How should non‑cirrhotic portal fibrosis be diagnosed and managed?

Non-Cirrhotic Portal Fibrosis: Diagnosis and Management

Overview

Non-cirrhotic portal fibrosis (NCPF), also termed idiopathic non-cirrhotic portal hypertension (INCPH) or hepatoportal sclerosis, should be diagnosed through liver biopsy to exclude cirrhosis combined with clinical evidence of portal hypertension, and managed following the same portal hypertension guidelines established for cirrhosis, with endoscopic therapy and non-selective beta-blockers as primary treatment modalities. 1, 2

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Diagnostic Approach

Clinical Presentation to Recognize

• Gastrointestinal bleeding from esophageal or gastric varices is the most common presentation, particularly in patients from developing countries 3, 1
• Massive splenomegaly occurs more commonly than in cirrhotic portal hypertension and is a distinguishing feature 3, 1, 4
• Preserved liver function with normal transaminases and synthetic function at initial diagnosis in the majority of patients 3, 1
• Absence of hepatic encephalopathy except in rare cases with massive portosystemic shunting 3
• Ascites presence indicates poor prognosis and should trigger more aggressive monitoring 3, 1

Diagnostic Criteria Required

The diagnosis demands meeting all of the following criteria 1, 2, 5:

1. Unequivocal clinical signs of portal hypertension (varices, splenomegaly, ascites, portovenous collaterals, or elevated hepatic venous pressure gradient)
2. Liver biopsy excluding cirrhosis and advanced fibrosis - this remains essential and non-negotiable 3, 1
3. Patent portal and hepatic veins confirmed by Doppler ultrasound or CT 1, 2
4. Exclusion of chronic liver diseases that cause cirrhosis or secondary non-cirrhotic portal hypertension 1, 5

Imaging Strategy

• Start with Doppler ultrasound as first-line investigation to assess portal vein patency and liver morphology 1, 4, 2
• Common misdiagnosis pitfall: Patients are frequently misclassified as cirrhotic on ultrasound due to liver surface nodularity and portal vein wall thickening 3, 1
• Low liver stiffness on transient elastography (<12 kPa) provides a clue to distinguish NCPF from cirrhosis 3
• CT imaging for diagnostic confirmation and assessment of disease extent 1, 2
• MR cholangiography if persistent cholestasis or biliary abnormalities suggesting portal biliopathy are present 2

Histopathological Features

Liver biopsy specimens must be adequate size (transjugular biopsies often insufficient) and demonstrate 3, 4:

• Phlebosclerosis (obliterative portal venopathy) - considered the primary lesion
• Nodular regenerative hyperplasia without cirrhotic nodules
• Perisinusoidal fibrosis with maintained lobular architecture
• Para-portal shunt vessels and sinusoidal dilatation
• Absence of piecemeal necrosis or significant hepatocyte necrosis

Critical caveat: Even adequate specimens can show normal histology in some NCPF patients, so diagnosis relies on combined clinical, radiological, and histological assessment 3

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Etiological Evaluation

Investigate the following potential causes systematically 3, 4, 5:

• Thrombophilic disorders (present in 40% of Western patients) - screen for inherited thrombophilias, myeloproliferative neoplasms, antiphospholipid syndrome
• Immunological disorders - common variable immunodeficiency, connective tissue diseases, Crohn's disease
• Medication exposure - azathioprine, didanosine, 6-thioguanine
• Infections - HIV, chronic infections
• Toxin exposure - arsenic-contaminated water, indigenous medications 4

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Management Strategy

Portal Hypertension Management

Follow the same evidence-based guidelines established for cirrhotic portal hypertension for both prevention and treatment of complications 1, 2:

Variceal Bleeding Management

• Endoscopic therapy controls acute variceal bleeding in 95% of INCPH patients 1, 2
• Endoscopic band ligation is preferred over sclerotherapy for both acute bleeding and secondary prophylaxis 2
• Non-selective beta-blockers for primary and secondary prophylaxis of variceal bleeding using the same approach as cirrhosis 1, 2
• Gastric varices can be managed with cyanoacrylate glue injection or surgery if endoscopic therapy fails 6

Refractory Cases

• TIPS placement should be considered for refractory variceal bleeding or ascites 2
• Surgical shunts (meso-Rex bypass in children, splenorenal shunts) for patients with accessible anatomy and failed endoscopic/medical therapy 2, 6
• Liver transplantation for progressive liver failure or unmanageable portal hypertension complications 3, 2

Surveillance and Monitoring

• Screen for portal vein thrombosis at least every 6 months as this develops commonly in INCPH patients 3, 2
• Early anticoagulation therapy leads to recanalization in 54% of patients who develop portal vein thrombosis 3
• Monitor for cardiopulmonary complications including hepatopulmonary syndrome 2
• Assess for precipitating factors if liver function deteriorates, as preserved function can be lost with intercurrent conditions 3

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Prognostic Considerations

• Mortality from variceal hemorrhage is significantly lower than in cirrhotic patients due to preserved liver synthetic function 3, 4
• Five-year survival approaches 95-100% when variceal bleeding is controlled 6, 7
• Hepatic encephalopathy complications are rare due to maintained liver function 2
• Higher incidence of portal vein thrombosis compared to cirrhotic patients requires vigilant monitoring 3
• Minority of patients develop progressive liver failure over time, potentially requiring transplantation 3
• Poor outcome indicators: presence of ascites, additional causes of liver damage, or precipitating factors 3, 1

Key distinction from cirrhosis: The benign prognosis in NCPF/INCPH relates directly to preserved hepatocellular function, making aggressive management of portal hypertension complications worthwhile with excellent long-term outcomes expected 3, 6, 7