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Questions and Answers
Which of the following is NOT a cause of chronic hepatitis and cirrhosis?
Which of the following is NOT a cause of chronic hepatitis and cirrhosis?
Children experiencing cholestasis are at risk for cirrhosis.
Children experiencing cholestasis are at risk for cirrhosis.
True
What is the life expectancy without a transplant for a patient in the decompensation stage of cirrhosis?
What is the life expectancy without a transplant for a patient in the decompensation stage of cirrhosis?
2 years
One of the symptoms associated with cirrhosis is _____ muscle wasting.
One of the symptoms associated with cirrhosis is _____ muscle wasting.
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Match the stage of liver disease with its primary feature:
Match the stage of liver disease with its primary feature:
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What is the main factor that determines variceal wall tension?
What is the main factor that determines variceal wall tension?
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Small varices (≤ 5 mm) have a bleeding risk of more than 10% per year.
Small varices (≤ 5 mm) have a bleeding risk of more than 10% per year.
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What is the initial IV dosage of Terlipressin for acute variceal bleeding?
What is the initial IV dosage of Terlipressin for acute variceal bleeding?
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Mortality from variceal bleeding ranges from _____ to _____ percent.
Mortality from variceal bleeding ranges from _____ to _____ percent.
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Match the following risk categories with their corresponding bleeding risk rates:
Match the following risk categories with their corresponding bleeding risk rates:
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Which of the following is NOT an indicator of a poor prognosis in acute liver failure?
Which of the following is NOT an indicator of a poor prognosis in acute liver failure?
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A prothrombin time greater than 100 seconds indicates a good prognosis in acute liver failure.
A prothrombin time greater than 100 seconds indicates a good prognosis in acute liver failure.
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What arterial pH level indicates a poor prognosis if it remains low for more than 24 hours after drug ingestion?
What arterial pH level indicates a poor prognosis if it remains low for more than 24 hours after drug ingestion?
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A serum creatinine level greater than ______ indicates poor prognosis in acute liver failure.
A serum creatinine level greater than ______ indicates poor prognosis in acute liver failure.
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Match the following indicators with their corresponding measurement:
Match the following indicators with their corresponding measurement:
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What is the threshold pressure for variceal rupture in HVPG?
What is the threshold pressure for variceal rupture in HVPG?
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Nodular compression of sinusoids is a mechanical cause of sinusoidal vasoconstriction.
Nodular compression of sinusoids is a mechanical cause of sinusoidal vasoconstriction.
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What is a common cause of pre-hepatic portal hypertension seen in young children?
What is a common cause of pre-hepatic portal hypertension seen in young children?
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The condition that is associated with hepatic vein obstruction is known as _____ Syndrome.
The condition that is associated with hepatic vein obstruction is known as _____ Syndrome.
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Match the following types of portal hypertension with their causes:
Match the following types of portal hypertension with their causes:
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What is the primary indication for endoscopic variceal ligation?
What is the primary indication for endoscopic variceal ligation?
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An HVPG greater than 10 mm Hg is considered normal.
An HVPG greater than 10 mm Hg is considered normal.
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What condition is confirmed by a Fibroscan reading of 13.5 kPa?
What condition is confirmed by a Fibroscan reading of 13.5 kPa?
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The Hepatic Venous Pressure Gradient (HVPG) is calculated by subtracting _____ from _____ .
The Hepatic Venous Pressure Gradient (HVPG) is calculated by subtracting _____ from _____ .
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Match the following Child-Pugh classification classes with their requirements:
Match the following Child-Pugh classification classes with their requirements:
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Which of the following is a complication of portal hypertension?
Which of the following is a complication of portal hypertension?
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Portal hypertension can only occur in patients with cirrhosis.
Portal hypertension can only occur in patients with cirrhosis.
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What is considered clinically significant portal venous pressure in mm Hg?
What is considered clinically significant portal venous pressure in mm Hg?
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The disappearance of fenestration in cirrhosis is caused by the presence of __________ and fibrous septa compressing the sinusoids.
