The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) continues to increase worldwide, partly because of rising rates of obesity and metabolic syndrome. However, a substantial proportion of patients with MAFLD are neither overweight nor obese and are classified as having lean MAFLD. The increasingly recognized phenotype of lean MAFLD challenges the traditional paradigm linking obesity to metabolic risk. Despite a normal body mass index (BMI), lean MAFLD is associated with substantial metabolic dysfunction and a range of extrahepatic manifestations. Evidence from systematic reviews and meta-analyses including more than 10 million individuals indicates that patients with lean MAFLD have metabolic profiles comparable to those of overweight or obese patients with MAFLD, including insulin resistance, dyslipidemia, and hypertension. Importantly, although cardiovascular and cancer-related mortality appear broadly similar across BMI categories, liver-related mortality is consistently higher in lean individuals, suggesting distinct hepatocentric vulnerability. Variation in all-cause mortality estimates is influenced by disease severity, study design, and ethnicity. Important mechanistic factors include genetic susceptibility, sarcopenia, and visceral adiposity. These findings support comprehensive metabolic and hepatic assessment in lean MAFLD beyond BMI-based risk classification. This review examines lean MAFLD as a hepatocentric phenotype with systemic effects beyond BMI.

Hepatocellular carcinoma (HCC) exhibits profound metabolic reprogramming, with enhanced aerobic glycolysis and excess lactate production as defining features. Lactate, once regarded simply as a metabolic byproduct, is now recognized as a powerful epigenetic driver through lysine lactylation, while tumor cells co-opt autophagy to endure metabolic stress. Although traditionally investigated as separate hallmarks of cancer, growing evidence points to their functional intersection. Here, we propose the concept of a coordinated “lactylation-autophagy axis” and clarify its role in remodeling the tumor immune microenvironment. Within this integrated metabolic-epigenetic-proteostatic network, lactate-induced histone lactylation, such as H3K18la, exerts transcriptional control over tumor-associated macrophages, shifting them toward an immunosuppressive M2-like state. Excess extracellular lactate and robust autophagic adaptation cooperate to impair the effector functions of CD8+ T cells and natural killer cells, while providing regulatory T cells with metabolic advantages. We further explore the bidirectional crosstalk within this axis: lactate modulates autophagic flux, potentially through mTOR signaling and non-histone lactylation of autophagy-related proteins (e.g., VPS34, TFEB), whereas autophagy in turn regulates intracellular metabolite pools and lactylation substrates. Notably, several nodes, particularly non-histone lactylation of VPS34, TFEB, and mTOR (K921), have been demonstrated mainly in non-HCC systems; we therefore grade each mechanism as confirmed in HCC, extrapolated from other systems, or hypothetical. This proposed self-reinforcing axis may sustain tumor plasticity, contribute to immune evasion and immunotherapy resistance, and we discuss rational combinatorial strategies—combined targeting of lactate metabolism, lactylation machinery, and autophagic pathways—to sensitize advanced HCC to immune checkpoint blockade.

Metabolic dysfunction–associated steatotic liver disease (MASLD) and alcohol–associated liver disease (ALD) are leading causes of chronic liver injury with overlapping clinical and histological presentations. This study evaluated a composite histologic pattern, termed the Alcohol Liver Pathology Signature (ALPS), for potential use in the differential diagnosis of ALD and MASLD and to explore potential clinical and demographic correlates.

In this retrospective diagnostic-accuracy study, we reviewed 292 liver biopsies performed between 2021 and 2023. ALPS comprised five histologic features: ductular reaction, bile stasis, neutrophilic satellitosis, portal inflammation, and advanced fibrosis (stage 3–4). Cases were categorized as absent (0–1 features), partial (2–3 features), or full (4–5 features). ALPS performance was then further evaluated in an independent temporal validation cohort of de-identified, mixed, and blindly reviewed liver biopsies collected between 2024 and 2025.

MASLD was the most common diagnosis (25.3%), whereas ALD accounted for 4.8%. Full ALPS was present in 92.8% of clinically diagnosed ALD cases. In MASLD, individual ALPS features were common, but only 20.3% showed full ALPS, corresponding to 79.7% specificity for distinguishing clinically diagnosed ALD from MASLD. The independent temporal validation cohort showed findings consistent with those of the original cohort. Finally, within MASLD, full ALPS was more frequent in African American than non-African American patients (29.2% vs. 3.8%).

