Correlation of endoscopic ultrasound-guided portal pressure gradient measurements with hepatic venous pressure gradient: a prospective study.

BACKGROUND: Hepatic venous portal gradient (HVPG) measurement remains the gold standard for estimating portal pressure gradient (PPG). This study aimed to evaluate the correlation between endoscopic ultrasound (EUS)-guided PPG and HVPG in patients with chronic portal hypertension. METHODS: Patients with chronic portal hypertension in whom HVPG assessment was clinically indicated were invited to undergo transjugular HVPG and EUS-PPG with a 22-G needle in separate sessions for comparison. Intraclass correlation coefficient (ICC) and the Bland-Altman method were used to evaluate the agreement between techniques. RESULTS: 33 patients were included. No significant differences in technical success were observed: EUS-PPG (31/33, 93.9%) vs. HVPG (31/33, 93.9%). Overall, 30 patients who underwent successful EUS-PPG and HVPG were analyzed. Correlation between the two techniques showed an ICC of 0.82 (0.65-0.91). Four patients had major discrepancies (≥5 mmHg) between HVPG and EUS-PPG. No significant differences in adverse events were observed. CONCLUSIONS: The correlation between EUS-PPG and HVPG was almost perfect. EUS-PPG could be a safe and reliable method for direct PPG measurement in patients with cirrhosis and a valid alternative to HVPG.

Endoscopic ultrasound-guided gallbladder drainage with long-term lumen-apposing metal stent indwell: 1-year results from a prospective nationwide observational study.

BACKGROUND AND AIM: This study aimed to determine safety and risk factors for adverse events (AEs) of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) with long-term indwell of lumen-apposing metal stents (LAMS). METHODS: This study is a multicenter prospective observational study on consecutive high surgical-risk patients requiring gallbladder drainage who underwent EUS-GBD with LAMS over 12 months. Centralized telephone follow-up interviews were conducted every 3 months for 1 year. Patients were censored at LAMS removal, cholecystectomy, or death. AE-free survival was determined using log-rank tests. Cumulative risks were estimated using life-table analysis. RESULTS: Eighty-two patients were included (53.7% male, median [interquartile range] age of 84.6 [76.5-89.8] years, and 85.4% with acute cholecystitis). Technical success was achieved in 79 (96.3%), and clinical success in 73 (89%). No patient was lost to follow-up; 45 patients (54.9%) completed 1-year follow-up with in situ LAMS. Median (interquartile range) LAMS indwell time was 364 (47-367) days. Overall, 12 (14.6%) patients presented 14 AEs, including 5 (6.1%) recurrent biliary events (3 acute cholangitis, 1 mild acute pancreatitis, and 1 acute cholecystitis). Patients with pancreatobiliary malignancy had an increased risk of recurrent biliary events (33% vs 1.5%, P = 0.001). The overall 1-year cumulative risk of recurrent biliary events was 9.7% (4.1-21.8%). The 1-year risk of AEs and of severe AEs was 18.8% (11-31.2%) and 7.9% (3.3-18.2%), respectively. Pancreatobiliary malignancy was the single risk factor for recurrent biliary events; LAMS misdeployment was the strongest risk factor for AEs. CONCLUSIONS: Long-term LAMS indwell does not increase the risk of delayed AEs following EUS-GBD.

Endoscopic management of pancreatic collections. Endoscopic Ultrasound Group, Spanish Society of Digestive Endoscopy (GSEED-USE) Clinical Guidelines.

Acute pancreatitis is associated with significant morbidity and mortality. It can develop complications such as fluid collections and necrosis. Infection of necrosis occurs in about 20-40 % of patients with severe acute pancreatitis, and is associated with organ failure and worse prognosis. In the past few years the treatment of pancreatic collections has shifted from open surgery to minimally invasive techniques such as endoscopic ultrasound-guided drainage. These guidelines from a selection of experts among the Endoscopic Ultrasound Group, Spanish Society of Gastrointestinal Endoscopy (GSEED-USE) are intended to provide advice on the management of pancreatic collections based on a thorough review of the available scientific evidence. It also reflects the experience and clinical practice of the authors, who are advanced endoscopists or clinical pancreatologists with extensive experience in managing patients with acute pancreatitis.

