Portal hypertension

Question 1

Define portal hypertension.

Answer 1

Clinically significant portal hypertension is defined as a portal vein pressure >10 mm Hg, most commonly attributable to liver disease.

Question 2

What is the normal venous pressure? What is the pressure in portal hypertension?

Answer 2

7-14mmHg

In portal hypertension: 20-50mmHg

Question 3

How common is portal hypertension? Who is usually affected?

Answer 3

• Alcoholic and viral liver disease are the most common causes of cirrhosis → portal hypertension
• 90% of those with cirrhosis develop portal hypertension
• Schistosomiasis is the main cause of portal hypertension worldwide

Question 4

When do oesophageal varices appear in portal hypertension?

Answer 4

When portal vein pressure rises to >10mmHg - variceal haemorrhage is the most serious complication of portal hypertension and aises when portal pressure is >12mmHg

Question 5

What is the aetiology of portal hypertension?(PH)

Answer 5

1.Conditions resulting in an increased resistance to flow, can be:

• Prehepatic - e.g. portal vein thrombosis, splenic vein thrombosis, congenital stenosis
• Hepatic - e.g. cirrhosis, ALD, primary biliary cirrhosis, schistosomiasis
• Posthepatic - e.g. Budd-Chiari syndrome, constrictive pericarditis, IVC obstruction, cor pulmonale, tricuspid regurgitation

2.Conditions causing increased portal flow

• Splanchnic arterial vasodilation mediated by local release of NO in PH
• Arterial-portal venous fistulae

Question 6

What is the pathophysiology of portal hypertension? Which site is most significant?

Answer 6

Raised pressure → expansion of collaterals between the portal and the systemic veins.

Varices at the gastro-oesophageal junction are most significant; they are superficial and drain into the azygos veins.

Under increased pressure, they may rupture causing haematemesis or melaena.

Rectal varices are found in 30% of cases. They may be differentiated from haemorrhoids which are lower in the anal canal.

Question 7

How is portal hypertension diagnosed?

Answer 7

Clinical diagnosis

• history and physical examination

Invasive and non-invasive procedures confirm diagnosis and determine severity

• FBC and platelets
• LFTs and albumin
• Clotting studies
• Hep B and C
• Iron, TIBC, ferritin
• ANA, ASMA, AMA, ceruloplasmin, alpha-1 antitrypsin
• Ascitec fluid analysis

Imaging:

• OGD - assess oesophageal varices
• Duplex US
• CT/MRI/MRA - if results of US are unequivocal

Question 8

What do ascitic fluid results suggest portal hypertension?

Answer 8

A serum to ascites albumin gradient (SAAG) ≥1.1 mg/dl = portal hypertension.

Polymorphonuclear cells ≥250 cells/ml or +ve Gram stain/culture = complicating spontaneous bacterial peritonitis (SBP)

Question 9

What is the management of acute portal hypertension?

Answer 9

Dietary sodium restriction to 2000mg/day - limits fluid overload

Serial large-volume paracentesis (LVP) - if over 5L removed, it can be replaced with albumin infusion (8-10g/L of ascitic fluid removed) to prevent circulatory dysfunction

IV diuretics (furosemide and spironolactone) - monitor renal function and electrolytes frequently

IV antibiotics against enteric bacteria if SBP

Surgical:

TIPS (transjugular intrahepatic portosystemic shunt) - may be placed if unresponsive to above treatment or in presence of variceal bleeding

Question 10

How is acute variceal haemorrhage managed?

Answer 10

• Crystalloids
• Blood product resuscitation
• IV octerotide
• Terlipressin/vasopressin or somatostatin
• Urgent UGI endoscopy with sclerotherapy/band ligation.
• Give empiric antibiotic therapy for SBP

Question 11

What is the management of chronic ascites?

Answer 11

Conservative:

• Dietary sodium restriction
• Abstinenece from alcohol or treatment for HepB/C
• Vaccination for Hep A/B

Medical:

• Diuretics - 40mg furosemide and 100mg spironolactpne to retain normal sodium levels
• Non-selective beta-blocker (propanolol and nadolol) - to reduce resting HR by 25% (prevents variceal bleeding)
• • long-acting nitrate (e.g. isosorbide-5-mononitrate) improves portal heamodynamics
• Antibiotic prophylaxis

Surgical:

• Intermittent LVP may be needed
• Hepatic transplantation for selected cases

Question 12

What are the complications of portal hypertension?