The disappearance of fenestration in cirrhosis is caused by the presence of __________ and fibrous septa compressing the sinusoids.
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Match the following features of the portal vein with their characteristics:
Match the following features of the portal vein with their characteristics:
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What is a major mechanical cause of increased sinusoidal pressure in cirrhosis?
What is a major mechanical cause of increased sinusoidal pressure in cirrhosis?
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Splenomegaly is a common feature in portal hypertension due to cirrhosis.
Splenomegaly is a common feature in portal hypertension due to cirrhosis.
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Name the two neurohormonal systems stimulated as a response to decreased effective circulatory volume in cirrhosis.
Name the two neurohormonal systems stimulated as a response to decreased effective circulatory volume in cirrhosis.
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In cirrhosis, increased peripheral ________________ leads to a hyperdynamic circulation state.
In cirrhosis, increased peripheral ________________ leads to a hyperdynamic circulation state.
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Match the following features of liver failure with their associated conditions:
Match the following features of liver failure with their associated conditions:
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What is the primary treatment for hemochromatosis?
What is the primary treatment for hemochromatosis?
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NASH has a poor outcome if not treated promptly.
NASH has a poor outcome if not treated promptly.
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What disease requires early penicillamine treatment?
What disease requires early penicillamine treatment?
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In cirrhosis, the normal lobular architecture of the liver is replaced by __________.
In cirrhosis, the normal lobular architecture of the liver is replaced by __________.
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Match the stages of hepatic fibrosis with their description:
Match the stages of hepatic fibrosis with their description:
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Which of the following is NOT included in routine screening?
Which of the following is NOT included in routine screening?
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The outcome for NASH is generally poor regardless of treatment.
The outcome for NASH is generally poor regardless of treatment.
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What stage of fibrosis involves bridging fibrosis extending to the next portal tract?
What stage of fibrosis involves bridging fibrosis extending to the next portal tract?
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Which of the following drugs is a common cause of drug-induced liver injury when taken in excess?
Which of the following drugs is a common cause of drug-induced liver injury when taken in excess?
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Mushroom toxicity is considered a dose-independent cause of acute liver failure.
Mushroom toxicity is considered a dose-independent cause of acute liver failure.
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What enzyme activity is defective in the pathophysiology of paracetamol toxicity?
What enzyme activity is defective in the pathophysiology of paracetamol toxicity?
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The maximum safe daily dose of paracetamol is _____ grams.
The maximum safe daily dose of paracetamol is _____ grams.
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Match the clinical features of paracetamol toxicity with their corresponding descriptions:
Match the clinical features of paracetamol toxicity with their corresponding descriptions:
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What is a consequence of decreased sex hormone binding globulins in females?
What is a consequence of decreased sex hormone binding globulins in females?
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Caput medusae refers to the flow of blood toward the umbilicus.
Caput medusae refers to the flow of blood toward the umbilicus.
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What condition can lead to encephalopathy and variceal bleeding?
What condition can lead to encephalopathy and variceal bleeding?
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Dihydrotestosterone is associated with increased risk of ________ and testicular atrophy.
Dihydrotestosterone is associated with increased risk of ________ and testicular atrophy.
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Match the following consequences of liver failure with their descriptions:
Match the following consequences of liver failure with their descriptions:
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Study Notes
Variceal Bleeds
- Main factor: Variceal wall tension
- Variceal wall tension is determined by: Vessel diameter and pressure.
