Gastroenterology & Hepatology
A 67 year old man presents to the Emergency Department with a 1 month history of weight loss and right upper quadrant pain. He has a past medical history of chronic hepatitis B infection. On examination you note ascites and cachexia. What is the most likely diagnosis?
Answer:
Chronic hepatitis B and C infections are associated with a significantly increased risk of hepatocellular carcinoma. Hepatocellular carcinoma is also an important consequence of liver cirrhosis and should be suspected in any patient with rapid development of weight loss on a background of cirrhosis. Investigations include serum alpha-fetoprotein, followed by either liver biopsy or computed tomography (CT) imaging. Resection is possible for early-stage cancers. The prognosis is extremely poor for non-resectable tumours, and there is a 20% 5-year survival rate for operable tumours.Hepatitis B
Gastroenterology & Hepatology / Sexual Health
Last Updated: 17th March 2023
Hepatitis B is an infectious disease of the liver caused by the hepatitis B virus. In adults and older children, it is usually a self-limiting condition marked by inflammation of the liver and transient infection. In more than 90% of people, lifelong immunity is achieved after clearing the infection. In infants and younger children, it is generally asymptomatic but often results in chronic infection.
Transmission
In the UK, the majority (95%) of chronic hepatitis B infections occur in migrant populations, having been acquired perinatally in the country of birth. Where new infections are acquired in adulthood, the source of infection is most commonly via sexual contact or sharing of drug injecting equipment.
- Transmission by blood-to-blood contact:
- Sharing of drug injecting equipment
- Occupational hazards e.g. needlestick injuries
- Blood transfusions and blood products
- Tattoos, body piercing or acupuncture
- Household contact and sharing of toiletry items e.g. razors or toothbrushes
- Sexual transmission:
- Transmission occurs via mucous membranes (vaginal, anal, and oral) during sex
- Vertical transmission:
- Perinatal transmission (during childbirth) is common in areas of high prevalence
- Transmission to the unborn fetus is relatively uncommon
- Hepatitis B cannot be transmitted to infants during breastfeeding
Risk factors
People at high risk of hepatitis B include:
- Injecting drug users and their close contacts.
- People who change sexual partners frequently, particularly if they are men who have sex with men.
- Travellers to areas with a high prevalence (usually via sexual exposure [largely heterosexual] or invasive medical procedures).
- People from a country with a high prevalence (due to high risk of perinatal transmission/subsequent acquisition in endemic areas).
- Sex workers and their clients.
- Household contacts of people with hepatitis B (a case or a carrier), including close family and carers.
- Families adopting a child from a country with a high prevalence of hepatitis B.
- People receiving regular blood or blood products (such as people with haemophilia) and their carers.
- People with chronic renal failure or chronic liver disease.
- People with an occupational risk (such as healthcare workers, laboratory staff, and morticians).
- Looked-after children and young people, including those living in care homes
- Prison inmates and staff.
- Infants born to women with hepatitis B infection.
- Hajj and Umrah pilgrims who have had their head shaved (risk when using unlicensed barbers).
Clinical features
- For acute infection, these include:
- A prodromal illness that includes fever, arthralgia, or a rash (that may appear about 2 weeks before the onset of jaundice, then resolves in acute hepatitis B).
- Non-specific malaise, fatigue, fever, nausea, and poor appetite.
- Right upper quadrant abdominal pain.
- Jaundice (with dark urine and/or pale stools if cholestasis).
- Extrahepatic manifestations such as glomerulonephritis, vasculitis, and polyarteritis.
- For chronic infection, there are often no physical signs. After many years of infection, depending on the severity and duration, there may be signs of chronic liver disease including:
- Spider naevi.
- Finger clubbing.
- Jaundice.
- Hepatosplenomegaly.
- In severe cases thin skin, bruising, ascites, liver flap and encephalopathy.
Investigations
- Hepatitis B serology.
- Hepatitis B Surface Antigen (HBsAg) — indicates presence of viral envelope, and suggests that the person is infectious, chronic HBV infection is indicated by the persistence of HBsAg for more than 6 months
- Hepatitis B e antigen (HBeAg) - detectable in acute infection and some chronic infection, usually associated with relatively high levels of virus replication and thus infectivity
- Antibody to HBeAg (Anti-HBe) - present following clearance of HBeAg, indicates decreased infectivity
- Antibody to HBcAg (anti-HBc) — indicates current or previous HBV infection, appears at onset of symptoms in acute infection and persists for life
- Antibody to HBsAg (anti-HBs) — indicates recovery from and immunity to HBV, anti-HBs without anti-HBc is a marker of immunisation
- HBV DNA - high levels are associated with a greater risk of progression to cirrhosis and hepatocellular cancer
- Hepatitis A, C, and D and HIV serology.
