Search Results (3,434)

Background/Objectives: In chronic hepatitis B infection (CHB), the hepatitis B surface antigen (HBsAg) continuously exhausts the hepatitis B surface antibody (HBsAb), which leads to the formation of immune tolerance. Accordingly, the hepatitis B virus (HBV) infection can be blocked by inhibiting the binding of the hepatitis B surface pre-S1/pre-S2 antigen to the hepatocyte receptor NTCP, but the clinical cure rate of pre-S-based vaccines for CHB is limited. Methods: In this study, we designed and prepared multivalent hepatitis B therapeutic mRNA vaccines encoding three hepatitis B surface antigen proteins (L, M, and S) at the cell membrane, verified via in vitro transfection and expression experiments. An in vivo immunization experiment in HBV transgenic (Tg) mice was first completed. Subsequently, an adeno-associated virus plasmid vector carrying the HBV1.2-fold genome (pAAV HBV1.2) model and the adeno-associated virus vector carrying HBV1.3-fold genome (rAAV HBV1.3) model were constructed and immunized with mRNA vaccines. The HBV antigen, antibodies, and HBV DNA in serum were detected. Indirect (enzyme-linked immunosorbent assay) ELISA were made to analyze the activated antigen-specific IgG in HBV Tg mice. Antigen-dependent T-cell activation experiments were carried out, as well as the acute toxicity tests in mice. Results: The L protein/pre-S antigens could be stably presented at the cell membrane with the support of the S protein (and M protein). After vaccinations, the vaccines effectively reactivated the production of high levels of HBsAb, disrupted immune tolerance, and activated the production of high-affinity antibodies against structural pre-S antigen in HBV Tg mice. The HBsAg seroconversion and serum HBV DNA clearance were achieved in two HBV mice models. Furthermore, pre-S antigen-dependent T-cell response against HBV infection was confirmed. The therapeutic vaccine also showed safety in mice. Conclusions: A novel therapeutic mRNA vaccine was developed to break through HBsAg-mediated immune tolerance and treat CHB by stably presenting the pre-S antigen at the membrane, and the vaccine has great potential for the functional cure of CHB. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Barcelona Clinic Liver Cancer (BCLC) guidelines recommend antiangiogenic agents with immune checkpoint inhibitors as first-line therapy for advanced HCC. We present our experience of treating HCC patients with Atezolizumab–Bevacizumab, their response rates, adverse events, survival, and response and survival predictors. Methods: This retrospective analysis included HCC patients diagnosed at All India Institute of Medical Sciences, New Delhi, India between July 2021 and April 2024 and receiving at least one dose of Atezolizumab–Bevacizumab. The primary outcome was overall response rate (ORR), comprising complete response (CR) and partial response (PR), as per mRECIST criteria. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and predictors of response and survival. Results: Sixty-three patients were analyzed {mean age: 56.0 + 12.7 years; 82.5% males}. Forty-three (68.2%) patients had BCLC stage C HCC. Thirty-five (55.5%) patients belonged to Child–Pugh class A and 28 (44.5%) belonged to Child–Pugh class B. At 1 year, OS was 39% and PFS was 27%. Among 43 patients with data for radiological response, ORR was 48.8% (CR—9.3% and PR—39.5%) and DCR was 62.7% with stable disease (SD) in 13.9% of patients. PD occurred in 37.2% of patients. AFP response predicted radiological response, while Child–Pugh class and BCLC stage predicted survival. Adverse events were reported in 49.2% of patients. Conclusions: Our study shows slightly lower survival than previous studies with Child–Pugh class being the most important determinant of survival. AFP response predicts radiological response and not survival. Full article

