1. Patient no 7 Primary Biliary Cirrhosis Lipoprotein X
A 42 year old female presented with jaundice, fatigue and intense pruritus, for the last 6 months. Her biochemical profile is as following:
Bilirubin: μmol/L (0-17)
Serum total proteins: g/L (65-80)
Albumin: g/L (35-50)
ALP: U/L (45-135)
AST: U/L (<42)
GGT: U/L (<38)
Cholesterol: mmol/L
Viral markers: Negative
Antimitochondrial antibodies: Positive
What is the most probable diagnosis?
Name ONE lipid fraction which will be most markedly raised in this patient?
Primary Biliary Cirrhosis
Lipoprotein X
Ref No 7
Clinical manifestations, diagnosis, and natural history of primary biliary cirrhosis

2. Primary Biliary Cirrhosis
Characterized by a T-lymphocyte-mediated attack on small intralobular bile ducts leading to their gradual destruction and eventual disappearance
Autoimmune disease, 95 percent of patients with PBC are women
Onset is usually between the ages of 30 to 65
Clinical Manifestations:
50 to 60 percent of patients are asymptomatic at diagnosis
Fatigue and pruritus are the most common.
Cause of the pruritus in primary biliary cirrhosis is unknown
Hyperpigmentation of skin. This change is due to melanin deposition, not jaundice.
Musculoskeletal complaints, frequently due to an inflammatory arthropathy, occur in approximately 40 percent of patients

3. Primary Biliary Cirrhosis
Laboratory Findings
Serum bilirubin concentration is usually normal early in the course of the disease but becomes elevated in most patients as the disease progresses. Both the direct and indirect fractions are increased
Serum levels of aminotransferases may be normal or slightly elevated, rarely increased more than fivefold above normal
Serum alkaline phosphatase concentration is almost always elevated in PBC, often to striking levels, and is of hepatic origin. The value tends to reach a plateau early in the course of the disease and then usually fluctuates within 20 percent of this value.
Serum levels of 5'-nucleotidase and gammaglutamyl transpeptidase parallel those of alkaline phosphatase.
Increased numbers of eosinophils have been demonstrated in the blood and liver
Antimitochondrial antibodies are the serologic hallmark of PBC. They are present in about 95 percent of patients
Antinuclear antibodies (ANA) are found in up to 70 percent of patients with PBC
Increased serum concentrations of IgM, ceruloplasmin, bile acids (which are strikingly elevated) and hyaluronate

4. Primary Biliary Cirrhosis
Hyperlipidemia 
Hypercholesterolemia is a common feature of primary biliary cirrhosis (PBC) and other forms of cholestatic liver disease
Elevated VLDL and LDL levels as well as markedly elevated HDL
Apolipoprotein A-1 is also elevated at all stages
Triglyceride levels normal or slightly elevated
Lp(a) levels are significantly decreased
Excess LDL in PBC is composed of an abnormal lipoprotein particle (lipoprotein X), which is seen in cholestatic liver disease. It is rich in free cholesterol and phospholipids. Lipoprotein X is believed to reduce the atherogenicity of LDL cholesterol by preventing LDL oxidation
Risk of atherosclerosis in patients with PBC and hypercholesterolemia is said to be low

5. Patient no 3
A 56 years old male has abdominal pain and mild jaundice. His biochemical profile shows:
Albumin: g/L (35-50)
ALP: U/L (30-120)
Gamma GT: U/L (<40)
ALT: U/L (<42)
AST: U/L (< 35)
Bilirubin: μmol (<17)
What is the most probable diagnosis?
Name the ratio of two enzymes which can be helpful to support your diagnosis.
Alcoholic hepatitis
AST/ ALT ratio (De Ritis Ratio ).
Ref No 3
Mona Botros, Kenneth A Sikaris. The De Ritis Ratio: The Test of Time Clin Biochem 2013;34(11):

6. Intracellular Location of AL & AST
ALT has mainly only one isoenzyme which is present only in the hepatocyte cytoplasm
AST has two genetically distinct isoenzymes i.e. Cytosolic AST (cAST) and mitochondrial AST (mAST) is present in the hepatocyte cytoplasm and mitochondria respectively
mAST is the more prevalent isoenzyme with approximately 80% of total AST activity in human liver contributed by mAST.

7. Biochemical Features of Alcoholic Hepatitis
Raised AST/ALT ratio (de Ritis) is typically high in patients with severe alcoholic hepatitis and cirrhosis
A patient with mild alcoholic hepatitis and longer elapsed period may have raised ALT.
Raised Gamma GT is hallmark of alcoholic hepatitis

8. Patient No 8
A premature neonate developed jaundice at the age of 9 days and was treated with fluorescent light. During the next week his bilirubin level dropped. After 24 hours he developed an intense grey-brown discoloration of the skin, serum, and urine. His lab investigations revealed:
Haemoglobin : 12 g/dl
Serum Bilirubin : 85 μmol/L
Serum ALT : 75 U/L
What is most probable diagnosis?
What is explanation of grey-brown discoloration of skin?
Bronze Baby Syndrome
Abnormal accumulation of photoisomer of bilirubin
Ref No 8
Mechanism of Development of Bronze Baby Syndrome in Neonates treated with Phototherapy
Pediatrics 1982-Onishi-273-6

9. Bronze Baby Syndrome
This phenomena can develop due to conversion of bilirubin into metabolites
Bilirubin IXa can be a major contributor of this pigmentation
Clinical importance of this phenomena is that the Clinicians sometimes take it as as marker of poor prognosis