of these enzymes are used for replication of the virus once a host is infected. When hepatitis C enters the bloodstream, the envelope glycoproteins E1 and E2 bind to apolipoproteins (B, C1, and E) found on circulating cholesterol. The cholesterol that it attaches to is primarily VLDL and LDL. The full viruses then circulate through the bloodstream connected to these lipoproteins and are designated lipoviral particles. This allows the virus to have access to the liver making entry into the liver cell easier because of its connection to the cholesterol molecule. Once the virus is in the cell, the RNA viral genome is replicated using the cells resources. The virus is then reassembled again attached to lipoproteins and released back into circulation.

The diagnosis of an HCV infection primarily relies upon the detection of antibodies to the virus and identifying the nucleic acid of the virus by PCR testing (polymerase chain reaction). The laboratory workup primarily involves an ELISA screening test (enzyme linked immunosorbent assay) that looks for the presence of antibody to the virus. Currently, most labs now use a third generation anti-HCV ELISA test called an ELISA-3. This ELISA test, however, can have a very high incidence of false positive results, especially if used in a low risk population.

If a patient tests positive for HCV antibody, in the past, the next step was to evaluate by a RIBA test (recombinant immunoblot assay). This test was similar to the Western Blot Assay used in evaluating infection of HIV (human immunodeficiency virus). The RIBA test was a series of different antibodies to other aspects of the hepatitis C virus, and if positive, would suggest that the patient was infected or at least had been previously exposed (versus a false positive antibody screening test if the RIBA was negative). Unfortunately, the RIBA test is no longer available as of 2012. Therefore, a positive HCV antibody screening test is now confirmed by the more specific test of HCV-RNA viral detection by PCR. The problem associated with the RIBA test no longer being available, is that it is not fully possible to tell a patient (who has a positive HCV antibody screen test result and a negative HCV-RNA PCR test result) whether the positive antibody screen result was a false positive test versus the fact that an infection did occur, but the patient now has a negative viral load. Not being able to differentiate between these 2 possibilities could theoretically affect insurability.

The mean time period from an HCV infection to the development of an anti-HCV antibody response is 12 weeks but can take up to 6 months in some cases. Therefore, during an acute episode of hepatitis, the anti-HCV antibody test may be negative. Therefore, in evaluating a patient for acute hepatitis, the HCV RNA-PCR test should be ordered. If an individual is confirmed to be infected with HCV by a positive HCV-RNA viral load, they should have liver function tests performed along with hepatitis C genotyping. Additionally, a consultation with gastroenterology is recommended to determine if a liver biopsy is indicated and whether the patient is a candidate for treatment (treatment based on the patient’s current medical status and the genotype involved).

 

Transmission of HCV:

The spread of Hepatitis C is by a percutaneous or permucosal pathway. Therefore, the transmission between individuals primarily occurs in the following ways:

·         Through Blood or Blood Products

·         Through IV Drug Abuse

·         Sexually

·         Perinatal Transmission

The risk of HCV transmission between family members or sexual partners seems to be low at less than 1% (but is not reported to be zero). In a study by Nakashima et al, of over 1100 residents in an HCV endemic area of Japan, anti-HCV antibody was detected in 14% of the population. However, the positive rate amongst sexually active spouses was only 7% with half of those tested showing different serotypes. In a study by Bresters et al, all 50 heterosexual partners of HCV positive individuals were HCV-RNA and anti-HCV negative.  The median duration of sexual relations was 13 years. Several other studies have also shown a low transmission rate by sexual activity (in the range of 1% or less). However, transmission can occur and it appears to be more common in patients with a history of multiple sexual partners. The sexual transmission rate to an uninfected person is also higher if the positive partner was infected through recurrent sources (IV drug abuse or multiple sexual partners).

This low transmission rate through sexual activity may be due to a low detection rate of the Hepatitis C virus in human secretions (other than blood). Therefore, the larger risk for HCV transmission in the population seems to stem from blood transmission such as transfusion with blood products, IV drug abuse, organ transplantation, or other external sources such as acupuncture, etc. As stated, the main area of concern when the transmission of hepatitis C was originally examined was its relation to post-transfusion hepatitis. Most studies revealed that the majority of post-transfusion hepatitis was caused by HCV. With the addition of anti-HCV testing and testing for the presence of virus by PCV of donated blood, the risk of developing post-transfusion hepatitis C infection is now less than 1 in a million units transfused. This testing of donated blood has markedly decreased the incidence of post-transfusion hepatitis in the United States. Though several papers report blood transfusion risks, the table below shows the approximant current risks of becoming infected through transfusion, per unit of blood transfused.

