OBJECTIVE:Contemporary surgical risk data from Southeastern Europe are limited. We assessed cumulative surgical probabilities, independent predictors of surgery, and the impact of evolving therapeutic strategies in a Bosnian tertiary referral cohort. METHODS:This retrospective cohort study included 153 patients with Crohn's disease treated at University Clinical Center Tuzla between 2009 and 2023. Calendar-period analysis estimated contemporary surgical risk, while natural-history analysis characterized progression from diagnosis. Sequential multivariable Weibull regression identified independent predictors of time to first surgery. RESULTS:Cumulative probabilities of surgery at 1, 5, and 10 years were 3, 11, and 34%, respectively. Five factors independently reduced surgical risk. Early biologic therapy showed the largest effect (hazard ratio: 0.22, 95% confidence interval: 0.07-0.73; P = 0.014), followed by colonic location (hazard ratio: 0.37, 95% confidence interval: 0.16-0.81; P = 0.014), inflammatory phenotype (hazard ratio: 0.53, 95% confidence interval: 0.32-0.85; P = 0.011), diagnosis during the biologic era (≥2017; hazard ratio: 0.56, 95% confidence interval: 0.35-0.88; P = 0.013), and early azathioprine initiation (hazard ratio: 0.61, 95% confidence interval: 0.40-0.93; P = 0.022). Sequential modeling confirmed additive protective effects of therapeutic exposures. Early surgery was associated with lower subsequent biologic use than no early surgery (27.5 vs. 81.4%; P < 0.001). CONCLUSION:Surgical risk in this Southeastern European cohort aligns with Western estimates. Colonic location and inflammatory phenotype were intrinsic protective factors, whereas early azathioprine, early biologic therapy, and biologic-era diagnosis independently reduced surgical risk. These findings support early combined therapy for high-risk patients.
OBJECTIVE:To compare lenvatinib (LEN) and atezolizumab plus bevacizumab (Atezo + Bev) as first-line therapy in super-older adults (≥80 years) with hepatocellular carcinoma (HCC) and evaluate whether early relative dose intensity (RDI) is associated with outcomes. METHODS:This retrospective cohort study included super-older adults initiating LEN or Atezo + Bev between May 2018 and August 2025. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and adverse events. Inverse probability of treatment weighting and multivariable Cox regression were performed. Within the LEN cohort, a day 56 landmark analysis evaluated the prognostic significance of 8-week RDI (RDI8 ≥ 75% vs. <75%). RESULTS:Median OS was 15.6 and 10.7 months with LEN and Atezo + Bev [hazard ratio: 0.77, 95% confidence interval (CI): 0.42-1.41], whereas median PFS was 6.73 and 9.73 months, respectively (hazard ratio: 1.18, 95% CI: 0.65-2.17). IPTW and multivariable analyses yielded similar results. Within the LEN cohort, RDI8 greater than or equal to 75% was independently associated with improved OS (30.8 vs. 14.7 months; adjusted hazard ratio: 0.23, 95% CI: 0.07-0.73, P = 0.013). Grade greater than or equal to 3 adverse events occurred in 37 and 50% of the LEN and Atezo + Bev cohorts, respectively. CONCLUSION:Although LEN and Atezo + Bev showed no statistically significant difference in real-world survival in this exploratory cohort, these findings require validation in larger studies. Higher early LEN dose intensity was consistently associated with improved survival and may represent an important therapeutic consideration in super-older adults with HCC.
BACKGROUND:Patients with cirrhosis frequently have metabolic comorbidities that complicate treatment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors provide cardiovascular and renal benefits in type 2 diabetes, but their effects in cirrhosis remain uncertain. We evaluated the association between SGLT2 inhibitor use and clinical outcomes in patients with cirrhosis. METHODS:We conducted a retrospective cohort study using the TriNetX Research Network. Adults with cirrhosis were stratified by SGLT2 inhibitor exposure. Propensity score matching balanced demographics, comorbidities, medication use, BMI, and laboratory variables. Outcomes included all-cause mortality, hepatic decompensation, acute kidney injury/hepatorenal syndrome (AKI/HRS), and hepatocellular carcinoma (HCC). RESULTS:After matching, 34 590 patients remained in each cohort. SGLT2 inhibitor use was associated with lower all-cause mortality [15.0 vs. 24.2%; hazard ratio: 0.67, 95% confidence interval (CI): 0.64-0.69, P < 0.001] and composite hepatic decompensation (28.6 vs. 36.3%; hazard ratio: 0.78, 95% CI: 0.76-0.80, P < 0.001). AKI/HRS was not increased on time-to-event analysis (hazard ratio: 0.99, 95% CI: 0.96-1.02, P = 0.346). HCC incidence was lower among SGLT2 inhibitor users (hazard ratio: 0.57, 95% CI: 0.39-0.86, P = 0.006). CONCLUSION:SGLT2 inhibitor use in patients with cirrhosis was associated with lower mortality, hepatic decompensation, and HCC incidence without increased AKI/HRS. These findings support prospective evaluation in selected patients with cirrhosis.
