Perception of the impact of intravenous biological treatment on the work and professional environment in patients with inflammatory bowel disease. / Percepción del impacto del tratamiento biológico endovenoso sobre el ámbito laboral y personal en pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: In the treatment of inflammatory bowel disease (IBD), we have biologic therapies administered intravenously and subcutaneously. Recently, some drugs can be administered by either of these routes. The real impact that intravenous administration has on the perception of the disease and the personal and work life of the patient is unknown. METHODS: All IBD patients receiving intravenous infliximab treatment for at least 6 months were anonymously invited to participate. They were provided with a specific structured questionnaire with visual analogue scales (0-10) at two reference centers in the Barcelona area. RESULTS: A total of 90 patients with a median age of 45 years (36-56) and a median infliximab treatment duration of 48 months (24-84) were included. The visit and therapy with infliximab in the day hospital were globally well evaluated (9, IQR 7-10). 78% of patients combined day hospital stays with other activities (26% employment). The personal impact was generally low (4, IQR 0-5.8), but the patient's job was threatened in 43% of patients on intensified treatment. CONCLUSIONS: The intravenous administration of biologic drugs on an outpatient basis is highly satisfactory among IBD patients. The impact on the work sphere appears to be more pronounced than on the personal sphere, an aspect that should be considered in shared decision-making with the patient.

Duration of smoking cessation in patients with inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: Smoking can worsen inflammatory bowel disease (IBD), although evidence regarding the duration of cessation is scarce. The objectives of the study were to determine the duration of abstinence and identify the characteristics of relapse in IBD patients. PATIENTS AND METHODS: Using the local database of a nationwide registry of patients with IBD, we identified patients who were active smokers at the time of IBD diagnosis and invited them to participate in the study. Patients were asked about their smoking habit and those who were ex-smokers constituted the study cohort. We obtained clinical and smoking-related data of ex-smokers from medical records and telephone interviews. We measured nicotine dependence using the Fagerström Test for Nicotine Dependence (FTND). RESULTS: We enrolled 121 IBD patients who were ex-smokers: 89 patients with Crohn's disease (CD) and 33 patients with ulcerative colitis (UC). The median age at cessation was lower in patients with CD (38 years) than in patients with UC (46 years) (p=0.002). Follow-up time was shorter in CD patients than in UC patients (114 vs. 168 months, p=0.035). No difference was found in the FTND score. Relapse was more common in CD patients (46%) than in UC patients (24%) (p=0.029), although time to first relapse was similar in both groups of patients (12 and 15 months, respectively; p=0.056). Nicotine dependence was the only independent factor associated with relapse. CONCLUSIONS: The risk of smoking relapse was high, especially in CD patients, although their dependence level was similar to that of UC patients.

Percepción de la necesidad de asesoramiento dietético y modificaciones alimentarias en pacientes con enfermedad inflamatoria intestinal / Perception of the need for dietary advice and dietary modifications in inflammatory bowel disease patients

Introducción: En la enfermedad inflamatoria intestinal (EII), la dieta puede percibirse como un desencadenante de recidivas o empeoramiento clínico, siendo frecuentes las modificaciones dietéticas no derivadas de asesoramiento profesional. Objetivos: Evaluar la percepción de necesidad de asesoramiento dietético en pacientes con EII, conocer las modificaciones dietéticas y su efecto sobre la EII. Métodos: Se invitó a participar anónima y consecutivamente durante tres meses a todos los pacientes visitados en consulta de EII y los pacientes en hospitalización de día durante la administración de fármacos biológicos, a rellenar un cuestionario estructurado con escala visual analógica (0-10). Resultados: Se obtuvieron 124 encuestas (54% colitis ulcerosa, 46% enfermedad de Crohn). La edad media fue de 47±12 años. El asesoramiento dietético impartido en consulta se valoró con una mediana de 7,0 (IIC, 4,50-9,00). El 40% buscó asesoramiento dietético externo, frecuentemente en el primer año tras el diagnóstico (70%). Estas recomendaciones externas fueron: dieta sin lácteos (29%), baja en grasas (27%), sin gluten (23%) y baja en fibra (21%). La ayuda percibida externa se valoró con mediana de 7,50 (IIC, 5,50-9,50), con mejoría percibida de la sintomatología digestiva (73%). El 61% excluyó algún alimento (57% permanentemente) y 11% realizó ayuno por iniciativa propia. Conclusiones: Los pacientes con EII muestran una clara necesidad de asesoramiento dietético, especialmente en el diagnóstico. Una información dietética precoz, específica incrementaría su satisfacción y evitaría la adopción de dietas de exclusión no justificadas.(AU)

