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Background and Aim: We assessed the effect of hepatitis B surface antigen (HBsAg) seroclearance (HBsAg‐loss) on liver fibrosis regression in patients with chronic hepatitis B (CHB) infection. Method: CHB patients with recent documented HBsAg‐loss were age‐ and gender‐matched with treatment‐naïve HBeAg‐negative CHB infection. Paired assessment with transient elastography and enhanced liver fibrosis (ELF) measurements were performed and repeated at 3 years. Fibrosis regression was arbitrarily defined as decrease in ≥ 1 fibrosis stage by ELF, or combining with reduction > 30% in liver stiffness. Results: A total of 142 HBsAg‐loss and 142 CHB subjects were recruited (median age 58.1 years, 51.4% male). A total of 1.8% (1.4% HBsAg‐loss vs 2.1% CHB) achieved combined endpoint of fibrosis regression at 3 years. When ELF‐only definition of fibrosis regression was used, 14.5% HBsAg‐loss and 16.9% CHB subjects achieved this endpoint, which was significantly associated with baseline ELF (hazard ratio (HR) 1.827, 95% confidence interval (CI) 1.085–3.075) and time since HBsAg‐loss (HR 2.688, 95% CI 1.257–5.748). While increasing time since HBsAg‐loss increased the proportion of ELF‐defined fibrosis regression, increasing age was also associated with significant fibrosis. Age of achieving HBsAg‐loss (ageSC) was independently associated with high baseline ELF values. Up to 52.3% and 63.8% subjects with ageSC > 50 had advanced fibrosis/cirrhosis at baseline and 3 years, respectively, compared with 5.9% and 20.6% in subjects with ageSC < 50. Conclusion: Fibrosis regression occurred in a minority of subjects achieving HBsAg‐loss, which was not significantly different compared with subjects with persistent overt CHB. Subjects after achieving HBsAg‐loss, especially among those with ageSC > 50, should receive ongoing surveillance for liver‐related complications. [ABSTRACT FROM AUTHOR]

Cigarette smoking is associated with worse clinical outcomes in patients with chronic hepatitis B (CHB) infection, but the effects on hepatitis B surface antigen (HBsAg) seroclearance are unclear. This study aimed to investigate the effect of active smoking on HBsAg seroclearance (SC) and its impact on peripheral blood lymphocytes in patients with CHB infection. Longitudinal follow‐up data was retrieved in 7833 antiviral‐treated CHB subjects identified from a centralised electronic patient record database (Part 1). Phenotypic analysis of peripheral blood mononuclear cells (PBMCs) from 27 CHB‐infected patients (6 active smokers; 13 with SC) was performed by flow cytometry to assess programmed death‐1 (PD‐1) expression and proportion of regulatory T cells (CD4+CD25+CD127lo). Effector function of HBV‐specific T cells was examined by comparing granzyme B (GZMB) and transforming growth factor beta (TGFβ) production in undepleted PBMCs and Treg‐depleted PBMCs after 7 days in vitro stimulation with HBV envelope protein overlapping peptides (Part 2). Over a median follow‐up of 5 years, smoking was associated with lower probability of SC (aHR 0.70, 95% CI 0.57–0.87). PD‐1 expression was increased in CD4+ T cells, CD8+ T cells and CD20+ B cells among smokers compared to non‐smokers and positively correlated with pack years (all p < 0.05). Treg depletion led to partial functional recovery of HBV‐specific T cells, with significantly bigger magnitude in smokers (p = 0.0451, mean difference = 4.68%) than non‐smokers (p = 0.012, mean difference = 4.2%). Cigarette smoking is associated with lower chance of HBsAg seroclearance, higher PD‐1 expression on lymphocytes, and impairment of effector functions of HBV‐specific T cells in CHB. [ABSTRACT FROM AUTHOR]

