Trending Topics in Gastroenterology | GastroAGI

Propranolol Adds No Benefit to Band Ligation in HCC-Related Variceal Bleeding | Gut

Introduction Secondary prevention of oesophageal variceal bleeding traditionally relies on combination therapy with non-selective beta-blockers and endoscopic band ligation in patients with cirrhosis. However, patients with hepatocellular carcinoma (HCC) represent a distinct high-risk population with advanced portal hypertension, impaired liver reserve and competing oncologic mortality, raising uncertainty about whether standard variceal prophylaxis strategies provide similar benefit in this setting. Problem Statement Although propranolol combined with endoscopic band ligation is widely accepted for secondary prophylaxis of variceal bleeding in cirrhosis, evidence specifically supporting this approach in patients with HCC has been limited. The balance between efficacy, tolerability and survival benefit in patients with advanced liver cancer and portal hypertension remains unclear. Summary This randomized trial demonstrates that adding propranolol to endoscopic band ligation does not improve outcomes in patients with HCC undergoing secondary prevention of oesophageal variceal bleeding. Rates of early re bleeding, cumulative recurrent bleeding and overall survival were similar between patients treated with combination therapy and those receiving band ligation alone. Importantly, the study population largely consisted of patients with advanced disease and impaired hepatic reserve, reflecting a clinically relevant real-world HCC cohort. Large varices emerged as the primary predictor of recurrent bleeding, emphasizing the dominant role of portal hypertensive severity rather than beta-blocker therapy in determining outcomes. These findings challenge the routine extrapolation of cirrhosis-based secondary prophylaxis strategies to patients with HCC and suggest that the additional use of propranolol may not provide meaningful clinical benefit in this population. The study supports a more individualized approach to variceal management in HCC, particularly in patients with advanced tumor burden and decompensated liver disease.

Biomarkers in HCC Surveillance: Gastroenterology | May 2026

Introduction and Summary This commentary discusses the role of serum biomarkers in hepatocellular carcinoma surveillance, particularly after a randomised trial by Hirode et al. evaluated whether adding AFP, AFP-L3, and DCP to routine ultrasound improves early HCC detection. The original trial found that adding these biomarkers to biannual ultrasound did not significantly improve early-stage HCC detection compared with ultrasound alone. This challenges the routine use of biomarker panels in all high-risk patients. However, the authors of this letter argue that biomarkers should not be dismissed too quickly. They highlight important methodological issues that may influence interpretation. Problem Statement HCC surveillance is difficult because ultrasound has variable sensitivity, especially in obesity, cirrhosis, and nodular liver disease. Biomarkers may help, but their value depends on patient risk, biomarker thresholds, tumour biology, and timing of measurement. The key question is not simply whether biomarkers should be added to ultrasound for everyone, but which patients may benefit most and how biomarkers should be interpreted longitudinally. Key Points Raised by the Authors 1. Baseline HCC Risk Was Not Clearly Stratified The authors note that although both trial groups appeared balanced clinically, baseline HCC risk scores were not clearly reported. This matters because lower-risk patients, especially those without cirrhosis, may reduce the apparent benefit of biomarkers. 2. Risk-Based Surveillance May Be Better Instead of a uniform surveillance strategy, the authors suggest using validated HCC risk scores to adjust surveillance intensity, biomarker cutoffs, and cost-effectiveness. 3. AFP-L3 May Have Limited Added Value Although AFP-L3 showed relatively better individual diagnostic accuracy, the GALAD score, which includes AFP-L3, numerically performed slightly worse than the ASAP model, which excludes it. This raises the possibility that AFP-L3 may add limited independent value in some populations. 4. AFP-L3 Should Be Tested in Specific Subgroups The authors suggest evaluating AFP-L3, particularly in patients with negative ultrasound and AFP <20 ng/mL, where its incremental value would be clinically more meaningful. 5. Ultrasound False Positives Remain a Major Problem A high proportion of positive ultrasound findings did not lead to HCC diagnosis. Biomarkers may be useful not only for detecting cancer but also for helping distinguish benign ultrasound abnormalities from true malignancy. 6. More Direct Comparison Is Needed The authors request performance data for ultrasound alone within the biomarker arm, so the true incremental value of biomarkers can be better quantified. 7. Longitudinal Biomarker Trends May Be More Informative Rather than analysing biomarkers only from baseline, aligning biomarker changes to the actual date of HCC diagnosis may reveal rising trends before cancer detection. Clinical Relevance This letter provides an important caution: a negative overall trial result does not mean biomarkers have no role in HCC surveillance. Their value may be greatest in selected high-risk patients, ultrasound-negative patients, patients with poor ultrasound visualisation, or those showing rising biomarker trends over time. For clinicians, the key message is that biomarkers should not replace ultrasound, and routine addition for all patients may not be justified. However, risk-adapted and longitudinal biomarker strategies may still improve future surveillance models. Conclusion The commentary supports the trial’s important finding that routine addition of AFP, AFP-L3, and DCP to ultrasound may not significantly improve early HCC detection in a broad surveillance population. However, it argues that further subgroup analysis, risk stratification, ultrasound false-positive assessment, and longitudinal biomarker kinetics are needed. The future of HCC surveillance may not be “ultrasound versus biomarkers,” but rather personalised surveillance using risk scores, imaging quality, biomarker combinations, and dynamic trends over time.