Answer 12

Most common complication - variceal bleeding. Risk of bleeding is 15% at 1yr

Hepatorenal syndrome (high-near term mortality). HRS may complicate SBP so diagnosis and appropriate prophylaxis against SBP is necessary.

Question 13

What is the prognosis with portal hypertension?

Answer 13

Any chronic liver disease will lead to cirrhosis.

Initially, cirrhosis will be compensated (median survival, >12 years), but once complications (ascites, variceal hemorrhage, encephalopathy, jaundice) develop, it becomes decompensated (median survival, 1.6 years). Hepatocellular carcinoma (HCC) can develop at any stage and precipitate decompensation and death.

Question 14

Why do you get hypersplenism in early portal hypertension/

Answer 14

Spleen grows and sequesters platelets and other formed blood cells, leading to hypersplenism.

Question 15

A 55-year-old man with chronic hepatitis C complains of fatigue. On physical examination, he has vascular spiders, palmar erythema, and a palpable left lobe of his liver. He has no ascites or asterixis. Laboratory analysis demonstrates aspartate aminotransferase 100, alanine aminotransferase 67, alkaline phosphatase 145, and platelet count of 120,000. CT scan shows a nodular liver contour, portosystemic collaterals, but no masses. Which of the following would you recommend as the next step?

1. Liver biopsy
2. Upper endoscopy
3. Start nonselective β-blockers
4. Start spironolactone
5. Magnetic resonance imaging of the liver

Answer 15

2 - any patient with newly diagnosed cirrhosis should undergo upper endoscopy to investigate the presence and size of gastroesophageal varices.

NB: β-Blockers should be initiated in patients with medium or large varices or in patients with high-risk small varices (i.e., those present in a Child class C patient or with red wale marks). β-Blockers are not useful in patients without varices and are associated with significant adverse events.

Question 16

Which of the following medications would you recommend at this point in a patient with cirrhosis and confirmed gastro-oesophageal varices on endoscopy?

1. No specific medication
2. Metoprolol
3. Nadolol
4. Spironolactone
5. Pantoprazole

Answer 16

Answer: 3 Nonselective β-blockers are the treatment of choice for the primary prevention of variceal bleeding. β 2 -blockade is the most important.

NB: β 1 -Specific blockers (atenolol, metoprolol) are not as effective as nonselective (β 1 and β 2 ) β-blockers (nadolol or propranolol) or a nonselective β-blocker with vasodilating properties (carvedilol) because the most important portal pressure–reducing effect results from β 2 -blockade.

Question 17

A 64-year-old obese man presents for evaluation of new ascites and peripheral oedema. He is a heavy smoker and moderate drinker but he has no history of liver disease. Physical examination reveals decreased breath sounds, moderate ascites, and peripheral oedema but no other abnormalities. Laboratory tests reveal a total bilirubin 1.2 mg/dL, AST 37 IU/mL, ALT 35 IU/mL, albumin 3.7 g/dL, and INR 1.4. Paracentesis discloses clear yellow fluid with the following characteristics: total protein 3.5 g/dL, albumin 1.7 g/dL, WCC 640/µL (12% neutrophils). Which one of the following is the most appropriate action?

1. Begin intravenous cefotaxime and await ascites culture results.
2. Perform a liver biopsy.
3. Obtain serum B-type natriuretic peptide and perform cardiac echocardiography.
4. Perform an abdominal CT scan to investigate peritoneal malignant disease.
5. Begin therapy for tuberculosis.

Answer 17

Answer: 3

This patient has ascites with a high serum-ascites albumin gradient (>1.1 g/dL), indicating ascites that is secondary to hepatic sinusoidal hypertension. The high protein content (>2.5 g/dL) indicative of normal “leaky” sinusoids, so the problem is unlikely to be in the liver. A liver biopsy would not be the most indicated test. In this clinical setting, the most likely possibility is right-sided heart failure, which should be evaluated, initially with an echocardiogram.

A high serum BNP has a high diagnostic accuracy in the diagnosis of ascites due to heart failure.

