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Natural History of Hepatitis C

March 2009

As with HIV, there are similar terms to describe the natural history of HCV infection.

Acute infection (0-6 months)

Acute infection refers to the first six months after hepatitis C (HCV) infection.

Unless it causes symptoms -- and about 80% people do not have symptoms -- HCV is rarely diagnosed in acute infection.

Symptoms, when they occur, include fever, fatigue, abdominal pain, nausea, vomiting, dark urine, and jaundice (yellowed skin and eyes).

However, because HIV treatment involves checking for liver function, higher liver enzyme levels has helped diagnose acute HCV infection in HIV-positive people.

In the first few months after HCV infection, some people clear the virus without any treatment. This occurs in perhaps up to 20% of HIV-positive people. This is called 'spontaneous clearance' and is more common if:

  • You have symptoms during acute HCV
  • You are a female
  • You are under 40 years old

HIV-positive people are only half as likely to spontaneously clear HCV. People of African decent are less likely to clear hepatitis C than Caucasians. The reasons for these differences are unclear.

People who have cleared the virus without treatment are no longer infected with HCV. They may test HCV-positive using with an antibody test, but the virus is not detectable in their blood.

If HCV does not clear spontaneously, some people choose HCV treatment during acute infection. This is because there are higher success rates at this stage. It is important to discuss the risks and benefits of treating acute HCV with your doctor.

Chronic infection (6+ months)

Chronic infection refers to any time after acute infection. This is usually from 6 months after infection.

In HIV-negative people, HCV progresses very slowly, usually over decades and there is a wide range of outcomes from chronic hepatitis C. HCV can affect other areas of the body. However, there have been reports of HCV progressing more quickly in HIV-positive gay men.

Whatever the timescale, some people will never have significant liver damage or symptoms, while others may develop mild-to moderate liver scarring (fibrosis), and experience symptoms such as fatigue, depression and confusion.

There seems to be no clear relationship between the degree of liver damage and the experience of symptoms.
Hepatitis C can contribute to a build-up of fat in liver cells called steatosis (or fatty liver), which worsens liver damage and makes HCV harder to treat.

  • Fatty liver is most common in people with HCV genotype 3.
  • In people with HCV genotype 1 fatty liver is more likely among people who are overweight, have insulin resistance or diabetes, who have a heavy alcohol intake and who have liver inflammation.

In people with HIV/HCV coinfection, fatty liver usually indicates more serious liver scarring. It is linked with several factors, including use of some HIV drugs (especially d4T and ddI), low levels of HDL ('good' cholesterol), being overweight and having lipodystrophy.

About 20-30% of people with chronic, untreated HCV will progress to cirrhosis (serious liver scarring). Even then, the liver can still function. When a cirrhotic liver can 'compensate' for the damage this is called compensated cirrhosis.

When the liver is too damaged to function properly, this is referred to as decompensated cirrhosis or end stage liver disease.

End stage liver disease

Factors that accelerate hepatitis C progression

  • HIV coinfection
  • Alcohol intake, especially more than 50 grams/day
  • Aging
  • Duration of infection
  • Older at time of infection (over 40 years of age)
  • Hepatitis B coinfection
  • Hepatitis C may progress faster in men than women
If compensated cirrhosis progresses to decompensated cirrhosis, a liver transplant is required.

Although it is a serious operation, successful liver transplants have been carried out in people with coinfection.

Each year, 1-5% of people with cirrhosis develop hepatocellular carcinoma (HCC, liver cancer).

This can also be successfully treated, especially if it is caught early.

Hepatitis C and your liver

What does your liver do?

Although hepatitis C also affects other parts of the body, it is your liver that is most affected.

Your liver is an essential organ that has hundreds of jobs, including.

  • Filtering chemicals and waste from the blood
  • Storing vitamins, minerals, and iron
  • Converting nutrients from food into energy
  • Helping to balance levels of sugar and hormones
  • Producing cholesterol
  • Making bile (necessary for digestion)
  • Creating the hormone that helps to produce platelets (to stop bleeding)

How does hepatitis C damage your liver?

Hepatitis C does not directly damage your liver.

How can you protect your liver?

There are many things that you can do to help your liver stay healthy. These include:

  • Getting hepatitis A and hepatitis B vaccines. Having another viral infection in your liver can worsen hepatitis C.
  • Drinking less, or stoping drinking alcohol. The less you drink, the better for your liver. Sometimes drinking less, or not at all, is more important than treating hepatitis C.
  • Maintaining normal weight. Being overweight increases your risk for fatty liver.
  • Drinking plenty of water, to help your liver filter out waste and toxins.
  • Eating fewer fatty, salty and high sugar foods.
  • Trying to eat more fresh fruit and vegetables, complex carbohydrates (whole grains, breads, rice, pasta, cereals, vegetables, fruits, beans, nuts and seeds), low-fat foods, high-fibre foods and an adequate amount of protein.
  • Using hepatitis C treatment to reduce liver damage
  • Asking questions and getting support. Talking with other people who are living with hepatitis C or HIV and HCV.
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. As the immune system attempts to isolate infected cells, scarring worsens.

