Trending Topics in Gastroenterology | GastroAGI

Liver Stiffness for HCC Risk in MASLD: Hepatology | July 2026

Introduction: Metabolic dysfunction–associated steatotic liver disease (MASLD) is now the fastest-growing cause of hepatocellular carcinoma (HCC). Because a substantial proportion of MASLD-related HCC develops before cirrhosis, better tools are needed to identify high-risk patients who may benefit from surveillance. This study evaluated whether liver stiffness measurement (LSM) by transient elastography can improve HCC risk stratification in MASLD. Why was this study needed? HCC increasingly develops in patients with MASLD, including those without cirrhosis. Current surveillance strategies miss many high-risk noncirrhotic patients. Reliable, noninvasive biomarkers for HCC risk stratification are lacking. Defining LSM thresholds could enable more cost-effective surveillance. Results: This retrospective study included more than 30,000 patients with MASLD from the Veterans Analysis of Liver Disease (VALID) cohort. HCC risk increased progressively with increasing liver stiffness, with every 5 kPa rise in LSM associated with an 18% increase in HCC risk. Patients with higher LSM values demonstrated stepwise increases in annual HCC incidence, reaching nearly 1% per year among those with LSM ≥25 kPa. Importantly, among patients without cirrhosis or clinically significant portal hypertension, those with diabetes and an LSM ≥10 kPa had an annual HCC incidence exceeding the accepted threshold for cost-effective HCC surveillance. Clinical Impact: LSM may become an important noninvasive tool for individualized HCC surveillance in MASLD. Rather than relying solely on cirrhosis status, integrating liver stiffness and diabetes status could identify high-risk noncirrhotic patients who are currently overlooked by existing surveillance recommendations. This approach may improve early HCC detection while optimizing resource utilization. Bottom Line: Liver stiffness is a strong predictor of HCC risk in MASLD. Noncirrhotic patients with MASLD, diabetes, and an LSM ≥10 kPa may be appropriate candidates for HCC surveillance.

Durvalumab Plus Tremelimumab in Real-World HCC: JGH | May 2026

Introduction: The HIMALAYA trial established durvalumab plus tremelimumab (STRIDE) as a first-line treatment for unresectable hepatocellular carcinoma (HCC). However, many real-world patients do not meet the strict eligibility criteria of clinical trials. This multicenter study evaluated the effectiveness and safety of STRIDE in routine clinical practice. Why was this study needed? • Many patients treated in routine practice would not have qualified for the HIMALAYA trial. • Real-world effectiveness of STRIDE outside trial criteria remains uncertain. • Better predictors of treatment outcomes are needed. • Liver function may be more important than trial eligibility alone. • Real-world data are essential to guide everyday clinical decision-making. Results: • Patients meeting the HIMALAYA eligibility criteria achieved longer progression-free and overall survival than those who did not meet trial criteria. • Among patients outside the HIMALAYA criteria, those with preserved liver function (ALBI Grade 1) achieved survival outcomes comparable to trial-eligible patients. • Poor liver function (ALBI ≥2), impaired performance status, and portal vein invasion were associated with worse clinical outcomes, emphasizing the importance of careful patient selection. Clinical Impact: This real-world study demonstrates that STRIDE remains effective beyond the strict HIMALAYA trial population, particularly in patients with well-preserved liver function. ALBI grade may be a more practical tool than trial eligibility alone when selecting patients for immunotherapy. Bottom Line: Preserved liver function—not simply trial eligibility—is the key determinant of successful STRIDE therapy. Patients with ALBI Grade 1 may derive meaningful benefit from durvalumab plus tremelimumab even if they would not have met the original HIMALAYA trial inclusion criteria.

ALBI Grade and Sarcopenia in Unresectable HCC: IJG | July 2026

Introduction: Prognosis in unresectable hepatocellular carcinoma (HCC) depends not only on tumor burden but also on liver function and nutritional status. This study evaluated the prognostic value of ALBI grade, EZ-ALBI grade, and sarcopenia in patients with intermediate- and advanced-stage HCC treated with TACE alone or TACE plus lenvatinib. Why was this study needed? • Reliable prognostic markers are needed to personalize treatment in unresectable HCC. • ALBI and EZ-ALBI provide objective assessment of liver function. • Sarcopenia is increasingly recognized as an important determinant of cancer outcomes. • Their combined prognostic value in TACE-based therapy remains unclear. • Better risk stratification may improve treatment selection and follow-up. Results: • ALBI and EZ-ALBI grades accurately predicted treatment response, disease progression, and progression-free survival in both intermediate-stage HCC treated with TACE and advanced-stage HCC treated with TACE plus lenvatinib. • Sarcopenia was associated with poorer treatment response and shorter progression-free survival in advanced HCC, but showed limited prognostic value in intermediate-stage disease treated with TACE alone. • These findings highlight the complementary role of liver reserve and muscle mass in predicting outcomes after locoregional and systemic therapy. Clinical Impact: Routine assessment of ALBI/EZ-ALBI grades and sarcopenia may improve prognostic stratification in unresectable HCC. While ALBI-based scores appear useful across disease stages, assessment of sarcopenia may be particularly valuable in patients receiving combination therapy with TACE and lenvatinib. Bottom Line: ALBI and EZ-ALBI are simple, effective prognostic tools for unresectable HCC. In advanced disease, sarcopenia identifies patients with poorer outcomes, emphasizing the importance of integrating nutritional and functional assessment into routine HCC management.

