Search Results (959)

Background: The aim of this study was to assess long-term trends in mortality due to digestive diseases among older adults in Poland. Methods: Mortality data for the years 2000–2022 were analyzed for individuals aged ≥65 years. Age-standardized death rates (SDRs) were calculated. Particular attention was paid to liver cirrhosis-related mortality, operationalized according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) joined categories K70 and K74. Temporal trends were assessed using joinpoint regression to estimate annual percentage change (APC) and average annual percentage change (AAPC) stratified by sex and age groups (65–74 and ≥75 years). The total number of deaths included in the statistical analysis was 6,645,408. Results: In early old age (65–74 years), the proportion of deaths due to digestive diseases increased in both men (from 3.6% to 5.0%) and women (from 4.1% to 4.5%), while a decrease was observed in late old age (≥75 years). The combined K70/K74-coded liver disease category represented an important component of digestive disease mortality. Among women aged 65–74 years, a significant upward trend in SDR was observed after 2015 (APC 3.5%, p < 0.05), with an increase from 54.7 to 70.8. In men of the same age, SDR remained relatively stable overall (160.5 to 171.6), although mortality due to liver-related diseases increased significantly after 2015 (APC 6.7%, p < 0.05). In older age groups, declining trends were observed until the late 2010s, followed by recent non-significant increases. Conclusions: Mortality patterns for alcohol-related liver disease and hepatic fibrosis/cirrhosis showed particularly unfavorable recent trends in adults aged 65–74 years. These findings highlight the need for continued surveillance and prevention of chronic liver disease in ageing populations. Full article

Policosanol (sugarcane wax alcohol), phosphatidylserine, and Ginkgo biloba leaf extract are Ministry of Food and Drug Safety (MFDS), Republic of Korea-listed functional foods for health-promoting effects. Herein, a combination of policosanol, phosphatidylserine, and G. biloba leaf extract (hereafter PPG) was investigated against metabolic stress induced by a high-cholesterol, high-galactose (HCHG) diet in hyperlipidemic and hyperglycemic zebrafish. After 9 weeks of feeding, the zebrafish following the HCHG diet co-supplemented with PPG exhibited a significant 14.1% (p < 0.02) reduction in body weight and higher zebrafish survivability compared to the HCHG-supplemented group. Significantly reduced total cholesterol (TC, 1.2-fold), triglycerides (TG, 1.4-fold), low-density lipoprotein cholesterol (LDL-C, 1.3-fold), and glucose levels (1.2-fold), along with a 1.5-fold (p = 0.003) elevated high-density lipoprotein cholesterol (HDL-C), were observed in the PPG co-supplemented group relative to the HCHG group. In addition, the HCHG-elevated plasma malondialdehyde (MDA), diminished ferric ion reduction activity (FRA), and paraoxonase (PON)-like activity significantly (p < 0.001) reverted by 1.6-fold, 1.4-fold, and 1.6-fold, respectively, by co-supplementation with PPG. Consistently, the plasma from the PPG-supplemented group showed greater ability to prevent carboxymethyllysine (CML)-induced apoptotic death, altered heart rate, and developmental deformities in zebrafish embryos. Moreover, PPG exerted significant protective effects against HCHG-induced hepatomegaly and fatty liver, accompanied by marked inhibition of hepatic interleukin (IL)-6 and reactive oxygen species (ROS) generation. Consistently, PPG supplementation inhibits ROS generation and senescence in the liver, intestine, brain, kidney, testis and ovary and protects the organ damage caused by exposure to HCHG. Similarly, in intestinal tissue, HCHG-induced fibrosis and oxidative stress were mitigated by the co-supplementation of PPG. The findings indicate that PPG is an effective combination for preventing dyslipidemia, oxidative stress, inflammation, and multi-organ damage associated with HCHG-mediated metabolic stress in zebrafish. Full article

As metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) grow increasingly prevalent, it is essential to improve understanding of the contributing factors and how these conditions may interact. Metabolic and alcohol-related liver injury frequently co-occur, prompting the introduction of the term metabolic dysfunction and alcohol-associated liver disease (MetALD) to describe individuals with MASLD who also consume significant amounts of alcohol. Among the exposures relevant to MetALD, dietary fructose is of particular interest because it shares multiple mechanisms of hepatotoxicity with alcohol. This review synthesizes current evidence for hepatotoxic interactions, emphasizing areas most relevant to MetALD pathogenesis. Epidemiologic data indicate substantial overlap between populations with high fructose and alcohol exposure, while clinical studies increasingly associate combined exposure with greater fibrosis progression and adverse liver outcomes. Several mechanistic pathways have been shown to overlap in terms of their interactions with fructose and ethanol, including endogenous fructose generation, cytochrome P450 2E1 (CYP2E1) induction, mitochondrial dysfunction, dysregulated lipid metabolism, uric acid-driven inflammasome signaling, and disruption of the gut–liver axis. Emerging evidence suggests that these pathways interact in ways that may amplify injury beyond the effects of either exposure alone. Greater integration of the alcohol and metabolic liver disease fields will be necessary to clarify mechanistic interactions, determine risk factors, and develop effective interventions for this increasingly common form of liver injury. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has become one of the most common chronic liver diseases worldwide, representing a major global health challenge closely linked to metabolic syndrome, obesity, and type 2 diabetes mellitus (TD2M). The condition is characterized by a multisystem nature driven by complex multifactorial mechanisms, including insulin resistance, lipotoxicity, mitochondrial dysfunction, genetic predispositions, and gut-liver axis alterations. Although liver biopsy remains the gold standard, non-invasive markers and advanced imaging methods are of key importance for early risk stratification. Furthermore, while liver-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) are significant, cardiovascular disease remains the leading cause of mortality in patients with MASLD. Current management relies primarily on lifestyle modifications, targeted pharmacotherapy (such as pioglitazone, GLP-1 receptor agonists, SGLT-2 inhibitors), and novel experimental therapies. Consequently, MASLD requires a multidisciplinary approach emphasizing early diagnosis, risk stratification, and comprehensive treatment of both hepatic and extrahepatic manifestations. Full article

CYB5R3 (NADH–cytochrome b5 reductase 3) and mARC1, the product of MTARC1, draw on the same cytochrome-b5 electron relay, so they are usually treated as two ends of one redox axis. Whether they behave as a unit across the continuum from metabolic dysfunction–associated steatotic liver disease (MASLD) to hepatocellular carcinoma (HCC) has not been established. In TCGA-LIHC, higher CYB5R3 expression was associated with shorter overall survival in a continuous multivariable Cox model adjusted for age, sex, and stage (n = 339, 114 deaths; HR 1.23 per SD, 95% CI 1.01–1.48, p = 0.035), although it added essentially nothing to a clinical model containing age, sex, and stage (change in Harrell C-index 0.005, 95% CI −0.015 to +0.037). The direction was reproduced in the only independent cohort examined, GSE14520 (n = 242, 96 deaths; unadjusted HR 1.42 per SD, 95% CI 1.14–1.76, p = 0.0015), in which higher MTARC1 was associated with longer survival (unadjusted HR 0.73 per SD, 95% CI 0.60–0.89, p = 0.0017); both single-gene estimates fall below conventional significance after adjustment for age, sex, and TNM stage (HR 1.24, 95% CI 0.99–1.56, p = 0.058 and HR 0.89, 95% CI 0.72–1.10, p = 0.29; n = 225, 86 deaths), although CYB5R3 remains nominally significant in an adjusted model containing both genes (HR 1.27, 95% CI 1.01–1.59, p = 0.039), so that cohort replicates direction rather than independent prognostic value. Across the primary tumors of the analysis set, no correlation between the two transcripts was detectable (Spearman r_s = −0.03, 95% CI −0.13 to +0.08, p = 0.62; n = 339), so the axis is not demonstrably a unit at the expression level. In three human liver-biopsy cohorts spanning the MASLD histological spectrum (393 biopsies with fibrosis staging), CYB5R3 gave estimates that differed in sign between cohorts and were uninformative when pooled (fibrosis stage, random-effects r_s = +0.01, 95% CI −0.24 to +0.26, q = 0.95, I² = 83%). MTARC1 behaved differently, falling with fibrosis stage in all three cohorts (pooled r_s = −0.22, 95% CI −0.32 to −0.13, q = 3 × 10⁻⁵, I² = 0%), as did PARP16 (−0.17, I² = 0%), while SCD rose in all three (+0.13, I² = 0%). This is consistent with the inconsistency being specific to CYB5R3 rather than a property of the cohorts, although the fibrogenic positive controls were themselves heterogeneous (I² = 53–62%), I² is estimated from only three cohorts, and the difference between the CYB5R3 and MTARC1 coefficients was not formally tested. These observations are associative and hypothesis-generating. They provide no support for the widely assumed corollary that hepatic CYB5R3 becomes deficient as steatotic liver disease advances, so a therapeutic strategy predicated on that corollary currently rests on mouse gain-of-function data alone, without corroboration from human tissue. What they do support is narrower: within a single physically coupled electron-transfer axis, the two members behave differently before malignancy—MTARC1 tracks fibrosis stage reproducibly while CYB5R3 shows no reproducible relationship—and carry opposite prognostic directions after malignancy, significant for MTARC1 only before covariate adjustment. Full article

