Liver function tests (LFT)

Liver function tests

Content

       Liver function tests

       Normal reference ranges of various lab parameters

       Various disease conditions correlated with liver function tests

Objective

After completion of this lecture, student will be able to:

       Explain the various liver function tests

       Explain the normal reference ranges of various lab parameters

       Explain the various disease conditions correlated with liver function tests

Functions of liver

Introduction

       Tests include:

                a) Tests to assess liver synthetic capabilities

                b) Tests to assess cholestatic disease and hepatocellular injury

Tests to assess liver synthetic capabilities

       Used to assess functional capabilities of liver

       Its synthetic products are measured [albumin, fibrinogen, prothrombin, hepatoglobin, transferin and other proteins]

       Most commonly used tests include

                                -albumin

                                -prothrombin time

       Occasionally

                                -total protein

                                -globulin (with albumin)

       Albumin:

                Reference range: 3.5 to 5 gms/dl

                -Synthesised from AA derived from gut/breakdown of RBC

                -Maintains oncotic pressure

                -Binds numerous hormones, anions, drugs and fatty acids

                -Liver synthesise 122 gm /day if needed it can double the synthesis

                -Serum half-life is 20 days

                -Albumins measurements are slow to fall after the onset of hepatic dysfunction due to long half –life

                -Complete cessation of albumin production results in only 25% decrease in serum concentration after 8 days

                -Albumin concentration remains unaltered in many liver disease when liver function is preserved – if disease progress its synthetic capacity impaired [severe hepatitis, cirrhosis]

       Non hepatic causes: Hypoalbuminemia: Malnutrition, malabsorption, overhydration, nephrotic syndrome, protein losing enteropathy, burns and chronic illness

       At very low concentration (2-2.5gm/dl) patients can develop peripheral edema, ascities or pulmonary edema

       Non hepatic causes:

               -Hyperalbuminemia:

                -Dehydration

                -Anabolic steroids

                     Does not cause any symptoms

       Prothrombin time:

                -It is one of the coagulation factor

                -Liver synthesises SIX coagulation factors: I, II, V, VII, IX and X

                Normal range: 10 to 13 seconds

                -PT is not specific for liver disease

Causes for prolongation of PT:

                - Inadequate vitamin K in the diet

                - Poor / inadequate nutrition

                - Drugs – warfarin, salicylates, moxalactum, cefoperazone, tetracycline

       If PT remains prolonged despite parenteral vitamin K (10mg), it is considered a sign of substantial hepatic dysfunction

       Treat the patient with vitamin K if no bleeding

       If bleeding present, treat with fresh frozen plasma

       Total protein:

                Reference range: 5.5 to 9gm/dl

                -Refers to sum of albumin and globulin

                -Any symptoms increase either albumin/ globulin also increases total protein

                -Its value is limited if albumin and globulin results are already known

       Globulin:

                Reference range: 2 to 3gm/dl

                -Refers to total measurements of immunoglobulins (antibodies) in serum

                -Synthesised by T lymphocytes

                -Ig – IgA, IgD, IgE, IgE, IgG and IgM

       Causes:

                -Malabsorption

                -Protein binding enteropathy

                -Hepatocellular dysfunction does not lower globulin concentration unless associated with malabsorption

                -Elevation of globulins is a sign of inflammation – may present in hepatitis

                -In chronic hepatitis  - albumin decreases and globulin increases

                -In primary biliary cirrhosis – Increase in IgM

                -Alcoholic patients – increase IgA

       Non – hepatic causes:

                -Chronic infections, chronic inflammatory states, multiple myeloma

                -In non-hepatic condition – globulin increases than albumin concentration and thus G;A ratio will be >1 (normal – 0.6) 

Tests to assess cholestatic disease and hepatocellular injury

       Liver disease:

                                -Cholestatic

                                -Hepatocellular damage

                                -Mixed

       Cholestatic – primary interference with the metabolism or secretion of bilurubin

       Hepatocellular damage – damage to hepatocytes or inflammation of hepatocytes

       Mixed type is due to:

