title: Lactulose reduces bacterial DNA translocation, which worsens neurocognitive shape in cirrhotic patients with minimal hepatic encephalopathy.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.|Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Moratalla
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.|Unit for the Clinical Management of Digestive Diseases, Hospital Universitario Valme de Sevilla, Sevilla, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ampuero
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.|Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bellot
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.|Unit for the Clinical Management of Digestive Diseases, Hospital Universitario Valme de Sevilla, Sevilla, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Gallego-Durán
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.|Servicio de Farmacología Clinica, Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Zapater
authors.affiliation: Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain.
authors.forename: Manuela
authors.initials: M
authors.lastname: Roger
authors.affiliation: Unit for the Clinical Management of Digestive Diseases, Hospital Universitario Valme de Sevilla, Sevilla, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Figueruela
authors.affiliation: Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Martínez-Moreno
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.|Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: González-Navajas
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.|Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
authors.forename: José
authors.initials: J
authors.lastname: Such
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.|Unit for the Clinical Management of Digestive Diseases, Hospital Universitario Valme de Sevilla, Sevilla, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gómez
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.|Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain.|Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
mesh_terms: D000368:Aged; D000641:Ammonia / Q000097:blood; D018988:Bacterial Translocation / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D003071:Cognition; D004269:DNA, Bacterial / Q000032:analysis; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D006501:Hepatic Encephalopathy / Q000175:diagnosis*; D006801:Humans; D007792:Lactulose / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011594:Psychometrics; D012720:Severity of Illness Index; D013030:Spain
chemical_list: D015415:Biomarkers; D004269:DNA, Bacterial; D005765:Gastrointestinal Agents; D007792:Lactulose; D000641:Ammonia
keywords: ammonia; bacterial translocation; cirrhosis; lactulose; minimal hepatic encephalopathy