Background: Pulmonary fibrosis (PF) is a progressive lung disease with limited therapies. Oral Pirfenidone (PFD), an approved anti-fibrotic, shows poor lung bioavailability and significant toxicity. S-Allylmercapto-N-acetylcysteine (ASSNAC) has been demonstrated to possess significant anti-inflammatory and antioxidant properties. Methods: In this study, dry powder inhaler formulations (DPIs) co-encapsulating ASSNAC and PFD in liposomes are reported. The formulation was prepared via spray freeze-drying (SFD) using L-leucine as both a cryoprotectant and a surface morphology modifier. The interfacial enrichment of L-leucine during atomization and freezing created a hydrophobic, corrugated surface that lowered particle surface energy, prevented liquid/solid bridge formation, and reduced hygroscopicity. Results: The resulting liposomal powders exhibited optimal aerosol performance: fine particle fraction (FPF) of 61.08% ± 2.45% and mass median aerodynamic diameter (MMAD) of 2.22 ± 0.11 µm. Cellular studies demonstrated that dual-loaded liposomes were efficiently taken up by Beas-2B and HFL-1 cells, with no cytotoxicity (cell viability > 90%) and negligible hemolysis. In the TGF-β1-induced in vitro fibrosis model, the combined treatment exerted prominent therapeutic effects. This regimen preserved normal epithelial morphology, accelerated wound repair, suppressed fibroblast invasiveness, and lowered the expression levels of Collagen I, Collagen III, and α-SMA. In bleomycin-induced pulmonary fibrosis rats, inhaled ASSNAC + PFD liposomal powder markedly relieved lung tissue injury and collagen accumulation. It restored redox balance and lowered pulmonary TGF-β1, hydroxyproline and collagen III levels. The formulation blocked TGF-β1 signaling and fibrotic gene expression. Conclusions: Pulmonary administration avoids oral pirfenidone-induced liver and stomach toxicity. Collectively, the ASSNAC + PFD co-encapsulated liposomal dry powder produced by SFD represents a safe and efficacious therapeutic strategy for PF. Full article

