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Evaluation of Liver Function tests in Primary Care
Abid
Suddle
Institute of Liver Studies, KCH
Liver Function tests
• Markers of hepatocellular
damage
• Cholestasis
• Liver synthetic function
Markers of Hepatocellular
damage Transaminases
• AST‐
liver, heart skeletal muscle, kidneys, brain, RBCs
• In liver 20% activity is cytosolic
and 80% mitochondrial
• Clearance performed by sinusoidal cells, half‐life 17hrs
• ALT
– more specific to liver, v.low
concentrations in kidney and skeletal muscles.
• In liver totally cytosolic.
• Half‐life 47hrs
Markers of Cholestasis
• ALP
–
liver and bone (placenta, kidneys, intestines )• Hepatic ALP present on surface of bile duct epithelia and
accumulating bile salts increase its release from cell surface. • ALP isoenzymes, 5‐NT or gamma GT may be necessary to
evaluate the origin of ALP
• Gamma‐GT
–
hepatocytes
and biliary
epithelial cells, pancreas, renal tubules and intestine
• Very sensitive but Non‐specific• Confirm hepatic source for a raised ALP• Alcohol
Markers of liver synthetic function Bilirubin, Albumin and PT (INR)
• Useful indicators of liver synthetic function
• In primary care when associated with liver enzyme abnormalities should raise concern
• Thrombocytopaenia
is a sensitive indicator of liver fibrosis
Patterns of liver enzyme alteration
• Hepatic vs
cholestatic
• Magnitude of enzyme alteration (ALT >10x vs
minor abnormalities)
• Rate of change
• Nature of the course of the abnormality (mild fluctuation vs
progressive increase)
COMMON CAUSES OF ABNORMAL LFTS IN THE UK
• Transient mild abnormalities
• Drugs – eg Statins• Alcohol excess• Viral hepatitis• Non‐Alcoholic Fatty Liver Disease
(NAFLD)
Investigation of Abnormal LFTs
PRINCIPLES• 2.5% of population have raised LFTs• Normal LFTs
do not exclude liver disease
• Interpret LFTs
in clinical context• Take a careful history for risk factors, drugs, alcohol,
comorbidity, autoimmunity• Physical examination for liver disease• Chase likely diagnosis rather than follow algorithm
unless there are no clues • If mild abnormalities and no risk factors or suggestion
of serious liver disease , repeat LFTs
after an interval (with lifestyle modification)
• Synthetic impairment/ signs of decompensation URGENT evaluation
Acute hepatitis (ALT>10xULN)
• Viral• Drugs/ Toxic• Ischemia
• Autoimmune
Investigation of acute hepatitis
• Urgent evaluation especially if jaundiced/ synthetic impairment
• Evaluation RFs
viral hepatitis, drug exposure
• Discontinue potential candidate drugs• Hep A IgM, HBV cIgM
+ SAg, HCV IgG, HEV IgM
• Ultrsound
Acute alcoholic hepatitis
• Spectrum: abnormal LFTs
→ ACLF
• History: malaise, abdo
pain anorexia
• Examination: PSCLD, Hepatomegaly
• Investigations: AST never >10xULN; AST:ALT>2; Bilirubin, PT
• Urgent evaluation if jaundiced• Steroids/ DF
ALT/AST 2‐5x ULN
• Transient• Drug effect• Chronic viral hepatitis• Alcohol• NAFLD• Autoimmune
• Metabolic liver disease
Common medication
• Statins• NSAIDs• Antibiotics• Antituberculosis
drugs
• Herbal remedies• Alternative medications
NAFLD
• Hepatic manifestation of metabolic syndrome
• Therefore risk factors• ALT, AST 2‐4x ULN• GGT• Fat on USS
Chronic viral hepatitis
• Hepatitis B Ethnic group, Risks for BBV
HBSAg
• Hepatitis C Blood product transfusion before 1992
IDU HCV Ab, RNA, genotype
Autoimmune
• Female sex
• Young• Previous/ family history AI disease
• Elevated globulin/ serum IgG
• Positive AAs: ANA, SMA, anti‐LKM
Metabolic liver disease
• Haemochromatosis Arthralgia, DM
Elevated serum ferritin
and TFS genetics
• Wilsons Young, undiagnosed liver disease
Psychaitric/ Neurologic
symptoms Caeruloplasmin
Cholestasis
• Transient• Drugs• Biliary
Obstruction
• PBC• PSC• Infiltration
Biliary obstruction
• Gallstones• Cancer head of pancreas• Cholangiocacinoma
• Ultrasound CT
Medications elevation of bilirubin and ALP
• Anabolic steroid• Allopurinol• Amoxicillin‐clavuronic
acid
• Captopril• Carbamazepine• Chlorpropamide• Cyproheptadine• Diltiazem• Erythromycin• Estrogens• Floxuridine• Flucloxacillin• Fluphenazine
• Gold salts• Imipramine• Indinavir• Iprindole• Nevirapine• Methytestosterone• Methylenedioxymethamphetamine• Oxaprozin• Pizotyline• Quinidine• Tolbutamide• TPN• Trimethoprim‐sulfamethoxazole
PBC
• Female predominant
• Elevated cholestatic
enzymes, no biliary obstruction, pruritis, xanthelasma
• AMA positive, IgM
PSC
• Young, IBD• ANCA• Secondary care evaluation
Diagnostic approach in elevated serum alkaline phosphatase
elevated ALP
History and PE
normal bilirubin, ALT, AST abnormal liver chemistries
GGT or 5’nucleotidase U/S
not hepatobiliary U/Sreview medication
AMA
CholangiographyCT
AMA
liver biopsy observation
as elevated ALT evaluation, liver biopsy, ERCP
negative positive
no duct dilatation
yes no
negative
> 6 months
γ‐glutamyltransferase (GGT)
• Sensitive but not specific• increase
– alcohol – drug
• anticonvulsant (CBZ, phenytoin, and barbiturate), OC
– almost all type of liver diseases
Important points
• Investigate abnormalities in light of clinical context
• Abnormalities associated with synthetic impairment or signs of decompensation require emergent evaluation