                                                   back pressure



                Cholestatic                <---------------->hepatocellular damage

                                                        swelling

       Elevation of liver enzymes are common findings in clinical practice

       The significance of the elevation has to be assessed whether or not mild non-specific elevation (e.g., viral / drug / liver disease)

Useful tests

                                                Enzymes                              Reference range

                                                ALP                                        30 – 120 U/L

                                                GGT                                       0 - 30U/L

                                                AST                                        0 – 35 U/L

                                                ALT                                         0 – 35 U/L

                                                LDH                                        110 – 220 U/L                    

                                Bilurubin

                                                total                                                       2 - 18 mmol/L

                                                direct (conjugated)                         0 - 4 mmol/L

                                               

                                Albumin                                                             3.5 – 5.0 gms/dl

                                Globulin                                                             2.0 – 3.0 gms/dl

                                Prothrombin time                                          10 – 13 seconds

Liver enzymes are most useful in differentiating hepatocellular damage from cholestasis

Extra-cellular (present in cells lining biliary canaliculi)                                                     

1. ALP                     

2. GGT     

Intra-cellular enzymes (present in cytosol of liver cells)                                                

1. AST                     

2. ALT                     

3. LDH

CHOLESTASIS

Intra-hepatic (obstruction in bile ducts within liver)

Causes:

      metastasis

Extra-hepatic (obstruction in bile ducts outside the liver)

Causes:

      gall stones

      cancer of head of pancreas

      inflammation

 á ALP & GGT Bone disorder (pagets disease, osteomalacia, 10, 20 malignancy of bone)

                á GGT (100-140 U/L) without any abnormality in liver  à Chronic alcoholism or phenytoin  

       If chronic alcoholism is associated with hepato-cellular damage, ALT increase along with GGT

       Chronic alcoholism can lead to fatty infiltration, alcoholic hepatitis and cirrhosis

Hepatocellular damage

       In hepatocellular damage, AST, ALT and LDH increases

       Both AST and ALT runs parallel

       Measure ALT as it is very specific to liver

Causes:

      Paracetamol overdose, ischemic / hypoxic hepatitis

                             Marked elevation of ALT and LDH, both of the same order (800-3000 U/L)

                             The ratio of ALT / LD is 0. 8 - 1.2

      Viral hepatitis

      both ALT and LDH increases

      ALT elevation is significantly > LDH

      ALT/LDH ratio is 1.2-2.0

      Infections mono-nucleousis (Epstein Bar virus)

      Liver and Spleen maybe swollen

      Simultaneous increased level of ALP, GGT, LDH and ALT between (200-600 U/L) occur

      Rhabdomylosis

      LD level will be markedly elevated (800-20,000 U/L) than ALT

      ALT: LDH ratio is  <  0. 8

      Due to muscle destruction CK level also increase (2,000 – 1,00,000 U/L)

      Increase CK does not occur in liver damage (liver does not contain CK)

Drugs involved in liver disorders

       Predominantly hepatocellular

      Allopurinol, aspirin, cytotoxic, diclofenac, anti TB drugs, methotrexate, paracetamol, phenytoin, propylthiouracil and quinidine

       Predominantly cholestasis

      Augmentin, CBZ, chlorpromazine, chlorpropamide, flucloxacillin, dicloxacillin, indomethacin, phenothiazines and tolbutamide

       Mixed

      Methyldopa, halothane, norfloxacin, PAS, ranitidine, sulindac, valproate co-trimaxozole

Summary

       Liver function tests include tests which assess the liver synthetic capabilities and  hepatocellular injury

       Hepatocellular dysfunction does not lower globulin concentration unless associated with malabsorption

       Hepatocellular damage – damage to hepatocytes or inflammation of hepatocytes

       The significance of the elevation has to be assessed whether or not mild non-specific elevation (e.g., viral / drug / liver disease)

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