BACKGROUND:Cirrhosis produces a rebalanced hemostatic state that predisposes patients to bleeding and thrombosis. We evaluated hepatic outcomes associated with deep vein thrombosis (DVT), pulmonary embolism, and portal vein thrombosis (PVT) in patients with cirrhosis. METHODS:We conducted a retrospective cohort study using the Nationwide Readmissions Database from 2016 to 2022. Adults with cirrhosis identified during January index hospitalizations were followed through the end of the same calendar year and classified as having no thromboembolism, DVT, pulmonary embolism, or PVT. The primary outcome was liver transplantation. Secondary outcomes included in-hospital mortality, ascites, esophageal or gastric varices, variceal hemorrhage, acute liver failure, and hepatic decompensation. Survey-weighted logistic regression estimated adjusted odds ratios (aORs). RESULTS:The weighted cohort included 365 467 patients: 363 007 without thromboembolism, 730 with DVT, 1036 with pulmonary embolism, and 694 with PVT. DVT was associated with lower odds of liver transplantation [aOR, 0.19; 95% confidence interval (CI), 0.05-0.83] and mortality (aOR, 0.54; 95% CI, 0.37-0.77). Pulmonary embolism was associated with lower odds of varices, ascites, acute liver failure, and hepatic decompensation. PVT was associated with higher odds of varices (aOR, 2.47; 95% CI, 1.95-3.13) and variceal hemorrhage (aOR, 2.83; 95% CI, 1.59-5.02). CONCLUSION:Thrombotic phenotypes in cirrhosis have distinct prognostic associations. PVT was associated with portal hypertensive complications, whereas apparently favorable associations with DVT and pulmonary embolism should be interpreted cautiously.
OBJECTIVE:Tenofovir alafenamide (TAF) offers favorable renal safety compared with tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB), but its long-term metabolic effects remain unclear. This study aimed to assess changes in lipids, atherogenic indices, fibrosis markers, and renal function after switching to TAF and identify baseline factors associated with lipid changes. METHODS:This single-center retrospective cohort included CHB patients treated with TDF or entecavir for ≥24 months, switched to TAF, and followed for ≥24 months. Patients with diabetes, dyslipidemia, or chronic kidney disease were excluded. Parameters were assessed 5 times over 2 years before and after switching. Mixed-effects models and Wilcoxon signed-rank tests assessed trends and pre-post changes. RESULTS:Fifty-nine patients were included (mean age, 52.7 ± 9.9 years; 91.5% previously on TDF). Lipid fractions increased, particularly total cholesterol (median Δ, +22.81 mg/dL; P < 0.001) and low-density lipoprotein (LDL) cholesterol (+14.29 mg/dL; P < 0.001). Ratio-based indices, including the atherogenic index of plasma (AIP), triglyceride/high-density lipoprotein (HDL), LDL/HDL, and non-HDL/HDL, remained stable. However, 22.0% crossed the AIP risk threshold, and 16.9% exceeded LDL and non-HDL cutoffs. Younger age and lower baseline LDL or HDL were associated with greater increases. Estimated glomerular filtration rate remained stable; creatinine rose without clinical significance. CONCLUSION:Switching to TAF was associated with clinically meaningful increases in absolute lipid fractions without worsening atherogenic ratios or renal function. Nevertheless, a minority transitioned to higher cardiometabolic risk categories, supporting individualized lipid monitoring, particularly in younger patients and those with low baseline LDL or HDL.
