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Table of Contents

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  • Hepatitis C Virus (HCV)
        • What sample is needed for the Hepatitis C Virus (HCV)?
        • What are the precautions for the Hepatitis C Virus (HCV)?
        • What are the indications for Hepatitis C Virus (HCV)?
        • How will you define the Hepatitis C Virus (HCV)?
        • How will you discuss the history of viruses, NANB, or HCV?
        • How will you discuss the biology and structure of the Hepatitis C Virus (HCV)?
        • What is the genetic variation of the Hepatitis C Virus (HCV)?
        • What is the Hepatitis C Virus (HCV) genome structure?
        • What is the mode of spread of the Hepatitis C Virus (HCV)?
        • What is the incubation period for the Hepatitis C Virus (HCV)?
        • What are the types of antigens and antibodies of the Hepatitis C virus (HCV)?
        • What are the signs and Symptoms of the Hepatitis C Virus (HCV?
        • What are the common symptoms of the Hepatitis C Virus (HCV)?
        • What is the Hepatitis C Virus (HCV) serological profile?
      • How will you diagnose the Hepatitis C Virus (HCV)?
        • What is the interpretation of the HCV-antigen (HCV-Ag)?
        • What is the interpretation of the HCV-antibody (HCV-IgG)?
        • How will you summarize Hepatitis C Virus (HCV) antigen and antibody?
        • What are the complications of Hepatitis C Virus (HCV) infection?
        • How will you treat the Hepatitis C Virus (HCV)?
        • How will you prevent the spread of the Hepatitis C Virus (HCV)?
      • Questions and answers:

Hepatitis C Virus (HCV)

What sample is needed for the Hepatitis C Virus (HCV)?

  1. The best sample is the patient’s serum.
  2. The anti-HCV serum is stable for 7 days at room temperature.
  3. This test can also be done on the plasma.
  4. This test can be performed on a random sample.

What are the precautions for the Hepatitis C Virus (HCV)?

  • Separate serum or plasma immediately to prevent viral degradation by white blood cells.

What are the indications for Hepatitis C Virus (HCV)?

  1. To diagnose the patient with HCV infection.
  2. For screening of the blood donor.
  3. This should be done to healthcare workers.
  4. Advised for the drug users.
  5. A person who has sex with a positive partner.
  6. In patients with HIV.
  7. In abnormal liver function tests.
  8. Blood transfusion or organ transplantation before July 1992.
  9. The patients with hemophilia were treated before 1987.

How will you define the Hepatitis C Virus (HCV)?

  1. This was formally called a non-A, non-B viral infection (NANB) because no tests were available. This was suspected by the exclusion of HBV and HAV.
  2. Hepatitis C is a blood-borne infection of the liver, and it leads to a high rate of chronic liver disease.

How will you discuss the history of viruses, NANB, or HCV?

  1. Later, the Hepatitis D virus was discovered and distinguished from NANB.
  2. NANB was also known as short-incubation and long-incubation viruses.
    1. The short-incubation virus was labeled as the Hepatitis E virus.
    2. The long-incubation name was still known as NANB.
  3. In 1991, the virus was identified as Hepatitis C Virus (HCV).
  4. The second-generation HCV test became available in 1993.
  5. A third-generation test for HCV was available in 1994.
  6. First and second-generation tests diagnose only HCV-IgG.
  7. HCV is the only virus with a long incubation period and was formerly known as the NANB virus.

How will you discuss the biology and structure of the Hepatitis C Virus (HCV)?

  1. Hepatitis C virus (HCV) is a hepatotropic virus. It belongs to the Flavivirus family.
  2. HCV  is a small enveloped virus measuring 55 to 65 nm.
  3. HCV is a small, positive-single-stranded RNA virus of the Flaviviridae family.
  4. HCV consists of 10,000 nucleotides of single-stranded RNA molecules in one common open reading frame.
  5. This was formally called a non-A, non-B viral infection because no test was available. This was suspected by the exclusion of HBV and HAV.
  6. HCV exists in 4 genotypes or strains:
    1. Core antigen.
    2. NS3 gene.
    3. NS4 antigen.
    4. NS5 antigen
  7. HCV infection differs from HBV infection in that it causes more than 60% of cases to become chronic.
  8. 20% of the patients develop cirrhosis and hepatocellular cancer.
Hepatitis C virus (HCV) structure

Hepatitis C virus (HCV) structure

What are the characteristic features of the Hepatitis C Virus (HCV)?