Houttuynia cordata Thunb. holds a longstanding reputation as a traditional folk remedy in East Asia, where it has been employed to treat a variety of inflammatory conditions, nephritis, hepatitis and cancer. Despite its extensive use, there exists a paucity of research examining its efficacy in managing thyroid disorders and diabetes. Moreover, the bioactive components responsible for modulating the molecular pathways remain elusive. Objectives: This research aimed to determine the key bioactive components in the ethanolic extract of H. cordata Thunb. (HCEE) responsible for its thyroid-modifying properties and examine its effects on rats with experimentally induced hypothyroidism and diabetes. Methods: Molecular docking was performed to investigate the possible mechanisms of thyroid regulation of HCEE constituents. Researchers induced hypothyroidism in rats by adding 6-propyl-2-thiouracil to their drinking water for a period of four weeks. To induce diabetes, the rats received an intraperitoneal injection of streptozotocin. The animals were then given daily oral doses of HCEE (500 mg/kg b.w.), levothyroxine (50 mg/kg b.w.), or glibenclamide (5 mg/kg b.w.) for 28 days. Following this treatment, standard methods were employed to measure biochemical parameters in the rats’ serum. Results: The results demonstrate that HCEE ameliorated hypothyroidism by increasing serum T3 (14.38%) and T4 (125.96%) levels and decreasing TSH (p < 0.01; −41.75%) levels. In diabetic rats with induced hypothyroidism, HCEE significantly (p < 0.001) increased T3 (149.51%) and T4 (73.54%) levels with reduced TSH (−64.39%) levels. In silico analysis demonstrated that the identified bioactive compounds from HCEE may enhance thyroid hormone function through interaction with the thyroid hormone receptor protein TRβ1 (PDB:3GWS), similar to the conventional pharmaceuticals levothyroxine and triiodothyronine (T3). Conclusions: HCEE exhibits potential as a natural alternative to synthetic medications in the prevention and treatment of thyroid dysfunctions. Full article

I started my research career (in 1965) on interferon by identifying polyacrylic acid (PAA) as an interferon inducer. Poly(I).poly(C), discovered by Maurice Hilleman’s group, proved to be more potent as an interferon inducer, and through its mRNA, we were able to clone and express human β-interferon. The discovery of the reverse transcriptase (RT) by Temin and Baltimore (in 1970) brought me to the detection of suramin as a powerful RT inhibitor and enabled Sam Broder and his colleagues to identify suramin as the first inhibitor of HIV replication. In this capacity, it was subsequently superseded by AZT and other 2′,3′-dideoxynucleoside (ddN) analogs, including d4T. In collaboration with Antonín Holý, we discovered several acyclic nucleoside phosphonates as potent inhibitors of both HIV and HBV (hepatitis B virus) replication. In collaboration with Paul Janssen, we identified various non-nucleoside RT inhibitors (NNRTIs) of HIV-1 replication. Of the nucleotide RT inhibitors (NtRTTs), tenofovir emerged as the most promising congener. It was derivatized to its oral prodrugs TDF and TAF. To enhance their efficacy, they were combined with other anti-HIV drugs, and two of them were pursued (and found efficacious) in the Pre-Exposure Prophylaxis (PrEP) of HIV infections. Full article

This paper introduces a novel framework for modeling nonlocal fractional system with a p-Laplacian operator under power nonlocal fractional derivatives (PFDs), a generalization encompassing established derivatives like Caputo–Fabrizio, Atangana–Baleanu, weighted Atangana–Baleanu, and weighted Hattaf. The core methodology involves employing a PFD with a tunable power parameter within a non-singular kernel, enabling a nuanced representation of memory effects not achievable with traditional fixed-kernel derivatives. This flexible framework is analyzed using fixed-point theory, rigorously establishing the existence and uniqueness of solutions for four symmetric cases under specific conditions. Furthermore, we demonstrate the Hyers–Ulam stability, confirming the robustness of these solutions against small perturbations. The versatility and generalizability of this framework is underscored by its application to an epidemiological model of transmission of Hepatitis B Virus (HBV) and numerical simulations for all four symmetric cases. This study presents findings in both theoretical and applied aspects of fractional calculus, introducing an alternative framework for modeling complex systems with memory processes, offering opportunities for more sophisticated and accurate models and new avenues for research in fractional calculus and its applications. Full article

Genetic factors have been hypothesized to contribute to the heterogeneity in the response to infectious diseases (IDs). The classical twin design provides a powerful tool to estimate the role of genetic contributions to variation in infection outcomes. With this design, the impact of heritability on the proneness as well as infection- and vaccine-induced immune responses have been documented for multiple infections, including tuberculosis, malaria, leprosy, otitis media, polio, mumps, measles, rubella, influenza, hepatitis B, and human papillomavirus infections, and recently, SARS-CoV-2. The current data show the heritable aspect in nearly all infections considered. In this contribution, we review and discuss human twin studies on the heritability of host characteristics in liability and response to IDs. This review emphasizes the importance of considering factors such as sex, disease stages, and disease presentation when assessing heritability and argues that the classical twin design provides a unique circumstance for exploring the genetic contribution as twins share levels of maternal antibodies, ancestral background, often the dates and number of vaccine doses, differences in vaccines’ manufacturing and storage, age, family environment, and other exposures. Additionally, we highlight the value of twin studies and the usefulness of combining the twin model with contemporary genomics technologies and advanced statistical tools to grasp a comprehensive and nuanced understanding of heritability in IDs. Full article

