Liver Hepatocellular Carcinoma Research Articles

Coexistence of liver abscess, hepatic cystic echinococcosis and hepatocellular carcinoma: A case report

BACKGROUND Human cystic echinococcosis (CE) is a life-threatening zoonosis caused by the Echinococcus granulosus (sensu lato). Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. The coexistence of CE and HCC is exceedingly rare, and only several well-documented cases have been reported. In addition to this coexistence, there is no report of the coexistence of CE, HCC, and liver abscess to date. Herein, we aimed to report a case of coexistence of liver abscess, hepatic CE, and HCC. CASE SUMMARY A 65-year-old herdsman presented to the department of interventional therapy with jaundice, right upper abdominal distension and pain for 10 d. Laboratory test showed that he had positive results for HBsAg, HBeAb, HBcAb, and echinococcosis IgG antibody. The test also showed an increased level of alpha fetoprotein of 3400 ng/mL. An abdominal computed tomography (CT) scan revealed an uneven enhanced lesion of the liver at the arterial phase with enhancement and was located S4/8 segment of the liver. In addition, CT scan also revealed a mass in the S6 segment of the liver with a thick calcified wall and according to current guideline and medical images, the diagnoses of hepatic CE (CE4 subtype) and HCC were established. Initially, transarterial chemoembolization was performed for HCC. In the follow-up, liver abscess occurred in addition to CE and HCC; thus, percutaneous liver puncture drainage was performed. In the next follow-up, CE and HCC were stable. The liver abscess was completely resolved, and the patient was discharged with no evidence of recurrence. CONCLUSION This is the first reported case on the coexistence of liver abscess, hepatic CE, and HCC. Individualized treatment and multidisciplinary discussions should be performed in this setting. Therefore, treatment and diagnosis should be based on the characteristics of liver abscess, hepatic CE, and HCC, and in future clinical work, it is necessary to be aware of the possibility of this complex composition of liver diseases.

Wireless sequential dual light delivery for programmed PDT in vivo

Using photodynamic therapy (PDT) to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light. Polymeric nanocarriers are widely used for photosensitizer delivery, while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy. Furthermore, the generated short-lived reactive oxygen spieces (ROS) can hardly diffuse out of nanocarriers, resulting in low PDT efficacy. Therefore, a smart nanocarrier system which can be degraded by light, followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy. A light-sensitive polymer nanocarrier encapsulating photosensitizer (RB-M) was synthesized. An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer. Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently. Optimal irradiation time, dose, and RB-M concentration were determined using an agent-based digital simulation method. In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose, which is a clinically significant event that enhances treatment safety.

Autoimmune hepatitis displays distinctively high multi-antennary sialylation on plasma N-glycans compared to other liver diseases

BackgroundChanges in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma. Autoimmune hepatitis (AIH) is a liver disease characterized by liver inflammation and raised serum levels of IgG, and is difficult to distinguish from other liver diseases. The aim of this study was to examine plasma and IgG-specific N-glycosylation in AIH and compare it with healthy controls and other liver diseases.MethodsIn this cross-sectional cohort study, total plasma N-glycosylation and IgG Fc glycosylation analysis was performed by mass spectrometry for 66 AIH patients, 60 age- and sex-matched healthy controls, 31 primary biliary cholangitis patients, 10 primary sclerosing cholangitis patients, 30 non-alcoholic fatty liver disease patients and 74 patients with viral or alcoholic hepatitis. A total of 121 glycans were quantified per individual. Associations between glycosylation traits and AIH were investigated as compared to healthy controls and other liver diseases.ResultsGlycan traits bisection (OR: 3.78 [1.88–9.35], p-value: 5.88 × 10− 3), tetraantennary sialylation per galactose (A4GS) (OR: 2.88 [1.75–5.16], p-value: 1.63 × 10− 3), IgG1 galactosylation (OR: 0.35 [0.2–0.58], p-value: 3.47 × 10− 5) and hybrid type glycans (OR: 2.73 [1.67–4.89], p-value: 2.31 × 10− 3) were found as discriminators between AIH and healthy controls. High A4GS differentiated AIH from other liver diseases, while bisection associated with cirrhosis severity.ConclusionsCompared to other liver diseases, AIH shows distinctively high A4GS levels in plasma, with potential implications on glycoprotein function and clearance. Plasma-derived glycosylation has potential to be used as a diagnostic marker for AIH in the future. This may alleviate the need for a liver biopsy at diagnosis. Glycosidic changes should be investigated further in longitudinal studies and may be used for diagnostic and monitoring purposes in the future.

