Patients can be referred to a gastroenterologist where the predominant problem is an abnormal blood test result following routine health screening.
By the very nature of these referrals, these patients are either asymptomatic or have very subtle symptoms or signs.
Although some of these issues may have been dealt with in other chapters within this booklet, we will approach these problematic blood test results in a rational and practical manner in this section.
The most commonly referred patients fall into three categories:
- Raised tumour markers (Alphafetoprotein [AFP], carcinoembryonic Antigen [CEA], carbohydrate antigen 19-9 [CA19-9])
- Abnormal liver function tests
1. Raised Tumour Markers
a. Alpha-fetoprotein (AFP)
In conjunction with abdominal ultrasonography, it is recommended that alphafetoprotein (AFP) be measured at six-monthly intervals in patients at high risk for hepatocellular carcinoma (especially those with liver cirrhosis related to hepatitis B or hepatitis C). A raised AFP is found in 80% of patients with hepatocellular carcinoma and in 40% of these patients, the AFP exceeds 1000 ng/mL.
However, AFP can be raised in other cancers, namely:
• Non-seminomatous germ cell tumours
• Gastric cancer
• Biliary tract cancer
• Pancreatic cancer
• Lung cancer
AFP can be raised in non-malignant conditions like:
• Viral hepatitis
• Ataxia telangiectasia
b. Carcinoembryonic Antigen (CEA)
Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in normal mucosal cells but increased amounts are associated with adenocarcinoma, especially colorectal cancer. Levels exceeding 10 ug/L are rarely due to benign disease. Sensitivity increases with advancing colorectal cancer state. However, poorly differentiated tumours are less likely to produce CEA.
CEA levels are useful in assessing prognosis (with other factors), detecting recurrence and monitoring treatment in patients with colorectal cancer.
Conditions which may have elevated CEA include:
• Colorectal cancer; tumours on the right side of the colon tend to produce higher CEA levels than tumours on the left side
• Breast cancer
• Lung cancer
• Gastric cancer, oesophageal cancer, pancreatic cancer
• Skeletal metastases
• Non-malignant liver disease, including cirrhosis, chronic active hepatitis
• Chronic kidney disease
• Pancreatic disease
• Inflammatory bowel disease, diverticulitis, irritable bowel syndrome
• Respiratory diseases, eg. pleural inflammation, pneumonia
c. Carbohydrate Antigen 19-9
Elevated levels of CA19-9, an intracellular adhesion molecule, occur primarily in patients with pancreatic and biliary tract cancers, but may be raised in colorectal, gastric, hepatocellular, oesophageal and ovarian cancers.
Benign conditions such as cirrhosis, cholestasis, cholangitis and pancreatitis also result in elevations, although values are usually less than 1000 u/mL. CA19-9 may be raised in diabetes mellitus.
Another abnormal blood test result that requires further evaluation and treatment is anaemia. For men, anaemia is typically defined as a haemoglobin level of less than 13.5g/dL and in women as haemoglobin of less than 12g/ dL. Some patients with anaemia have no symptoms but can be symptomatic if the haemoglobin is significantly low.
Anaemia can be categorized as microcytic (MCV less than 80FL), normocytic (MCV 80-100FL) or macrocytic (MCV more than 100FL). The most common cause of microcytic anaemia is iron deficiency anaemia, although hereditary disorders like alpha thalassaemia or beta thalassaemia needs to be excluded.
The most common causes of iron deficiency anaemia are:
• A lack of iron in the diet of vegans and vegetarians
• Heavy menstruation
• Rapid childhood growth
• Peptic ulcer disease (H. pylori, NSAIDs)
• Gastrointestinal malignancy (colorectal, gastric and small intestinal)
• Coeliac disease
• Crohn’s disease
• Colonic polyps
• Haemorrhoids Macrocytic anaemia may be caused by Vitamin B12 deficiency.
