Search Results (473)

Vanishing bile duct syndrome (VBDS) is a rare cholestatic liver disease often associated with drug-induced liver injury, yet systematic data on pharmaceutical triggers remain limited. Using WHO VigiBase, we applied Bayesian disproportionality analysis (IC_0.25) to identify drug-event associations that may not be readily apparent in clinical trials or pre-marketing studies. Product labels approved by Swissmedic or the FDA, as well as LiverTox, were reviewed to determine whether VBDS was already acknowledged as an adverse event. Signal detection was deliberately restricted to reports naming a single suspect drug. Among these single-agent reports, 22 drugs demonstrated a positive IC_0.25 signal, of which nevirapine, dapsone and azithromycin showed the strongest disproportionality signal. Only one of these agents (carbamazepine) explicitly labelled VBDS as an adverse event. These findings are based on spontaneous reporting data: disproportionality analysis is a hypothesis-generating signal-detection method that does not establish causality and requires further validation. This study expands the current understanding of drug-induced VBDS by reinforcing the associations with known drugs and generating pharmacovigilance signals for new potential VBDS triggers across several drug categories. Full article

Background/Objectives: Obesity can cause metabolic disorders and hepatic steatosis. Continuous hepatic influx of dietary lipids leads to adaptive metabolic changes, including increased fatty acid oxidation (FAO) and ketogenesis. However, these adaptations are not enough to counter the detrimental accumulation of lipids, resulting in hepatic steatosis. Apabetalone is a clinical-stage Bromodomain and Extra-Terminal domain inhibitor (BETi) that attenuated the increase in hepatic fibrosis score (FS) and reduced the rate of ischemic major adverse cardiovascular events and hospitalizations for heart failure in a subgroup of patients having a high likelihood of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in the phase 3 clinical trial, BETonMACE. Methods: To analyze apabetalone’s effects on lipid and ketone metabolism, RNA seq, Oil Red staining and triglyceride quantification were performed in livers from a mouse model of diabetes-induced obesity and ketones were measured in plasma. Results: Mice fed a high-fat diet (HFD) were obese and demonstrated liver steatosis. Apabetalone treatment maintained the beneficial metabolic adaptation induced by HFD (increased FAO) and decreased hepatic triglycerides and lipid droplets. This inhibition of lipid anabolism redirected substrates to FAO and ketogenesis, resulting in increased plasma ketones, showing for the first time the role of BETi in ketogenesis. In the heart, apabetalone treatment reduced cardiac oxidative stress and plasma NT-proBNP levels. Conclusions: Apabetalone improves hepatic lipid handling, favoring ketogenesis. As ketones have demonstrated beneficial effects on cardiac function, increased ketones induced by apabetalone may not only contribute to the observed attenuation of FS in patients, but also a reduction in cardiac events among patients with high likelihood of MASLD, as well as in the overall trial population. Full article

Background/Objectives: The aim of this study was to evaluate the efficacy and safety of avatrombopag in patients with chronic liver disease (CLD) and thrombocytopenia scheduled for elective invasive/minimally invasive procedures, providing clinical guidance for patients requiring platelet (PLT) elevation. Methods: In this single-center, prospective study, patients with CLD and PLT counts <50 × 10⁹/L were scheduled for elective invasive/minimally invasive surgery, receiving 5-day avatrombopag plus standard CLD management. PLT response, dynamics, and safety were assessed. Results: A total of 108 patients with CLD and baseline PLT counts <50 × 10⁹/L were enrolled, showing an 83.33% response rate. Responders exhibited significantly higher baseline white blood cell (WBC, p = 0.009), neutrophil (p = 0.016), hemoglobin (HGB, p = 0.011), and PLT (p = 0.001) levels compared to non-responders. Baseline PLT correlated positively with age (p = 0.014), WBC (p = 0.046), HGB (p = 0.001), and prothrombin activity (p = 0.023). Logistic regression identified baseline PLT as an independent predictor of treatment response (p = 0.002). PLT began rising by day 5 post-treatment, peaked around day 10, and declined to baseline by day 40 in overall cases and responders. Non-responders showed only mild PLT elevation by day 5 (remaining <50 × 10⁹/L), with no further increase by day 10. No adverse events were observed. No thrombotic or bleeding events were recorded in this small cohort; however, the limited sample size precludes definitive conclusions on thrombosis risk. Conclusions: Avatrombopag demonstrated high efficacy and favorable safety for elevating PLT in patients with CLD, with a higher baseline PLT predicting a better response. Full article