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.

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.

Hepatitis C outside the liver

Hepatitis C (HCV) can cause other serious medical conditions that occur outside of the liver during chronic infection. Some are more common than others. These conditions can be treated (or will resolve if HCV treatment is successful). Many are related to problems with your immune system.

Diabetes: inadequate production or use of insulin.

Essential mixed cryoglobulinemia: the presence of abnormal proteins in the bloodstream that thicken the blood, causing blood vessels to become inflamed. Essential mixed cryoglobulinaemia involves a mixture of different antibodies that can cause joint pain and swelling, Raynaud's phenomenon (pain and whitening of fingertips and toes in cold weather) purplish patches on the skin, enlargement of the spleen, and neurological, renal and cardiac disease.

HCV-related arthritis: Inflammation and swelling of small joints.

Keratoconjunctivitis sicca: eye dryness, caused by a deficiency in the production of tears.

Lichen planus: a skin condition causing flat, purplish, itchy patches inside the mouth and on the wrists, ankles, legs, lower back, neck, genitals and -- less commonly -- the nails and scalp (leading to hair loss).

Non-Hodgkin B-cell lymphoma: a cancer occurring in lymphocytes (white blood cells). Symptoms may include swollen glands, fever, night sweats, fatigue and weight loss.

Porphyria cutanea tarda: a skin disorder that causes extreme sensitivity to sunlight; blisters may develop in areas exposed to the sun and skin may become very fragile. Pigmentation and hair growth may increase.

Sjögren's Syndrome: dryness of the eyes and mouth, occurring with joint inflammation. Can also cause skin dryness, rash, thyroid problems, fatigue, fever, nasal irritation and bleeding, and vaginal dryness.

Vitiligo: loss of skin pigment, resulting in pale patches.

HIV and hepatitis C coinfection

Although many people have lived with HIV and hepatitis C (HCV) for many years, often without knowing that they were coinfected, HIV makes HCV progress more quickly.

The risk of serious liver damage is greatest if your CD4 count under 200 cells/mm3.

HIV drugs have enabled many people to lead much longer lives. This means that people with HCV are now living long enough for the hepatitis to be a concern. End-stage liver disease from HCV coinfection is now a leading cause of death among HIV-positive people in the developed world.

However, HCV can be treated, regardless of a person’s HIV status and some of these deaths are related to late diagnosis of HCV, or late treatment, after severe liver damage has already occurred.

Effect of hepatitis C on HIV

Hepatitis C (HCV) is not thought to worsen HIV, but it may make HIV treatment more complicated.

This is mainly because the liver processes most HIV drugs. Having HCV puts you at greater risk for liver-related side effects from HIV drugs.

But, the benefit of HIV treatment still outweighs the risk of side effects. The doses of some HIV drugs can be individually adjusted for people with advanced, liver disease by measuring drug levels in a sample of blood.

Hepatitis C progression in HIV-positive people

HCV progression

Acute infection (0-6 months)

In acute HCV only 20% people have any symptoms (fever, fatigue, loss of appetite, abdominal pain, nausea, vomiting, jaundice).

Up to 20% percent of HIV-positive people can clear hepatitis C without treatment in the first few months.

HCV Treatment Option: early treatment has a higher success rate

Most HIV-positive people go on to have chronic hepatitis C. HCV can progress more quickly in people who have been HIV+ for many years.

Up to 20% people do not develop any further significant liver damage

Chronic infection (6 months-30+ years)

Around 60% people develop mild to moderate liver scarring (fibrosis) and may experience symptoms, such as fatigue and depression.

HCV Treatment Option: treat before serious liver damage

Up to 40% people do not develop serious liver damage. HCV treatment is not always needed.

20-30% HIV-positive people may develop serious liver scarring (compensated cirrhosis) after 10-15 years. The liver can still function, despite damage.

HCV Treatment Option: treatment much less effective at this stage

1-5% of people with compensated cirrhosis develop liver cancer each year.

If cirrhosis progresses to decompensated liver disease a liver transplant is the only option.

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This article was provided by HIV i-Base. It is a part of the publication Hepatitis C for People Living With HIV. Visit HIV i-Base's website to find out more about their activities, publications and services.