- Gastroesophageal varices are the cause of 50% of cirrhosis
- Without varices, the rate of development is 8% per year
- Variceal hemorrhage occurs at a rate of 5-15% per year
-
Risk of bleeding:
- Small varices (≤ 5 mm): < 10%/year
- Large varices: 30%/year
- Mortality from variceal bleeding: 15-30%
-
Acute variceal bleeding:
-
Bleeding:
-
Terlipressin (IV):
- 2 mg Q6h x 48 hours (initial dose)→
- Stat dose → 50 µg/hour
- IV Octreotide 50 µg stat → 50 µg/hour
- ** antibiotics**
- Replace blood volume
- Intubation to be considered
-
Terlipressin (IV):
-
Upon failure:
- Endoscopy: Variceal ligation or Sclerotherapy
-
Upon failure:
- TIPSS (Transjugular Intrahepatic Portosystemic Shunt)
-
Bleeding:
Chronic Hepatitis - Cirrhosis
-
Causes:
- NASH (Non-Alcoholic steatohepatitis)
- Alcohol
- HBV/HCV
- Autoimmune disease
- Wilson's disease
- Hemochromatosis
- Budd Chiari Syndrome
- Biliary cirrhosis
-
In children:
- Cholestasis
- α-1 Antitrypsin deficiency
- Indian childhood cirrhosis
Disease Progression
- Stage | Features
- Chronic Hepatitis | Usually asymptomatic. Can be screened for with LFTs. May present with hepatomegaly.
- Cirrhosis | Shrinkage of the liver seen
- Portal HTN | Hepatocellular carcinoma
- Decompensation | Life expectancy 2 years without transplant. Liver failure.
Features
- Fatigue
- Altered sleep rhythm
- Muscle wasting
- Loss of libido
- Hepatomegaly (if seen)
Management
-
Laboratory Investigation:
- ALT/AST ↑ ( AST > ALT in alcoholic hepatitis)
- Continuous monitoring of liver enzymes
- Fibroscan: Quantitative test to ascertain degree of fibrosis.
Acetaminophen Cases
-
King's College Hospital Indicators of a Poor Prognosis in Acute Liver Failure:
- Arterial pH < 7.35 more than 24 hours after drug ingestion
- All of the following:
- Prothrombin time > 100 sec or INR > 6.5
- Serum creatinine level > 3.4 mg/dL (300 mmol/L) or anuria
- Grade 3 to 4 encephalopathy
Management of Portal Hypertension
-
Patient with risk factors for chronic hepatitis:
- Deranged LFT + USG: fatty liver + Negative serology (AST / ALT < 150)
- Confirms chronic hepatitis (NASH)
- Fibroscan: 13.5 kPa
- Cirrhosis
- Splenomegaly (+), ↓ Platelet
- Portal Hypertension (+)
-
HVPG (Hepatic Venous Pressure Gradient): WHVP - FHVP
- Prehepatic | Normal | Normal | Normal
- Presinusoidal | Normal | Normal | Normal
- Sinusoidal | Increased | Normal | Increased
- Postsinusoidal | Increased | Normal | Increased
- >10 mm Hg
-
Endoscopy:
- Large varices → Mild/moderate varices → Conservative management
- Indications for endoscopic variceal ligation:
- Intolerant to β-blocker therapy:
- Asthma
- COPD
- β-blockers contraindicated:
- Severe bradycardia
- Target HVPG not achieved with β-blocker
- Intolerant to β-blocker therapy:
Modified Child-Pugh Scoring System
-
Parameters Assessed:
- Ascites
- Encephalopathy
- Bilirubin
- Albumin
- Prothrombin time (seconds increased)
-
Classes:
- A
- B → Requires Transplant
- C
Sinusoidal Vasoconstriction in Portal HTN
- Resistance due to: P=FXR:R↑=P↑P = FXR: R↑ = P↑P=FXR:R↑=P↑
-
Mechanical cause:
- Nodule compressing sinusoid
-
Functional cause:
- ↓ intrasinusoidal NO
- Contraction of sinusoid
- Defenestration
-
HVPG (Hepatic Venous Pressure Gradient)
- HVPG | Description
- 1-5 mm Hg | Normal value