AIM:To clarify the optimal sequencing strategy of systemic therapies for unresectable hepatocellular carcinoma that maximizes efficacy and patient outcomes. METHODS:We established a multicenter retrospective Tokai Post ICI Sequential Therapy Registry cohort across four Tertiary-Care Hospitals in Japan, enrolling patients who received first-line immune checkpoint inhibitor (ICI)-based therapy between October 2020 and May 2025. Tumor response was assessed every 2-3 months by Response Evaluation Criteria in Solid Tumors version1.1 as the primary outcome. Logistic regression models evaluated predictors of response with hospital-level mixed effects. RESULTS:A total of 368 patients were included [median age 74 years (interquartile range: 68-80 years); 303 (82%) male]; 307 (83.4%) received atezolizumab plus bevacizumab and 61 (16.6%) durvalumab plus tremelimumab. Following discontinuation, 151 (47.0%) proceeded to second-line therapy, predominantly lenvatinib ( n = 124, 82%). Second-line lenvatinib achieved objective response rates of 12-25% and disease control rates (DCRs) exceeding 60%, independent of prior ICI regimen or response. Of 56 patients receiving third-line therapy, the sequences of atezolizumab plus bevacizumab-lenvatinib-durvalumab plus tremelimumab and durvalumab plus tremelimumab-lenvatinib-atezolizumab plus bevacizumab ( n = 19, 28.6%) demonstrated significantly higher DCR compared with other sequences (52.6 vs. 29.7%) despite comparable liver function reserve and tumor burden. In addition, durvalumab plus tremelimumab following atezolizumab plus bevacizumab-lenvatinib showed numerically higher DCR compared with durvalumab plus tremelimumab directly after atezolizumab plus bevacizumab (53.3 vs. 29.4%). CONCLUSION:Consistent efficacy of second-line lenvatinib and favorable outcomes with ICI-lenvatinib-ICI sequences may underscore the clinical importance of therapy sequencing in advanced hepatocellular carcinoma, warranting prospective evaluation of optimal strategies.
INTRODUCTION AND OBJECTIVES:Metabolic-dysfunction associated steatotic liver disease (MASLD) is a major cause of liver disease and frequently associated with obesity. This observational study with prospective enrollment aimed to evaluate the clinical and metabolic characteristics of MASLD and to compare the diagnostic accuracy of noninvasive methods versus liver histology in detecting MASLD. PATIENTS AND METHODS:Adults with a BMI > 35 kg/m2 were enrolled. Data collected included clinical, metabolic, and hepatic parameters, as well as lifestyle and physical examination findings. Liver histology, obtained according to clinical practice, was compared with noninvasive diagnostic tools: Fatty Liver Index (FLI), NAFLD fibrosis score, aspartate aminotransferase/platelet ratio index test, liver elastography, fibrosis-4 index score, and ultrasound imaging. RESULTS:Ninety-five patients (median age 35 years, predominantly female) were included. Comorbidities were rare. Laboratory results were largely normal, except for elevated insulin and triglyceride levels. Hepatic histology was available in 64 patients (67%). Steatosis was prevalent (84%) with a median score of 2. Ultrasound bright liver patterns and high FLI values (median 98) supported the histological findings. A median Histology Activity Index of 4 and fibrosis stage of 1 indicated mild inflammation and fibrosis, confirmed by noninvasive tests. Multivariate analysis showed a significant linear correlation between FLI and histological steatosis (P = 0.001), with FLI being the most accurate non-invasive predictor (area under the receiver operating characteristic: 0.765; P = 0.001). CONCLUSIONS:In this young with obesity cohort, MASLD was common but with limited liver damage progression. FLI seems to be the best predictor of steatosis. Hypertriglyceridemia and hyperinsulinemia were associated with higher steatosis levels, reflecting the metabolic dysfunction of MASLD.
BACKGROUND:Digital single-operator cholangiopancreatoscopy (DSOC) is an important adjunct to endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and treatment of complex biliary and pancreatic diseases. However, data regarding its safety and efficacy in elderly patients remain limited. AIM:To evaluate the safety and efficacy of DSOC in patients aged 75 years compared with a younger population. METHODS:We retrospectively analyzed consecutive patients who underwent ERCP with DSOC at a tertiary referral center between January 2017 and July 2025. Patients were stratified according to age (≥75 vs. <75 years). The primary outcome was procedure-related adverse events, defined according to American Society for Gastrointestinal Endoscopy criteria. Secondary outcomes included technical and clinical success rates and factors associated with complications. RESULTS:A total of 136 patients underwent 170 DSOC procedures. Elderly patients had more comorbidities and higher American Society of Anesthesiologists scores compared with younger patients. Overall adverse event rates were comparable between elderly and younger patients (8 vs. 13%; P = 0.44), while technical and clinical success rates were high in both groups. Multivariate analysis showed that age was not independently associated with adverse events. CONCLUSION:In this retrospective single-center study, DSOC was feasible in selected elderly patients, with complication rates and procedural outcomes comparable to those of younger individuals. The lack of formal frailty assessment and procedural burden metrics limits generalizability to frail or unselected elderly populations. In this retrospective single-center study, DSOC was feasible in selected elderly patients, with complication rates and procedural outcomes comparable to those of younger individuals. The lack of formal frailty assessment and procedural burden metrics limits generalizability to frail or unselected elderly populations.