- Liver function tests.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may be significantly increased (usually between 500 and 10,000 IU/L).
- Bilirubin may be elevated (usually between 85.5 and 171 micromols/L but can reach up to 500 micromols/L).
- Alkaline phosphatase is generally < 2x the upper limit of normal, but higher if there is cholestasis.
- Full blood count and prothrombin time.
- Prothrombin time may be prolonged (5 seconds or more suggests severe hepatitis and 50 seconds or more suggests acute liver failure).
- Tests for hepatocellular carcinoma, including serum alpha fetoprotein and liver ultrasound scan.
| Disease State | Serology |
|---|---|
| Acute hepatitis B |
|
| Chronic hepatitis B (active) |
|
| Chronic hepatitis B (inactive carrier) |
|
| Immunity following infection |
|
| Immunity due to vaccination |
|
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)
Management
- Refer anyone who is found to be HBsAg positive to a hepatologist or to a gastroenterologist or infectious disease specialist with an interest in hepatology (depending on local service provision), to consider the need for additional treatment, follow up, and monitoring.
- Treatment is not usually required for acute disease, other than symptomatic care.
- Treatment is indicated for chronic disease. The goals are to prevent disease progression to cirrhosis and end stage liver disease, hepatocellular carcinoma and death. Treatment generally does not offer a cure, but it does help delay or prevent cirrhosis for people who respond.
- Treatment options include:
- Peginterferon alfa-2a
- Antiviral treatments e.g. tenofovir or entecavir
- Liver transplant
- Advise 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 B, including:
- Avoiding drinking alcohol.
- Taking steps to minimise the risk of transmission to partners and contacts.
Post-exposure prophylaxis
Use clinical judgement (based on the person's risk of already having been exposed to hepatitis B) to determine the requirement for serology testing for immunity to hepatitis B at the same time as vaccination. People at high risk of previous exposure include:
- Babies born to mothers infected with hepatitis B.
- People with needlestick injury.
- Sexual assault victims.
- Injecting drug users.
- People who change sexual partners frequently, particularly men who have sex with men, and sex workers.
- Close family contacts of a person with hepatitis B.
For most people requiring pre- or post-exposure prophylaxis against hepatitis B, use a rapid immunisation schedule (given at zero, one and two months, or over 21 days if very rapid protection is needed, such as for needlestick injuries or imminent travel to a highly endemic area). For people where there is a high likelihood of compliance and rapid protection is not required, consider a three dose course of vaccine at zero, one and six months. If immunity to hepatitis B is demonstrated following initial serology testing, do not give the remaining doses of vaccine.
Arrange for immunoglobulin prophylaxis to be given at the same time as vaccination for people without proven hepatitis B immunity, following exposure to potentially infected blood or body fluids (including via needlestick, bite, or scratch injuries, contact with infected potentially material via mucous membranes [eyes or mouth], or broken skin, and unprotected sexual contact within last seven days with a person with hepatitis B). If immunoglobulin prophylaxis is thought to be indicated, discuss this with a microbiologist/the local health protection unit before giving treatment. Hepatitis B immunoglobulin is given intramuscularly ideally within 48 hours of exposure, and at the same time as the first dose of vaccine.
Complications
- Fulminant hepatitis
- Rare complication of acute hepatitis B infection (affects less than 1% of people). If present, however, it can progress rapidly to life-threatening liver failure with coagulopathy, encephalopathy, and cerebral oedema.
- Chronic hepatitis B infection
- Occurs when there is failure of the immune system to clear the virus, causing persistence of hepatitis B surface antigen (HBsAg) in the circulation for more than 6 months.
- Chronic hepatitis, cirrhosis and hepatocellular cancer
- Hepatitis B virus-infected hepatocytes become inflamed and necrotic, not as a direct result of infection, but via the host cellular immune response. The resultant liver damage may eventually lead to cirrhosis and hepatocellular cancer.
- Extrahepatic manifestations
- Such as glomerulonephritis, vasculitis, and polyarteritis - can occur with both acute and chronic infection.
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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 |
