Haemodynamic effects of acute and chronic administration of low-dose carvedilol, a vasodilating β-blocker, in patients with cirrhosis and portal hypertension

Background: Carvedilol is a non‐selective vasodilating β‐blocker with weak α1 receptor antagonism. Recent studies have demonstrated its potential as a portal hypotensive agent. Aim: To assess the haemodynamic effects and patient tolerability of the acute and chronic administration of low‐dose carvedilol. Methods: Haemodynamic measurements were performed in ten cirrhotic patients before and 1 h after the administration of 12.5 mg oral carvedilol. The study was repeated 4 weeks after daily administration of 12.5 mg carvedilol. Results: After acute administration of carvedilol, there was a 23% reduction in the hepatic venous pressure gradient from 16.37 ± 2.14 to 12.56 ± 3.91 mmHg (P < 0.05), with significant falls in the heart rate, mean arterial pressure and cardiac output. Chronic administration resulted in a further fall in the hepatic venous pressure gradient from a baseline of 16.37 ± 0.71 to 9.27 ± 1.40 mmHg (P < 0.001) with the mean arterial pressure being unaffected. The drug was well tolerated with only one patient experiencing asymptomatic hypotension. Conclusions: The results show that low‐dose carvedilol is an extremely potent portal hypotensive pharmacological agent, and is worthy of further investigation in large randomized trials to assess its effect in preventing variceal haemorrhage

The glycosylation pattern of alpha-1-acid glycoprotein (agp) could indicate progression from hepatitis to cirrhosis

This meeting abstract discusses the glycosylation pattern of alpha-1-acid glycoprotein (agp) could indicate progression from hepatitis to cirrhosi

Cerebral near infrared spectroscopy for the measurement of indocyanine green elimination in cirrhosis

Background: Indocyanine green (ICG) clearance is a useful indicator of hepatic function but most measurement methods are invasive. Aim: To validate a less invasive technique using cerebral near infrared spectrophotometry (NIRS) to measure ICG elimination, and to compare it with the established methods for the determination of ICG clearance in a group of normal controls and patients with cirrhosis. Method: NIRS was used to measure ICG elimination in 41 cirrhotic patients and nine healthy volunteers. The first 13 of the cirrhotic patients also had their ICG clearance measured by the conventional spectrophotometric technique. Results: NIRS ICG elimination rate (ICG‐k) and spectrophotometry ICG‐k values correlated strongly (r= 0.828, P < 0.001, n=13). There was a significant reduction in the mean NIRS‐k in cirrhotic patients and within Child–Pugh classes A, B, and C (P < 0.001). Conclusion: Measurement of ICG elimination by the NIRS method is at least as reliable as the conventional spectrophotometric technique in normals and in patients with cirrhosis. This technique merits further development for use as a bedside, less invasive liver function test

A preliminary evaluation of the differences in the glycosylation of alpha-1-acid glycoprotein between individual liver diseases.

During the acute phase response (APR) to tissue injury or infection, the liver is responsible for the level of mediators such as cytokines required at the site of inflammation and providing the essential components for wound healing and tissue repair. Additionally there are substantial alterations in the expression of plasma proteins of hepatic origin such as alpha-1-acid glycoprotein (AGP). The APR also results in alterations to the branching, sialylation and fucosylation of the oligosaccharide chains of AGP. This study investigated whether liver damage could be correlated with changes in AGP glycosylation in groups of patients with various liver diseases (alcoholic liver disease, hepatitis B, hepatitis C, cirrhosis). Hyperfucosylation occurred in all cases of liver disease, although the hepatitis B and C samples showed a more significant increase in comparison with the others. Additionally N-acetylgalactosamine (GalNAc) was detected in the majority of the hepatitis C samples, which was unexpected since this monosaccharide is not a usual component of the N-linked oligosaccharide chains. It was also determined by concanavalin (con) A chromatography that there is a shift towards the increased branching of the oligosaccharide chains in inflammatory liver diseases compared to normal serum

Endothelin‐1 contributes to maintenance of systemic but not portal haemodynamics in patients with early cirrhosis: a randomised controlled trial

BACKGROUND AND AIMS: Increased endothelin (ET)‐1 activity may contribute to the complications of cirrhosis and portal hypertension. The aim of this study was to assess the systemic and portal haemodynamic effects of selective ET‐A and ET‐B receptor antagonism in patients with cirrhosis. METHODS: Sixteen patients with cirrhosis and portal hypertension (aged 52 (1) years, Pugh score 6.2 (0.3)) underwent 24 studies with infusions of: (A) selective ET‐A antagonist, BQ‐123 (n = 8), at 1000 and 3000 nmol/min; (B) selective ET‐B antagonist, BQ‐788 (n = 8), at 100 and 300 nmol/min; or (C) matched saline placebo (n = 8) in a double blind randomised manner. Haemodynamic measurements were performed through pulmonary artery, hepatic venous, and femoral artery catheters. RESULTS: Baseline patient characteristics were well matched. Compared with placebo, BQ‐123 decreased mean arterial pressure (MAP −15 (11) mm Hg (−18%); p<0.02) and pulmonary vascular resistance index (PVRI −81 (54) dyn×s×m(2)/cm(5) (−64%); p<0.05), with no effect on hepatic venous pressure gradient (HVPG), cardiac index (CI), or systemic vascular resistance index (SVRI). Compared with placebo, BQ‐788 increased MAP (+11 (3) mm Hg (+12%); p<0.03) and SVRI (+1101 (709) dyn×s×m(2)/cm(5) (+50%); p<0.05), reduced CI (−1.0 (0.4) l/min/m(2) (−29%); p = 0.05) with no effect on HVPG or PVRI. CONCLUSIONS: ET‐1 contributes to maintenance of systemic and pulmonary haemodynamics without acutely affecting HVPG in patients with early cirrhosis. In this group of patients, the use of selective ET‐A and ET‐B antagonists for the management of variceal haemorrhage is likely to be limited