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What is the most common classical neurological manifestation in individuals age ≤20?
What is the most common classical neurological manifestation in individuals age ≤20?
Kayser-Fleischer rings are formed by copper deposits in the descemet membrane.
Kayser-Fleischer rings are formed by copper deposits in the descemet membrane.
True
What is the primary treatment for familial cholestatic syndrome?
What is the primary treatment for familial cholestatic syndrome?
Chelation therapy
In conditions like Wilson's disease, deposits in the corneal membrane can form a ______ ring.
In conditions like Wilson's disease, deposits in the corneal membrane can form a ______ ring.
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Match the following manifestations with their associated conditions:
Match the following manifestations with their associated conditions:
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What is the most characteristic histopathological finding in Primary Sclerosing Cholangitis?
What is the most characteristic histopathological finding in Primary Sclerosing Cholangitis?
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Cholangiocarcinoma is commonly associated with Primary Sclerosing Cholangitis.
Cholangiocarcinoma is commonly associated with Primary Sclerosing Cholangitis.
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Which medication is used to reduce the progression of biliary cirrhosis in PSC?
Which medication is used to reduce the progression of biliary cirrhosis in PSC?
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In Primary Sclerosing Cholangitis, approximately 95% of patients test positive for _______.
In Primary Sclerosing Cholangitis, approximately 95% of patients test positive for _______.
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Match the following features with their corresponding characteristics:
Match the following features with their corresponding characteristics:
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Which of the following is a confirmatory test for metabolic liver diseases?
Which of the following is a confirmatory test for metabolic liver diseases?
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Irreversible organ damage can occur in the skin and liver in metabolic liver diseases.
Irreversible organ damage can occur in the skin and liver in metabolic liver diseases.
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What is the primary function of weekly phlebotomy in the management of metabolic liver diseases?
What is the primary function of weekly phlebotomy in the management of metabolic liver diseases?
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Transferrin saturation greater than _____% is indicative of metabolic liver disease.
Transferrin saturation greater than _____% is indicative of metabolic liver disease.
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Match the organ involvement with the associated disease in metabolic liver diseases:
Match the organ involvement with the associated disease in metabolic liver diseases:
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Which of the following treatments is commonly used for Primary Biliary Cirrhosis (PBC)?
Which of the following treatments is commonly used for Primary Biliary Cirrhosis (PBC)?
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Primary Sclerosing Cholangitis (PSC) is primarily classified as an autoimmune disease.
Primary Sclerosing Cholangitis (PSC) is primarily classified as an autoimmune disease.
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What is a common histological feature observed in liver biopsies for conditions like Primary Sclerosing Cholangitis?
What is a common histological feature observed in liver biopsies for conditions like Primary Sclerosing Cholangitis?
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Primary Biliary Cirrhosis is commonly associated with ______ syndrome.
Primary Biliary Cirrhosis is commonly associated with ______ syndrome.
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Match the features with the correct diseases:
Match the features with the correct diseases:
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Which protein is primarily responsible for moving iron out of the enterocyte's basolateral membrane?
Which protein is primarily responsible for moving iron out of the enterocyte's basolateral membrane?
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Iron absorption occurs primarily in the ileum.
Iron absorption occurs primarily in the ileum.
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What best screening test is indicated for assessing iron overload conditions?
What best screening test is indicated for assessing iron overload conditions?
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Prussian blue staining is used to observe iron deposition within __________ hepatocytes.
Prussian blue staining is used to observe iron deposition within __________ hepatocytes.
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Match the following iron-related conditions with their characteristics:
Match the following iron-related conditions with their characteristics:
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What is the most common symptom of Primary Biliary Cirrhosis?
What is the most common symptom of Primary Biliary Cirrhosis?
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Primary Biliary Cirrhosis affects men more than women.
Primary Biliary Cirrhosis affects men more than women.
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Name the antibody that is present in 95% of Primary Biliary Cirrhosis cases.
Name the antibody that is present in 95% of Primary Biliary Cirrhosis cases.
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Primary Biliary Cirrhosis is characterized by the autoimmune destruction of small intrahepatic/intralobular ______.