Metabolic dysfunction-associated steatotic liver disease: Navigating terminological evolution, diagnostic frontiers and therapeutic horizon-an editorial exploration

Metabolic dysfunction-associated steatotic liver disease (MASLD), once known as non-alcoholic fatty liver disease (NAFLD), represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes. The redefinition of NAFLD in 2023 marked a significant reposition in terminology, emphasizing a broader understanding of liver steatosis and its associated risks. MASLD is now recognized as a major risk factor for liver cirrhosis, hepatocellular carcinoma, and systemic complications such as cardiovascular diseases or systemic inflammation. Diagnostic challenges arise, particularly in identifying MASLD in lean individuals, necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools. Therapeutically, there is an urgent need for effective treatments targeting MASLD, with emerging pharmacological options focusing on, among others, carbohydrate and lipid metabolism. Additionally, understanding the roles of bile acid metabolism, the microbiome, and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches. There is a strong need to emphasize the importance of collaborative efforts in understanding, diagnosing, and managing MASLD to improve physicians’ approaches and patient outcomes.

Immortalized hepatocyte-like cells: A competent hepatocyte model for studying clinical HCV isolate infection.

More than 58 million individuals worldwide are inflicted with chronic HCV. The disease carries a high risk of end stage liver disease, i.e., cirrhosis and hepatocellular carcinoma. Although direct-acting antiviral agents (DAAs) have revolutionized therapy, the emergence of drug-resistant strains has become a growing concern. Conventional cellular models, Huh7 and its derivatives were very permissive to only HCVcc (JFH-1), but not HCV clinical isolates. The lack of suitable host cells had hindered comprehensive research on patient-derived HCV. Here, we established a novel hepatocyte model for HCV culture to host clinically pan-genotype HCV strains. The immortalized hepatocyte-like cell line (imHC) derived from human mesenchymal stem cell carries HCV receptors and essential host factors. The imHC outperformed Huh7 as a host for HCV (JFH-1) and sustained the entire HCV life cycle of pan-genotypic clinical isolates. We analyzed the alteration of host markers (i.e., hepatic markers, cellular innate immune response, and cell apoptosis) in response to HCV infection. The imHC model uncovered the underlying mechanisms governing the action of IFN-α and the activation of sofosbuvir. The insights from HCV-cell culture model hold promise for understanding disease pathogenesis and novel anti-HCV development.

Cytokine Response of Natural Killer Cells to Hepatitis B Virus Infection Depends on Monocyte Co-Stimulation

Hepatitis B virus (HBV) is a major driver of chronic hepatic inflammation, which regularly leads to liver cirrhosis or hepatocellular carcinoma. Immediate innate immune cell response is crucial for the rapid clearance of the infection. Here, natural killer (NK) cells play a pivotal role in direct cytotoxicity and the secretion of antiviral cytokines as well as regulatory function. The aim of this study was to further elucidate NK cell responses triggered by an HBV infection. Therefore, we optimized HBV in vitro models that reliably stimulate NK cells using hepatocyte-like HepG2 cells expressing the Na+-taurocholate co-transporting polypeptide (NTCP) and HepaRG cells. Immune cells were acquired from healthy platelet donors. Initially, HepG2-NTCP cells demonstrated higher viral replication compared to HepaRG cells. Co-cultures with immune cells revealed increased production of interferon-γ and tumor necrosis factor-α by NK cells, which was no longer evident in isolated NK cells. Likewise, the depletion of monocytes and spatial separation from target cells led to the absence of the antiviral cytokine production of NK cells. Eventually, the combined co-culture of isolated NK cells and monocytes led to a sufficient cytokine response of NK cells, which was also apparent when communication between the two immune cell subpopulations was restricted to soluble factors. In summary, our study demonstrates antiviral cytokine production by NK cells in response to HBV+ HepG2-NTCP cells, which is dependent on monocyte bystander activation.

