Viral hepatitis

• What is hepatitis
• Acute hepatitis
• Chronic hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis C
• Hepatitis D
• Hepatitis E
• Diagnosis of hepatitis
• Reactivation of hepatitis B
• Immune reconstitution inflammatory syndrome

What is hepatitis?

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:

• Alcohol
• Drug toxicity or allergy
• Gall bladder disease
• Autoimmune disease
• Metabolic disease — fatty liver (non-alcoholic steatohepatitis)
• Infections by parasites, bacteria, fungi, and viruses.

What is viral hepatitis?

Viral hepatitis is liver inflammation caused by infection with 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:

• Adenovirus
• Cytomegalovirus
• Epstein-Barr virus (infectious mononucleosis, glandular fever)
• Herpes simplex virus (cold sore virus).

Acute hepatitis

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 and HEV are often asymptomatic. HEV is the most common cause of acute viral hepatitis.

Common symptoms of acute viral hepatitis include fever, loss of appetite, nausea, vomiting, diarrhoea, yellowing of the skin and eyes, 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 and eyes – 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:

• Ascites (fluid) in the abdomen due to low levels of circulating albumin (a blood protein)
• Unchecked bleeding because the liver stops making blood-clotting proteins. Coagulation tests show raised prothrombin time and INR (International Normalised Ratio)
• Raised blood sugar in severe hepatitis
• Encephalopathy due to a build-up of toxins in the brain, which causes confusion, drowsiness and personality changes, and eventually loss of consciousness or coma
• Overwhelming infection with other organisms such as Vibrio vulnificus and Escherichia coli.

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 can be fatal or may require liver transplantation.

Chronic hepatitis

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. [see Skin signs of viral hepatitis]

Hepatitis A

HAV is an RNA virus that is transmitted mostly by the faecal-oral route, for example by drinking untreated water or from 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.

Who is at risk of hepatitis A?

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.

Prevention

• Hepatitis A vaccine can be administered to adults and children aged over one year, and is recommended for travellers to the developing world.
• Avoid exposure to contaminated water or untreated tap water – if in doubt, drink bottled drinks or boil water.
• Ensure meat and seafood have been thoroughly cooked – do not eat raw shellfish.
• Avoid cream products such as mayonnaise, cheese or yoghurt.
• Practice good hygiene by washing hands frequently and drying with paper towel.

Treatment for hepatitis A

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.

Hepatitis B

HBV is a partially double-stranded DNA genome virus of the Hepadnaviridae 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.

Who is at risk of hepatitis B?

HBV is found in blood, saliva, semen, and vaginal secretions. An infected mother may transmit HBV to her baby during birth – this is called vertical transmission.

Prevention of hepatitis B

• Vaccination offers good protection against infection.
• Prevent or reduce exposure by using latex condoms and not sharing drug or tattoo needles.
• Health workers should be careful to avoid needle stick injury.
• HBV immune globulin and vaccine should be given within 12 hours of birth to infants of HBV positive mothers.

Treatment for hepatitis B

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.

Hepatitis C

HCV 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 infected 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.

Who is at risk of hepatitis C?

Hepatitis C 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.

Prevention for hepatitis C

• There is no vaccine for HCV.
• Avoid risky behaviours such as sharing needles or personal items such as toothbrushes and razors.

Treatment of hepatitis C

If acute hepatitis C does not resolve within 2 to 3 months, it should be managed with drug therapy.

Various treatments are available to treat chronic HCV infection. They include:

• Pegylated interferon and ribavirin
• Boceprevir
• Ledipasvir with sofosbuvir
• Paritaprevir with ritonavir and ombitasvir
• Dasabuvir and ribavirin

Hepatitis D

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.

Hepatitis E

HEV is a zoonotic virus transmitted by direct contact with an infected animal (particularly pigs), faecal-oral spread, vertically from an infected mother to baby, or parenterally via blood transfusion or organ transplant. Sexual transmission has not been demonstrated.

People at most risk are international travellers visiting developing countries.

There is no vaccine for HEV. As for HAV, avoid consuming contaminated food or water, and practise good hygiene and sanitation.

Hepatitis E usually resolves over several weeks to months. However, chronic HEV infection has been reported in immunocompromised patients and transplant recipients.

Diagnosis of hepatitis

Blood tests may include:

• Liver function, particular transaminase levels (AST, ALT) and bilirubin.
• Coagulation (blood clotting) tests to evaluate prothrombin time
• Renal (kidney) function
• Glucose
• Serology

Urine is tested for bilirubin.

Liver biopsy may be recommended for the initial assessment of disease severity in patients with chronic HBV or HCV.

Serological tests for hepatitis

• IgM antibodies appear early in acute infection.
• IgG appears later.

HBV

• Anti-HBs antibodies becomes detectable in late convalescence. It indicates immunity following infection and remains detectable for life. It is not seen in chronic carriers.
• HBsAg (Hepatitis B surface antigen) can be present in acute and chronic HBV infection. Persistence in the blood for greater than six months is suggestive of chronic infections.
• HBe is a secreted protein of unknown function. Expression is greatest when the virus is rapidly replicating. Anti-HBe antibodies become detectable as viral replication falls. It indicates low infectivity in a carrier.

HCV

• Anti-HCV antibodies indicate prior exposure or infection. The third generation assays for these antibodies are highly sensitive and specific and can detect antibodies within 4 to 10 weeks of infection.
• PCR for HCV particles is the most specific test. PCR can be used to diagnose acute HCV infection before antibodies develop.

HEV

• HEV serology assay

Reactivation of viral hepatitis

Immunosuppressive medications may reactivate HBV or HCV. For example:

• Chemotherapy for cancer
• Biological treatments for psoriasis, Crohn disease, and rheumatoid arthritis
• Long term systemic steroids

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 takes time to work and may not prevent progression to liver failure if delayed.

Patients with underlying liver disease may also be at increased risk of hepatotoxicity with these drugs.

Immune reconstitution inflammatory syndrome

Immune reconstitution inflammatory syndrome (IRIS) can occur in patients with human immunodeficiency virus (HIV) infection when 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 if there is pre-existing HBV or HCV infection.

The pre-existing infection may have been previously diagnosed and treated or may have remained subclinical. Other infections most commonly associated with IRIS include cytomegalovirus, herpes zoster, Mycobacterium avium complex (MAC) [see Atypical mycobacterial infection], pneumocystis pneumonia, and Mycobacterium tuberculosis (tuberculosis, TB).