ALPS may serve as a histologic prompt for further assessment of potential alcohol exposure but should not be considered etiologically specific. Prospective validation incorporating objective measures of alcohol exposure is warranted.

Hepatic stellate cell (HSC) activation has traditionally been described as a binary transition from vitamin A-rich quiescent cells to alpha-smooth muscle actin-positive, collagen-producing myofibroblast-like cells. Advances in single-cell RNA sequencing, single-nucleus RNA sequencing, spatial transcriptomics, and chromatin-accessibility profiling now reveal a more complex and dynamic landscape. During chronic liver injury, HSCs can adopt five overlapping activation-associated states characterized by injury sensing, inflammatory signaling, proliferation, extracellular matrix production and contractility, together with a senescent state that represents a possible fate of activated HSCs. These states differ in their molecular markers, spatial distribution, regulatory pathways, and interactions with hepatocytes, liver sinusoidal endothelial cells, macrophages, natural killer cells, and cholangiocytes. Importantly, they are not fixed lineages and may coexist or interconvert during fibrosis progression and regression. This review revisits the classical quiescent-activated framework and proposes a state-based approach for interpreting HSC heterogeneity. We summarize the defining features and translational relevance of six major HSC functional states, discuss their multicellular niches, and highlight the opportunities and limitations of function-selective therapeutic targeting. A reproducible classification that integrates molecular identity, spatial context, and causal function may help refine antifibrotic treatment strategies.

Rising resistance in Helicobacter pylori to metronidazole, clarithromycin, and fluoroquinolones has significantly reduced eradication efficacy. This narrative review explores evidence-based strategies that minimize the impact of antibiotic resistance. Current practical approaches include empirical therapy (EMT), in which regimens are selected without individual susceptibility testing based on local or regional resistance patterns, previous antibiotic exposure, guideline recommendations, and expected effectiveness, and susceptibility-guided therapy (SGT), which avoids antibiotics to which the infecting strain is resistant. EMT does not simply exclude every antibiotic with a high resistance prevalence because regimen-level efficacy may remain high despite resistance to one component. When susceptibility testing is unavailable, optimized 14-day bismuth quadruple therapy is a guideline-preferred empirical regimen and can remain effective despite metronidazole resistance with adequate dosing and treatment duration. Rifabutin-based triple therapy provides an additional empirical or rescue option for selected patients without penicillin allergy. SGT is not universally superior to well-selected EMT, but may improve eradication rates in selected populations, particularly in settings with high clarithromycin resistance or where rapid molecular testing is available. However, susceptibility testing may be time-consuming, costly, and limited to only a few antibiotics. Emerging approaches include potassium-competitive acid blockers (PCABs), antimicrobial stewardship, probiotics, N-acetylcysteine, nanomaterial-based drug delivery, and vaccination. Among these, vonoprazan-based regimens are the most clinically mature. Vonoprazan-amoxicillin dual therapy can reduce exposure to resistance-prone antibiotics, although its use should reflect regional effectiveness, availability, and cost. Other non-antibiotic approaches remain investigational. In conclusion, management should move from undifferentiated empirical regimen selection toward risk-stratified precision treatment. Locally validated EMT remains appropriate when susceptibility testing is unavailable, whereas SGT should be prioritized after treatment failure or in patients at high risk of resistance. Rifabutin-based and vonoprazan-amoxicillin therapies provide additional options according to treatment history, penicillin allergy, regional evidence, and accessibility.

Artificial intelligence (AI)-based computer-aided detection (CADe) has been associated with improved adenoma detection during colonoscopy. However, prior meta-analyses synthesized earlier trials, and whether the benefit remains consistent in recent contemporary trials is uncertain. This meta-analysis aimed to estimate the effects of current-generation AI-assisted colonoscopy on adenoma detection rate (ADR) as the primary outcome and polyp detection rate (PDR) as the secondary outcome in randomized and quasi-randomized trials published from August 1, 2024, to August 18, 2026, without re-pooling trials included in earlier comprehensive meta-analyses.