Background/objectives: The real-world survival of patients with unresectable hepatocellular carcinoma (uHCC) treated with lenvatinib has been explored retrospectively with a small sample size. We conducted a prospective observational 2-year extension study (510 study) of a 1-year observational post-marketing study of lenvatinib (504 study) to evaluate the long-term overall survival (OS) of patients with uHCC treated with lenvatinib and associated factors with a large sample size. Methods: Patients with uHCC included (July 2018 to January 2019) in the 504 study and who consented were eligible for the 510 study and were followed for up to 3 years after lenvatinib treatment initiation. Using the data from the 504 study and 510 study of the 504 study analysis set, we estimated the OS, the time from the first lenvatinib dose to all-cause death by the Kaplan–Meier method (ClinicalTrials.Gov Registration ID, 504 study: NCT03663114; 510 study: NCT04008082). Results: The 703 patients included in the analysis were followed for a median period (min, max) of 12.5 months (0.1, 44.8). The median OS (95% confidence interval) was 16.6 months (15.4, 18.5). OS was significantly (p < 0.05) associated with bile duct invasion (hazard ratio [HR]: 1.621), portal vein invasion (HR: 1.365), ≥ 4 intrahepatic lesions (HR: 1.437), extrahepatic lesions (HR: 1.357), Child–Pugh B/C (HR: 1.515), mALBI Grade 2a (HR: 1.331), and Grade ≥ 2b (HR: 1.811). Conclusions: This large-scale, prospective, real-world study demonstrated a long OS, comparable to that reported in the global Phase III REFLECT trial. More advanced-stage tumors and worse hepatic function have been suggested as OS-associated factors, consistent with previous reports. Full article

Feline infectious peritonitis virus (FIPV) remains as one of the leading causes of morbidity and mortality in young cats from shelters and catteries worldwide. Since little is known about the molecular characteristics of currently circulating FIPV strains in Long Island, New York, samples from two shelter cats submitted to the Pathology Diagnostic Services of the Long Island University College of Veterinary Medicine, with gross and microscopic lesions consistent with those of FIP were processed for virus isolation, molecular characterization and full-length genome decoding. The younger shelter cat, a 1-year-old male (A15) was found dead without previous signs of illness. Postmortem examination revealed gross and microscopic lesions characterized by vasculitis, necrosis, hemorrhage, and pyogranulomatous inflammation confined to the colon and associated lymph nodes. The second cat, a 7-year-old spayed female (A37) had an identical clinical history and similar but widespread lesions, including fibrinous peritoneal effusion, cecal, colonic, renal, and hepatic involvement. The gross and microscopic diagnosis of FIP in these cats was confirmed by immunohistochemistry (IHC) demonstration of feline coronavirus antigen using mouse anti-FIPV3-70 monoclonal antibody. Virus isolation from saved frozen kidney and colon tissue was performed through several subsequent blind passages in MDCK and Vero cell lines. Confirmation of the FIPV isolation was done through qRT-PCR, IFA, western blot using N protein antibodies, and NGS of the full-length genome sequencing. The full-length genome sequences of the virus isolate from the two cats were decoded using next-generation sequencing (NGS) and deposited in the GenBank as accession numbers PQ192636 and PQ202302. The genome size of these isolates was (29355 and 29321) nucleotides (nt) in length, respectively. While their genome organization was consistent with other FIPV genomes as follows (5’UTR-ORF1ab-S-3abc-M-E-7b-3’UTR-3’), marked differential mutations were observed in the ORF1a/b, S, 3Abc, and 7b protein genes of the two FIPV isolates. One notable deletion of 34 nucleotides was observed in the 7b genes of one of these isolates but was absent in the other. We confirmed the potential recombination events during the evolution of those two FIPV field isolates with the potential parent virus as FECoV-US isolated in 1970 and the potential minor parent as the Canine coronavirus. Our results provide a comprehensive molecular analysis of two novel FIPV isolates causing fatal disease in shelter cats from Long Island. Diagnostic surveillance with molecular characterization and sequencing analysis of circulating FIPV strains within animal shelters may help early detect unique emerging clinical and pathological manifestations of the disease and develop more targeted prophylactic and therapeutic approaches to control it. Full article