Prospective multicenter assessment of the impact of EUS-guided gastroenterostomy on patient quality of life in unresectable malignant gastric outlet obstruction.

BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) is increasingly used for malignant gastric outlet obstruction (GOO) in inoperable patients. However, the impact of EUS-GE on patient quality of life (QoL) has not been evaluated prospectively. METHODS: Consecutive patients with unresectable malignant GOO who underwent EUS-GE between August 2019 and May 2021 at 4 Spanish centers were prospectively assessed using the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 at baseline and 1 month after the procedure. Centralized follow-up by telephone calls was undertaken. The Gastric Outlet Obstruction Scoring System (GOOSS) was used to assess oral intake, defining clinical success as a GOOSS ≥2. Differences between baseline and 30-day QoL scores were assessed using a linear mixed model. RESULTS: Sixty-four patients were enrolled, 33 (51.6%) men, with a median age of 77.3 years (interquartile range, 65.5-86.5). The most common diagnoses were pancreatic (35.9%) and gastric (31.3%) adenocarcinoma. Thirty-seven patients (57.9%) presented a 2/3 baseline Eastern Cooperative Oncology Group performance status score. Oral intake was restarted within 48 hours in 61 patients (95.3%), and the median postprocedure hospital stay was 3.5 days (interquartile range, 2-5). The 30-day clinical success rate was 83.3%. A clinically significant increase of 21.6 points (95% confidence interval, 11.5-31.7) in the global health status scale was documented, with significant improvements in nausea and vomiting, pain, constipation, and appetite loss. CONCLUSIONS: EUS-GE relieves GOO symptoms in patients with unresectable malignancy, allowing rapid oral intake and hospital discharge. It also provides a clinically relevant increase in QoL scores at 30 days from baseline. (Clinical trial registration number: NCT04660695.).

Endoscopic removal of lumen-apposing metal stents - risk factors for stent embedment, complex removals, and adverse events: analysis from a multicenter prospective case series.

BACKGROUND: Removing lumen-apposing metal stents (LAMSs) may be difficult and even harmful, but these features have seldom been analyzed. We aimed to generate a comprehensive assessment of the feasibility and safety of LAMS retrieval procedures. METHODS: A prospective multicenter case series including all technically successfully deployed LAMSs between January 2019 and January 2020 that underwent endoscopic stent removal. All retrieval-related data were prospectively recorded using standardized telephone questionnaires as part of centralized follow-up that ended after stent removal had been performed. Multivariable logistic regression models assessed the potential risk factors for complex removal. RESULTS: For the 407 LAMSs included, removal was attempted in 158 (38.8 %) after an indwell time of 46.5 days (interquartile range [IQR] 31-70). The median (IQR) removal time was 2 (1-4) minutes. Removal was labelled as complex in 13 procedures (8.2 %), although advanced endoscopic maneuvers were required in only two (1.3 %). Complex removal risk factors were stent embedment (relative risk [RR] 5.84, 95 %CI 2.14-15.89; P = 0.001), over-the-wire deployment (RR 4.66, 95 %CI 1.60-13.56; P = 0.01), and longer indwell times (RR 1.14, 95 %CI 1.03-1.27; P = 0.01). Partial and complete embedment were observed in 14 (8.9 %) and five cases (3.2 %), respectively. The embedment rate during the first 6 weeks was 3.1 % (2/65), reaching 15.9 % (10/63) during the following 6 weeks (P = 0.02). The adverse event rate was 5.1 %, including seven gastrointestinal bleeds (5 mild, 2 moderate). CONCLUSIONS: LAMS removal is a safe procedure, mostly requiring basic endoscopic techniques attainable in conventional endoscopy rooms. Referral to advanced endoscopy units should be considered for stents with known embedment or long indwell times, which may require more technically demanding procedures.

Intracystic Glucose and Carcinoembryonic Antigen in Differentiating Histologically Confirmed Pancreatic Mucinous Neoplastic Cysts.