Summary: Background: Optimal glycaemic control has well‐established health benefits in patients with diabetes mellitus (DM). It is uncertain whether optimal glycaemic control can benefit liver‐related outcomes. Aims: To examine the association of optimal glycaemic control with hepatocellular carcinoma (HCC) and liver‐related mortality. Methods: In a population‐based cohort, we identified patients with newly diagnosed DM between 2001 and 2016 in Hong Kong. Optimal glycaemic control was defined as mean haemoglobin A1c (HbA1c) <7% during the 3‐year lead‐in period after DM diagnosis. By applying propensity score matching to balance covariates, we analysed glycaemic control via competing risk models with outcomes of interest being HCC and liver‐related mortality. Results: We identified 146,430 patients (52.2% males, mean age 61.4 ± 11.8 years). During a median follow‐up duration of 7.0 years, 1099 (0.8%) and 978 (0.7%) patients developed HCC and liver‐related deaths. Optimal glycaemic control, when compared to suboptimal glycaemic control, was associated with reduced risk of HCC (subdistribution hazard ratio [SHR] 0.70, 95% CI 0.61–0.79). The risk of HCC increased with incremental HbA1c increases beyond >7% (SHR 1.29–1.71). Significant associations with HCC were also found irrespective of age (SHR 0.54–0.80), sex (SHR 0.68–0.69), BMI <25 or ≥25 kg/m2 (SHR 0.63–0.75), smoking (SHR 0.61–0.72), hepatic steatosis (SHR 0.67–0.68) and aspirin/statin/metformin use (SHR 0.67–0.75). A lower risk of liver‐related mortality in relation to optimal glycaemic control was also observed (SHR 0.70, 95% CI 0.61–0.80). Conclusions: Glycaemic control is an independent risk factor for HCC and liver‐related mortality, and should be incorporated into oncoprotective strategies in the general DM population. [ABSTRACT FROM AUTHOR]

Background and Aim: Spontaneous seroclearance of hepatitis B surface antigen (HBsAg) is a rare event that occurs in patients that are chronically infected with the hepatitis B virus. As the functional cure and ultimate treatment endpoint of chronic hepatitis B (CHB), HBsAg seroclearance is an important milestone in the natural history of CHB and serves great clinical value. This study aims to identify host and viral factors associated with HBsAg seroclearance. Methods: This is a retrospective study carried out in the Queen Mary Hospital, Hong Kong. By analyzing the plasma retrieved from the serum archive (collected during 2011–2021) of 100 CHB patients attending the hospital's liver clinic, the longitudinal cytokine profiles between the HBsAg‐losers and the control groups were compared. Results: Data revealed that plasma levels of IP‐10 were significantly lower at 3–5 years prior to HBsAg seroclearance compared with patients who remained HBsAg positive (P < 0.05). Receiver operating characteristic curve analysis reveals that plasma IP‐10 levels at multiple time points before HBsAg seroclearance return area under receivor‐operating characteristic curve (AUC) greater than 0.7. Plasma IP‐10 levels at 42.39 pg/mL produced an AUC = 0.723 with 74.0% sensitivity and 75.5% specificity to predict subsequent HBsAg seroclearance in the next 3–5 years. Low plasma IP‐10 identified 91.4% patients with quantitative HBsAg < 100 IU/mL who would subsequently develop HBsAg seroclearance, compared with 37% with higher plasma IP‐10 levels (P < 0.001). Conclusions: Low plasma levels of IP‐10 are associated with subsequent HBsAg seroclearance, suggesting potential clinical utilities of measurement of IP‐10 in predicting HBsAg seroclearance, especially among patients with low HBsAg. [ABSTRACT FROM AUTHOR]

The article discusses a case study of a 58-year-old man with obstructive jaundice caused by hepatic artery aneurysms compressing the common bile duct. The patient underwent endoscopic and vascular interventions to manage the biliary obstruction and aneurysmal bleeding successfully. The article highlights the importance of multidisciplinary care and careful treatment selection in managing hepatic artery aneurysms causing biliary obstruction. [Extracted from the article]

