Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure.

BACKGROUND AND AIMS: Around 750,000 patients per year will be cured of HCV infection until 2030. Those with compensated advanced chronic liver disease remain at risk for hepatic decompensation and de novo HCC. Algorithms have been developed to stratify risk early after cure; however, data on long-term outcomes and the prognostic utility of these risk stratification algorithms at later time points are lacking. APPROACH AND RESULTS: We retrospectively analyzed a cohort of 2335 patients with compensated advanced chronic liver disease (liver stiffness measurement≥10 kPa) who achieved HCV-cure by interferon-free therapies from 15 European centers (median age 60.2±11.9 y, 21.1% obesity, 21.2% diabetes).During a median follow-up of 6 years, first hepatic decompensation occurred in 84 patients (3.6%, incidence rate: 0.74%/y, cumulative incidence at 6 y: 3.2%); 183 (7.8%) patients developed de novo HCC (incidence rate: 1.60%/y, cumulative incidence at 6 y: 8.3%), with both risks being strictly linear over time.Baveno VII criteria to exclude (FU-liver stiffness measurement <12 kPa and follow-up platelet count >150 g/L) or rule-in (FU-liver stiffness measurement ≥25 kPa) clinically significant portal hypertension (CSPH) stratified the risk of hepatic decompensation with proportional hazards. Estimated probability of CSPH discriminated patients developing versus not developing hepatic decompensation in the gray zone (ie, patients meeting none of the above criteria).Published HCC risk stratification algorithms identified high-incidence and low-incidence groups; however, the size of the latter group varied substantially (9.9%-69.1%). A granular "HCC-sustained virologic response" model was developed to inform an individual patient's HCC risk after HCV-cure. CONCLUSIONS: In patients with compensated advanced chronic liver disease, the risks of hepatic decompensation and HCC remain constant after HCV-cure, even in the long term (>3 y). One-time post-treatment risk stratification based on noninvasive criteria provides important prognostic information that is maintained during long-term follow-up, as the hazards remain proportional over time.

Performance of spleen stiffness measurement to rule out high-risk varices in patients with porto-sinusoidal vascular disorder.

BACKGROUND AND AIMS: Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is ≤40 kPa as they have a low probability of high-risk varices (HRV). Conversely, screening endoscopy is required in all patients with porto-sinusoidal vascular disorder (PSVD). This study aimed to evaluate the performance of SSM-VCTE to rule out HRV in patients with PSVD and signs of portal hypertension. APPROACH AND RESULTS: We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without a history of variceal bleeding, who underwent an SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. One hundred fifty-four patients were included in the derivation cohort; 43% had HRV. By multivariable logistic regression analysis, SSM-VCTE >40 kPa and serum bilirubin ≥1 mg/dL were associated with HRV. SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL had a sensitivity of 96% to rule out HRV and could spare 38% of screening endoscopies, with 4% of HRV missed, and a 95% negative predictive value. In the validation cohort, including 155 patients, SSM combined with bilirubin could spare 21% of screening endoscopies, with 4% of HRV missed and a 94% negative predictive value. CONCLUSIONS: This study gathering a total of 309 patients with PSVD showed that SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL identifies patients with PSVD and portal hypertension with a probability of HRV <5%, in whom screening endoscopy can be spared.

Post-treatment LSM rather than change during treatment predicts decompensation in patients with cACLD after HCV cure.