Background and aim: In inflammatory bowel disease (IBD), diet can be perceived as a trigger for relapses or clinical worsening, dietary modifications are frequent and not derived from professional advice. The aim of this study was to evaluate the perception of the need for dietary advice in patients with IBD, to know the dietary modifications adopted and, it's effect on IBD. Methods: An anonymous structured questionnaire with a visual analog scale (0–10) was distributed to consecutive outpatients from our IBD unit. Results: A total of 124 complete the questionnaire (54% ulcerative colitis, 46% Crohn's disease). Mean age was 47±12 years. Dietary advice provided in the clinic was assessed with a median score of 7 (IIC, 4.50–9.00). 40% sought external dietary advice, often during the first year after diagnosis (70%). The most frequent dietary recommendations from an external professional were: dairy free diet (29%), low fat (27%), gluten free (23%), and low fiber (21%). Dietary advice from external source was assessed with a median score of 7.50 (IIC, 5.50–9.50), improving digestive symptoms in 73% of cases. Regarding dietary modifications, 61% excluded some foods (57% permanently) and 11% fasted on their own decision. Conclusions: IBD patient show a clear need for dietary advice, especially at the time of IBD diagnosis. Early specific and in-depth dietary information would increase patient satisfaction and could prevent the adoption of unjustified exclusion diets.(AU)

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy / Resultados clínicos y endoscópicos de pacientes con enfermedad de Crohn colónica tratados con 5-aminosalicilatos como monoterapia

Background: In spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. Methods: Patients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. Results: Out of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48–234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5–187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. Conclusions: 5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.(AU)

Antecedentes: A pesar de la falta de evidencia sobre los beneficios clínicos de los 5-aminosalicíilatos (5-ASA) orales en la enfermedad de Crohn (EC), estos medicamentos se utilizan con frecuencia en la práctica clínica diaria, particularmente para la EC cólica. Nuestro objetivo es evaluar el uso y los resultados clínicos del 5-ASA en aquellos pacientes con EC cólica tratados con 5-ASA en monoterapia. Métodos: Los pacientes diagnosticados con EC cólica aislada y tratados con 5-ASA pero nunca expuestos a inmunosupresores o agentes biológicos fueron identificados a partir de las bases de datos locales de 5 centros de referencia. Se realizó una revisión retrospectiva de los resultados clínicos y endoscópicos. Resultados: De 545 pacientes con EC cólica aislada, 106 (19%) fueron tratados con 5-ASA oral en monoterapia como terapia de mantenimiento. La mediana de seguimiento fue de 144 meses (rango intercuartílico: 48-234). Casi todos los pacientes (92%) presentaban un patrón inflamatorio y un 11% desarrollaron enfermedad perianal. La mitad de los pacientes ya habían recibido 5-ASA en el momento del diagnóstico y la mediana de duración del tratamiento con 5-ASA fue de 107 meses (rango intercuartílico: 22,5-187). La remisión endoscópica, definida por la ausencia de úlceras en la última colonoscopia completa, se observó en el 65% de los pacientes a los que se les realizó al menos una colonoscopia durante el seguimiento. El género masculino y las manifestaciones extraintestinales se asociaron con una menor probabilidad de lograr la remisión endoscópica. Nueve pacientes requirieron colectomía, pero en su mayoría poco después del diagnóstico de EC. Conclusiones: Los 5-ASA parecen ser beneficiosos a largo plazo en una quinta parte de los pacientes con EC cólica como única terapia de mantenimiento y deben considerarse en pacientes frágiles con EC con afectación exclusiva del colon.(AU)

Perception of the need for dietary advice and dietary modifications in inflammatory bowel disease patients. / Percepción de la necesidad de asesoramiento dietético y modificaciones alimentarias en pacientes con enfermedad inflamatoria intestinal.

