Hepatitis C Virus :- Part 1 – Hepatitis C Virus, HCV Profile

Sample

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

Precaution

• Separate serum or plasma immediately to avoid degradation of the virus by the white blood cells.

Indications

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

Pathophysiology

1. This was formally called non-A, non-B viral infection because no test was available. This was suspected by the exclusion of HBV and HAV.
2. Hepatitis C virus (HCV) is a hepatotropic virus.
   1. HCV  is a small enveloped virus measuring 55 to 65 nm.
   2. HCV is a single-stranded RNA virus of the Flaviviridae family.
   3. This was formally called non-A, non-B viral infection because no test was available. This was suspected by the exclusion of HBV and HAV.
3. HCV infection is unlike HBV because this gives rise to more than 60 % as a chronic disease.
4. 20 % of the patient develop cirrhosis and hepatocellular cancer.
5. The incubation period is 2 to 12 weeks after the exposure. (other references give 2 to 52 weeks and the average period being 7 or 8 weeks).
   1. HCV-Ab (IgG) appears 3 to 4 months. and disappears in 2 years.
      1. The anti-HCV can be detected in acute hepatitis-C during the initial phase of elevated aminotransferases activity. This antibody may never be detected in 5 to 10% of the patient with acute Hepatitis-C and anti-HCV may become undetectable after the recovery from acute hepatitis.
6. The current screening test detects antibodies against HCV.
   1. An anti-HCV screening test is available for less than 10 years.
7. This is the unique virus in which in acute infection you can find an Anti-HCV antibody and also the antigen HCV-RNA.
8. The presence of Anti-HCV remain for many years, therefore anti-HCV test positive indicate infection or carrier state but not infectivity or immunity.

Signs and Symptoms

1. HCV infection also called a silent disease.
2. Only 15% develop acute infection rest goes into a chronic disease.
3. Chronicity of the infection is seen in the 50 to 80% of the cases (another reference says 70 to 80%).

4. Fulminant hepatitis is seen in 1 to 2% of the patient.
5. HCV infection symptoms may not appear or very mild for years.
6. Chronic infection is often asymptomatic.
7. The silent disease still causes damage to the liver.
8. The patient with the silent disease may come with chronic liver disease and may develop cirrhosis and liver cell carcinoma.
9. Common symptoms of HCV are :
   1. Tiredness
   2. Loss of appetite
   3. Nausea and vomiting
   4. Abdominal pain
   5. Joints pain
   6. Fever
   7. dark urine  and gray-colored stool
   8. Ultimately patient develops jaundice
10. This virus chronic infection can lead to liver cell carcinoma.

Mode of spread

1. The mode of spread is like HBV with some differences.
2. One of the modes is blood transfusion or blood products (Now it is rare because of screening tests available since 1987).
3. Vertical transmission from mothers to a newborn is not as common as HBV infection.
4. This can spread through sexual contacts, but some believe that sexual transmission is uncommon.
   1. This is seen in sex doing with multiple partners and unprotected.
5. This is seen in organ transplantation (before 1992).
6. This is common in the I/V drug users.
7. Tattooing in the unhygienic atmosphere.
8. This may be seen in HIV patients.
9. Sharing personal items like toothbrushes, or shaver which may have blood contamination.
10. Now it is believed that 50% of the cases mode of transmission is not known.

Hepatitis C profile

1. An anti-HCV screening test is available for less than 10 years.
2. Anti-HCV antibodies are IgM and IgG type.
   1. Anti-HCV antibodies:
      1. Anti-HCV Ab seen against:
         1. Core antigen.
         2. NS3 gene.
         3. NS4 antigen.
         4. NS5 antigen.

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

Genetic variation of HCV

1. Genotypes of HCV are detected because of its response to treatment.
2. There are 6 genotypes with several sub-types.
   1. Type 1 genotype progress to chronicity and to cirrhosis. It is less responsive to treatment.
   2. Type 2 and 3 genotypes are very responsive to antiviral treatment.
3. 75% of the Americans have genotype 1 and it has subtype  1a and 1b.
   1. 20 to 25% have genotype 2 and 3.
   2. The smaller percentage has genotype 4, 5, 6.
4. Genotype 4 is more common in African countries.
5. Genotype 5 is more common in South Africa and Asia.
6. Genotype 6 is more common in Southeast Asia.
7. HCV genome structure consists of N- terminal and C-terminal.
   1. There are core proteins, envelope proteins, and non-structural proteins.

Lab diagnosis

1. Interpretation of HCV profile:
   1. 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 HCV genome.
      2. Quantitative HCV RNA PCR.
         1. PCR (polymerase chain reaction) will tell the presence of the virus in the blood.
         2. PCR is the confirmatory test for HCV infection.
         3. PCR is done in patients to start the treatment.
   3. Chronic infection = Almost 85 % shows Anti-HCV antibody.
   4. Positive HCV-Ab indicates present or past infection.
   5. Table showing HCV markers in various conditions:
      

      Test	Acute	Chronic	Carrier	Recovery
      Anti-HCV	+	+	+	None
      PCR	+	+	+	+

The complication of HCV infection

1. There are chances for:
   1. Fulminant hepatitis is seen in 1 to 2% of the patients.
   2. Cirrhosis is seen in 5% of the cases.
   3. Liver failure.
   4. Liver cancer risk is 15%.
   5. HCV infection is unlike HBV because this gives rise to more than 60% as a chronic disease.
      1. (some references says chronicity is from 50 to 80%)

Treatment Options

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

Prevention

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

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