Globally, especially in the Asia Pacific region, chronic hepatitis B infection has led to an undesirable escalating morbidity and mortality with acute-on chronic liver failure, end-staged liver cirrhosis, and hepatocellular carcinoma. This has happened despite the past four decades of major scientific advances made in screening methods, vaccination strategies, highly effective low-cost anti-viral therapies, and surveillance strategies for early detection of hepatocellular carcinoma. To address this health threat, APASL has formed a Viral Elimination Taskforce to unite key opinion leaders from its member countries and regions. The ongoing shifts in hepatitis B epidemiology, socioeconomic changes, and advancements in technology are taken into consideration. With the conjoint efforts of all the members of the APASL Viral Elimination Taskforce, these clinical practice guidelines have been formulated aiming to facilitate healthcare professionals, policy-makers, and patients in making practical and cost-effective management decisions for chronic hepatitis B infection. Altogether, it provides recommendations in 13 major areas related to screening, vaccination, treatment, and HCC surveillance. The implementation of these clinical practice guidelines represents major APASL effort toward elimination of the disease burden due to chronic hepatitis B infection in Asia Pacific region.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with chronic hepatitis B (CHB) accounting for more than half of the cases. Regular surveillance, including abdominal ultrasonography with alpha-fetoprotein testing every 6 months, enables early tumor detection and curative treatment; however, current guideline recommendations based mainly on age, sex, and race/ethnicity insufficiently capture individual risk variation, particularly among patients with CHB who do not have cirrhosis. In addition, real-world adherence to HCC surveillance is suboptimal-fewer than 40% of eligible patients receive surveillance at the recommended 6-month intervals. To improve both efficiency and impact, surveillance resources should be reallocated to patients whose estimated risk exceeds the cost-effective surveillance threshold. Recent studies support biomarker-based risk stratification as a more precise approach. For example, in untreated CHB, HBeAg-negative patients meeting inactive disease criteria with HBsAg <100 IU/mL have an annual HCC incidence below the 0.2% cost-effectiveness threshold, suggesting that routine surveillance may be unnecessary. In antiviral-treated CHB, models such as PAGE-B and its derivatives can accurately identify low-risk patients who may safely forgo HCC surveillance. Conversely, for patients at extremely high risk, including those with cirrhosis, intensified strategies-such as abbreviated MRI or combined biomarker algorithms-may enhance early detection. Collectively, these findings support a transition from a categorical, one-size-fits-all approach toward a precision surveillance paradigm that tailors the need for and intensity of HCC surveillance to biomarker-defined risk, thereby optimizing resource use, improving adherence, and maximizing clinical benefit. Nevertheless, further large-scale, prospective studies across diverse populations are needed to validate biomarker thresholds and confirm the long-term safety of exempting very-low-risk patients with CHB from HCC surveillance.

The prognostic value of on-treatment hepatitis B virus (HBV) RNA, hepatitis B core-related antigen (HBcrAg), and quantitative hepatitis B surface antigen (HBsAg) for hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B (CHB) remains uncertain. We evaluate the predictive roles of these viral markers in patients with CHB receiving long-term entecavir therapy. This prospective, multicenter study enrolled patients with CHB-related cirrhosis undergoing long-term entecavir treatment and HCC surveillance in Taiwan. Serum HBV RNA, HBcrAg, and HBsAg levels were measured at enrollment. Multivariable regression identified predictors of HBV RNA positivity and HCC development. Overall, 451 patients were included. After a median of 6.2 years of antiviral therapy, the median levels of HBV RNA, HBcrAg, and HBsAg were 0.9 log10 copies/mL, 3.2 log10 U/mL, and 2.4 log10 IU/mL, respectively. During a median 3.3-year follow-up, 55 developed HCC. 57.2

