Biochemical findings in liver diseases
The era of enzymochemistry
The introduction of : alkaline phosphatase – 1933 cholistenesterase- 1938 transaminases – 1955 gamma-glutamyl transferase -1961
Difficulties of laboratory liver diagnosis
Owing to the liver’s large functional reserve capacity and its outstanding regenarative ability, morphological damage may evade biochemical detection the damage may remain „biochemically silent”
Difficulties of laboratory liver diagnosis
A great number of liver tests are nonspecific, and their results are pathological in other diseases as well.
It is necessary to consider the specificity, sensitivity and clinical validity of the respective tests when setting up the diagnistic procedure.
Difficulties of laboratory liver diagnosis
It often happens that only certain partial funtions or
cellular structures are impaired.
For the detection of hepatocellular damage or disorders of hepatic funtions, a variety of examination methods will have to be employed
Difficulties of laboratory liver diagnosis
With increasing duration of liver or biliary tract diseases, but also simultaneous apperance of complications, biochemical findings become more and more ambiguous and misleading
The classification of the hepatobiliary enzymes
Indicator enzymes : Alanine aminotransferase ALT=GPT
Aspartate aminotransferase AST=GOT
Lactate dehydrogenase LDH
The classification of the hepatobiliary enzymes
Secretory enzymes: -Cholinesterase ChE Excretory enzymes: -Alkaline phospatase ALP or AP -Gamma glutamyl transferese -GT or GGT
Liver check list of biochemical findings
Hepatocellular damage ALT AST -GT LDH Iron/ferritin
Liver check list of biochemical findings
Cholestasis: Alkaline phospatase –AP -GT Bile acids Direct bilirubin Cholesterol copper
Liver check list of biochemical findings
Hepatic function: INR Albumin Ammonia Fibrinogen
Indirect bilirubin
The elevation of transaminases is a reliable marker of hepatocellular damage
AST/ALT ratio (De Ritis ratio) inflamatory type - ASTALT ≥1
in severe alcoholic or malignant liver disease AST>ALT ≥ 2
Extra hepatic causes of increased AST/ALT activity
1.
2.
3. 4. 5.
6.
7. 8.
Cardiac diseases (cardiac infarction, heartstroke) Muscular diseases, excessive physical exercise Pulmonary embolism Hypo-/hyperthyreosis Long term venous stasis Coeliac disease Hypertermia Long term fasting
ALT(GPT)
Elevated GPT is the most sensitive indicator of hepatocellular damage. An exclusive rise in ALT is, as a rule, of hepatocellular origin.
AST (GOT)
The diagnostic sensivity of AST is significantly lower than of ALT This is understandable, since it is only the cytoplasmic portion of the AST (20%) which will enter the blood if the liver cell membrane is damage. AST is mainly present in the heart and skeletal muscles, also in the kidney, brain, pancreas, lung.
Elevated transaminases
Any determination of elevated transaminases requires remeasurment after 14 days (or earlier) 1.After normalization, there will be no futher consequences (e.g. the condition was caused by secondary hepatic reaction to an infection) 2.A marked increase is indicative of the development of acute viral hepatitis or progressive intoxication, both of which have to be clarified 3. A persistent elevation requires futher diagnostic steps for final differentiation of the active liver disease.
-GT (GGT)
liver bile ducts
kidney pancreas epipidymis heart lung small intestine bone marrow salivary glands thymus spleen, brain
There is no -GT activity in muscle, bone and erythrocytes.
GGT
Elevation of GGT is found in: Cholestasis liver cirrhosis, viral hepatitis, fatty liver, porphyria, toxic liver damage, pancreatitis, pancreatic cancer,myocardial infarction, nephrotic syndrome, diabetes mellitus, right heart failure, obesity, nicotine abuse, and brain tumours. A permament rise in -GT due to liver cirrhosis suggests primary liver cell carcinma.
Riddle 1
AST – 220 U/l
ALT – 150 U/l ALP – 200 U/l
GGT – 2300 U/l
Riddle 2
AST – 2220 U/l
ALT – 3150 U/l ALP – 200 U/l
GGT – 150 U/l
Riddle 3
AST – 250 U/l
ALT – 400 U/l ALP – 1200 U/l
GGT – 1500 U/l
Non viral liver diseases
Fatty liver
Autoimmune hepatitis Metabolic diseases
hemochromatosis, Wilson’s disease, α1antitripsin deficiency
Drug related hepatitis Alcoholic liver disease Primary biliary cirrhosis Primary sclerosing cholangitis
Autoimmune hepatitis (AIH)
affects mainly young women clinical symptoms: fatigue, right upper quadrant pain,
polymyalgia or arthralgia, sometimes jaundice
lab-tests: ALT↑, AST↑, gamma-globulins↑, IgG ↑, autoantibodies: ANA, SMA, LKM
AIH
Treatment: Corticosteroids + azathioprine Absolute indications: severe hepatic inflammation, histological changes of bridging necrosis or multilobular collapse AST > 10-fold times normal AST > 5-fold times normal and Gamma-globulins > 2-fold times normal Relative indications fatigue, elevated AST and gamma-globulins histological features of interface hepatitis Patients with inactive cirrhosis, portal or mild interface hepatitis and no symptoms, decompensated cirrhosis do not require immunosuppressive therapy
Steatosis of the liver and nonalcoholic steatohepatitis (NASH)
Fatty liver is the most common but underprecipitated liver
disease
This is the most common reason of elevated transaminases
activity
The levels are usually < than 4x the normal value Fatty infiltration can be identified by US or CT
The diagnosis of NASH requires the liver biopsy. In addition
to fatty infiltration we see pericental fibrosis, inflammation, liver cell necrosis and Mallory’s bodies (like in alcoholic liver disease)
Steatosis appears to have benign course NASH can progress to cirrhosis Liver failure is uncommon
Fatty liver disease - treatment
No available therapy is known
Weight loss is strongly recommended (in obese patients)
Physical activity
Restriction of all alcohol intake Treatment of diabetes (if it coexists with) – good glycemic
control Therapy of hyperlipidemia UDCA? Vit. E?