Viral Hepatitis

• Hepatitis A–E
• Cytomegalovirus
• Epstein-Barr virus
• Adenovirus
• Herpes simplex (rarely)

Viral infection is responsible for around half of all cases of acute hepatitis.¹
A recently discovered DNA virus, SEN-V, is apparently responsible for cases of post-transfusion hepatitis and a possible cause of non-A/non-E hepatitis, although this is far from established.²
Despite their name, the hepatropic viruses (particularly B and C) can cause extrahepatic disease. Viral agents can cause acute, chronic and subclinical liver disease.

Hepatitis A–E account for about 95% of cases of acute viral hepatitis seen in the USA.¹
A survey in 2005 found that hepatitis C has an incidence of 41.8 cases per 100 person years among new injecting drug users in London.³
It is estimated that there is an annual incidence of roughly 100,000 cases of viral hepatitis in the UK population.

Acute infection may present with:

• Nausea and vomiting
• Myalgia
• Fatigue/malaise
• Right upper quadrant pain
• Change in sense of smell or taste
• Coryza
• Photophobia
• Headache

Diarrhoea (with pale stools and dark urine) may also be present.¹
However, often no signs are seen unless jaundice develops. Hepatomegaly, splenomegaly and lymphadenopathy may then be present.

Chronic infection

This is most commonly a consequence of infection with hepatitis B or C.

• About 90% of neonates and 5% of adults with acute hepatitis B, and up to 85% of cases of acute hepatitis C will evolve to chronic hepatitis (diagnosed on histological grounds).
• Presentation is highly varied and may be asymptomatic; subclinical infection causes only vague symptoms like fatigue and dyspepsia.
• It may lead to chronic liver disease and cirrhosis.
• About 20% of patients with chronic hepatitis B or C go on to develop cirrhosis, histologically. Cirrhosis can remain asymptomatic or cause serious illness.
• Chronic hepatitis and cirrhosis can take months to decades to develop. Signs of chronic liver disease may be apparent.

• Full blood count
• Urea and electrolytes
• Liver function tests
• International normalised ratio
• Serology (see below)
• Imaging with ultrasound/CT/MRI to assess presence of cirrhosis or other causes of symptoms.

• Acute: Drugs, toxins, alcohol, infectious mononucleosis, cytomegalovirus, Q fever, leptospirosis, syphilis, malaria, yellow fever, obstructive jaundice
• Chronic: Alcohol, drugs, autoimmune hepatitis, haemochromatosis, Wilson's disease

May occur in outbreaks in institutions. Is common in travellers. Most infections pass unnoticed in childhood. It is a small, unenveloped, symmetrical RNA virus (picornavirus).⁴

Routes of transmission

It is normally spread by the faecal-oral route but can also be spread occasionally through blood.⁵

Clinical features

• 2-6 weeks incubation
• Prodrome of anorexia, nausea, joint pain, and fever, preceding the jaundice
• Diarrhoea, particularly in children
• Tender hepatomegaly, splenomegaly, and lymphadenopathy may occur
• 15% have prolonged or relapsing illness for 6-9 months

Investigations

• Serum transaminases rise 22-40 days after exposure
• Specific antibodies rise from 25 days
• IgM signifies recent infection, and IgG remains detectable for life

Management

• Mainly supportive
• Avoid alcohol until LFTs normal
• Admit patients with severe systemic upset or intractable vomiting for rehydration and observation

Prevention

• After infection immunity is probably life-long
• Good hygiene and sanitation, avoidance of tap water in high risk areas
• Passive immunisation; normal human immunoglobulin (0.02 ml/kg IM) gives <3 months' passive immunity to those at risk (eg travellers; all household contacts) and during incubation
• Active immunisation:
  • Havrix Monodose®, an inactivated protein derived from hepatitis A virus
  • Dose: if >16yrs old, one IM dose (1 ml to deltoid) gives immunity for 1yr (10yrs if further booster is given at 6 months)
  • Use Havrix Monodose Junior® if < 15yrs old
  • Use Havrix Junior® if 1–15yrs old

Prognosis

• Usually self-limiting (rarely fulminant)
• There is no carrier state, and chronic liver disease does not occur

This is a double-stranded DNA virus which replicates by reverse transcription (hepadnaviridae family).
It is endemic with more than 350 million people infected worldwide.⁶ See separate Hepatitis B article.

Route of transmission

The parenteral route - may be through unsafe sex, blood products (particularly if pooled, e.g. pre-recombinant Factor VIII for haemophiliacs), needlestick injury/surgical transmission in healthcare workers, recreational intravenous drug use, haemodialysis.

