Portal hypertension

Portal hypertension is the pathological elevation of portal venous pressure resulting from obstructions in portal blood flow, which can be prehepatic (e.g., portal vein thrombosis), hepatic (e.g., liver cirrhosis), or posthepatic (e.g., right-sided heart failure). The subsequent backflow of blood may lead to portosystemic anastomoses, splenomegaly, and/or ascites. A diagnosis of portal hypertension can be made based on clinical signs and knowledge of an underlying cause. In suspected cases, medical imaging and laboratory tests are used to support the diagnosis. Management involves treating the underlying condition and reducing portal pressure with nonselective beta blockers (NSBBs) and portosystemic shunts. Acute hemorrhage of esophageal varices is a potentially life-threatening complication of portal hypertension and is caused by increased blood flow via portosystemic anastomoses.

Causes of portal hypertension are described based on the anatomical location of the lesion.

Prehepatic [1]

• Portal vein thrombosis
• Splenic vein thrombosis
• Mesenteric vein thrombosis [2]
• Congenital abnormalities of the portal vein system (e.g., portal vein agenesis)
• Compression of portal or splenic veins [3]
• Arteriovenous fistula

Hepatic [1][4]

Hepatic etiologies of portal hypertension are described anatomically in relation to the hepatic sinusoids.

• Presinusoidal
  • Hepatosplenic schistosomiasis (most common cause of noncirrhotic portal hypertension worldwide) [5]
  • Granulomatous diseases (e.g., sarcoidosis, tuberculosis) [3]
  • Malignancy (e.g., lymphoma) causing portal vein occlusion
  • Biliary diseases (e.g., primary biliary cholangitis, primary sclerosing cholangitis)
  • Developmental or genetic abnormalities (e.g., polycystic kidney disease, arteriovenous fistula)
• Sinusoidal
  • Cirrhosis (most common cause of portal hypertension in the US)
  • Massive hepatic metastases
  • Steatohepatitis
  • Congenital hepatic fibrosis
  • Amyloidosis
  • Drug-induced liver injury (e.g., methotrexate-induced) or toxin-related liver injury (e.g., copper)
  • Alcohol-associated liver disease
  • Infiltrative diseases (e.g., Gaucher disease)
  • Inflammatory and infectious conditions (e.g., viral hepatitis, chronic Q fever)
  • Portosinusoidal vascular disorder
• Postsinusoidal
  • Sinusoidal obstruction syndrome
  • Vascular malignancy (e.g., angiosarcoma)
  • Granulomatous changes (due to, e.g., sarcoidosis or Mycobacterium avium)
  • Sclerosis of the hepatic vein (due to, e.g., alcohol or hypervitaminosis A)

Posthepatic [1][3]

• Budd-Chiari syndrome
• Right-sided heart failure [6]
• Constrictive pericarditis
• Obstruction of IVC (e.g., IVC thrombosis)

Prehepatic [1][7]

Obstruction of portal vein or splenic vein → ↑ hydrostatic pressure in the tributaries of the obstructed vein

Hepatic [1][7]

• Presinusoidal: obstruction of outflow in portal vein at the porta hepatis or in the portal venules within liver → ↑ hydrostatic pressure in the portal vein and its tributaries
• Sinusoidal: ↑ resistance to blood flow in the hepatic sinusoids (e.g., due to hepatic fibrosis and ↓ intrahepatic nitric oxide production in cirrhosis) → ↑ hydrostatic pressure in the hepatic sinusoids → ↑ hydrostatic pressure in the portal vein and its tributaries
• Postsinusoidal: obstruction of outflow in the central vein and/or hepatic venules → ↑ hydrostatic pressure in the hepatic sinusoids → ↑ hydrostatic pressure in the portal vein and its tributaries

Posthepatic [1][7]

Hepatic vein congestion or obstruction of hepatic vein outflow → ↑ hydrostatic pressure in the hepatic sinusoids → ↑ hydrostatic pressure in the portal vein and its tributaries

The etiology determines whether portal hypertension manifests as acute or chronic.

• Signs and symptoms of underlying disease, e.g.:
  • Clinical features of cirrhosis
  • Clinical features of right-sided heart failure
• Signs and symptoms of complications: features of increased blood flow via portosystemic anastomoses
  • Gastrointestinal bleeding [9]
    • Hematemesis and/or melena (e.g., due to esophageal varices or gastric varices)
    • Hematochezia (e.g., due to hemorrhoidal or anorectal varices)
  • Caput medusae
  • Signs of hypersplenism due to congestive splenomegaly (e.g., thrombocytopenia)
  • Abdominal distention due to ascites
  • Hepatic encephalopathy

Patients usually present with signs of their underlying disease and/or symptoms related to the complications of portal hypertension.

