Liver function

HEPATOBILIARY INVESTIGATION

الدكتور خلدون ذنون- كلية طب نينوى
المرحلة الرابعة
Objectives
1. To know the range of liver investigations used for the diagnosis.
2. How to differentiate between hepatitic and cholestatic liver disease.
3. How to reach to the exact cause of liver disease.
4. Indications of liver biopsy.

Major hepatic functions

Nutrient metabolism: carbohydrates, proteins, lipids.
Protein synthesis: albumin, coagulation factors, complement factors, haptoglobin, ceruloplasmin, transferrin, protease inhibitor.
Storage: glycogen, iron, copper, vitamins A, D, B12, K, folic acid.
Urea synthesis from excess amino acids.
Metabolism & Excretion of bilirubin, bile salts, phospholipids, cholesterol, drugs, alcohol, toxins.
Metabolise vitamins to more active components e.g tryptophan, vitamin D, vitamin K (X, IX, VII, and II).
Immune regulation: through kupffer cells, macrophages, NK cells, B&T lymphocytes.
20% of liver is composed of cells other than hepatocytes: A- Kupffer cells: from blood monocytes , phagocytic : bacteria ,
viruses, RBC, Ag-Ab complexes & endotoxin. Cytokine
production, lipoprotein & lipopolysaccharide uptake &
metabolism.
B- Stellate cells: Regulate blood flow through the liver, uptake and
Storage of vitamin A, role in liver fibrosis.
C- Endothelial cells: hyaluronan uptake, lipoprotein binding
&uptake, IgG complexes, cytokine production.


Investigations
Liver enzymes :
Alanine aminotransferase (ALT-SGPT) & aspartate aminotransferase (AST-SGOT).
- located in cytoplasm and mitochondria.
- present in other body tissues, but ALT-SGPT mainly present in the
Liver and is more specific for hepatocellular damage.
- Both enzymes increase in liver cell damage e.g viral hepatitis,
autoimmune hepatitis, drugs, toxins .

2. Alkaline phosphatase ALP

- Group of enzymes with different isoenzymes present in liver, GIT,
bone & placenta .
- In liver: localised in the sinusoidal & biliary canalicular membrane.
- Increased several folds in biliary obstruction, hepatic cholestasis with
small increase in hepatitis.

3. Gamma glutamyl transferase GGT

- Microsomal enzyme found in many tissues of the body, largest
concentration in the liver .
- It assesses enzyme induction , it is increased by biliary obstruction &
Drugs: barbiturates, carbamazepine, ethanol, glucocorticoides,
Griseofulvin, INH, Meprobamate, phenytoin, primidon, rifampicin.


Hepatocellular damage: large increase in ALT & AST with small
increase in ALP.
Biliary obstruction : small increase in ALT & AST with large increase
in ALP &GGT.

Serum albumin: truly assesses liver function, it is decreased in liver dysfunction; maintain normal colloidal oncotic pressure, liver produces 8-14 gm/day.

Coagulation tests :

- Vitamin K activates factors X, IX, IIV, and II in the liver.
- Severe liver damage & prolonged biliary obstruction
(Decrease vitamin K absorption) lead to reduced plasma
Fibrinogen& prolongation of prothrombin time PT (I,II,V,V11,X), t of
clotting factors is 5-72 hours so changes in PT occur
quickly following liver damage & provide valuable prognostic
information in acute & chronic liver disease.
- Increased PT is evidence of severe liver damage in chronic liver
disease provided vitamin K 10 mg given by slow i.v infusion to
exclude deficiency.
-Hypercoagulation can lead to hepatic venous thrombosis &
Budd-Chiari syndrome.


Full blood count and microscopy:
Normochromic normocytic anaemia: reflect acute upper GIT bleeding from oesophago-gastric varices or peptic ulcer disease which is more common in liver disease.
Chronic hypochromic microcytic anaemia: chronic blood loss from peptic ulcer or portal hypertensive gastropathy.
Macrocytosis: alcohol misuse, target cells in jaundiced patients
Erythrocytosis: due to ectopic erythropoietin from hepatocellular cancer.
Leucopenia & thrombocytopenia: may occur in hypersplenism due to portal hypertension.
Leucocytosis: cholangitis, alcoholic hepatitis, liver abscess.
Thrombocytosis: active GIT bleeding & rarely in liver cancer.
Atypical lymphocytes: hepatitis due to infectious mononucleosis.

Severe liver disease ( hyponatreamia.

Liver dysfunction ( decreased blood urea.
Hepatorenal failure: increase in B.urea, S.creatinine, low urinary
sodium, carries grave prognosis.
Abnormal EEG: Hepatic encephalopathy.
Ascitic fluid examination: ascites.
Endoscopy: oesophago-gastric varices, peptic ulcers.
Laparoscopy: in ascites and liver malignancy.
Viral study: viral hepatitis (A, B, C, D, E), CMV, EBV.
Antimitochondrial antibody: primary biliary cirrhosis.
Antismooth muscle antibody: autoimmune hepatitis.
(-fetoprotein: large increase in hepatocellular cancer.


Imaging techniques
Ultrasound: Initial investigation in any liver disease, gall stones, biliary obstruction, primary & secondary tumors of the liver if >2cm size (echogenic), cysts, abscess.
Colour doppler U/S: measures blood flow in hepatic artery&vein,
Portal vein.
Endoscopic & laparoscopic U/S: provide high-resolution images of
the pancreas, biliary tree&the liver.

CT scan & MRI: same purposes as U/S but detect smaller focal lesions and stage malignancy.

ERCP: images bile ducts, pancreatic ducts & ampulla of Vater to diagnose obstruction due to stone, fibrosis or tumors. Therapeutic indication: removal of biliary stone, dilatation of biliary stricture, insertion of biliary stents across malignant strictures.

MRCP: as good as ERCP, images the biliary tree & it is less invasive but it is not therapeutic.

PTC: images the biliary tree but it does not image the pancreatic ducts & the ampulla, used when not possible to access the bile duct endoscopically.

Hepatic arteriography

Seldom used nowadays, but used for therapeutic embolization of vascular tumors
Hepatic & portal venography
Rarely performed but useful in Budd-Chiari syndrome.

Liver biopsy

Can give cause & severity of liver disease.
Trucut or Menghini needle, intercostal space, local analgesia.
Complications: Mortality 0.05% , abdominal & shoulder pain,
bleeding, biliary peritonitis .
For safe liver biopsy: PT < 4seconds prolonged &
platelet > 80,000/mm3, no biliary obstruction.
Defective haemostasis is corrected by fresh frozen plasma & platelet
transfusion.
Routes: percutaneous, transjugular both under U/S control, operative
or laparoscopic liver biopsy used to stage lymphoma.
Avoid liver biopsy in resectable malignancy due to risk of dissemination..


Indications of liver biopsy
Hepatic steatosis (accumulation of fat within hepatocytes), e.g
alcoholic liver disease, diabetes mellitus (non-alcoholic hepatosteatitis).
Acute & chronic hepatitis e.g viral , alcoholic , drugs, autoimmune,
haemochromatosis.
3. Cirrhosis
4. Malignancy: lymphoma
5. Chronic infections: detect granuloma in miliary TB & brucellosis.

Non-invasive markers of hepatic fibrosis

Can obviate the need of liver biopsy.
Serological markers (fibrotest): procollagen type peptide, metalloproteinases, hyalouronic acid.
Fibroscan: ultrasound based shock waves.











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