BACKGROUND/PURPOSE:Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare variant of intrahepatic cholangiocarcinoma (ICC). We aim to analyze the differences in the clinical and radiological features of LELCC and ICC. METHODS:Between January 2003 and December 2019, a total of 21 patients diagnosed with LELCC were retrospectively enrolled, and 84 patients with ICC were selected through propensity score matching by sex, age, and initial cancer stage. The clinical characteristics, pathological findings, and radiological features were analyzed. The differences in overall survival (OS) between LELCC and ICC were evaluated using the Kaplan-Meier method. RESULTS:The serum carbohydrate antigen 19-9 (CA 19-9) level was higher in the ICC group than in the LELCC group (77.9 vs 30.0 U/mL, p = 0.004). Non-rim arterial phase hyperenhancement (47.1% vs 13.7%, p = 0.005) and portovenous washout (35.3% vs 4.1%, p = 0.001) were more frequently observed in the LELCC group than in the ICC group. Intrahepatic duct dilatation was a distinct feature of the ICC group. The 5-year OS rates in the LELCC and ICC groups were 69.3% and 58.2%, respectively (p = 0.047). The 5-year OS of patients with stages I and II LELCC between ICC were not significantly different (90.0% vs 83.4%, p = 0.464). However, the 5-year OS of patients with stages III and IV LELCC was more favorable than that of patients with ICC (29.2% vs 23.0%, p = 0.017). CONCLUSIONS:LELCC had a favorable outcome and several different clinicoradiological features compared with ICC.

Hepatocellular carcinoma (HCC) remains a major health burden in Asia. Advances in antiviral therapies are reshaping the etiological landscape of HCC. This study evaluated temporal shifts in HCC etiology across Asian countries and their clinical implications. This multinational study analyzed 6,261 newly diagnosed HCC patients registered in the APASL Hepatology/Oncology Consortium (A-HOC) from 19 centers across seven Asian countries and regions between 2013 and 2023. Data on demographics, tumor characteristics, etiology, and treatment patterns were collected. Etiologies included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), metabolic dysfunction-associated fatty liver disease (MAFLD), MAFLD plus excess alcoholic intake (MAFLD + eAL), autoimmune liver disease, cryptogenic, and others. Temporal trends and regional variations were assessed. In many countries, HBV remained predominant (43.3

Purpose: This study aimed to investigate the clinical significance of MAP4 in hepatocellular carcinoma (HCC), particularly its association with metastasis-related early recurrence after curative hepatic resection. Patients and Methods: We enrolled 172 patients with hepatitis B virus-associated HCC (HBV-HCC) who underwent curative resection in our cohort. After excluding potential confounders such as vascular invasion and portal vein thrombosis, 101 patients were selected for MAP4 gene expression analysis by qRT-PCR. Kaplan-Meier and Cox regression analyses were conducted to evaluate its association with early recurrence and prognostic factors. Our findings were further validated in an independent cohort. Results: MAP4 expression was upregulated in HCC cell lines and tumor tissues, compared to their corresponding non-tumorous controls. The clinical analysis showed that high MAP4 overexpression in liver tumor tissues was positively correlated with early (p = 0.042) rather than late recurrence (p = 0.221) in our cohort. Moreover, it was linked to shorter recurrence-free survival (p = 0.023) and reduced overall survival (p = 0.015). The expression level of serum alpha-fetoprotein (p = 0.001), tumor size (p = 0.012), tumor number (p = 0.018), satellite tumor (p = 0.001), and MAP4 expression (p = 0.042) were correlated with HCC early recurrence by univariate analysis. Consistent clinical findings were observed in the validation cohort. Conclusion: This study demonstrated that MAP4 overexpression in liver tumor tissue was positively correlated with early recurrence in HBV-HCC patients following curative hepatic resection, providing insights into its clinical significance and potential involvement in underlying molecular mechanisms, particularly in metastasis-related early recurrence.

The global intersection of chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) has revealed an intriguing clinical paradox: hepatic steatosis is frequently associated with lower hepatitis B virus (HBV) viral loads, higher rates of HBsAg seroclearance, and even favorable clinical outcomes. Accumulating data suggest that lipid accumulation transforms hepatocytes into a hostile microenvironment for HBV through at least four pathways, including immune modulation, metabolic reprogramming, endoplasmic reticulum stress, and impaired autophagy. Deciphering these molecular pathways not only explains the unique natural history of CHB patients with concurrent MASLD but also highlights novel therapeutic targets such as selective modulators of cellular stress that could complement existing antivirals or immune enhancers to facilitate functional cure. In this review, the current evidence regarding the cellular mechanisms underlying the suppressive effect of steatosis on HBV is summarized, providing a translational roadmap for exploiting these virus-host metabolic interactions to develop next-generation, novel host-targeting therapies against HBV.

