Dahiya, Dushyant Singh

Atezolizumab-bevacizumab and durvalumab-tremelimumab have established immunotherapy as a first-line standard of care in advanced hepatocellular carcinoma (HCC). Yet, objective response rates (ORRs) remain confined to approximately 15-20%, and no validated predictive biomarker exists for patient selection. Unlike melanoma and lung cancer, conventional markers, including programmed death-ligand 1, microsatellite instability-high status, and tumor mutational burden, have not demonstrated reliable predictive value in HCC. Prior narrative reviews comprehensively catalogued the biomarker landscape through 2022 but predate a wave of clinically significant publications. This narrative review synthesizes evidence published between 2020 and 2026, with particular emphasis on 2023–2026 data, within a unified clinical framework not provided by prior reviews. We critically evaluate tissue-based biomarkers, including the AI-derived Atezolizumab-Bevacizumab Response Signature-Pathology model, spatial multiplex immunohistochemistry, and β-catenin mutational profiling; blood-based biomarkers encompassing circulating tumor DNA for minimal residual disease detection and peripheral immune phenotyping; and serum indices including the CRAFITY score and neutrophil-to-lymphocyte ratio. Hepatitis B virus etiology and non-alcoholic steatohepatitis are discussed as biological modifiers of biomarker performance. We propose an original biomarker-guided clinical algorithm, a comparative clinical readiness table, and a disease-continuum biomarker timeline as practical tools for clinicians and trialists. Prospective biomarker-enrichment trials represent the most critical next step toward clinical translation.

Background: Liver transplantation (LT) remains the definitive treatment for end-stage liver disease; however, post-LT outcomes may differ depending on underlying disease etiology. Our study aimed to compare post-LT outcomes between alcoholic and non-alcoholic steatohepatitis (NASH)-related liver transplant recipients in the United States. Methods: A retrospective cohort study was conducted using the TriNetX Research Network. Adult liver transplant recipients (≥18 years) were categorized into two mutually exclusive cohorts: alcoholic liver disease and NASH-related liver disease. Propensity score matching (1:1) was performed to balance baseline characteristics. Clinical outcomes were assessed. Comparative analyses included risk ratios, risk differences, odds ratios, Kaplan–Meier survival analysis, and hazard ratios with log-rank testing. Results: Compared with NASH recipients, alcoholic LT recipients had a significantly higher risk of rejection (14.5% vs. 12.1%; RR 1.195, 95% CI 1.076–1.327; p = 0.001) and hepatic encephalopathy (14.3% vs. 8.3%; RR 1.720, 95% CI 1.526–1.938; p < 0.001). Acute kidney injury was also more frequent in the alcoholic cohort (47.3% vs. 43.6%; RR 1.084, 95% CI 1.036–1.133; p < 0.001). In contrast, sepsis (15.6% vs. 18.0%; RR 0.869, 95% CI 0.794–0.952; p = 0.003) and CKD (46.1% vs. 51.1%; RR 0.901, 95% CI 0.863–0.939; p < 0.001) occurred less frequently in alcoholic LT patients. No significant differences were observed for liver transplant failure or ascites. Kaplan–Meier analyses demonstrated significantly lower rejection-free survival (HR 1.241, p < 0.001), higher hepatic encephalopathy (HR 1.808, p < 0.001), increased AKI risk (HR 1.150, p < 0.001) and higher all-cause mortality in the alcoholic cohort (HR 1.106, p = 0.031). Conclusions: In this large real-world matched cohort study, alcoholic LT recipients demonstrated higher risks of complications and all-cause mortality compared with NASH LT recipients.

Colorectal cancer (CRC) is responsible for a high cancer burden and a high number of deaths all over the world, although effective screening can make it preventable to a significant extent. Stool-based tests, such as the fecal immunochemical test (FIT) and multitarget stool DNA (mt-sDNA) testing, are gaining considerable popularity as non-invasive procedures that can be a replacement for colonoscopies for people at an average risk for colon cancer. Despite evidence from several randomized controlled trials supporting the use of these tests for colorectal cancer screening, their external validity in a real-world setting is influenced by many factors such as adherence, timely follow-up post testing, the healthcare cost burden, accessibility and the capacity of the health system. In this article, we have performed an extensive narrative literature review of research published between 2020 and 2025 comparing FIT and the mt-sDNA test with reference to diagnostic accuracy, cost-effectiveness, adherence and outcomes of implementation. We discuss the issues of sensitivity and specificity, look at post-test requirements for colonoscopy and check if there is any discrimination in healthcare. These findings suggest that FIT and mt-sDNA tests should not be considered competing technologies but rather complementary screening methods, with their overall effectiveness contingent upon appropriate patient selection and widespread system-level implementation. It is crucial to combine strategic test selection with a robust follow-up infrastructure to ensure that the entire population benefits from the CRC prevention program.