Background: Viral hepatitis, particularly hepatitis B (HBV) and hepatitis C (HCV), is highly prevalent in Mongolia. Moreover, Mongolia has the highest prevalence of hepatitis delta virus (HDV) globally, with over 60% of HBV-infected individuals also co-infected with HDV. Since HBV/HDV infections accelerate liver disease progression more compared to HBV infection alone, urgent national health measures are required. Method: This study presents a clinicopathological analysis of 49 hepatocellular carcinoma cases surgically resected at the Mongolia–Japan Hospital of the Mongolian National University of Medical Sciences. Results: HBV infection was found in 27 (55.1%) cases of all HCC cases. Immunohistochemical staining of the liver revealed that 14 (28.6%) cases were HDV antigen-positive in the HCC cases. HDV-positive cases exhibited significantly higher inflammatory activity compared to HDV-negative cases, with lymphocytic infiltrates predominantly composed of CD4-positive cells. Furthermore, HDV-positive cells were spatially distinct from HBs antigen-positive cells, suggesting that HDV-infected cells may interfere with HBV replication. No significant differences in fibrosis or in tumor characteristics were observed between the HDV-positive and negative cases. Early diagnosis of HBV/HDV infections is essential for appropriate treatment and to prevent further domestic transmission of the virus. However, routine testing for HDV infection is rarely conducted in Mongolia. Since HDV-positive cells are morphologically indistinguishable from surrounding HDV-negative cells, routine histopathological analysis may not be sufficient enough to detect HDV infection. Conclusions: Based on this clinicopathological study, CD4 and CD8 immunostaining can be considered an adjunctive diagnostic tool in cases with significant lymphocytic infiltration and hepatocellular damage. Additionally, HDV screening using blood and tissue samples may be recommended to ensure accurate diagnosis. Full article

We have previously shown that the hepatitis C virus (HCV) E1E2 envelope glycoprotein can regulate HIV-1 long-terminal repeat (LTR) activity through disruption to NF-κB activation. This response is associated with upregulation of the endoplasmic reticulum (ER) stress response pathway. Here, we demonstrate that the SARS-CoV-2 S, M, and E but not the N structural protein can perform similar downmodulation of HIV-1 LTR activation, and in a dose-dependent manner, in both HEK293 and lung BEAS-2B cell lines. This effect is highest with the SARS-CoV-2 Wuhan S strain and decreases over time for the subsequent emerging variants of concern (VOC), with Omicron providing the weakest effect. We developed pseudo-typed viral particle (PVP) viral tools that allowed for the generation of cell lines constitutively expressing the four SARS-CoV-2 structural proteins and utilising the VSV-g envelope protein to deliver the integrated gene construct. Differential gene expression analysis (DGEA) was performed on cells expressing S, E, M, or N to determine cell activation status. Gene expression differences were found in a number of interferon-stimulated genes (ISGs), including IF16, IFIT1, IFIT2, and ISG15, as well as for a number of heat shock protein (HSP) genes, including HSPH1, HSPA6, and HSPBP1, with all four SARS-CoV-2 structural proteins. There were also differences observed in expression patterns of transcription factors, with both SP1 and MAVS upregulated in the presence of S, M, and E but not the N protein. Collectively, the results indicate that gene expression patterns associated with ER stress pathways can be activated by SARS-CoV-2 envelope glycoprotein expression. The results suggest the SARS-CoV-2 infection can modulate an array of cell pathways, resulting in disruption to NF-κB signalling, hence providing alterations to multiple physiological responses of SARS-CoV-2-infected cells. Full article