Primary Biliary Cirrhosis is characterized by the autoimmune destruction of small intrahepatic/intralobular ______.
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Match the following presentations with their descriptions in Primary Biliary Cirrhosis:
Match the following presentations with their descriptions in Primary Biliary Cirrhosis:
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Which of the following antibodies is most specific for Type-I Autoimmune Hepatitis?
Which of the following antibodies is most specific for Type-I Autoimmune Hepatitis?
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Fatigue and hepatomegaly are common presentations in Chronic Hepatitis.
Fatigue and hepatomegaly are common presentations in Chronic Hepatitis.
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Name one condition that can lead to fulminant hepatic failure.
Name one condition that can lead to fulminant hepatic failure.
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The presence of _____________ is indicative of Primary Biliary Cirrhosis.
The presence of _____________ is indicative of Primary Biliary Cirrhosis.
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Match the following laboratory markers to their respective conditions:
Match the following laboratory markers to their respective conditions:
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What is the mode of inheritance for hereditary hemochromatosis?
What is the mode of inheritance for hereditary hemochromatosis?
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Alcohol consumption decreases the risk of cirrhosis in hereditary hemochromatosis.
Alcohol consumption decreases the risk of cirrhosis in hereditary hemochromatosis.
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Which gene is primarily associated with hereditary hemochromatosis?
Which gene is primarily associated with hereditary hemochromatosis?
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A patient with a homozygous mutation in the HFE gene is diagnosed with ______.
A patient with a homozygous mutation in the HFE gene is diagnosed with ______.
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Match the following gene mutations with their associated conditions:
Match the following gene mutations with their associated conditions:
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What is the critical value for copper estimation in a liver biopsy for confirming Wilson's disease?
What is the critical value for copper estimation in a liver biopsy for confirming Wilson's disease?
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Trientine is the preferred treatment for Wilson's disease during pregnancy.
Trientine is the preferred treatment for Wilson's disease during pregnancy.
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What is the primary medication used for the treatment of Wilson's disease?
What is the primary medication used for the treatment of Wilson's disease?
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A falsely elevated ceruloplasmin level may be observed in a _____ state.
A falsely elevated ceruloplasmin level may be observed in a _____ state.
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Match the treatments with their characteristics:
Match the treatments with their characteristics:
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Which of the following is a diagnostic marker for Autoimmune Hepatitis Type - 1?
Which of the following is a diagnostic marker for Autoimmune Hepatitis Type - 1?
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Autoimmune Hepatitis Type - 1 commonly affects men in their second to third decade of life.
Autoimmune Hepatitis Type - 1 commonly affects men in their second to third decade of life.
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Name one histological finding associated with Autoimmune Hepatitis Type - 1.
Name one histological finding associated with Autoimmune Hepatitis Type - 1.
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Autoimmune Hepatitis Type - 1 is associated with _______ disorders.
Autoimmune Hepatitis Type - 1 is associated with _______ disorders.
