Reprioritization of liver export protein synthesis in patients with decompensated alcoholic liver disease

Rafferty, M.J., McMillan, D.C. , Preston, T.C. , Hamid, R., Small, A.C., Joshi, N. and Stanley, A.J. (2016) Reprioritization of liver export protein synthesis in patients with decompensated alcoholic liver disease. Journal of Hepatology and Gastrointestinal Disorders, 2(3), 1000135. (doi: 10.4172/2475-3181.1000135)

Abstract

Background: Decompensated alcoholic liver disease is associated with abnormalities in protein synthesis. The relationship of this to reprioritisation of hepatic export proteins and markers of the systemic inflammatory response is unclear. We examined the longitudinal relationship between albumin and fibrinogen synthetic rates and disease severity in decompensated alcoholic liver cirrhosis. Patients and Methods: Hepatic protein synthetic rates were measured in patients with decompensated Childs grade B or C alcohol-related cirrhosis using a validated technique, based on incorporation of deuterated phenylalanine into the plasma pool of albumin and fibrinogen. As a measure of liver export protein reprioritisation, we calculated the fibrinogen and albumin synthetic rates and the Acute Phase Protein Quotient (APPQ; the ratio of these rates). Serum CRP and fibrin D-Dimer were recorded. Measurements were at baseline and on clinical recovery at 4-6 weeks. Results: 17 patients were studied. All patients had hypoalbuminaemia with elevated median C-reactive protein (CRP), D-dimer, bilirubin and prothrombin times. Median albumin and fibrinogen synthetic rates were reduced resulting in marginally increased APPQ. On follow up (n=10), there was reduction in Child-Pugh score (p<0.01), plasma concentrations of Fibrin D-dimer (p<0.01), CRP (p<0.01), bilirubin (p<0.01) and prothrombin time (p<0.01). Plasma albumin concentrations increased (p<0.01) and synthetic rates of both albumin (p<0.05) and fibrinogen (p<0.10) increased marginally such that median APPQ remained similar. Conclusion: Patients with decompensated alcohol-related cirrhosis had low albumin and fibrinogen synthetic rates and raised CRP indicative of systemic inflammation. On recovery, albumin synthetic rate increased and CRP levels fell, although albumin and fibrinogen synthetic rates remained below normal. Further studies assessing the interaction between protein synthesis and systemic inflammation in chronic liver disease are indicated.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Preston, Professor Tom and Small, Mrs Sandra and McMillan, Professor Donald and Stanley, Dr Adrian
• Authors: Rafferty, M.J., McMillan, D.C., Preston, T.C., Hamid, R., Small, A.C., Joshi, N., and Stanley, A.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing; College of Science and Engineering > Scottish Universities Environmental Research Centre
• Journal Name: Journal of Hepatology and Gastrointestinal Disorders
• Publisher: OMICS International
• ISSN: 2475-3181
• ISSN (Online): 2475-3181
• Published Online: 08 August 2016
• Copyright Holders: Copyright © 2016 Rafferty MJ, et al.
• First Published: First published in Journal of Hepatology and Gastrointestinal Disorders 2(3):1000135
• Publisher Policy: Reproduced under a Creative Commons License