AGA Guidelines on HCC Surveillance: Gastroenterology | May 2026

Introduction Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality in patients with cirrhosis. Despite advances in treatment, outcomes are largely determined by stage at diagnosis, making surveillance critical. Current strategies rely on ultrasound with AFP, but limitations in sensitivity and poor real-world uptake have created a need for better risk stratification and improved surveillance tools. Why This Guideline Is Required Traditional surveillance approaches are suboptimal due to: Underuse in clinical practice Limited sensitivity of ultrasound Changing epidemiology (rise of MASLD and alcohol-related liver disease) Lack of validated biomarkers and risk-based strategies This guideline focuses on improving risk stratification, surveillance efficiency, and early detection. 20 Key Takeaways for Clinicians 1. Prevention of cirrhosis is the most effective HCC strategy Treat viral hepatitis, alcohol use, and metabolic syndrome early. 2. Surveillance saves lives Early detection improves access to curative therapies and survival. 3. Standard surveillance = Ultrasound + AFP every 6 months Still the recommended global standard. 4. Semiannual surveillance is superior to annual surveillance. It detects earlier-stage tumours and improves outcomes. 5. Ultrasound has limitations Reduced sensitivity in obesity, MASLD, and advanced liver disease. 6. AFP improves sensitivity when added to ultrasound A combination is better than ultrasound alone. 7. Surveillance is underutilised Less than 25% of eligible cirrhosis patients undergo regular screening. 8. Target population = All cirrhosis patients Regardless of aetiology. 9. Select non-cirrhotic HBV patients need surveillance Based on age, ethnicity, and risk scores. 10. No routine surveillance in non-cirrhotic MASLD or HCV Unless better risk stratification tools are available. 11. Surveillance not useful in limited life expectancy Especially non-transplant candidates with advanced disease. 12. Harms of surveillance must be considered False positives, anxiety, cost, and unnecessary procedures. 13. Biomarkers like GALAD are promising but not ready Do not replace ultrasound + AFP yet. 14. Liquid biopsy is the future—but still experimental Requires validation in large prospective trials. 15. Multicancer detection panels should NOT be used Not validated for HCC surveillance populations. 16. MRI has higher sensitivity, but is not routine Cost, access, and practicality limit widespread use. 17. Abbreviated MRI is promising May become a future alternative in selected patients. 18. Risk stratification is the future of surveillance Not all cirrhosis patients have equal risk. 19. Current risk models are imperfect Limited validation and modest predictive performance. 20. HBV risk scores (PAGE-B, REAL-B) are useful Can guide surveillance decisions in non-cirrhotic HBV patients. Practical Clinical Message HCC surveillance is evolving from a uniform approach to a personalised strategy. While ultrasound + AFP remains the backbone, future progress will depend on risk-based surveillance, better biomarkers, and improved patient selection. Conclusion This guideline reinforces that current surveillance methods are effective but imperfect. The next phase in HCC care lies in precision surveillance, combining clinical risk, biomarkers, and imaging innovations to improve early detection while minimising harm.

