Hepatitis C is a viral infection of the liver by the blood-borne Hepatitis C Virus. It results in liver inflammation and over time, can lead to chronic liver disease. Previously called “non-A non-B”, the hepatitis C virus was conclusively identified in 1988. In Australia, over 280,000 people are estimated to have been exposed to the hepatitis C virus. About 18,000 South Australians are estimated to have been exposed to hepatitis C. World-wide, an estimated 170 million people are infected with hepatitis C.
The hepatitis C virus is slow-acting and for most people will not result in serious disease or death.
About 25 out of 100 people infected by the hepatitis C virus clear the virus spontaneously within 12 months. The remaining 75% go on to have chronic hepatitis.
Among people with chronic infection, 5-10% will develop cirrhosis (serious liver scarring) after 20 years of infection and possibly 20% by 40 years of infection.
The longer a person’s been infected, the higher the risk of cirrhosis and liver cancer. Other factors which affect the progression of liver disease include:
- age when first infected;
- alcohol use;
- co-infection with hepatitis B virus and/or HIV; and
- obesity
Hepatitis C is totally different from HIV and hepatitis A and B. One of these viruses do not lead to the other.
Genotypes
The hepatitis C virus (HCV) is an RNA virus related to the flavivirus family, which includes yellow fever, dengue fever, West Nile fever and Japanese encephalitis. RNA viruses are genetically less stable than DNA viruses, and are prone to mutate during replication. It’s a common misconception that hepatitis C is just one virus, but in reality (as a result of mutation over hundreds of years), it’s a group of very closely related strains. They are similar enough to be called HCV, but based on genetic differences, they can be classified into distinct groups called genotypes.
There are at least six major genotypes. Within the major genotype groups there are more closely related strains called subtypes. There are many subtypes. These have designated lower case letters, such as 1a, 1b and1c. Different genotypes respond differently to treatment.
Quasispecies
As the virus continues to replicate in each person, there is the potential for quasispecies to form. Quasispecies are very closely related mutations of the original virus the person was infected with. Over time, the diversity of quasispecies increases and may affect response to treatment.
Genotypes and Disease Progression
This is still a controversial area. Many studies have shown genotype 1, especially type 1b, to be associated with more advanced liver disease. However, these patients are generally older and have a longer duration of infection. Poynard et al assessed factors associated with fibrosis progression in a large study involving 2,235 patients. No link was found between genotype and fibrosis progression.
Genotypes and Treatment
Research has shown people with genotypes 2 or 3 have a higher sustained response rate (approximately 80%) to combination therapy than genotype 1 (approximately 50%). However, other factors such as stage of fibrosis or cirrhosis, viral load, age, gender, duration of disease and excessive alcohol consumption also influence response to therapy.
Furthermore, the duration of treatment is also influenced by genotype. Previously untreated patients with genotype 1 double their chance of a sustained response when treated for 12 months instead of 6 months. Conversely, 12 months of treatment for patients with genotypes 2 or 3 does not improve response rates over just 6 months of treatment.
Modes of Transmission
Genotyping can been used to study the ways hepatitis C is transmitted. It has been used to identify the source of infection in cases of patient-to-patient transmission, and is also useful in the study of other modes such as vertical transmission (mother to baby), transmission during sexual activity and needle-stick injuries.
Genotype Testing
Genotyping is routinely performed prior to therapy. Genotype testing is covered by Medicare if you are considering treatment.
Global Genotype Distribution
Some hepatitis C genotypes are largely (but not exclusively) associated with different parts of the world. Genotype 4 is present in over 90% of HCV infections in central Africa, and accounts for the majority of infections in the Middle East. Genotype 5 is found in over 50% of South African infections. Genotype 6 is mainly restricted to South East Asia. Genotypes 1, 2 and 3 are widely distributed through western countries and the Far East.
Australian Genotype Distribution
Several studies have been performed to determine the genotype distribution in Australia, all with similar results. At Westmead Hospital, the study ‘Molecular Epidemiology of Hepatitis C in Australia’ involved 420 patients, and showed the most common genotypes present in this group were:
- Genotype 1 (52%) 219 patients
- Genotype 3 (32%) 132 patients
Less common genotypes were:
- Genotype 2 (9.3%) 39 patients
- Genotype 4 (5.5%) 23 patients
- Genotype 6 (1.7%) 7 patients
The study also aimed to determine other factors associated with the particular genotypes found. It discovered that 93% of Australian- or NZ-born patients had genotype 1 or genotype 3. Patients with genotype 1 were more likely to be older with a longer duration of disease. Of the 53 Asian-born patients, genotypes 1b (49%) and 2 (21%) were the most common, and all seven of the patients with genotype 6 were born in Asia (six in Vietnam, and one in China). Half of the Mediterranean-born patients had 1b (52%), and 33% had genotype 2. All but 2 of the patients with genotype 4 were born in the Middle East—one was born in Italy, while the other had a blood transfusion in Egypt.