General principles [10][11]

• CSPH is confirmed in patients with either: [10]
  • HVPG measurement ≥ 10 mm Hg
  • Surrogate markers of CSPH:
    • Complications of portal hypertension: e.g., esophageal varices on EGD, portosystemic collaterals on abdominal imaging
    • Abnormal noninvasive tests: transient elastography with PLT count [12]
• Once confirmed, identify the underlying causes of portal hypertension.
  • Obtain a diagnostic workup for the most likely cause (e.g., diagnostics for cirrhosis).
  • Consult hepatology if the diagnosis remains unclear.

The combination of elevated liver stiffness and thrombocytopenia provides the most reliable estimation of CSPH using noninvasive tests. [10]

Laboratory studies [6][10]

Findings are nonspecific but may further support the diagnosis and help to identify the underlying cause.

• CBC
  • Thrombocytopenia (most common laboratory finding in portal hypertension)
  • Anemia related to an underlying condition
• Liver chemistries: transaminitis and/or hyperbilirubinemia suggest liver disease.
• Coagulation panel: coagulopathy is a sign of advanced liver disease
• Ascitic fluid analysis: high SAAG ≥ 1.1 g/dL [6]

Imaging studies [10][13]

Transient elastography [10][12]

• Indications: Obtain for all patients with nonconfirmed disease.
• Findings: Correlate with PLT levels to increase diagnostic yield.
  • CSPH is confirmed with the following findings : [10]
    • Liver stiffness > 25 kPa (regardless of PLT level)
    • Liver stiffness 20–25 kPa (if PLT < 150,000/mm³)
    • Liver stiffness 15–20 kPa (if PLT ≤ 110,000/mm³)
  • CSPH is ruled out if liver stiffness < 15 kPa and platelets ≥ 150,000/mm³. [10]

Transient elastography is the recommended noninvasive test for diagnostic confirmation in patients with suspected portal hypertension. [10]

Abdominal imaging [10]

Findings may help establish the diagnosis and identify the underlying cause.

• Modalities
  • MR elastography
    • For diagnostic uncertainty after transient elastography [12]
    • Liver stiffness ≥ 5.1 kPa on MR elastography suggests CSPH. [12]
  • Doppler ultrasound abdomen: Obtain to assess portal circulation.
  • CT or MRI abdomen are usually reserved for:
    • Concerns for extrahepatic obstruction
    • Preprocedural planning
• Specific findings of CSPH: sufficient to establish a diagnosis of portal hypertension [10][14]
  • Portosystemic collateral circulation
  • Blood flow reversal in the portal system
• Nonspecific findings
  • Portal and/or splenic vein dilation > 10 mm
  • Decreased portal vein velocity on Doppler ultrasound
  • Splenomegaly, ascites, and/or varices
  • Findings that suggest the underlying cause, e.g.:
    • Cirrhosis (e.g., nodular liver)
    • Liver masses
    • Portal vein thrombosis

Hepatic venous pressure gradient (HVPG) measurement [10][11][15]

• Indication: reserved for diagnostic confirmation in cases of uncertainty (gold standard test) [10]
• Method: Free and wedge occlusion pressures of the hepatic vein are measured via catheterization, using ultrasound or fluoroscopy. [11]
• Interpretation of HVPG levels [10]
  • > 5 mm Hg: mild portal hypertension
  • ≥ 10 mm Hg: clinically significant portal hypertension (CSPH) [6]
  • > 12 mm Hg: associated with complications (e.g., variceal bleeding) [6]

Esophagogastroduodenoscopy (EGD) [10][11]

• Indications (all of the following)
  • Diagnosis of cirrhosis or compensated advanced chronic liver disease
  • Non-invasive methods to diagnose CSPH (e.g., transient elastography) are unavailable
• Interpretation: The presence of esophageal varices of any size confirms the diagnosis of CSPH. [10]

General principles [10][11][13]

Consult hepatology for specialist-guided management that includes:

• Management of the underlying causes of portal hypertension (mainstay of treatment)
• Pharmacotherapy with NSBBs
• Portosystemic shunts for refractory disease
• Management of complications of portal hypertension, e.g., treatment of ascites, treatment of hepatic encephalopathy, treatment of esophageal varices

Pharmacotherapy (off-label) [10][11]

• NSBBs: used to prevent hepatic decompensation (e.g., variceal bleeding)
  • Indicated in patients with CSPH and cirrhosis (unless there are contraindications for beta blockers) [10]
  • Preferred agent: carvedilol [10][11]
  • Alternative agents: propranolol, nadolol
• Reduce dose or discontinue in patients with complications of advanced liver disease.