Background: Bile leaks complicate 5–25% of liver transplants and are among the most common early postoperative biliary events. Their management within the first 14 postoperative days has traditionally been framed around the timing of intervention. Objective: To evaluate whether leak characteristics and patient stability provide more consistent guidance than intervention timing for early post-transplant bile leaks. Methods: A structured narrative review using a dual-source search (AI-assisted semantic search [Elicit Plus] and PubMed/MEDLINE) was conducted. A PICO-informed (Population, Intervention, Comparator, Outcome) framework guided inclusion; two independent reviewers preformed screening, with senior adjudication, yielding 37 sources. Because “early” was defined heterogeneously—by leak onset in most studies (definitions exceeding 14 days) and by intervention timing in others—and no study compared timing within a 14-day window, quantitative pooling was not undertaken. Results: No included study directly compared intervention timing within the first 14 postoperative days. In the largest available analysis of ERCP timing, resolution and adverse event rates did not differ by whether endoscopy was performed within one day, on days two to three, or after three days; endoscopic success was consistently high (80–98%) across temporal windows. Leak type was a consistent correlate of management intensity and resolution: anastomotic leaks were associated with higher surgical-intervention rates (40% vs. 8.3% for T-tube exit-site leaks in one cohort) and lower resolution rates (58–69%) than non-anastomotic leaks (90–100%). Within endoscopic therapy, bridging stent placement—not leak location—was the strongest independent predictor of resolution, and any bile leak, irrespective of subtype, independently predicted subsequent biliary stricture (pooled adjusted OR ≈ 4). Ultra-early leaks (≤72 h), frequently technical failures, formed the one subset favoring early surgical re-exploration. Conclusions: The absence of a demonstrated timing effect reflects a lack of direct comparative data rather than proof that timing is unimportant. Leak type, patient stability, and management modality offer more consistent and actionable guidance than temporal urgency, forming the basis for a leak-stratified framework. Prospective multicenter registries with standardized timing strata and leak type stratification are needed to test whether timing independently influences outcomes. Full article

Background: Hepatotoxicity induced by atomoxetine (ATX) and methylphenidate (MPH) when used to treat ADHD is a rare but potentially serious complication. This study aims to describe the hepatic adverse drug reactions (ADRs) reported for ATX and MPH by analysing data from the EudraVigilance database. Methods: Individual case safety reports (ICSRs) listing ATX and/or MPH as suspected drugs and reporting at least one adverse event (AE) within the ‘hepatobiliary disorders’ system organ class (SOC) were extracted for the period from 1 January 2012 to 20 May 2025. Descriptive and disproportionality analyses were then performed. Results: During the study period, 421 ICSRs reporting AEs classified under the “hepatobiliary disorders” SOC and involving ATX and/or MPH as suspected drugs were retrieved (ATX, N = 232; MPH, N = 181). Most cases involved adult (N = 261) and female (N = 222) patients. The majority of reports were classified as serious (N = 349). Overall, 375 AEs were identified. Drug-induced liver injury (DILI) was the most frequently reported AE (N = 103 ATX; N = 47 MPH), followed by hepatitis (N = 20 ATX; N = 9 MPH) and jaundice (N = 15 ATX; N = 20 MPH). The disproportionality analysis, based on a head-to-head comparison, showed a higher reporting frequency of hepatobiliary disorders for ATX compared to MPH (ROR 2.41 [95%CI 2.11–3.11]). Specifically, ATX was associated with significantly higher reporting frequencies than MPH for the AEs of DILI, hepatitis, and jaundice (6.42 [4.45–9.06]; 6.48 [2.95–14.24]; and 2.19 [1.12–4.27], respectively). Conclusions: This analysis, based on the EudraVigilance database, suggests that both drugs are associated with hepatobiliary adverse drug reactions, with a higher overall reporting frequency observed for ATX. Full article

