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: 340 μmol/L (0-17) Serum total proteins: 86 g/L (65-80) Albumin: 31 g/L (35-50) ALP: 540 U/L (45-135) AST: 93 U/L (<42) GGT: 234 U/L (<38) Cholesterol: 7.6 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 WWW.UpToDate.com

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

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

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

Patient no 3 A 56 years old male has abdominal pain and mild jaundice. His biochemical profile shows: Albumin: 45 g/L (35-50) ALP: 180 U/L (30-120) Gamma GT: 788 U/L (<40) ALT: 104 U/L (<42) AST: 248 U/L (< 35) Bilirubin: 36 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):117-130

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.

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

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

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