Nucleos(t)ide analogues (NAs) are effective in suppressing the replication of the hepatitis B virus. However, NAs cannot effectively induce hepatitis B surface antigen (HBsAg) seroclearance, which represents the optimal treatment endpoint in chronic hepatitis B (CHB). Hence, most CHB patients are advised for indefinite NA therapy, but recent data has supported the concept of finite NA therapy before HBsAg seroclearance. This article covered the latest evidence on stopping NAs in CHB, with a focused analysis on international guidelines. Articles were retrieved by a literature search on PubMed with the keywords 'chronic hepatitis B,' 'antiviral therapy,' 'nucleos(t)ide analogue,' 'cessation,' 'stopping', and 'finite.' Studies up till 1 December 2022 were included. Finite NA therapy in CHB has the potential in enhancing HBsAg seroclearance, however it also carries rare but potentially severe risks. NA cessation before HBsAg seroclearance is only suitable for a highly selected group of patients, whereas the majority of CHB patients should be treated indefinitely or until HBsAg seroclearance. Current guidelines have provided recommendations on stopping NAs, but further research is required to optimize the monitoring and retreatment protocol after stopping NAs. [ABSTRACT FROM AUTHOR]

Background and Aim: Liver fibrosis and steatosis are important factors affecting chronic hepatitis B (CHB) disease outcome. Multiparametric magnetic resonance (MR) imaging of the liver measures fibroinflammation, fat, and iron through iron‐corrected T1 relaxation time (cT1), proton density fat fraction (PDFF), and T2*‐weighted imaging, respectively. We assessed the utility of MR metrics for prognostication in CHB. Methods: Chronic hepatitis B patients receiving nucleos(t)ide analogs with advanced fibrosis documented by vibration‐controlled transient elastography were recruited. Paired multiparametric MR liver and transient elastography were performed at baseline and after at least 2 years. Adverse outcomes including death, hepatocellular carcinoma (HCC), and liver decompensation were monitored. Results: One hundred and ninety‐two patients (mean age 60.3 ± 8.5 years; 76.0% male) were recruited. Eight patients (4.2%) developed HCC after 11.6 (8.8–22.8) months, and increased baseline liver iron independently predicted HCC (hazard ratio 2.329 [1.030–5.266]; P = 0.042). Liver MR metrics were not predictive of death or hepatic decompensation. Among 150 patients with follow‐up liver MR at 30.3 (25.2–35.6) months, longitudinal liver PDFF increase was associated with liver cT1 increase (odds ratio 1.571 [1.217–2.029]; P = 0.001). Ninety patients received simultaneous multiparametric MR pancreas during the follow‐up MR. Pancreatic PDFF correlated with liver PDFF (r = 0.501, P < 0.001), while pancreatic T1 had no correlation with liver cT1 (r = −0.092, P = 0.479). Pancreatic T1 and PDFF were not associated with adverse outcomes. Conclusion: Among CHB patients with advanced disease, liver iron level on MR predicts HCC. Multiparametric MR can also simultaneously assess the pancreas and the liver. Multiparametric MR should be further studied as a one‐stop option for monitoring and prognosticating CHB. [ABSTRACT FROM AUTHOR]

In this prospective study involving 337 chronic hepatitis B patients who achieved spontaneous hepatitis B surface antigen (HBsAg) seroclearance (SC), serum enhanced liver fibrosis (ELF) before SC was associated with hepatocellular carcinoma (HCC) (hazard ratio 2.588), and ELF <10.8 was associated with >97% reduction in risk of HCC development in patients with age SC ≥ 50 (n = 190). [ABSTRACT FROM AUTHOR]