HCC Surveillance Saves Lives: Frontline Gastroenterology | July 2026

Introduction: Hepatocellular carcinoma (HCC) surveillance enables earlier diagnosis and improves survival. This largest UK multicenter study evaluated how patients are diagnosed in routine clinical practice and identified major gaps in the surveillance pathway. Why was this study needed? • Early HCC detection remains suboptimal despite established surveillance guidelines. • Real-world data on surveillance performance across the UK have been limited. • Understanding where surveillance fails is essential to improve outcomes. • Earlier diagnosis increases eligibility for curative treatment. • Better surveillance pathways could reduce HCC-related mortality. Results: • Only 28% of HCC cases were detected through surveillance, while nearly half of patients presented with symptoms, reflecting missed opportunities for early diagnosis. • Surveillance identified smaller tumors at an earlier stage, resulting in substantially lower 1-year mortality compared with incidental or symptomatic presentation. • Failures occurred throughout the surveillance pathway, including missed cirrhosis diagnosis, failure to enroll eligible patients, and inadequate surveillance delivery. Clinical Impact: This study highlights that the greatest opportunity to improve HCC outcomes lies before the cancer develops—by identifying patients with cirrhosis, enrolling them into surveillance programs, and ensuring regular high-quality follow-up. Strengthening every step of the surveillance pathway could substantially increase early detection and access to curative therapies. Bottom Line: HCC surveillance works—but it is underutilized. Fewer than 1 in 3 high-risk patients are diagnosed through surveillance, despite clear evidence that earlier detection saves lives. Improving surveillance implementation should be a major priority in HCC care.

Yttrium-90 Radioembolization for HCC: The Lancet Regional Health | July 2026

Introduction: Selective internal radiation therapy (SIRT) using yttrium-90 (Y90) glass microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), but guideline recommendations remain inconsistent. This large prospective multicenter study evaluated the real-world effectiveness, safety, quality of life, and survival outcomes of Y90 radioembolization. Why was this study needed? • High-quality prospective real-world data on Y90 radioembolization are limited. • Current international guidelines differ regarding the role of Y90 in HCC. • The impact of personalized dosimetry on survival remains uncertain. • More evidence is needed in patients with portal vein tumor thrombosis (PVT). • The potential role of Y90 as a bridge to curative surgery requires further validation. Results: • Y90 radioembolization achieved encouraging overall survival with a favorable safety profile across all BCLC stages, including patients with portal vein tumor thrombosis. • Higher radiation doses to the tumor (especially ≥400 Gy) were associated with significantly longer survival, supporting personalized dosimetry-guided treatment. • Approximately 1 in 10 patients were successfully downstaged to curative surgery after Y90, achieving excellent long-term survival, while quality of life remained well preserved. Clinical Impact: This landmark real-world study strengthens the role of dosimetry-guided Y90 radioembolization as an effective and safe treatment for selected patients with HCC. It also highlights Y90 as an important downstaging strategy before curative surgery and supports broader incorporation into future treatment guidelines. Bottom Line: Personalized Y90 radioembolization delivers meaningful survival with low toxicity in HCC. Higher tumor radiation doses improve outcomes, and successful downstaging to surgery offers the best long-term survival, reinforcing the importance of dosimetry-guided treatment planning.