 

                    Table: Current estimated risks of transmitting infection per unit of blood

                             transfused from Units that are negative in laboratory testing.

 

                                                Hepatitis B                  1 in 200,000 units transfused

                                                Hepatitis C                  < 1 in 1,000,000 units transfused

                                                HIV I & II                   < 1 in 2,000,000 units transfused

 

Immunoglobulins have been used in medicine for years to help prevent or reduce the risk of infections (for example serum immune globulin, hepatitis B immune globulin, varicella zoster immune globulin, etc.). In addition, anti-D immune globulin (Rh-hyper-immuneglobulin) has nearly eliminated Rh sensitization in the United States. The safety of these products over the years has been excellent, despite the fact that these immune globulin products come from pooled plasma where some donors probably carry transmissible infections. In the mid 1990’s, there were reports of Hepatitis C transmission following the administration of some brands of serum immune globulin. The frequency of this occurrence today is negligible and there has not been a reported case of HCV transmission in nearly 20 years.

Immune globulin production starts with a fractionation procedure that effectively removes most if not all potentially infectious agents. However, due to these reported HCV transmissions (from the over 20 years ago), most products (especially those used in the United States) add other purification steps such as a solvent-detergent treatment or a low pH treatment and pepsin. Therefore, Hepatitis C transmission with these products will hopefully stay non-existent in the future.

Lastly, nearly every study on patients with illicit drug abuse and addiction have found that about 70% to 75% of those infected with hepatitis C report that they had intravenous use. However, how the other 25% became infected (if intravenous drug use had not occurred) is uncertain. Newer research is suggesting that another mode of blood transmission might occur through the sharing of snorting utensils. Some of these patients (who chronically snort) develop sores in the nasal cavity, and this might lead to blood contamination of the snorting utensil. If this utensil is shared, then the blood of the infected user could gain access through the nasal mucosa of another user leading to possible infection.

 

Perinatal Transmission of HCV:

Vertical transmission from an infected mother to the infant does occur during pregnancy. Several hundred studies have been published on the topic of perinatal transmission during the past 15 years and the data is still not completely clear. When studies are combined, the rate of perinatal HCV transmission in pregnant patients who are anti-HCV antibody positive is about 5% (with a range of 0% to about 10%). These variations in percent transmission may be due to differences in those who are viral RNA positive in the bloodstream at the time of delivery and other factors. More recent data have determined that transmission primarily only occurs in patients who are HCV-RNA positive at the time of delivery (however, the laboratory that performs the PCR testing is important, because it is an extremely sensitive test). In addition, in patients who are HCV infected and are also HIV positive, the rate of perinatal transmission increases to a range of 15% to 25%.

The HCV positive carrier rate in studies of pregnant populations from Japan to Europe to the United States ranges from 0.5% to 3% (meaning 1 in 33 to 1 in 200 pregnant women are HCV antibody positive). It is important to understand that all babies born to women who are HCV-antibody positive are HCV-antibody positive at birth. This does not mean they are infected. The newborn’s positive antibody test is caused by the mother’s antibody that crossed the placenta. Mother’s IgG antibodies can freely cross the placenta, but unfortunately, they are not protective to the newborn. Most of these newborns clear the antibody by 12 months of age. However, this maternal antibody can remain positive for up to 18 months following delivery in some uninfected children.

Another question that has not been fully answered is whether the virus can cross the placenta and infect the child prior to delivery. Most studies would suggest that this is not the case. Delamare et al tested the amniotic fluid obtained by genetic amniocentesis in 16 HCV-RNA positive women and in 15, the HCV-RNA probe was negative by PCR. The HCV-RNA was positive in one case at a very low level of 230 copies per ml of fluid. However, the amniocentesis procedure went through the placenta in a mother whose viral load was 340,000 copies per ml. This child and 9 others were tested at birth and all were negative for HCV-RNA. Therefore, the one positive amniotic fluid was probably caused by maternal blood contamination of the specimen. (Levels of HCV-RNA in the blood that are less than 10,000 copies per ml are considered low titers). PCR testing is very sensitive and can detect as few as 10 to 20 copies of virus in one milliliter of fluid. Therefore, a very tiny contamination can result in false positive results.

