Key facts
Hepatitis C Virus (HCV) is a major public health problem infecting approximately 200 million people worldwide. Infection persists in 60-80% of patients, 25% of who progress to cirrhosis with the associated complication of hepatic failure and hepatocellular carcinoma.
HCV is a virus of the flaviviridae family in the herpicivrus genus. It is an enveloped virus of about 50nm in size and consists of a positive strand RNA of approximately 9.6kb. The HCV genome encodes a large polyprotein that is proteolytically cleaved to produce 10 viral proteins during translation. These consist of the virion structural proteins: the basic core (C) protein, and glycoproteins E1 and E2 which plays an important role in the initial viral attachment. This is followed by a small integral membrane protein, p7 and the remainder of the genome encodes the nonstructural (NS) proteins NS2, NS3, NS4A, NS4B, NS5A and NS5B, which coordinate the intracellular processes of the virus life cycle. These proteins are the targets for the Direct Acting Antivirals which can effectively suppress the virus leading to a high cure rate.
Treatment
Treatment of chronic HCV infection has 2 goals. The first is to achieve sustained eradication of HCV (ie, sustained virologic response (SVR)), which is defined as the absence of HCV RNA in serum 6 months or more after completing antiviral treatment. Patients achieving SVR are effectively cured of the disease leading to the second goal to prevent progression to cirrhosis, hepatocellular carcinoma (HCC), and decompensated liver disease requiring liver transplantation.
HCV is divided among six genotypes with numerous subtypes. Depending on the HCV genotype, length of treatment can differ. The SVR rates varies with the different genotypes with SVR rates from 40% to 45% among patients with genotype 1 after 1 year of treatment to 75% to 80% in patients with genotype 2 or 3 infection after 6 months of treatment. The other genotypes receive the same duration of therapy as genotype 1 and clinical data on response to treatment are not as comprehensive as genotype 1,2 and 3.
The treatment has evolved over the last 20 years initially interferon alone at first achieving a SVR of less than 10% with 6 months of therapy. Then with ribavirin, was an empirically derived, nonspecific treatment with broad biologic properties improved the SVR to about 40% after a year of treatment. Further improvements came with the combination therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV) which has remained the standard of care for chronic hepatitis C for over a decade achieving an SVR of approximately 50%. However newer Direct Acting Antivirals are now available to achieve cure rates of > 95% for all genotypes.
- Hepatitis C is a liver disease caused by the hepatitis C virus: the virus can cause both acute and chronic hepatitis infection, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness.
- The hepatitis C virus is a bloodborne virus and the most common modes of infection are through unsafe injection practices; inadequate sterilization of medical equipment in some health-care settings; and unscreened blood and blood products.
- 180-200 million people globally have chronic hepatitis C infection.
- A significant number of those who are chronically infected will develop liver cirrhosis or liver cancer.
- 350 000 to 500 000 people die each year from hepatitis C-related liver diseases.
- Hepatitis C is curable
- Antiviral treatment is successful in 50–95% of persons treated, depending on the treatment used, and has also been shown to reduce the development of liver cancer and cirrhosis.
- There is currently no vaccine for hepatitis C, however research in this area is ongoing.
Hepatitis C Virus (HCV) is a major public health problem infecting approximately 200 million people worldwide. Infection persists in 60-80% of patients, 25% of who progress to cirrhosis with the associated complication of hepatic failure and hepatocellular carcinoma.
HCV is a virus of the flaviviridae family in the herpicivrus genus. It is an enveloped virus of about 50nm in size and consists of a positive strand RNA of approximately 9.6kb. The HCV genome encodes a large polyprotein that is proteolytically cleaved to produce 10 viral proteins during translation. These consist of the virion structural proteins: the basic core (C) protein, and glycoproteins E1 and E2 which plays an important role in the initial viral attachment. This is followed by a small integral membrane protein, p7 and the remainder of the genome encodes the nonstructural (NS) proteins NS2, NS3, NS4A, NS4B, NS5A and NS5B, which coordinate the intracellular processes of the virus life cycle. These proteins are the targets for the Direct Acting Antivirals which can effectively suppress the virus leading to a high cure rate.
Treatment
Treatment of chronic HCV infection has 2 goals. The first is to achieve sustained eradication of HCV (ie, sustained virologic response (SVR)), which is defined as the absence of HCV RNA in serum 6 months or more after completing antiviral treatment. Patients achieving SVR are effectively cured of the disease leading to the second goal to prevent progression to cirrhosis, hepatocellular carcinoma (HCC), and decompensated liver disease requiring liver transplantation.
HCV is divided among six genotypes with numerous subtypes. Depending on the HCV genotype, length of treatment can differ. The SVR rates varies with the different genotypes with SVR rates from 40% to 45% among patients with genotype 1 after 1 year of treatment to 75% to 80% in patients with genotype 2 or 3 infection after 6 months of treatment. The other genotypes receive the same duration of therapy as genotype 1 and clinical data on response to treatment are not as comprehensive as genotype 1,2 and 3.
The treatment has evolved over the last 20 years initially interferon alone at first achieving a SVR of less than 10% with 6 months of therapy. Then with ribavirin, was an empirically derived, nonspecific treatment with broad biologic properties improved the SVR to about 40% after a year of treatment. Further improvements came with the combination therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV) which has remained the standard of care for chronic hepatitis C for over a decade achieving an SVR of approximately 50%. However newer Direct Acting Antivirals are now available to achieve cure rates of > 95% for all genotypes.