BACKGROUND & AIMS: Baveno VII has defined a clinically significant (i.e., prognostically meaningful) decrease in liver stiffness measurement (LSM) in cACLD as a decrease of ≥20% associated with a final LSM <20 kPa or any decrease to <10 kPa. However, these rules have not yet been validated against direct clinical endpoints. METHODS: We retrospectively analysed patients with cACLD (LSM ≥10 kPa) with paired liver stiffness measurement (LSM) before (BL) and after (FU) HCV cure by interferon-free therapies from 15 European centres. The cumulative incidence of hepatic decompensation was compared according to these criteria, considering hepatocellular carcinoma and non-liver-related death as competing risks. RESULTS: A total of 2,335 patients followed for a median of 6 years were analysed. Median BL-LSM was 16.6 kPa with 37.1% having ≥20 kPa. After HCV cure, FU-LSM decreased to a median of 10.9 kPa (<10 kPa: 1,002 [42.9%], ≥20 kPa: 465 [19.9%]) translating into a median LSM change of -5.3 (-8.8 to -2.4) kPa corresponding to -33.9 (-48.0 to -15.9) %. Patients achieving a clinically significant decrease (65.4%) had a significantly lower risk of hepatic decompensation (subdistribution hazard ratio: 0.12, 95% CI 0.04-0.35, p <0.001). However, these risk differences were primarily driven by a negligible risk in patients with FU-LSM <10 kPa (5-year cumulative incidence: 0.3%) compared to a high risk in patients with FU-LSM ≥20 kPa (16.6%). Patients with FU-LSM 10-19.9 kPa (37.4%) also had a low risk of hepatic decompensation (5-year cumulative incidence: 1.7%), and importantly, the risk of hepatic decompensation did not differ between those with/without an LSM decrease of ≥20% (p = 0.550). CONCLUSIONS: FU-LSM is key for risk stratification after HCV cure and should guide clinical decision making. LSM dynamics do not hold significant prognostic information in patients with FU-LSM 10-19.9 kPa, and thus, their consideration is not of sufficient incremental value in the specific context of HCV cure. IMPACT AND IMPLICATIONS: Liver stiffness measurement (LSM) is increasingly applied as a prognostic biomarker and commonly decreases in patients with compensated advanced chronic liver disease achieving HCV cure. Although Baveno VII proposed criteria for a clinically significant decrease, little is known about the prognostic utility of LSM dynamics (changes through antiviral therapy). Interestingly, in those with a post-treatment LSM of 10-19.9 kPa, LSM dynamics did not provide incremental information, arguing against the consideration of LSM dynamics as prognostic criteria. Thus, post-treatment LSM should guide the management of patients with compensated advanced chronic liver disease achieving HCV cure.

Efficacy and safety of endoscopic ultrasound-guided hepaticogastrostomy: a meta-regression analysis.

BACKGROUND: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is a valid option for EUS-guided biliary drainage that has been increasingly used in the last decade. The aims of this study were to provide a systematic review with meta-analysis and meta-regression of the features and outcomes of this procedure. METHODS: The MEDLINE, Scopus, Web of Science, and Cochrane databases were searched for literature pertinent to EUS-HGS. Meta-analysis of the proportions and meta-regression of potential modifiers of the main outcome measures were applied. The main outcome was technical success; secondary outcomes were clinical success and procedure-related adverse events (AEs). RESULTS: 33 studies, including 1644 patients, were included in the meta-analysis. Malignant biliary obstruction (MBO) was the underlying cause in almost all cases (99.6%); the main indications for EUS-HGS were duodenal/papillary invasion (34.8%), surgically altered anatomy (18.4%), and hilar stenosis (16.0%). The pooled technical success of EUS-HGS was 97.7% (95%CI 96.1%-99.0%; I 2 = 0%), the intention-to-treat clinical success rate was 88.1% (95%CI 84.7%-91.2%; I 2 = 33.9%), and procedure-related AEs occurred in 12.0% (95%CI 9.8%-14.5%; I 2 = 20.4%), with cholangitis/sepsis (2.8%) and bleeding (2.3%) the most frequent. The rate of procedure-related AEs was lower with the use of dedicated stents on univariable meta-regression analysis. Meta-regression showed that technical success and clinical success rates were modified by the centers' experience (>4/year). CONCLUSIONS: EUS-HGS represents an effective and safe procedure for EUS-guided biliary drainage in patients with MBO. Future studies should address the impact of center experience, patient selection, and the use of dedicated stents to improve performance of this technique.

Diagnostic accuracy of FibroScan-AST (FAST) score for the non-invasive identification of patients with fibrotic non-alcoholic steatohepatitis: a systematic review and meta-analysis.

