Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol‐related liver ...disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal‐specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti–Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90‐day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11‐8.82; P = 0.031). Conclusion: Patients with alcohol‐associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.
Background and Aims
Alcoholic hepatitis (AH) is a severe manifestation of alcohol‐associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little ...is known about the effects of the viral microbiome (virome) in patients with ALD.
Approach and Results
We extracted virus‐like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus‐like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia‐, Enterobacteria‐, and Enterococcus phages were over‐represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End‐Stage Liver Disease score, and associated with increased 90‐day mortality.
Conclusions
In conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.
Helicobacter pylori(H. pylori) affects nearly half of the world’s population and, thus, is one of the most frequent and persistent bacterial infections worldwide. H. pylori is associated with peptic ...ulcer disease, gastric ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Various diagnostic methods exist to detect infection, and the choice of one method or another depends on several factors, such as accessibility, advantages and disadvantages of each method, cost, and the age of patients. Once H. pylori infection is diagnosed, the clinician decides whether treatment is necessity, according to the patient’s clinical condition. Typically, eradication of H. pylori is recommended for treatment and prevention of the infection. Cure rates with the standard triple therapy are acceptable, and effective quadruple therapies, sequential therapies, and concomitant therapies have been introduced as key alternatives to treat H. pylori infection. In this work, we review the main diagnostic methods used to identify H. pylori infection and to confirm eradication of infection. In addition, key factors related to treatment are reviewed.
Background & Aims
Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the ...administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort.
Methods
This was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end‐stage liver disease (MELD). We evaluated bacterial infections, liver‐related complications, mortality and liver function tests after 90 days.
Results
Twenty‐one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute‐on‐chronic liver failure (ACLF) linked to infections within the treatment group. Liver‐related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment.
Conclusions
Rifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients.
The 10‐item Alcohol Use Disorders Identification Test (AUDIT‐10) and its shorter form, AUDIT‐Consumption (AUDIT‐C), are questionnaires used to characterize severity of drinking. We hypothesized that ...liver injury and short‐term outcomes of alcohol‐associated hepatitis (AH) would correlate with a patient’s recent alcohol consumption as determined by AUDIT‐10 and AUDIT‐C. We analyzed a prospective international database of patients with AH diagnosed based on the National Institute on Alcohol Abuse and Alcoholism (NIAAA) standard definitions. All patients were interviewed using AUDIT‐10. Primary outcomes included the discriminatory ability of the AUDIT‐10 and AUDIT‐C scores for predicting survival status at 28 and 90 days and severity of liver injury, as measured by Model for End‐Stage Liver Disease–sodium (MELD‐Na). The relationship between AUDIT scores and survival status was quantified by calculating the area under the curve of the receiver operating characteristic analysis. The relationship between AUDIT scores and MELD‐Na was examined using correlation coefficients. In 245 patients (age range 25‐75 years; 35% female), we found no correlation between AUDIT‐10 or AUDIT‐C scores and either 28‐ or 90‐day mortality. Similarly, there was no correlation between AUDIT‐10 and AUDIT‐C and MELD‐Na scores. There was a strong positive correlation between MELD‐Na and 28‐ and 90‐day mortality. Additional measures of severity of alcohol use (average grams of alcohol consumed per day, years of drinking, convictions for driving under the influence, and rehabilitation attempts) and psychosocial factors (marriage, paid employment, and level of social support) had no influence on MELD‐Na. In patients presenting with AH, AUDIT‐10 and AUDIT‐C were predictors of neither clinical severity of liver disease nor short‐term mortality, suggesting that level of alcohol consumption in the prior year is not key to the presenting features or outcome of AH.
Clostridium difficile NAP1/ribotype 027 is associated with severe disease and high mortality rates. Our aim was to determine the prevalence of NAP1/ribotype 027 among C. difficile isolates in a ...tertiary care hospital, and review the main clinical data.