HCC with PVTT: Liver Cancer | April 2026

Introduction Hepatocellular carcinoma with portal vein tumor thrombus represents one of the most aggressive forms of liver cancer, associated with poor prognosis and limited survival. Standard treatment relies on systemic therapy, including targeted agents and immunotherapy, but outcomes remain suboptimal. Increasingly, combining systemic therapy with locoregional approaches such as transarterial chemoembolization or hepatic arterial infusion chemotherapy is being explored to improve disease control. Problem Statement Systemic therapy alone provides limited survival benefit in HCC with PVTT, and the role of combined locoregional and systemic treatment strategies is not well established. Summary This propensity score–matched study demonstrates that combining locoregional therapy (TACE or HAIC) with systemic therapy significantly improves outcomes compared to systemic therapy alone in patients with HCC and PVTT. The combination approach nearly tripled median overall survival (15.7 vs. 5.9 months) and significantly improved progression-free survival and disease control rates. Importantly, the survival benefit was particularly pronounced in patients with advanced PVTT (Vp4) and those with poorer liver function (Child-Pugh B), suggesting that this strategy may be especially valuable in high-risk groups. Although adverse events were more frequent with combination therapy, severe toxicities were comparable between groups, indicating acceptable safety. Clinically, this study supports a shift toward multimodal therapy in advanced HCC with vascular invasion. It challenges the traditional reliance on systemic therapy alone and suggests that integrating locoregional approaches can meaningfully improve survival in selected patients.

Nutrition in MASLD: Frontline Gastroenterology | 2026

Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the leading cause of chronic liver disease worldwide and closely parallels the epidemics of obesity and type 2 diabetes. Lifestyle modification remains the first-line, evidence-based treatment, but in real practice there is often a major gap between guideline advice and what patients are actually able to follow. This review focuses on nutrition as the central modifiable factor in MASLD care, while also recognizing the importance of physical activity, sleep, culture, affordability, and food access. Problem Statement The major challenge in MASLD is not only knowing that diet matters, but translating broad recommendations into realistic, culturally sensitive, affordable, and sustainable nutrition advice for individual patients in busy clinical practice. Summary This review makes a strong case that nutrition should be at the centre of MASLD management. The main dietary message is to reduce ultra-processed foods, sugar-sweetened beverages, commercially produced fructose, saturated fats, and excess calories, while encouraging whole foods, vegetables, fruits, legumes, wholegrains, nuts, seeds, olive or rapeseed oil, and oily fish. The Mediterranean diet remains the most evidence-supported pattern because it improves liver fat and cardiometabolic health, sometimes even without significant weight loss. However, the authors rightly stress that the best diet is the one a patient can actually follow long term, so dietary advice must be personalized and culturally adapted. The review also explains the role of macronutrients and micronutrients. Fructose and saturated fat promote steatosis, while fibre, unsaturated fats, and adequate protein intake are protective. Micronutrients such as vitamin E, vitamin D, vitamin C, zinc, and polyphenols may influence liver health, although routine supplementation is not broadly recommended unless there is deficiency or a specific indication. Alcohol avoidance is emphasized, especially in more advanced disease. A particularly valuable part of this paper is its practical approach. It recognizes food insecurity, cost, and social context as real barriers. It gives adaptable Mediterranean-style advice for South and Southeast Asian, African, and lower-income populations, and even provides simple clinic checklists and sample menus. The overall message is clear: MASLD nutrition care should move from generic advice to compassionate, individualized, practical counselling that patients can sustain.

Adjuvant Immunotherapy in HCC: JGH | March 2026

Introduction Hepatocellular carcinoma remains a major global cancer burden, with high recurrence rates even after curative therapies such as resection or ablation. Historically, effective adjuvant treatments have been lacking, and surveillance has been the standard approach. With the success of immune checkpoint inhibitors in advanced HCC, there is growing interest in moving these therapies earlier into the adjuvant setting to reduce recurrence and improve survival outcomes. Problem Statement The role of immune checkpoint inhibitors as adjuvant therapy after curative treatment of HCC remains uncertain, with conflicting evidence and lack of definitive randomized trial data. Summary This meta-analysis of 18 studies involving over 3400 patients provides encouraging evidence that ICI-based adjuvant therapy significantly improves outcomes compared with surveillance alone. Recurrence-free survival was nearly halved (HR ~0.51), and overall survival also showed a meaningful improvement. Importantly, both ICI monotherapy and combination strategies with TKIs or anti-angiogenic agents demonstrated similar benefits, suggesting flexibility in therapeutic approaches. The benefit was consistent across subgroups, including patients undergoing resection or ablation, and regardless of prior treatments such as TACE. This reinforces the potential of immunotherapy to address the key challenge of post-curative recurrence. However, the evidence is largely derived from observational and region-specific studies, limiting generalizability. High-quality global randomized phase III trials with longer follow-up are urgently needed before routine adoption. Clinically, this study signals a paradigm shift—from passive surveillance to active adjuvant intervention—but caution is warranted until stronger prospective data confirm these findings.