OBJECTIVE: A simple combined score with liver stiffness, controlled attenuation parameter and serum aspartate aminotransferase (AST), the FibroScan-AST (FAST) score, has been proposed to non-invasively identify patients with fibrotic non-alcoholic steatohepatitis (NASH). We performed a systematic review and meta-analysis of published studies to evaluate the overall diagnostic accuracy of the FAST score in identifying patients with fibrotic NASH. DESIGN: We systematically searched MEDLINE, Ovid Embase, Scopus and Cochrane Library electronic databases for full-text published articles in any language between 3 February 2020 and 30 April 2022. We included original articles that reported data for the calculation of sensitivity and specificity of the FAST score for identifying adult patients with fibrotic NASH adults, according to previously described rule-out (≤0.35) and rule-in (≥0.67) cut-offs. RESULTS: We included 12 observational studies for a total of 5835 participants with biopsy-confirmed non-alcoholic fatty liver disease. The pooled prevalence of fibrotic NASH was 28% (95% CI 21% to 34%). The FAST score's pooled sensitivity was 89% (95% CI 82% to 93%), and the pooled specificity was 89% (95% CI 83% to 94%) according to the aforementioned rule-in/rule-out cut-offs. The negative predictive value and positive predictive value of the FAST score were 92% (95% CI 91% to 95%) and 65% (95% CI 53% to 68%), respectively. Subgroup analyses and influential bias analyses did not alter these findings. CONCLUSION: The results of our meta-analysis show that the FAST score has a good performance for non-invasive diagnosis of fibrotic NASH. Therefore, this score can be used to efficiently identify patients who should be referred for a conclusive liver biopsy and/or consideration for treatment with emerging pharmacotherapies. PROSPERO REGISTRATION NUMBER: CRD42022350945.

The non-invasive evaluation of liver involvement in patients with cystic fibrosis: A prospective study.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) has been described as the prominent pathology in liver explants of patients with cystic fibrosis (CF), but data outside the transplant setting are lacking. We aimed to investigate the prevalence of portal hypertension (PH) in CF-associated liver disease (CFLD) and develop an algorithm to classify liver involvement in CF patients. METHODS: This is a cross-sectional study of consecutive paediatric and adult patients in a tertiary centre between 2018 and 2019, who underwent ultrasound, liver (LSM) and spleen stiffness (SSM) measurement. CFLD was defined according to physical examination, liver tests and ultrasound findings. PSVD was likely if there were PH signs in the absence of advanced chronic liver disease (CF-ACLD, LSM <10 kPa). A historical cohort was used to validate the prognostic significance of the new definitions. RESULTS: Fifty (27.5%) patients met CFLD criteria. At least one sign of PH was found in 47 (26%) patients, but most (81%) had LSM <10 kPa and were likely to have PSVD; only 9 (5%) had CF-ACLD. PSVD and CFLD (LSM <10 kPa) co-existed in most (23/36) cases. In the historical cohort (n = 599 patients), likely PSVD and CFLD+PH were independently associated with a 2-fold and 3.5-fold increase in mortality compared to patients without PH, respectively. In 34 patients with SSM, values <21 and >50 kPa accurately diagnosed specific signs of PH. CONCLUSIONS: PSVD is the prevailing cause of PH in CF patients. We developed a new diagnostic algorithm based on clinical and elastosonography criteria to classify liver involvement in patients with CF.

Kawasaki disease, multisystem inflammatory syndrome in children, and adenoviral infection: a scoring system to guide differential diagnosis.

Children with Kawasaki disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), and Adenovirus infections (AI) of the upper respiratory tract show overlapping features. This study aims to develop a scoring system based on clinical or laboratory parameters to differentiate KD or MIS-C from AI patients. Ninety pediatric patients diagnosed with KD (n = 30), MIS-C (n = 26), and AI (n = 34) admitted to the Pediatric Emergency Unit of S.Orsola University Hospital in Bologna, Italy, from April 2018 to December 2021 were enrolled. Demographic, clinical, and laboratory data were recorded. A multivariable logistic regression analysis was performed, and a scoring system was subsequently developed. A simple model (clinical score), including five clinical parameters, and a complex model (clinic-lab score), resulting from the addition of one laboratory parameter, were developed and yielded 100% sensitivity and 80% specificity with a score ≥2 and 98.3% sensitivity and 83.3% specificity with a score ≥3, respectively, for MIS-C and KD diagnosis, as compared to AI. CONCLUSION: This scoring system, intended for both outpatients and inpatients, might limit overtesting, contribute to a more effective use of resources, and help the clinician not underestimate the true risk of KD or MIS-C among patients with an incidental Adenovirus detection. WHAT IS KNOWN: • Kawasaki Disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C) and adenoviral infections share overlapping clinical presentation in persistently febrile children, making differential diagnosis challenging. • Scoring systems have been developed to identify high-risk KD patients and discriminate KD from MIS-C patients. WHAT IS NEW: • This is the first scoring model based on clinical criteria to distinguish adenoviral infection from KD and MIS-C. • The score might be used by general pediatricians before referring febrile children to the emergency department.

