Hepato-splanchnic fluxes during exercise in patients with cirrhosis—a pilot study

Abstract

In cirrhotic patients, compromised hepatocyte function combined with disturbed hepatic blood flow could affect hepato-splanchnic substrate and metabolite fluxes and exacerbate fatigue during exercise. Eight cirrhotic patients performed incremental cycling trials (3 × 10 min; at light (28 [19–37] W; median with range), moderate (55 [41–69] W), and vigorous (76 [50–102] W) intensity). Heart rate increased from 68 (62–74) at rest to 95 (90–100), 114 (108–120), and 140 (134–146) beats/min (P < 0.05), respectively. The hepatic blood flow, as determined by constant infusion of indocyanine green with arterial and hepatic venous sampling, declined from 1.01 (0.75–1.27) to 0.69 (0.47–0.91) L/min (P < 0.05). Hepatic glucose output increased from 0.6 (0.5–0.7) to 1.5 (1.3–1.7) mmol/min, while arterial lactate increased from 0.8 (0.7–0.9) to 9.0 (8.1–9.9) mmol/L (P < 0.05) despite a rise in hepatic lactate uptake. Arterial ammonia increased in parallel to lactate from 47.3 (40.1–54.5) to 144.4 (120.5–168.3) μmol/L (P < 0.05), although hepatic ammonia uptake increased from 19.5 (12.4–26.6) to 69.5 (46.5–92.5) μmol/min (P < 0.05). Among the 14 amino acids measured, glutamate was released in the liver, while the uptake of free fatty acids decreased. During exercise at relatively low workloads, arterial lactate and ammonia levels were comparable to those seen in healthy subjects at higher workloads, while euglycemia was maintained due to sufficient hepatic glucose production. The accumulation of lactate and ammonia may contribute to exercise intolerance in patients with cirrhosis.