Clinical features

• Similar to hepatitis A; 1-6 months incubation
• Signs and symptoms less common in children and 30% cases may have none
• Urticaria and arthralgia may also occur

Investigations

Serological markers for HBV infection

Management

• Post-exposure: see needle-stick injury
• Acute phase:
  • Mainly supportive
  • It is not known whether anti-viral agents have any effect in the acute phase of hepatitis B
  • Avoid alcohol
• Chronic phase:
  • Interferon-a, lamivudine and adefovir dipivoxil (latter two are synthetic nucleotide analogues) used in specialist centres
  • They can have severe side effects and patients initiating or discontinuing therapy need close observation
  • NICE have issued guidelines on their use⁷
  • Immunise sexual contacts

Prevention

• Screening of at-risk individuals
• Hepatitis B vaccination
• Pre- or post-exposure prophylaxis (see needle-stick injury)
• Safe sex
• Blood product screening
• Risk prevention strategies
• New technologies in surgery/venesection etc

This is an enveloped RNA virus in the flaviviridae family with a narrow host range (humans and chimpanzees). See separate Hepatitis C article.

• In the UK, 0.4 - 1.0% of the population have the hepatitis C virus.⁸
• Approximately 170 million people worldwide (3% of the world's population) are infected - hence it is a very major health issue.

Route of transmission

Hepatitis C is transmitted via the parenteral route, especially by intravenous drug use. It also acquired by blood transfusion (received before September 1991), haemodialysis, sexual contact with an infected individual, needlestick injury and perinatal transmission from an infected mother.

Clinical features

Acute HCV Infection:

• The majority are asymptomatic.
• 20-30% present with jaundice or deranged liver enzymes (ALT), some have non-specific symptoms such as anorexia, lethargy or abdominal pain.
• Average time from exposure to onset of symptoms is 6-7 weeks, and to seroconversion is 8-9 weeks (can take up to 9 months).

• Occurs in 75-85% of patients.
• It is indicated by persistently elevated or fluctuating liver enzyme levels.
• 5% develop cirrhosis and 15% of these risk hepatic carcinoma.

Investigations

FBC, LFT, GGT, Glucose, INR, serum ferritin (to exclude haemochromatosis), autoantibodies/immunoglobulins, hepatitis B serology and USS liver.

Management

• Refer to a specialist with a particular interest in HCV.
• Patients should be advised that excess alcohol consumption appears to hasten the progression of disease. Abstinence from alcohol is advisable.
• Consideration should be given to entering patients with established cirrhosis into surveillance programmes for hepatocellular carcinoma (provided their general health is good enough that emerging cancers could be appropriately treated).
• Peginterferon alfa-2a (or alfa-2b) and ribavirin can be prescribed in line with current NICE guidelines.⁹

Prevention

• No vaccine is currently available.
• Patients and at risk groups should be counselled to minimise transmission.

This is an unusual, single-stranded, circular RNA virus.

• 18 million people (5%) of HBV carriers also have HDV.
• It is an important cause of acute and severe chronic liver damage in some parts of the world (Mediterranean, parts of Eastern Europe, Middle East, Africa, and South America).

Route of transmission

It needs hepadnavirus to function and for its propagation in hepatocytes, and is therefore acquired as a co-infection with Hepatitis B, or as a superinfection in those with existing chronic Hepatitis B.

Clinical features

• Co-infection: increased risk of fulminant hepatic failure.
• Superinfection: progression to cirrhosis believed more common.

Investigations

Anti-HDV antibody

Management

Interferon-a has limited success in treatment of HDV infection.

Prevention

As for hepatitis C

This is a non-enveloped, single-stranded, RNA virus of the Caliciviridae family.
In some areas it is the commonest viral cause of hepatitis in adults and older children, causing major epidemics in the Indian subcontinent, Central and South-East Asia, the Middle East, and parts of Africa. Mortality if pregnant may be up to 20%.¹⁰ Intrauterine infection (± stillbirth) is common.

Route of transmission

This is similar to hepatitis A.

Clinical features

• These are also similar to hepatitis A with no apparent risk of chronic liver disease.
• Incubation is 2-9 weeks.
• Usually a self-limiting illness.

Investigations

Hepatitis serology

Management

This is mainly supportive, as hepatitis A.

Prevention

• Good hygiene and sanitation
• Avoidance of tap water in high risk areas (most outbreaks associated with contaminated drinking water)
• Gammaglobulin is ineffective
• No vaccine currently available

These were originally identified in the blood of a surgeon (GB) with jaundice.¹¹

• Two distinct viruses were identified initially when tamarind monkeys were inoculated with the serum of this patient (GBV-A and GBV-B).
• The third virus, GBV-C, was later isolated from a human specimen (this was the new "hepatitis G" virus separately identified in 1996).
• All three are members of the flaviviridae family of viruses and share significant homology with HCV.
• HGV RNA is found in 1.5% to 4% of routine blood donors and is readily transmitted by blood product transfusion.
• Evidence now suggests this virus is not hepatotropic and doesn't have a role in either acute or chronic liver disease, although there may be an association with aplastic anaemia (controversial).

This was first described in 1997 - TT being the initials of a patient in Japan with post-transfusion hepatitis.^12,13

• It is an unenveloped single stranded DNA virus, which was described in the sera of 3/5 patients with biopsy proved non-A to G post-transfusion hepatitis in Japan.
• It may be a cause of chronic hepatitis, although UK and US studies have failed to demonstrate a pathogenic role in hepatitis.¹