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BackgroundScientific literature shows a high prevalence of Small Intestinal Bacterial Overgrowth (SIBO) in patients with Cystic Fibrosis (CF). The role of SIBO in nutritional status and gastrointestinal symptoms in CF is not known. Our aim was to study epidemiology and clinical impact of SIBO while assessing the efficacy of rifaximin in eradicating SIBO in CF patients.MethodsSymptoms questionnaire and Glucose Breath Test (GBT) were given to 79 CF patients (median age 19.6 years; 9.2–36.9). Subjects with a positive GBT were enrolled in a randomized controlled trial and received rifaximin 1200 mg for 14 days or no treatment. Questionnaire and GBT were repeated 1 month after the end of treatment or 45 days after the first negative GBT.ResultsOut of 79 patients, 25 were affected by SIBO (31.6%) with a significant correlation with lower BMI, SDS-BMI (p < 0.05) and serum albumin levels (p < 0.05), independently from pancreas insufficiency. Twenty-three patients took part in the randomized trial, 13 patients (56.5%) in rifaximin group and 10 patients (43.5%) in control group. Eradication rate of SIBO was 9/10 (90%) in rifaximin group and 2/6 (33.3%) in control group (p < 0.05). In the rifaximin group, gastrointestinal symptom improvement was observed in 4/5 patients aged ≤ 14 years and in 0/5 patients aged > 14 years (p < 0.05); in 2/6 patients in the control group.ConclusionsCF patients show a high prevalence of SIBO, related to a poorer nutritional status. Rifaximin therapy is well tolerated and the results are promising in terms of efficacy in eradicating small intestinal bacterial overgrowth in CF.

Ulcerative colitis (UC) management encompasses conventional and advanced treatments, including biological therapy and small molecules. Surgery, particularly in the form of ileal pouch-anal anastomosis (IPAA), is indicated in cases of refractory/severe disease. IPAA can lead to acute complications (e.g., acute pouchitis) as well as late complications, including chronic inflammatory disorders of the pouch. Chronic pouchitis, including the antibiotic-dependent (CADP) and antibiotic-refractory (CARP) forms, represents a significant and current therapeutic challenge due to the substantial need for evidence regarding viable treatment options. Biological therapies have shown promising results, with infliximab, adalimumab, ustekinumab, and vedolizumab demonstrating some efficacy in chronic pouchitis; however, robust randomized clinical trials are only available for vedolizumab. This narrative review focuses on the evidence concerning small molecules in chronic pouchitis, specifically Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor (S1P-R) modulators. According to the preliminary studies and reports, Tofacitinib shows a potential effectiveness in CARP. Upadacitinib presents variable outcomes from the case series, necessitating further evaluation. Filgotinib and ozanimod demonstrate anecdotal efficacy. This review underscores the need for high-quality studies and real-world registries to develop robust guidelines for advanced therapies in post-IPAA inflammatory disorders, supported by vigilant clinical monitoring and ongoing education from international IBD specialist societies.

ObjectivesThe number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. We compared the presenting features and outcome of HCC in elderly (≥70 years) and younger patients (<70 years).DesignMulticentre retrospective cohort study and nested case–control study.Patients614 elderly and 1104 younger patients from the ITA.LI.CA database, including 1834 HCC cases consecutively diagnosed from January 1987 to December 2004. Both groups were stratified according to treatment: hepatic resection, percutaneous procedures, transarterial chemoembolisation (TACE). Survival was assessed in the whole population and in each treatment subgroup. Age, sex, aetiology, cirrhosis, comorbidities and cancer stage (CLIP score) were tested as predictors of survival. In each subgroup, differences in patient survival were also assessed after adjustment and matching by propensity score.ResultsAgeing was associated with a higher prevalence of comorbidities, better liver function and CLIP score. Regardless of age, two-thirds of patients underwent radical treatments or TACE. Elderly patients underwent more ablative procedures and fewer resections or TACE sessions. The survival of elderly and younger patients was comparable in each treatment subset, and was predicted by CLIP score. This result was confirmed by the propensity analysis.ConclusionsThe overall applicability of radical or effective HCC treatments was unaffected by old age. However, treatment distribution differed, elderly individuals being more frequently treated with percutaneous procedures and less frequently with resection or TACE. Survival was unaffected by age and primarily predicted by cancer stage, assessed by the CLIP system, both in the overall population and in treatment subgroups.