Background/Objectives: Lutetium (¹⁷⁷Lu) TLX591 (¹⁷⁷Lu-TLX591) is a radio antibody–drug conjugate (rADC) that utilizes a novel monoclonal antibody-based approach for treatment of patients with prostate-specific membrane antigen (PSMA)-expressing metastatic castration-resistant prostate cancer (mCRPC). ProstACT SELECT (NCT04786847) was a multicenter, single-arm, open-label Phase 1 trial evaluating patient selection for ¹⁷⁷Lu-TLX591 therapy using ⁶⁸Ga-PSMA-11 PSMA positron emission tomography (PET) in a heterogenous sample of patients with mCRPC. Primary and key secondary objectives were to evaluate safety and tolerability, biodistribution, and organ radiation dosimetry of ¹⁷⁷Lu-TLX591 in combination with the best standard of care (SOC) for patients with PSMA-expressing mCRPC who progressed despite prior treatment with an androgen receptor pathway inhibitor. Methods: Thirty patients received ¹⁷⁷Lu-TLX591 intravenously in combination with investigator-determined SOC. Cohort 1 (n = 5) received an imaging dose of ¹⁷⁷Lu-TLX591 (1 GBq [27 mCi]), followed 14 days later by one therapeutic dose (2.8 GBq [76 mCi]). Cohort 2 received two therapeutic doses of ¹⁷⁷Lu-TLX591, 14 days apart. Baseline ⁶⁸Ga-PSMA-11 PET was performed to confirm eligibility and was qualitatively compared with serial ¹⁷⁷Lu-TLX591 single-photon emission computed tomography (SPECT)/CT, which was performed at five timepoints following the first ¹⁷⁷Lu-TLX591 administration and also used to evaluate organ radiation dosimetry. Safety assessments included monitoring for treatment-emergent adverse events and collection of laboratory samples at specified timepoints used for biomarker analyses. Results: Tumor targeting observed on ¹⁷⁷Lu-TLX591 SPECT/CT imaging was qualitatively consistent with uptake observed on ⁶⁸Ga-PSMA-11 PET imaging. No new safety signals were observed. Radiation exposure was within safety limits, with the highest absorbed dose to liver (clearance organ; 2.44 ± 0.56 Gy/GBq) and with lower exposure to salivary glands (0.07 ± 0.03 Gy/GBq) and kidneys (0.64 ± 0.17 Gy/GBq). Activity was retained in tumor lesions through to the final protocol-specified imaging timepoint (312 h) following administration. Conclusions: In this Phase 1, single-arm study, ⁶⁸Ga-PSMA-11 PET supported patient selection for ¹⁷⁷Lu-TLX591 therapy. In a heterogenous population representative of a real-world setting, ¹⁷⁷Lu-TLX591 therapy in combination with SOC demonstrated a manageable and predictable safety profile, durable retention, and low salivary gland radiation exposure. Further evaluation in larger, randomized studies is warranted. Full article