The study compares the effects of policosanol (Poli), atorvastatin (Ator), and their combination (Poli+Ator) in mitigating high-cholesterol and high-galactose (HCHG) diet-induced metabolic stress and organ damage in zebrafish. After 22 weeks of feeding, the lowest survival probability was observed in the Ator-supplemented group (0.64). In comparison, the Poli and Poli+Ator-supplemented groups showed higher survival probabilities of 0.76 and 0.71, respectively. Compared with Poli, Ator supplementation had a greater effect in mitigating HCHG-induced dyslipidemia. Nonetheless, Poli+Ator demonstrated a significantly greater effect than Ator and Poli in reducing total blood cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and in elevating the HDL-C/TC ratio. No significant effect of Ator supplementation was observed on the HCHG-induced elevations in blood glucose and malondialdehyde (MDA) levels or the diminished sulfhydryl content; however, Poli alone and Poli+Ator significantly improved blood glucose, MDA, and sulfhydryl content. Consistently, the non-significant effect of Ator on the amputated tail fin regeneration was substantially improved by the Poli+Ator supplementation. In addition, Poli and Poli+Ator markedly reduce liver steatosis, neutrophil infiltration, and interleukin (IL)-6 production, while inhibiting the generation of oxidative species and senescent-positive cells in the kidney and preventing intestinal fibrosis. Also, Poli and Poli+Ator substantially minimize HCHG-triggered oxidative stress in reproductive organs, enhance spermatozoa count in the testis and substantially improve the embryo-producing ability of zebrafish. The study outlines the beneficial effect of Poli and Poli+Ator in mitigating HCHG-induced dyslipidemia, organ damage, and reproductive health. Full article

Radiation-induced liver disease (RILD) remains a clinically significant complication of radiotherapy for malignant neoplasms of the liver and upper abdomen, restricting achievable therapeutic doses and adversely affecting patient outcomes. Conventional photon-based radiotherapy (X-rays/γ-rays) exposes substantial volumes of healthy liver parenchyma and adjacent organs to ionizing radiation, increasing the risk of hepatocellular damage, inflammation, and progressive fibrosis. Electron irradiation (β-particles) represents a promising alternative owing to its limited tissue penetration (~2–3 cm) and steep dose fall-off, which significantly reduces exit dose and may reduce exit dose and limit exposure of paratumoral healthy tissues compared with photon therapy. However, the molecular mechanisms underlying electron-induced hepatic damage and strategies for its prevention remain insufficiently characterized. This review systematically analyzes the pathogenesis of radiation-induced liver damage, encompassing direct DNA damage, oxidative stress, mitochondrial dysfunction, NF-κB-mediated inflammation, cellular senescence, and TGF-β/Smad-driven fibrosis. The comparative dosimetric and radiobiological advantages of electron irradiation over photon therapy are discussed, with particular attention to intraoperative radiotherapy, FLASH, and very high-energy electron techniques. Current radioprotective strategies are critically evaluated, with emphasis on the limitations of amifostine and the multifunctional radioprotective potential of ascorbic acid, including free radical scavenging, attenuation of lipid peroxidation, stimulation of endogenous antioxidant defense, and direct inhibition of radiation-induced DNA strand breaks. Existing gaps in the evidence base are identified, and recommendations for future experimental and clinical research are proposed. Full article

