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Author: Dr Nick Turnbull, Dermatology registrar, Auckland and Greenlane Hospital, Auckland, 2010.
Hepatitis is a nonspecific term for inflammation of the liver. There are acute and chronic forms of hepatitis, which may result in nausea, jaundice, fatigue and abnormal liver function blood tests.
Hepatitis may be caused by:
The term “viral hepatitis” is often used to describe infection by a virus from the hepatotrophic family. These infections are called hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV) and hepatitis E (HEV).
Newly discovered pathogens (e.g. virus SEN-V) may account for additional cases of non-A/non-E hepatitis.
Many other virus infections can cause hepatitis including:
After the initial infection, acute viral hepatitis may cause a self-limited illness or go unnoticed. Acute infections with HAV and HBV are usually symptomatic, but acute infections with HCV are usually unnoticed.
Common symptoms of acute viral hepatitis include fever, loss of appetite, nausea, vomiting, diarrhoea and jaundice and dark urine.
The injured liver fails to break down bile properly resulting in high levels of circulating bilirubin, a greenish pigment. This stains the skin – jaundice. Liver function tests show high levels of aminotransferase (ALT).
Severe viral hepatitis due to HAV, HBV or HEV (in Asia) results in acute liver failure or fulminant hepatitis in up to 1% of cases. Clinical features of fulminant hepatitis include:
Most cases of acute viral hepatitis resolve over days to weeks. Supportive care may be all that is necessary. Fulminant hepatitis may also resolve with supportive care but may require liver transplantation or result in death.
Acute viral hepatitis may evolve into chronic hepatitis; this is particularly common with HBV and HCV infections. HAV and HEV never progress to chronic hepatitis.
The majority of newborn babies infected with HBV develop chronic infection (90%) whereas a minority of adults with HBV develop chronic infection (5%).
HCV results in chronic infection in 70% of cases.
Many of these patients remain well, despite the infection. However, 20% develop liver cirrhosis – this may take decades to evolve but can eventually be life-threatening. Chronic hepatitis can also affect joints, muscles, the nervous system, kidneys and skin.
HAV is an RNA virus that is transmitted mostly by the faecal-oral route, for example by drinking untreated water or by eating contaminated food. It can be carried by houseflies.
It has an incubation period of approximately four weeks, though this is quite variable. It is excreted in the stool from the first week of infection. Adults with acute infection are in general more unwell than children and have a higher chance of dying from it.
HAV never causes a chronic infection.
HAV infection is common in the developing world, especially in the Middle East. Most people in these regions become infected as children, but adult travellers are at risk of the disease.
There is no specific treatment for HAV infection, which usually resolves spontaneously over several weeks.
People at high risk of disease within two weeks of exposure to infection may be prescribed the blood product intravenous immunoglobulin, which provides short-term immunity.
HBV is a partially double-stranded DNA genome virus of the hepadnavirus family. There are eight different genotypes (A-H). It is usually transmitted by blood or blood products or by sexual contact.
Initial infection is usually not symptomatic, but 1-2% of people will develop liver failure early after their initial infection. A similar number will develop chronic infection, which can lead to cirrhosis or liver cancer (25-40%). HBV may also result in kidney disease (glomerulonephritis). Infected newborns are more likely than adults to progress to chronic hepatitis B.
HBV is found in blood, saliva, semen and vaginal secretions. An infected mother may transmit HBV to her baby at the time of birth – this is called vertical transmission.
Most people with acute HBV infection recover completely without treatment. If the infection is severe, lamivudine or another antiviral medication may be prescribed.
Carriers may be offered treatment to reduce the chance of cirrhosis and liver cancer. Alpha interferon and pegylated interferon slow the replication of the virus and stimulate immune clearance of the virus. Other effective drugs include lamivudine, adefovir dipivoxil, entecavir, and telbivudine.
HCV virus is an RNA virus and is a major cause of acute and chronic hepatitis. There are at least six major genotypes. It is transmitted by injected blood.
Most patients with acute hepatitis C infection are asymptomatic, but 70% develop chronic infection. This can lead to progressive liver disease, cirrhosis, and liver cancer (hepatocellular carcinoma) in approximately 20% of those infected.
Hepatitis is usually acquired by blood transfusions (in the absence of screening for HCV), through unsafe sex and IV drug use – horizontal transmission. Hepatitis C affects all races and both sexes equally. It is disproportionately associated with poverty. The peak age for infection is 30-50 years; it is rarely seen in children.
If acute hepatitis C does not resolve on its own within 2 to 3 months, it should be managed with drug therapy.
Various treatments are available to treat chronic HCV infection. They include:
HDV is spread through infected blood at the same time as infection with HBV or in people who are already infected with HBV. The same preventative measures are important.
Chronic hepatitis D is usually treated with pegylated interferon.
HEV is transmitted by faecal-oral spread (via food or water contaminated by faeces from an infected person).
People at most risk are international travellers visiting developing countries and those who have unprotected sex with an infected person.
There is no vaccine for HEV. As for HAV, avoid drinking contaminated water and practising good hygiene and sanitation.
Hepatitis E usually resolves on its own over several weeks to months.
Blood tests may include:
Urine is tested for bilirubin.
Liver biopsy may be recommended for the initial assessment of disease severity in patients with chronic HBV or HCV.
Immunosuppressive medications may reactivate HBV or HCV. For example:
Patients are often tested for chronic hepatitis before starting these medications. Hepatitis treatment such as lamivudine may be prescribed one to two weeks before the immunosuppressive and continued long term. Antiviral therapy should be started immediately after an HBV flare is recognised as antiviral therapy take time to work and may not prevent progression to liver failure to if delayed.
Patients with underlying liver disease may also be at increased risk of hepatotoxicity with these drugs.
Immune reconstitution inflammatory syndrome occurs in patients with human immunodeficiency virus (HIV) infection treated with active antiretroviral therapy (HAART). As the HIV infection lessens, the immune system begins to recover and over-reacts to a pre-existing infection. This can result in a severe inflammatory reaction including severe hepatitis.
The pre-existing infection may have been previously diagnosed and treated or may have remained subclinical. Infections most commonly associated with IRIS include cytomegalovirus, herpes zoster, Mycobacterium avium complex (MAC), Pneumocystis pneumonia, and Mycobacterium tuberculosis (TB).
Chronic liver failure from cirrhosis or hepatocellular carcinoma often results in changes to the skin.
At least 20% of patients with chronic hepatitis due to HBV or HCV develop a skin disorder. It can be due to direct viral infection of skin cells. However, few of these are diagnostic of viral hepatitis, and several are classified as autoimmune in origin.
Many other skin disorders have been described in patients with viral hepatitis, but the relationship with the infection is unknown.
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