Discussion:
Since its introduction in 1986, EVL (Endoscopic Variceal Ligation) has been widely recommended as the first-line treatment for esophageal varices in liver cirrhosis by clinical guidelines in numerous countries. When compared to EIS (Endoscopic Injection Sclerotherapy), EVL demonstrates significant superiority in terms of rebleeding rate, variceal eradication rate, and complications[1-6]. Consequently, an increasing number of clinicians consider EVL as the preferred treatment for patients experiencing esophageal variceal rupture and bleeding. Reported complications of EVL mainly encompass esophageal stenosis, ulcer bleeding, esophageal perforation, esophageal hematoma[7-9], pneumonia, and spontaneous bacterial peritonitis[10-12]. However, there have been few reports documenting liver function failure following EVL surgery. Through a comprehensive literature review, we discovered that only one case of elevated bilirubin levels with subsequent liver dysfunction after EVL surgery has been documented thus far. This case involved a 51-year-old female patient with primary biliary cholangitis (PBC) and esophageal variceal rupture and bleeding, who underwent EVL treatment. Following the procedure, the patient experienced an increase in bilirubin levels from 4.0mg/dL to 9.5mg/dL, ultimately necessitating liver transplantation due to the worsening of liver function failure[13].
The mechanism behind liver function failure after EVL surgery remains unclear. In the context of cirrhosis, both hepatic and splanchnic systemic oxygen uptake (VO2) are reduced[14, 15]. Our hypothesis suggests that the cause of liver failure in patients after EVL may be attributed to increased portal pressure, decreased cardiac output, and reduced oxygen delivery following the procedure. Previous studies have reported that 68% of patients undergoing endoscopic variceal ligation experience an elevation in portal vein pressure[16]. It is postulated that the sudden rise in portal vein pressure could exacerbate liver congestion, impair oxygen utilization by liver cells, and subsequently lead to liver cell necrosis. However, a study conducted in 2003 revealed no significant change in the portal vein pressure gradient before and after EVL surgery in patients with liver cirrhosis and esophageal variceal rupture and bleeding[17]. Consequently, further investigation is required to explore whether an increase in portal vein pressure occurs after EVL surgery.
As early as 1996, reports emerged highlighting a related phenomenon wherein EVL surgery may exacerbate liver tissue ischemia and hypoxia. This study observed a decrease in cardiac output and oxygen delivery immediately after EVL surgery, although the underlying causes and implications were not fully understood at the time[18]. This hypoxic condition is particularly pronounced in patients with varicose veins and anemia. Research has shown that patients with liver cirrhosis exhibit a high dynamic circulation, which enhances oxygen delivery but impairs the uptake and utilization of oxygen by tissues, resulting in sustained liver cell hypoxia[19]. Furthermore, all tissues of patients with liver cirrhosis experience a certain degree of hypoxia due to arteriovenous shunting[20]. Therefore, a sudden decrease in cardiac output and oxygen delivery could further intensify liver cell hypoxia, leading to acute massive necrosis of liver cells.Overall, the precise mechanisms underlying liver function failure after EVL surgery necessitate further investigation. The potential impact of increased portal pressure, reduced cardiac output, oxygen delivery, and the exacerbation of liver cell hypoxia requires comprehensive exploration. Future research should focus on elucidating these mechanisms to enhance our understanding and potentially develop strategies for mitigating liver function failure following EVL surgery.
Furthermore, there have been reports suggesting the potential involvement of endogenous nitric oxide in the regulation of systemic hemodynamics in patients with compensated cirrhosis. Serum nitrate and nitrite, which are metabolic byproducts of endogenous nitric oxide, exhibit a sudden decrease in concentration in patients after EVL[21, 22]. Previous studies have demonstrated that nitric oxide can alleviate ischemia-reperfusion injury of the liver and expedite the recovery of liver function[23]. Nitric oxide’s protective effects on liver tissue may play a role in the context of EVL surgery, although further research is required to investigate the specific mechanisms and implications of nitric oxide modulation in this setting.
It has been reported in studies that compared to patients with Child-Pugh A/B, patients with Child-Pugh C cirrhosis exhibit higher rates of rebleeding and mortality following EVL[24]. In the case of our patient, their liver function reserve was evaluated as Child-Pugh B upon admission. However, after undergoing emergency EVL, the patient experienced a significant increase in bilirubin levels and developed coagulation dysfunction. We speculate that these effects may be attributed to the blockage of collateral circulation caused by acute bleeding and the impact of EVL surgery, particularly in the context of poor liver function reserve. This could exacerbate liver congestion symptoms. Additionally, the decrease in cardiac output further intensifies the ischemia and hypoxia experienced by liver cells, ultimately leading to acute necrosis and liver failure. It is important to note that the occurrence of liver failure after EVL surgery is relatively rare, and our understanding of its underlying mechanism is based on plausible pathological and physiological considerations. Further research is required to delve into the intricate mechanisms involved and provide conclusive evidence.