Allocation of deceased-donor livers to patients with chronic liver failure is improved by prioritising patients by 5-year liver transplantation survival benefit. The Barcelona Clinic Liver Cancer (BCLC) staging has been proposed as the standard means to assess for prognosis of patients with hepatocellular carcinoma. We aimed to create a prediction model linking the BCLC stage of patients with hepatocellular carcinoma to their 5-year liver transplant benefit. A large cohort of consecutive patients with hepatocellular carcinoma (n=1328) from the ITA.LI.CA database (n=2951) were judged as potentially eligible for liver transplantation according to the following criteria: absence of macroscopic vascular invasion or metastases, age 70 years or younger, and absence of relevant extra-hepatic comorbidities. To assess the correlation between BCLC staging and non-liver transplantation survival, we did Cox univariate and multivariate analyses including the following covariates: BCLC stage, year of diagnosis, age, sex, cause of cirrhosis, model for end-stage liver disease score, α-fetoprotein concentrations, and treatment. Liver-transplantation survival benefit for patients was calculated, using Monte Carlo simulation analysis, as the patient's 5-year life expectancy with liver transplantation (estimated by the Metroticket model) minus the 5-year life expectancy without liver transplantation according to BCLC stage. 83 (6%) of 1328 patients had BCLC 0 stage disease, 614 (46%) had BCLC A, 500 (38%) had BCLC B–C, and 131 (10%) had BCLC D. In the Cox non-liver transplantation survival multivariate model, hazard ratios associated with increasing BCLC stages were 1·530 (95% CI 1·107–2·116) for BCLC A versus BCLC 0, 1·572 (1·350–1·830) for BCLC B–C versus BCLC A, and 1·470 (1·164–1·856) for BCLC D versus BCLC B–C. Results of the Monte Carlo simulation analysis confirmed the significant effect of BCLC classification on transplant benefit; in the adjusted model, a median 5-year transplant benefit of 11·19 months (IQR 10·73–11·67) for BCLC 0, 13·49 months (11·51–15·57) for BCLC A, 17·36 months (15·06–19·28) for BCLC B–C, and 28·46 months (26·38–30·34) for BCLC D. Liver transplantation could result in survival benefit for patients with hepatocellular carcinoma and advanced liver cirrhosis (BCLC stage D) and in those with intermediate tumours (BCLC stages B–C), regardless of the nodule number–size criteria (ie, Milan criteria), provided that macroscopic vascular invasion and extra-hepatic disease are absent. None.

The gut microbiota has emerged as a critical player in metabolic and liver health, with its influence extending to the pathogenesis and progression of steatotic liver diseases. This review delves into the gut-liver axis, a dynamic communication network linking the gut microbiome and liver through metabolic, immunological, and inflammatory pathways. Dysbiosis, characterized by altered microbial composition, contributes significantly to the development of hepatic steatosis, inflammation, and fibrosis via mechanisms such as gut barrier dysfunction, microbial metabolite production, and systemic inflammation. Dietary patterns, including the Mediterranean diet, are highlighted for their role in modulating the gut microbiota, improving gut-liver axis integrity, and attenuating liver injury. Additionally, emerging microbiota-based interventions, such as fecal microbiota transplantation and bacteriophage therapy, show promise as therapeutic strategies for steatotic liver disease. However, challenges such as population heterogeneity, methodological variability, and knowledge gaps hinder the translational application of current findings. Addressing these barriers through standardized approaches and integrative research will pave the way for microbiota-targeted therapies to mitigate the global burden of steatotic liver disease.

Background: Ustekinumab and vedolizumab represent both valid therapeutic options in patients with Crohn’s Disease. Data comparing the safety and efficacy of these drugs are indirect, with conflicting results reported. We aim to conduct a systematic review and metanalysis to assess the safety and effectiveness profile of ustekinumab and vedolizumab in patients with Crohn’s Disease, including only studies that applied propensity scores to reduce confounding bias. Methods: We identified 59 reports that compared ustekinumab and vedolizumab after a propensity score match analysis, of which 16 were assessed for eligibility, and finally, ten retrospective studies were included. The main outcomes considered were clinical steroid-free remission at 14 ± 4, 24 ± 4, and 52 ± 4 weeks, drug discontinuation rate, adverse events, serious infections, and hospitalization during the first year of treatment. Results: A total of 4398 patients were treated with ustekinumab (n = 2774, 63.1%) or vedolizumab (1624, 36.9%). Steroid-free clinical remission was not significantly different between ustekinumab and vedolizumab at 12 ± 4 weeks (OR 1.31, 95%CI 0.88–1.94, p = 0.180), at 24 ± 4 weeks (OR 1.18, 95%CI 0.79–1.75, p = 0.420), and at 52 ± 4 weeks (1.35, 95%CI 0.91–2.01, p = 0.140). In patients receiving ustekinumab, the rate of adverse events (OR 0.54, 95%CI 0.35–0.83, p = 0.005), infection (OR 0.61, 95%CI 0.47–0.80, p < 0.001) and the need of hospitalization at 1-year (OR 0.68, 95%CI 0.58–0.80, p < 0.001) appeared to be lower. Conclusion: Ustekinumab and vedolizumab do not significantly differ in inducing and maintaining clinical steroid-free remission, while ustekinumab was associated with a lower risk of serious infections and hospitalization during the first year of treatment.