The Delamare report and most other studies suggest that the majority of perinatal transmission (when it occurs) takes place around the time of delivery. Because of this finding, the next question is whether the type of delivery affects this transmission rate. The majority of studies on this topic have reported that the mode of delivery did not seem to affect the perinatal transmission rate. However, it is important to note that nearly all of these studies did not separate the cesarean section group into elective cesarean prior to the onset of labor and those c-sections performed for obstetrical reasons after labor begins or membranes have been ruptured. One recent study by Gibb et al reported on the perinatal transmission rate in 441 mother-child pairs from Ireland and England using an estimation statistical approach. The perinatal transmission rate in 339 vaginal deliveries was estimated at 7.7% and the transmission rate in 54 non-elective c-sections was 5.9%. However, the transmission rate in 31 elective c-sections was 0%. Despite this finding, these percentages were not statistically different. On-the-other-hand, the European Pediatric Hepatitis C Network reported on 1,787 mother-child pairs and the transmission rate for elective cesarean delivery was 7.3% versus 5.4% for the vaginal delivery / non-elective cesarean delivery group. Therefore, further studies are needed that analyze whether there is a difference between elective cesarean delivery and routine obstetrical delivery.

The final issue regarding pregnant women infected with HCV and their newborns is breastfeeding. No studies to date have ever proven transmission to a newborn through breastfeeding. Several studies have tested breast milk for the presence of HCV-RNA and most have not detected the virus. In a few studies, HCV-RNA was detected in breast milk, but at very low levels (of < 1000 copies per ml) and usually, this was only seen in colostrum. Furthermore, it is also uncertain whether the virus can withstand the elements of the intestinal tract. According to the American College of Obstetricians and Gynecologists and American Academy of Pediatrics, breastfeeding is not contraindicated in women who are HCV positive.

Treatment of HCV:

At the present time, there is no available Hepatitis C immune globulin or vaccine that can be used in preventing this infection. The current recommendations for treatment are still very complex. Therapy in the past was limited to interferon (or its variation) along with ribavirin and was dependent upon the patient’s age, general state of health, risk of cirrhosis, likelihood of response, and life expectancy. In the past several years, numerous anti-hepatitis C anti-viral agents have been developed and marketed. Some of these include Boceprevir, Telaprevir, and Faldaprevir (NS3/4A protease inhibitors) made for treating Genotype 1. Sofosbuvir (a nucleoside inhibitor of HCV RNA-dependent RNA polymerase) and Velpatasvir (NS5A inhibitor) for treating most all genotypes. Many other direct acting antiviral agents are being tested against other protein/glycoprotein parts of the virus. Patients usually have a liver biopsy before starting treatment, which also establishes the individual’s baseline liver status. Only patients who are HCV-RNA positive should be treated (and usually ones with elevated liver function tests). Patients who are active heavy alcohol users, active IV drug users, and patients with decompensated cirrhosis are usually not be treated. Patients with genotype 1 are usually treated for up to 48 months versus 24 months with types 2 through 7. Patients treated with interferon would often rebound (up to 50%) after treatment was completed, but this occurs less with the new direct acting antiviral drugs.

No vaccine is currently available, and many hurdles still exist in its development.  The first hurdle in this regard is testing. The only way to test for the potential of infectivity is by PCR for the presence of HCV-RNA. Secondly, the only species that can be infected are humans and chimpanzees, which limit animal testing. The third issue is that many of the HCV viral proteins have a high mutation rate (meaning they are not the same from genotype to genotype). Finally, and possibly the most important, is that researchers currently have not identified an antibody that kills the virus (for example, anti-HBsAg antibody kills the hepatitis B virus). The best hope for a vaccine might be one that prevents the development of the chronic carrier state.   

In summary, HCV has rapidly become a difficult and confusing topic with many questions still unanswered.  However, the future impact of this virus on society and healthcare is massive. Therefore, further research is needed along with increasing public awareness of this infection. Hopefully, the future will bring an effective immune globulin and vaccine for prevention and research will identify a better mechanism to follow potential infectivity.

 

References or Suggested Reading:

1.         Choo QL, Kuo G, Weiner AJ, Overby LR, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989;244:359-62.

2.         Kuo G, Choo QL, Alter HJ, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 1989;244:362-4.

3.         Alter HJ, Purcell RH, Shih JW, et al. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic Non-A, Non-B hepatitis. N Engl J Med 1989;321:1494-1500.