Bridging the Gap in HCC Care: CGH | April 2026

Introduction Hepatocellular carcinoma (HCC) outcomes are critically dependent on stage at diagnosis, with early-stage disease offering opportunities for curative therapies such as resection, ablation, or transplantation. Despite advances in imaging, surveillance strategies, and treatment modalities, a substantial proportion of patients continue to be diagnosed at advanced stages. This reflects persistent gaps in cirrhosis recognition, suboptimal screening uptake, and healthcare access disparities. Understanding real-world patterns of HCC diagnosis, staging, treatment, and survival is essential to guide quality improvement in liver care. Problem Statement There is limited contemporary, system-level data evaluating how patients with HCC are diagnosed and managed across large healthcare systems. Key uncertainties remain regarding the proportion of patients diagnosed early, factors influencing treatment access, and determinants of survival—particularly in relation to screening and engagement in liver care. Summary In this Veterans Health Administration cohort (2023), only 56.7% had known cirrhosis prior to HCC diagnosis, highlighting under-recognition of at-risk patients. Early-stage diagnosis (T1/T2) occurred in ~60% but was strongly associated with prior cirrhosis recognition and screening, with 86.3% of screen-detected cases diagnosed early. Most patients (75.8%) received treatment, with Y-90 radioembolization being the most common. Survival was significantly better in patients diagnosed early, those undergoing screening, with preserved liver function, and those receiving curative therapies. This study underscores a central message for clinical practice: screening and structured liver care engagement are the most powerful modifiable factors to improve HCC outcomes, emphasizing the need for system-level interventions to close existing care gaps.

Fibrolamellar Carcinoma: Hepatology | March 2026

Introduction Fibrolamellar carcinoma (FLC) is a rare and biologically distinct primary liver cancer that predominantly affects adolescents and young adults without cirrhosis or other chronic liver disease. Unlike conventional hepatocellular carcinoma, FLC usually presents with normal or minimally elevated alpha-fetoprotein and often behaves aggressively despite occurring in otherwise healthy livers. A major advance in the field was the discovery of the DNAJB1::PRKACA fusion, which is now recognized as the central molecular driver in nearly all classical cases and has fundamentally changed the diagnostic and therapeutic framework of this disease. Because FLC responds poorly to treatments borrowed from conventional HCC or hepatoblastoma, this guideline is important in establishing a disease-specific approach to diagnosis, surgery, locoregional therapy, systemic treatment, and supportive care. Key Takeaways FLC should no longer be viewed as a subtype of conventional hepatocellular carcinoma, because it is a biologically separate disease with a different molecular driver, clinical pattern, and treatment response. The diagnosis of FLC requires three essential components: a primary liver tumor, characteristic histology, and molecular confirmation of DNAJB1::PRKACA fusion or, in very rare cases, PRKAR1A loss. Histology alone is not sufficient for diagnosis, because some conventional HCCs, especially scirrhous tumors, can mimic fibrolamellar morphology. Core needle biopsy is preferred over fine needle aspiration because preservation of fibrotic architecture is important for accurate diagnosis. The DNAJB1::PRKACA fusion is the defining molecular hallmark of classical FLC and should be actively tested for using targeted RNA-based assays, RT-PCR, or FISH. FLC usually affects adolescents and young adults with noncirrhotic livers and normal or minimally elevated AFP, and this clinical profile strongly supports the diagnosis. A large liver mass with a central scar on imaging is suggestive of FLC, but this finding is not specific and should never be used alone to make the diagnosis. FLC has a striking tendency to spread to regional lymph nodes, peritoneum, and lungs, making nodal assessment much more important than in conventional HCC. Baseline ancillary work-up should include broad NGS testing, HER2 immunohistochemistry, and serum ammonia measurement, because these may influence therapeutic planning and supportive care. Hyperammonemia and hyperammonemic encephalopathy are clinically important complications in FLC and may occur independently of liver failure. Surgery remains the cornerstone of treatment because FLC is only modestly responsive to systemic therapy and many patients tolerate aggressive liver surgery due to preserved underlying liver function. Patients with apparently classic and easily resectable FLC may occasionally proceed directly to surgery without preoperative biopsy when imaging and clinical context are highly convincing. Routine regional lymph node sampling or lymphadenectomy is strongly recommended even when imaging does not clearly show nodal disease, because occult nodal spread is common. Repeat surgery for recurrence, including metastasectomy and staged resection, can meaningfully prolong survival and is an accepted strategy in selected patients. Debulking surgery may still be worthwhile in advanced disease, including selected patients with lymph node, peritoneal, lung, brain, or bone metastases, especially when disease biology is indolent. Liver transplantation should be considered in patients with unresectable disease confined to the liver, even when the tumor does not fit traditional Milan criteria. Locoregional therapies such as Y-90 radioembolization, TACE, and SBRT are recommended both for palliation and as bridges to definitive surgery or control of unresectable disease. For advanced unresectable disease, the guideline supports GEMOX, GEMOX plus lenvatinib, or ipilimumab plus nivolumab as the most favored first-line systemic options based on available evidence and expert consensus. Clinical trial participation should be offered whenever possible because no universal standard systemic regimen exists and several promising fusion-directed or immunotherapy-based strategies are under active investigation. FLC care must include psychosocial, palliative, and multidisciplinary support, because this disease affects adolescents and young adults during a highly vulnerable stage of life and often imposes major emotional, social, fertility, and financial burdens. Conclusion This guideline is highly important because it formally establishes FLC as a unique liver cancer that requires its own diagnostic criteria and treatment strategy. The most practice-changing message is that molecular confirmation of the DNAJB1::PRKACA fusion, aggressive surgery with nodal assessment, and thoughtful use of systemic and locoregional therapies should define modern management. At present, surgery remains central, but the future of FLC care is clearly moving toward fusion-directed immunotherapy, biologically informed clinical trials, and more personalized multimodality treatment.