Parameters Characteristic features
  • Family
  • Flaviviridae
  • Genus
  • Not named
  • Genome
  • ssRNA
  • Genome size
  • 9.5 kb
  • Size of the virus
  1. Virion = 30 to 60 nm, spherical
  • Envelope
  • It is present
  • Incubation period
  1. 40 to 120 days
  2. Average incubation is 6 to 8 weeks
  3. But may see 2 weeks to one year
  • Common age group
  • Adults
  • Any seasonal incidence
  • It is present throughout the year
  • Its presence in urine
  • Probably absent
  • Fever
  • It is less common
  • Liver function test (LFT)
  • Abnormal 1 to >6 months
  • Transmission
  1. Parenteral
  2.  Close Contacts
  3. Sexually transmitted
  4. It is found in serum, semen, and saliva (3 S)
  • Prevalence
  • Moderate
  • Fulminant disease
  • It is rare
  • Chronicity
  • It is common (>50%)
  • Stability
  1. It is ether sensitive
  2. It is acid-sensitive
  • As an oncogenic virus
  • It can form liver cell carcinoma

What is the genetic variation of the Hepatitis C Virus (HCV)?

  1. HCV genotypes are detected based on treatment response.
  2. There are 6 genotypes with several subtypes.
  3. Genotype 1 progresses to chronicity and cirrhosis. It is less responsive to treatment.
  4. Genotypes 2 and 3 are very responsive to antiviral treatment.
    1. 75% of Americans have genotype 1, subtypes 1a and 1b.
    2. 20% to 25% have genotypes 2 and 3.
  5. Genotype 4 is more common in African countries.
  6. Genotype 5 is more common in South Africa and Asia.
  7. Genotype 6 is more common in Southeast Asia.
    1. The smaller percentage has genotypes 4, 5, and 6.

What is the Hepatitis C Virus (HCV) genome structure?

  1. It consists of an N-terminal and a C-terminal.
  2. There are core proteins, envelope proteins, and non-structural proteins.
Hepatitis C virus (HCV) proteins

Hepatitis C virus (HCV) proteins

What is the mode of spread of the Hepatitis C Virus (HCV)?

  1. Blood (Serum).
  2. Saliva.
  3. Semen.
  4. Major risk groups are:
    1. Blood transfusion.
    2. I/V drug abusers.
    3. Blood products.
  5. The mode of spread is like HBV, with some differences.
  6. In 50% of cases, the source of the cases is unknown.
  7. One of the modes is blood transfusion or blood products (now rare because screening tests have been available since 1987).
  8. HCV hepatitis (post-transfusion hepatitis)  is quite common in volunteer blood donors who are HBV-negative.
  9. Vertical transmission from mothers to newborns is not as common as HBV infection.
  10. This can spread through sexual contact, but some believe that sexual transmission is uncommon.
    1. This is seen in sex with multiple partners and unprotected sex.
    2. Male homosexuals are less likely to be infected as compared to HBV.
    3. It is also seen in smaller numbers in heterosexual groups.
  11. This is seen in organ transplantation (before 1992).
  12. This is common in I/V drug users.
  13. Tattooing in an unhygienic atmosphere.
  14. This may be seen in HIV patients.
  15. Sharing personal items, such as toothbrushes or shavers, that may be contaminated with blood.
  16. It is estimated that 50% of cases have an unknown mode of transmission.
  17. Fetal and neonatal transmission is uncommon.
  18. Passive transfer of anti-HCV antibodies is quite common.
Hepatitis C virus (HCV) mode of spread

Hepatitis C virus (HCV) mode of spread

What is the incubation period for the Hepatitis C Virus (HCV)?

  1. It is 2 to 12 weeks after exposure. (Other references give 2 to 52 weeks) and the average period is 7 or 8 weeks.
    1. Incubation of 2 weeks to one year is also reported.

What are the types of antigens and antibodies of the Hepatitis C virus (HCV)?

