Natural history of HCV infection


Natural history of HCV

The natural history of an infection is the term for describing what happens without treatment.

Modern HCV drugs (DAAs) can cure HCV in more than 95% of people using their first treatment.

Without treatment, he natural history of HCV infection includes three possible stages:

  • Acute infection.
  • Chronic infection.
  • End stage liver disease (ESLD).

Acute infection

Acute infection refers to the first six months after HCV infection.

Unless it causes symptoms – and about 80% of people do not have any symptoms–acute HCV is rarely diagnosed. Symptoms, when they do occur, include fever, fatigue, abdominal pain, nausea, vomiting, dark urine, pale faeces and jaundice.

Acute HCV infection in HIV positive people has generally been detected because of routine monitoring on ART. Unexplained abnormal liver enzymes should prompt checking for acute HCV.

HIV positive gay men should have an annual screen for HCV.

In the first few months after infection, up some people clear the virus without HCV treatment.

This is called spontaneous viral clearance and is more common if:

  • You had symptoms during acute HCV.
  • You are female.
  • You are under 40 years old.
  • You have certain genes – see HCV, genetics and race).
  • Your CD4 cell count is high.

HIV positive people are only half as likely to spontaneously clear HCV as HIV negative people. People of African descent are less likely to clear HCV than Caucasians.

Genetics are part of the reason for these differences, but other factors that we don’t know are also involved.

People who clear HCV without treatment are no longer infectious. They may still test positive to an HCV antibody test because they were previously infected, but HCV will not be detectable in blood.

Whether or not to treat acute infection is complicated by three medical factors.

  1. Waiting to see whether HCV clears naturally without treatment.
  2. Whether you are worried about transmitting HCV to sexual partners.
  3. The difference between access to old compared to new HCV drugs.

Currently, main guidelines disagree.

Some guidelines (including from the European Liver Association, EASL) recommend using DAAs in acute infection, even though these drugs are only approved for chronic infection.

UK guidelines – due to be updated – still recommend treating acute HCV with old HCV drugs (pegylated interferon and ribavirin). These drugs would not now be used.

Treating acute infection is discussed in more detail here.

European Liver Association (EASL) guidelines for treating hepatitis C at

Chronic infection

Chronic infection refers to any time after acute infection (the first six months after infection).

In HIV negative people, untreated HCV usually progresses very slowly, often over decades.

Some people never develop serious liver damage or symptoms. But most people will have mild to moderate liver scarring (fibrosis) or symptoms such as fatigue, depression and confusion. Untreated HCV can also cause other health problems.

HIV increases the risk for, and speeds up the rate of liver damage from HCV. This is why access to DAAs may be easier for people with coinfection.

Currently in the UK, people with pre-cirrhosis and cirrhosis are getting DAA treatment. But it is important to be treated before serious liver damage develops.

Treating (and curing) HCV before HCV causes serious liver damage prevents liver failure and liver cancer.

People with cirrhosis need to be treated by a liver specialist. Although DAAs do not work as well for people with cirrhosis, the cure rate is at least 80%.

The risk for liver cancer remains high for people with cirrhosis, even after being cured and requires continued screening.

Last updated: 17 August 2017.