Background/Objectives: Microplastics (MPs) are emerging environmental contaminants with potential implications for human health. Experimental studies suggest that MPs accumulate in the liver and promote inflammatory and fibrotic changes, but evidence from human tissues remains limited. This study investigated the presence of suspected MP-like particles in post-mortem human liver tissue and their associations with clinical, biochemical, hematological and histopathological parameters. Methods: Post-mortem liver tissue samples were collected from 55 adults. Suspected MP-like particles were extracted using hydrogen peroxide digestion, filtration, Nile Red staining and image-based quantification. Histopathological evaluation assessed inflammation, fibrosis, necrosis and fatty liver degeneration. Polarized light microscopy was used as a supportive morphological assessment method. Statistical analyses included Mann–Whitney U tests, Fisher’s exact tests and Spearman correlation analysis. Results: Detectable hepatic suspected MP-like particles were identified in 9 of 55 individuals (16.4%). Individuals with detectable suspected MP-like particles had significantly lower alanine aminotransferase (ALT) levels and leukocyte counts. The hepatic suspected MP-like particle burden showed weak positive correlation with liver fibrosis and inflammation and weak inverse correlation with ALT levels and leukocyte count. Fisher’s exact test showed that liver fibrosis and liver inflammation were significantly associated with detectable hepatic suspected MP-like particles, with higher unadjusted odds observed in the corresponding 2 × 2 contingency tables. No statistically significant associations were found for liver necrosis or fatty liver degeneration. Conclusions: Detectable suspected MP-like particles were identified in post-mortem human liver tissues and were more closely associated with fibrotic and inflammatory histopathological changes than with routine biochemical abnormalities. Larger studies using standardized detection methods are needed to confirm these results. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is associated with progressive hepatic alterations, including steatosis and fibrosis, which may affect liver mechanical properties. Shear wave elastography (SWE) is a non-invasive imaging technique that enables quantitative assessment of tissue stiffness; however, its application in diabetic animal models remains limited. This study aimed to evaluate liver elasticity using SWE in a high-fat diet (HFD) and streptozotocin (STZ)-induced rat model of T2DM, using histopathological examination as the reference standard. Methods: Twenty-four rats were randomly allocated to either a control group (n = 12) or a diabetic group (n = 12). Diabetes was induced using HFD feeding followed by low-dose STZ administration. Liver elasticity was assessed in vivo using SWE at two examination sessions. Shear wave velocity measurements were obtained from eight liver regions of interest and expressed in meters per second (m/s). Following euthanasia, liver tissues were subjected to histopathological evaluation using hematoxylin and eosin, Masson’s trichrome, and periodic acid–Schiff staining. Results: Diabetic rats demonstrated marked histopathological alterations, including macrovesicular and microvesicular steatosis, hepatocellular vacuolization, increased collagen deposition, and glycogen depletion. Collagen deposition was significantly greater in diabetic animals, while glycogen content was significantly reduced (3.70 ± 1.05 vs. 26.87 ± 2.87; p < 0.05). SWE revealed consistently higher liver shear wave velocities in diabetic rats compared with controls at both examination sessions. Although liver stiffness increased over time in both groups, these changes did not reach statistical significance. Conclusions: HFD/STZ-induced diabetes was associated with increased liver stiffness and histopathological evidence of hepatic injury and fibrosis. SWE may represent a feasible non-invasive approach for assessing diabetes-related changes in liver mechanical properties. Full article

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors comprising three isoforms—PPARα, PPARγ, and PPARβ/δ—that regulate hepatic lipid metabolism, glucose homeostasis, inflammation, bile acid synthesis, and fibrogenesis. Because liver diseases involve overlapping metabolic, inflammatory, cholestatic, and fibrotic pathways, PPAR agonists have emerged as a versatile therapeutic class across a spectrum of hepatic conditions. PPARα agonists (e.g., fenofibrate) promote fatty acid β-oxidation and suppress de novo lipogenesis; PPARγ agonists (e.g., pioglitazone) improve insulin sensitivity and exert anti-inflammatory and antifibrotic effects; and PPARδ agonists (e.g., seladelpar) regulate bile acid and cholesterol metabolism. Dual agonists (elafibranor [PPARα/δ] and saroglitazar [PPARα/γ]) and pan-PPAR agonists (lanifibranor [PPARα/γ/δ] and bezafibrate) aim to simultaneously address multiple pathogenic mechanisms. In primary biliary cholangitis (PBC), elafibranor and seladelpar received accelerated FDA approval in 2024 based on phase 3 trials (ELATIVE and RESPONSE, respectively), demonstrating significant biochemical response rates of 51% and 62% versus 4% and 20% with the placebo. Long-term open-label extension data from the ELATIVE trial have demonstrated sustained improvements in cholestatic biomarkers and stabilization of fibrosis markers over three years, with durable benefits on fatigue and pruritus. The ASSURE open-label study has confirmed the durability of seladelpar’s effects on biochemical response and pruritus through up to two years of treatment. Saroglitazar, a dual PPARα/γ agonist, has shown positive topline phase 3 results in the EPICS-III trial and received an FDA priority review designation. Bezafibrate has shown a survival benefit in large retrospective analyses and is used as a second-line therapy in Europe and Japan; notably, bezafibrate functions as a dual PPAR/pregnane X receptor (PXR) agonist, inducing CYP3A4 and efflux transporters that contribute to bile acid detoxification. In metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH), pioglitazone remains the most extensively studied PPAR agonist, with meta-analytic evidence supporting MASH resolution and fibrosis reduction regardless of diabetes status. Lanifibranor demonstrated histological improvement in the phase 2b NATIVE trial and is currently in phase 3 development (NATiV3). PPAR agonists have also demonstrated therapeutic effects on liver fibrosis inhibition through direct modulation of hepatic stellate cell activation and suppression of fibrogenic signaling. This narrative review synthesizes the molecular pharmacology of PPAR isoforms; the available clinical and preclinical evidence for mono-, dual-, and pan-PPAR agonists; and their therapeutic applications across MASLD/MASH, alcohol-associated liver disease (ALD), PBC, primary sclerosing cholangitis (PSC), intestinal failure-associated liver disease (IFALD), and advanced chronic liver disease (ACLD). The evolution from single-isoform to multi-isoform PPAR agonism reflects the recognition that overlapping pathogenic mechanisms in liver diseases may require broader receptor coverage for optimal therapeutic efficacy. Full article