  1. HCV-Ab (IgG) appears in 3 to 4 months and disappears in 2 years.
    1. Most cases develop HCV-IgG antibodies by 6 weeks, with and range of 5 to 30 weeks after the onset of symptoms.
    2. The anti-HCV can be detected in acute hepatitis C during the initial phase of elevated aminotransferase activity.
    3. This antibody may never be detected in 5% to 10% of the patients with acute Hepatitis, and anti-HCV may become undetectable after the recovery from acute hepatitis.
  2. The current screening test detects antibodies against HCV.
    1. An anti-HCV screening test has been available for less than 10 years.
  3. This is a unique virus in which, during acute infection, you can detect anti-HCV antibodies and HCV RNA.
  4. Anti-HCV remains for many years. Therefore, a positive anti-HCV test indicates infection or carrier state but not infectivity or immunity.

What are the signs and Symptoms of the Hepatitis C Virus (HCV?

  1. HCV infection is also called a silent disease.
  2. The clinical S/S is like an HBV infection but less severe.
  3. It is in 12% to 25% of cases of sporadic hepatitis that are not related to parenteral inoculation or sexual transmission.
  4. Only 15% develop acute infection, and the rest develop chronic disease.
  5. Chronicity of the infection is seen in 50% to 80% of cases (another reference reports 70% to 80%).
    1. Chronicity is more common than HBV infection.
    2. It is seen in 60% of post-transfusion cases and may take 10 years.
    3. 30% of cases may develop cirrhosis in around 10 years.
    4. HCV infection may lead to chronic active hepatitis and cirrhosis.
    5. In one of the studies, chronic active hepatitis was seen in <20%, and 3% had cirrhosis.
Hepatitis C virus (HCV) acute infection

Hepatitis C virus (HCV) acute infection

  1. Fulminant hepatitis is seen in 1% to 2% of patients.
  2. HCV infection symptoms may not appear or may be very mild for years.
  3. Chronic infection is often asymptomatic.
  4. The silent disease still causes damage to the liver.
  5. The patient with the silent disease may come with chronic liver disease and may develop cirrhosis and liver cell carcinoma.
    1. It is considered a significant etiology for liver cell carcinoma.

What are the common symptoms of the Hepatitis C Virus (HCV)?

  1. Jaundice is seen in only 25% of acute hepatitis.
  2. Tiredness
  3. Loss of appetite
  4. Nausea and vomiting
  5. Abdominal pain
  6. Joints pain
  7. Fever
  8. Dark urine and gray-colored stool.
  9. Ultimately, the patient develops jaundice.
  10. This chronic viral infection can lead to liver cell carcinoma.

What is the Hepatitis C Virus (HCV) serological profile?

  1. An anti-HCV screening test has been available for less than 10 years.
    1. Anti-HCV Ab (IgG) indicates:
      1. Convalescent stage.
      2. Old HCV infection.
  2. Anti-HCV antibodies are IgM and IgG types.
  3. Anti-HCV Ab seen against:
    1. Core antigen.
    2. NS3 gene.
    3. NS4 antigen.
    4. NS5 antigen.
Hepatitis C virus (HCV) serology in chronic disease

Hepatitis C virus (HCV) serology in chronic disease

  1. HCV PCR, which detects HCV RNA, is used to confirm the diagnosis.
    1. Viral load advises quantitative PCR.
  2. Usually, SGPT (ALT) is raised in this infection and in chronic cases.
  3. A negative anti-HCV antibody test does not exclude HCV infection because seroconversion may not occur for up to 6 months after exposure.
Hepatitis C virus (HCV) chronic hepatitis and fluctuating SGPT level

Hepatitis C virus (HCV), chronic hepatitis, and fluctuating SGPT level

How will you diagnose the Hepatitis C Virus (HCV)?

  1. Interpretation of HCV profile:
  2. Acute infection = Anti-HCV antibody will be positive.
    1. Anti-HCV by ELIZA is confirmatory.
    2. PCR can confirm the diagnosis.
      1. Qualitative PCR for the HCV genome.
      2. Quantitative HCV RNA PCR.
      3. PCR (polymerase chain reaction) will show the virus’s presence in the blood.
      4. PCR is the confirmatory test for HCV infection.
      5. PCR is performed in patients to initiate treatment.
Clinical features of Acute HCV infection
  1. Jaundice or increased ALT (SGPT)
  2. Acute illness
Laboratory workup
  1. HBs-antigen is negative
  2. HAV-IgM is negative
  3. Anti-HCV is positive
  4. PCR HCV is positive
  5. ALT (SGPT) is >7 times the normal

Chronic infection: almost 85% show anti-HCV antibodies.