Bleeding Risk with Immunotherapy in Advanced HCC: JHEP Reports | July 2026

Introduction: Atezolizumab–bevacizumab (A/B) and durvalumab–tremelimumab (STRIDE) are preferred first-line treatments for advanced hepatocellular carcinoma (HCC). Because bevacizumab inhibits VEGF, concerns remain regarding bleeding and thromboembolic complications in patients with underlying cirrhosis and portal hypertension. Why was this study needed? • Direct real-world safety comparisons between A/B and STRIDE are limited. • The anti-VEGF component of bevacizumab may increase bleeding risk. • Clinicians need evidence to guide treatment selection in patients at high bleeding risk. • The comparative risk of variceal bleeding and thromboembolic events remains uncertain. • Better safety data are needed to individualize first-line immunotherapy. Results: • Atezolizumab–bevacizumab was associated with significantly more overall and severe bleeding events, which also occurred earlier than with durvalumab–tremelimumab. • Variceal bleeding and thromboembolic event rates were similar between the two treatment groups despite the higher overall bleeding risk with A/B. • Treatment with A/B independently predicted bleeding risk, suggesting that the VEGF inhibitor contributes to this increased risk. Clinical Impact: These findings suggest that STRIDE may be the preferred first-line immunotherapy in patients with advanced HCC who have a high baseline bleeding risk, particularly those with portal hypertension or previous bleeding episodes. As this was a retrospective study, treatment decisions should still be individualized pending prospective confirmation. Bottom Line: Atezolizumab–bevacizumab increases overall bleeding risk compared with durvalumab–tremelimumab, while variceal bleeding and thromboembolic events remain similar. Careful bleeding risk assessment should guide first-line immunotherapy selection in advanced HCC.

AGA Updates HCC Risk Stratification and Surveillance : Gastroenterology | Jun 2026

Introduction: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality among patients with chronic liver disease and cirrhosis. Outcomes are substantially better when HCC is detected at an early stage, allowing access to potentially curative therapies. However, surveillance remains underutilized, and currently recommended tools have important limitations in sensitivity and implementation. As the epidemiology of liver disease shifts toward metabolic dysfunction–associated steatotic liver disease (MASLD) and alcohol-associated liver disease, there is growing interest in improving risk stratification and surveillance strategies. Problem Statement: Current HCC surveillance relies primarily on semiannual ultrasound with α-fetoprotein (AFP), but this approach fails to detect a significant proportion of early-stage tumors. At the same time, numerous emerging biomarkers, risk prediction models, and imaging approaches have been proposed, creating uncertainty regarding their role in routine clinical practice. Clear guidance is needed on how these evolving tools should be incorporated into patient care. Summary: In this AGA Clinical Practice Update, experts reaffirm that semiannual ultrasound combined with AFP remains the preferred surveillance strategy for patients at risk of HCC, particularly those with cirrhosis and selected patients with chronic hepatitis B infection. The document emphasizes that prevention of cirrhosis through viral hepatitis treatment, alcohol use disorder management, and metabolic risk factor control remains the most effective strategy for reducing HCC-related morbidity and mortality. While several promising blood-based and radiologic biomarkers, including GALAD, are undergoing clinical validation, current evidence is insufficient to support their routine use as replacements for guideline-recommended surveillance. Similarly, multicancer blood-based screening panels are not recommended for HCC surveillance at present. The update also highlights the growing need for individualized risk stratification as HCC increasingly arises in patients with nonviral liver disease, where annual cancer risk may differ substantially from traditional viral hepatitis populations. Although numerous HCC risk prediction models have been developed, few have demonstrated sufficient validation for widespread clinical use. An exception is chronic hepatitis B without cirrhosis, where PAGE-B and REAL-B scores may help identify patients at higher future risk. Overall, the guidance advocates for evidence-based surveillance while encouraging continued development and validation of novel biomarkers and precision risk-stratification tools to improve early HCC detection.

PRISM Study: Real-World Outcomes for Unresectable HCC: Liver Cancer | May 2026

• PRISM is one of the largest prospective real-world studies evaluating systemic therapy for unresectable hepatocellular carcinoma in routine clinical practice across Japan. • This analysis reports outcomes from the first 1,000 prospectively enrolled patients, providing important validation of results seen in clinical trials. • Among evaluable patients, the vast majority received atezolizumab plus bevacizumab (82.8%), while 15.2% received lenvatinib as first-line therapy. • Median overall survival reached 21.8 months with Atezo+Bev and 20.8 months with lenvatinib, demonstrating excellent real-world outcomes. • Survival outcomes were numerically better than those reported in the original registration trials, suggesting that careful patient selection, multidisciplinary management, and effective sequential therapy may be improving outcomes in practice. • Progression-free survival remained consistent with clinical trial data at 7.7 months for Atezo+Bev and 6.7 months for lenvatinib. • Objective response rates were impressive for both regimens, confirming that real-world effectiveness closely mirrors clinical trial efficacy. • Sorafenib was rarely used and showed substantially lower response rates compared with modern first-line therapies. • Grade 3 or higher treatment-related adverse events occurred in approximately 22% of patients, with no unexpected safety concerns. • Importantly, nearly 50% of patients were able to receive second-line therapy, highlighting the growing importance of sequential treatment strategies in advanced HCC. • The most common sequencing pattern was: Atezolizumab + bevacizumab → lenvatinib Lenvatinib → atezolizumab + bevacizumab • Second-line therapy provided a median progression-free survival of approximately 4 months, while benefit progressively decreased with later treatment lines. • The study demonstrates that modern systemic therapies can be safely delivered to a broad real-world population, not just highly selected clinical trial patients. • PRISM also highlights the importance of maintaining liver function and performance status to allow access to sequential therapies, which likely contributes significantly to prolonged survival. • Future analyses are expected to provide valuable information regarding special populations, including elderly patients, those with impaired liver function, and different molecular or clinical subgroups. Bottom line: The PRISM study confirms that atezolizumab plus bevacizumab and lenvatinib achieve reproducible real-world outcomes in unresectable HCC, with median overall survival exceeding 20 months and nearly half of patients successfully receiving subsequent lines of therapy.