Transjugular intrahepatic portosystemic shunt (TIPS or TIPSS) [16][17]

• Definition: implantation of a stent between the hepatic vein and portal vein
• Goals
  • Ensure blood drainage from the portal to the systemic system bypasses the liver, thus lowering portal pressure
  • Reduce the risk of variceal bleeding and reduce the formation of ascites
• Indications
  • Persistent, recurring, or treatment-resistant upper gastrointestinal bleeding resulting from portal hypertension, e.g., from esophageal varices
  • Other complications of portal hypertension refractory to medical therapy, e.g.: [16]
    • Ascites
    • Hepatic hydrothorax
    • Budd-Chiari syndrome
    • Chronic complete portal vein thrombosis
• Contraindications [16][17]
  • Refractory overt hepatic encephalopathy
  • Severe circulatory diseases, i.e.:
    • Heart failure
    • Severe pulmonary hypertension (mPAP > 45 mm Hg)
    • Severe untreated valvular heart disease, e.g., tricuspid regurgitation
  • Ongoing infection or sepsis
  • Severe, uncorrectable coagulopathy (relative contraindication) [17]
  • Anatomical barriers (relative contraindication) [17]
• Procedure [10][18]
  • Access site: internal jugular vein
  • The hepatic vein is catheterized and an expandable stent is placed between the hepatic and portal veins.
• Complications [17][19]
  • Procedure-related, e.g., inadvertent carotid artery puncture, stent migration, stent occlusion
  • Portosystemic shunt-related, e.g., hepatic encephalopathy, TIPS-induced hemolysis
• Prevention of complications: Periprocedural rifaximin may be used to reduce the risk of hepatic encephalopathy. [17]

Shunt implementation results in reduced hepatic elimination of ammonia and may lead to worsening of encephalopathy.

Surgical portosystemic shunts [20][21]

• Indications [20][22]
  • Recurrent variceal bleeding after TIPS
  • Contraindications to TIPS
• Techniques
  • Total (nonselective) portosystemic shunts: The portal vein is completely shunted to the vena cava, reducing portal pressure. [21]
  • Selective portosystemic shunts
    • The portal vein is partially shunted to the vena cava, reducing portal pressure.
    • The partial shunt prevents variceal bleeding while continuing to allow portal perfusion. [21]

• Life-threatening esophageal variceal bleeding
• Portal hypertensive gastropathy
• Ascites
• Spontaneous bacterial peritonitis
• Hepatorenal syndrome
• Impaired liver function (see “Cirrhosis”)
• Hepatic encephalopathy
• Pulmonary complications of portal hypertension (e.g., hepatopulmonary syndrome, portopulmonary hypertension)
• Cirrhotic cardiomyopathy
• Gastric antral vascular ectasia

We list the most important complications. The selection is not exhaustive.

• Definition: gastric venous and capillary ectasia resulting from CSPH [10]
• Epidemiology
  • Prevalence among patients with compensated cirrhosis: approx. 50–80% [10]
  • More common in patients with medium or large gastroesophageal varices than in those with no or small gastroesophageal varices
• Clinical features
  • Often asymptomatic
  • Symptoms of iron-deficiency anemia from chronic blood loss
  • Features of overt GI bleeding (rare) [10]
• Diagnostics
  • EGD (first-line) [10]
    • Proximal lesions [23]
    • Mosaic pattern (“snakeskin” mucosa)
    • Intramucosal hemorrhage (red or black-brown markings)
    • Portal hypertension (PH) related polyps may be visible. [10]
  • Other modalities: CT, MRI, capsule endoscopy [23]
• Management [10]
  • Acute GI bleeding from severe PHG
    • Vasoactive therapy (e.g., octreotide) at doses used for variceal bleeding for 2–5 days
    • See “Management of esophageal variceal hemorrhage.”
  • Chronic management
    • NSBBs to prevent decompensation or rebleeding
    • Management of chronic blood loss [23]
      • Iron supplementation
      • Blood transfusions
      • TIPS for patients who are transfusion-dependent despite NSBB therapy
      • Argon plasma coagulation

Rule out H. pylori infection (a common differential diagnosis) before initiating prophylactic therapy with NSBBs. [10]

• Definition: dilation of small mucosal and submucosal blood vessels in the gastric antrum
• Associated conditions [23]
  • Portal hypertension, cirrhosis
  • Chronic kidney disease
  • Connective tissue disorders (e.g., systemic sclerosis)
  • Cardiovascular disease
  • Bone marrow transplantation
• Clinical features [24]
  • Often asymptomatic
  • Symptoms of iron-deficiency anemia from chronic blood loss
  • Features of overt GI bleeding (rare)
• Diagnostics: EGD [23]
  • Distal linear erythematous streaks
  • Classically described as “watermelon stomach”
  • Biopsy in selected cases for diagnostic confirmation (e.g., when the diagnosis is uncertain) [23]
• Management
  • Endoscopic therapy, e.g., argon plasma coagulation, radiofrequency ablation, band ligation [24][25]
  • Management of chronic blood loss, e.g., iron supplementation, transfusions
  • Initial management of overt GI bleeding

While GAVE is associated with portal hypertension, it is not thought to be caused by portal hypertension, and medication to reduce CSPH is ineffective in the management of GAVE. [23]