Can Liver Ultrasound Elastography Predict the Risk of Hepatocellular Carcinoma Recurrence After Radiofrequency Ablation? A Systematic Review and Meta-Analysis.

PURPOSE: The role of liver stiffness (LS) on ultrasound elastography in the prediction of hepatocellular carcinoma (HCC) recurrence after treatment with radiofrequency ablation (RFA) is still unclear. Our aim was to perform a systematic review and meta-analysis to assess whether LS can predict the recurrence of HCC after RFA. MATERIALS AND METHODS: Medline via PubMed, Embase, Scopus, and Cochrane Library databases, and abstracts of international conference proceedings were searched up to June 30, 2020. Cohort studies were included if they assessed the association between LS values measured by ultrasound elastography before RFA and HCC recurrence. RESULTS: 9 studies including 1373 patients with HCC treated by RFA, 643 of whom developed HCC recurrence, were identified. The mean value of LS before RFA was significantly higher in patients who developed HCC recurrence than in those who did not (weighted mean difference=11.98 kPa, 95%CI: 7.60-16.35, I2=63.8%). There was a significant positive association between LS value and HCC recurrence both at univariate (unadjusted HR=1.03, 95%CI: 1.00-1.07, I2=72.7%) and multivariate analysis (adjusted HR=1.03, 95%CI: 1.02-1.04, I2=0). Patients with LS value ≥13-14 kPa or >1.5 m/s have a higher risk of both HCC recurrence (unadjusted HR=2.18, 95%CI: 1.46-3.25, I2=49.7%; adjusted HR=2.41, 95%CI: 1.53-3.79, I2=0) and overall mortality (adjusted HR=4.38; 95%CI: 2.33-8.25, I2=0) in comparison with those with LS below these cutoffs. CONCLUSION: Liver ultrasound elastography appears to be a reliable tool to predict HCC recurrence and overall survival after RFA. This technique may be useful for the management of patients with HCC treated by RFA.

Osteosarcopenia in NAFLD/MAFLD: An Underappreciated Clinical Problem in Chronic Liver Disease.

Chronic liver disease (CLD), including non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), affects a significant portion of the population worldwide. NAFLD is characterised by fat accumulation in the liver, while NASH is associated with inflammation and liver damage. Osteosarcopenia, which combines muscle and bone mass loss, is an emerging clinical problem in chronic liver disease that is often underappreciated. The reductions in muscle and bone mass share several common pathophysiological pathways; insulin resistance and chronic systemic inflammation are the most crucial predisposing factors and are related to the presence and gravity of NAFLD and to the worsening of the outcome of liver disease. This article explores the relationship between osteosarcopenia and NAFLD/MAFLD, focusing on the diagnosis, prevention and treatment of this condition in patients with CLD.

A Combined Baveno VII and Spleen Stiffness Algorithm to Improve the Noninvasive Diagnosis of Clinically Significant Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease.

INTRODUCTION: A noninvasive diagnosis of clinically significant portal hypertension (CSPH) has important prognostic and therapeutic implications for patients with compensated advanced chronic liver disease. We aimed to validate and improve the available algorithms for the CSPH diagnosis by evaluating spleen stiffness measurement (SSM) in patients with compensated advanced chronic liver disease. METHODS: This is a retrospective study including patients with liver stiffness measurement (LSM) ≥10 kPa, no previous decompensation, and available measurements of hepatic venous pressure gradient, LSM, and SSM by transient elastography referring to our center in Bologna. The diagnostic algorithms were adequate if negative and positive predictive values were >90% when ruling out and ruling in CSPH, respectively; these models were validated in a cohort from Verona. The 5-year decompensation rate was reported. RESULTS: One hundred fourteen patients were included in the derivation cohort. The Baveno VII diagnostic algorithm (LSM ≤15 kPa + platelet count ≥150 × 10 9 /L to rule out CSPH and LSM >25 kPa to rule in CSPH) was validated; however, 40%-60% of the patients remained in the gray zone. The addition of SSM (40 kPa) to the model significantly reduced the gray zone to 7%-15%, maintaining adequate negative and positive predictive values. The diagnostic algorithms were validated in a cohort of 81 patients from Verona. All first decompensation events occurred in the "rule-in" zone of the model including SSM. DISCUSSION: The addition of SSM significantly improves the clinical applicability of the algorithm based on LSM and platelet count for CSPH diagnosis. Our models can be used to noninvasively identify candidates for nonselective beta-blocker treatment and patients at a high risk of decompensation.