Background: Chronic liver disease (CLD) represents a substantial global health challenge, with significant morbidity and mortality worldwide. Biological aging may be involved in CLD-related outcomes, but the associations of diverse DNA methylation (DNAm) aging algorithms with CLD phenotypes and long-term mortality remain incompletely characterized. Methods: Using a US nationally representative cohort, we analyzed 12 DNAm aging algorithms in 2522 adults aged ≥50. CLD was classified into viral, alcohol-related, metabolic syndrome (MetS)-related liver disease, or uncharacterized groups. Advanced fibrosis was defined by AST-to-platelet ratio index ≥0.7. Associations of algorithms with CLD and all-cause mortality (followed through 2019) were assessed using multivariable-adjusted regression and logistic regression models and Cox models, accounting for complex sampling. Results: Among participants with CLD, DNAm aging algorithms showed only nominal associations with APRI-defined advanced fibrosis. GrimAgeMortAcc, GrimAge2MortAcc, HannumAgeAcc, PhenoAgeAcc, DunedinPoAm, and HorvathTelo were significantly associated with all-cause mortality. GrimAge-based measures and PhenoAgeAcc showed the strongest associations with all-cause mortality across CLD-related phenotypes (HRs ranged from 1.31 to 1.82). HorvathTelo was inversely associated with mortality risk (HR = 0.71, 95% CI: 0.62–0.82). Conclusions: DNAm aging algorithms, particularly GrimAge-based measures, are strongly associated with long-term all-cause mortality among individuals with CLD-related phenotypes. Although associations with fibrosis-related outcomes varied according to fibrosis definitions, DNAm aging algorithms may provide additional biological information for mortality risk stratification among individuals with CLD-related phenotypes. Full article

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with substantial morbidity, and hepatic fibrosis stage is the strongest predictor of long-term outcomes. Although liver biopsy remains the reference standard for fibrosis assessment, its invasiveness has driven the development of noninvasive diagnostic tools, including transient elastography (TE) and serum-based fibrosis scores. To evaluate and compare the diagnostic performance of TE and commonly used serum-based fibrosis scores for detecting clinically significant fibrosis (≥F2) in patients with biopsy-proven MASLD. Materials and Methods: This retrospective cross-sectional exploratory diagnostic accuracy study included 30 adults with biopsy-confirmed MASLD. Patients were classified into clinically significant fibrosis (CSF, ≥F2; n = 9) and no/mild fibrosis (NMF, F0–F1; n = 21) groups. Among the nine patients with CSF, six had stage F2 fibrosis and three had stage F3 fibrosis. TE, FIB-4, APRI, NAFLD Fibrosis Score (NFS), BARD score, and HOMA-IR were evaluated. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis, optimal cutoff values, dual-cutoff strategies, and confusion matrix analysis. Results: TE, FIB-4, and APRI demonstrated the highest diagnostic performance (AUROC: 0.93 for each). TE showed the most balanced diagnostic accuracy (sensitivity 88.9%, specificity 90.5%), whereas APRI provided the highest specificity (95.2%) and the strongest positive likelihood ratio (+LR: 18.67). FIB-4 achieved 100% sensitivity with lower specificity (76.2%). NFS demonstrated moderate diagnostic performance (AUROC: 0.83) with a relatively wide gray zone (56.7%), whereas BARD and HOMA-IR showed limited discriminative ability. When fibrosis categories automatically assigned by the TE device were evaluated, the overall diagnostic accuracy was 93.3%. Conclusions: TE, FIB-4, and APRI demonstrated promising diagnostic performance as noninvasive tools for identifying clinically significant fibrosis in biopsy-proven MASLD. These findings generate the hypothesis that a sequential diagnostic strategy using serum-based fibrosis scores for initial risk stratification followed by TE for confirmation may reduce the need for liver biopsy. However, this hypothesis requires confirmation in larger prospective validation studies. Full article