Vitamin B12 deficiency may be due to:
• Pernicious anaemia
• Strict vegetarianism
• Long-term alcoholism
• Intestinal strictures (Crohn’s disease), blind loop syndrome and bacterial overgrowth (postsurgery)
3. Abnormal Liver Function Tests
Patients with no or minimal symptoms and abnormal liver function test results are common. These abnormal liver function tests fall in three main groups:
i. Isolated hyperbilirubinemia
ii. Predominantly raised serum alkaline phosphatase (SAP) and gamma-GT
iii. Predominantly raised alanine transaminase (ALT) and Aspartate transaminase (AST)
i. Causes of isolated hyperbilirubinemia include:
• Gilbert’s syndrome, Crigler- Najjar syndrome, Dubin-Johnson syndrome
• Chronic liver disease
ii. Causes of raised serum alkaline phosphatase (SAP) and gamma-GT (Cholestasis) include:
• Primary biliary cirrhosis
• Drugs (tricyclic antidepressants, erythromycin, oral contraceptive pill, anabolic steroids)
• Primary sclerosing cholangitis
• Cardiac failure
• Space-occupying hepatic lesion (hepatoma or secondaries)
• Head of pancreas neoplasm
• Biliary malignancy
iii. Predominately raised ALT/AST (‘Hepatitic picture’) include:
• Non-alcoholic steatohepatitis (NASH)
• Alcoholic hepatitis
• Medication (Statins, Isoniazid, Phenytoin, Paracetamol overdose)
• Chronic hepatitis B, C
• Autoimmune hepatitis
• Acute hepatitis A, B, C, EBV and CMV infection
• Metabolic-Glycogen Storage disorders, Wilson’s disease
Patients presenting with raised tumour markets (AFP, CEA, CA19-9) may have relatively few symptoms.
However, a history of hepatitis B or C, significant alcohol intake and family history of hepatoma would be pertinent in patients with a raised AFP. Besides, through abdominal examination, inspection of the testes in men to exclude non-seminomatous germ cell tumours is useful. Further investigations would include a transabdominal ultrasound and upper gastrointestinal endoscopy would be required in the evaluation of patients with a raised AFP.
If the patient has a raised CEA, a history of smoking and symptoms suggestive of colorectal (per rectum bleeding, change in bowel habits) and lung (cough, hemoptysis) malignancy needs to be inquired for. Cross-sectional imaging (CT, MRI) of the thorax, abdomen and pelvis followed by endoscopy (gastroscopy, colonoscopy) should be performed where appropriate.
Patients with a raised CA19-9 would require cross-sectional imaging to exclude pancreatic and biliary malignancy and a gastroscopy and colonoscopy where appropriate. Patients with anaemia may be asymptomatic or may experience fatigue, have palpitations or become short of breath.
Symptoms of excessive blood loss (gastrointestinal-per-rectal bleeding, malena or excessive menstruation) should be elucidated. A dietary history is essential. Further evaluation would depend on the likely cause of anaemia and may include endoscopy or referral to a dietician or gynaecologist.
If the predominant problem is that of an abnormal liver function test results, the evaluation would require a complete history of one’s lifestyle (including recent travel, transfusions, unprotected sexual intercourse, alcohol intake, diabetes mellitus, obesity, hyperlipidemia, family history) and a thorough clinical examination for stigmata of chronic liver disease, hepatosplenomegaly, ascites and obesity.
The diagnostic algorithm would depend on the predominant problem, for example the exclusion of hemolysis for isolated hyperbilirubinemia is important. However, if the main problem is that of a ‘hepatitic picture’, on liver function tests, viral serology eg. Hepatitis B & C, cytomegalovirus (CMV), Epstein-Barr virus and possibly HIV may be more appropriate. Autoantibody screen eg. antimitochandrial antibody, anti-smooth muscle antibody and antinuclear antibody should be performed. Exclusion of Wilson’s disease or Glycogen Storage disease would be appropriate in some circumstances.
Transabdominal ultrasound is noninvasive and a useful screening test to detect structural abnormalities before more detailed cross-sectional imaging (CT, MRI, MRCP) is ordered.
The treatment of these patients is dependent on the final diagnosis following evaluation.