Hepatitis C Virus (HCV)

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 for Hepatitis C Virus

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

Indications for Hepatitis C Virus (HCV)

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 with hemophilia were treated before 1987.

Definition of Hepatitis C Virus

1. This was formally called non-A, non-B viral infection (NANB) because no tests were available. This was suspected by the exclusion of HBV and HAV.
2. Later on, the Hepatitis D virus was discovered, and this virus was separated from NANB.
3. In 1991 virus identified was named Hepatitis C Virus (HCV).
4. The second-generation test for HCV was available in 1993.
5. A third-generation test for HCV was available in 1994.
6. First and second-generation tests diagnose only HCV-IgG.

Biology and structure of  Hepatitis C Virus (HCV)

1. Hepatitis C virus (HCV) is a hepatotropic virus. It belongs to the Flavivirus family.
   1. HCV  is a small enveloped virus measuring 55 to 65 nm.
   2. HCV is a small positive-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.
2. HCV exists in 4 genotypes or strains:
   1. Core antigen.
   2. NS3 gene.
   3. NS4 antigen.
   4. NS5 antigen
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.

Characteristic features of Hepatitis C Virus (HCV)

Parameters	Characteristic features
Family	Flaviviridae
Genus	Not named
Genome	ssRNA
Genome size	9.5 kb
Size of virus	Virion = 30 to 60 nm, spherical
Envelope	It is present
Incubation period	40 to 120 days
Commonage 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	Parenteral
Prevalence	Moderate
Fulminant disease	It is rare
Chronicity	It is common (>50%)
Stability	It is ether sensitive It is acid sensitive
As an oncogenic virus	It can form liver cell carcinoma

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 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 subtypes 1a and 1b.
   1. 20 to 25% have genotypes 2 and 3.
   2. The smaller percentage has genotypes 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.

HCV genome structure consists of N- terminal and C-terminal.

1. There are core proteins, envelope proteins, and non-structural proteins.

Hepatitis C Virus (HCV) is found in:

1. Blood (Serum).
2. Saliva.
3. Semen.
4. Major risk groups are:
   1. Blood transfusion.
   2. I/V drug abusers.
   3. Blood products.

Mode of the spread of Hepatitis C Virus:

1. The mode of spread is like HBV with some differences.
   1. In 50%,  the source of the cases is not known.
2. One of the modes is blood transfusion or blood products (Now, it is rare because of screening tests available since 1987).
   1. HCV hepatitis (post-transfusion hepatitis)  is quite common in the volunteer’s blood donors who were HBV-negative.
3. Vertical transmission from mothers to newborns is not as common as HBV infection.
4. This can spread through sexual contact, but some believe that sexual transmission is uncommon.
   1. This is seen in sex doing with multiple partners and unprotected.
   2. Male homosexuals are less likely to be infected as compared to HBV.
   3. It is also seen less in number in heterosexual groups.
5. This is seen in organ transplantation (before 1992).
6. This is common in 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 shavers that may have blood contamination.
10. Now it is believed that 50% of the case’s mode of transmission is not known.
11. Fetal and neonatal transmission is uncommon.
12. Passive transfer of anti-HCV antibodies is quite common.

The incubation period:

1. It 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. Incubation of 2 weeks to one year is also reported.

Type of antigens and antibodies:

1. HCV-Ab (IgG) appears 3 to 4 months. and disappears in 2 years.
   1. Most of the cases develop HCV-IgG antibody by 6 weeks and the range is 5 to 30 weeks after onset of the symptoms.
   2. 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.
2. The current screening test detects antibodies against HCV.
   1. An anti-HCV screening test is available for less than 10 years.
3. This is the unique virus in which in acute infection you can find an Anti-HCV antibody and also the antigen HCV-RNA.
4. The presence of Anti-HCV remains for many years, therefore anti-HCV test positive indicates infection or carrier state but not infectivity or immunity.

Signs and Symptoms of  Hepatitis C Virus (HCV)

1. HCV infection is also called a silent disease.
   1. The clinical S/S are like HBV infection but these are less severe.
   2. It is in 12% to 25% of cases of sporadic hepatitis that is not related to parenteral inoculation or sexual transmission.
2. Only 15% develop acute infection rest goes into a chronic disease.
3. Chronicity of the infection is seen in 50% to 80% of the cases (another reference says 70 to 80%).
   1. Chronicity is more common than HBV infection.
   2. It is seen in 60% of the post-transfusion cases and it 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 seen in <20% and 3% has cirrhosis.

4. Fulminant hepatitis is seen in 1 to 2% of the patient.
5. HCV infection symptoms may not appear or are 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.
   1. It is considered a major etiology for liver cell carcinoma.
9. Common symptoms of HCV are :
   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 patient develops jaundice
10. This virus chronic infection can lead to liver cell carcinoma.

Hepatitis C Virus serological 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.

Lab diagnosis of Hepatitis C Virus (HCV)

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	Normal	Early infection	Acute	Chronic	Carrier	Recovery
      Anti-HCV	Negative	Negative	+	+	+	+
      PCR	Negative	+	+	+	+	Negative

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.

Preventions

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

---