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INTRODUCTION — Portal hypertension often develops in the setting of cirrhosis, schistosomiasis, or extrahepatic portal vein thrombosis. It is the result of resistance to portal blood flow and may lead to complications such as variceal bleeding and ascites.
This topic will review the development, clinical manifestations, and diagnosis of portal hypertension in adults. The causes of portal hypertension and the treatment of its complications are discussed in detail elsewhere:
●(See "Primary and pre-primary prophylaxis against variceal hemorrhage in patients with cirrhosis" and "Methods to achieve hemostasis in patients with acute variceal hemorrhage" and "Prevention of recurrent variceal hemorrhage in patients with cirrhosis".)
PATHOPHYSIOLOGY — Portal hypertension develops when there is resistance to portal blood flow and is aggravated by increased portal collateral blood flow . The resistance most often occurs within the liver (as is the case in cirrhosis), but it can also be prehepatic (eg, portal vein thrombosis) or posthepatic (eg, Budd-Chiari syndrome). (See "Noncirrhotic portal hypertension", section on 'Etiology'.)
There are two components to the increased resistance, structural changes and dynamic changes . Structural changes occur when there is distortion of the liver microcirculation by fibrosis, nodules, angiogenesis, and vascular occlusion. Dynamic changes occur when there is contraction of activated hepatic stellate cells and myofibroblasts that surround hepatic sinusoids and are in the fibrous septa and vascular smooth muscle cells of the hepatic vasculature. The dynamic changes are thought to be due to increased production of vasoconstrictors (eg, endothelins, angiotensin-II, norepinephrine, thromboxane A2) and reduced release of endothelial vasodilators (eg, nitric oxide).
As portal hypertension worsens, splanchnic blood flow is increased because of local release of vascular endothelial growth factor, nitric oxide, and other splanchnic vasodilators that cause splanchnic arteriolar vasodilation and angiogenesis. In addition to worsening the portal hypertension, these changes also lead to systemic hypotension, vascular underfilling, stimulation of endogenous vasoactive systems, plasma volume expansion, and increased cardiac output, factors that are important in the development of ascites. (See "Pathogenesis of ascites in patients with cirrhosis", section on 'Portal hypertension'.)
ETIOLOGY — The two most common causes of portal hypertension worldwide are cirrhosis and hepatic schistosomiasis . In Western countries, portal hypertension is typically the result of cirrhosis, with noncirrhotic portal hypertension accounting for less than 10 percent of cases. In other parts of the world, noncirrhotic portal hypertension due to causes such as schistosomiasis and portal vein thrombosis are the leading causes of portal hypertension (table 1 and table 2). (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis" and "Noncirrhotic portal hypertension", section on 'Etiology'.)
Among asymptomatic patients with cirrhosis, 80 to 90 percent will have an elevated portal pressure gradient (the difference in pressure between the portal vein and inferior vena cava, normally ≤5 mmHg), 40 percent of whom will have esophageal varices . Among those who do not have varices, varices develop at a rate of approximately 6 percent per year. (See "Primary and pre-primary prophylaxis against variceal hemorrhage in patients with cirrhosis", section on 'Screening for varices'.)
CLINICAL MANIFESTATIONS — Portal hypertension is often asymptomatic until complications develop. The clinical manifestations of portal hypertension include splenomegaly, abdominal wall collateral vessels, and thrombocytopenia. Many of the other clinical manifestations seen in patients with portal hypertension are related to the underlying cause of the portal hypertension (eg, spider angiomata and gynecomastia in a patient with cirrhosis) or the complications of portal hypertension. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis", section on 'Clinical manifestations' and "Noncirrhotic portal hypertension".)
Complications of portal hypertension include:
●Portal hypertensive gastropathy
●Spontaneous bacterial peritonitis
The clinical manifestations associated with these complications include:
●Variceal hemorrhage: Patients with variceal hemorrhage typically present with hematemesis and/or melena. If the bleeding is severe, there may be signs of hemodynamic instability. (See "Approach to acute upper gastrointestinal bleeding in adults", section on 'Bleeding manifestations'.)
●Portal hypertensive gastropathy: Portal hypertensive gastropathy (congestive gastropathy), while extremely common in patients with portal hypertension, is an uncommon cause of significant bleeding in these patients. When portal hypertensive gastropathy is the sole cause of bleeding, there is diffuse mucosal oozing with no other lesions such as varices to account for the gastrointestinal bleeding and anemia. The mucosa is friable, and bleeding presumably occurs when the ectatic vessels rupture. The severity of gastropathy is related to the level of portal pressure, the level of hepatic vascular resistance, and the degree of reduction in hepatic blood flow (See "Portal hypertensive gastropathy".)
