Probiotic supplementation for 24 weeks in patients with non-alcoholic steatohepatitis: the PROBILIVER randomized clinical trial.

Background and aim: Considering the increasing prevalence of non-alcoholic steatohepatitis (NASH) and treatment gaps, this study aimed to evaluate the effect of probiotic supplementation on liver function markers, nutritional status, and clinical parameters. Methods: This double-blind, randomized clinical trial (ClinicalTrials.gov ID: NCT0346782) included adult outpatients with biopsy-proven NASH. The intervention consisted of 24 weeks of supplementation with the probiotic mix Lactobacillus acidophilus (1 × 109 CFU) + Lactobacillus rhamnosus (1 × 109 CFU) + Lactobacillus paracasei (1 × 109 CFU) + Bifidobacterium lactis (1 × 109 CFU), or placebo, twice a day. The following parameters were evaluated: demographic and clinical data, transient elastography (FibroScan), liver enzymes, NAFLD fibrosis score, fatty liver index, laboratory assessment, serum concentration of toll-like receptor-4 (sTLR-4) and cytokeratin 18 (CK-18), anthropometric data, dietary intake, and physical activity. Regarding data analysis, the comparison between the groups was based on the delta of the difference of each variable analyzed (value at the end of treatment minus the baseline value) using the t-test for independent samples or the Mann-Whitney U-test. Results: Forty-four patients with NASH completed the trial (51.4 ± 11.6 years). At baseline, 87% of participants had a mild liver fibrosis degree on biopsy, normal values of liver enzymes, transient elastography values consistent with grade 1 fibrosis in both groups, increased waist circumference (WC), a BMI of 30.97 kg/m2, and 76% presented with metabolic syndrome (MetS). After the intervention, no differences were observed between the probiotic and placebo groups in terms of MetS, WC, BMI scores, or liver enzyme levels (p > 0.05 for all). The elastography values remained consistent with grade 1 fibrosis in both groups. Although CK-18 was reduced in both groups, a larger effect size was noted in the probiotic group (D = 1.336). sTLR-4 was also reduced in both groups, with no difference between groups (p = 0.885). Conclusion: Intervention with probiotics in the early stages of NASH demonstrated no significant change in hepatic and clinical parameters. Clinical trial registration: ClinicalTrials.gov, identifier NCT0346782.

Oral 24-week probiotics supplementation did not decrease cardiovascular risk markers in patients with biopsy proven NASH: A double-blind placebo-controlled randomized study.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease (CVD) is the major cause of death in non-alcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Probiotics are often indicated for the disease, but their results are controversial in part due to the poor quality of studies. Thus, we investigated the impact of 24-week probiotics supplementation on cardiovascular risk (CVR) in biopsy-proven non-alcoholic steatohepatitis (NASH) patients. PATIENTS AND METHODS: Double-blind, placebo-controlled, single-center study (NCT03467282), adult NASH, randomized for 24 weeks daily sachets of probiotic mix (109CFU of Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus paracasei and Bifidobacterium lactis) or placebo. Clinical scores (atherogenic indexes, atherosclerotic cardiovascular disease-ASCVD and systematic coronary risk evaluation-SCORE), biochemistry, miR-122, miR-33a, plasminogen activator inhibitor-1 (PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), were determined before and after the intervention. RESULTS: Forty-six patients were enrolled (23 received probiotics and 23 placebo), with a mean age of 51.7 years, most of them females and whites. Clinical and demographic features were similar between the groups at the baseline. The Median NAFLD activity score was 4.13 in both groups. Fibrosis was mild in most patients (15.2% and 65.2% F0 and F1, respectively). Treatment did not promote any clinically significant changes in body mass index or laboratory, including lipid and glucose profile. High CVR patients through atherogenic indexes decreased from baseline in both groups, as well as PAI-1 and miR-122 levels, although there was no difference between probiotics and placebo. CONCLUSIONS: A 24-week probiotic mix administration was not superior to placebo in reducing CVR markers in patients with NASH.

Sinusoidal obstruction syndrome secondary the intake of Senecio brasiliensis: A case report.

Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease histologically characterized by edema, necrosis, detachment of endothelial cells in small sinusoidal hepatic and interlobular veins and intrahepatic congestion, which leads to portal hypertension and liver dysfunction. In the Western world, most HSOS cases are associated with myeloablative pretreatment in a hematopoietic stem cell transplantation setting. Here we report a case of a 54 years old female patient, otherwise healthy, with no history of alcoholic ingestion, who presented with jaundice and signs of portal hypertension, including ascites and bilateral pleural effusion. She had no history of liver disease and denied any other risk factor for liver injury, except Senecio brasiliensis ingestion as a tea, prescribed as a therapy for menopause. Acute viral hepatitis and thrombosis of the portal system were excluded in complementary investigation, as well as sepsis, metastatic malignancy and other liver diseases, setting a RUCAM score of 6. Computed tomography demonstrated a diffuse liver parenchymal heterogeneity (in mosaic) and an extensive portosystemic collateral venous circulation, in the absence of any noticeable venous obstruction. HSOS diagnosis was confirmed through a liver biopsy. During the following-up period, patient developed refractory pleural effusion, requiring hemodialysis. Right before starting anticoagulation, she presented with abdominal pain and distention, with findings compatible of mesenteric ischemia by computed tomography. A laparotomy was performed, showing an 80cm segment of small bowel ischemia, and resection was done. She died one day after as a result from a septic shock refractory to treatment. The presented case was related to oral intake of S. brasiliensis, a plant containing pyrrolidine alkaloids, which are one of the main causes of HSOS in the East, highlighting the risk of liver injury with herbs intake.

