Ascites is the most frequent complication of cirrhosis, signaling the transition from compensated to decompensated liver disease. While traditionally linked to portal hypertension, arterial vasodilation, and renal sodium retention, previous research has broadened our understanding of its pathophysiology. The hepatic and splanchnic lymphatic systems are increasingly recognized as potential contributors to decompensation in cirrhosis. The elevated sinusoidal pressure in cirrhosis markedly increases lymph production, which is initially compensated by expanded lymphatics and lymphangiogenesis. However, progressive cirrhosis impairs lymphatic function by inducing abnormal lymphangiogenesis, vessel dilation, and poor contractility, which collectively reduce drainage. When lymph overproduction exceeds the maximum drainage capacity of the lymphatic system, the fluid leaks through the subcapsular lymphatics, leading to leakage of protein-rich lymph through the liver surface into the peritoneal cavity—a phenomenon often referred to as a “weeping liver.” The osmotic gradient of this protein-rich fluid, combined with hydrostatic pressures and lymphatic failure, may draw additional fluid from the splanchnic circulation and contribute to ascites development and progression. Simultaneously, dysfunction of the gut-splanchnic lymphatic axis may promote intestinal edema, bacterial translocation, and systemic inflammation, thereby reinforcing portal hypertension and contributing to downstream manifestations such as intestinal lymphangiectasia and refractory ascites. Yet, despite its pathophysiological relevance, the contribution of lymphatic failure to the complications of cirrhosis remains widely underappreciated. Recognizing this critical axis may help identify novel therapeutic targets in patients with cirrhosis. This review provides a detailed overview of lymphatic failure as a contributor to altered fluid dynamics and secondary complications in cirrhosis, offering a contextual evaluation of its therapeutic implications.
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Kumar et al. (2026) studied this question.
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