Constructing immune and prognostic features associated with ADCP in hepatocellular carcinoma and pan-cancer based on scRNA-seq and bulk RNA-seq

AimDespite the significant therapeutic outcomes achieved in systemic treatments for liver hepatocellular carcinoma (LIHC), it is an objective reality that only a low proportion of patients exhibit an improved objective response rate (ORR) to current immunotherapies. Antibody-dependent cellular phagocytosis (ADCP) immunotherapy is considered the new engine for precision immunotherapy. Based on this, we aim to develop an ADCP-based LIHC risk stratification system and screen for relevant targets.MethodUtilizing a combination of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, we screened for ADCP modulating factors in LIHC and identified differentially expressed genes along with their involved functional pathways. A risk scoring model was established by identifying ADCP-related genes with prognostic value through LASSO Cox regression analysis. The risk scoring model was then subjected to evaluations of immune infiltration and immunotherapy relevance, with pan-cancer analysis and in vitro experimental studies conducted on key targets.ResultsBuilding on the research by Kamber RA et al., we identified GYPA, CLDN18, and IRX5 as potential key target genes regulating ADCP in LIHC. These genes demonstrated significant correlations with immune infiltration cells, such as M1-type macrophages, and the effectiveness of immunotherapy in LIHC, as well as a close association with clinical pathological staging and patient prognosis. Pan-cancer analysis revealed that CLDN18 was prognostically and immunologically relevant across multiple types of cancer. Validation through tissue and cell samples confirmed that GYPA and CLDN18 were upregulated in liver cancer tissues and cells. Furthermore, in vitro knockdown of CLDN18 inhibited the malignancy capabilities of liver cancer cells.ConclusionWe have identified an ADCP signature in LIHC comprising three genes. Analysis based on a risk scoring model derived from these three genes, coupled with subsequent experimental validation, confirmed the pivotal role of M1-type macrophages in ADCP within LIHC, establishing CLDN18 as a critical ADCP regulatory target in LIHC.

Expanding indications for chronic hepatitis B treatment: Is it really desirable to treat everyone?

Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma. On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030, there is an increasing call to expand the indications for treatment of chronic hepatitis B. Currently, the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the virus. There are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment duration. This editorial addresses key questions about the topic and whether indications for treatment should be expanded.

Hepatitis B: Model Systems and Therapeutic Approaches.

Hepatitis B virus (HBV) infection is a major global health issue and ranks among the top causes of liver cirrhosis and hepatocellular carcinoma. Although current antiviral medications, including nucleot(s)ide analogs and interferons, could inhibit the replication of HBV and alleviate the disease, HBV cannot be fully eradicated. The development of cellular and animal models for HBV infection plays an important role in exploring effective anti-HBV medicine. During the past decades, advancements in several cell culture systems, such as HepG2.2.15, HepAD38, HepaRG, hepatocyte-like cells, and primary human hepatocytes, have propelled the research in inhibiting HBV replication and expression and thus enriched our comprehension of the viral life cycle and enhancing antiviral drug evaluation efficacy. Mouse models, in particular, have emerged as the most extensively studied HBV animal models. Additionally, the present landscape of HBV therapeutics research now encompasses a comprehensive assessment of the virus's life cycle, targeting numerous facets and employing a variety of immunomodulatory approaches, including entry inhibitors, strategies aimed at cccDNA, RNA interference technologies, toll-like receptor agonists, and, notably, traditional Chinese medicine (TCM). This review describes the attributes and limitations of existing HBV model systems and surveys novel advancements in HBV treatment modalities, which will offer deeper insights toward discovering potentially efficacious pharmaceutical interventions.

Strategies to enhance the response of liver cancer to pharmacological treatments.

In contrast to other types of cancers, there is no available efficient pharmacological treatment to improve the outcomes of patients suffering from major primary liver cancers, i.e., hepatocellular carcinoma and cholangiocarcinoma. This dismal situation is partly due to the existence in these tumors of many different and synergistic mechanisms of resistance, accounting for the lack of response of these patients, not only to classical chemotherapy but also to more modern pharmacological agents based on the inhibition of tyrosine kinase receptors (TKIs) and the stimulation of the immune response against the tumor using immune checkpoint inhibitors (ICIs). This review summarizes the effort to develop strategies to overcome this severe limitation, including searching for novel drugs derived from synthetic, semisynthetic, or natural products with vectorial properties against therapeutic targets to increase drug uptake or reduce drug export from cancer cells. Besides, immunotherapy is a promising line of research that is already starting to be implemented in clinical practice. Although less successful than in other cancers, the foreseen future for this strategy in treating liver cancers is considerable. Similarly, the pharmacological inhibition of epigenetic targets is highly promising. Many novel "epidrugs", able to act on "writer", "reader" and "eraser" epigenetic players, are currently being evaluated in preclinical and clinical studies. Finally, gene therapy is a broad field of research in the fight against liver cancer chemoresistance, based on the impressive advances recently achieved in gene manipulation. In sum, although the present is still dismal, there is reason for hope in the non-too-distant future.

