Epidemiology

The estimated global prevalence of cirrhosis and other chronic liver disease was above 1.5 billion in 2017.[10] In 2010, more than 1,000,000 people died from cirrhosis worldwide.[11] The age-standardized cirrhosis mortality rate decreased by 22%, largely due to the decreasing cirrhosis mortality rates in China, the US, and countries in Western Europe.[11]

In Europe, a decline in mortality from cirrhosis in the first half of the 1980s was related to a decrease in per capita alcohol consumption.[12] However, in the 1990s, the UK saw a steep rise in cirrhosis mortality related to increasing alcohol consumption. In 2002, mortality from cirrhosis in Scotland was 45.2 per 100,000 in men and 19.9 per 100,000 in women - one of the highest rates in Western Europe.[13]

In the US, in 2018 there were 4.5 million adults with diagnosed liver disease (constituting 1.8% of the adult population) and in 2022 there were 54,803 deaths attributable to chronic liver disease and cirrhosis (16.4 per 100,000 population).[14] Using National Health And Nutrition Examination Survey data, the prevalence of cirrhosis in the United States has been estimated to be 0.27%.[15]

Gastroesophageal varices are present in almost half of patients at the time of diagnosis of cirrhosis.[16] The 1-year incidence of bleeding is 5% with small varices, and 15% with large varices.[4] Development of varices and their progression from small to large occur at a rate of approximately 7% to 8% per year.[4][8] One clinical audit in the UK suggested that variceal hemorrhage is associated with overall 30-day mortality of 15%.[17] A systematic review of cohort studies (that assessed acute variceal hemorrhage outcomes) reported a 6-week mortality rate of 18%.[18] Without additional therapy, late rebleeding occurs in approximately 60% of patients within 1-2 years of the index event.[4][19]

Risk factors

Portal hypertension leading to the formation of porto-systemic collaterals is the underlying cause of esophageal varices. Although a small proportion of patients may have varices when the hepatic venous pressure gradient (HVPG) is >5 mmHg and <10 mmHg (mild portal hypertension), varices mostly develop when the HVPG is >10 mmHg.[22] HVPG ≥10 mmHg has been defined as the threshold for clinically significant portal hypertension.[5]

In the majority of patients this is due to chronic liver disease (of any etiology) resulting in cirrhosis. In the US, alcoholic liver disease is the most common cause of cirrhosis. However, metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease) is an increasingly common cause of cirrhosis, and chronic viral hepatitis (B and C) is also relevant.[23][24]​ Direct antiviral agents are expected to reduce the burden of chronic hepatitis C.[25]

Autoimmune liver disease, hemochromatosis, and Wilson disease may also result in cirrhosis. Less commonly, other recognized causes of portal hypertension, such as Budd-Chiari syndrome, myeloproliferative disorders, and sarcoidosis, may also lead to esophageal variceal development.

Multiple studies have shown that medium to large varices are more likely to bleed than small varices.[4][26][27]

Variceal size is the most important factor for prediction of variceal bleeding, with the greatest risk at 15% per year for large varices.[3][4]

Endoscopic red wale marks (defined as longitudinal dilated venules resembling whip marks on the variceal surface) have been shown to predict increased risk of variceal bleeding.[3][5]

Decompensated cirrhosis (Child-Pugh class B/C) has been shown to predict increased risk of variceal bleeding.[3]

Patients with decompensated cirrhosis have a higher risk of esophageal varices.

Ascites is thought to be a sign of increased portal blood flow and pressure in esophageal varices. Approximately half of patients presenting with esophageal variceal bleeding have concomitant ascites.

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