●Ascites: Ascites is the accumulation of fluid within the peritoneal cavity. Patients with ascites typically report progressive abdominal distension that may be painless or associated with abdominal discomfort. Patients may also complain of weight gain, shortness of breath, early satiety, and dyspnea resulting from fluid accumulation and increased abdominal pressure. Physical examination findings include abdominal distension, dullness to percussion, and a fluid wave. (See "Evaluation of adults with ascites", section on 'Clinical manifestations'.)
●Spontaneous bacterial peritonitis: Clinical manifestations of spontaneous bacterial peritonitis include fever, abdominal pain, abdominal tenderness, and altered mental status. Some patients are asymptomatic and present with only mild laboratory abnormalities. The new onset of renal failure should prompt an investigation for spontaneous bacterial peritonitis. (See "Spontaneous bacterial peritonitis in adults: Clinical manifestations".)
●Hepatorenal syndrome: Hepatorenal syndrome refers to the development of renal impairment in the setting of cirrhosis. Arterial vasodilatation in the splanchnic circulation, which is triggered by portal hypertension, appears to play a central role in the hemodynamic changes and the decline in renal function in hepatorenal syndrome. Hepatorenal syndrome is characterized by a generally benign urine sediment, a very low rate of sodium excretion, and a progressive rise in the plasma creatinine concentration. (See "Hepatorenal syndrome".)
●Hepatic hydrothorax: Hepatic hydrothorax is defined as the presence of a pleural effusion in a patient with cirrhosis and no evidence of underlying cardiopulmonary disease. It results from the movement of ascitic fluid into the pleural space through defects in the diaphragm and is usually right-sided. The negative intrathoracic pressure generated during inspiration favors the passage of fluid from the peritoneal to the pleural space. Thus, many patients have only mild or no clinically detectable ascites. Patients usually present with shortness of breath, cough, hypoxemia, and/or chest discomfort. (See "Hepatic hydrothorax".)
●Hepatopulmonary syndrome: Hepatopulmonary syndrome is defined by the presence of liver disease, an increased alveolar-arterial gradient while breathing room air, and evidence for intrapulmonary vascular abnormalities. The clinical features of hepatopulmonary syndrome are the consequences of both hepatic and pulmonary dysfunction. More than 80 percent of patients present with symptoms of liver disease; the remainder experience dyspnea as their initial symptom. Hypoxia is a common finding. (See "Hepatopulmonary syndrome in adults: Prevalence, causes, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)
●Portopulmonary hypertension: As the name implies, portal hypertension-associated pulmonary hypertension (portopulmonary hypertension) refers to the presence of pulmonary hypertension in patients with portal hypertension. Patients with portopulmonary hypertension may present with fatigue, dyspnea, peripheral edema, chest pain, or syncope. (See "Portopulmonary hypertension", section on 'Clinical presentation'.)
●Cirrhotic cardiomyopathy: Cirrhotic cardiomyopathy is defined by chronic cardiac dysfunction in the setting of cirrhosis. It is characterized by decreased contractile responsiveness to stress or altered diastolic relaxation with electrophysiologic abnormalities. It is thought to be related to both portal hypertension and cirrhosis. (See "Definition and classification of the cardiomyopathies", section on 'Cirrhotic cardiomyopathy'.)
DIAGNOSIS — A diagnosis of portal hypertension can be made if a patient with a known risk factor for portal hypertension (eg, cirrhosis) has clinical manifestations of portal hypertension. In such cases, additional testing is not needed to confirm the diagnosis. However, if the diagnosis is in doubt, the hepatic venous pressure gradient (HVPG) can be determined to help confirm the diagnosis. The HVPG may also aid in the management of patients receiving nonselective beta blockers as part of their treatment. (See "Primary and pre-primary prophylaxis against variceal hemorrhage in patients with cirrhosis", section on 'Dose titration'.)
In patients with portal hypertension who do not have a previously identified risk factor, additional testing is required to determine the cause. (See 'Evaluation for an underlying cause' below.)