4.         Mera J, Vellozzi C, Hariri S, Et al. Identification and clinical management of persons with chronic hepatitis C virus infection – 2012-2015. MMWR 2016;65:461-66.

5.         Cottrell EB, Chou R, Wasson N, et al. Reducing risk for mother-to-infant transmission of hepatitis C virus: a systematic review for the U.S. Preventative Services Task Force. Ann Int Med 2013;158:109-13.

6.         Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and Velpatasvir for HCV genotypes 1, 2, 4, 5, and 6 infection. NEJM 2015;373;2599-607.

7.         Church S, Barton K, Elson F, et al. Risk factors for hepatitis C virus infection among young adults – Massachusetts, 2010. MMWR 2011;60:1457.

8.         Zibbell JE, Iqbal K, Patel RC, et al. Increases in hepatitis C virus infection related to injection drug use among persons aged < 30 years – Kentucky, Tennessee, Virginia, and West Virginia 2006-2012. MMWR 2015;64:453-8.

9.         Aach RD, Stevens CE, Hollinger B, et al. Hepatitis C virus infection in post-transfusion hepatitis. N Engl J Med 1991;325:1325-9.

10.       Consensus Statement – EASL International Consensus Conference on Hepatitis C.  J Hepatol  1999;31(suppl):3-8.

11.       Marcellin P.  Hepatitis C: the clinical spectrum of the disease.  J Hepatol  1999;31(suppl):9-16.

12.       Simmonds P.  Viral heterogeneity of the hepatitis C virus.  J Hepatol   1999;31(suppl):54-60.

13.       Nakashima K, Ikematsu H, Hayashi J, et al. Intrafamilial transmission of hepatitis C virus among the population of an endemic area of Japan. JAMA 1995;274:1459-61.

14.       Bresters D, Mauser-Bunschoten EP, Reesink HW, et al. Sexual transmission of hepatitis C virus. Lancet 1993;342:210-11.

15.       Osmond DH, Padian NS, Sheppard HW, et al. Risk factors for hepatitis C virus seropositivity in heterosexual couples. JAMA 1993;269:361-65.

16.       Brettler DB, Mannucci PM, Gringeri A, et al. The low risk of hepatitis C virus transmission among sexual partners of hepatitis C-infected hemophilic males: an international, multicenter study. Blood 1992;80:540-43.

17.       Hsu HH, Wright TL, Luba D, et al. Failure to detect hepatitis C virus genome in human secretions with the polymerase chain reaction. Hepatology 1991;14:763-67.

18.       Terada S, Kawanishi K, Katayam K. Minimal hepatitis C infectivity in semen. Ann Intern Med 1992;117:171-72.

19.       Salleras L, Bruguera M, Vidal J, et al.  Importance of sexual transmission of hepatitis C in seropositive pregnant women: a case-control study. J Med Virol. 1997;52:164-7.

20.       Wejstal R.  Sexual transmission of hepatitis C virus.  J Hepatol 1999;31(suppl):92-5.

21.       YU MW, Mason BL, Guo ZP, et al. Hepatitis C transmission associated with intravenous immunoglobulins. Lancet 1995;345:1173-74.

22.       Outbreak of hepatitis C associated with intravenous immunoglobulin administration-United States, October 1993-June 1994. MMWR 1994;43:505-09.

23.       Schiff RI. Hepatitis C and immune globulin. N Engl J Med 1995;332:1236-37.

24.       Weintrub PS, Veereman-Wauters G, Cowan MJ, Thaler MM. Hepatitis C virus infection in infants whose mothers took street drugs intravenously. J Pediatr 1991;119:869-74.

25.       Giovannini M, Tagger A, Ribero ML, et al. Maternal-infant transmission of hepatitis C virus and HIV infections: a possible interaction. Lancet 1990;335:1166.

26.       Lam JPH, McOmish F, Burns SM, et al. Infrequent vertical transmission of hepatitis C virus. J Infect Dis 1993;167:572-6.

27.       Zanetti AR, Tanzi E, Newell ML.  Mother-to-infant transmission of hepatitis C virus.  J Hepatol 1999;31:96-100.

28.       Hillemanns P, Dannecker C, Kimmig R, et al. Obstetric risks and vertical transmission of hepatitis C virus infection in pregnancy.  Acta Obstet Gynecol Scand  2000;79:543-7.

29.       Conte D, Fraquelli M, Prati D, et al. Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women. Hepatology 2000;31:751-5.