Trial sequential analysis of EUS-guided gallbladder drainage versus percutaneous cholecystostomy in patients with acute cholecystitis.

BACKGROUND AND AIMS: Meta-analytic comparison of EUS-guided gallbladder drainage (EUS-GBD) versus percutaneous gallbladder drainage (PT-GBD) for acute cholecystitis (AC) brings the risk of spurious results if too few studies are included. Trial sequential analysis (TSA) can overcome this, providing information about its credibility. METHODS: Comparative studies between EUS-GBD, using lumen-apposing metal stents, and PT-GBD for AC until July 2021 were used for conventional meta-analysis and TSA, which allowed the use of monitoring boundaries and the estimation of the required information size (RIS) needed to prove credibility. RESULTS: Four studies accrued 535 patients. Technical success was in favor of PT-GBD (relative risk [RR], .967; P = .036), but TSA estimated that 1663 participants would be needed to avoid a Type I error (false positive). Clinical success was similar (RR, .965; P = .146), and TSA supported the absence of any demonstrable superiority of one therapy rather than a Type II error (false negative). EUS-GBD reduced overall adverse events (RR, .424; P < .001) and unplanned readmissions (RR, .215; P < .001), and TSA confirmed the avoidance of a Type I error, with early RIS achievement, providing necessary credibility. EUS-GBD had fewer reinterventions (RR, .244; P < .001), but a Type I error was not avoided, needing additional 97 patients to the accrued 535 to prove credibility. CONCLUSIONS: PT-GBD can provide superior technical success than EUS-GBD if a very large sample size is accrued, thus limiting the single-patient benefit. Clinical success is probably equivalent. EUS-GBD convincingly decreased overall adverse events and unplanned readmissions, whereas the need for reinterventions requires additional studies.

Adherence to international guidelines for the management of Helicobacter pylori infection among gastroenterologists and gastroenterology fellows in Italy: A Survey of the Italian Federation of Digestive Diseases - FISMAD.

BACKGROUND: Information on the management of Helicobacter (H.) pylori infection by gastroenterologists and gastroenterology fellows are scarce. We aimed to assess practice of gastroenterologists and gastroenterology fellows and their adherence to guidelines for diagnosis and treatment of H. pylori infection in Italy. MATERIALS AND METHODS: All gastroenterologists and gastroenterology fellows attending the National Congress of Digestive Diseases - FISMAD were invited to fill-in an on-line questionnaire. The questionnaire included questions on the diagnosis and treatment of H. pylori infection. RESULTS: A total of 279 gastroenterologists and 61 gastroenterology fellows participated to the study. The 13 C-urea breath test was the most preferred method among gastroenterologists and fellows for the diagnosis of H. pylori infection (40.4% and 57.6%, respectively) and the confirmation of eradication (61.3% and 70%, respectively). Sequential therapy was the most preferred first-line treatment of H. pylori for both gastroenterologists and gastroenterology fellows (31.8% and 44%, respectively), followed by bismuth quadruple therapy (31% and 27.6%, respectively) and clarithromycin triple therapy (26.8% and 22.4%, respectively). Only 30% of gastroenterologists and 38.5% of fellows used the clarithromycin triple therapy for the recommended duration of 14 days. Bismuth quadruple therapy was the most preferred second-line therapy for both gastroenterologists and fellows. The majority of gastroenterologists and fellows would prefer an empirical therapy at third line (72.6% and 62.5%, respectively) and a susceptibility-guided therapy at fourth line (46.7% and 71.4%, respectively). CONCLUSIONS: Practices of gastroenterologists and gastroenterology fellows are in line with guidelines' recommendations, apart for the first-line treatment of H. pylori infection. Targeted educational interventions to improve adherence to guidelines are needed.