INTRODUCTION: Differentiating mucinous neoplastic pancreatic cysts (MNPC) from cysts without malignant potential can be challenging. Guidelines recommend using fluid carcinoembryonic antigen (CEA) to differentiate MNPC; however, its sensitivity and specificity vary widely. Intracystic glucose concentration has shown promise in differentiating MNPC, but data are limited to frozen specimens and cohorts of patients without histologic diagnoses. This study aimed to compare glucose and CEA concentrations in differentiating MNPC using fresh fluid obtained from cysts with confirmatory histologic diagnoses. METHODS: This multicenter cohort study consisted of patients undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic cysts during January 2013-May 2020. Patients were included if the cyst exhibited a histologic diagnosis and if both CEA and glucose were analyzed from fresh fluid. Receiver operating curve (ROC) characteristics were analyzed, and various diagnostic parameters were compared. RESULTS: Ninety-three patients, of whom 59 presented with MNPC, met the eligibility criteria. The area under the receiver operating curve (AUROC) was 0.96 for glucose and 0.81 for CEA (difference 0.145, P = 0.003). A CEA concentration of ≥192 ng/mL had sensitivity of 62.7% and specificity of 88.2% in differentiating MNPC, whereas glucose concentration of ≤25 mg/dL had sensitivity and specificity of 88.1% and 91.2%, respectively. DISCUSSION: Intracystic glucose is superior to CEA concentration for differentiating MNPC when analyzed from freshly obtained fluid of cysts with histologic diagnoses. The advantage of glucose is augmented by its low cost and ease of implementation, and therefore, its widespread adoption should come without barriers. Glucose has supplanted CEA as the best fluid biomarker in differentiating MNPC.

EUS-guided gastroenterostomy versus duodenal self-expandable metal stent for malignant gastric outlet obstruction: results from a nationwide multicenter retrospective study (with video).

BACKGROUND AND AIMS: Traditionally, palliative treatment of malignant gastric outlet obstruction (GOO) has been surgical, but surgical treatment carries significant morbidity and mortality rates. Endoscopic placement of a duodenal self-expandable metal stent (D-SEMS) has been proven to be successful for this indication in the short term. However, D-SEMSs are likely to malfunction over time. EUS-guided gastroenterostomy (EUS-GE) may help overcome these limitations. We aimed to evaluate stent failure-free survival at 3 months. METHODS: A nationwide multicenter, observational study of D-SEMS and EUS-GE procedures for patients with malignant GOO was conducted at 7 academic centers from January 2015 to June 2020. Stent failure-free survival at 1, 3, and 6 months; technical and clinical success; adverse events (AEs); and patient survival were evaluated in both groups and compared. RESULTS: Ninety-seven patients were included in the D-SEMS group and 79 in the EUS-GE group. Pancreatic cancer was the main underlying malignancy in 53.4%. No statistically significant differences regarding technical (92.8% vs 93.7%) or clinical success (83.5% vs 92.4%) were found. AE rates did not differ between groups (10.3% vs 10.1%), although 2 events in the EUS-GE group required surgical management. Patients in the EUS-GE group had improved stent patency when compared with those patients in the D-SEMS group at 3 months (92.23% vs 80.6%; adjusted hazard ratio, .37; P = .033). CONCLUSIONS: EUS-GE seems to have improved patency outcomes when compared with D-SEMS placement for palliative treatment of malignant GOO. Prospective trials are needed to fully compare their efficacy and AE profile.

Classification, outcomes, and management of misdeployed stents during EUS-guided gastroenterostomy.

