Željko Puljiz, MD.

, PhD
 Metabolic
• Synthesis
• Breakdown
• Other functions (storage vit. A, B12, D, F)
 Excretion
• Different products into bile
 Vascular
• Storage of blood
 Protein Metabolism
• aminoacids syntesis
 Carbohydrate Metabolism
• gluconeogenesis
• glycogenolysis
• glycogenesis
 Lipid Metabolism
• lipogenesis
• cholesterol synthesis
• production of factors I, II, V, VII, IX, and X
 Breaks down insulin and other hormones
 Breaks down hemoglobin
 Breaks down and modifies toxic supstances
(methylation)
 Convert ammonia to urea
 Two different circulations

Nutritive
Portal vein

Functional
Hepatic artery
 Alanin-aminotransferase (ALT)
 Aspartat-aminotransferase (SGOT)
 Albumin
 Bilirubin
 to screen for liver infections
 to monitor the side effects of certain
medications
 if you already have a liver disease, to monitor
the disease and how well particular treatment
is working
 to measure the degree of scarring in the liver
 if you’re experiencing the symptoms of a liver
disorder
 if you’re planning on getting pregnant
 ALT predominant AST predominant
• Chronic Hep B / C • Alcohol-related liver disease
• Acute A-E, EBV, CMV • Steatosis/ Steatohepatitis
• Steatosis / Steatohep • Cirrhosis
• Hemochromatosis
Non-hepatic source
• Medications / Toxins • Hemolysis
• Autoimmune • Myopathy
Hepatitis • Thyroid disease
• Alpha-1-antitrypsin
• Wilson’s Disease
• Celiac Disease
 Acute Viral Hepatitis
 does not predict outcome
 Ischemic Hepatitis
 hypotension
 sepsis
 hemorrhage-shock
 MI
 Elevated in liver ischemia
 LDH types of isoenzymes

 LDH-1: heart and red blood cells

 LDH-2: heart and red blood cells
 LDH-3: lymph tissue, lungs, platelets, pancreas
 LDH-4: liver and skeletal muscle
 LDH-5: liver and skeletal muscle
 Albumin
 Prothrombine time (PT/INR)
 Albumin decrease doesn’t occur acutely
 Related to cirrhosis
 Attention: low albumin also occurs in
NEPHROTIC syndrome
(so always check the urine for protein)
 Vitamin K is involved in proaction of factors
II, VII, IX and X.
 The liver is involved in activating vitamin K.
 Giving vitamin K has no effect on INR if
patient has impaired synthetic function.
 INR normal range 1 to 1.3
 Found in hepatocytes that lines the bile
canaliculi
 Level is raised in:
 primary biliary disease (PBC, PSC, AIC)
 biliar obstruction (malignant, benign)

 Can be found in BONE and PLACENTA

 GGT is elevated in alcohol liver disease
and in bile duct obstruction
 But GGT is not specific
 Marker of alcohol abuse
 Water insoluble product of heme metabolism
 Taken up by liver and conjugated to become
water soluble so it can be excreted in bile and
into bowel.
 Patient looks jaundiced if bilirubin is >30
Direct bilirubin Indirect bilirubin
(conjugated) (unconjugated)

cirrhosis hepatitis B, C
bile duct obstruction hemolysis

pale stool
dark urine
 Inherited
 Toxic
 Alcohol
 Infective
 Autoimmnune
 Biliary tract
 Fatty liver
 Alpha 1-atitripsine deficiency

 Hemochromatosis

 Wilson disease

 Gilbert syndrome (and others)

 Alcoholic liver disease

 Drug induced
 Autoimmune hepatitis

 Primary Biliary Cirrhosis

 Primary Sclerosing Cholangitis

 Alpha 1-atitripsine deficiency
 Haemochromatosis
 Wilson disease
 Alpha1-antitrypsine deficit

 Symptoms: asthma, cirrhosis

 Diagnosis: level of enzyme

 Therapy: liver transplantion

 Primary 0.6% poulation men 24x > women
 Autosomal recessive (HSE gens) C282Y
mutation
 Increased Fe absorption from gut
 Secondary cirrhosis
 Iron overload in liver and pancreas diabetes

Diagnosis: ferritin , gene mutations, liver biopsy

Therapy: phlebotomy (1x/month), transplantion
 Autosomal recessive, ceruloplasmine
dificiency are abnormally low (<0.2 g/L) in 80–
95% of cases
 Young people
 Copper acumulation in liver/brain psychosis

cirrhosis
Diagnosis: AST, ALT, bilirubin, 24 h urine copper
liver biopsy, copper in dry liver sample
Therapy: penicilamin, transplantation
 Autoimmune disease

 Cause unknown

 Young pepople

 Female>male
 Fatigue

 Flu-like symptoms

 Abdominal pain

 Loss of appetite

 Unexplained weight loss

 Type 1

 Type 2
 Serum markers
 ASTMA type 1
 SLA/LP
 Anti LKM type 2
 Antinuclear antibody-ANA
 AST, ALT, GGT, bilirubin, AP
 Liver biopsy
 Ultrasound
 Corticosteroids

 Azathyoprin

 How long? We don’t know (5 yrs)

 Often relapses after stopping therapy

 Transplantation
 Autoimmune disease

 Young women mostly

 Symptoms as in every cirrhosis - often

itching

 Very often overlap syndromes (PBC+AIH),

(PBC+PSC)
 Antimitohondrial antibody (AMA)
 Anti-M2 antibody
 Antinuclear antibody-ANA
 AST, ALT 5-10X, AP 3x, bilirubin
 Ultrasound
 Liver biopsy
 No specific drug

 Ursodeoxycolic acid (Usrofalk) releases

symptoms
extend time to transplantation

 Corticosteroids

 Prognosis: cirrhosis
 Autoimmune disease of biliary ducts
 Intrahepatic, extrahepatic or both
 Stenosis and dilation
 Often overlaps with AIH and PBC
 70% pts with PSC have ulcerose colitis
 5% pts with ulcerose colitis have PSC

 Symptoms: jaundice, repeating cholangitis

 Autoimmune cholangiopathy
 Chronic inflammation of liver
 Variant syndrome of autoimmune hepatitis
(AIH)
 AMA negative type of PBC
 Symptoms: pruritus, fatigue, jaundice
 Diagnosis: ANA, ASMA, IgG4, AMA (-), AP,
GGT
 Therapy: in case of jaundice
 PBC

8%
AIC PSC
10% 6%
AUTOIMMUNE
HEPATITIS
 GGT, AP, AST, ALT, bilirubin
 Antinuclear antibody-ANA
 Perinuclear anti-mitochondrial cytoplasmatic
antibody-pANCA)
 MRCP
 ERCP
 Liver biopsy
 Corticosteroids

 Azathyoprin

 Endoscopic dilatations

 Plastic or metal stents

 Liver transplantation
 Hepatocellular carcinoma- HCC

 Cholangiocellular carcinoma -CHC

 Risk factors for HCC: chronic C hepatitis,
cirrhosis
 Risk factors for CHC: PSC up to 30% pts
 Surgery
 Liver resection if no metastases
 No response to chemotherapy
 No response to irradiation therapy
 Liver transplantation
 Symptomatic therapy