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Hepatitis C

Hepatitis is the inflammation of the liver cells known as Hepatocytes caused by viruses. Such viruses have an attraction towards the liver. When there is an involvement of HCV (Hepatitis C virus) which is a RNA virus leading to liver infection, it is termed as Hepatitis C.

Causes of Hepatitis C

Hepatitis C virus spreads via parenteral route. The most common routes of infection are as follows:

  • Intravenous drug abusers
  • Blood transfusions
  • Reuse of syringes
  • Multiple sex partners
  • Homosexuals
  • Sex with commercial sex providers
  • Tattoos
  • Needle stick injury
  • Shaving by barbers
  • Any kind of sharp object injury
  • Perinatal transmission

Hepatitis C

Hepatitis C Prevalence

Hepatitis C is the major cause of chronic liver disease. According to the (WHO) World Health Organization, there are more than 170 million people in the world who are infected with hepatitis C virus.

Chronic Hepatitis C Progress

Hepatitis C starts with an acute form of disease which can go either way. Patient may recover or progress to chronic disease. Usually chronic Hepatitis C is a silent disease which is diagnosed during routine screening or if patient comes to a doctor for symptoms like abdominal pain or jaundice where the patient is advised for liver function test, in which serum ALT is elevated.

Such patient goes for further workup in which Anti HCV (antibodies to Hepatitis C Virus) and HBsAg (Hepatitis B surface Antigen) are done, which are the initial screening tests to rule out Hepatitis B and C.

Acute Hepatitis C

Acute Viral Hepatitis C is defined as presence of either signs and symptoms or biochemical markers or both for a period lasting for less than 6 months of duration. Absence of HCV RNA in patients with Acute Hepatitis makes prognosis better but unfortunately this is the case in only 20% of population.

  • Total Incubation period – 2 to 26 weeks
  • Mean Incubation Period – 6 to 12 weeks
  • HCV RNA – 1 to 3 weeks (indicates disease)
  • Serum ALT levels elevations – 6 to 12 weeks; 10 to 30 times higher than ULN (upper limit of Normal).
  • Anti HCV – Approximately after 8 weeks (both types of antibodies; IgM and IgG appears showing recovery, IgG antibodies remain for years)

Chronic Hepatitis C

The progression of acute to chronic Hepatitis C Virus infection occurs in approximately 80% of patients. If the acute disease does not get resolved after six months it is called Chronic HCV infection.

HCV RNA is not eliminated in such patients and can develop Cirrhosis in next 20 to 30 years.

Signs and Symptoms of Hepatitis C

Interestingly, most of the patients do not manifest any signs or symptoms. Some patients might present with following:

  • Fatigue
  • Dark Urine
  • Loss of appetite
  • Malaise
  • Nausea
  • Right upper quadrant pain (abdominal pain)
  • Muscle and joint pains
  • Jaundice

Period of illness – 2 to 12 weeks

Diagnosis of Hepatitis C

The diagnosis of Hepatitis is confirmed by HCV RNA which is usually done by PCR (Polymerase Chain Reaction). The pattern of diagnosis is as follows:

  • Serum aminotransferases (ALT and AST) levels are checked; elevated levels indicates injury to liver cells.
  • If serum aminotransferases levels are higher than normal levels, then Anti HCV (antibodies to Hepatitis C virus) are checked.
  • If Anti HCV are positive, then HCV RNA by PCR is done.
  • There are 2 types of HCV RNA: Qualitative HCV RNA and Quantitative HCV RNA.
  • Qualitative HCV RNA is done usually to detect HCV RNA in the blood to establish the diagnosis of Hepatitis C Virus infection.
  • Quantitative HCV RNA is usually done to see the viral load which helps in determining the treatment response.

Significance of Genotypes of HCV

  • There are 6 genotypes of Hepatitis C Virus.
  • Genotypes 2 and 3 are considered easy to treat because they have good response to current available treatment options.
  • Genotypes 1 and 4 are considered difficult to treat because the success rates are lower than that for Genotypes 2 and 3.
  • Genotypes 5 and 6 are relatively uncommon and response rates are poor among them too.