- ≥ 10 mmHg | Clinically significant portal hypertension
- ≥ 12 mm Hg | Threshold pressure for variceal rupture
- ≥ 20 mm Hg | ↑ Risk of death
Causes
-
Pre-hepatic: First order portal vein occlusion AKA Extrahepatic portal venous obstruction (EHPVO)
- Seen in 3-8 year olds
- Severe upper gastrointestinal bleed
- Massive splenomegaly
- No cirrhosis (good prognosis)
- Cause:
- Umbilical sepsis
- Splenic vein thrombosis (rare)
-
Pre-sinusoidal: (3rd order portal vein)
-
a.NCPF (Non-cirrhotic portal fibrosis)/ Idiopathic portal hypertension
- Presentation: Young adults with upper GI bleed, splenomegaly
- Cirrhosis (rare)
-
b.Other causes
- Schistosomiasis
- Sarcoidosis
-
a.NCPF (Non-cirrhotic portal fibrosis)/ Idiopathic portal hypertension
-
Post-hepatic:
-
a.Cause: Hepatic vein obstruction AKA Budd Chiari Syndrome
- Classical findings: Ascites, hepatomegaly
-
b.Other causes
- Right heart failure
- Tricuspid regurgitation
- Restrictive cardiomyopathy
- Constrictive pericarditis (↑ JVP)
- Right heart failure
-
a.Cause: Hepatic vein obstruction AKA Budd Chiari Syndrome
-
Post-sinusoidal: Intrahepatic
-
Sinusoidal:
- Cause: Sinusoidal obstruction syndrome/ veno occlusive disease
- A/W Post-hematopoietic stem cell transplant following myeloablative therapy with alkylating agents (10-30 days after)
-
Sinusoidal:
Complications of Cirrhosis
PORTAL HTN
-
Pathology:
-
A. ↑ Sinusoidal Pressure
-
Mechanical Cause:
- Compression by Nodules
-
Functional Cause:
- ↓ Intrasinusoidal NO
- Sinusoidal Vasoconstriction and Defenestration
-
Mechanical Cause:
- ↑ Resistance (Sinusoidal pressure & Recritance)
- B.Gut endotoxemia
-
C.↑ Systemic NO: Widespread splanchnic vasodilation
- Profound loss in Peripheral vascular resistance
- Hyperdynamic circulation (↑F)
-
A. ↑ Sinusoidal Pressure
-
↓ Effective circulatory volume
- Stimulation
- RAAS
- ADH
- ↑ Intravascular volume
- Features: ↑ splenic vein pressure
- Stimulation
-
Features:
- Splenomegaly (Hypersplenism)
- Thrombocytopenia (Trapping of PLT's)
LIVER FAILURE
-
Features:
- Hyperdynamic circulation:
- Palmar erythema
- Hyperpigmentation
- Hyperdynamic circulation:
-
A/W Alcohol Consumption:
- Alopecia
- Parotid Swelling
- Dupuytren's contracture
-
↑ Pressure
- Portal
- HTN
Portal Hypertension
- Portal hypertension can manifest with or without cirrhosis.
-
Portal Hypertension leads to:
- Hepatic encephalopathy
- Variceal Bleeding
- Ascites - 1st sign of decompensation
- Hepatorenal syndrome
Clinical Anatomy and Pathogenesis
-
PATHOGENESIS
- Portal venous pressure ≥ 12 mm Hg
- Sinusoidal pressure ≥ 6 mm Hg (Clinically significant if ≥ 10 mm Hg) ↑ in pressure ↑ Portal venous pressure = complication
-
Mechanism of Hypertension
- Cirrhosis: Loss of fenestration, compression by nodules & septae
- Increased Splenic Pressure: Leads to splenomegaly (earliest clinical), Thrombocytopenia (earliest biochemical)
Hepatic Vasculature
-
Development of Portal Vein
- Inferior segment of left and right vitelline veins join/to form portal vein.
- Splenic vein and superior mesenteric veins join behind the neck of pancreas.
-
Portal Vein Features
- 7.5 cm long
- Hilum posterior to hepatic and bile duct
- Portal vein has high compliance, low resistance.
- Hepatic buffer response - Hepatic ischemia is rare d/t dual blood supply (Portal v.& Hepatic A.)
