Portal pressure-lowering drugs efficiently decrease liver stiffness

Introduction: Liver stiffness (LS) measured by transient elastography (TE) is increasingly used to non-invasively assess liver fibrosis. Although LS highly correlates with portal pressure it still remains unresolved whether LS could serve as a non-invasive parameter to monitor the pharmacological efficiency of portal pressure-lowering drugs such as propranolol and others to prevent variceal bleeding.

Methods: Thirty male Wistar rats were allocated into groups (n = 6) and fibrosis was induced with i.p. thioacetamide (TAA) injections (200 mg/kg bodyweight twice a week) for 8 weeks. Under isoflurane sedation, 1 ml 0.9% NaCl as control, NO-releasing glyceroltrinitrate (GTN) (0.25 g), non-selective ß-blocker Propranolol (0.6 mg) and AT1 antagonist Losartan (10 mg/kg bodyweight) were administered intravenously to lower portal pressure. Pressures (arterial and portal) were invasively measured in real-time using the Powerlab device (AD Instruments, New Zealand) for 30 min after drug injection. LS was measured continuously using µFibroscan (Echosens, Paris).

Results: TAA treatment caused a significant increase of LS (3.9 vs. 19.4 kPa) and portal pressure (8.6 vs. 12.3 mmHg) compared to untreated control animals while mean arterial pressure (MAP) and heart rate remained unchanged. GTN and Losartan significantly lowered portal pressure from 12.3 to 8.7 mmHg and LS from 19.3 to 13.9 kPa. In addition, MAP decreased significantly from 86.5 to 61.8 mmHg. Propranolol injection drastically reduced the heart rate but only a slight and non-significant decrease of LS, portal pressure and MAP were observed. No significant changes in LS were recorded in control animals following NaCl injection. Pearson correlation analysis showed an excellent association (P < 0.01) between decrease of LS and portal pressure for GTN (r = 0.565), Losartan (r = 0.632) but not Propranolol (r = 0.117). Portal pressure itself correlated best with MAP (r = 0.715).

Conclusion: Our data indicate that LS allows to non-invasively monitor the pharmacological changes in systemic hemodynamics followed by portal-pressure lowering drugs. Even at highly cirrhotic values, LS remains responsive to changes in perfusion pressures. Thus, LS could help to optimize drug administration in the future.