Antibody–drug conjugates (ADCs) are reshaping the therapeutic approach to advanced gastrointestinal cancers by integrating tumor-specific monoclonal antibodies with potent cytotoxic payloads to improve targeted tumor cell destruction while minimizing systemic exposure. Compared to traditional chemotherapy, trastuzumab deruxtecan has significantly improved objective response rates and overall survival in HER2-positive gastric and gastroesophageal junction tumors after trastuzumab-based therapy. This supports its role as an important second-line or later treatment option. The ongoing advancement of ADCs targeting CLDN18.2, TROP2, and CEACAM5 indicates that this therapeutic category will continue to expand across gastrointestinal neoplasms. Nonetheless, these advancements are accompanied by a specific and clinically significant toxicity profile. Hematologic suppression, gastrointestinal side effects, hepatotoxicity, and notably interstitial lung disease (ILD) are essential consequences that may need inpatient assessment and care. Interstitial lung disease (ILD), although uncommon, may be severe or lethal if not identified immediately and treated swiftly with medication cessation and corticosteroids. In hospitalized patients, distinguishing ADC-related toxicity from infection or disease progression is often difficult owing to overlapping clinical manifestations, requiring meticulous evaluation and interdisciplinary cooperation. As ADCs are integrated into earlier treatment lines and across a broader patient population, hospital systems must evolve to ensure prompt identification, consistent management protocols, and efficient collaboration between oncology and inpatient teams. This study analyzes the mechanisms, clinical effectiveness, and safety profile of ADCs in gastrointestinal oncology, pointing out the importance of institutional preparedness to safely incorporate these medicines into standard clinical practice. These features also align ADC therapy with personalized medicine by emphasizing biomarker-guided patient selection and individualized toxicity monitoring.

Motility disorders, particularly gastroparesis, are prevalent complications following solid organ transplantation, significantly impacting quality of life, nutritional status, graft survival, and mortality. This comprehensive review synthesises evidence from PubMed, Scopus, and Embase databases on pathophysiology, clinical manifestations, diagnosis, management, and prognostic factors across transplant types. Mechanisms include vagal nerve injury (highest in lung transplants, prevalence 40–91%), immunosuppressive effects (e.g., tacrolimus accelerates motility; mycophenolate impairs it), surgical trauma, microbiome dysbiosis (reduced Firmicutes/Bacteroidetes ratio), and metabolic factors like post-transplant diabetes (OR 5.17 in kidney recipients). Pediatric and thoracic recipients face the highest risks, with lung transplant gastroparesis conferring a 2.7-fold increased mortality/retransplantation hazard (p < 0.05). Diagnosis relies on gastric emptying scintigraphy (gold standard, sensitivity 85–95%) and wireless motility capsules (100% sensitivity for delay), while management encompasses prokinetics (60–80% response), endoscopic G-POEM (85% success), gastric electrical stimulation (100% quality-of-life improvement in series), and nutritional support. Prognostic factors include younger age (better intervention response), aetiology (anatomical worse than metabolic), and early therapy success. Outcomes vary: lung recipients experience severe impacts on chronic allograft dysfunction (83% oesophageal motility abnormalities correlate with 66–67% rejection). Future directions emphasise microbiome therapies, AI predictive models (AUC 0.85), and wearables for continuous monitoring. Multidisciplinary approaches are essential to balance immunosuppression with GI management, addressing ethical dilemmas like drug interactions and access disparities. Ultimately, early screening and personalised interventions can mitigate complications, enhancing long-term transplant success.

Abstract Background Inflammatory bowel disease (IBD) predisposes individuals to frailty, linked with adverse outcomes. While the Fried Frailty Index (FFI) is a well-established phenotypic tool to assess frailty, its administration is cumbersome. The FRAIL scale, simpler but not widely used in IBD patients, presents an alternative. We aimed to assess the prevalence of frailty and compare the FRAIL scale with the FFI. Methods Two hundred and nine confirmed IBD patients underwent assessment using both the FFI and the FRAIL scale. Patients were categorized as non-frail, pre-frail, or frail. Pearson coefficients evaluated correlation, and unadjusted analyses assessed frailty risk factors. ROC curve analysis evaluated the FRAIL scale. Results Among participants (53.5% female, median age 44), 37% were non-frail, 50% pre-frail, and 13% frail. The FRAIL scale exhibited strong correlation with the FFI for all three categories. Age showed no significant association with frailty. Frail individuals displayed higher inflammatory markers and more severe clinical disease, with frailty more prevalent in UC than CD patients. Frail individuals also exhibited lower hemoglobin, creatinine, and albumin levels. Conclusion Frailty and pre-frailty are prevalent in the IBD population, not necessarily linked with older age. The FRAIL scale demonstrated excellent correlation with the FFI, offering a practical tool for identifying frailty in IBD without physical measurements. Future studies should explore multivariable models incorporating frailty risk factors and interventions to mitigate adverse outcomes in the IBD population.

ABSTRACTObjectiveAlcohol‐related liver disease (ALD) has emerged as a significant public health concern, particularly among younger populations. ALD remains the leading cause of alcohol‐attributable deaths. This study aims to forecast ALD mortality trends up to 2030, focusing on individuals under 55 years.MethodsWe utilized data from the CDC WONDER database (1999–2022) to examine ALD‐related deaths, identified by ICD‐10 codes (K70.0–K70.9). Crude mortality rates (CMRs) per 100 000 were analyzed and temporal trends were assessed using annual and average annual percent changes (APC/AAPC) with empirical quantile confidence intervals. An Autoregressive Integrated Moving Average (ARIMA) model was employed to project mortality rates until 2030, validated through time series cross‐validation.ResultsFrom 1999 to 2022, there were 181 862 ALD‐related deaths among individuals under 55, with mortality rates increasing from 3.9 per 100 000 in 1999 to 9.7 per 100 000 in 2022 (AAPC 4.66%, 95% CI: 3.90%–5.86%). Projections suggest rates will continue to rise, reaching 14.4 per 100 000 by 2030. From 1999 to 2022, the 25–34 age group experienced the highest increase, with an AAPC of 10.27% (95% CI: 9.19%–11.35%), while the 35–44 and 45–54 age groups showed more moderate increases, with AAPCs of 5.03% and 4.38%, respectively. Projections indicate an AAPC of 3.86% for ages 25–34, 3.90% for ages 35–44, and 6.17% for ages 45–54 by 2030.ConclusionForecasts indicate a continued rise in ALD mortality among individuals under 55, necessitating immediate public health strategies to mitigate this trend.