Characterization and targeting of serpins alteration in chronic liver disease and hepatocellular carcinoma

Characterization and targeting of serpins alteration in chronic liver disease and hepatocellular carcinoma

Clinical outcomes of transarterial chemoembolization in Child-Turcotte Pugh class A patients with a single small (≤3cm) hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics. This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy. One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8months, P=0.001). Median RFS was 19.1months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2cm) were poor prognostic factors of OS. The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3cm) HCC in CTP class A patients.

The cuproptosis-related gene UBE2D2 functions as an immunotherapeutic and prognostic biomarker in pan-cancer.

Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown. Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis. The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cells、Macrophages M2、CD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers. We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy.

Exploring the role of CDCA4 in liver hepatocellular carcinoma using bioinformatics analysis and experiments.

Liver hepatocellular carcinoma (LIHC) encompasses diverse therapeutic approaches, among which targeted therapy has gained significant prominence in recent years. The identification of numerous targets and the increasing clinical application of targeted drugs have greatly improved LIHC treatment. However, the precise role of CDCA4 (Cell Division Cycle Associated 4), as well as its underlying mechanisms and prognostic implications in LIHC, remains unclear. CDCA4 expression levels in LIHC were analyzed using multiple databases including the cancer genome atlas (TCGA), gene expression profiling interactive analysis (GEPIA), and ULCAN, as well as the datasets E_TABM_36, GSE144269, GSE14520, and GSE54236. The prognostic value of CDCA4 was then evaluated. Subsequently, the association between CDCA4 and immune cells was investigated. Enrichment analysis (GSEA) was utilized to investigate the functional roles and pathways linked to CDCA4. Additionally, the methylation patterns and drug sensitivity of CDCA4 were examined. A predictive model incorporating immune genes related to CDCA4 was developed. The TISCH dataset was used to investigate the single-cell expression patterns of CDCA4. Finally, validation of CDCA4 expression levels was conducted through RT-PCR, Western blotting, and immunohistochemistry. CDCA4 exhibited significant overexpression in LIHC and demonstrated significant correlations with clinical features. High expression of CDCA4 is associated with a poorer prognosis. Analysis of immune infiltration and enrichment revealed its association with the immune microenvironment. Furthermore, its expression is correlated with methylation and mutation patterns. CDCA4 is associated with 19 drugs. Prognostic models utilizing CDCA4 demonstrate favorable effectiveness. T cell subtypes were found to be associated with CDCA4 through single-cell analysis. The conclusive experiment provided evidence of significant upregulation of CDCA4 in LIHC. The high expression of CDCA4 in LIHC is associated with prognostic significance and is highly expressed in T cell subtypes, providing a new therapeutic target and potential therapeutic strategy for LIHC.

Design and synthesis of novel JNK inhibitors targeting liver pyruvate kinase for the treatment of non-alcoholic fatty liver disease and hepatocellular carcinoma

Non-alcoholic fatty liver disease (NAFLD) comprises a broad range of liver disease including hepatocellular carcinoma (HCC) with is no FDA-approved drug. Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP generation in liver presenting a potential target for the treatment of NAFLD. Based on our recent finding of JNK-5A's effectiveness in inhibiting PKLR expression through a drug repositioning pipeline, this study aims to improve its efficacy further. We synthesized a series of JNK-5A analogues with targeted modifications, guided by molecular docking studies. These compounds were evaluated for their activities on PKL expression, cell viability, triacylglyceride (TAG) levels, and the expressions of steatosis-related proteins in the human HepG2 cell line. Subsequently, the efficacy of these compounds was assessed in reducing TAG level and toxicity. Compounds 40 (SET-151) and 41 (SET-152) proved to be the most efficient in reducing TAG levels (11.51 ± 0.90 % and 10.77 ± 0.67 %) and demonstrated lower toxicity (61.60 ± 5.00 % and 43.87 ± 1.42 %) in HepG2 cells. Additionally, all synthesized compounds were evaluated for their anti-cancer properties revealing that compound 74 (SET-171) exhibited the highest toxicity in cell viability with IC50 values of 8.82 µM and 2.97 µM in HepG2 and Huh7 cell lines, respectively. To summarize, compounds 40 (SET-151) and 41 (SET-152) show potential for treating NAFLD, while compound 74 (SET-171) holds potential for HCC therapy.