Determinants of outcomes of transmural EUS-guided gallbladder drainage: systematic review with proportion meta-analysis and meta-regression.

BACKGROUND AND AIMS: Transmural EUS-guided gallbladder drainage (EUS-GBD) has been increasingly used in the treatment of gallbladder diseases. Aims of the study were to provide a comprehensive meta-analysis and meta-regression of features and outcomes of this procedure. METHODS: MEDLINE, Scopus, Web of science, and Cochrane databases were searched for literature pertinent to transmural EUS-GBD up to May 2021. Random-effect meta-analysis of proportions and meta-regression of potential modifiers of outcome measures considered were applied. Outcome measures were technical success rate, overall clinical success, and procedure-related adverse events (AEs). RESULTS: Twenty-seven articles were identified including 1004 patients enrolled between February 2009 and February 2020. Acute cholecystitis was present in 98.7% of cases. Pooled technical success was 98.0% (95% CI 96.3, 99.3; heterogeneity: 23.6%), the overall clinical success was 95.4% (95% CI 92.8, 97.5; heterogeneity: 35.3%), and procedure-related AEs occurred in 14.8% (95% CI 8.8, 21.8; heterogeneity: 82.4%), being stent malfunction/dislodgement the most frequent (3.5%). Procedural-related mortality was 1‰. Meta-regression showed that center experience proxied to > 10 cases/year increased the technical success rate (odds ratio [OR]: 2.84; 95% CI 1.06, 7.59) and the overall clinical success (OR: 3.52; 95% CI 1.33, 9.33). The use of anti-migrating devices also increased the overall clinical success (OR: 2.16; 95% CI 1.07, 4.36) while reducing procedure-related AEs (OR: 0.36; 95% CI 0.14, 0.98). CONCLUSION: Physicians' experience and anti-migrating devices are the main determinants of main clinical outcomes after EUS-GBD, suggesting that treatment in expert centers would optimize results.

Spleen Stiffness Measurements Predict the Risk of Hepatic Decompensation After Direct-Acting Antivirals in HCV Cirrhotic Patients.

PURPOSE: Little evidence is available regarding the risk of hepatic decompensation (HD) after direct-acting antivirals (DAAs) in patients with advanced chronic liver disease. Our aim was to assess the risk of decompensation and the prognostic role of noninvasive tests, such as liver (LSM) and spleen (SSM) stiffness measurements, in the prediction of decompensation after sustained virologic response (SVR) by DAAs. MATERIALS AND METHODS: A cohort study involving 146 cirrhotic patients treated with DAAs in our tertiary center with LSM and SSM available both before and six months after treatment (SVR24). A historical cohort of 92 consecutive cirrhotic patients with active HCV was used as a control group. A propensity score inverse probability weighting method was used to account for differences between the groups. Time-dependent models for the prediction of decompensation were applied to account for changes in noninvasive tests after therapy. RESULTS: The decompensation incidence in the DAA cohort was 7.07 (4.56-10.96) per 100 person-years (PYs), which was significantly lower than in the active HCV cohort. The DAA therapy was an independent protective factor for HD development (SHR: 0.071, 95 %-CI: 0.015-0.332). SSM ≥ 54 kPa was independently associated with decompensation despite SVR achievement (SHR: 4.169, 95 %-CI: 1.050-16.559), alongside with a history of decompensation (SHR: 7.956, 95 %-CI: 2.556-24.762). SSM reduction < 10 % also predicted the risk of decompensation after SVR24. CONCLUSION: The risk of decompensation was markedly reduced after DAA therapy, but it was not eliminated. Paired SSM values stratified the risk of decompensation after SVR better than other noninvasive tests.

Gut microbiota signatures and clinical manifestations in celiac disease children at onset: a pilot study.