Prophylactic clip closure after endoscopic submucosal dissection (ESD) may be beneficial in the prevention of adverse events. In this meta-analysis of randomized controlled trials, we have evaluated the role of prophylactic clipping after ESD. We reviewed multiple databases from inception to 24 January 2026. Outcomes of interest included post-ESD bleeding, perforation, and post-ESD coagulation syndrome. Risk ratios with 95% confidence intervals (CIs) were calculated. Data were analyzed using a random-effects model. Heterogeneity was assessed using the I2 statistic. Five randomized controlled trials with 772 patients were included. Prophylactic clipping was associated with a lower risk of post-ESD bleeding (risk ratio: 0.35, 95% CI: 0.18, 0.65). There was no significant difference in risk of post-ESD coagulation syndrome (risk ratio: 1.06, 95% CI: 0.73, 1.53), and perforation (risk ratio: 0.72, 95% CI: 0.23, 2.30) between the groups. In conclusion, this meta-analysis demonstrates the benefits of prophylactic clipping after colorectal ESD in the prevention of post-ESD bleeding.
OBJECTIVES:Gluten-free diet (GFD) is, to date, the only effective therapeutic intervention for coeliac disease (CeD). Evaluation of dietary adherence is of the utmost importance in the management of CeD. However, in the paediatric population, there is limited data concerning the adherence to the GFD in patients diagnosed via bioptic confirmation compared to those diagnosed through the biopsy-sparing method, according to the ESPGHAN 2012 guidelines. In this multicentric study, we investigated dietary adherence in a group of adolescents with CeD, comparing patients diagnosed with the two different diagnostic modalities, and we proposed the validation of an evaluation tool for the GFD compliance in this population. METHODS:A total of 206 patients aged 14-18 years, diagnosed between 2012 and 2019, all with CeD and on a GFD for at least 2 years, were included. Adherence was assessed using the Leffler questionnaire [Celiac Dietary Adherence Test (CDAT)] and the Biagi score. RESULTS:Among participants, 81.1% had been diagnosed through biopsy. No significant difference in Biagi scores was observed between the two groups ( P = 0.057). Regarding the CDAT, poor or suboptimal adherence (score: ≥13) was identified in 66 patients diagnosed by biopsy and 12 patients diagnosed by the biopsy-sparing approach ( P = 0.362). A multivariate analysis exploring the influence of diagnostic method, age at diagnosis, and education level on CDAT scores did not reach statistical significance ( P = 0.1, R2 = 0.031). CONCLUSION:Adherence to a GFD does not differ between adolescents diagnosed by biopsy and those diagnosed through the biopsy-sparing approach, irrespective of age at diagnosis or educational level.
BACKGROUND:Hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure in chronic hepatitis B (CHB), yet the risk of hepatocellular carcinoma (HCC) may persist. This study aimed to evaluate HCC incidence and identify risk factors after HBsAg seroclearance. METHODS:This retrospective single-center cohort included 259 CHB patients who achieved HBsAg seroclearance between 2013 and 2023. Patients with pre-existing HCC were excluded. During follow-up, 22 patients developed HCC. Clinical, demographic, and laboratory variables were analyzed. Independent risk factors were determined using multivariate logistic regression. RESULTS:HCC developed in 22 (8.49%) patients after seroclearance. In multivariate logistic analysis, a higher cirrhosis, age, male sex, platalet count, and hepatitis B score and shorter HBV infection duration were independently associated with HCC development after HBsAg seroclearance ( P < 0.005). Male sex and older age were significant in univariate analysis but not in multivariate analysis. Markers of liver dysfunction and fibrosis were significantly worse in patients who developed HCC. CONCLUSION:HBsAg seroclearance reduces but does not eliminate the risk of HCC. Patients with advanced liver disease and high-risk profiles remain vulnerable, underscoring the need for continued, risk-adapted HCC surveillance after seroclearance.