Microbial Metabolism follwoing TACE: Journal of Hepatology | April 2026

Introduction Transarterial chemoembolization (TACE) remains one of the most important treatments for unresectable hepatocellular carcinoma, but its clinical benefit is often limited by post-procedural liver injury. Traditionally, this injury has been attributed mainly to ischemia and chemotherapy-related damage to non-tumoral liver tissue. However, this explanation does not fully account for the variability in liver injury seen after TACE, suggesting that additional biological mechanisms are involved. This study explores whether disruption of the gut microbiota contributes to TACE-related liver injury. Problem Statement TACE-induced liver injury is a common complication that can compromise tolerance to repeated treatment and adversely affect long-term survival. Although direct hepatic injury is well recognized, the role of the gut–liver axis in this setting has remained poorly understood. Identifying modifiable microbial mechanisms could open a new strategy to reduce post-TACE complications and improve outcomes in HCC. Summary This study shows that TACE is associated with significant gut microbiota disturbance, and that this disturbance is not merely an epiphenomenon but a contributor to liver injury. In both rats and patients, TACE reduced the abundance of Limosilactobacillus reuteri and lowered levels of its tryptophan-derived metabolite indole-3-lactic acid (ILA). Lower levels of both were associated with more severe liver injury and poorer overall survival. Importantly, administration of live L. reuteri or ILA significantly reduced TACE-induced liver injury. Mechanistically, ILA suppressed macrophage-driven inflammation by inhibiting the HSP90–NLRP3 inflammasome pathway. This work identifies a novel microbiota-mediated mechanism of TACE toxicity and suggests that microbial or metabolite supplementation may become a practical adjunct to improve safety and prognosis in patients undergoing TACE.

BCLC Classification and AI-Based Image Quantification in HCC: Journal of Hepatology | March 2026

Introduction The Barcelona Clinic Liver Cancer (BCLC) classification has remained the cornerstone for staging, prognosis, and treatment allocation in hepatocellular carcinoma for more than two decades. Its strength lies in its simplicity and clinical applicability, integrating tumor burden, liver function, and performance status into a unified framework. However, modern imaging contains far more quantitative information than is currently utilized in BCLC. With the rapid evolution of artificial intelligence, there is now an opportunity to extract complex imaging features automatically and integrate them into clinical decision-making. This article explores how AI can complement, rather than replace, the BCLC system to enable more precise and personalized management of HCC. Summary This review highlights that while BCLC remains robust and widely validated, it underutilizes the wealth of data embedded in imaging. AI-based tools can quantify tumor volume, assess intratumoral heterogeneity, detect vascular invasion, evaluate portal hypertension through surrogate markers such as spleen volume, and even estimate body composition to reflect patient performance status. These parameters have shown strong associations with prognosis and treatment response in early studies. However, despite promising results, most AI applications remain confined to retrospective research settings due to poor reproducibility, lack of standardization, absence of prospective validation, and limited integration into clinical workflows. The article emphasizes that the key challenge is not technological capability but translational implementation. AI must be seamlessly embedded into routine workflows, supported by structured reporting, validated across diverse populations, and aligned with clinical frameworks such as BCLC. Importantly, the authors reinforce that clinical decision-making in HCC is inherently influenced by complexity, uncertainty, subjectivity, and emotion, and AI should support, not replace, this human-centered process. The future likely lies in a hybrid model where BCLC provides the clinical backbone, and AI adds quantitative refinement to improve prognostication and treatment selection.