Hepatitis C: Disease course and symptoms

Progress of the disease

What are the consequences of hepatitis C infection for the health of the liver? What are the symptoms of liver disease in hepatitis C infection?

Stage 1 – Acute hepatitis: The period of the first six months after infection is called acute hepatitis C infection. During this time the immune system battles intensively with the virus. In 20 to 50% of cases this can lead to a spontaneous clearance of the virus. Symptoms (e.g. exhaustion, mild nausea, occasionally also a yellowing of the skin and eyes) may become noticeable six to nine weeks after exposure – however, this is not the case for everyone. Hepatitis C can also progress without any symptoms. If the acute infection is detected promptly and treated the chances of cure are very good, at around 90%.1Meanwhile, similar cure rates are also achieved in chronic hepatitis C with new antiviral treatments. Studies are ongoing to establish their role in the treatment of acute hepatitis C.

Stage 2 – Chronic hepatitis: For 50 to 80% of people who are have hepatitis C infection, the immune system alone cannot eliminate the virus within six months. The liver inflammation (hepatitis) then becomes chronic.

Glossary

acute infection

In hepatitis, the first six months of infection. See also ‘chronic infection’.

cirrhosis

Scarring of the liver – the structure of the liver is altered. See also ‘fibrosis’, which is moderate scarring. See also ‘compensated cirrhosis’ and ‘decompensated cirrhosis’.

decompensated cirrhosis

The later stage of cirrhosis, during which the liver cannot perform some vital functions and complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.

fibrosis

Scarring of the liver – the development of hard, fibrous tissue. See also ‘cirrhosis’, which is more severe scarring.

genotype

A strain or subtype of a virus. For hepatitis C, genotypes are identified by a number (e.g. genotypes 1,2,3,4,5 and 6); some subtypes have also been identified (e.g. genotypes 1a and 1b). For hepatitis B, genotypes are identified by a letter (A to H). The genotype may influence the risk of disease progression for both viruses; some genotypes respond differently to some treatments.

rate

The number of events that we would expect to occur during a specified period of follow-up (e.g. 100 person-years). Particularly useful when follow-up periods vary from person to person in a study, or where a person may experience more than one event.

RNA

Ribonucleic acid, the form in which a virus stores its genetic material.In hepatitis C, RNA (viral load) testing is used for diagnosis, to help predict treatment outcome and to monitor response to treatment.

spontaneous clearance

When, during acute viral hepatitis infection, the immune system responds effectively to the virus and eliminates it from the body, without medicines. This is a cure.

stage

The stage of hepatitis infection refers to the amount of liver scarring (fibrosis) detected by biopsy. Usually measured on scales of 0 to 4, or 0 to 6 (higher numbers indicated more severe inflammation). 

Stage 3 – Fibrosis: Untreated chronic hepatitis can lead to a scarring of the liver over years or decades. At first the destroyed liver cells can be replaced by new liver cells, but later in the course of the disease the gaps created by the destruction of liver cells are closed up by connective tissue cells, which have no function (scar tissue). This increasing scarring of the liver is called fibrosis. Fibrosis is a precursor of cirrhosis.

Stage 4 – Cirrhosis of the liver: When the scarring is so far advanced that it causes structural changes with nodular alterations, this is called cirrhosis of the liver. See Cirrhosis for further information.

If hepatitis C remains untreated, up to 40% of people develop cirrhosis within 30 years.1 The rate of progression of liver damage appears to be affected by a number of factors, including hepatitis C genotype, alcohol intake, smoking, older age, body weight, co-morbidities and gender. A large French study found that the average time to the development of fibrosis among men infected after the age of 40 was 13 years, while women who were infected before the age of 40 and did not drink alcohol took an average of 42 years to progress to fibrosis.2

Liver disease progression is more likely, and occurs more rapidly, in people with HIV/HCV-co-infection (see HIV and hepatitis C co-infection for further information).

Stage 5 – Liver cancer: Liver cancer is a possible consequence of chronic liver diseases and may also occur in hepatitis C patients, mostly due to the development of cirrhosis. Liver cancer is one of the most difficult types of cancer to treat and on the whole it does not have a good prognosis. The likelihood of dying within the first year of the diagnosis is 33%.3 A cure through surgery, radiofrequency ablation or transplantation is possible in a minority of people. Other procedures, such as chemoembolisation or using medication, such as sorafenib, may prolong survival.

Important note

  • The absence or presence of symptoms does not predict the speed at which liver damage will progress. Some people may develop decompensated cirrhosis despite few previous symptoms. In others, moderate liver damage that is progressing slowly may nevertheless cause noticeable symptoms.
  • The quantity of the virus (HCV RNA) that is detectable in the blood has no impact on the progress of chronic hepatitis C. People with low viral load can suffer rapid progression of liver damage, while others may have high viral load for many years and yet experience little or no liver damage.1 There is one exception, however: in people with HCV who undergo liver transplantation, high viral load does tend to predict faster progression of liver disease.4

Why doesn’t liver inflammation cause pain?

Pain, the warning signal which is present with many diseases, does not occur with chronic diseases of the liver. There are no nerve fibres, which could convey pain signals, in the liver itself. The destruction of liver cells and the associated inflammation cause the person with liver inflammation no pain.

Pain in the area around the liver can occur if the liver capsule (the outer layer of the liver) becomes stressed, in particular, if the liver swells up.

This information was originally adapted from Hepatitis C: Understanding a silent killer, published by the European Liver Patients Association. It was updated in 2016.

References

  1. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. J Hepatol 55:245-264, 2011
  2. Poynard T et al. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet Mar 22;349(9055):825-32, 1997
  3. Yang JD, Roberts LR Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol 7:448-458, 2010
  4. Roche B et al. Risk factors for hepatitis C recurrence after liver transplantation. J Viral Hepat. Nov;14Suppl 1:89-96, 2007