Hepatic venous pressure gradient — The HVPG is measured to approximate the gradient in pressure between the portal vein and the inferior vena cava (IVC). It can quantify the degree of portal hypertension due to sinusoidal resistance to blood flow (the most common cause of portal hypertension) (table 3). A normal HVPG is between 1 and 5 mmHg [3,4]. Portal hypertension is present if the HVPG is ≥6 mmHg. Portal hypertension typically becomes clinically significant when the HVPG is ≥10 mmHg, at which point varices may develop. Once the HVPG is ≥12 mmHg, patients are at risk for variceal bleeding and the development of ascites.
The portal pressure gradient can also be determined by direct measurement of the pressure in the portal vein and IVC. However, direct measurement of pressure in the portal is more invasive and is associated with a risk of intraperitoneal bleeding, so it is rarely used. (See 'Contraindications and limitations' below.)
Prognostic implications of HVPG thresholds — The risk of developing complications of portal hypertension and mortality rates increase as HVPG values increase . Various HVPG thresholds have been noted to have prognostic significance among patients with cirrhosis :
●In patients with compensated cirrhosis:
•HVPG 10 mmHg: Development of gastroesophageal varices, development of hepatocellular carcinoma, decompensation after surgery for hepatocellular carcinoma
•HVPG 12 mmHg: Variceal bleeding
•HVPG 16 mmHg: First clinical decompensation in patients with varices, mortality
●In patients with decompensated cirrhosis:
•HVPG 16 mmHg: Variceal rebleeding, mortality
•HVPG 20 mmHg (in patients with active variceal hemorrhage): Failure to control active variceal hemorrhage, low one-year survival
•HVPG 22 mmHg: Mortality in patient with alcoholic cirrhosis and acute alcoholic hepatitis
•HVPG 30 mmHg: Spontaneous bacterial peritonitis
Technique — The HVPG is calculated by subtracting the free hepatic venous pressure (FHVP, which reflects intra-abdominal pressure) from the wedged hepatic venous pressure (WHVP, which reflects portal venous pressure) [2,3]. These values are obtained by hepatic vein catheterization. The FHVP is determined by direct measurement of pressure in the hepatic vein. The WHVP is typically obtained by balloon occlusion of the hepatic vein, though it can also be estimated by wedging the catheter in the end tributaries of a hepatic vein. The balloon occlusion technique estimates the pressure from a larger portion of the liver than is obtained if the catheter is wedged in an end tributary.
After giving the patient light conscious sedation (eg, midazolam), a balloon-tipped catheter is introduced through the right jugular vein, often under ultrasound guidance . The catheter is advanced through the right atrium into the IVC and then into the right hepatic vein using fluoroscopic guidance. Alternatively, the femoral or antecubital veins can be used to for venous access.
To obtain the FHVP, the catheter is maintained in the hepatic vein 2 to 4 cm from its takeoff from the IVC. Typically, the difference in pressure between the IVC (measured at the hepatic vein ostium) and hepatic vein is ≤1 mmHg . A difference >1 mmHg suggests incorrect placement of the catheter (too deep into the hepatic vein). Pressure in the right atrium cannot be used to approximate the FHVP.
To obtain the WHVP, the hepatic vein is occluded by inflating the balloon at the tip of the catheter. A small amount of contrast dye (5 mL) is injected to confirm that the hepatic vein is occluded. If it is occluded, there should be no reflux of the dye above the balloon, and it should not washout via communications with other hepatic veins. Veno-venous communications may lead to washout of the contrast. These communications are rare in cirrhosis, though they are commonly seen in idiopathic portal hypertension [6,7]. The pressure should not be recorded until a stable value is obtained, which often takes 45 to 60 seconds .
Once the FHVP and WHVP are determined, the HVPG is calculated by subtracting the FHVP from the WHVP.
Contraindications and limitations — A limitation of the HVPG is that the WHVP is a measure of pressure within the hepatic sinusoids. As a result, pre-sinusoidal causes of portal hypertension may be associated with a normal FHVP, WHVP, and HVPG (table 3) . In addition, the HVPG may be normal with post-sinusoidal causes of portal hypertension that increase pressure both in the hepatic vein and in the sinusoids. However, in this situation, both the FHVP and the WHVP will be abnormal. If pre-sinusoidal portal hypertension is suspected and the HVPG is normal, direct measurement of the pressure in the portal vein and IVC can be obtained to determine the portal perfusion gradient. Direct measurement is performed using transhepatic or transvenous catheterization of the portal vein.