Background:Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are 2 of the leading causes of vision loss worldwide. As population aging and diabetes prevalence increase, timely detection of these conditions has become essential. However, limited professionalism and insufficient training in ophthalmic screening among general medicine physicians may lead to delayed diagnosis and treatment. Artificial intelligence (AI)-assisted diagnostic tools may help to improve the screening of DR and AMD in routine clinical practice. Objective:This study aims to evaluate the clinical effectiveness and cost-effectiveness of AI-assisted fundus imaging for DR and AMD screening in adults with diabetes and older adults at risk of macular degeneration. Methods:This multicenter, 2-arm, parallel-group, open-label, individual-level randomized controlled trial and patient recruitment are performed at the settings of Family Medicine and Geriatric and Gerontology Care over 4 medical centers in Taiwan. Eligibility includes (1) diabetic individuals aged ≥20 years for DR screening, and (2) individuals aged ≥50 years for AMD screening. The study protocol has been approved by the ethics committees of all participating hospitals, and all participants will provide written informed consent. Results:The study was funded in September 2024, began on October 2, 2025, and is expected to be completed in December 2027. After the pilot implementation phase without randomization, participants will be randomized 1:1 into two groups: (1) AI-assisted screening, and (2) usual physician-only screening. The primary outcomes will include the detection rates (defined as participants with confirmed DR or AMD among all screened participants) and the positive predictive values (defined as participants with confirmed DR or AMD among those who tested positive). Cost-effectiveness analyses will be performed using data derived from the trial results. Conclusions:This study will provide robust evidence on the effectiveness of AI-assisted ophthalmic screening in improving patient eye health outcomes through timely screening and accurate early detection. This strategy may be cost-effective.

Contrast-enhanced computed tomography (CT) is recommended in clinical guidelines for managing hepatocellular carcinoma (HCC), yet complete multi-phase acquisition is often unavailable. Here, we present DuoProto, a novel dualbranch, prototype-guided framework that leverages limited multi-phase CT during training to enhance single-phase ER prediction in HCC. DuoProto aligns class-level representations across single- and multi-phase inputs via prototype learning, incorporates clinically informed ranking, and infers with single-phase only. Under conditions of class imbalance and missing phase, DuoProto consistently outperforms existing methods, achieving absolute gains of $3-9 \%$ across all metrics. The proposed framework provides a clinically aligned solution, enabling more informed decision-making. Code is available at https://github.com/idssplab/DuoProto.

BACKGROUND & AIMS:Novel regimens aimed at achieving functional cure of chronic hepatitis B (CHB) in virologically suppressed participants require the withdrawal of nucleos(t)ide analogue (NA). However, data from clinical trials are limited. METHODS:Piranga is a Phase 2 platform trial that evaluated 4 xalnesiran regimens with or without an immunomodulator in virologically suppressed participants with CHB. All participants continued the established NA therapy until NA stopping criteria were met at the end of treatment or during follow-up. Participants who stopped NA were monitored and restarted NA if restarting criteria were met. This post hoc evaluation reports the NA discontinuation events and outcomes. RESULTS:Among 121 participants, 58 (48%) met NA stopping criteria and 40 (33%) discontinued NA. Of these 40, 17 (43%) met NA restarting criteria, 16 (40%) restarted NA, and 24 (60%) remained off NA by the end of the study (EOS). Among participants who remained off NA, 5 achieved and maintained HBsAg loss (HBsAg <0.05 IU/mL) and HBV DNA undetectable (HBV DNA <10 IU/mL); all were in treatment arms with an immunomodulator. Of the 40 participants who discontinued NA, 19 (48%) experienced virological relapse (VR), 3 (8%) of whom further developed clinical relapse (CR). The majority of participants restarted NA following VR. VR and CR events were associated with preserved liver function and resolved without sequelae. CONCLUSIONS:NA discontinuation after xalnesiran-based therapy was safely managed with the application of prespecified NA stopping and restarting criteria and close monitoring. Five participants achieved and maintained HBsAg loss and undetectable HBV DNA while off NA until EOS. CLINICAL TRIAL NUMBER:NCT04225715.