The evidence on the role of gut microbiota in post-infectious irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively affect IBS symptoms, although the mechanisms through which ...probiotics exert their beneficial effects are largely unknown. The aim of the study is to evaluate the role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model.
Ex vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea predominant subtype (D) patients, and 10 healthy controls (HC) were treated with LPS, LC-DG and PB. Interleukin (IL)-1α, IL-6, IL-8 and IL-10 mRNA levels were assessed by real-time PCR and Toll like receptor 4 (TLR-4) protein expression by Western blotting.
At baseline, IL-1α, IL-6 and IL-8 mRNA levels as well as TLR-4 protein expression were significantly higher while IL-10 mRNA levels were lower in PI-IBS D than in HC in both ileum and colon. LC-DG and PB significantly reduced the mRNA levels of pro-inflammatory cytokines and TLR-4 while increased that of IL-10 after LPS stimulation. The protective effect was more pronounced for PB than LC-DG treatment.
LC-DG and its PB attenuate the inflammatory mucosal response in an ex-vivo organ culture model of PI-IBS D.
The presence of significant fibrosis is an indicator for liver disease staging and prognosis. The aim of the study was to determine reproducibility of real-time shear wave elastography using a ...hepatic biopsy as the reference standard to identify patients with chronic liver disease. Forty patients with chronic liver disease and 12 normal subjects received shear wave elastography performed by skilled operators. Interoperator reproducibility was studied in 29 patients. Fibrosis was evaluated using the Metavir score. The median and range shear wave elastography values in chronic liver disease subjects were 6.15 kPa and 3.14-16.7 kPa and were 4.49 kPa and 2.92-7.32 kPa in normal subjects, respectively. With respect to fibrosis detected by liver biopsy, shear wave elastography did not change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3 and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4 groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index did not affect shear wave elastography measurements. Using receiver operator characteristic curves, two threshold values for shear wave elastography were identified: 5.62 kPa for patients with fibrosis (≥F2; sensitivity 80%, specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe fibrosis (≥F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall interobserver agreement was excellent and was analysed using an interclass correlation coefficient (0.94; CI 0.87-0.97).This study shows that shear wave elastography executed by skilled operators can be performed on almost all chronic liver disease patients with high reproducibility. It is not influenced by age, sex or body mass index, identifies severely fibrotic patients and is also related to inflammatory activity.
The prevalence of metabolic disorders, such as type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease (NAFLD), which are common risk factors for cardiovascular disease (CVD), has ...dramatically increased worldwide over the last decades. Although dietary habit is the main etiologic factor, there is an imperfect correlation between dietary habits and the development of metabolic disease. Recently, research has focused on the role of the microbiome in the development of these disorders. Indeed, gut microbiota is implicated in many metabolic functions and an altered gut microbiota is reported in metabolic disorders. Here we provide evidence linking gut microbiota and metabolic diseases, focusing on the pathogenetic mechanisms underlying this association.
Hepatic encephalopathy (HE) is a severe complication of advanced liver disease and acute liver failure. The clinical spectrum ranges from minor cognitive dysfunctions to lethargy, depressed ...consciousness, and coma and significantly impact the quality of life, morbidity, and mortality of the patients. It is commonly accepted that the gut milieu is essential for the development of HE; however, despite intensive research efforts, the pathogenesis of HE is still not fully elucidated. As our knowledge of gut microbiota moves from the pioneering era of culture-dependent studies, the connection between microbes, inflammation, and metabolic pathways in the pathogenesis of HE is becoming increasingly clear, providing exciting therapeutic perspectives. This review will critically examine the latest research findings on the role of gut microbes in the pathophysiological pathways underlying HE. Moreover, currently available therapeutic options and novel treatment strategies are discussed.
Lactose intolerance (LI) is characterized by diarrhea, abdominal pain, or bloating occurring after lactose consumption in patients with lactose malabsorption. The National Institute of Health (NIH) ...proposed a double-blind placebo testing to identify LI individuals correctly. However, until now, no study used this approach in a real-life setting. We aimed to assess double-blind placebo challenge accuracy in diagnosing LI in patients with self-reported symptoms of LI. 148 patients with self-reported LI were consecutively enrolled and blindly underwent hydrogen breath test (HBT) after 25 g lactose or 1 g glucose (placebo) load. One week later, the subjects were challenged with the alternative substrate. Each subject completed a validated questionnaire, including five symptoms (diarrhea, abdominal pain, vomiting, bowel sounds, and bloating) scored on a 10-cm visual analog scale. Home questionnaire (HQ) referred to symptoms associated with the consumption of dairy products at home, while lactose questionnaire (LQ) and placebo questionnaire (PQ) referred to symptoms perceived throughout the 4-h after the administration of the substrates, respectively. After lactose load, HBT was positive in 81 patients (55%), of whom 60 (74%) reported relevant symptoms at LQ (lactose malabsorbers, LM). After placebo challenge, 45 out of 60 with a positive lactose challenge did not complain of symptoms and therefore were diagnosed as lactose intolerant, according to NIH definition. The blinded oral challenges with lactose and placebo accurately diagnose LI and identify patients who will likely benefit from a lactose-free diet.