Clinical Features and Complications
- Jaundice + Liver failure - Decompensation: Average survival 2 years without transplant. Mean survival without decompensation/transplant: 12 years
- Disappearance of fenestration in cirrhosis (Nodule and fibrous septa compress the sinusoids).
Hepatology Notes
-
Routine Screening:
- NASH
- HBV/HCV
- Wilson's disease
- Hemochromatosis
- Autoimmune hepatitis
-
Treatment:
- Outcome is very good if treated before/during progression.
- Hemochromatosis: Early phlebotomy
- Wilson's disease: Early penicillamine
- NASH: Good outcome
- Weight loss: (implied treatment method or consequence)
- Outcome is very good if treated before/during progression.
Cirrhosis
- Description: Normal lobular architecture of the liver is lost and replaced by nodules connected by fibrous septa.
-
Microscopic Images:
- Image A (Normal liver): Shows a normal liver structure.
- Image B (Normal liver microscopy): Shows microscopic details of a normal liver.
- Image C (Cirrhotic liver): Shows a cirrhotic liver, characterized by the loss of normal liver structure, with tan-brown color, irregular surface and nodular texture and disorganized architecture with regenerative nodules surrounded by fibrous septa.
Staging of Hepatic Fibrosis
- Stage | Description
- 1 | Mild periportal fibrosis
- 2 | 1+ Septation
- 3 | 2+ Bridging fibrosis; Fibrosis extending to the next portal tract
- 4 | 3+ Nodules; Full blown cirrhosis
Acute Hepatitis & Acute Liver Failure
-
Alcohol (1 mortality)
-
DILI (Drug-induced liver injury):
- Paracetamol (most common in Europe)
- Rifampicin (idiosyncratic)
-
DILI (Drug-induced liver injury):
Drugs Causing Acute Liver Failure (ALF)
-
Dose-Dependent:
- Paracetamol (max dose: 4g/day, toxic dose > 7.5g/day)
- Mushroom
-
Dose-Independent (Idiosyncratic):
- Rifampicin (single dose)
- Carbamazepine
- Propylthiouracil (PTU)
- Nitrofurantoin
- Phenytoin
- INH
- Valproate
Other Causes
- Wilson's disease
- Acute fatty liver of pregnancy (AFLP)
- Autoimmune hepatitis
- Budd-Chiari syndrome
- Rat poison
Clinical Features
- Hepatic encephalopathy: due to increased intracranial pressure (ICP) and cerebral edema, leading to seizures.
- Coagulopathy: INR > 1.5, increasing risk of bleeding
Paracetamol Toxicity
-
Pathophysiology:
- Defective CYP2E1 enzyme activity in zone 3 of the liver.
- Paracetamol is not metabolized properly, causing depletion of glutathione stores and leading to the accumulation of NAPQI, a hepatotoxic metabolite.
Clinical Features (Paracetamol Toxicity):
- Stage | Features
- I (4.5 mg/dL, acute tubular necrosis (ATN) - sepsis & renal failure, hypoglycemia, hyponatremia, metabolic encephalopathy, lactic acidosis, multiple organ dysfunction syndrome (MODS).(Determines survival)
- IV (>96hrs) | MODS
Recovery phase
Hepatology
-
No 5-α Reductase: NO DHT
- Dihydrotestosteron
- Gynecomastia
- Testicular atrophy
-
Consequences:
- Decrease sex hormone binding globulins in females → Hypoestrogenism
- Caput medusae (flow away from umbilicus)
- Jaundice (Sign of liver failure → Decompensation)
Decompensation
- Full developed Portal HTN with Ascites → Encephalopathy → Variceal bleed → Decompensated cirrhosis
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Description
This quiz covers the critical aspects of variceal bleeds, including their causes, risks, and management strategies. Focus areas include the factors affecting variceal wall tension, the rates of hemorrhage based on variceal size, and treatment options such as medication and endoscopic procedures.
