Module 3: HCV prevalence and course of HCV infection - section 3

In this document:

Liver damage and course of HCV infection

Activity: Small group work and presentation
Section Time: Approximately 30 minutes

This section looks at how HCV affects the liver, the natural course of HCV infection and the main factors that influence disease progression.

Participants should be asked to form small groups to undertake the next stage of the exercise.  As an introduction explain that when describing liver damage and the progression of HCV infection, a range of common but unfamiliar medical terms are used. Understanding these terms can help develop confidence and knowledge around the natural history of HCV infection.

Show Slide 3.9 (Group work) and ask each group to take 20 minutes to consider the questions and record their answers on flip chart paper:


Facilitate group feedback by:

  • Clarifying answers to support understanding of the terms.
  • Then showing Slide 3.10 (HCV and liver damage over time) and referring to accepted terms, outline how HCV affects the liver and, how over time, infection prevents the liver from functioning normally and that this process can be described in stages:

Over years or decades, a proportion of people with chronic hepatitis C will develop severe liver disease including advanced fibrosis, cirrhosis, and hepatocellular carcinoma, a form of liver cancer. Hepatitis C does not directly damage your liver but after infection, the immune system reacts to hepatitis C by trying to rid the liver of infected cells. It is this immune response that can cause liver inflammation, and this inflammation leads to scarring (fibrosis). As the liver becomes more scarred, it hardens and becomes less elastic. This makes it increasingly difficult for blood and other fluids to flow through it significantly impeding its function. Liver fibrosis doesn’t occur at the same rate in all individuals, and in some people fibrosis remains stable or may even regress over time.

Even though the liver can operate when badly damaged, the continuous effect of hepatitis C can slowly interfere with liver function. Complications then occur when the liver is unable to carry out important tasks. These complications include: fatty liver (steatosis), jaundice, oesophageal varices, ascites, encephalopathy, portal hypertension, kidney damage, thyroid disease, diabetes, and appetite and weight loss resulting in malnutrition.

Several factors influence fibrosis progression. Fibrosis occurs more rapidly in men than in women, and also in older people, particularly those over age 50. Progression does not seem to be linear; that is, the process appears to accelerate later in the course of disease. Immune system compromise for example, due to co-infection with HIV or use of immunosuppressive drugs after a liver transplant also has been shown to accelerate fibrosis. Heavy alcohol consumption is strongly associated with worsening fibrosis and cirrhosis.

Even though the liver can operate when badly damaged, the continuous effect of hepatitis C can slowly interfere with liver function. Complications then occur when the liver is unable to carry out important tasks. These complications include: fatty liver (steatosis), jaundice, oesophageal varices, ascites, encephalopathy, portal hypertension, kidney damage, thyroid disease, diabetes, and appetite and weight loss resulting in malnutrition.

Several factors influence fibrosis progression. Fibrosis occurs more rapidly in men than in women, and also in older people, particularly those over age 50. Progression does not seem to be linear; that is, the process appears to accelerate later in the course of disease. Immune system compromise for example, due to co-infection with HIV or use of immunosuppressive drugs after a liver transplant also has been shown to accelerate fibrosis. Heavy alcohol consumption is strongly associated with worsening fibrosis and cirrhosis.

Activity: Large group work and lecture summary presentation
Section Time: Approximately 30 minutes

Using Slide 3.11 (Group work) ask participants the questions and list their answers on flip chart:


Once the answers have been established the next slides are used to build understanding. Show Slide 3.12 (Natural history of HCV progression) :


Explain how this is representative of untreated disease progression and that progression is determined by various factors including age at time of infection, gender – being male, concurrent HBV and/or HIV infection, high alcohol use and other lifestyle factors.

Referring back to responses from last activity use Slides 3.13 (Acute infection); 3.14 (Chronic infection); 3.15 (Late stage chronic infection) and 3.16 (Factors affecting disease progression) to expand by offering more detail on the stages of HCV disease progression:





Supporting content:

HCV has two distinct phases, acute and chronic. The acute phase occurs immediately after infection and lasts for about six months. A proportion of infected individuals develops an immune response and clears the virus from their bodies, usually within 6 months of infection. The remaining 75 to 85 percent or so are unable to clear the virus, and they develop chronic hepatitis. Chronic HCV infection requires treatment to eliminate the virus.

However, the course of HCV is unpredictable and people infected with the virus may not progress through all these stages. Additionally, disease progression will be affected and potentially complicated by co-infection with HIV. This will be discussed in more detail in Module 9.

Acute phase - Acute infection is a term for the first six months after a person gets HCV – it bears no relation to acuteness of symptoms, or severity of disease.