Background: Cytochrome P450 2B6 (CYP2B6) is a sexually dimorphic, anti-obesity CYP enzyme responsible for the metabolism of xeno- and endobiotics, including the metabolism of polyunsaturated fatty acids (PUFAs) into 9-hydroxyoctadecadienoic acid (9-HODE) and 9-hydroxyoctadecatrienoic acid (9-HOTrE). However, humanized CYP2B6 transgenic (hCYP2B6-Tg) mice are sensitive to diet-induced hepatic steatosis despite their resistance to obesity. The purpose of this study was to determine if 9-HODE, 9-HOTrE, or other factors contribute to the sexually dimorphic steatosis observed in hCYP2B6-Tg mice. Results: Cyp2b9/10/13-null (Cyp2b-null) mice were injected with either 9-HODE or 9-HOTrE for 2 days and were then subjected to a fasting period of 20 h to induce steatosis. Serum lipids were moderately increased, especially in females, after 9-HODE (triglycerides (TGs), very low-density lipoproteins (VLDLs)) and 9-HOTrE (high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), cholesterol) treatment. No change in hepatic lipids and few changes in hepatic gene expression were observed in mice treated with either oxylipin, suggesting that these oxylipins had minimal to moderate effects. Therefore, to further investigate CYP2B6’s role in steatosis, hCYP2B6-Tg and Cyp2b-null mice were subjected to a 20 h fast and compared. Both male and female hCYP2B6-Tg mice exhibited increased steatosis compared to Cyp2b-null mice. Serum cholesterol, triglycerides, HDLs, and VLDLs were increased in hCYP2B6-Tg males. Serum triglycerides and VLDLs were decreased in hCYP2B6-Tg females, suggesting the greater hepatic retention of lipids in females. Hepatic oxylipin profiles revealed eight perturbed oxylipins in female hCYP2B6-Tg mice and only one in males when compared to Cyp2b-null mice. RNA-seq also demonstrated greater effects in females in terms of the number of genes and gene ontology (GO) terms perturbed. There were only a few overlapping GO terms between sexes, and lipid metabolic processes were enriched in hCYP2B6-Tg male mice but were repressed in hCYP2B6-Tg females compared to Cyp2b-nulls. Conclusions: hCYP2B6-Tg mice are sensitive to fasting-mediated steatosis in males and females, although the responses are different. In addition, the oxylipins 9-HODE and 9-HOTrE are unlikely to be the primary cause of CYP2B6’s pro-steatotic effects. Full article

Hepatitis C virus (HCV) is susceptible to resistance-associated substitutions (RASs) in the NS3, NS5A, and NS5B nonstructural genes, key targets of the direct-acting antivirals (DAAs). This study aimed to assess the prevalence and distribution of RASs across different HCV subtypes in Mexico. A Genbank dataset of 566 HCV sequences was analyzed. Most sequences were from Mexico City (49.1%, 278/566) and Jalisco (39.4%, 223/566). The NS5B region was the most sequenced (59.7%, 338/566). The most frequent HCV subtypes were 1a (44.0%, 249/566), 1b (28.6%, 162/566), 2b (9.5%, 54/566), and 3a (6.2%, 35/566). Subtypes 1a (57.4%, 128/223) and 3a (12.6%, 28/223) were significantly higher in Jalisco than in Mexico City (34.2%, 95/278 and 2.5%, 7/278), whereas subtype 1b was higher in Mexico City (34.5%, 96/278 vs. 14.8%, 33/223). Subtype 1a increased from 2019 to 2024, representing 49.4% (123/249) of all reported cases. RASs were detected in NS3 (6.7%, 1/15), NS5A (2.9%, 3/102), and NS5B (0.3%, 1/349), with the most frequent mutations being Q80K, Y93H, and S282T, respectively, and detected in subtypes 1b (n = 3), 1a (n = 1), and 2a (n = 1). In conclusion, Mexico’s HCV sequencing-based surveillance is limited. Subtype 1a predominated, but frequencies varied across states. The prevalence of RASs varied by gene from 0.3% to 6.7%. Establishing regional sequencing centers for NS3, NS5A, and NS5B is crucial to monitoring Mexico’s DAA-resistant mutations and HCV subtype genetic diversity. Full article