A relative contraindication to HVPG measurement is an allergy to iodinated contrast . This can be overcome by using carbon dioxide in place of contrast when confirming balloon occlusion. In patients with a history of cardiac arrhythmias, care should be taken when moving the catheter in the right atrium. Finally, patients with thrombocytopenia or an elevated international normalized ratio may require platelets or fresh frozen plasma, respectively, prior to performing an HVPG measurement. (See "Cirrhosis in adults: Overview of complications, general management, and prognosis", section on 'Thrombocytopenia or elevated INR'.)
Complications — Complications with HVPG measurement are uncommon and typically are related to local injury at the venous access site . Arrhythmias, which are usually transient, may be seen as the catheter is moved within the right atrium.
Associated procedures — Other procedures that can be performed at the same time as HVPG measurement include transjugular liver biopsy, measurement of hepatic blood flow and indocyanine green clearance, and wedged hepatic retrograde portography using carbon dioxide. (See "Transjugular liver biopsy", section on 'Technique' and "Tests of the liver's capacity to transport organic anions and metabolize drugs", section on 'Indocyanine green'.)
Noninvasive tests — Less invasive methods for diagnosing portal hypertension have been evaluated and include ultrasonography and transient elastography. However, neither test has replaced HVPG measurement for confirming the diagnosis.
Ultrasonography — Findings on transabdominal ultrasound with Doppler imaging may support a diagnosis of portal hypertension, but lack sensitivity . Findings that may be seen in patients with portal hypertension include :
●Portal flow mean velocity <12 cm/second
●Inversion of flow in the portal vein,
●Portosystemic collaterals (patent-paraumbilical vein, splenorenal collaterals, dilated left and short gastric veins)
●Portal vein diameter >13 mm
●Decreased or no respiratory variation in splenic and superior mesenteric vein diameter
●Portal/splenic/superior mesenteric vein thrombosis
Transient elastography — Transient elastography using ultrasound is a noninvasive method for detecting hepatic fibrosis. Studies are also looking at it as an option for noninvasively diagnosing portal hypertension. (See "Noninvasive assessment of hepatic fibrosis: Ultrasound-based elastography", section on 'Transient elastography'.)
Studies have reported areas under the receiver operating characteristic (AUC) curve of 0.77 to 0.99 for transient elastography predicting portal hypertension, with variable optimal liver stiffness cutoff values (13.6 to 34.9 kPa) [9-13]. It has been suggested that a value <13.6 kPa can be used to rule out portal hypertension, whereas a value ≥21.1 kPa can be used to rule it in . Values between 13.6 and 21.1 kPa are considered to be indeterminant.
Evaluation for an underlying cause — If portal hypertension is diagnosed in a patient who does not have a known risk factor for portal hypertension, the evaluation should first determine whether cirrhosis is present. If cirrhosis is present, additional testing to determine the cause is indicated. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis", section on 'Diagnosis'.)
DIFFERENTIAL DIAGNOSIS — In patients with signs and symptoms of portal hypertension, such as ascites or splenomegaly, it is important to consider causes of these findings other than portal hypertension. In most cases, the etiology of the findings can be differentiated from portal hypertension based on history, laboratory tests, and imaging studies. If the diagnosis is not clear, measurement of the hepatic venous pressure gradient can often confirm the presence of portal hypertension.
Examples of diagnoses that should be considered in addition to portal hypertension include:
●Hematemesis or melena: Peptic ulcer disease, Dieulafoy's lesion, Mallory-Weiss tear. (See "Causes of upper gastrointestinal bleeding in adults", section on 'Differential diagnosis'.)
●Ascites: Malignant ascites, nephrogenic ascites, tuberculosis. (See "Evaluation of adults with ascites", section on 'Etiology'.)
●Splenomegaly: Hematologic malignancy, infections, inflammation. (See "Approach to the adult with splenomegaly and other splenic disorders", section on 'Causes of splenomegaly'.)
●Bacterial peritonitis: Secondary bacterial peritonitis (eg, from intestinal perforation). (See "Spontaneous bacterial peritonitis in adults: Diagnosis", section on 'Distinguishing spontaneous from secondary bacterial peritonitis'.)
●Hydrothorax: Malignancy, sarcoidosis, nephrotic syndrome. (See "Diagnostic evaluation of a pleural effusion in adults: Initial testing".)
●Hypoxemia: Heart failure, central nervous system depression, muscular weakness. (See "Oxygenation and mechanisms of hypoxemia", section on 'Mechanisms of hypoxemia'.)