BACKGROUND AND AIM: Recent researches have shown an altered gut microbiota in celiac disease (CD) patients compared with healthy controls (HCs). This study aims to evaluate the composition of the microbiota of CD children at onset and the relationship between bacterial abundances and symptoms. METHODS: Celiac disease patients were consecutively enrolled at a pediatric unit referring for suspected CD. HCs were also included in the study. Stool and duodenal samples were collected and evaluated by a high taxonomic fingerprint microbiota array. RESULTS: Thirty-seven subjects enrolled: 21 CD patients and 16 HCs. Fourteen subjects were male (38%). The mean age was 75 months (standard deviation 31.5) for CD patients and 71 months (standard deviation 34.9) for HCs. Duodenal microbiota of CD patients showed a dominance of Enterobacteriaceae and subdominance of Bacteroidetes/Streptococcus. Stool microbiota showed a lower abundance of Bacteroides-Prevotella (P = 0.013), Akkermansia (P = 0.002), and Staphylococcaceae (P = 0.001) in CD patients compared with HC. At symptoms level, an increased mean relative abundance of Bacillaceae and Enterobaeriaceae in patients with abdominal pain (P = 0.007 and P = 0.010) was found. CD patients with diarrhea had reduced mean relative abundance of Clostridium cluster XIVa (P = 0.044) and Akkermansia (P = 0.033) and an increase in Bacillaceae (P = 0.048) and Fusobacterium (P = 0.048). CONCLUSIONS: Gut microbiota of CD children at disease onset is different from that of HC. Pro-inflammatory microbiota imbalances were associated with CD symptoms. Further studies are needed to assess whether dysbiosis is associated with CD early onset and symptoms.

Liver Stiffness Measurement Allows Early Diagnosis of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Adult Patients Who Undergo Hematopoietic Stem Cell Transplantation: Results from a Monocentric Prospective Study.

Veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life-threatening complication affecting patients undergoing hematopoietic stem cell transplantation (HSCT). The survival rate is higher when specific therapy is initiated early; thus, improving early, noninvasive diagnosis of VOD/SOS is an important need. In an adult population undergoing HSCT, we aimed to assess the role of liver stiffness measurement (LSM), evaluated by transient elastography (TE), for diagnosing VOD/SOS. Between April 2016 and March 2018, 78 consecutive adult patients with indications for allogeneic HSCT were prospectively included. LSM was performed before HSCT and at days +9/10, +15/17, and +22/24 post-HSCT. New European Society for Blood and Marrow Transplantation criteria were used to establish VOD/SOS diagnosis. Four patients developed VOD/SOS (5.1%) during the study period, with a median time of +17 days post-HSCT. A sudden increase in LSM compared with previously assessed values and pre-HSCT values, was seen in all patients who developed VOD/SOS. LSM increases occurred from 2 to 12 days before clinical SOS/VOD appearance. The VOD/SOS diagnostic performance of increased LSM over pre-HSCT assessment showed an area under the receiver operating characteristic curve of 0.997 (sensitivity 75%; specificity 98.7%). LSM gradually decreased following successful VOD/SOS-specific treatment. Interestingly, LSM values did not increase significantly in patients experiencing hepatobiliary complications (according to the Common Terminology Criteria) other than VOD/SOS. LSM by TE can be considered a promising method to perform an early, preclinical diagnosis and follow-up of VOD/SOS.

A combined model based on spleen stiffness measurement and Baveno VI criteria to rule out high-risk varices in advanced chronic liver disease.