Summary: The degree of liver fibrosis in chronic hepatitis B (CHB) infection influences outcome and management. Existing data describing the long‐term dynamic changes of liver fibrosis are limited. This study aimed to evaluate the evolution of liver fibrosis in CHB across a 10‐year period. CHB patients with liver stiffness measurement (LSM) by transient elastography 10 years ago were recruited for follow‐up LSM. Fibrosis stages were classified according to EASL‐ALEH guidelines. Fibrosis progression/regression was arbitrarily defined as ≥1 fibrosis stage change from baseline. A total of 459 hepatitis B e antigen (HBeAg)‐negative patients (224 untreated, 235 treated with nucleos(t)ide analogues [NAs]) were recruited. The mean age at baseline LSM was 41.7 ± 9.0 years (56.2% male). Over 10 years, the proportion of patients with advanced fibrosis/cirrhosis significantly reduced from 16.3% to 5.7% (P < 0.001). Fibrosis progression and regression were observed in 8.7% and 37.5%, respectively. No treatment with NAs (OR 2.259, 95% confidence interval [CI]: 1.032‐4.945), metabolic syndrome (OR 4.379, 95% CI: 1.128‐16.999) and hepatic steatosis (OR 7.799, 95% CI: 2.271‐26.776) was associated with fibrosis progression. Liver stiffness decline demonstrated positive correlation with the time after HBsAg seroclearance (r = −0.50, P < 0.001). Median liver stiffness was higher both at baseline (14.0 vs 6 kPa, P < 0.001) and 10 years (9.1 vs 4.9 kPa, P < 0.001) in patients with cirrhosis‐related complications/hepatocellular carcinoma compared with those without. In conclusion, CHB‐related liver fibrosis changed dynamically across 10 years. Metabolic syndrome and hepatic steatosis were associated with fibrosis progression, while antiviral therapy was associated with fibrosis regression. Patients with HBsAg seroclearance demonstrated time‐dependent decline in liver stiffness. [ABSTRACT FROM AUTHOR]

Background & Aims: It is unknown how concomitant hepatic steatosis affects disease progression in chronic hepatitis B (CHB). Adipokines such as fibroblast growth factor 21 (FGF21) and adipocyte fatty acid‐binding protein (AFABP) have been associated with non‐alcoholic fatty liver disease. We determined the significance of these metabolic markers in CHB‐related liver injury. Methods: We recruited CHB patients on antiviral treatment for transient elastography assessment to determine liver stiffness (advanced fibrosis/cirrhosis, F3/F4, defined by EASL‐ALEH criteria) and controlled attenuation parameter (hepatic steatosis, defined as ≥ 248 dB/m). Plasma FGF‐21, AFABP and adiponectin levels were measured. Results: A total of 415 patients [mean age 59.6 years, 71.6% male, median treatment duration 6.2 years] were recruited. Patients with F3/F4 (N = 151) had lower FGF‐21 (11.7 vs 13.6 pg/mL, P = 0.055), higher AFABP (126.8 vs 84.1 pg/mL, P < 0.001) and HOMA‐IR (7.1 vs 5.1, P = 0.004) levels compared to those without F3/F4 (N = 264). Multivariate analysis showed that FGF‐21 level was associated with hepatic steatosis (OR 1.005, 95% CI 1.001‐1.009) and F3/F4 (OR 0.993, 95% CI 0.989‐0.998), while AFABP level (OR 1.001, 95% CI 1‐1.002), body mass index (BMI) (OR 1.107, 95% CI 1.037‐1.182) and presence of diabetes mellitus (OR 2.059, 95% CI 1.206‐3.516) were associated with F3/F4. With the combined presence of BMI ≥ 25 kg/m2, diabetes and AFABP > 105.9 pg/mL, the odds ratio for F3/F4 was 3.712 (95% CI 1.364‐10.105, P = 0.010). Conclusions: Low FGF‐21 and high AFABP levels were associated with advanced fibrosis/cirrhosis in CHB patients on antiviral treatment. Plasma AFABP, together with other metabolic risk factors, may aid identification of patients lacking fibrosis improvement during antiviral treatment. [ABSTRACT FROM AUTHOR]