MEDLINE/PubMed, Embase, CENTRAL, Scopus, and Google Scholar were searched for peer-reviewed parallel-group randomized and quasi-randomized trials enrolling adults undergoing screening, surveillance, or diagnostic colonoscopy and comparing real-time AI-based CADe-assisted with conventional high-definition white-light colonoscopy. Tandem designs were excluded. The primary and secondary outcomes were ADR and PDR, respectively. Random-effects risk ratios with 95% confidence intervals (CIs) were calculated; heterogeneity and leave-one-out sensitivity were assessed.

Seventeen trials comprising 15,242 patients were included for ADR; 12 trials comprising 8,665 patients reported extractable PDR data. The pooled risk ratio was 1.14 (95% CI 1.09–1.20; I² = 53.8%) for ADR and 1.13 (95% CI 1.07–1.20; I² = 63.4%) for PDR.

This meta-analysis supports an average improvement in adenoma and polyp detection with AI-assisted colonoscopy; however, moderate-to-substantial heterogeneity and variability across settings and platforms warrant cautious interpretation rather than an unqualified recommendation for routine adoption.

Viral hepatitis caused by A to E imposes a substantial global burden of liver disease. Despite US control strategies, long-term national data covering serologic markers of all five hepatitis viruses remain limited. In this study, we analyzed epidemiologic trends from 2011 to 2023 and aimed to identify prevention gaps.

We analyzed National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2023 using weighted logistic regression, with stratification by age, sex, and race/ethnicity.

Current hepatitis B virus (HBV) infection remained stable at 0.3%, while HBV susceptibility was 71.3%. Among individuals born in 1991 or later, HBV vaccination coverage declined from 90.0% to 83.6% during 2011–2020 (P for trend = 0.012); 57.0% of participants reporting vaccination were serologically susceptible. Anti-HDV positivity among participants with current HBV infection was 1.3%. Anti-hepatitis C virus (HCV) seroprevalence remained 1.6%, while active HCV viremia decreased from 0.8% to 0.4%, and viremia among anti-HCV-positive participants fell from 65.5% to 31.3% (P = 0.004). Hepatitis A virus antibody seroprevalence increased from 41.6% to 48.0% (P < 0.001) with stable vaccination coverage. Anti-HEV IgM positivity increased from 1.6% to 1.7% (P = 0.004).

US viral hepatitis trends diverged from 2011 to 2023. The decrease in detectable HCV RNA was consistent with progress in HCV control, whereas persistent HBV susceptibility, declining vaccination coverage in younger birth cohorts, and increasing hepatitis A virus seroprevalence and hepatitis E virus IgM positivity indicate ongoing prevention and surveillance needs.

Hepatitis B virus (HBV) reactivation is a well-recognized complication in patients with lymphoma receiving immunosuppressive therapy, particularly rituximab-containing regimens. We describe a 58-year-old man with diffuse large B-cell lymphoma and an atypical baseline HBV serological profile: hepatitis B surface antibody (anti-HBs) positivity (102.00 U/L), antibody to hepatitis B core antigen negativity, a low-level hepatitis B surface antigen (HBsAg) result (0.35 COI, reported as negative by the local laboratory), and undetectable HBV DNA. Thirteen days after initiation of the fourth cycle of modified R-CHOP (rituximab, cyclophosphamide, pirarubicin, vinorelbine and dexamethasone) chemoimmunotherapy, the anti-HBs titer had decreased to 1.31 S/CO, the HBsAg level to 0.02 S/CO, and HBV DNA was not reassessed until reactivation. Approximately 16 weeks after treatment completion, the patient developed fatigue, anorexia, and jaundice. HBsAg increased from 28.66 S/CO to 8048.30 IU/mL, hepatitis B e antigen became positive, and HBV DNA increased to 1.94 × 109 IU/mL. Despite treatment with tenofovir alafenamide fumarate and plasma exchange, the patient died of refractory liver failure and hepatic encephalopathy. These findings suggest that atypical serological profiles may not reliably indicate a low risk of severe HBV reactivation during intensive immunosuppressive therapy. Comprehensive pretreatment risk assessment and long-term monitoring of anti-HBs titers, HBsAg, and HBV DNA during and after therapy may facilitate earlier detection and intervention.