●Pulmonary hypertension: Idiopathic pulmonary arterial hypertension, valvular heart disease, connective tissue diseases. (See "Classification and prognosis of pulmonary hypertension in adults", section on 'Classification'.)
TREATMENT — Management in patients with portal hypertension is aimed at preventing and treating its complications. In the case of varices, this includes endoscopy to screen for varices, nonselective beta blockers and/or endoscopic variceal ligation to prevent bleeding, and treatment of active hemorrhage with endoscopic therapy or transjugular intrahepatic portosystemic shunt placement. In patients with ascites, treatment often starts with dietary sodium restriction and diuretics. (See "Primary and pre-primary prophylaxis against variceal hemorrhage in patients with cirrhosis" and "Methods to achieve hemostasis in patients with acute variceal hemorrhage" and "Prevention of recurrent variceal hemorrhage in patients with cirrhosis" and "Ascites in adults with cirrhosis: Initial therapy" and "Ascites in adults with cirrhosis: Diuretic-resistant ascites".)
Patients also require treatment for the underlying cause of the portal hypertension (eg, cirrhosis, schistosomiasis). (See "Cirrhosis in adults: Overview of complications, general management, and prognosis", section on 'General management' and "Noncirrhotic portal hypertension".)
The prevention and management of the other complications of portal hypertension are discussed in detail elsewhere:
SUMMARY AND RECOMMENDATIONS
●Portal hypertension develops when there is resistance to portal blood flow and is aggravated by increased portal collateral blood flow. The resistance most often occurs within the liver (as is the case in cirrhosis), but it can also be prehepatic (eg, portal vein thrombosis) or posthepatic (eg, Budd-Chiari syndrome). (See 'Pathophysiology' above.)
●The two most common causes of portal hypertension worldwide are cirrhosis and hepatic schistosomiasis. In Western countries, portal hypertension is typically the result of cirrhosis. In other parts of the world, noncirrhotic portal hypertension due to causes such as schistosomiasis and portal vein thrombosis are the leading causes of portal hypertension (table 1 and table 2). (See 'Etiology' above.)
●Portal hypertension is typically asymptomatic until complications develop. The clinical manifestations of portal hypertension include splenomegaly, abdominal wall collateral circulation, and thrombocytopenia. Many of the clinical manifestations seen in patients with portal hypertension are related to the underlying cause of the portal hypertension (eg, spider angiomata and gynecomastia in a patient with cirrhosis) or the complications of portal hypertension. (See 'Clinical manifestations' above.)
●The complications of portal hypertension include variceal hemorrhage, portal hypertensive gastropathy, ascites, and spontaneous bacterial peritonitis. Other complications include hepatorenal syndrome, hepatic hydrothorax, hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy. (See 'Clinical manifestations' above.)
●A diagnosis of portal hypertension can be made if a patient with a known risk factor for portal hypertension (eg, cirrhosis) has clinical manifestations of portal hypertension. In such cases, additional testing is not needed to confirm the diagnosis. However, if the diagnosis is in doubt, the hepatic venous pressure gradient (HVPG) can be determined to help confirm the diagnosis. (See 'Diagnosis' above.)
●The HVPG is measured to approximate the gradient in pressure between the portal vein and the inferior vena cava. It can quantify the degree of portal hypertension due to sinusoidal resistance to blood flow (the most common cause of portal hypertension). A normal HVPG is between 1 and 5 mmHg. Portal hypertension is present if the HVPG is ≥6 mmHg. Portal hypertension typically becomes clinically significant when the HVPG is ≥10 mmHg, at which point varices may develop. Once the HVPG is ≥12 mmHg, patients are at risk for variceal bleeding and the development of ascites. (See 'Hepatic venous pressure gradient' above.)
●In addition to management of the underlying cause of the portal hypertension (eg, cirrhosis, schistosomiasis), patients also need treatment to prevent and treat the complications of portal hypertension. In the case of varices, this includes endoscopy to screen for varices, nonselective beta blockers and/or endoscopic variceal ligation to prevent bleeding, and treatment of active hemorrhage with endoscopic therapy or transjugular intrahepatic portosystemic shunt placement. In patients with ascites, treatment often starts with dietary sodium restriction and diuretics. (See 'Treatment' above.)
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- Sánchez-Conde M, Miralles P, Bellón JM, et al. Use of transient elastography (FibroScan®) for the noninvasive assessment of portal hypertension in HIV/HCV-coinfected patients. J Viral Hepat 2011; 18:685.
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