Background: Plasma pregenomic hepatitis B virus RNA (pgRNA) is a novel biomarker in chronic hepatitis B infection (CHB). We aimed to describe the longitudinal profile of pgRNA and factors influencing its levels in CHB patients on nucleoside analogue (NUC)., Methods: Serial plasma samples from 1354 CHB patients started on first-line NUC were evaluated. Time of NUC initiation was taken as baseline (year 0), followed by 1-year, 3-year and 5-year of NUC therapy. pgRNA was measured by Research Use Only RealTime HBV RNA v2.0 (0.2 mL) (Abbott Diagnostics) with lower limit of detection of 0.8 log U/mL (~20 copies/mL)., Results: Among 1354 subjects (median age at baseline 49.8 (interquartile range [IQR] 40.2-57.3) years, 65.2% male, 16.1% HBeAg-positive, 28.6% cirrhotic), baseline median HBV RNA was 3.68 (IQR 2.42-5.19) log U/mL. Upon NUC therapy, median pgRNA levels were 2.45 (IQR 1.82-3.62), 2.23 (IQR 1.67-3.05) and 2.14 (IQR 1.48-2.86) log U/mL at 1, 3 and 5 years respectively, with the corresponding log U/mL reductions of 0.82, 1.20 and 1.54. Undetectable/ unquantifiable pgRNA was achieved in 13.5%, 15.9% and 20.1% of patients at 1, 3 and 5 years respectively. Older age, male sex, HBeAg-negativity and high PAGE-B score were associated with lower pgRNA., Conclusion: Plasma pgRNA declines are modest under NUC therapy, with only 16.3% achieving RNA undetectability after 5 years of first-line NUC indicating cccDNA silencing has not been achieved in the majority of patients. Clinical characteristics should be taken into consideration when interpreting the plasma pgRNA level.

Background and Aims: HCC recurrence frequently occurs after curative surgery. Histological microvascular invasion (MVI) predicts recurrence but cannot provide preoperative prognostication, whereas clinical prediction scores have variable performances., Approach and Results: Recurr-NET, a multimodal multiphasic residual-network random survival forest deep-learning model incorporating preoperative CT and clinical parameters, was developed to predict HCC recurrence. Preoperative triphasic CT scans were retrieved from patients with resected histology-confirmed HCC from 4 centers in Hong Kong (internal cohort). The internal cohort was randomly divided in an 8:2 ratio into training and internal validation. External testing was performed in an independent cohort from Taiwan.Among 1231 patients (age 62.4y, 83.1% male, 86.8% viral hepatitis, and median follow-up 65.1mo), cumulative HCC recurrence rates at years 2 and 5 were 41.8% and 56.4%, respectively. Recurr-NET achieved excellent accuracy in predicting recurrence from years 1 to 5 (internal cohort AUROC 0.770-0.857; external AUROC 0.758-0.798), significantly outperforming MVI (internal AUROC 0.518-0.590; external AUROC 0.557-0.615) and multiple clinical risk scores (ERASL-PRE, ERASL-POST, DFT, and Shim scores) (internal AUROC 0.523-0.587, external AUROC: 0.524-0.620), respectively (all p < 0.001). Recurr-NET was superior to MVI in stratifying recurrence risks at year 2 (internal: 72.5% vs. 50.0% in MVI; external: 65.3% vs. 46.6% in MVI) and year 5 (internal: 86.4% vs. 62.5% in MVI; external: 81.4% vs. 63.8% in MVI) (all p < 0.001). Recurr-NET was also superior to MVI in stratifying liver-related and all-cause mortality (all p < 0.001). The performance of Recurr-NET remained robust in subgroup analyses., Conclusions: Recurr-NET accurately predicted HCC recurrence, outperforming MVI and clinical prediction scores, highlighting its potential in preoperative prognostication., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is a favorable treatment endpoint in chronic hepatitis B (CHB). Nonetheless, functional cure is rarely attained with the current treatment modalities of nucleos(t)ide analogues (NUCs) and pegylated interferon alpha (Peg-IFNα). Multiple novel virus-targeting agents and immunomodulators are under development for HBV with functional cure as the treatment goal. Among virus-targeting agents, antisense oligonucleotides (ASOs) and small-interfering RNA (siRNAs) are the most advanced in the developmental pipeline, and can induce potent and sustainable HBsAg suppression. The other virus-targeting agents have varying effects on HBsAg and HBV DNA, depending on the drug mechanism. In contrast, immunomodulators have modest effects on HBsAg and have limited roles in monotherapy. Multiple combination regimens incorporating RNA interference agents with immunomodulators have been studied through many ongoing clinical trials. These combination strategies demonstrate synergistic effects in inducing functional cure, and will likely be the future direction of development. Despite the promising results, research is warranted to optimize treatment protocols and to establish criteria for NUC withdrawal after novel therapies. Functional cure is now an attainable target in CHB, and the emerging novel therapeutics will revolutionize CHB management.