BACKGROUND AND AIMS: Stent misdeployment (SM) has hindered the dissemination of EUS-guided gastroenterostomy (EUS-GE) for gastric outlet obstruction (GOO) management. We aimed to provide a classification system for SM during EUS-GE and study clinical outcomes and management accordingly. METHODS: This is a retrospective study involving 16 tertiary care centers (8 in the United States, 8 in Europe) from March 2015 to December 2020. Patients who developed SM during EUS-GE for GOO were included. We propose classifying SM into 4 types. The primary outcome was rate and severity of SM (per American Society for Gastrointestinal Endoscopy lexicon), whereas secondary outcomes were clinical outcomes and management of dislodgement according to the SM classification type, in addition to salvage management of GOO after SM. RESULTS: From 467 EUS-GEs performed for GOO during the study period, SM occurred in 46 patients (9.85%). Most SMs (73.2%) occurred during the first 13 EUS-GE cases by the performing operators. SM was graded as mild (n = 28, 60.9%), moderate (n = 11, 23.9%), severe (n = 6, 13.0%), or fatal (n = 1, 2.2%), with 5 patients (10.9%) requiring surgical intervention. Type I SM was the most common (n = 29, 63.1%), followed by type II (n = 14, 30.4%), type IV (n = 2, 4.3%), and type III (n = 1, 2.2%). Type I SM was more frequently rated as mild compared with type II SM (75.9% vs 42.9%, P = .04) despite an equivalent rate of surgical repair (10.3% vs 7.1%, P = .7). Overall, 4 patients (8.7%) required an intensive care unit stay (median, 2.5 days). The median length of stay was 4 days after SM. CONCLUSIONS: Although SM is not infrequent during EUS-GE, most are type I, mild/moderate in severity, and can be managed endoscopically with a surgical intervention rate of approximately 11%.

Clinical and technical outcomes of patients undergoing endoscopic ultrasound-guided gastroenterostomy using 20-mm vs. 15-mm lumen-apposing metal stents.

BACKGROUND: Most studies on endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) for palliation of malignant gastric outlet obstruction (GOO) utilized a 15-mm lumen-apposing metal stent (LAMS). More recently, a 20-mm LAMS has become available. This study aimed to compare rates of technical and clinical success and adverse events (AEs) in patients undergoing EUS-GE using a 20-mm vs. 15-mm LAMS. METHODS: Patients who underwent EUS-GE with 15-mm or 20-mm LAMS for malignant GOO during the period from January 2018 to October 2020 were included. The primary outcome was clinical success, defined as an increase in the gastric outlet obstruction score (GOOS) by at least 1 point during follow-up. Secondary outcomes were technical success, maximum tolerated diet, re-intervention rate, and rate/severity of AEs. RESULTS: 267 patients (mean age 67 years, 43 % women) with malignant GOO from 19 centers underwent EUS-GE. Clinical success rates were similar for the 15-mm and 20-mm stents (89.2 % [95 %CI 84.2 %-94.2 %] vs. 84.1 % [77.4%-90.6 %], respectively). However, a significantly higher proportion of patients in the 20-mm group tolerated a soft solid/complete diet at the end of follow-up (91.2 % [84.4 %-95.7 %] vs. 81.2 % [73.9 %-87.2 %], P = 0.04). Overall, AEs occurred in 33 patients (12.4 % [8.4 %-16.3 %]), with similar rates for 15-mm and 20-mm stents (12.8 % [7.5 %-18.2 %] vs. 11.8 % [6 %-17.6 %]), including incidence of severe/fatal AEs (2 % [0.4 %-5.8 %] vs. 3.4 % [0.9 %-8.4 %]). CONCLUSIONS: The 20-mm and 15-mm LAMS show similar safety and efficacy for patients undergoing EUS-GE for malignant GOO. The 20-mm LAMS allows a more advanced diet and is, thus preferred for EUS-GE.

Predictors of adverse events after endoscopic ultrasound-guided through-the-needle biopsy of pancreatic cysts: a recursive partitioning analysis.

