Lactulose reduces bacterial DNA translocation, which worsens neurocognitive shape in cirrhotic patients with minimal hepatic encephalopathy.

Abstract

BACKGROUND & AIMS:

Minimal hepatic encephalopathy is associated with poor prognosis and mortality in patients with cirrhosis. We aimed at investigating whether bacterial-DNA translocation affects hyperammonaemia and neurocognitive scores in patients with mHE according to the use of lactulose.

METHODS:

Observational study including 72 mHE cirrhotic patients, as defined by a psychometric hepatic encephalopathy score (PHES)<-4 and/or a critical flicker frequency (CFF)<39 Hz. Bacterial-DNA, serum ammonia, pro-inflammatory cytokines and nitric oxide levels were evaluated. A second cohort of 40 lactulose-untreated patients were evaluated before and 6-month after lactulose administration (30-60 mL/d).

RESULTS:

In the first cohort, bacterial-DNA rate was significantly higher in patients without lactulose (39% vs 23%, P=.03). Serum ammonia and inflammatory markers were significantly increased in patients with bacterial-DNA, regardless the use of lactulose, and correlated with the amount of amplified bacterial-DNA. Neurocognitive scores were significantly worse in bacterial-DNA positive vs negative patients (PHES -7.6±1.1 vs -5.5±1.0; CFF 32.5±2.6 vs 36.2±2.8, P=.01). Lactulose was associated with improved neurocognitive scores in patients without bacterial-DNA. Serum ammonia levels inversely correlated with neurocognitive scores in patients with bacterial-DNA (PHES r=-.84; CFF r=-.72, P=.001). In the second cohort, lactulose reduced bacterial-DNA translocation (36%-16%, P=.02). Neurocognitive scores were significantly improved in bacterial-DNA positive patients who cleared bacterial-DNA during the period on lactulose. Serum ammonia levels correlated with both neurocognitive scores in patients with bacterial-DNA, either before or after lactulose.

CONCLUSION:

Bacterial-DNA translocation worsens neurocognitive scores in mHE patients and it is reduced by lactulose, enhancing the relevance of controlling bacterial antigen translocation in these patients.

• Authors: Alba Moratalla, Javier Ampuero, Pablo Bellot, Rocío Gallego-Durán, Pedro Zapater, Manuela Roger, Blanca Figueruela, Belén Martínez-Moreno, José M González-Navajas, José Such, Manuel Romero-Gómez, Rubén Francés
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 37 Issue 2 Pg. 212-223 (02 2017) ISSN: 1478-3231 [Electronic] United States
• PMID: 27388776 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• DNA, Bacterial
• Gastrointestinal Agents
• Lactulose
• Ammonia

Topics

• Aged
• Ammonia (blood)
• Bacterial Translocation (drug effects)
• Biomarkers (blood)
• Cognition
• DNA, Bacterial (analysis)
• Female
• Gastrointestinal Agents (administration & dosage)
• Hepatic Encephalopathy (diagnosis)
• Humans
• Lactulose (administration & dosage)
• Liver Cirrhosis (complications)
• Male
• Middle Aged
• Prospective Studies
• Psychometrics
• Severity of Illness Index
• Spain