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Match the HLA type with its associated condition:
Match the HLA type with its associated condition:
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Study Notes
Primary Sclerosing Cholangitis (PSC)
- Progressive fibrosing destruction of intra and extrahepatic bile duct
- IgG4 disease due to leaky gut
- More common in men in their 2nd and 3rd decades
- Associated with HLA B-8, DR-3
- Presents with fatigue, pruritis, leaky gut, and cholestasis
- Associated with cholangiocarcinoma
- 2/3 of patients with PSC have ulcerative colitis
- 5% of patients with ulcerative colitis have PSC
- Characterized by atypical P-ANCA, type pancholitis with rectal sparing
- Associated with colorectal carcinoma
- Treatment is only by transplant
Laboratory Features
- Raised ALP
- AMA (Type IgM) - positive in 95% of patients
- ANA - positive in 50% of patients
Histopathological Features
- Early feature is loss of the canal of hering
- Ductopenia is the most common finding
- Florid duct lesions with granulomas are characteristic
- Granulomas are non-caseating
Treatment
- Ursodeoxycholic acid (UDCA) slows the progression of biliary cirrhosis
- Obeticholic acid is a Farnesoid Receptor agonist
Metabolic Diseases of Liver
- Chronic cirrhosis of the liver
- Type 3C Diabetes Mellitus
- Dilated cardiomyopathy (DCM) in juveniles, which can progress to restrictive cardiomyopathy (RCMP)
- Pseudoosteroarthritis due to CPPD crystal deposition
- Hook-like osteophytes
- Involvement of MCP/wrist joints
- Hypogonadotropic hypogonadism (decreased GNRH leading to decreased FSH and LH) caused by pituitary positioning
- Slate grey hyperpigmentation and bronzing of the skin
- Acquired hypopituitarism due to involvement of the pituitary stalk
- Hemochromatosis
- Langerhan histiocytosis
- Sarcoidosis
Metabolic Diseases of Liver Management
- Screening test: Transferrin saturation > 45% and serum ferritin > 1000 ng/mL
- Confirmatory test: HFE gene mutation analysis for the C282Y mutation
- Treatment: Weekly phlebotomy
- Target serum ferritin values < 50-500 ng/mL monthly
- Good response is expected if cirrhosis is absent
- Joint and gonadal damage are irreversible
- Risk of HCC remains after transplant
- Subcutaneously administered desferrioxamine is given 5 days a week
Hepatology
- Radiological investigation: MRCP (10C) and ERCP
- Histological features: Concentric periductal onion skin fibrosis
- Treatment: Surgical intervention (25% recurrence)
PBC vs PSC
- PBC is an autoimmune disease that affects mainly perimenopausal women.
- PSC is a fibrosing disease that affects mostly young men.
- PBC is associated with Sjogren's syndrome, while PSC is linked to ulcerative colitis.
- PBC is not associated with HLA, while PSC is.
- Smoking increases PBC risk but is protective against PSC.
- AMA antibodies are diagnostic for PBC, while MRCP is diagnostic for PSC.
- UDCA treats PBC, while a transplant is needed for PSC.
- PBC is not premalignant but PSC is associated with cholangiocarcinoma.
Hereditary Hemochromatosis
- Autosomal recessive disorder of iron metabolism
- Characterized by defective HFE gene on chromosome 6p
- Homozygous for HFE = Hemochromatosis
- Heterozygous for HFE = Porphyria cutanea tarda & Non-Alcoholic Fatty Liver Disease (NASH)
- Non-HFE gene: Hemojuvelin & Hepcidin (Juvenile)
- Alcohol increases the risk of cirrhosis in hereditary hemochromatosis
Pathophysiology of Hereditary Hemochromatosis
- Mucosal iron absorption in the apical membrane greater than 4 g/day in the duodenum.
- Iron absorption is regulated by hepcidin produced by the liver.
- The HFE gene is affected by hepcidin.
- Iron transport out of the intestinal cell on the basolateral membrane.
- DMT-1 is a transporter protein that facilitates iron absorption.
- Ferroportin is a transporter protein that moves iron out of the basolateral membrane of the enterocyte.
Investigations for Hereditary Hemochromatosis
- S. Ferritin: Increased
- S. Iron: Increased
- Total TIBC (Total Iron Binding Capacity): Decreased - Indirect marker of S.Transferrin
- Transferrin Saturation: Increased (above 45%)
- Formula: (S.Fe × 100) / TIBC = 33% (Normal)
- Best screening test: MRI (Magnetic Resonance Imaging)
Histopathological Features in Hereditary Hemochromatosis
- Hemosiderosis - more pronounced in the peripheral zone in histologic samples.
- Periportal hepatocytes stain Prussian blue.
- Iron is deposited in the liver but to a lesser extent in the spleen.
- MRI shows low intensity iron deposition in the liver.
Biliary Cirrhosis
- Autoimmune disease: chronic, progressive destruction of small intrahepatic bile ducts.
- Characterized by non-suppurative inflammation and mediated by both T-cells and B-cells.
- AMA is present in 95% of patients.
- Targets PDHEZ.
- More common in women (9:1 ratio) in their 4th and 5th decade.