Objectives: To evaluate associations between shrinkage of ablated liver area on computed tomography (CT) over time after radiofrequency ablation (RFA) and clinical parameters related to liver function and fibrosis. Methods: Patients with hepatocellular carcinoma who underwent RFA and follow-up CT were retrospectively reviewed. The ablated area volume (AAV) on CT obtained within 1 week and around 6 months after RFA was measured, and reduction rate of AAV was calculated. The AAV reduction rate was compared among Child-Pugh classification, modified albumin-bilirubin (mALBI) grades, FIB-4 index categories, and lesion locations using generalized estimating equations (GEE). Univariable and multivariable GEE analyses were performed to evaluate associations between the AAV reduction rate and clinical parameters. Results: Fifty-three lesions in 41 patients (median age, 76 [range, 38–88] years, 24 men) were evaluated. The AAV reduction rate was significantly lower in Child-Pugh class B than class A (p < 0.001) and in mALBI grade 2b than grade 1 (p < 0.001) or grade 2a (p = 0.004). Significant differences were also observed among FIB-4 index groups (p < 0.001) and among lesion locations, with lower AAV reduction rates in medial and anterior segments than in lateral (p < 0.001) and posterior (p = 0.017) segments. Univariable GEE analyses showed significant associations between AAV reduction rate and cholinesterase, albumin, total bilirubin (T-Bil), prothrombin time, platelet count, and FIB-4 index (p < 0.05). Multivariable GEE analysis demonstrated that both albumin and T-Bil remained independently associated with AAV reduction rate (p < 0.001). Conclusions: The AAV reduction rate tended to be lower in patients with impaired liver function and advanced liver fibrosis. Full article

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection remain leading causes of cirrhosis and hepatocellular carcinoma (HCC) worldwide, and continue to represent a major challenge despite the growing contribution of alcohol-related and metabolic dysfunction-associated steatotic liver disease. Direct-acting antivirals now cure most patients with chronic HCV infection, while nucleos(t)ide analogues durably suppress HBV replication, producing a rapidly expanding population of treated and cured patients. Many nonetheless retain residual fibrosis, portal hypertension and long-term cancer risk, creating a need for non-invasive long-term liver assessment. Multiparametric ultrasound (MPUS) integrates the evaluation of morphology, fibrosis, steatosis, haemodynamics and perfusion within a single examination. This narrative review summarises the evidence supporting MPUS in chronic viral hepatitis, covering elastographic fibrosis assessment, Baveno VII liver and spleen stiffness criteria for clinically significant portal hypertension, contrast-enhanced ultrasound characterisation of focal liver lesions, and emerging techniques such as microvascular and viscosity-sensitive imaging. Particular attention is given to the confounding effect of inflammatory activity on liver stiffness. MPUS is presented here as a proposed evaluation framework for organising complementary measurements within a single examination, and not as an approach of demonstrated clinical superiority: no comparative or outcome-based study has yet shown that acquiring these parameters together improves clinical decisions relative to the individual techniques applied according to current guidelines. Within this framework, the most plausible role of MPUS in the elimination era is longitudinal assessment of the treated liver, a proposition that requires prospective validation against clinical endpoints. Full article