LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS

A routine blood sample sent to the laboratory for liver biochemistry will be processed by an automated multichannel analyser to produce serum levels of bilirubin, aminotransferases, alkaline phosphatase, Y-glutamyl transpepti-dase (y-GT) and total proteins. These tests are often referred to as ‘liver function tests' (LFTs) but this term is misleading as they do not accurately reflect how well the liver is functioning. These tests are best referred to as ‘liver blood tests' or ‘liver biochemistry'. Liver synthetic function is deter-mined by measuring the prothrombin time (clotting factors are synthesized in the liver) and serum albumin, which are increased and reduced, respec-tively, with impaired function. Hypoalbuminaemia is also found in hypercata-bolic states (e.g. chronic inflammatory disease and sepsis) and where there is excessive renal (nephrotic syndrome) or intestinal (protein-losing entero-pathy) loss of albumin. A prolonged prothrombin time may also occur as a result of vitamin K deficiency in biliary obstruction (low concentration of intestinal bile salts results in poor absorption of vitamin K); however, unlike in liver disease, clotting is corrected by giving vitamin K 10 mg intravenously for 2-3 days.

■ Bilirubin (normal range <17 |imol/L, 1.00 mg/dL) is the breakdown product of haemoglobin (see p. 145). An isolated rise in serum bilirubin with otherwise normal liver biochemistry is likely to be due to an inherited defect in bilirubin metabolism (usually Gilbert's disease), haemolysis or ineffective erythropoiesis (premature death of the red cell in the bone marrow). Hyperbilirubinaemia caused by hepatobiliary disease is almost always accompanied by other abnormalities of liver biochemistry; very high levels occur most frequently in biliary tract obstruction. Serial measurements are useful in following the progress of some diseases, e.g. primary biliary cirrhosis, or the response to treatment, e.g. after placement of a stent in cancer of the head of the pancreas.

■ Aminot/ansterases. These enzymes are present in hepatocytes and leak into the blood with liver cell damage. Very high levels may occur with acute hepatitis (20-50 times normal). Aspartate aminotransferase (AST, normal range 10-40 U/L) is also present in heart and skeletal muscle, and raised serum concentrations are also seen with myocardial infarction and skeletal muscle damage. Alanine aminotransferase (ALT, normal range 5-40 U/L) is more specific to the liver than AST.

■ Alkaline phosphatase (normal range 25-115 U/L) is situated in the canal-icular and sinusoidal membranes of the liver. Raised serum concentra-tions are seen in cholestasis (bile flow is impaired or completely halted) from any cause, whether intra- or extrahepatic disease. Circulating alka-line phosphatase is also derived from the placenta and bone, and raised serum levels occur in pregnancy, Paget's disease, osteomalacia, growing children and bony metastases. Measurement of alkaline phosphatase isoenzymes or serum Y-GT, see below) will determine if a raised serum alkaline phosphatase is predominantly of bone or liver origin.

■ ỵ-GT (normal range: male <50 U/L, female <32 U/L) is a liver microsomal enzyme which may be induced by alcohol and enzyme-inducing drugs, e.g. phenytoin. A raised serum concentration is a useful screen for alcohol abuse. In cholestasis the Y-GT rises in parallel with the serum alkaline phosphatase because it has a similar pathway of excretion.

Approach to interpretation of abnormal liver biochemistry

A predominant elevation of serum aminotransferases indicates hepatocellular injury. Elevation of the serum bilirubin and alkaline phosphatase in excess of aminotransferases indicates a cholestatic disorder such as primary biliary cirrhosis, primary sclerosing cholangitis or extrahepatic bile duct obstruction. An isolated rise in bilirubin is most likely to be due to Gilbert's disease. The approach to investigating a rise in serum bilirubin is discussed under ‘Jaundice' (p. 145). A careful history (alcohol consumption, exposure to hepatotoxic drugs, risk factors for chronic liver disease), physical examination (particularly features of chronic liver disease), simple laboratory tests (to look for viral hepatitis, metabolic and autoimmune liver disease, Table 4.1), and an ultrasound (US) examination of the liver are the usual first steps in patients with a persistent elevation of serum aminotransferases. A liver biopsy (p. 143) may subsequently be necessary.

OTHER INVESTIGATIONS IN LIVER AND BILIARY DISEASE

Imaging with abdominal US and computed tomography (CT) is widely used in the investigation of liver and biliary disease. US is usually performed first and is a more useful test for lesions in the gall bladder and bile duct. Endo-scopic US (p. 69) is used to detect and stage pancreatic tumours, assess the bile ducts, confirm malignancy (using US guided fine needle aspiration of tumours), and for tube placement to drain pancreatic fluid collections.