Importance of Treatment for Hepatitis C Infection

Hepatitis C Virus infection must be treated because it gradually destroys the entire liver.

  • Hepatic destruction will start from necrotic cell death
  • Which will lead to fibrosis
  • Followed by Cirrhosis
  • Finally Hepatic Decompensation and failure
  • Patient may progress to Liver Cancer

This progression can take 20 – 30 years or even more. The rate of progression of disease may be increased due to following factors:

  • If patient is alcoholic
  • Smoking
  • Concurrent HCV – HBV infection
  • Concurrent HCV – HIV infection

All patients who develop cirrhosis ultimately lead to complications of Hepatitis C.

Treatment for HCV Infection

Hepatitis C Virus Infection is treated with the use of Interferon in combination with Ribavirin.

There are 2 types of Interferon which are used in the treatment of HCV infection:

  • Interferon alpha-2a
  • Interferon alpha-2b

Previously, Conventional Interferon’s were used to treat Hepatitis C infection but due to poor success rates, they are no longer advisable but still they are used in few countries due to low cost. Conventional Interferon’s are administered every alternate day with 3 injections per week.

Pegylated Interferon’s have replaced conventional Interferon’s due to once/weekly dosing schedule and higher success rates.

  • The duration of treatment varies according to the Genotype involved.
  • For Genotype 2 or 3 – 6 months, combination therapy with Pegylated Interferon and 800 mg Ribavirin.
  • For Genotype 1, 4, 5 & 6 – 12 months, combination therapy with Pegylated Interferon and 800 – 1200 mg Ribavirin.

Calculating Treatment Response

SVR or Sustained Virological Response is the goal of therapy in Hepatitis C infection. The treatment response in patients with HCV infection is calculated as follows:

  • Start of therapy – HCV RNA detectable; start treatment.
  • After 4 weeks of therapy – HCV RNA detectable; continue treatment.
    • If HCV RNA is not detectable, then also continue treatment.
    • Un detectable HCV RNA after 4 weeks of therapy is known as RVR (Rapid Virological Response).
    • RVR shows good response to treatment.
  • After 12 weeks of therapy – HCV RNA detectable; treatment continuation will depend on viral load;
    • HCV Genotyping should be done if not done previously.
    • Quantitative HCV RNA will determine the treatment response with respect to viral load
    • If viral load is not decreased significantly, discontinue the treatment.
    • If HCV RNA is not detectable, then continue treatment for 6 months in Genotype 2 or 3.
    • If HCV RNA is not detectable, then continue treatment for 6 months in Genotype 1 or 4.
    • Un detectable HCV RNA after 12 weeks of therapy is known as EVR (Early Virological Response).
    • EVR shows good response to treatment.
  • At the end of therapy – HCV RNA detectable; discontinue treatment.
  • If HCV RNA is undetectable at the end of therapy, then HCV RNA is repeated after 6 months.
  • Undetectable HCV RNA after 6 months of completion of therapy is known as SVR; Sustained Virological Response.

If SVR is achieved in HCV patient, it is considered that the patient is cured, but such patients are also advised to check HCV RNA on yearly basis as chances of relapse are always there.

  • References
    • 1. Robbins, Stanley L., Vinay Kumar, and Ramzi S. Cotran. Robbins and Cotran Pathologic Basis of Disease. Philadelphia, PA: Saunders/Elsevier, 2010. 851-54. Print.
    • 2. Mauss, Stefan. Short Guide to Hepatitis C 2011. Düsseldorf: Flying, 2011. 26-47. Print.
    • 3. Mushahwar, I. K. Viral Hepatitis: Molecular Biology, Diagnosis, Epidemiology, and Control. Amsterdam: Elsevier, 2004. 127-72. Print.

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