Causes of Portal Hypertension

Anatomical Classification of Causes

• The American Association for the Study of Liver Diseases suggests that portal hypertension is classified by the site of increased resistance to blood flow into three main categories 1, 2
• Portal vein thrombosis is the most common prehepatic cause of portal hypertension, according to the American College of Gastroenterology 2
• Splenic vein thrombosis is a prehepatic cause of portal hypertension, as stated by the Hepatology society 1
• The European Association for the Study of the Liver recommends that cirrhosis from any chronic liver disease is considered the single most common cause of portal hypertension overall 3
• Chronic viral hepatitis B/C is an intrahepatic cause of portal hypertension, as reported by the Journal of Hepatology 4
• Alcoholic liver disease is an intrahepatic cause of portal hypertension, according to the Hepatology society 1
• Non-alcoholic steatohepatitis (NASH) is an intrahepatic cause of portal hypertension, as stated by the Hepatology society 1
• Autoimmune hepatitis is an intrahepatic cause of portal hypertension, as reported by the Journal of Hepatology 4
• Primary biliary cirrhosis can develop portal hypertension even before established cirrhosis, according to the Journal of Hepatology and the American Association for the Study of Liver Diseases 4, 3
• Hereditary hemochromatosis is an intrahepatic cause of portal hypertension, as reported by the Journal of Hepatology 4
• Wilson's disease is an intrahepatic cause of portal hypertension, as reported by the Journal of Hepatology 4
• Idiopathic non-cirrhotic portal hypertension (INCPH) is a non-cirrhotic cause of portal hypertension, caused by thrombophilia, immunological disorders, specific medications, and infections, as stated by the Journal of Hepatology and the American College of Gastroenterology 5, 4, 2
• Schistosomiasis is a non-cirrhotic cause of portal hypertension, as reported by the Journal of Hepatology and the American Association for the Study of Liver Diseases 4, 2
• Congenital hepatic fibrosis is a non-cirrhotic cause of portal hypertension, as reported by the Journal of Hepatology and the American College of Gastroenterology 4, 2
• Sarcoidosis is a non-cirrhotic cause of portal hypertension, as reported by the Journal of Hepatology and the American Association for the Study of Liver Diseases 4, 2
• Sinusoidal obstruction syndrome (veno-occlusive disease) is a posthepatic cause of portal hypertension, as stated by the Hepatology society 1
• Budd-Chiari syndrome is a posthepatic cause of portal hypertension, characterized by thrombosis of hepatic veins or inferior vena cava, according to the American College of Gastroenterology 2
• Right heart failure is a posthepatic cause of portal hypertension, as stated by the Hepatology society 1

Pathophysiological Mechanisms

• The American Association for the Study of Liver Diseases states that portal hypertension develops through two primary mechanisms, including increased intrahepatic vascular resistance and increased portal venous inflow 3

Critical Diagnostic Considerations

• The Journal of Hepatology recommends that liver biopsy remains essential to exclude cirrhosis in suspected non-cirrhotic portal hypertension 5, 2
• The Hepatology society states that the hepatic venous pressure gradient (HVPG) measurement pattern differs by etiology, and in prehepatic and presinusoidal causes, HVPG remains normal because wedged pressure does not reflect portal pressure 1

Portal Hypertension Without Liver Disease

Non-Cirrhotic Causes and Diagnostic Approach

• Idiopathic non-cirrhotic portal hypertension (INCPH) is caused by thrombophilia, immunological disorders, specific medications, or HIV infection, with a 40% prevalence of thrombophilia, according to the European Association for the Study of the Liver 6
• Nodular regenerative hyperplasia can cause portal hypertension even in precirrhotic stages, as stated by the American Association for the Study of Liver Diseases 7
• When evaluating portal hypertension without known liver disease, a systematic exclusion of all causes is necessary, starting with imaging, specifically Doppler ultrasound to assess portal and hepatic vein patency, as recommended by the European Association for the Study of the Liver 6
• Liver biopsy is essential to exclude cirrhosis and identify specific pathology like nodular regenerative hyperplasia or obliterative portal venopathy, according to the European Association for the Study of the Liver 6
• A thrombophilia workup is necessary if INCPH is suspected, as 40% of patients have underlying prothrombotic conditions, as stated by the European Association for the Study of the Liver 6
• Patients with non-cirrhotic portal hypertension typically present with splenomegaly and hypersplenism, variceal bleeding, normal or near-normal liver function at diagnosis, and a better prognosis than cirrhotic portal hypertension, according to the European Association for the Study of the Liver 6

Portal Vein Hypertension Classification and Diagnosis

Anatomical Classification System

• The American College of Radiology recommends classifying portal hypertension into three categories based on the site of increased resistance to blood flow: prehepatic, intrahepatic, and posthepatic, with mesenteric vein obstruction being a prehepatic cause 8
• The American College of Radiology states that cirrhosis from any chronic liver disease accounts for the majority of portal hypertension cases in Western countries 8

Hemodynamic Definitions

• The American College of Radiology defines clinically significant portal hypertension (CSPH) as ≥10 mmHg, which is when complications like varices and ascites develop 8
• The American College of Radiology states that a hepatic venous pressure gradient (HVPG) of ≥16 mmHg is independently associated with higher mortality in both compensated and decompensated cirrhosis 8

Portal Hypertension Causes and Mechanisms

Intrahepatic Causes

• The American Association for the Study of Liver Diseases notes that primary biliary cirrhosis can develop portal hypertension even before established cirrhosis develops, with a study published in 2007 9
• Increased intrahepatic resistance is driven by a structural component (70%) due to architectural distortion from fibrous tissue, regenerative nodules, vascular distortion, and microthrombi, as well as a functional component (30%) due to active intrahepatic vasoconstriction, according to a study published in Hepatology in 2007 9
• Splanchnic arteriolar vasodilation occurs concomitantly with collateral formation, paradoxically increasing portal blood flow despite the development of portosystemic collaterals, as reported in a study published in Hepatology in 2007 9

Special Population Considerations

• Patients with hepatitis C and bridging fibrosis can develop varices even without established cirrhosis, with a prevalence of 16%, as noted in a study published in Hepatology in 2007 9