Gastroenterology & Hepatology
A 68 year old man is brought to the Emergency Department by his family. He has become increasingly fatigued over the previous week and in the last day the family have noticed a "yellow appearance". On examination you note tenderness in the right upper quadrant. He has recently returned from a business trip to India. You consider hepatitis A within your differentials. Regarding hepatitis A, which of the following statements is CORRECT?
Answer:
Transmission is by the faecal-oral route and the incubation period is is 28–30 days, with a range of 15–50 days. Hepatitis A does not cause chronic liver disease, has no chronic carrier state, and results in lifelong immunity. Treatment is supportive, antivirals have no clinical benefit. A hepatitis A vaccine is available recommended for travellers to high prevalence areas, patients with chronic liver infections and individuals with high risk occupations e.g. healthcare workers, sewage workers.Hepatitis A
Gastroenterology & Hepatology
Last Updated: 12th February 2021
Hepatitis A virus is a non-enveloped single-stranded RNA virus, which is classified in the hepatovirus genus of the Picornaviridae family. The virus replicates in hepatocytes, interfering with cell function and causing inflammation of the liver. Around 85% of people with hepatitis A infection make a complete recovery within three months. Almost all people with hepatitis A recover fully within six months. Hepatitis A does not cause chronic liver disease, has no chronic carrier state, and results in lifelong immunity.
Transmission
Transmission of hepatitis A is by the faecal-oral route. The mean incubation period is 28–30 days, with a range of 15–50 days. Hepatitis A virus is excreted in bile, and shed in the faeces of infected people.
Hepatitis A is uncommon in the UK and other high-income countries. Hepatitis A is endemic in many low-income countries, where standards of sanitation and food hygiene may be poor. In countries where hepatitis A is highly endemic, it is mainly transmitted by close personal contact or via faeces-contaminated food and water. In countries where hepatitis A is uncommon, new infections occur via travel to places where the virus is highly endemic. People who have acquired the infection abroad may then transmit the virus to others upon their return.
Risk factors
- Travellers to areas with a high prevalence
- People with clotting factor disorders (factor VIII and factor IX concentrates have been identified as rare sources of hepatitis A infection)
- Men who have sex with men, and people with risky sexual behaviours (sexual practices involving oral-anal or digital-rectal contact, those who have multiple sexual partners, anonymous partners, sex in public places, and group sex)
- Injecting drug users and their close contacts (at risk of poor standards of personal hygiene, with possible faecal contamination of shared drug equipment and other paraphernalia)
- People at occupational risk (such as laboratory workers, staff of large residential institutions, sewage workers, and people who work with primates
Clinical features
The clinical features of acute hepatitis A are common to all forms of acute viral hepatitis, and it cannot easily be distinguished by history, examination, or by routine biochemistry tests. Note that most children and up to half of adults are asymptomatic or have mild nonspecific symptoms with little or no jaundice.
- Prodromal phase (usually lasts 3 - 10 days)
- Flu-like symptoms (such as general fatigue, malaise, joint and muscle pain, low-grade fever up to 39°C).
- Gastrointestinal symptoms (such as anorexia, nausea, vomiting, and right upper quadrant abdominal discomfort).
- There may be accompanying headache, cough, sore throat, constipation, diarrhoea, itch, or urticaria.
- Icteric phase (usually lasts 1 - 3 weeks but can last longer)
- Jaundice, pale stools and dark urine if cholestasis.
- Pruritus (present in 40% of those with jaundice).
- Fatigue, anorexia, nausea, and vomiting — symptoms often improve once jaundice occurs.
- Hepatomegaly (85%), splenomegaly (15%), lymphadenopathy (5%), and hepatic tenderness are often present on examination.
- Convalescent phase (may take up to 6 months)
- Malaise, anorexia, muscle weakness, and hepatic tenderness.
Hepatitis serology and liver function tests should be carried out if hepatitis A is suspected.
Differential diagnosis
The differential diagnoses of hepatitis include:
- Viral hepatitis caused by other viruses (such as hepatitis B, C, D, and E), Epstein-Barr virus (infectious mononucleosis), or cytomegalovirus (CMV)
- Non-alcoholic fatty liver disease
- Alcohol-induced hepatitis
- Drug-induced liver disease
- Acute HIV infection.
- Autoimmune hepatitis
- Hepatitis caused by bacteria, such as Leptospirosis and Coxiella burnetii
- Granulomatous disorders
- Metabolic and genetic disorders (such as Wilson's disease, hereditary haemochromatosis, alpha1 antitrypsin deficiency)
Diagnosis
Public Health England uses the following case definitions for hepatitis A:
- Clinical case (possible):
- A person with an acute illness, discrete onset of symptoms AND jaundice or elevated serum aminotransferase levels.
- Probable case:
- Meets the clinical case definition (above) and has an epidemiological link to a confirmed hepatitis A case, OR
- Meets the clinical case definition and has IgM antibody to the hepatitis A virus.
- Confirmed case:
- Meets the clinical case definition and has IgM and IgG antibodies to hepatitis A, OR
- Has hepatitis A RNA (HAV RNA) detected regardless of clinical features, OR
- Is asymptomatic with no recent history of immunisation, but has anti HAV IgM in oral fluid or serum, and has an epidemiological link to a confirmed hepatitis A case.
Management
There is no specific treatment for hepatitis A.
- Provide supportive symptomatic care as required:
- Self-care advice regarding rest, hydration, itching etc.
- Analgesia
- Antiemetics
- Anti-itch treatment
- Notify the Health Protection Unit (HPU) promptly to facilitate appropriate surveillance and contact tracing.
- Provide the person with information and advice about hepatitis A, including:
- Avoiding drinking alcohol during the acute illness.
- Avoiding work, school, or nursery, until they are no longer infectious (typically 7 days after the onset of jaundice, or 7 days after the onset of symptoms if there is no history of jaundice).
- Taking steps to minimise the risk of transmission to partners and contacts.
If a person presents who has been in contact with someone with known hepatitis A infection, contact the local Health Protection Unit (HPU) immediately, who will advise on further management if the person has not previously received hepatitis A vaccine. This may include giving hepatitis A vaccination and/or arranging for the administration of human normal immunoglobulin, depending on the timing and circumstances of contact, as well as other factors including the person's age and comorbidities.
Complications
- In around 15% of infected symptomatic people, fever, pruritus, diarrhoea, jaundice, weight loss, and malabsorption can exhibit a relapsing course persisting for several months.
- Fulminant liver failure occurs in around 0.4% of people and can lead to coagulopathy and hepatic encephalopathy. It usually manifests during the first four weeks of illness and is more common in people with concurrent chronic liver disease including chronic hepatitis B or C infection. It has a mortality rate of 40% without liver transplantation.
- Other (rare to very rare) complications include acalculous cholecystitis, pancreatitis, aplastic anaemia, autoimmune haemolysis, autoimmune thrombocytopenic purpura, haemolysis (G6PD deficiency), Guillain-Barre syndrome, mononeuritis multiplex, post-viral encephalitis, transverse myelitis, acute renal failure, cutaneous vasculitis, cryoglobulinaemia, and reactive arthritis.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