30.       Delamare C, Carbonne B, Heim N, et al.  Detection of hepatitis C virus RNA (HCV RNA) in amniotic fluid: a prospective study.  J Hepatol 1999;31:416-20.

31.       Gibb DM, Goodall RL, Dunn DT, et al.  Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission.  Lancet 2000;356:904-7.

32.       Breastfeeding and the risk of Hepatitis C virus transmission.  ACOG Committee Opinion #220 August 1999.

33.       Polywka S, Schroter M, Feucht HH, et al. Low risk of vertical transmission of hepatitis C by breast milk.  Clin Infect Dis  1999;29:1327-9.

34.       Garland SM, Tabrizi S, Robinson P, et al. Hepatitis C – role of perinatal transmission.  Aust N Z J Obstet Gynaecol  1998;38:424-7.

35.       Poynard T, Bedossa P, Chevallier M, Mathurin P, et al. A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. N Engl J Med 1995;332:1457-62.

36.       Hoofnagel JH. Management of hepatitis C: current and future perspectives.  J Hepatol 1999;31(suppl):264-8.

37.       Heathcote EJ, Shiffman ML, Cooksley GE, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis.  N Engl J Med 2000;343:1673-80.

38.       Zeuzem S, Feinman SV, Rasenack J, et al.  Peginterferon alfa-2a in patients with chronic hepatitis C.  N Engl J Med 2000;343:1666-72.

39.       Abrignani S, Houghton M, Hsu HH.  Perspectives for a vaccine against hepatitis C virus.  J Hepatol  1999;31(suppl):259-63.

About the Author(s)

Dr. Tamerou Asrat is a Board Certified in Obstetrics & Gynecology as well as Maternal-Fetal Medicine (Perinatology). He currently is the Residency and Medical Student Education Coordinator at Kaiser Permanente Medical Center in Santa Clara, California. He serves as a peer-review manuscript reviewer for several journals including the American Journal of Obstetrics and Gynecology and Obstetrics and Gynecology. In addition, he was the Medical Director of Region VIII for the California Diabetes in Pregnancy Program. Dr. Asrat has received numerous teaching awards and has more than 50 publications in various medical journals. Dr. Asrat reports no conflicts of interest.