BACKGROUND AND STUDY AIMS : Endoscopic ultrasound-guided through-the-needle biopsy (TTNB) of pancreatic cystic lesions (PCLs) is associated with a non-negligible risk for adverse events (AEs). We aimed to identify the hierarchic interaction among independent predictors for TTNB-related AEs and to generate a prognostic model using recursive partitioning analysis (RPA). PATIENTS AND METHODS : Multicenter retrospective analysis of 506 patients with PCLs who underwent TTNB. RPA of predictors for AEs was performed and the model was validated by means of bootstrap resampling. RESULTS : Mean cysts size was 36.7 mm. Most common diagnoses were intraductal papillary mucinous neoplasm (IPMN, 45 %), serous cystadenoma (18.8 %), and mucinous cystadenoma (12.8 %). Fifty-eight (11.5 %) AEs were observed. At multivariate analysis, age (odds ratio [OR] 1.32, 1.09-2.14; p = 0.05), number of TTNB passes (OR from 2.17, 1.32-4.34 to OR 3.16, 2.03-6.34 with the increase of the number of passes), complete aspiration of the cyst (OR 0.56, 0.31-0.95; p = 0.02), and diagnosis of IPMN (OR 4.16, 2.27-7.69; p < 0.001) were found to be independent predictors of AEs, as confirmed by logistic regression and random forest analyses. RPA identified three risk classes: high-risk (IPMN sampled with multiple microforceps passes, 28 % AEs rate), low-risk (1.4 % AE rate, including patients < 64 years with other-than-IPMN diagnosis sampled with ≤ 2 microforceps passes and with complete aspiration of the cyst) and middle-risk class (6.1 % AEs rate, including the remaining patients). CONCLUSION : TTNB should be selectively used in the evaluation of patients with IPMN. The present model could be applied during patient selection as to optimize the benefit/risk of TTNB.

Arsenic exposure and human blood DNA methylation and hydroxymethylation profiles in two diverse populations from Bangladesh and Spain.

BACKGROUND: Associations of arsenic (As) with the sum of 5-mC and 5-hmC levels have been reported; however, As exposure-related differences of the separated 5-mC and 5-hmC markers have rarely been studied. METHODS: In this study, we evaluated the association of arsenic exposure biomarkers and 5-mC and 5-hmC in 30 healthy men (43-55 years) from the Aragon Workers Health Study (AWHS) (Spain) and 31 healthy men (31-50 years) from the Folic Acid and Creatinine Trial (FACT) (Bangladesh). We conducted 5-mC and 5-hmC profiling using Infinium MethylationEPIC arrays, on paired standard and modified (ox-BS in AWHS and TAB in FACT) bisulfite converted blood DNA samples. RESULTS: The median for the sum of urine inorganic and methylated As species (ΣAs) (µg/L) was 12.5 for AWHS and 89.6 for FACT. The median of blood As (µg/L) was 8.8 for AWHS and 10.2 for FACT. At a statistical significance p-value cut-off of 0.01, the differentially methylated (DMP) and hydroxymethylated (DHP) positions were mostly located in different genomic sites. Several DMPs and DHPs were consistently found in AWHS and FACT both for urine ΣAs and blood models, being of special interest those attributed to the DIP2C gene. Three DMPs (annotated to CLEC12A) for AWHS and one DHP (annotated to NPLOC4) for FACT remained statistically significant after false discovery rate (FDR) correction. Pathways related to chronic diseases including cardiovascular, cancer and neurological were enriched. CONCLUSIONS: While we identified common 5-hmC and 5-mC signatures in two populations exposed to varying levels of inorganic As, differences in As-related epigenetic sites across the study populations may additionally reflect low and high As-specific associations. This work contributes a deeper understanding of potential epigenetic dysregulations of As. However, further research is needed to confirm biological consequences associated with DIP2C epigenetic regulation and to investigate the role of 5-hmC and 5-mC separately in As-induced health disorders at different exposure levels.

Over-the-scope clip for acute esophageal variceal bleeding.

Over-the-scope clip (OTSC) has been reported to control non-variceal bleeding; however, the use of this device for acute variceal hemorrhage (AVH) is very limited. We report our experience regarding the use of OTSC in patients with AVH in terms of technical success and safety. A retrospective clinical experience case series study was conducted from October 2017 to June 2019 at two tertiary care centers. Adult patients with AVH as a result of small varices managed with OTSC after endoscopic band ligation (EBL) failure were enrolled. Standard gastroscope and OTSC 'type a' with a cap of 11 mm in diameter were used in all procedures. Total of five patients with chronic liver disease (Child-Pugh score ≤8) and portal hypertension (hepatic venous pressure gradient, mean 14.4 ± 1.3 mmHg) were included. Four of them presented collapse of the bleeding varix, and one had wall disruption associated with fibrosis secondary to prior banding. We were able to stop AVH in all patients without clip-related adverse events during a 30-day follow-up period. Two patients developed solid food dysphagia after 3 months of clip deployment that resolved after removal using a bipolar cutting device. Twin grasper or anchor were not used to aid or facilitate the approximation of opposite edges in any patient. No additional local therapies or new endoscopic session for variceal eradication were required. This case series shows preliminary success controlling AVH with OTSC after EBL failure in patients with small varices. Esophageal dysphagia may appear as a complication during follow up but it can be resolved by clip removal.