  1. Positive HCV-Ab indicates present or past infection.
Clinical features of chronic HCV infection
  • Usually asymptomatic
Laboratory workup of chronic HCV infection
  1. Anti-HCV is positive
  2. PCR positive
  3. HBs-antigen is negative
  4. HAV-IgM is negative

What are the HCV markers in various diseases?

Test Normal Early infection Acute Chronic Carrier Recovery
  • Anti-HCV
  • Negative
  • Negative
  • Positive
  • Positive
  • Positive
  • Positive
  • PCR
  • Negative
  • Positive
  • Positive
  • Positive
  • Positive
  • Negative

What is the interpretation of the HCV-antigen (HCV-Ag)?

  1. Nucleic acid probe without PCR:
    1. It appears about 3-4 weeks after infection.
  2. Nucleic acid probe with PCR:
    1. It becomes undetectable near the end of active infection, at the beginning of convalescence.
    2. RNA-PCR is positive after the second week of infection.
    3. It is undetectable after the end of active infection, beginning of the convalescent stage.

What is the interpretation of the HCV-antibody (HCV-IgG)?

  1. Done by ELIZA:
    1. It appears about 3-4 months after infection.
    2. 80% by 5 -6 weeks after the symptoms.
    3. It is undetectable in 7% of cases within 1.5 years.
    4. 7%-66% is negative by 4 years.

How will you summarize Hepatitis C Virus (HCV) antigen and antibody?

  1. HCV-antigen indicates acute infection.
  2. HCV-IgG indicates active, convalescent stage.
    1. It may also indicate an old infection.

What are the complications of Hepatitis C Virus (HCV) infection?

  1. There are chances for:
  2. Fulminant hepatitis is seen in 1% to 2% of patients.
    1. Cirrhosis is seen in 5% of cases.
    2. Liver failure.
    3. Liver cancer risk is 15%.
  3. HCV infection differs from HBV infection in that it causes more than 60% of cases to become chronic.
    1. (Some references say chronicity is from 50% to 80%)

How will you treat the Hepatitis C Virus (HCV)?

  1. Alfa-interferon alone. It benefits <50% of cases. Relapse is common when you stop the treatment.
    1. Interferon (IFN-α2, 3,000,000 U) is given subcutaneously 3 times per week for 1 year.
    2. It prevents the development of liver cell carcinoma.
    3. Monitor with SGPT, SGOT, and HCV PCR.
    4. Retreatment can be given in  50% to 80% of the relapse cases.
  2. Type 2 and 3 genotype-positive patients are three times more sensitive to antiviral treatments such as alpha-interferon or combination therapy with Ribavirin.
  3. Alfa-interferon with  Ribavirin as combination therapy.
  4. The latest therapy can cure 95% of patients.
  5. To label the patient as cured, PCR HCV is negative for 3 months after completion of treatment.

How will you prevent the spread of the Hepatitis C Virus (HCV)?

  • There is no vaccination available for HCV.
  • Proper testing of blood donors for transfusion-related HCV has decreased the incidence.

How will you summarize the differences between HAV, HBV, and HCV viruses?

Characteristic features HAV HBV HCV
  • Genome
  • RNA
  • DNA
  • RNA
  • Mode of transmission
  • Feco-oral route
  1. Blood
  2. Sexual
  • Blood
  • Chronic stage
  • None
  • Present
  • Most common
  • Cancer risk
  • None
  • May be
  • May be
  • Vaccine
  • Available
  • Available
  • None

Questions and answers:

Question 1: What is the chronicity in HCV infection as compared to HBV?
Show answer
Chronicity is (50% to 80%) HCV is more than the HBV infection.
Question 2: Is there any possibility of a vaccine for HCV?
Show answer
Still no vaccine developed for HCV infection. It keeps on changing the envelope, and there are genetic variations .

Possible References Used
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Comments

Manuela Russo Reply
July 21, 2020

Here you say anti hcv last 2 years then you write many years. What is true?

Dr. Riaz Reply
July 21, 2020

Thanks for the question. I have elaborated on the statement in the text. Please see the link.
https://www.labpedia.net/hepatitis-c-virus-part-1-hcv-profile/

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