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.
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.
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...
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...
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...
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...
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,...
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...
We are pioneers in clinical intelligence, dedicated to helping gastroenterologists harness the power of artificial intelligence to drive precision, efficiency, and patient growth.