Magnetic resonance imaging (MRI) This is the most sensitive investiga-tion of focal liver disease. It is also useful in patients with allergies to iodine-based contrast materials in whom contrast-enhanced CT scan could not be performed. A specific technique (magnetic resonance cholangiopancreatog-raphy, MRCP) produces high-quality images of the pancreatic and bile ducts that are similar in appearance to those obtained by endoscopic retrograde cholangiopancreatography (ERCP) (see below). This non-invasive technique is replacing diagnostic, but not therapeutic, ERCP.

Endoscopic retrograde cholangiopancreatography (ERCP) involves the passage of an endoscope to the second part of duodenum and is

Table 4.1 Causes of chronic liver disease and cirrhosis

Cause

Non-invasive markers of aetiology

Common

Alcohol

History of excess alcohol, T serum Y-GT, T MCV

Hepatitis B ± D

HBsAg ± HBeAg/DNA in serum

Hepatitis C

HCV antibodies and HCV RNA in serum

Others

Primary biliary cirrhosis

Serum antimitochondrial antibodies, T serum IgM

Secondary biliary cirrhosis Dilated extrahepatic ducts on imaging

Autoimmune hepatitis

Serum autoantibodies (p. 159), T serum IgG

Haemochromatosis

Family history, T serum ferritin, T transferrin saturation, HFE gene

Budd-Chiari syndrome

Presence of known risk factors (p. 177), caudate lobe hypertrophy, abnormal flow in major hepatic veins on US

Wilson’s disease

<40 years old, i serum caeruloplasmin, i serum total copper, T 24-h urinary copper excretion, Kayser—Fleischer rings

Drugs

Drug history, e.g. methotrexate

a1-antitrypsin (AAT) deAciency

Young age, associated emphysema, i serum AAT

Cystic íibrosis (CF)

Presence of extrahepatic manifestations of CF

NAFLD

Features of the metabolic syndrome, hyperechoic liver on US

Sclerosing cholangitis: primary (PSC) and secondary

Most PSC patients have IBD and serum p-ANCA (p. 299), multifocal stricturing and dilatation of bile ducts on cholangiography (either MRCP or ERCP)

Metabolic storage diseases

Presence of extrahepatic features

Idiopathic (cryptogenic)

Absence of any identiíiable cause including on liver biopsy

NAFLD, non-alcoholic fatty liver disease; IBD, inflammatory bowel disease; γ-GT,
γ-glutamyl transpeptidase; MCV, mean corpuscular volume; ERCP, endoscopic
retrograde cholangiopancreatography; MRCP, magnetic resonance
cholangiopancreatography; p-ANCA, peripheral antineutrophilic cytoplasmic antibody.

performed under intravenous sedation. The pancreatic and bile ducts are imaged after the injection of radiographic contrast medium via the ampulla of Vater. Stones in the ducts can be removed and stents placed to relieve obstruction caused by strictures. Complications of ERCP include bleeding (after cutting of the sphincter to aid bile duct cannulation or stone removal), acute pancreatitis, perforation and cholangitis.

Percutaneous transhepatic cholangiopancreatography (PTC) involves injection of contrast into the biliary system via a percutaneously placed needle inserted into an intrahepatic duct. It is performed in patients with biliary dilatation in whom ERCP has failed or is not possible. If an obstruction in the bile duct is seen, a bypass stent can be inserted, draining either externally or internally, for long-term use.

Liver, biliary tract and pancreatic disease

Liver biopsy for histological examination is usually performed via a per-cutaneous approach under local anaesthesia. Contraindications include an uncooperative patient, a prolonged prothrombin time (by more than 3-5 s), platelet count <50 X 109/L, extrahepatic cholestasis and suspected haem-angioma. An US or CT guided biopsy is also performed when specific lesions need to be biopsied. Complications include biliary peritonitis and bleeding into peritoneum or into the bile duct (haemobilia).

Assessment of liver tibrosis and cirrhosis is usually made by histo-pathological examination of a liver biopsy specimen. Disadvantages of liver biopsy are sampling error and its invasive nature. Imaging (US, CT and MRI) will detect advanced liver disease such as nodularity and portal hypertension but will not assess the earlier stages of fibrosis. Non-invasive techniques recently developed are US- and MRI-elastography, which measure hepatic tissue stiffness as an indicator of fibrosis, and serum tests that measure a panel of biomarkers (Fibrotest/Fibrosure) to provide an assessment of sever-ity of fibrosis. They are very accurate at excluding fibrosis. These methods are still under evaluation, but may restrict liver biopsy in patients with chronic liver disease of known cause to those in whom non-invasive testing does not reliably show the stage of fibrosis/cirrhosis

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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