A retrospective, multicenter analysis of incidents associated with Axios™ lumen-apposing stents.

INTRODUCTION: there is controversy with regard to the risks associated with lumen-apposing metal stents (LAMSs), with significant variations between available reports. OBJECTIVES: to describe the types and proportions of complications that arise during the permanence time and removal of Axios™ LAMS. Furthermore, the relationship between patency time, therapeutic target and the presence of complications was also described. METHODS: a retrospective, multicenter case series study was performed of all patients with an implanted LAMS to access extra-luminal structures during 2017. Only technically successful cases were recorded. RESULTS: a total of 179 patients from seven sites (range, 4-68 cases/site) were included in the study, with a mean age of 64.3 years (SD: 15.8; range: 24.6-98.8 years) and 122 (68.2%) were male. Most common indications included encapsulated necrosis (58, 32.4%), pseudocysts (31, 17.3%) and gallbladder drains (26, 14.5%). Complications during LAMS stay were reported in 19 patients (10.9%); stent lumen or gastroduodenal obstruction (8, 4.5%) and bleeding (7, 3.9%) were the most common. LAMS were not removed in 86 (48%) patients due to the following reasons: a permanent stent was used (46, 53.5%), loss to follow-up (18, 20.9%), patient demise (16, 18.6%) and stent migration (6, 7%). Five (5.4%) complications were reported during stent removal, which were three bleeds and two perforations. No association was found between stent duration and complications (p = 0.67). CONCLUSION: complications secondary to LAMS insertion are uncommon but may be serious. This study found no association between complications and stent duration.

Cooperation between Paxillin-like Protein Pxl1 and Glucan Synthase Bgs1 Is Essential for Actomyosin Ring Stability and Septum Formation in Fission Yeast.

In fungal cells cytokinesis requires coordinated closure of a contractile actomyosin ring (CAR) and synthesis of a special cell wall structure known as the division septum. Many CAR proteins have been identified and characterized, but how these molecules interact with the septum synthesis enzymes to form the septum remains unclear. Our genetic study using fission yeast shows that cooperation between the paxillin homolog Pxl1, required for ring integrity, and Bgs1, the enzyme responsible for linear ß(1,3)glucan synthesis and primary septum formation, is required for stable anchorage of the CAR to the plasma membrane before septation onset, and for cleavage furrow formation. Thus, lack of Pxl1 in combination with Bgs1 depletion, causes failure of ring contraction and lateral cell wall overgrowth towards the cell lumen without septum formation. We also describe here that Pxl1 concentration at the CAR increases during cytokinesis and that this increase depends on the SH3 domain of the F-BAR protein Cdc15. In consequence, Bgs1 depletion in cells carrying a cdc15ΔSH3 allele causes ring disassembly and septation blockage, as it does in cells lacking Pxl1. On the other hand, the absence of Pxl1 is lethal when Cdc15 function is affected, generating a large sliding of the CAR with deposition of septum wall material along the cell cortex, and suggesting additional functions for both Pxl1 and Cdc15 proteins. In conclusion, our findings indicate that CAR anchorage to the plasma membrane through Cdc15 and Pxl1, and concomitant Bgs1 activity, are necessary for CAR maintenance and septum formation in fission yeast.

Cyst wall brushing. Exploring the limits of cytology.

With the increasingly widespread use of imaging techniques pancreatic cystic lesions (PCLs) are now commonly identified. Their prevalence among the symptom-free population ranges from 2.4% to 13.5%. However, a recent study by our group revealed PCLs in up to 21.5% of patients undergoing endoscopic ultrasound (EUS) for non-pancreas conditions, an incidence that increases with age. Identifying PCLs in an otherwise asymptomatic population has become a significant clinical issue.

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

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.