Background: Benign biliary anastomotic strictures (BAS) remain among the most frequent complications after living donor liver transplantation (LDLT). Although multiple plastic stents (MPS) have traditionally been considered the standard endoscopic treatment, fully covered self-expandable metal stents (FCSEMS) and intraductal fully covered self-expandable metal stents (ID-FCSEMS) have emerged as alternative strategies. This study aimed to compare the efficacy and safety of MPS, FCSEMS, and ID-FCSEMS in the management of post-transplant biliary anastomotic strictures. Methods: This retrospective single-center cohort study included consecutive adult patients who developed benign biliary anastomotic strictures after LDLT and underwent ERCP-based treatment between January 2020 and January 2025. Patients were categorized according to the initial stent strategy: MPS (n = 32), FCSEMS (n = 30), and ID-FCSEMS (n = 25). Primary outcome was overall treatment success. Secondary outcomes included recurrence, number of ERCP sessions, treatment duration, post-procedural hospitalization, stent migration, and procedure-related adverse events. Results: A total of 87 patients were included. Clinical success was achieved in 81.3% of patients treated with MPS, 83.3% treated with FCSEMS, and 92.0% treated with ID-FCSEMS (p = 0.501). Recurrence rates were 18.8%, 10.0%, and 12.0%, respectively (p = 0.579). Patients treated with metal stents required significantly fewer ERCP sessions than those treated with MPS (median 5 vs. 2 vs. 2; p < 0.001). Median treatment duration was significantly shorter in the FCSEMS and ID-FCSEMS groups compared with the MPS group (12 vs. 10 vs. 9 months; p < 0.001). Post-procedural hospitalization was also reduced with metal stents (7 vs. 4 vs. 3 days; p < 0.001). Adverse event rates, including cholangitis, pancreatitis, bleeding, perforation, and mortality, were comparable among groups. Stent migration occurred in 21.9% of MPS patients, 23.3% of FCSEMS patients, and 12.0% of ID-FCSEMS patients (p = 0.525). On multivariable analysis, MELD score was the only independent predictor of treatment success (adjusted OR 0.90, 95% CI 0.83–0.98; p = 0.012). Conclusions: MPS, FCSEMS, and ID-FCSEMS achieved comparable rates of stricture resolution, recurrence, and adverse events in the treatment of biliary anastomotic strictures after LDLT. However, FCSEMS and ID-FCSEMS significantly reduced the number of ERCP procedures, treatment duration, and hospitalization compared with conventional plastic stenting. Among the evaluated strategies, ID-FCSEMS demonstrated the highest numerical success rate and lowest migration rate, suggesting a potential procedural advantage while maintaining comparable safety and efficacy. Full article

Metabolic dysfunction–associated steatotic liver disease (MASLD) has become the leading global cause of chronic liver disease, driving cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and a disproportionate burden of major adverse cardiovascular events (MACEs). Fibrosis stage remains the strongest prognostic hepatic determinant, yet liver biopsy and Hepatic Venous Pressure Gradient (HVPG)—despite their diagnostic value—are invasive and unsuitable for population-level risk assessment. Over the past two decades, non-invasive tools (NITs), including serological scores, elastography-based techniques, and composite models, have transformed fibrosis and portal hypertension (PH) evaluation, though their accuracy declines in obese or comorbid patients and their ability to predict long-term hepatic and extrahepatic outcomes remains limited. These gaps have catalyzed the emergence of AI-driven, multimodal predictive systems capable of integrating biochemical, imaging, clinical, and histopathological data into individualized and dynamically updated risk profiles. This narrative review synthesizes current evidence on traditional and next-generation NITs, highlighting how AI-enhanced approaches may overcome long-standing diagnostic constraints and enable a unified assessment of hepatic and cardiometabolic risk. Collectively, these innovations outline a path toward precision hepatology, with the potential to reshape surveillance strategies, refine prognostic stratification, and improve outcomes across the full spectrum of MASLD. Full article

Background/Objectives: Arterial hypertension (AH) and hepatitis C virus (HCV) infection are interlinked, with AH increasing the risk of severe liver disease and HCV contributing to cardiovascular issues. Treating HCV in hypertensive patients is critical, though data on direct-acting antivirals (DAAs) in this group remain limited. Methods: This retrospective study evaluated the effects of DAAs in AH patients with HCV using data from the 2015–2023 EpiTer-2 project, a multicenter study in Poland. Results: Among the 18,968 HCV-infected DAA-treated patients, 5976 had AH. These patients were older, predominantly women, and had higher rates of obesity, comorbidities, cirrhosis, hepatocellular carcinoma, and genotype 1b infection. Sustained virologic response rates were high and comparable between the AH and non-AH groups in the intent-to-treat (94.8% vs. 94.2%) and per-protocol analyses (97.6% vs. 97.6%). AH was not independently associated with treatment failure (OR 0.87, 95% CI: 0.69–1.10). Predictors of failure included genotype 3, decompensated liver function, cirrhosis, thrombocytopenia, and treatment with asunaprevir + daclatasvir. While therapy discontinuation was more common in the AH patients, most completed treatment, with fatigue being the most frequent adverse event. Although not directly evaluated, the overall safety outcomes suggest that potential drug–drug interactions with antihypertensive therapies are unlikely to have a major clinical impact in routine practice. Conclusions: This study highlights the safety and efficacy of DAAs in AH patients and emphasizes the importance of early HCV detection and treatment in this population. Full article