BACKGROUND AND AIM: In inflammatory bowel disease (IBD), diet can be perceived as a trigger for relapses or clinical worsening, dietary modifications are frequent and not derived from professional advice. The aim of this study was to evaluate the perception of the need for dietary advice in patients with IBD, to know the dietary modifications adopted and, it's effect on IBD. METHODS: An anonymous structured questionnaire with a visual analog scale (0-10) was distributed to consecutive outpatients from our IBD unit. RESULTS: A total of 124 complete the questionnaire (54% ulcerative colitis, 46% Crohn's disease). Mean age was 47±12 years. Dietary advice provided in the clinic was assessed with a median score of 7 (IIC, 4.50-9.00). 40% sought external dietary advice, often during the first year after diagnosis (70%). The most frequent dietary recommendations from an external professional were: dairy free diet (29%), low fat (27%), gluten free (23%), and low fiber (21%). Dietary advice from external source was assessed with a median score of 7.50 (IIC, 5.50-9.50), improving digestive symptoms in 73% of cases. Regarding dietary modifications, 61% excluded some foods (57% permanently) and 11% fasted on their own decision. CONCLUSIONS: IBD patient show a clear need for dietary advice, especially at the time of IBD diagnosis. Early specific and in-depth dietary information would increase patient satisfaction and could prevent the adoption of unjustified exclusion diets.

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy.

BACKGROUND: In spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. METHODS: Patients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. RESULTS: Out of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48-234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5-187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. CONCLUSIONS: 5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.

Phase angle by electrical bioimpedance is a predictive factor of hospitalisation, falls and mortality in patients with cirrhosis.

The phase angle is a versatile measurement to assess body composition, frailty and prognosis in patients with chronic diseases. In cirrhosis, patients often present alterations in body composition that are related to adverse outcomes. The phase angle could be useful to evaluate prognosis in these patients, but data are scarce. The aim was to analyse the prognostic value of the phase angle to predict clinically relevant events such as hospitalisation, falls, and mortality in patients with cirrhosis. Outpatients with cirrhosis were consecutively included and the phase angle was determined by electrical bioimpedance. Patients were prospectively followed to determine the incidence of hospitalisations, falls, and mortality. One hundred patients were included. Patients with phase angle ≤ 4.6° (n = 31) showed a higher probability of hospitalisation (35% vs 11%, p = 0.003), falls (41% vs 11%, p = 0.001) and mortality (26% vs 3%, p = 0.001) at 2-year follow-up than patients with PA > 4.6° (n = 69). In the multivariable analysis, the phase angle and MELD-Na were independent predictive factors of hospitalisation and mortality. Phase angle was the only predictive factor for falls. In conclusion, the phase angle showed to be a predictive marker for hospitalisation, falls, and mortality in outpatients with cirrhosis.

Frailty in outpatients with cirrhosis: A prospective observational study.

BACKGROUND AND AIM: Frailty is increasingly recognized as a major prognostic factor in cirrhosis in addition to conventional liver insufficiency scores. The aim was to compare the prevalence and characteristics of frailty between patients with cirrhosis and controls, and to analyse its prognostic value. METHODS: We included outpatients with cirrhosis and age- and gender-matched non-cirrhotic controls. Frailty was defined according to the Fried frailty criteria. In patients with cirrhosis, we analysed the ability of the degree of frailty to predict a composite endpoint, consisting of hospitalization, admission to a long-term care centre, falls or death. RESULTS: We included 135 patients with cirrhosis and 135 controls. The prevalence of frailty was higher among patients with cirrhosis: 35 (25.9%) frail, 74 (54.8%) pre-frail and 26 (19.2%) robust vs 14 (10.4%) frail, 67 (49.6%) pre-frail and 54 (40%) robust (P < .001) in controls. This difference was mainly as a result of decreased muscle strength in patients with cirrhosis. During follow-up, frail patients with cirrhosis showed a higher probability of composite endpoint, hospitalization and falls than pre-frail and robust cirrhotic patients but mortality was similar. MELD-Na score and frailty were independent predictive factors for hospitalization, frailty for falls, and MELD-Na score and albumin for survival. Vitamin D deficiency and increased cystatin C were associated with frailty. CONCLUSIONS: Frailty was more frequent in outpatients with cirrhosis than in controls, mainly because of a decrease in muscle strength, and it could be a predictive factor for hospitalization and falls in these patients.

Noninvasive assessment of liver fibrosis in Crohn's disease patients exposed to methotrexate.

