MEDLInC CLINICAL PATHWAYS: ABNORMAL LIVER FUNCTION TESTS
What is normal varies by ethnic origin and age. The term "normal range" introduces further confusion, as the values reflect a statistical range and not a definition of what is not pathological. Results outside
of these ranges, therefore, do not necessarily indicate disease. The first step is to evaluate the clinical context in which abnormal tests are found. In particular, whether the observed biochemical abnormality is associated with a history suggestive of liver disease
and/or symptoms and signs of liver disease, or with the presence of extrahepatic conditions that may involve the liver. TRANSAMINASES: Abnormal transaminases in asymptomatic patients without risk factors for, or clinical features of, liver disease: If raised and <3x upper limit of normal - recheck in 1-3 months If still raised (two measurements, six months apart) - further investigation indicated.
If more than three times upper limit of normal (single measurement), further investigation indicated as shown in the table Abnormal transaminases in patients with risk factors for, or clinical features of, liver disease? Further investigations are advised for any enzyme rise associated with risk factors for, or clinical evidence of, liver disease except where an apparent cause is found (hypertriglyceridaemia, diabetes,
alcohol, overweight), for which a six month trial of appropriate intervention is recommended. Investigations in asymptomatic patients with raised liver enzymes Test Abnormality Interpretation Suggested first investigation Full blood count
Suggests alcohol excess if gamma glutamyl
transferase also raised. Possible hypersplenism
Strongly suggestive of autoimmune hepatitis
Possible haemochromatosis, modest levels
common in alcoholic fatty liver disease, alcoholic hepatitis, and non-alcoholic fatty liver disease - seek advice if raised
Chronic infection proved. Referral required
Chronic infection possible. Confirm viraemia with
If no diagnosis obtained Liver ultrasound
T-transglutamase antibodies Alpha 1 antitrypsin
Suggests deficiency; phenotype required (possible
urine copper) as dictated by clinical context GAMMA GLUTAMYL TRANSFERASE Elevation typically indicates cholestasis or, when alkaline phosphatase is normal, induction of hepatic metabolic enzymes, often in response to long term exposure to excessive alcohol or drugs. MEDLInC CLINICAL PATHWAYS: ABNORMAL LIVER FUNCTION TESTS
MEDICATION AND ABNORMAL LIVER FUNCTION TESTS Antibiotics: Penicillin, Ciprofloxacin, Nitrofurantoin, Fluconazole, Isoniazid, Rifampicin
Antiepileptic: Phenytoin, carbamazepine Statins, NSAID, ACE inhibitors Herbal remedies
Drugs and substances of abuse: Cocaine, ecstasy, glues and solvents RAISED BILIRUBIN IN AN ASYMPTOMATIC ADULT:
Values up to 20% more than the upper limit of normal are likely to be statistically rather than clinically "abnormal"
Values <1.5 times the upper limit of normal - retest in 1-3 months unless clinical suspicion of disease Values >1.5 the upper limit of normal - confirm proportion of indirect (unconjugated) bilirubin. If >70% of bilirubin is unconjugated, the diagnosis is probably Gilbert's syndrome: no further testing is
needed if the bilirubin is not rising on interval retesting, unless haemolysis is suspected. If unconjugated bilirubin is rising on retesting, consider haemolysis and test haptoglobin, lactate dehydrogenase, and full blood count with reticulocyte count
Values >3 times the upper limit of normal - clinical disease is likely and further investigation is required. Consider: Ultrasound (if >50% of bilirubin is conjugated) or Tests for haemolysis (if >70% is unconjugated).
RAISED ALKALINE PHOSPHATAE IN AN ASYMPTOMATIC ADULT: Think of causes outside the liver such as fracture , Paget's disease, osteomalacia, pregnancy and
growing children. TWO COMMON CLINICAL CONDITIONS: Alcoholic liver disease:
This is one of the most common reasons for mildly abnormal aminotransferase levels in the Western world. The quantity and duration of alcohol use are important for establishing a diagnosis. A clue to the diagnosis is that the AST/ALT ratio in these patients is typically 2:1 or more. When a patient's history
is not reliable, increased GGT levels with normal ALP levels and macrocytosis make alcohol induced liver damage more likely.
Fatty infiltration of the liver or non-alcoholic steatohepatosis (NASH). Fatty infiltration of the liver, with or without associated inflammation and fibrosis, is thought to be the
most common cause of mild abnormality of aminotransferase levels in the general population in Western countries. Nevertheless, the exact prevalence of non-alcoholic fatty liver disease is quite difficult to ascertain because the disease is asymptomatic and there are no blood tests to confirm the
diagnosis. Furthermore, although risk factors for non-alcoholic fatty liver disease, such as obesity, diabetes mellitus, and hyperlipidaemia, are present in a variable proportion of affected patients they are not
specific. Therefore the initial evaluation of a patient with abnormal liver function tests and suspected non-alcoholic fatty liver disease should include a complete serological evaluation to exclude other
causes of liver disease Just because liver function tests are normal, you should not assume that the patient doesn't have liver disease. For example about one third of patients with hepatitis C have normal ALT levels despite inflammation on liver biopsy.
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BOOK REVIEW PAUL JANSSEN: PIONEER IN PHARMA & IN CHINA Dundee: Dundee University Press, 2008, 258 pp. (incl. appendices and bibliography), The history of Janssen Pharmaceutica and its evolvement in China is central to this homage to Paul Janssen, who set up the company in 1953; led it through a merger with Johnson & Johnson in 1961; built up relations with China from the 1960s