Objective: Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain., Design: Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)<7%. Outcomes of interest included colorectal cancer (CRC) and colonic adenoma development. We used propensity score (PS) matching with competing risk models to estimate subdistribution HRs (SHRs). We further analysed the combined effect of baseline and postbaseline glycaemic control based on time-weighted mean HbA1c during follow-up., Results: Of 88 468 PS-matched patients with DM (mean (SD) age: 61.5 (±11.7) years; male: 47 127 (53.3%)), 1229 (1.4%) patients developed CRC during a median follow-up of 7.2 (IQR: 5.5-9.4) years. Optimal glycaemic control was associated with lower CRC risk (SHR 0.72; 95% CI 0.65 to 0.81). The beneficial effect was limited to left-sided colon (SHR 0.71; 95% CI 0.59 to 0.85) and rectum (SHR 0.71; 95% CI 0.57 to 0.89), but not right-sided colon (SHR 0.86; 95% CI 0.67 to 1.10). Setting suboptimal glycaemic control at baseline/postbaseline as a reference, a decreased CRC risk was found in optimal control at postbaseline (SHR 0.79), baseline (SHR 0.71) and both time periods (SHR 0.61). Similar associations were demonstrated using glycaemic control as a time-varying covariate (HR 0.75). A stepwise greater risk of CRC was found (P trend <0.001) with increasing HbA1c (SHRs 1.34, 1.30, 1.44, 1.58 for HbA1c 7.0% to <7.5%, 7.5% to <8.0%, 8.0% to <8.5% and ≥8.5%, respectively). Optimal glycaemic control was associated with a lower risk of any, non-advanced and advanced colonic adenoma (SHRs 0.73-0.87)., Conclusion: Glycaemic control in patients with DM was independently associated with the risk of colonic adenoma and CRC development with a biological gradient., Competing Interests: Competing interests: C-LC received research funding from AstraZeneca, Merck KGaA and Taiho. L-YM is an advisory board member of Gilead Sciences. WKL received speaker’s fees from AbbVie, Ferring Pharmaceuticals and Janssen. MFY received research funding from Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex, Roche and is an advisory board member and/or received research funding from AbbVie, Aligos therarpeutics, Arbutus Biopharma, Bristol Myer Squibb, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals, Roche. W-KS received speaker’s fees from AstraZeneca, is an advisory board member and received speaker’s fees of Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. The other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Both artificial intelligence (AI) and distal attachment devices have been shown to improve adenoma detection rate and reduce miss rate during colonoscopy. We studied the combined effect of Endocuff and AI on enhancing detection rates of various colonic lesions., Methods: This was a 3-arm prospective randomized colonoscopy study involving patients aged 40 years or older. Participants were randomly assigned in a 1:1:1 ratio to undergo Endocuff with AI, AI alone, or standard high-definition (HD) colonoscopy. The primary outcome was adenoma detection rate (ADR) between the Endocuff-AI and AI groups while secondary outcomes included detection rates of polyp (PDR), sessile serrated lesion (sessile detection rate [SDR]), and advanced adenoma (advanced adenoma detection rate) between the 2 groups., Results: A total of 682 patients were included (mean age 65.4 years, 52.3% male), with 53.7% undergoing diagnostic colonoscopy. The ADR for the Endocuff-AI, AI, and HD groups was 58.7%, 53.8%, and 46.3%, respectively, while the corresponding PDR was 77.0%, 74.0%, and 61.2%. A significant increase in ADR, PDR, and SDR was observed between the Endocuff-AI and AI groups (ADR difference: 4.9%, 95% CI: 1.4%-8.2%, P = 0.03; PDR difference: 3.0%, 95% CI: 0.4%-5.8%, P = 0.04; SDR difference: 6.4%, 95% CI: 3.4%-9.7%, P < 0.01). Both Endocuff-AI and AI groups had a higher ADR, PDR, SDR, and advanced adenoma detection rate than the HD group (all P < 0.01)., Discussion: Endocuff in combination with AI further improves various colonic lesion detection rates when compared with AI alone., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Advanced hepatocellular carcinoma (HCC) is traditionally associated with limited treatment options and a poor prognosis. Sorafenib, a multiple tyrosine kinase inhibitor, was introduced in 2007 as a first-in-class systemic agent for advanced HCC. After sorafenib, a range of targeted therapies and immunotherapies have demonstrated survival benefits in the past 5 years, revolutionizing the treatment landscape of advanced HCC. More recently, evidence of novel combinations of systemic agents with distinct mechanisms has emerged. In particular, combination trials on atezolizumab plus bevacizumab and durvalumab plus tremelimumab have shown encouraging efficacy. Hence, international societies have revamped their guidelines to incorporate new recommendations for these novel systemic agents. Aside from treatment in advanced HCC, the indications for systemic therapy are expanding. For example, the combination of systemic therapeutics with locoregional therapy (trans-arterial chemoembolization or stereotactic body radiation therapy) has demonstrated promising early results in downstaging HCC. Recent trials have also explored the role of systemic therapy as neoadjuvant treatment for borderline-resectable HCC or as adjuvant treatment to reduce recurrence risk after curative resection. Despite encouraging results from clinical trials, the real-world efficacy of systemic agents in specific patient subgroups (such as patients with advanced cirrhosis, high bleeding risk, renal impairment, or cardiometabolic diseases) remains uncertain. The effect of liver disease etiology on systemic treatment efficacy warrants further research. With an increased understanding of the pathophysiological pathways and accumulation of clinical data, personalized treatment decisions will be possible, and the field of systemic treatment for HCC will continue to evolve., Competing Interests: Competing interests: MF Yuen is an advisory board member and/or received research funding from AbbVie, Arbutus Biopharma, Assembly Biosciences, Bristol Myer Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals; and received research funding from Arrowhead Pharmaceuticals, Fujirebio Incorporation and Sysmex Corporation. WK Seto received speaker’s fees from AstraZeneca, is an advisory board member and received speaker’s fees of Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. The remaining authors have no conflict of interests., (Copyright: © 2024 Wu TKH et al.)

Competing Interests: Wai-Kay Seto is on the speakers’ bureau for AstraZeneca. He advises and is on the speakers’ bureau for Abbott. He received grants from Alxion Pharmaceuticals, Boehringer Ingelheim, Pfizer, and Ribo Life Science. He advises, is on the speakers’ bureau for, and received grants from Gilead Sciences. Man-Fung Yuen consults for, advises, is on the speakers’ bureau for, and received grants from Fujirebio Incorporation, Gilead Sciences, Roche, and Sysmex Corporation. He consults for, advises, and received grants from AbbVie, Assembly Biosciences, Arrowhead Pharmaceuticals, and Immunocore. He consults for and advises Abbott Diagnotics, Aligos Therapeutics, AiCuris, Antios Therapeutics, Arbutus Biopharma, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Janssen, Precision Biosciences, Tune Therapeutics, Vir Biotechnology, and Visirna Therapeutics. He advises and/or received grants from Bristol Myer Squibb, Merck Sharp and Dohme, and Springbank Pharmaceuticals. The remaining authors have no conflicts to report.