Most people do not seem to experience symptoms during the acute phase. Other people may have vague flu-like symptoms, including fever, tiredness, loss of appetite, stomach pains, nausea and vomiting. These occur a few weeks after initial infection. A small proportion develop jaundice, which shows as a yellowing of the skin and the whites of the eyes caused by excess bilirubin in the blood as a result of compromised liver function.

As most symptoms are similar to many other short term infections most people are unlikely to seek medical attention. The lack of clear and identifiable symptoms is a main reason that many health care providers fail to suspect HCV, leaving patients undiagnosed.

Spontaneous clearance - Approximately one in five people will fight off the hepatitis C virus and completely clear the virus during the acute phase. This is the spontaneous clearing of HCV by the immune system through elimination of all viral particles in circulation and destruction all infected cells. Evidence of this infection in the form of antibodies to HCV will possibly always remain in the body. Unlike some other diseases these antibodies do not provide immunity against a further HCV infection at a later date.

Contributory factors to clearing hepatitis C during the acute phase

It is not clear exactly why some people clear the virus while others do not, but some common factors are known:

  • The younger a person is at the time of HCV infection; the more chance they have of clearing the virus
  • Women are more likely to clear the virus than men
  • People who develop symptoms during the acute phase seem to have a greater chance of clearing the virus.
  • A healthy immune system particularly the T cell response to the virus plays an important part
  • Low alcohol consumption
  • Genotype. There is some evidence that people with genotype 3 have a higher chance of clearing the virus than those with genotype 1.
  • The amount of virus transmitted at the time of infection. People who contracted the virus through transfusion and so have a higher viral load appear to be at greater risk of developing chronic hepatitis C than people with some other sources of infection.
  • Genetics. The IL28B gene is associated with spontaneous clearance of HCV and specific variants of this gene predict treatment-related viral clearance.
HCV treatment is most effective during acute infection

Finding out that you have HCV during acute infection can make a big difference, because HCV treatment is much more likely to work—meaning it will get rid of the virus—during acute stage. People who have acute HCV should wait for about 12 weeks before they start HCV treatment, since they may spontaneously clear the virus and not need treatment. However, it may be unrealistic for people to know when they became infected, or indeed, that they have access to testing and this will need consideration when discussing the availability of optimal treatment responses.

Chronic stage

While some people clear the virus in the very early stages after initial infection, most will go on to develop a long term or chronic infection. Hepatitis C is said to be chronic when someone has been infected for longer than six months. Having chronic HCV does not always mean that serious liver damage will occur.

The experiences of those with chronic infection tend to be variable with many remaining asymptomatic for years, while others will have more evident symptoms which can be severely debilitating including fatigue, depression, digestive problems and other symptoms among the many varied extra-hepatic (outside of the liver) complications of hepatitis C infection. Confusingly symptoms are not necessarily an indication of liver damage. One person may have almost no liver damage and yet their quality of life maybe severely affected by symptoms, while somebody with extensive scarring of the liver may be symptom free.

It was originally thought that HCV only infected liver cells. However, recently it has become clear that HCV also infects parts of the immune system and some blood cells meaning that HCV is also a systemic disease, in that it can affect other organs in the body.

Liver damage from HCV happens slowly, usually over decades. It can take from 15 to 50 years for a PLWHCV to develop cirrhosis. The longer a person has been infected, the more likely they are to develop liver damage. People with serious liver damage (cirrhosis) are at risk for very serious complications, such as liver cancer and liver failure.

Compensated cirrhosis

Liver damage from HCV happens slowly, usually over decades. It can take from 15 to 50 years for a person who has chronic HCV to develop cirrhosis.  About one in five people with chronic hepatitis C will develop cirrhosis. Cirrhosis is scarring of the liver as a result of long-term, continuous damage to the liver. It is a serious condition where healthy tissue in the liver is destroyed and replaced by scar tissue, which starts to block the flow of blood through your liver. Compensated cirrhosis means that the liver can still carry out its normal functions although these may be increasingly compromised.

A number of factors are associated with disease progression and cirrhosis, notably alcohol use and co-infection with HIV and hepatitis B.

Decompensated cirrhosis

A few people with compensated cirrhosis will deteriorate further and develop decompensated cirrhosis and are at risk for very serious complications, such as liver cancer and failure. Once decompensated cirrhosis is established serious complications are almost inevitable and there is usually a very high frequency of readmissions to hospital with likelihood of liver transplant being required.

The overall risk of developing liver cancer or hepatocellular carcinoma (HCC) for people infected with HCV is relatively small. It usually develops decades after infection and is almost exclusively confined to people who have already progressed to cirrhosis. There are no exact figures for the chances that people with HCV will develop liver cancer. However, it seems that around 6% of people who have been infected with HCV for over twenty years will develop liver cancer or HCC.

Once liver cancer does develop the survival rates are very low. It is unlikely that someone with liver cancer will survive for more than five years. In such cases a liver transplant will likely be considered as an option.

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