BACKGROUND & AIMS: Recently, Baveno VI guidelines suggested that esophagogastroduodenoscopy (EGD) can be avoided in patients with compensated advanced chronic liver disease (cACLD) who have a liver stiffness measurement (LSM) <20 kPa and platelet count >150,000/mm3. We aimed to: assess the performance of spleen stiffness measurement (SSM) in ruling out patients with high-risk varices (HRV); validate Baveno VI criteria in a large population and assess how the sequential use of Baveno VI criteria and SSM could safely avoid the need for endoscopy. METHODS: We retrospectively analyzed 498 patients with cACLD who had undergone LSM/SSM by transient elastography (TE) (FibroScan®), platelet count and EGDs from 2012 to 2016 referred to our tertiary centre. The new combined model was validated internally by a split-validation method, and externally in a prospective multicentre cohort of 115 patients. RESULTS: SSM, LSM, platelet count and Child-Pugh-B were independent predictors of HRV. Applying the newly identified SSM cut-off (≤46 kPa) or Baveno VI criteria, 35.8% and 21.7% of patients in the internal validation cohort could have avoided EGD, with only 2% of HRVs being missed with either model. The combination of SSM with Baveno VI criteria would have avoided an additional 22.5% of EGDs, reaching a final value of 43.8% spared EGDs, with <5% missed HRVs. Results were confirmed in the prospective external validation cohort, as the combined Baveno VI/SSM ≤46 model would have safely spared (0 HRV missed) 37.4% of EGDs, compared to 16.5% when using the Baveno VI criteria alone. CONCLUSIONS: A non-invasive prediction model combining SSM with Baveno VI criteria may be useful to rule out HRV and could make it possible to avoid a significantly larger number of unnecessary EGDs compared to Baveno VI criteria only. LAY SUMMARY: Spleen stiffness measurement assessed by transient elastography, the most widely used elastography technique, is a non-invasive technique that can help the physician to better stratify the degree of portal hypertension and the risk of esophageal varices in patients with compensated advanced chronic liver disease. Performing spleen stiffness measurement together with liver stiffness measurement during the same examination is simple and fast and this sequential model can identify a greater number of patients that can safely avoid endoscopy, which is an invasive and expensive examination.

Idiopathic chronic intestinal pseudo-obstruction syndrome is strongly associated with low serum levels of vitamin D.

Idiopathic chronic intestinal pseudo-obstruction (CIPO) is associated with intestinal inflammation and malabsorption and may cause serum vitamin D deficiency. We aimed to assess whether there is an association between idiopathic CIPO and serum levels of 25-hydroxy-vitamin D. Consecutive patients with confirmed diagnosis of idiopathic CIPO were prospectively enrolled and matched with healthy controls by gender, age, and BMI. Median serum level of 25-hydroxy-vitamin D of patients with CIPO was compared with that of healthy subjects using the Wilcoxon signed-rank test for matched samples. A total of 35 patients with CIPO and 35 matched healthy subjects were enrolled. All patients with CIPO had a 25-hydroxy-vitamin D deficiency with serum levels <12 ng/ml. The median serum level of vitamin D was significantly lower in patients with CIPO than in healthy controls (5.7 vs. 29.7 ng/ml, P  < 0.0001). Serum level of vitamin D was not associated with gender ( P  = 0.27), age ( P  = 0.22), BMI ( P  = 0.95), high (>10 000 × ml) WBC count ( P  = 0.08), or high (>5 mg/l) C-reactive protein ( P  = 0.87) among patients with CIPO. CIPO seems to be strongly associated with low serum levels of 25-hydroxy-vitamin D.

Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: An Updated Meta-analysis and Meta-regression.

PURPOSE: Transarterial radioembolization (TARE) has emerged as a promising therapeutic approach for unresectable intrahepatic cholangiocarcinoma (ICCA). We updated our previous meta-analysis with meta-regression to explore the efficacy of TARE in the context of ICCA. METHODS: We searched PubMed and Scopus for studies published up to September 1, 2023. The primary outcome was overall survival. Secondary outcomes were tumor overall response rate, severe adverse events, and downstaging to surgery. Meta-analysis employed a random-effects model, and meta-regression was utilized to explore sources of heterogeneity. RESULTS: We included 27 studies, involving 1365 patients. Pooled survival estimates at 1, 2, and 3 years were 52.6%, 27%, and 16.8%, respectively. Meta-regression revealed that the proportion of patients naïve to treatment was the only pre-TARE predictor of survival (1-, 2-, and 3-year survival of 70%, 45%, and 36% for treatment-naïve patients, mean survival 19.7 months vs. 44%, 18%, and 7% for non-naïve patients, mean survival 12.2 months). Overall response according to RECIST 1.1 and mRECIST was 19.6% and 67%, respectively. Effective downstaging to surgery was possible in varying rates (3-54%); the mean survival in these patients was 34.8 months (1-, 2-, and 3-year survival of 100%, 87%, and 64%). About 45.7% of patients experienced adverse events, but only 5.9% were severe. CONCLUSIONS: Our study benchmarked the survival rates of patients undergoing TARE for unresectable ICCA and showed that this is a valid option in these patients, especially if naïve to previous treatments. Downstaging to surgery is feasible in selected patients with promising results.