Liver health is integral to overall human well-being and the pathogenesis of various diseases. In recent years, kynurenine and its derivatives have gradually been recognized for their involvement in various pathophysiological processes, especially in the regulation of liver diseases, such as acute liver injury, non-alcoholic fatty liver disease, cirrhosis, and liver cancer. Kynurenine and its derivatives are derived from tryptophan, which is broken down by the enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO), converting the essential amino acid tryptophan into kynurenine (KYN) and other downstream metabolites, such as kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and quinolinic acid (QA). In liver diseases, kynurenine and its derivatives can promote the activity of the transcription factor aryl hydrocarbon receptor (AhR), suppress T cell activity for immune modulation, inhibit the activation of inflammatory signaling pathways, such as NF-κB for anti-inflammatory effects, and inhibit the activation of hepatic stellate cells to slow down fibrosis progression. Additionally, kynurenine and other downstream metabolites can influence the progression of liver diseases by modulating the gut microbiota. Therefore, in this review, we summarize and explore the mechanisms by which kynurenine and its derivatives regulate liver diseases to help develop new diagnostic or prognostic biomarkers and effective therapies targeting the kynurenine pathway for liver disease treatment. Full article

Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) continue to be global public health issues. Globally, about 39.9 million persons live with HIV in 2023, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2024 Fact Sheet. Consequently, the World Health Organisation (WHO) reported that about 1.5 million new cases of HBV occur, with approximately 820 thousand mortalities yearly. Conversely, the lower percentage of HBV (30%) cases that receive a diagnosis is a setback in achieving the WHO 2030 target for zero HBV globally. This has necessitated a public health concern to repurpose antiretroviral (ARV) drugs for the treatment of HBV diseases. This review provides an introductory background, including the pros and cons of repurposing antiretrovirals (ARVs) for HBV treatment. We examine the similarities in replication mechanisms between HIV and HBV. We further investigate some clinical studies and trials of co-infected and mono-infected patients with HIV–HBV. The topical keywords including repurposing ARV drugs, repurposing antiretroviral therapy, Hepatitis B drugs, HBV therapy, title, and abstracts are searched in PubMed, Web of Science, and Google Scholar. The advanced search includes the search period 2014–2024, full text, clinical trials, randomized control trials, and review. The search results filtered from 361 to 51 relevant articles. The investigations revealed that HIV and HBV replicate via a common route known as ‘reverse transcription’. Clinical trial results indicate that an early initiation of ARVs, particularly with tenofovir disoproxil fumarate (TDF) as part of a regimen, significantly reduced the HBV viral load in co-infected patients. In mono-infected HBV, timely and correct precise medication is essential for HBV viral load reduction. Therefore, genetic profiling is pivotal for successful ARV drug repurposing in HBV treatment. Pharmacogenetics enables the prediction of the right dosages, specific individual responses, and reactions. This study uniquely explores the intersection of pharmacogenetics and drug repurposing for optimized HBV therapy. Additional in vivo, clinical trials, and in silico research are important for validation of the potency, optimum dosage, and safety of repurposed antiretrovirals in HBV therapy. Furthermore, a prioritization of research collaborations comprising of regulators and funders to foster clinically adopting and incorporating repurposed ARVs for HBV therapy is recommended. Full article

In recent years, novel findings have progressively and promisingly supported the potential role of Artificial intelligence (AI) in transforming the management of various neoplasms, including hepatocellular carcinoma (HCC). HCC represents the most common primary liver cancer. Alarmingly, the HCC incidence is dramatically increasing worldwide due to the simultaneous “pandemic” spreading of metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD currently constitutes the leading cause of chronic hepatic damage (steatosis and steatohepatitis), fibrosis, and liver cirrhosis, configuring a scenario where an HCC onset has been reported even in the early disease stage. On the other hand, HCC represents a serious plague, significantly burdening the outcomes of chronic hepatitis B (HBV) and hepatitis C (HCV) virus-infected patients. Despite the recent progress in the management of this cancer, the overall prognosis for advanced-stage HCC patients continues to be poor, suggesting the absolute need to develop personalized healthcare strategies further. In this “cold war”, machine learning techniques and neural networks are emerging as weapons, able to identify the patterns and biomarkers that would have normally escaped human observation. Using advanced algorithms, AI can analyze large volumes of clinical data and medical images (including routinely obtained ultrasound data) with an elevated accuracy, facilitating early diagnosis, improving the performance of predictive models, and supporting the multidisciplinary (oncologist, gastroenterologist, surgeon, radiologist) team in opting for the best “tailored” individual treatment. Additionally, AI can significantly contribute to enhancing the effectiveness of metabolomics–radiomics-based models, promoting the identification of specific HCC-pathogenetic molecules as new targets for realizing novel therapeutic regimens. In the era of precision medicine, integrating AI into routine clinical practice appears as a promising frontier, opening new avenues for liver cancer research and treatment. Full article