We included 106 stool samples from 106 patients. Samples were tested for A&B toxins and were cultured on CCFA agar. The genes tcdA, tcdB, tcdC, cdtA, and cdtB were amplified using PCR in clinical isolates. The tcdA 3'-end deletion analysis, PCR-ribotyping, and pulsed-field gel electrophoresis (PFGE) were also performed. Stool samples that were positive for culture were tested by the GeneXpert C. difficile assay. Clinical data were collected.
Thirty-six patients tested positive for A&B toxins; and 22 patients had positive culture for C. difficile, 14 of which tested positive for the A&B toxins and all 22 patients tested positive by the GeneXpert C. difficile assay. Risk factors included an average hospital stay of 16.1 days prior to toxin detection, average antibiotic use for 16.2 days, and a median of 3 antibiotics used. The 30-day crude mortality rate was 8.4%. Six of the 22 patients died, and 3 of those deaths were directly attributed to C. difficile infection. The majority of isolates, 90.9% (20/22), carried genes tcdB, tcdA, cdtA, and cdtB; and these strains carried the corresponding downregulator gene tcdC, with an 18-bp deletion. PFGE was performed on 17 isolates, and one main pattern was observed. Analysis of the ribotyping data showed similar results.
The above findings represent the clonal spread of C. difficile in our institution, which mainly includes the NAP1/027 strain. This is the first report of C. difficile ribotype NAP1/027 in Mexico.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The intensity of the inflammation induced by Helicobacter pylori colonization is associated with the development of distal gastric cancer (GC). The host response to H. pylori has been related to ...genetic polymorphisms that influence both innate and adaptive immune responses.Our aim was to investigate whether the presence of the TLR4 Asp299Gly, TLR4 Thr399Ile and IL-8-251 A/T polymorphisms had any influence in the development of distal GC in a Mexican population.
We studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of H. pylori in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for TLR4 Asp299Gly polymorphism by pyrosequencing, for TLR4 Thr399Ile by PCR-RFLP and for IL8-251 by the amplification refractory mutation system (ARMS)-PCR.
The non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square H-W = 0.58 for IL8-251, 0.42 for TLR4 Asp299Gly and 0.17 for TLR4 Thr399Ile). The frequencies of mutated alleles (homozygous plus heterozygous) were compared between cases and controls. We found no significant difference for TLR4- Asp299Gly the 7.7% of distal GC patients and 7.7 % non-cancer controls (p = 0.82) and for TLR4 Thr399Ile the 1.3% of GC patients and the 5% of the control population (p = 0.2). In contrast, for IL-8-251 A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1-4.2) (p = 0.023).
This study showed that the IL8-251*A allele could be related to the development of distal gastric cancer in this Mexican population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality
. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated ...liver disease. The gut microbiota promotes ethanol-induced liver disease in mice
, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis
-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.
The mechanisms responsible for the development of acute pancreatitis (AP) and its complications are not fully understood.
To assess the role of clinical and host molecular factors for the development ...and outcome of persistent systemic inflammatory response syndrome (SIRS) in patients with AP.
We included 191 patients with AP in the study. The considered variables were demographic characteristics, prognosis and outcome, etiology, laboratory findings and complications. Interleukin (IL) 10 (-1082 G/A, -592 C/A), TNFA-308 (G/A) and ILB-31 (C/T) polymorphisms were determined by pyrosequencing. An amplification refractory mutation system-polymerase chain reaction method was used to genotype the IL8-251 (A/T) polymorphism.
Demographic characteristics were not statistically significant risk factors for the acquisition of persistent SIRS in patients with AP. Patients with hypertriglyceridemia were more likely to develop persistent SIRS (P < 0.05). No association with the TNFA, ILB, IL8-251 (A/T) and IL10 single-nucleotide polymorphisms was detected from the allele, genotype or haplotype frequencies.
Patients with hypertriglyceridemia-induced AP were more likely to develop persistent SIRS.
AbstractMultiple biliary hamartomas are rare benign malformations of the intrahepatic bile ducts first described by von Meyenburg in 1918. They originate from embryonic bile ducts that fail to ...involute. These are generally asymptomatic and usually encountered as an incidental finding at imaging, laparotomy or autopsy.
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