Background/Objectives: Discontinuation of long-term denosumab (Dmab) remains a major clinical challenge because of rebound activation of bone remodeling and increased vertebral fracture risk. Intravenous zoledronate (ZOL) is widely recommended as sequential therapy, although evidence after very prolonged Dmab exposure is limited. We report a patient who developed two rare adverse events—acute hepatocellular injury and delayed inflammatory polyarthritis—following a single ZOL infusion administered after 12 years of continuous Dmab treatment. The subsequent management of persistent rebound bone turnover with oral alendronate (ALN) highlights the therapeutic challenges encountered when repeat ZOL administration is not feasible. Methods: A 65-year-old woman with postmenopausal osteoporosis received a single 5 mg ZOL infusion 6 months after her final Dmab injection following 12 years of continuous therapy. Within 24 h, she developed a typical acute phase response. Three days later, marked hepatocellular injury was detected, characterized by substantial elevations in transaminases and gamma-glutamyl transferase, while viral and autoimmune hepatitis were excluded. Liver enzymes normalized within five days with supportive management. Thirty-two days after ZOL administration, she developed inflammatory polyarthritis in the absence of previous rheumatologic disease and with negative immunologic testing. Treatment with low-dose prednisone (5 mg/day) resulted in rapid clinical and biochemical remission. At 6 months, bone turnover markers remained markedly elevated (CTX 0.82 ng/mL, P1NP 95 ng/mL), indicating insufficient suppression of rebound bone turnover after Dmab discontinuation. Because of the adverse events, the patient declined repeat ZOL administration. Results: Weekly oral alendronate (ALN) (70 mg) was initiated and was associated with partial suppression of bone turnover markers. Despite a decline in bone mineral density (BMD) of approximately 5% at both the lumbar spine and total hip over 12 months, BMD remained within the osteopenic range, and no new fragility fractures occurred during follow-up. Conclusions: This case illustrates two rare sequential immune-mediated adverse events following ZOL infusion and underscores the therapeutic challenges of managing Dmab discontinuation after long-term treatment when repeat ZOL administration is contraindicated. Sequential intravenous ZOL and oral ALN therapy was associated with partial suppression of bone turnover markers and protection from incident fractures during follow-up, despite a modest decline in BMD of approximately 5%. Full article

Background/Objectives: Psilocibin (PSY), a serotonergic hallucinogen, has attracted increasing scientific interest due to its therapeutic potential, particularly in treatment-resistant depression. In parallel with its growing clinical and research relevance, important questions have emerged regarding its safety profile, including potential effects on the liver, kidneys, cardiovascular system, and immune function. The aim of this narrative review was to systematically collect, critically appraise, and organize the dispersed evidence regarding potential multi-organ safety signals associated with PSY exposure. Methods: A narrative review was conducted including preclinical studies, pharmacological investigations, available clinical data, and published case reports, including reports of mushroom-related intoxications involving PSY-containing species. All available sources addressing potential toxicological outcomes associated with PSY were considered, regardless of exposure context, in order to reflect the current state of evidence. Results: The available evidence base is limited and heterogeneous, consisting primarily of case reports, observational data, and mechanistic preclinical studies. Reported adverse events are rare and frequently confounded by polysubstance use, uncertainty of dose, co-ingestion of other compounds, and lack of exposure standardization. Despite these limitations, biologically plausible mechanisms related to serotonergic receptor activation provide a rationale for further investigation of potential organ-specific effects. However, current controlled clinical data do not provide consistent evidence supporting intrinsic multi-organ toxicity of PSY. Conclusions: Current evidence does not confirm clinically meaningful intrinsic multi-organ toxicity of PSY under controlled conditions. Nevertheless, the available literature suggests the presence of potential safety signals that warrant further systematic evaluation. In the context of growing clinical interest in PSY, this review provides a structured synthesis of current knowledge and highlights critical gaps in understanding its organ-specific safety profile. Full article

