What is the pathophysiology of portal vein pathology and how is it managed in a patient with potential complications such as variceal bleeding, ascites, and hepatic encephalopathy?

Pathophysiology of Portal Vein Pathology and Management

Pathophysiology

Portal hypertension develops when the hepatic venous pressure gradient (HVPG) rises ≥5 mmHg, with clinically significant portal hypertension (CSPH) defined as HVPG ≥10 mmHg, which directly predicts the development of life-threatening complications including variceal bleeding, ascites, and hepatic encephalopathy. 1

Mechanisms of Portal Hypertension

• Increased intrahepatic vascular resistance is the primary driver, resulting from structural changes in the liver including fibrosis, cirrhosis, and increased hepatic vascular tone 2
• The structural changes appear in early stages of cirrhosis and progressively worsen, creating a pathological pressure gradient 1
• Pre-sinusoidal mechanisms can occur in conditions like primary sclerosing cholangitis (PSC), where ductular proliferation and portal fibrosis increase resistance even without full cirrhosis 3
• In PSC specifically, nodular regenerative hyperplasia and obliterative portal venopathy can cause portal hypertension without histological cirrhosis (occurring in 3.3% of transplanted PSC patients) 3
• HVPG may underestimate portal hypertension in pre-sinusoidal conditions, as gastroesophageal varices can develop with HVPG <10 mmHg in PSC, unlike alcohol-related or viral cirrhosis 3

Clinical Consequences by Pressure Threshold

• HVPG ≥10 mmHg (CSPH): Risk of developing ascites, varices, and first decompensation 4, 1
• HVPG ≥12 mmHg: Threshold for variceal bleeding to occur 5
• HVPG >20 mmHg: Defines high-risk patients requiring pre-emptive TIPS within 72 hours of acute bleeding 3

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Management of Variceal Bleeding

Acute Variceal Bleeding

Combination therapy with vasoactive drugs (octreotide or terlipressin) plus endoscopic band ligation (EBL) is mandatory as first-line treatment, achieving 77% hemostasis at 5 days versus 58% with endoscopy alone. 6, 7

• Immediate resuscitation followed by vasoactive agent administration before endoscopy 5, 8
• Antibiotic prophylaxis is mandatory in all cirrhotic patients with acute upper GI bleeding, as it reduces mortality, bacterial infections, and rebleeding 6, 7
• Endoscopic variceal ligation (EVL) for esophageal varices achieves control in up to 85% of cases 3, 5
• Endoscopic variceal obturation (EVO) for gastric varices (GOV2/IGV1) 3

Rescue Therapy for Refractory Bleeding

• TIPS is strongly indicated for variceal bleeding refractory to endoscopic and pharmacological therapy 3, 6, 7
• Pre-emptive TIPS within 72 hours should be performed in high-risk patients: Child-Pugh C, MELD ≥19, or HVPG >20 mmHg at presentation 3, 7
• Covered stents are preferred over bare metal stents due to superior patency 7
• Balloon tamponade is a temporizing measure only when other therapies fail 8

Primary Prophylaxis (Prevention of First Bleed)

• Non-selective beta-blockers (NSBBs) are first-line for patients with medium-to-large varices, as they reduce portal pressure and prevent multiple complications 6, 7, 4
• NSBBs are preferred over EBL alone for primary prophylaxis 6, 7
• Target: Reduce resting heart rate by 25% or to 55 bpm, whichever is lower 6
• Propranolol dosing: Start 40 mg twice daily, titrate to 80 mg twice daily (or maximum tolerated dose) 6
• Alternative: Carvedilol may be considered in compensated cirrhosis with CSPH 4
• EBL is recommended only if NSBBs are contraindicated or not tolerated 3

Secondary Prophylaxis (Prevention of Rebleeding)

Combined therapy with NSBBs plus EBL is mandatory for secondary prophylaxis, as this significantly decreases rebleeding compared to monotherapy. 3, 6, 7