Abstract Background and study aims The diagnostic yield of small-bowel capsule endoscopy (SBCE) in suspected small bowel bleeding (SSBB) is highly variable. Different reimbursement systems and ...equipment costs also limit SBCE use in clinical practice. Thus, minimizing non-diagnostic procedures is advisable. This study aimed to assess the SBCE diagnostic yield and identify factors predicting diagnostic findings in a cohort of patients with SSBB. Patients and methods In this retrospective cohort study, we analyzed the medical records of patients who consecutively underwent SBCE for SSBB over 9 years. By logistic regression, we identified covariates predicting diagnostic findings at SBCE. Finally, we performed a post-hoc cost analysis based on previous gastroenterologist or endoscopist consultations versus direct SBCE ordering by other specialists. Results The final analysis included 584 patients. Most SBCEs were ordered by a gastroenterologist or endoscopist (74%). The number of SBCEs without any finding was significantly lower in the gastroenterologist/endoscopist group P<0.001). The SBCE diagnostic yield ordered by a gastroenterologist or endoscopist was significantly higher than that by other specialists (63% vs 52%, odds ratio OR 1.57; 95% confidence interval CI 1.07–2.26, P=0.019). At multivariate analysis, older age (OR 1.7, 95%CI 1.2–2.4, P=0.005), anemia (OR 4.9, 95%CI 1.9–12, P=0.001), small bowel transit time (OR 1, 95%CI 1–1.02, P=0.039), and referring physician (OR 1.8, 95%CI 1.1–2.7, P=0.003) independently predicted diagnostic findings. Implementing prior gastroenterologist or endoscopist referral vs direct SBCE ordering would reduce medical expenditures by 16%. Conclusions The professional background of referring physicians significantly improves the diagnostic yield of SBCE and contributes to controlling public health costs.
We aimed at assessing the impact of surveillance on long-term survival in HCC patients.
From the ITA.LI.CA database, we selected 1028 cases with long (≥5 years, LS group) and 2721 controls with ...short-term survival (<5 years, SS group). The association between surveillance and LS was adjusted for confounders by multivariable logistic regression analysis. Survival of surveilled patients was presented both as observed and corrected for the lead-time bias, and the comparison of survival between surveillance and no surveillance groups was also performed after balancing the baseline characteristics with inverse probability weights (IPW).
LS patients were more frequently diagnosed under surveillance (
< 0.0001), and had more favorable baseline characteristics. Surveillance was an independent predictor of LS (OR = 1.413, 95% CI 1.195-1.671;
< 0.0001). The observed and the lead-time corrected survival of surveilled patients were significantly longer compared to the survival of not surveilled patients (
< 0.0001 and
= 0.0008, respectively). In IPW adjusted populations, no survival differences were demonstrated between the two groups (
= 0.30).
Surveillance, increasing early-stage diagnosis and applicability of curative treatments, is a fundamental determinant of long-term survival in HCC patients. A wide implementation of surveillance programs should be pursued in order to improve HCC patients' prognosis.
Summary
Background
Chronic use of proton pump inhibitors (PPIs) in patients with impaired liver function may worsen cytochrome P450 (CYP450) activity, predisposing them to clinically relevant ...drug–drug interactions. The 13C‐aminopyrine breath test (13C‐ABT) is a non‐invasive tool to study CYP450‐dependent liver function.
Aims
To assess 13C‐ABT modifications with different PPIs in patients with cirrhosis
Methods
Sixty consecutive patients with HCV‐related cirrhosis and indication to start PPI therapy were randomised to receive omeprazole 20 mg/day, esomeprazole 20 mg/day, lansoprazole 15 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day. 13C‐ABT was performed at baseline and on the 15th day of PPI therapy.
Results
At baseline, mean values of max 13C% dose/h and 13C% cum dose at 120 minutes did not differ significantly among groups. On the 15th day of therapy, max 13C% dose/h and 13C% cum dose at 120 minutes did not significantly differ with respect to baseline for pantoprazole (P = 0.184 and P = 0.309, respectively) or rabeprazole (P = 0.536 and P = 0.286, respectively), but were significantly decreased on omeprazole (P = 0.013 and P = 0.015, respectively), esomeprazole (P = 0.009 and P = 0.001, respectively), and lansoprazole (P = 0.033 and P = 0.035, respectively).
Conclusions
In patients with cirrhosis, omeprazole, esomeprazole and lansoprazole inhibit microsomal activity while pantoprazole and rabeprazole do not have a significant impact. Should our data be confirmed in larger cohort studies, pantoprazole and rabeprazole could be safely recommended for patients with cirrhosis.
LINKED CONTENT
This article is linked to Rocco et al and Celsa & Cammà papers. To view these articles, visit https://doi.org/10.1111/apt.16239 and https://doi.org/10.1111/apt.16250
Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of ...this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort.
We analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC.
MAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002-2003, to 77.3% and 28.9% in 2018-2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006).
The prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.
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