Disease Association of Biliary Cirrhosis
- Sjogren's syndrome with arthritis
- Distal RTA (Type D)
- Gallstones
Presentation of Biliary Cirrhosis
- Most commonly, it presents with no symptoms.
- Fatigue is the most common symptom.
- Pruritus is another common symptom.
- Jaundice is seen in only 10% of patients and is associated with a poor prognosis.
- Hypercholesterolemia suggests poor prognosis.
- Dihydrolipoyl transacetylase is the exception to hypercholesterolemia being a poor prognosis.
- Xanthelasmas are present in some cases.
- Hyperpigmentation may also be present.
- Hepatomegaly is present in 30 to 40% of patients.
- Splenomegaly can occur, though less common than hepatomegaly.
Autoimmune Hepatitis Type 1
- Age of onset is usually women in their 2nd and 3rd decade.
- ANA is positive in 100% of cases.
- Associated with drug-induced lupus erythematosus and mixed connective tissue disease.
Associations of Autoimmune Hepatitis type 1
- HLA-DR03 - associated with SLE (Systemic Lupus Erythematosus) and Lupus-like hepatitis.
- HLA-DR04 - associated with Rheumatoid Arthritis.
- Type 1 DM - associated with type 1 diabetes.
- Autoimmune Thyroid disorders - associated with autoimmune thyroid disorders.
Pathophysiology of Autoimmune Hepatitis type 1
- Lymphoplasmacytic inflammation is a key feature.
- Interface Hepatitis (Piecemeal Necrosis) is a characteristic histological finding.
- Portal tract involvement is another essential histological characteristic.
- Emporripolesis, the engulfing of cells without killing, is a specific histological method for describing this finding.
- Rosette formation is another feature.
- Inflammatory process is a characteristic aspect of this condition.
Hepatology Investigations for Wilson Disease
- Screening Test for Wilson's Disease: S.Ceruloplasmin > 20 mg/dL rules out Wilson's disease.
- If S.Ceruloplasmin levels are between 10-20 mg/dL then:
- Total Serum Cu2+ decreases, as both Ceruloplasmin and Non-ceruloplasmin Bound Cu2+ decrease.
- Bound Cu2+/ free Cu2+ ratio increases.
- Urine free Cu2+ increases.
- If S.Ceruloplasmin values are less than 10 mg/dL:
- A liver biopsy is confirmatory.
- Quantitative Cu2+ estimation is critical.
250 µg/g dry weight is a critical value.
- This estimation is performed using Neutron Activation Analysis or Atomic Absorption Spectrometry.
Falsely Elevated Ceruloplasmin
- Acute inflammation
- Hyper estrogenic states, such as pregnancy.
- Monitoring following copper therapy (NCBC).
Biochemical Parameters in Wilson Disease
| Parameter | Basal 24 hr | Liver |
|---|---|---|
| S.Ceruloplasmin | ↓ | |
| S.Copper | ↓ | ↑ |
| Urine Cu | ↑ |
Nazar Prognostic index
- S.bilirubin
- AST
- PT
Treatment for Wilson Disease
-
D-Penicillamine - Drug of Choice
- Start dose: 250 mg/day
- Increase to 1.5 g/day
- Taken empty stomach
- Risks:
- Drug-induced Lupus Erythematosus
- Membranous Nephropathy
- Myasthenia Crisis
- Aplastic Anemia
- Pyridoxine deficiency (Pyridoxine 25 mg to be given)
- **Trientine ** - Not available in India - Dose: 1-1.2 gm/day - Less side effects - Preferred during pregnancy
-
Tetrathiomolybdate
- For neuro Wilson disease
- Not available
-
Zinc
- 50 mg TDS (3 times a day)
- Induces metallothionase
- Competes with Cu for DMT-1
- Given to all patients
- Preferred during pregnancy
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Description
This quiz explores Primary Sclerosing Cholangitis (PSC), a liver disease characterized by the progressive damage to bile ducts. It covers clinical features, laboratory findings, histopathology, and treatment options related to PSC. Test your knowledge on this important hepatic condition and its associations with other diseases.