ICI Before Liver Transplant in HCC: irAEs Signal Rejection Risk: Gut | June 2026

* Immune checkpoint inhibitors are increasingly used in patients with hepatocellular carcinoma before liver transplantation, but post-transplant allograft rejection remains a major concern. * This multicenter Chinese retrospective study evaluated 209 patients with HCC who received immune checkpoint inhibitors before liver transplantation. * Allograft rejection occurred in 17.2% of patients, highlighting that rejection is a clinically meaningful risk after pretransplant immunotherapy. * Rejection was much more frequent in patients who developed immune-related adverse events before transplant. * Patients with irAEs had a rejection rate of 58.3%, compared with 13.3% in those without irAEs. * Any-grade irAE was the strongest independent predictor of allograft rejection, suggesting that irAEs may reflect a heightened immune activation state. * Other independent risk factors included younger age below 40 years and a short ICI washout interval of less than 30 days. * A predictive model combining irAEs, age, and ICI washout interval performed better than any individual factor alone. * Importantly, rejection was not just a laboratory or histological event; it was associated with worse survival. * One-year survival was significantly lower in patients who developed allograft rejection. * The study suggests that irAEs should be considered a practical pretransplant biomarker of immune risk. * Patients with irAEs may require longer washout intervals, closer perioperative immune monitoring, and individualized immunosuppression strategies. * The findings support a more cautious transplant selection pathway for HCC patients previously exposed to ICIs. * This does not mean that ICIs should be avoided in all transplant candidates, but they should be used with careful planning and multidisciplinary coordination. * Prospective validation is needed before universal cutoffs for washout period or immunosuppression protocols can be standardized. Bottom line: In HCC patients receiving immune checkpoint inhibitors before liver transplantation, the development of immune-related adverse events strongly predicts post-transplant allograft rejection and may help guide washout timing, monitoring intensity, and immunosuppressive strategy.

CRAFITY Score May Guide First-Line Therapy Selection in Unresectable HCC: Liver Cancer | June 2026

* Atezolizumab plus bevacizumab remains the most widely used first-line therapy for unresectable hepatocellular carcinoma, while lenvatinib continues to be an important alternative. * This international multicenter study evaluated whether the CRAFITY score can help identify which patients may benefit more from one treatment over the other. * The CRAFITY score is based on two simple biomarkers: * CRP ≥1 mg/dL * AFP ≥100 ng/mL Patients receive a score of 0, 1, or 2. * The analysis included 994 patients treated across Japan and Taiwan, making it one of the largest real-world comparisons of Atezo+Bev and lenvatinib stratified by CRAFITY score. * In patients with CRAFITY score 0, progression-free survival and overall survival were similar between Atezo+Bev and lenvatinib. * Similar results were observed in patients with CRAFITY score 1, suggesting both treatment options remain reasonable choices in this group. * The key finding emerged in patients with CRAFITY score 2, representing the highest-risk subgroup. * In CRAFITY-2 patients, lenvatinib achieved significantly longer progression-free survival compared with Atezo+Bev. * This suggests that highly inflammatory, biologically aggressive HCC characterized by elevated CRP and AFP may respond less favorably to immunotherapy-based treatment. * Overall survival did not differ significantly between the two treatment groups, but progression control clearly favored lenvatinib in the CRAFITY-2 population. * The study demonstrated a significant interaction between CRAFITY score and treatment efficacy, supporting the concept of biomarker-driven treatment selection. * One major advantage of the CRAFITY score is its simplicity. Both CRP and AFP are routinely available worldwide and do not require expensive molecular testing. * These findings challenge the current “one-size-fits-all” approach in first-line HCC treatment and suggest that not every patient may derive the same benefit from Atezo+Bev. * Before changing routine practice, prospective validation studies are required because this analysis was retrospective. * Nevertheless, the study provides one of the strongest signals to date that a simple clinical biomarker score may help personalize first-line therapy in advanced HCC. Bottom line: In unresectable HCC patients with a CRAFITY score of 2, lenvatinib achieved superior progression-free survival compared with atezolizumab plus bevacizumab, suggesting that CRAFITY may become a practical tool for first-line treatment selection.