Dynamic liver volume change in predicting hepatic decompensation and long-term effects of stereotactic body radiation therapy.

This study aimed to investigate the association between liver volume change and hepatic decompensation and compare the risk of hepatic decompensation in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) who underwent stereotactic body radiation therapy (SBRT). A retrospective review of SBRT-treated HCC and compensated LC without HCC patients was conducted. Liver volume was measured using auto-segmentation software on liver dynamic computed tomography scans. The decompensation event was defined as the first occurrence of refractory ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. We evaluated the association between the rate of liver volume decrease and hepatic decompensation and compared decompensation events between the SBRT and LC cohorts using propensity score matching. A total of 138 patients from the SBRT cohort and 488 from the LC cohort were analyzed. The rate of liver volume decrease was associated with the risk of decompensation events in both cohorts. The 3-year rate of decompensation events was significantly higher in the group with a liver volume decreasing rate>7%/year compared with the group with a rate<7%/year. In the propensity score-matched cohort, the 3-year rate of decompensation events after a single session of SBRT was not significantly different from that in the LC cohort. The rate of liver volume decrease was significantly associated with the risk of hepatic decompensation in both HCC patients who received SBRT and LC patients. A single session of SBRT for HCC did not result in a higher decompensation rate compared with LC.

The comprehensive roles of lncRNA FAM99A/FAM99B in hepatocellular carcinoma: Expressions, regulatory mechanisms and functional pathway analysis

AimsThe incidence and mortality of liver hepatocellular carcinoma (LIHC) were increasing year by year. The aim of this study was to investigate the comprehensive roles of lncRNA FAM99A and FAM99B in LIHC. Main methodsAccording to the data of TCGA and GTEx, the expression levels of FAM99A and FAM99B in LIHC were evaluated, and the overall survival (OS), disease-free survival (DFS), immune cell infiltration and tumor stage were analyzed. The subcellular localization of FAM99A and FAM99B in various cancer cell lines was predicted by lncATLAS database. In addition, we also used ENCORI, KEGG, LinkedOmics, Metascape and other databases. It was verified by in vivo and in vitro experiments. Key findingsCompared with adjacent normal tissues, FAM99A and FAM99B were down-regulated in LIHC tissues, and significantly correlated with immune cell infiltration. With the progression of tumor stage and grade, the expression of FAM99A and FAM99B showed a decreasing trend, and the prognosis of patients were also poor. In addition, the biological functions, signaling pathways and protein interactions of FAM99A and FAM99B in LIHC were enriched to study the potential molecular mechanisms. The overlapping RNA binding proteins (RBP) of FAM99A and FAM99B mainly included CSTF2T, BCCIP, RBFOX2 and SF3B4. Finally, experiments showed that overexpression of FAM99A attenuated the proliferation, invasion, colony formation and tumor growth of LIHC cells. SignificanceTaken together, the above studies demonstrated that FAM99A and FAM99B had an inhibitory effect on the progression of LIHC, which might be promising diagnostic biomarkers and therapeutic targets for LIHC patients.