Wilson’s disease (WD) is traditionally known as a monogenic disorder of copper transport, but immune activation is now being increasingly recognized in a subset of patients. In a single-center retrospective cohort study of 86 treatment-naïve WD patients who were rigorously diagnosed using the Leipzig score, Jiang et al. systematically evaluated the prevalence, clinical impact, and prognostic significance of autoimmune phenomena (AP), defined by autoantibody positivity and/or elevated immunoglobulin G (IgG). They found that 55.8% of patients met the criteria for AP, with about half showing at least one autoantibody, primarily low-titer antinuclear antibodies (ANAs), indicating that immune activation is common in newly diagnosed WD. Notably, patients with WD and AP (AP-WD) had more advanced hepatic dysfunction at baseline, including higher bilirubin levels, worse synthetic function, greater cirrhosis and ascites burden, and higher composite liver scores, as well as increased urinary copper excretion. Histological analysis in a subset of patients who underwent biopsy showed more intense portal inflammation and plasma cell infiltration in AP-WD, suggesting a distinct immunopathological phenotype. Over a 60-month period, AP-WD patients had a higher incidence of liver-related adverse events (death or liver transplantation), with a nearly fourfold increased hazard compared to patients without AP. Collectively, these findings support AP as a clinically significant modifier of disease expression and outcome in WD, emphasizing the importance of routine assessment of autoantibodies and IgG at diagnosis to improve risk stratification and guide follow-up care. Full article

Background: Alcohol-related liver disease (ALD) affects 4.8% of the global population. Among these patients, between 13.4% and 19.6% suffer from alcoholic hepatitis (AH), which, in its severe form, is associated with significant short- and long-term mortality. Current therapeutic options are limited, offering only modest short-term survival benefits. Recent studies suggest that microbiota-based therapies may offer a novel therapeutic opportunity for patients with ALD. Methods: Databases including Embase, Medline, and CENTRAL were searched until 4 February 2026. The pre-registered protocol on PROSPERO (CRD42023467455) was followed without deviation. Studies comparing adult patients with ALD, treated with fecal microbiota transplantation (FMT) or standard of care (SOC), were included. Outcomes investigated included overall survival, alcoholic recidivism, adverse events (AEs), and disease severity scores. Risk of bias (ROB) was assessed using the ROBINS-I and ROB 2 tools. Hazard ratios (HR) were calculated for FMT versus SOC groups. Results: Overall, 10 studies were eligible for inclusion, with 339 patients eligible for synthesis. In these patients, FMT was associated with significantly improved overall survival compared to the SOC, with an HR of 0.50 (95% confidence interval (CI): 0.35–0.72; p = 0.0002). When comparing FMT with pentoxifylline, the HR was 0.45 (95% CI: 0.21–0.96; p = 0.0345), and when FMT was compared with nutritional support alone, the HR was 0.36 (95% CI: 0.19–0.66; p = 0.0001). But FMT did not reach statistical significance when compared to glucocorticoids. ROB analysis showed a moderate to high risk of bias, and the overall certainty of evidence was low. Discussion: FMT is a promising therapeutic option for improving short- and medium-term survival in patients with severe alcoholic hepatitis (SAH), particularly in those who are ineligible or unresponsive to corticosteroid therapy. However, given the risk of bias and low certainty of evidence, clinical significance remains uncertain. Confirmation in well-designed studies is needed. Full article

