Evaluation of Liver Function tests in Primary Care. Abid Suddle Institute of Liver Studies, KCH
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1 Evaluation of Liver Function tests in Primary Care Abid Suddle Institute of Liver Studies, KCH
2 Liver Function tests Markers of hepatocellular damage Cholestasis Liver synthetic function
3 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
4 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
5 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
6 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)
7 COMMON CAUSES OF ABNORMAL LFTS IN THE UK Transient mild abnormalities Drugs egstatins Alcohol excess Viral hepatitis Non Alcoholic Fatty Liver Disease (NAFLD)
8 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
9 Acute hepatitis (ALT>10xULN) Viral Drugs/ Toxic Ischemia Autoimmune
10 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
11 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
12 ALT/AST 2 5x ULN Transient Drug effect Chronic viral hepatitis Alcohol NAFLD Autoimmune Metabolic liver disease
13 Common medication Statins NSAIDs Antibiotics Antituberculosis drugs Herbal remedies Alternative medications
14 NAFLD Hepatic manifestation of metabolic syndrome Therefore risk factors ALT, AST 2 4x ULN GGT Fat on USS
15 Chronic viral hepatitis Hepatitis B Ethnic group, Risks for BBV HBSAg Hepatitis C Blood product transfusion before 1992 IDU HCV Ab, RNA, genotype
16 Autoimmune Female sex Young Previous/ family history AI disease Elevated globulin/ serum IgG Positive AAs: ANA, SMA, anti LKM
17 Metabolic liver disease Haemochromatosis Arthralgia, DM Elevated serum ferritin and TFS genetics Wilsons Young, undiagnosed liver disease Psychaitric/ Neurologic symptoms Caeruloplasmin
18 Cholestasis Transient Drugs Biliary Obstruction PBC PSC Infiltration
19 Biliary obstruction Gallstones Cancer head of pancreas Cholangiocacinoma Ultrasound CT
20 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
21 PBC Female predominant Elevated cholestatic enzymes, no biliary obstruction, pruritis, xanthelasma AMA positive, IgM
22 PSC Young, IBD ANCA Secondary care evaluation
23 Diagnostic approach in elevated serum alkaline phosphatase elevated ALP History and PE normal bilirubin, ALT, AST abnormal liver chemistries GGT or 5 nucleotidase negative positive not hepatobiliary U/S review medication AMA no duct dilatation liver biopsy yes Cholangiography CT observation > 6 months U/S no AMA negative as elevated ALT evaluation, liver biopsy, ERCP
24 γ glutamyltransferase (GGT) Sensitive but not specific increase alcohol drug anticonvulsant (CBZ, phenytoin, and barbiturate), OC almost all type of liver diseases
25 Important points Investigate abnormalities in light of clinical context Abnormalities associated with synthetic impairment or signs of decompensation require emergent evaluation
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