Viral Hepatitis (particularly D and E)

The term viral hepatitis is generally used to refer to liver inflammation caused by the hepatropic viruses including:

• Hepatitis A (HAV)
• Hepatitis B (HBV)
• Hepatitis C (HCV)
• Hepatitis D (HDV)
• Hepatitis E (HEV)
• Other viruses, which may cause hepatitis but which do not primarily infect the liver, include:
  • Cytomegalovirus (CMV)
  • Epstein-Barr virus
  • Adenovirus
  • Herpes simplex virus (rarely)

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.¹
Despite their name, the hepatropic viruses (particularly B and C) can cause extrahepatic disease. Viral agents can cause acute, chronic and subclinical liver disease.

• Viral infection is responsible for around half of all cases of acute hepatitis.²
• Hepatitis A–E account for about 95% of cases of acute viral hepatitis seen in the USA.²
• It is estimated that worldwide most acute hepatitis is caused by HBV (4 million cases) followed by HAV (1.4 million cases).
• it is estimated that 350 million people are chronically infected with HBV.
• Figures for acute HCV infection are particularly difficult to estimate because patients are often asymptomatic. About 170 million people are chronically infected with HCV worldwide.
• 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.²
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 scanning to assess presence of cirrhosis or other causes of symptoms.

• Acute:
  • Drugs
  • Toxins
  • Alcohol
  • Infectious mononucleosis
  • CMV
  • Q fever
  • Leptospirosis
  • Syphilis
  • Malaria
  • Yellow fever
  • Obstructive jaundice
• Chronic:
  • Alcohol
  • Drugs
  • Autoimmune hepatitis
  • Haemochromatosis
  • Wilson's disease

HAV may occur in outbreaks in institutions. It is common in travellers. Most infections pass unnoticed in childhood. It is a small, unenveloped, symmetrical RNA virus (picornavirus).⁴ See separate Hepatitis A article.

HBV is a double-stranded DNA virus which replicates by reverse transcription (Hepadnaviridae family).
It is endemic with more than 350 million people infected worldwide.⁵ See separate Hepatitis B article.

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

HDV is an unusual, defective, single-stranded RNA virus. It requires the presence of HBV to replicate. HDV infection develops only in patients who are positive for the hepatitis B surface antigen (HBsAg). Infection may be acquired along with HBV (co-infection) or after HBV infection (superinfection).

Epidemiology

• 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 HBV, or as a superinfection in those with existing chronic HBV infection. Therefore transmission is, like HBV, by exposure to infected blood and blood products. It can be transmitted percutaneously and sexually. Perinatal transmission is rare.

Clinical features

• The acute HDV co-infection (or simultaneous infection) is often short-lived with fewer than 5% of patients developing chronic HDV infection.
• The incubation period of HDV is approximately 35 days.
• Superinfection tends to cause a more severe acute infection and progression to cirrhosis is possibly more common.
• Around 80% of co-infected patients will go on to develop chronic liver disease, including cirrhosis. This is much higher than with HBV infection alone when between 15 and 20% of patients go on to develop chronic liver disease. Co-infection also carries an increased risk of fulminant hepatic failure.

Investigations

Anti-HDV antibody.

Management

Interferon-a has limited success in treatment of HDV infection. Lamivudine appears also to be ineffective and so treatment is supportive.

Prevention

As for hepatitis C.

HEV is a non-enveloped, single-stranded, RNA virus of the Caliciviridae family. The mode of transmission is similar to HAV and it is the primary cause of enterically transmitted non-A, non-B hepatitis. Most outbreaks occur in developing countries.

Epidemiology

In some areas it is the most common 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 is high in pregnancy.⁶ Intrauterine infection (± stillbirth) is common.

Route of transmission

• This is by the faecal-oral route and similar to hepatitis A.
• Contaminated drinking water is the most common source of infection.
• Person-to-person transmission is rare but maternal-neonatal transmission does occur.
• Zoonotic spread may occur as other animals (primates, cows, pigs, sheep, goats, and rodents) are susceptible to infection.

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.
• There are no reports of chronic infection with HEV.
• HEV usually causes an acute self-limiting illness like HAV. Fulminant disease occurs in about 10% of cases.
• In pregnancy, the mortality rate may be as high as 15-20%.

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 is currently available

HGVs were originally identified in the blood of a surgeon (initials 'GB') with jaundice.⁷

• 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).

1. Akiba J, Umemura T, Alter HJ, et al; SEN virus: epidemiology and characteristics of a transfusion-transmitted virus. Transfusion. 2005 Jul;45(7):1084-8. [abstract]
2. Wolf DC; Hepatitis, Viral. eMedicine. July 2009.
3. Judd A, Hickman M, Jones S, et al; Incidence of hepatitis C virus and HIV among new injecting drug users in London: prospective cohort study. BMJ. 2005 Jan 1;330(7481):24-5. Epub 2004 Nov 12.
4. Ryder SD, Beckingham IJ; ABC of diseases of liver, pancreas, and biliary system: Acute hepatitis. BMJ. 2001 Jan 20;322(7279):151-3.
5. Dept. of Health; Hep B Immunisation (DOH Green Book); [As PDF].
6. Scharschmidt BF; Hepatitis E: a virus in waiting. Lancet. 1995 Aug 26;346(8974):519-20.
7. Simons JN, Leary TP, Dawson GJ, et al; Isolation of novel virus-like sequences associated with human hepatitis. Nat Med. 1995 Jun;1(6):564-9. [abstract]

• Management of the Viral Hepatitides A, B and C, British Association for Sexual Health & HIV (2008)
• FACE IT! - Hepatitis C Awareness website
• The Hepatitis C Trust