1. Epidemiology and Incidence

Portal hypertension is the primary driver of progression from compensated to decompensated cirrhosis. As the underlying liver disease worsens and the hemodynamic burden increases, the risk of developing varices and subsequent bleeding rises significantly.

• Prevalence of esophageal varices:
  • In compensated cirrhosis, varices are found in approximately 50–60% of patients.
  • This number increases to as high as 85% in patients with decompensated cirrhosis.
• Annual first-bleed incidence: For patients with identified high-risk varices, the risk of a first hemorrhage is about 10–15% per year.
• Mortality: Despite advances in care, the six-week mortality rate following an acute variceal hemorrhage remains high at 15–20%.
• Geographic and etiologic variations:
  • In regions where schistosomiasis is endemic, non-cirrhotic portal hypertension is a common cause.
  • In Western countries, where alcohol-related liver disease and viral hepatitis are more prevalent, cirrhotic portal hypertension and its complications dominate.
• Data in the critically ill: Specific data on variceal bleeding in the ICU are limited. However, factors common in critical illness, such as multi-organ failure, coagulopathy, and the need for invasive procedures, are thought to substantially increase the risk of bleeding.

2. Pathophysiology of Portal Hypertension

Elevated portal pressure is the result of two concurrent hemodynamic processes: an increase in intrahepatic vascular resistance and a rise in portal venous inflow from splanchnic hyperemia. This dual mechanism drives the formation of collateral vessels, including esophageal varices.

A. Increased Intrahepatic Vascular Resistance

• Structural Component: This is a fixed resistance caused by the physical distortion of the liver’s architecture. Progressive fibrosis and the formation of regenerative nodules compress sinusoids and hepatic venules, obstructing blood flow.
• Functional Component: This is a dynamic and modifiable resistance, accounting for roughly 30% of the total. It stems from hepatic endothelial dysfunction, which leads to decreased production of the vasodilator nitric oxide (NO) and increased activity of vasoconstrictors like endothelin-1. This results in active contraction of hepatic stellate cells and myofibroblasts, further narrowing the sinusoidal channels.

B. Splanchnic Vasodilation and Collateral Formation

• In contrast to the liver, the splanchnic (gut) circulation experiences profound vasodilation, primarily driven by overproduction of NO. This creates a hyperdynamic circulatory state, characterized by increased cardiac output and a massive influx of blood into the portal system.
• This increased portal inflow exacerbates the already high portal pressure.
• When the hepatic venous pressure gradient (HVPG) reaches a threshold of ≥10 mm Hg, the body forms portosystemic collaterals (varices) via angiogenesis to decompress the high-pressure portal system.

3. Major Risk Factors

The risk of developing portal hypertension and variceal bleeding is modulated by a combination of the underlying etiology, the severity of liver disease, coexisting medical conditions, and crucial social determinants of health.

• Etiologies of Cirrhotic Portal Hypertension: The most common causes include alcoholic liver disease, chronic viral hepatitis (B and C), non-alcoholic steatohepatitis (NASH), and, globally, schistosomiasis. Less common causes include primary biliary cholangitis and Budd–Chiari syndrome.
• Non-Cirrhotic Portal Hypertension (NCPH): Some patients develop portal hypertension without cirrhosis. Key causes include idiopathic non-cirrhotic portal hypertension (INCPH) and extrahepatic portal vein thrombosis.
• Comorbidities: Several conditions accelerate liver disease progression and increase bleeding risk. These include obesity, diabetes, ongoing hepatocellular injury (e.g., alcohol relapse), renal dysfunction, and systemic infections (which increase portal pressure).
• Social Determinants of Health: These factors are critical but often overlooked. Barriers to care, such as limited access to medications (e.g., NSBBs), low health literacy, poor adherence to follow-up appointments, and socioeconomic challenges can prevent effective screening and prophylaxis.

4. Clinical Presentation of Variceal Hemorrhage

An acute variceal bleed is a medical emergency that manifests as overt gastrointestinal blood loss and signs of hemodynamic compromise. Recognizing early warning signs and common precipitants can guide prompt, life-saving intervention.

Symptoms and Signs

• Symptoms: The most dramatic symptom is hematemesis (vomiting of red blood or “coffee grounds”). Other symptoms include melena (black, tarry stools), hematochezia (passage of fresh blood per rectum, indicating a very brisk bleed), dizziness, syncope, and profound weakness.
• Signs: Physical exam often reveals hypotension and tachycardia. Stigmata of chronic liver disease are typically present, such as splenomegaly, ascites, and caput medusae (dilated periumbilical veins). Key lab findings include thrombocytopenia (platelets <150×10³/mm³).

Early Warning Signs and Precipitants

• Early Warning Signs: A gradual drop in hemoglobin (progressive anemia), new or worsening ascites, or the appearance of portal hypertensive gastropathy on a surveillance endoscopy can herald an impending bleed.
• Common Precipitants: Bleeding is often triggered by a secondary event that acutely increases portal pressure. Common triggers include bacterial infections (especially spontaneous bacterial peritonitis), acute kidney injury, an alcohol binge, or any activity that increases intra-abdominal pressure (e.g., severe coughing, straining).

5. Summary and Clinical Implications

Effective management of portal hypertension hinges on early identification of at-risk patients using a combination of clinical, laboratory, and noninvasive tools. This allows for targeted primary prophylaxis to prevent the first variceal bleed. A holistic approach that addresses comorbidities and social factors is essential to optimize outcomes.

High-Risk Populations for Intervention

• Patients with established CSPH (HVPG ≥10 mm Hg or noninvasive equivalent).
• Endoscopic findings of large varices or those with red wale marks.
• Advanced liver dysfunction, as indicated by a high Child-Pugh or MELD score.
• Presence of significant comorbidities like renal failure or active infection.

Early Interventions and Surveillance

• Primary Prophylaxis: The cornerstones are nonselective β-blockers (e.g., carvedilol, propranolol) to reduce portal inflow or endoscopic variceal ligation (EVL) to mechanically obliterate varices.
• Surveillance: Strategy depends on risk. Patients with cirrhosis and no varices are rescreened every 2-3 years. Those with small varices are screened every 1-2 years. Noninvasive risk stratification (LSM + platelets) can help tailor surveillance intervals.

Research Gaps and Key Takeaways

• Research Gaps: More data are needed on the epidemiology and outcomes of variceal hemorrhage specifically in critically ill populations. The development and validation of dynamic, real-time noninvasive markers of portal pressure remain a key area of research.
• Key Takeaways:
  • Understanding the dual hemodynamic drivers of portal hypertension (resistance + inflow) is fundamental to pharmacologic prevention with β-blockers.
  • Social determinants and comorbidities are modifiable risk factors. Integrating patient education, social support services, and comorbidity management into routine care is critical for success.