• For gastric varices (GOV2/IGV1): Repeated EVO or retrograde transvenous obliteration (RTO/BRTO) is preferred, with BRTO showing lower rebleeding rates (7.4%) than TIPS (22.8%) 3
• Elective TIPS is indicated for treatment failures/intolerance to secondary prophylaxis or refractory ascites 3

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Management of Ascites

Medical Management

Ascites management follows a stepwise approach: treat underlying liver disease, dietary sodium restriction (<2g/day), diuretic therapy (spironolactone ± furosemide), and large-volume paracentesis for grade 3 ascites. 3

• Spironolactone is first-line diuretic therapy 3
• Large-volume paracentesis (>5L) requires albumin replacement (6-8g per liter removed) to prevent post-paracentesis circulatory dysfunction 3
• Albumin infusion (25-50g weekly) may improve diuretic responsiveness in select patients 3

Refractory Ascites

• TIPS is recommended for selected patients with refractory or recurrent ascites who fail medical management 3, 6, 7
• Patient selection is critical: Avoid TIPS in patients with bilirubin >50 μmol/L, platelets <75×10⁹, pre-existing encephalopathy, active infection, severe cardiac failure, or severe pulmonary hypertension 6
• Hepatic hydrothorax: TIPS may be considered, though evidence is limited 3, 6

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Management of Hepatic Encephalopathy

Prevention and Treatment

• Hepatic encephalopathy affects approximately one-third of patients after TIPS 6
• Most cases respond to simple measures and medical therapy (lactulose, rifaximin) 6
• In severe refractory cases, it may be necessary to reduce the diameter of or occlude the TIPS 6
• Pre-TIPS assessment for encephalopathy risk is mandatory, with particular attention to baseline cognitive function 3

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TIPS: Indications, Contraindications, and Technical Considerations

Indications

1. Refractory acute variceal bleeding (failure of endoscopic + pharmacological therapy) 3, 6, 7
2. Pre-emptive TIPS within 72 hours for high-risk patients (Child-Pugh C, MELD ≥19, HVPG >20 mmHg) 3, 7
3. Refractory or recurrent ascites in selected patients 3, 6, 7
4. Secondary prophylaxis failures (rebleeding despite NSBBs + EBL) 3

Absolute Contraindications

• Bilirubin >50 μmol/L 6
• Platelets <75×10⁹ 6
• Pre-existing severe hepatic encephalopathy 6
• Active infection 6
• Severe cardiac failure 6
• Severe pulmonary hypertension 6

Special Considerations

• Portal vein thrombosis (PVT) is not an absolute contraindication, though cavernoma is associated with high failure rates 3
• PSC patients: Enhanced risk of TIPS infection through infected bile ducts; TIPS may be contraindicated if dilated intrahepatic ducts are in the TIPS tract 3
• Idiopathic non-cirrhotic portal hypertension (INCPH): TIPS indications similar to cirrhosis, covered stents preferred 3
• Referral to high-volume centers (≥10 TIPS annually) is recommended 7

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Liver Transplantation

All patients with decompensated cirrhosis and portal hypertension should undergo liver transplant evaluation, as transplantation is the only curative therapy for end-stage liver disease. 7

• Indications: MELD ≥15, or any decompensation event (ascites, variceal bleeding, encephalopathy, jaundice) 7
• TIPS as bridge to transplant: May be used for intractable variceal bleeding in patients with severe hepatic insufficiency, but transplantation remains definitive treatment 7
• Do not delay transplant evaluation in decompensated patients, as mortality increases rapidly with each decompensation event 7

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Critical Pitfalls to Avoid

• Do not perform TIPS in Child-Pugh C with MELD >18 unless as bridge to urgent transplantation, as post-TIPS liver failure carries high mortality 7
• Do not use TIPS for hepatorenal syndrome outside clinical trials, as evidence is insufficient 7
• Do not delay antibiotic prophylaxis in acute variceal bleeding—it must be given immediately 6, 7
• Do not use NSBBs alone for secondary prophylaxis—combination with EBL is mandatory 3, 6, 7
• Ensure multidisciplinary coordination between hepatology, interventional radiology, and transplant surgery for optimal outcomes 3, 7