Copper @ eggshell nanocomposite/chitosan gelified carbon paste electrode as an electrochemical biosensor for l-tyrosine analysis as a biomarker in the serum of normal and liver disease patients

L-Tyrosine (L-Tyr), an amino acid, has emerged as a potential biomarker for the detection and monitoring of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). By analysing the serum levels of L-Tyr, healthcare professionals can gain insights into the progression and development of these liver diseases. The utilization of L-Tyr as a biomarker holds potential for early detection and timely intervention, improving patient outcomes and treatment options. In this study we developed a novel nanocomposite based on eggshell waste and copper nanoparticles to modify carbon paste electrode (CPE) using chitosan gel as a binder for sensitive estimation of L-Tyr in human serum samples. The use of chitosan gel avoids the insulating effect of paraffin oil that was usually used for fabrication of CPE and enhance the sensitivity and selectivity of the modified electrode. Square wave voltammetry (SWV) was used to optimize the electrochemical parameters of the oxidation of L-Tyr onto the surface of the fabricated electrode (CuNPs@ESh/CS/CPE). The prepared composite was characterized using X-ray diffraction (XRD), Fourier Transform − Infrared spectroscopy (FT-IR), UV–VIS spectroscopy and scan electron microscopy (SEM) and electrochemical impedence spectroscopy (EIS). The fabricated biosensor could estimate L-Tyr levels in controls, LC and HCC patients’ serum with high accuracy and sensitivity. The obtained results demonstrated the presence of significant difference in L-Tyr levels in the three studied groups. This indicates that L-Tyr amino acid may serve as a crucial biomarker for the evaluation of such liver diseases.

Long-term results of liver thermal ablation in patients with hepatocellular carcinoma and colorectal cancer liver metastasis regarding spatial features and tumor-specific variables

Colorectal cancer liver metastasis (CRLM) and hepatocellular carcinoma (HCC) are widely treated using microwave and radiofrequency ablation. Local tumor progression (LTP) may develop depending on the shortest vascular distance and large lesion diameter. This study aims to explore the effect of these spatial features and to investigate the correlation between tumor-specific variables and LTP. This is a retrospective study covering the period between January 2007 and January 2019. One hundred twenty-five patients (CRLM: HCC: 64:61) with 262 lesions (CRLM: HCC: 142:120) were enrolled. The correlation between LTP and the variables was analyzed using the chi-square test, Fischer's exact test, or the Fisher-Freeman-Halton test where applicable. The local progression-free survival (Loc-PFS) was analyzed using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to identify prognostic factors. Significant correlations were observed for LTP in both CRLM and HCC at a lesion diameter of 30-50 mm (P = 0.019 and P < 0.001, respectively) and SVD of ≤3 mm (P < 0.001 for both). No correlation was found between the ablation type and LTP (CRLM: P = 0.141; HCC: P = 0.771). There was no relationship between residue and the ablation type, but a strong correlation with tumor size was observed (P = 0.127 and P < 0.001, respectively). In CRLM, LTP was associated with mutant K-ras and concomitant lung metastasis (P < 0.001 and P = 0.003, respectively). In HCC, a similar correlation was found for Child-Pugh B, serum alpha-fetoprotein (AFP) level of >10 ng/mL, predisposing factors, and moderate histopathological differentiation (P < 0.001, P = 0.008, P = 0.027, and P < 0.001, respectively). In CRLM, SVD of ≤3 mm proved to be the variable with the greatest negative effect on Loc-PFS (P = 0.007), followed by concomitant lung metastasis (P = 0.027). In HCC, a serum AFP level of >10 ng/mL proved to be the variable with the greatest negative effect on Loc-PFS (P = 0.045). In addition to the lesions' spatial features, tumor-specific variables may also have an impact on LTP.

Low preoperative serum uric acid is associated with early acute kidney injury after living donor liver transplantation.

Liver transplantation is treatment option for patients with end stage liver disease and hepatocellular carcinoma. Renal function deterioration significantly impacts the survival rates of liver recipients, and serum uric acid (SUA) is associated with both acute and chronic renal function disorders. Thus, our study aimed to assess the relationship and predictive value of preoperative SUA level and postoperative acute kidney injury (AKI) in living donor liver transplantation (LDLT). We conducted a prospective observational study on 87 patients undergoing LDLT. Blood samples were collected immediately prior to LDLT, and renal function status was followed up for 3 consecutive days postoperatively. Low SUA levels (cutoff value 4.15 mg/dL) were associated with a high risk of early post-transplantation AKI. The area under the curve was 0.73 (sensitivity, 79.2%; specificity, 59.4%). Although not statistically significant, there were no deaths in the non-AKI group but two in the early AKI group secondary to liver graft dysfunction in addition to early AKI within the first month after LDLT. AKI after liver transplantation may lead to a deterioration of patient status and increased mortality rates. We determined low preoperative SUA levels as a possible risk factor for early postoperative AK.