NB: Although the ascites total white blood cell count is somewhat elevated, it is not consistent with SBP, which is based on more than 250 neutrophils/µL. In peritoneal causes of ascites (carcinomatosis, tuberculosis), the ascites protein is high and the serum-to-ascites albumin gradient is low (<1/1 g/dL) because fluid formation does not result from sinusoidal hypertension.

Question 18

A 53-year-old woman with cirrhosis secondary to PBC presents with 2 weeks of weight gain and an increase in abdominal girth.

On physical examination, she has gained 8 pounds, and she has a modestly distended abdomen with flank dullness and shifting dullness. No asterixis.

Her laboratory tests include creatinine 0.8, blood urea nitrogen 24, Na 136, K 3.5. Analysis of her ascitic fluid shows no SBP. No hepatic masses. Appropriate management at this point should be:

1. Large-volume paracentesis.
2. Salt and water restriction alone.
3. Transjugular intrahepatic portosystemic shunt (TIPS).
4. Spironolactone.
5. Intravenous furosemide.

Answer 18

Answer: 4

1. The mainstay of therapy is sodium restriction and diuretics. Water restriction is not indicated unless her serum sodium concentration is below 125 mEq/L.
2. The most effective diuretic is spironolactone, which should be initiated alone at a dose of 100 mg once daily in the morning, particularly in patients with modest ascites.
3. Large-volume paracentesis is indicated to decrease discomfort in patients with tense ascites and is first-line therapy for patients with refractory ascites.
4. TIPS placement is second-line therapy for patients with refractory ascites.

Question 19

A 48-year-old man with chronic hepatitis C virus infection, cirrhosis, and ascites presents with 2 days of confusion. He denies fever, chills, hematemesis, or melena. He is confused and agitated, and asterixis is present. His abdomen has tense ascites but is nontender, and his stool is negative for blood. His laboratory tests include white blood cell 8.6, creatinine 2.1 (previously 0.8), and bilirubin 7.7 (previously 2.3). He is making only small amounts of urine, but his urinalysis is normal. Which of the following is the most appropriate test?

1. Diagnostic paracentesis and blood cultures
2. Large-volume paracentesis
3. Upper endoscopy
4. Brain CT
5. Renal ultrasound

Answer 19

Answer: 1

The presence of unexplained encephalopathy or deterioration in renal function in a patient with ascites should always raise the suspicion of spontaneous bacterial peritonitis (SBP);

Large-volume paracentesis could lead to further deterioration in renal function. There is no evidence of gastrointestinal bleeding, so endoscopy is not indicated. Brain scan is not an initial test in encephalopathy unless there is a history of trauma.

Question 20

What are the causes of a SAAG <1.1g/dL?

Answer 20

Indicates a peritoneal cause of ascites including malignancy, infection (e.g.TB), pancreatitis, nephrotic syndrome.

Low protein causes (<35mg/L): cirrhosis, hypoproteinaemia, HF

Question 21

What are the causes of SAAG >1.1g/dL?

Answer 21

Portal hypertension including:

• cirrhosis
• alcoholic hepatitis
• portal vein thrombosis
• HF

Question 22

Is spironolactone useful in portal hypertension?

Answer 22

Spironolactone may reduce portal pressure but has not been shown to prevent first variceal haemorrhage.

Question 23

Is spironolactone useful in portal hypertension?

Answer 23

Spironolactone may reduce portal pressure but has not been shown to prevent first variceal haemorrhage.

Question 24

Why should you take ascites cultures alongside blood culture in suspected SBP?

Answer 24

The ascites culture is negative in about 40% of patients with SBP, so ascites and blood cultures should be performed whenever SBP is suspected.

Question 25

Why should you take ascites cultures alongside blood culture in suspected SBP?

Answer 25

The ascites culture is negative in about 40% of patients with SBP, so ascites and blood cultures should be performed whenever SBP is suspected.

Question 26

Can furosemide be used to treat ascites?

Answer 26

Furosemide is not as effective as spironolactone

… because sodium that is not reabsorbed in the loop of Henle is taken up at the distal and collecting tubules as a result of the hyperaldosteronism that is present in most patients with cirrhosis and ascites.