High Prevalence of Multidrug Resistant Bacteria in Cirrhotic Patients with Spontaneous Bacterial Peritonitis: Is It Time to Change the Standard Antimicrobial Approach?

Introduction: Spontaneous bacterial peritonitis (SBP) has a deleterious clinical impact in end-stage liver disease, and multidrug resistance has increased, raising concern about effectiveness of traditional antibiotic regimens. Patients and Methods: Single-center retrospective study of ascitic fluid infections in cirrhotic patients. Results: We analyzed medical records related to 2129 culture-positive ascitic fluid and found 183 samples from cirrhotic patients. There were 113 monobacterial SBP cases from 97 cirrhotic patients; 57% of patients were male; hepatitis C and alcohol were the main etiologies for cirrhosis. Multidrug resistant bacteria were isolated in 46.9% of SBP samples, and third-generation cephalosporin and quinolone resistant reached 38.9% and 25.7% of SBP cases. Conclusion: SBP due to multidrug resistant bacteria is a growing problem, and one should consider reported resistance profiles for the decision-making process of empirical first-line treatment prescription.

Características clínicas y de laboratorio en pacientes cirróticos asociada con desnutrición moderada o severa / Clinical and laboratory characteristics of cirrhotic patients associated with moderate and severe malnutrition

Context and objective: Protein-energy malnutrition is described Context and objective: Protein-energy malnutrition is described in 25-100% of patients with cirrhosis. The aim of this study was to evaluate the nutritional status of cirrhotic patients, to identify clinical and laboratory variables associated with moderate to severe malnutrition and to correlate them with cirrhosis prognostic factors (Child-Pugh Classification). Design and setting: This cross-sectional study evaluated cirrhotic individuals admitted to University Hospital from December 2011 to August 2012. Methods: Nutritional status was evaluated by Subjective Global Assessment (SGA), total lymphocyte count and serum albumin. Bivariate analysis was used to identify variables associated with Child C and with moderate to severe malnutrition in different nutritional classifications. Results: Sixty-seven patients were included (mean age 54.4 ± 11.7 years; 74.6% men). The mean MELD score was 14.5 ± 6.5, and almost 30% of the individuals were classified as Child C. With respect to nutritional status, 20.9% showed severe malnutrition by SGA, 14.9% malnutrition by total lymphocyte count, and 40.3% by albumin levels. In all methods employed, moderate to severe malnutrition was correlated with Child classification grade C. The rate of moderate to severe malnutrition by SGA was lower than that evidenced by laboratory methods. Nevertheless, SGA indicated a greater proportion of Child C patients with moderate to severe malnutrition. Conclusion: Due to the high prevalence of malnutrition and its correlation to the severity of cirrhosis, the nutritional evaluation ofcirrhotic patients is an essential step that can be performed through simple methods in routine hospital care.

Contexto y objetivo: la desnutrición proteico-calórica es reportada en 25 a 100 % de los pacientes con cirrosis. El objetivo de este estudio fue evaluar el estado nutricional de los pacientes cirróticos e identificar las variables clínicas y de laboratorio asociadas a la desnutrición moderada a severa y correlacionarlas con los factores de pronósticos de la cirrosis (clasificación de Child-Pugh). Diseño y montaje: Este es un estudio transversal que evaluó pacientes cirróticos ingresados en el Hospital Universitario de diciembre 2011 a agosto 2012. Métodos: El estado nutricional se consiguió mediante la Evaluación Subjetiva Global (ESG), recuento total de linfocitos (RTL) y albúmina sérica. Un análisis bivariado se utilizó para identificar las variables asociadas con el Child C y con la desnutrición Moderada-severa en diferentes clasificaciones nutricionales. Resultados: 67 pacientes fueron incluidos con una edad media de 54,4 ± 11,7 años, 74,6 % hombres. La media del registro MELD fue de 14,5 ± 6,5 y casi 30% de los individuos eran Child C. En cuanto al estado nutricional, el 20,9 % tenían desnutrición severa por ESG, 14,9 % por RTL, y el 40,3 % por albúmina. Para todos los métodos, la malnutrición moderada severa se correlacionó con Child C. La tasa de malnutrición moderada a grave detectada en la población por ESG fue más baja que la demostrada por los métodos de laboratorio. Sin embargo, el ESG indica una mayor proporción de pacientes Child C y con desnutrición moderada a severa. Conclusiones: Dada la alta prevalencia de desnutrición y su correlación con la gravedad de la cirrosis, la evaluación nutricional de los pacientes con cirrosis hepática es un paso esencial que se puede lograr a través de métodos simples y de rutina del hospital.