Background and Objectives: HCV infection represents a main risk factor for type 2 diabetes (T2D). This real-world analysis investigated the HCV-positive (HCV+) population with a T2D co-diagnosis in Italy. Methods: From 2017 to 2021, HCV+ patients were identified from administrative databases and stratified into T2D-HCV+ and HCV+-only cohorts in the presence/absence of a T2D diagnosis. Both cohorts were further divided by treatment with direct-acting antivirals (DAAs). The subgroups were compared for demographic variables, comorbidity profiles, most frequent hospitalizations, and drug prescriptions before inclusion. A sensitivity analysis was performed on patients included after 2019, the year of widespread use of pangenotypic DAAs. Results: Considering HCV+ patients aged ≥55 years, T2D-HCV+ patients (N = 1277) were significantly (p < 0.001) older than HCV+-only (N = 6576) ones and burdened by a worse comorbidity profile (average Charlson index: 1.4 vs. 0.3, p < 0.05). Moreover, regardless of T2D presence, DAA-treated patients were older (p < 0.001) and had a worse Charlson index than the untreated ones. T2D-HCV+ patients showed tendentially higher hospitalization rates and co-medication prescriptions compared to the HCV+-only patients. After 2019, a trend towards reduced co-medication use in DAA-treated patients was noticed, especially antibiotics and cardiovascular drugs. Conclusions: The co-presence of T2D in HCV+ patients resulted in a worse clinical status, as confirmed by the more frequent requirement of hospitalizations and complex polypharmacy regimens.

Surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on ultrasonography and alpha-fetoprotein (AFP) measurement, is widely used. Its effectiveness depends on liver function, which affects the feasibility of treatments and cirrhosis-related mortality. We assessed whether patients with intermediate/advanced cirrhosis benefit from surveillance. We selected 468 Child-Pugh class B and 140 class C patients from the ITA.LI.CA database, including 1,834 HCC patients diagnosed from January 1987 to December 2004. HCC was detected in 252 patients during surveillance (semiannual 172, annual 80 patients; group 1) and in 356 patients outside surveillance (group 2). Survival of surveyed patients was corrected for the estimated lead time. Child-Pugh class B: cancer stage (P < 0.001) and treatment distribution (P < 0.001) were better in group 1 than in group 2. The median (95% CI) survivals were 17.1 (13.5-20.6) versus 12.0 (9.4-14.6) months and the survival rates at 1, 3, and 5 yr were 60.4%versus 49.2%, 26.1%versus 16.1%, and 10.7%versus 4.3%, respectively (P= 0.022). AFP, gross pathology, and treatment of HCC were independent prognostic factors. Child-Pugh class C: cancer stage (P= 0.001) and treatment distribution (P= 0.021) were better in group 1 than in group 2. Nonetheless, median survival did not differ: 7.1 (2.1-12.1) versus 6.0 (4.1-7.9) months (P= 0.740). These results suggest surveillance be offered to class B patients and maintained for class A patients who migrate to the subsequent class. Surveillance becomes pointless in class C patients probably because the poor liver function adversely affects the overall mortality and HCC treatments.

Although the etiology of liver disease affects the features of hepatocellular carcinoma (HCC) diagnosed during surveillance, it is not known whether it influences patients' survival. We analyzed the impact of etiology on the characteristics and outcome of HCC detected during surveillance. In this cohort study, 742 patients with HCC detected during semiannual or annual surveillance were selected from the ITA.LI.CA database, including 1,834 consecutive patients observed in three primary and seven tertiary care settings for HCC. Patients were grouped according to etiology: hepatitis B virus (HBV, 87), hepatitis C virus (HCV, 461), alcohol (59), and multietiology (135). In all etiologic groups, most HCCs were unifocal (51-68%) and most of them were

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