BACKGROUND: Methotrexate is widely used to treat some inflammatory chronic disorders, though it is hampered by the risk of liver fibrosis. Many recommendations have been made to assess methotrexate-related hepatotoxicity, including liver biopsy. However, other noninvasive methods to assess liver fibrosis have been developed and could be implemented for patients treated with methotrexate. AIM: The aim of the study was to compare the prevalence of liver fibrosis by means of noninvasive methods [aspartate transaminase-to-platelet ratio index (APRI) Forns index, and transient elastography] in patients with Crohn's disease exposed or not to methotrexate, and to identify risk factors for liver fibrosis. METHODS: Prospective, cross-sectional study. All patients with Crohn's disease exposed to methotrexate were included and compared to an unselected cohort of outpatients with Crohn's disease never exposed to methotrexate. RESULTS: A total of 84 patients with Crohn's disease, 56 exposed to methotrexate, and 28 controls, were included. Significant liver fibrosis was found in 7% of methotrexate-exposed patients with Crohn's disease and 10% of controls as measured by transient elastography, and in 7% of controls as measured by the Forns index. No cases of liver fibrosis were detected by APRI. Only alcohol consumption, diabetes mellitus, and age were associated with significant liver fibrosis. CONCLUSIONS: Significant liver fibrosis is uncommon among patients with Crohn's disease, even among those exposed to methotrexate. The risk of liver fibrosis in Crohn's disease seems to depend on common risk factors for liver disease.

Impact of pain associated with the subcutaneous administration of adalimumab / Impacto del dolor asociado a la administración subcutánea de adalimumab

Background: There is limited information regarding the impact of patients' perception of injection pain on adherence to treatments, specifically in inflammatory bowel disease (IBD) patients. Therefore, we aimed to determine the impact of the pain associated with the subcutaneous administration of adalimumab in patients with IBD treated with the old formulation and the new low-volume/citrate-free formulation. Methods: A specifically-designed questionnaire was completed by 76 patients with IBD, who started treatment with adalimumab before the availability of the low-volume/citrate-free formulation and were switched to this new formulation. Intensity of pain was measured by using visual analog scales (VAS). Results: A total of 62 patients (82%) experienced injection-related pain with the initial formulation. The perception of pain was associated with a decreased adherence to the treatment (37%), an increase in pre-administration anxiety (25%) or, as a consequence, the patient required someone else to carry out the injection (21%). Younger age was the only factor associated with pain perception. After switching to the new formulation, perception of pain persisted only in 2 patients (3%). Among those who felt pain with the initial formulation, pre-administration anxiety disappeared in 44%; 32% and 42% stated that the new formulation eased adherence and self-administration. Conclusions: The perception of pain related to the subcutaneous administration of therapy negatively impacts on treatment adherence in IBD patients. Improved formulations for subcutaneous administration of drugs can positively impact patients' convenience and adherence

Introducción: La información sobre el impacto de la percepción del dolor asociada a inyección sobre la adherencia a los tratamientos subcutáneos es limitada específicamente en pacientes con enfermedad inflamatoria intestinal (EII). Nuestro objetivo fue determinar el impacto del dolor asociado con la administración subcutánea de adalimumab en pacientes con EII y tratados con la fórmula antigua y la nueva de bajo volumen/sin citrato. Materiales y métodos: Setenta y seis pacientes con EII que iniciaron tratamiento con adalimumab antes de la disponibilidad de la formulación de bajo volumen/sin citrato y se cambió a esta nueva formulación completaron un cuestionario diseñado específicamente. La intensidad del dolor se midió mediante escalas visuales analógicas (EVA). Resultados: Sesenta y dos pacientes (82%) experimentaron dolor relacionado con la inyección con la formulación inicial. La percepción de dolor se asoció con menor adherencia al tratamiento (37%), aumento de la ansiedad pre-administración (25%) o, como consecuencia, el paciente rehuyó la autoinyección (21%). La edad más joven fue el único factor asociado a la percepción del dolor. Tras cambiar a la nueva formulación, la percepción del dolor persistió solo en 2 pacientes (3%). Entre los que referían dolor con la formulación inicial, la ansiedad pre-administración desapareció en el 44%; el 32 y 42% afirmaron que la nueva formulación facilitaba la adherencia y la autoadministración. Conclusiones: La percepción del dolor relacionada con la administración subcutánea de fármacos tiene un impacto negativo en la adherencia en pacientes con EII. Las formulaciones optimizadas de administración subcutánea pueden tener un impacto positivo en la comodidad y adherencia

Impact of pain associated with the subcutaneous administration of adalimumab.