Background: Hepatocellular carcinoma (HCC) represents the most common primary liver cancer and a significant cause of global cancer-related mortality, with the majority of patients diagnosed at advanced or unresectable stages. Historically, tyrosine kinase inhibitor (TKI) monotherapies such as sorafenib and lenvatinib served as the primary systemic standard of care. However, the emergence of immune checkpoint inhibitor (ICPI)-based combinations has significantly transformed the treatment landscape. We aim to perform a comparative analysis of ICPI-based combination treatment versus TKI monotherapy among advanced HCC patients. Methods: This study utilized a reconstructed individual patient data (IPD) pooled analysis derived from nine phase 3 randomized clinical trials, adhering to PRISMA-IPD reporting guidelines. A total of 6161 patients were included in the analysis, which categorized treatment into five primary strategies: ICPI monotherapy, ICPI plus bevacizumab, dual ICPI therapy (duplet), ICPI plus TKI, and TKI monotherapy as the control group. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and the incidence of grade 3 or higher adverse events (AEs). Results: The analysis demonstrated that ICPI-based combinations provided a significant survival advantage over TKI monotherapy. Key hazard ratios (HRs) for OS compared to TKIs were 0.76 (95% CI: 0.67–0.85, p < 0.001) for dual ICPI, 0.76 (95% CI: 0.68–0.85, p < 0.001) for ICPI plus TKI, and 0.70 (95% CI: 0.61–0.81, p < 0.001) for ICPI plus bevacizumab. Median OS was numerically highest for ICPI plus TKI at 19.68 months and dual ICPI at 19.58 months compared to 14.84 months for the TKI group. Among FDA-approved regimens, nivolumab plus ipilimumab (NivoIpi) achieved the longest median OS of 24.08 months. From a safety standpoint, the ICPI plus TKI group had the highest incidence of grade 3/4 AEs at 69.1%. Conversely, TKI monotherapy showed a 50.1% incidence, while dual ICPI therapy exhibited the most favorable safety profile at 32.7%. Conclusions: ICPI-containing combination therapies are superior to TKI monotherapy for the first-line treatment of advanced HCC, providing marked improvements in survival outcomes. Dual ICPI therapy represents the most balanced approach between efficacy and safety, achieving high survival with the lowest rates of severe toxicity. Among approved options, NivoIpi exhibited a numerically favorable survival signal, while DurvaTreme offered the highest tolerability, supporting a personalized treatment approach based on individual patient risk factors and hepatic reserve. Full article

Background/Objectives: Adults with single-ventricle physiology (SVP) represent a growing population with complex cardiovascular conditions and an increasing need for noncardiac surgical and interventional procedures. However, perioperative outcomes in this group remain poorly characterized. This study aimed to provide a descriptive characteristic of perioperative management, complications and mortality in adults with SVP undergoing noncardiac surgical and interventional procedures. Methods: We conducted a retrospective cohort study including all adult patients (≥18 years) with SVP who underwent noncardiac surgical and interventional procedures requiring anesthesia or sedation at a tertiary university hospital between 1 January 1995 and 30 November 2023. Demographic data, comorbidities, type of procedure and anesthetic technique were collected. Complications were defined as intraoperative or postoperative adverse events requiring intervention or associated with hemodynamic, respiratory, or cardiovascular instability. Primary outcomes were perioperative complications and all-cause mortality at 24 h, 30 days, and one year, with mortality reported at the patient level. Results: A total of 114 procedures were performed in 67 patients (mean age 32.3 ± 10.8 years). Most procedures were elective (78.9%) and minimally invasive, frequently performed under sedation, with or without local anesthesia (67.5%). Common comorbidities included arrhythmias (46.3%), liver disease (49.3%), and heart failure (17.9%). The overall complication rate was 6.1% (2.6% intraoperative, 3.5% postoperative). Mortality was 1.5% in 24 h, 2.9% in 30 days and 5.9% at one year. Most clinically relevant adverse events occurred in patients with earlier-stage palliation, advanced functional limitation or multiple comorbidities. Conclusions: Perioperative outcomes in adults with SVP undergoing noncardiac surgical and interventional procedures were acceptable when procedures were elective and managed in specialized settings. Risk remains heterogeneous and appears to be influenced by physiological status and stage of palliation. Full article