Examination

  1. The hepatitis C virus has been classified as a separate genus to the
    1. calcivirus family
    2. flavivirus family
    3. enterovirus family
    4. herpesvirus family
    5. parvovirus family
  2. Based on current information, it is estimated that there are over
    1. 2 million carriers worldwide, with 400 thousand in the United States.
    2. 20 million carriers worldwide, with 400 thousand in the United States.
    3. 200 million carriers worldwide, with 4 million in the United States.
    4. 2 billion carriers worldwide, with 400 million in the United States.
    5. 400 million carriers worldwide, with 2 million in the United States.
  3. Regarding acute HCV infections, __________ individuals have no symptoms and do not realize they were infected.
    1. 4 out of 5
    2. 1 out of 2
    3. 1 out of 3
    4. 5 out of 7
    5. 3 out of 7
  4. Once a person becomes HCV infected, 85% become chronic carriers. Chronic hepatitis C is slowly progressive and it is estimated that ________ progress to cirrhosis after 20 years.
    1. 1% to 3%
    2. 30% to 50%
    3. 3% to 5%
    4. 10% to 30%
    5. 5% to 10%
  5. Of individuals with chronic Hepatitis C who progress to cirrhosis, the risk of developing hepatocellular carcinoma is
    1. 20% to 50% per year.
    2. 2% to 5% per decade.
    3. 2% to 5% per year.
    4. 15% to 20% per year.
    5. 15% to 20% every three years.
  6. Which of the following statements is TRUE?
    1. Attempts at culturing the virus have not been successful.
    2. The diagnosis of an HCV infection primarily relies upon the detection of antibodies to the virus and identifying the nucleic acid of the virus by PCR.
    3. The laboratory workup primarily involves the result of the RIBA (recombinant immunoblot assay) screening test.
    4. The ELISA test is used to confirm a positive HCV-RNA viral load.
    5. The ELISA test has a low false positive rate in a low risk population.
  7. The mean period of time from an HCV infection to the development of an anti-HCV antibody response is 12 weeks but can take up to ______ in some cases.
    1. 6 years
    2. 3 months
    3. 3 years
    4. 12 months
    5. 6 months
  8. In evaluating a patient for an acute Hepatitis C infection, the ______ test should be ordered.
    1. HCV RNA-PCR
    2. ELISA-3
    3. RIBA-3
    4. HCV DNA-PCR
    5. ELISA first generation test
  9. The spread of Hepatitis C between individuals primarily occurs in all of the following ways EXCEPT
    1. through blood or blood products
    2. sexually
    3. through IV drug abuse
    4. contaminated shellfish
    5. from mother to baby
  10. The risk of HCV transmission between family members or sexual partners
    1. seems to be high (in the range of 40% to 50%).
    2. seems to be high (in the range of 15% to 25%).
    3. seems to be low (in the range of 10% to 15%).
    4. seems to be low (in the range of 5% to 10%).
    5. seems to be low (in the range of less than 1%).
  11. The current estimated risk of transmitting an HCV infection per unit of blood transfused from units that are negative in laboratory testing is
    1. 1 in 200,000
    2. < 1 in 1,000,000
    3. 1 in 500,000
    4. < 1 in 2,000,000
    5. 1 in 750,000
  12. In the production of immune globulins, the initial purification step starts with a (an) _____ that effectively removes most if not all potentially infectious agents.
    1. fractionation procedure
    2. solvent-detergent treatment
    3. alcohol sterilization treatment
    4. low pH treatment
    5. pepsin treatment
  13. Vertical transmission from an infected mother to the infant does occur during pregnancy. When studies are combined, the rate of perinatal HCV transmission in pregnant patients who are anti-HCV antibody positive is
    1. about 20% (with a range of 10% to about 30%).
    2. about 50% (with a range of 40% to about 60%).
    3. about 30% (with a range of 20% to about 40%).
    4. about 5% (with a range of 0% to about 10%).
    5. about 15% (with a range of 10% to about 25%).
  14. It is important to understand that all babies born to women who are HCV-antibody positive are HCV-antibody positive at birth. Which of the following statements is TRUE?
    1. The presence of this antibody means the newborn is infected.
    2. The newborn’s positive antibody test is caused by the baby producing it after an infection that occurred in utero.
    3. Mother’s IgG antibodies can freely cross the placenta, but unfortunately only IgM antibodies are protective to the newborn.
    4. Most of these newborns continue to remain positive beyond 2 years of age.
    5. The newborn’s positive antibody test is caused by the mother’s antibody that crossed the placenta.
  15. Most studies suggest that the majority of perinatal transmission (when it occurs) takes place
    1. in utero early on in gestation.
    2. in utero late in gestation.
    3. around the time of delivery.
    4. after delivery through breastfeeding.
    5. around the time of conception.
  16. Regarding the issue of women infected with HCV and breastfeeding their newborns, which of the following statement is TRUE?
    1. Most studies to date have proven that transmission to a newborn through breastfeeding occurs.
    2. Studies show that HCV can withstand the elements of the intestinal tract.
    3. According to the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics, breastfeeding is not contraindicated in women who are HCV positive.
    4. HCV RNA is almost always detected in breast milk.
    5. When HCV RNA is detected in breast milk concentrations usually exceed 1 million copies per ml
  17. Treating with interferon (or its variation) along with ribavirin was dependent upon all of the following EXCEPT
    1. the patient's age
    2. the patient's general state of health
    3. the risk of cirrhosis
    4. the titer level of the patient’s positive HCV RNA viral load
    5. life expectancy
  18. Patient’s infected with HCV who have any of the following problems should probably not be treated EXCEPT
    1. active heavy alcohol users
    2. active IV drug users
    3. patients with decompensated cirrhosis
    4. patients who are HCV-RNA negative
    5. patients with genotype 2
  19. Unfortunately, ______ of HCV infected people treated with interferon would rebound after treatment was completed.
    1. up to 50%
    2. up to 30%
    3. up to 25%
    4. up to 15%
    5. up to 10%
  20. No vaccine is currently available in the prevention of HCV infections and many hurdles still exist in its development including all of the following EXCEPT
    1. The only way to test for the potential of infectivity is by PCR for the presence of HCV-RNA.
    2. The virus cannot be replicated or cultured in vitro at the present time.
    3. The only species that can be infected are humans and chimpanzees, which limit animal testing.
    4. Many of the HCV viral proteins have a high mutation rate (meaning they are not the same from genotype to genotype).
    5. Researchers currently have not identified an antibody that kills the virus.