BACKGROUND: There is limited information regarding the impact of patients' perception of injection pain on adherence to treatments, specifically in inflammatory bowel disease (IBD) patients. Therefore, we aimed to determine the impact of the pain associated with the subcutaneous administration of adalimumab in patients with IBD treated with the old formulation and the new low-volume/citrate-free formulation. METHODS: A specifically-designed questionnaire was completed by 76 patients with IBD, who started treatment with adalimumab before the availability of the low-volume/citrate-free formulation and were switched to this new formulation. Intensity of pain was measured by using visual analog scales (VAS). RESULTS: A total of 62 patients (82%) experienced injection-related pain with the initial formulation. The perception of pain was associated with a decreased adherence to the treatment (37%), an increase in pre-administration anxiety (25%) or, as a consequence, the patient required someone else to carry out the injection (21%). Younger age was the only factor associated with pain perception. After switching to the new formulation, perception of pain persisted only in 2 patients (3%). Among those who felt pain with the initial formulation, pre-administration anxiety disappeared in 44%; 32% and 42% stated that the new formulation eased adherence and self-administration. CONCLUSIONS: The perception of pain related to the subcutaneous administration of therapy negatively impacts on treatment adherence in IBD patients. Improved formulations for subcutaneous administration of drugs can positively impact patients' convenience and adherence.

Effect of a Multistrain Probiotic on Cognitive Function and Risk of Falls in Patients With Cirrhosis: A Randomized Trial.

Probiotics can modulate gut microbiota, intestinal permeability, and immune response and could therefore improve cognitive dysfunction and help avoid potential consequences, such as falls, in patients with cirrhosis. The aim of this study was to evaluate the effect of a multistrain probiotic on cognitive function, risk of falls, and inflammatory response in patients with cirrhosis. Consecutive outpatients with cirrhosis and cognitive dysfunction (defined by a Psychometric Hepatic Encephalopathy Score [PHES] < -4) and/or falls in the previous year were randomized to receive either a sachet of a high-concentration multistrain probiotic containing 450 billion bacteria twice daily for 12 weeks or placebo. We evaluated the changes in cognitive function (PHES); risk of falls (Timed Up and Go [TUG] test, gait speed, and incidence of falls); systemic inflammatory response; neutrophil oxidative burst; intestinal barrier integrity (serum fatty acid-binding protein 6 [FABP-6] and 2 [FABP-2] and zonulin and urinary claudin-3); bacterial translocation (lipopolysaccharide-binding protein [LBP]); and fecal microbiota. Thirty-six patients were included. Patients treated with the probiotic (n = 18) showed an improvement in the PHES (P = 0.006), TUG time (P = 0.015) and gait speed (P = 0.02), and a trend toward a lower incidence of falls during follow-up (0% compared with 22.2% in the placebo group [n = 18]; P = 0.10). In the probiotic group, we observed a decrease in C-reactive protein (P = 0.01), tumor necrosis factor alpha (P = 0.01), FABP-6 (P = 0.009), and claudin-3 (P = 0.002), and an increase in poststimulation neutrophil oxidative burst (P = 0.002). Conclusion: The multistrain probiotic improved cognitive function, risk of falls, and inflammatory response in patients with cirrhosis and cognitive dysfunction and/or previous falls.

Ascitic fluid regulates the local innate immune response of patients with cirrhosis.

Ascitic neutrophils from cirrhotic patients with spontaneous bacterial peritonitis (SBP) exhibit an impaired oxidative burst that could facilitate bacterial infection. However, the influence of the cell-free ascitic fluid of these patients on neutrophil function has not been investigated. To analyze this influence, we determined the ascitic levels of cytokines, resistin, and lactoferrin and their association with neutrophil function, disease severity score, and SBP resolution. We analyzed NETosis induction by microscopy and oxidative burst by the flow cytometry of healthy neutrophils cultured in ascitic fluid from cirrhotic patients with sterile ascites (SA) and with SBP before and after antibiotic treatment. Resistin, IL-6, IL-1 receptor antagonist, IL-1ß, and lactoferrin levels were measured in ascitic fluids and supernatants of cultured neutrophils and PBMCs by ELISA. Upon stimulation, healthy neutrophils cultured in SBP ascitic fluid produced lower NETosis and oxidative burst than those cultured in SA. Ascitic resistin levels were negatively correlated with NETosis, oxidative burst, and ascitic glucose levels; and positively correlated with the model for end-stage liver disease score. After an E. coli or TNF-α stimulus, neutrophils were the major resistin producers. Resistin indirectly reduced the oxidative burst of neutrophils and directly reduced the inflammatory phenotype of monocytes and TNF-α production. Bacterial-induced resistin production can down-regulate the inflammatory response of macrophages and neutrophil function in ascitic fluid. Consequently, this down-regulation may jeopardize the elimination of bacteria that translocate to ascitic fluid in patients with cirrhosis.

Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites.

AIM: To assess the relationship between the presence of toll-like receptor 4 (TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites. METHODS: We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period. Patients with human immunodeficiency virus (HIV) infection or any other immunodeficiency, patients with advanced hepatocellular carcinoma (beyond Milan's criteria) or any other condition determining poor short-term prognosis, and patients with a permanent urinary catheter were excluded. The presence of D299G and/or T399I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections, other complications of cirrhosis, hepatocellular carcinoma, and mortality during follow-up. A multivariate analysis to identify predictive variables of mortality in the whole series was performed. RESULTS: We included 258 patients: 28 (10.8%) were carriers of D299G and/or T399I TLR4 polymorphisms (polymorphism group) and 230 patients were not (wild-type group). The probability of developing any bacterial infection at one-year follow-up was 78% in the polymorphism group and 69% in the wild-type group (P = 0.54). The one-year probability of presenting infections caused by gram-negative bacilli (51% vs 44%, P = 0.68), infections caused by gram-positive cocci (49% vs 40%, P = 0.53), and spontaneous bacterial peritonitis (29% vs 34%, respectively, P = 0.99) did not differ between the two groups. The one-year probability of transplant-free survival was 55% in the polymorphism group and 66% in the wild-type group (P = 0.15). Multivariate analysis confirmed that age, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy, hepatocellular carcinoma and serum creatinine were associated with a higher risk of death during follow-up. CONCLUSION: Genetic polymorphisms D299G and/or T399I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections.

Impact of ornithine phenylacetate (OCR-002) in lowering plasma ammonia after upper gastrointestinal bleeding in cirrhotic patients.

BACKGROUND: Ornithine phenylacetate (OP) has been proven effective in lowering ammonia plasma levels in animals, and to be well tolerated in cirrhotic patients. A trial to assess OP efficacy in lowering plasma ammonia levels versus placebo in cirrhotic patients after an upper gastrointestinal bleeding was performed. The primary outcome was a decrease in venous plasma ammonia at 24 hours. METHODS: A total of 38 consecutive cirrhotic patients were enrolled within 24 hours of an upper gastrointestinal bleed. Patients were randomized (1:1) to receive OP (10 g/day) or glucosaline for 5 days. RESULTS: The primary outcome was not achieved. A progressive decrease in ammonia was observed in both groups, being slightly greater in the OP group, with significant differences only at 120 hours. The subanalysis according to Child-Pugh score showed a statistically significant ammonia decrease in Child-Pugh C-treated patients at 36 hours, as well as in the time-normalized area under the curve (TN-AUC) 0-120 hours in the OP group [40.16 µmol/l (37.7-42.6); median (interquartile range) (IQR)] versus placebo group [65.5 µmol/l (54-126);p = 0.036]. A decrease in plasma glutamine levels was observed in the treated group compared with the placebo group, and was associated with the appearance of phenylacetylglutamine in urine. Adverse-event frequency was similar in both groups. No differences in hepatic encephalopathy incidence were observed. CONCLUSIONS: OP failed to significantly decrease plasma ammonia at the given doses (10 g/day). Higher doses of OP might be required in Child-Pugh A and B patients. OP appeared well tolerated.

Alteration of the serum microbiome composition in cirrhotic patients with ascites.

The progression of cirrhosis is associated with alterations in the composition of the gut microbiome. To assess microbial translocation, we compared the serum microbial composition of patients with and without ascites and characterized the ascitic fluid microbiome using 16S rDNA high-throughput sequencing data. A complex and specific microbial community was detected in the serum and ascitic fluid of patients with cirrhosis but barely detectable in the serum of healthy controls. The serum microbiome of patients with ascites presented higher levels of lipopolysaccharide binding protein, a marker of microbial translocation, associated with higher diversity and relative abundance of Clostridiales and an unknown genus belonging to the Cyanobacteria phylum compared to patients without ascites. The composition of the fecal microbiome was also more altered in patients with than without ascites, confirming previous studies on fecal microbiome. We propose that alteration of the serum and fecal microbiome composition be considered indicators of cirrhosis progression.