Time course of compromised urea synthesis in patients with alcoholic hepatitis

<p><b>Objectives</b>: Alcoholic hepatitis (AH) markedly decreases the urea synthesis capacity. We aimed to investigate the time course of this compromised essential liver function in patients with AH and its relation to treatment and survival.</p> <p><b>Materials and methods</b>: Thirty patients with AH were included in a prospective cohort study. We measured the substrate-independent urea synthesis capacity, i.e., the functional hepatic nitrogen clearance (FHNC), in the patients at study entry and again at three months (survivors/available: <i>n</i> = 17). Patients with severe disease (Glasgow Alcoholic Hepatitis Score ≥9, <i>n</i> = 17) were randomized to receive either prednisolone or pentoxifylline and were in addition examined after 14 days (<i>n</i> = 9).</p> <p><b>Results</b>: FHNC (normal range = 25–45 L/h) was markedly decreased at study entry (median = 5.6 (IQR = 3.0–9.6) L/h) and increased by three-fold in survivors at three months (15.1 (12.0–22.9) L/h; <i>p</i> < .001). In patients with severe AH, FHNC was also increased after 14 days of pharmacologic treatment and showed the greatest increase in the patients taking prednisolone (prednisolone 25.4 (20.6–26.2) L/h vs. pentoxifylline 12.3 (8.0–15.3) L/h; <i>p</i> = .05). FHNC at study entry was lower in 90-day non-survivors than in survivors (<i>p</i> = .04).</p> <p><b>Conclusions</b>: The decrease in the urea synthesis capacity in patients with AH was the most marked in short-term non-survivors and partly recovered in survivors at three months. In patients on pharmacologic treatment, recovery was observed already after 14 days, and it was nearly complete in those on prednisolone. Thus, metabolic liver failure in AH seems to be prognostically important, is potentially reversible, and may recover more rapidly following treatment with prednisolone.</p

Relationship between the functional hepatic nitrogen clearance and galactose elimination capacity.

<p>Relationship between the functional hepatic nitrogen clearance (FHNC) and galactose elimination capacity (GEC) in patients with non-severe (hollow circles) (GAHS<9, N = 8) and severe (circles) (GAHS≥9, N = 10) alcoholic hepatitis. No significant correlation was observed between the FHNC and GEC.</p

Baseline characteristics of the patients with alcoholic hepatitis and healthy controls.

<p>Baseline characteristics of the patients with alcoholic hepatitis and healthy controls.</p

Relationship between the functional hepatic nitrogen clearance and Model for End-Stage Liver Disease score.

<p>Relationship between the functional hepatic nitrogen clearance (FHNC) and Model for End-Stage Liver Disease (MELD) score in patients with non-severe (hollow circles) (GAHS<9, N = 9) and severe (circles) (GAHS≥9, N = 11) alcoholic hepatitis. The linear regression line shows the correlation (rho = -0.49; P<0.05).</p

Functional hepatic nitrogen clearance in patients with non-severe and severe alcoholic hepatitis and healthy controls.

<p>Functional hepatic nitrogen clearance (FHNC) in patients with non-severe (GAHS<9, N = 9) and severe (GAHS≥9, N = 11) alcoholic hepatitis and healthy controls (N = 7). The solid horizontal lines indicate the mean values. The FHNC was decreased in the AH patients compared with the healthy controls (P<0.01) and the largest decrease was observed in those with severe AH (P<0.05).</p