World J Hepatol [JOURNAL]
Sun
200 papers
Systemic treatment of liver cancer: Current status and future perspectives.
Li CB, Ning YT, Shen NY … +3 more , Wang B, Xiao H, Luo G
World J Hepatol · 2025 Jul · PMID 40747233 · Full text
Primary liver cancer, a common malignant tumor of the digestive tract, ranks fifth in global cancer incidence and shows high morbidity and mortality. Liver cancer patients who are diagnosed early have the option of surgi...
Primary liver cancer, a common malignant tumor of the digestive tract, ranks fifth in global cancer incidence and shows high morbidity and mortality. Liver cancer patients who are diagnosed early have the option of surgical resection, which offers the possibility of a radical cure. However, due to the insidious disease onset, most patients are diagnosed in the intermediate or advanced stages, and surgery is no longer a viable option. Therefore, systemic treatment options play an essential role in the management of advanced liver cancer. These treatments aim to suppress disease progression, prolong survival, and improve quality of life. This article reviews the latest research in the field of systemic therapy of liver cancer, including molecular targeted therapy, immunotherapy, and their combination strategies. At first, the application and efficacy of first-line molecularly targeted drugs are discussed. Next, the revolutionary advances in immune checkpoint blockers are presented. Subsequently, the clinical effects of the combination of molecularly targeted therapy and immunotherapy are analyzed. Finally, this article summarizes the current challenges faced by the systemic treatment of liver cancer and introduces the prospect of future treatment trends.
Evaluating serum extra spindle pole bodies-like 1 protein p53 antibody for hepatitis B virus-related hepatocellular carcinoma diagnosis.
Feng YF, Zhou HK, Hu BB … +8 more , Wang H, Liang HK, Wei L, Li QM, Su TM, Yin QB, Su MH, Jiang JN
World J Hepatol · 2025 Jul · PMID 40747232 · Full text
BACKGROUND: Hepatitis B virus (HBV) infection is a leading cause of global hepatocellular carcinoma (HCC). Conventional biomarkers such as alpha-fetoprotein (AFP) demonstrate suboptimal sensitivity and specificity. Emerg...
BACKGROUND: Hepatitis B virus (HBV) infection is a leading cause of global hepatocellular carcinoma (HCC). Conventional biomarkers such as alpha-fetoprotein (AFP) demonstrate suboptimal sensitivity and specificity. Emerging evidence suggests that serum extra spindle pole bodies like 1 (ESPL1) protein and p53 antibody may improve diagnostic accuracy. AIM: To assess and compare the diagnostic performance of serum ESPL1 protein and p53 antibody in HBV-related HCC (HBV-HCC). METHODS: This case-control study from the First Affiliated Hospital of Guangxi Medical University enrolled 30 patients with chronic hepatitis B (CHB), 30 with HBV-related liver cirrhosis (HBV-LC), 55 with HBV-HCC, and 30 healthy controls. Serum ESPL1 protein and p53 antibody levels were quantified ELISA. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis, including sensitivity, specificity, and correlation with AFP. RESULTS: Serum ESPL1 protein levels progressively increased across disease stages (CHB: 89.9 ng/L; HBV-LC: 188.83 ng/L; HBV-HCC: 317.63 ng/L), with a significantly higher area under the ROC curve (AUC = 0.917) than either p53 antibody (AUC = 0.725) or AFP (AUC = 0.678). p53 antibody levels were significantly elevated only in the HBV-HCC group. ESPL1 demonstrated superior sensitivity and concordance with histopathological findings. A significant correlation between ESPL1 and p53 antibody levels was observed exclusively in the HBV-HCC group ( = 0.320, = 0.017), suggesting potential interplay in malignant transformation. CONCLUSION: Serum ESPL1 protein, a promising biomarker for early HBV-HCC detection, outperforms p53 antibody in diagnostic reliability. Higher ESPL1 levels correlate with increased HCC risk in chronic HBV patients.
Deciphering the oncogenic role of Rac family small GTPase 3 in hepatocellular carcinoma through multiomics integration.
Liu R, Li JC, Li SD … +5 more , Li JD, He RQ, Chen G, Feng ZB, Wei JL
World J Hepatol · 2025 Jul · PMID 40747231 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) remains a lethal malignancy due to its molecular complexity and chemoresistance. Rac family small GTPase 3 (RAC3), a tumorigenic GTPase understudied in HCC, drives recurrence E...
BACKGROUND: Hepatocellular carcinoma (HCC) remains a lethal malignancy due to its molecular complexity and chemoresistance. Rac family small GTPase 3 (RAC3), a tumorigenic GTPase understudied in HCC, drives recurrence E2F transcription factor 1 (E2F1)-mediated transcriptional activation. This study integrates multiomics and clustered regularly interspaced short palindromic repeats (CRISPR) screening to delineate RAC3's roles. RAC3 overexpression correlates with advanced HCC and patient age, while its knockout suppresses proliferation. Mechanistically, RAC3 dysregulates cell-cycle checkpoints through E2F1 binding. Pharmacological RAC3 inhibition disrupts tumor growth and synergizes with chemotherapy to overcome resistance. AIM: To explore RAC3's expression, clinical links, and HCC mechanisms multiomics and functional genomics. METHODS: Multiomic integration of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and Genotype-Tissue Expression datasets was performed to analyze RAC3 mRNA expression. Immunohistochemistry quantified RAC3 protein in 108 HCC/adjacent tissue pairs. Kaplan-Meier/Cox regression assessed prognostic significance using TCGA data. CRISPR screening validated RAC3's necessity for HCC proliferation. Functional enrichment identified associated pathways; hTFtarget/JASPAR predicted transcription factors, validated chromatin immunoprecipitation sequencing (ChIP-seq). RESULTS: RAC3 exhibited significant mRNA and protein overexpression in HCC tissues, which was correlated with advanced tumor stages and reduced overall survival rates (hazard ratio = 1.82, 95%CI: 1.31-2.53). Genetic ablation of RAC3 suppressed HCC cell proliferation across 16 cell lines. Pathway analysis revealed RAC3's predominant involvement in cell-cycle regulation, DNA replication, and nucleocytoplasmic transport. Mechanistic investigations identified E2F1 as a pivotal upstream transcriptional regulator, and ChIP-seq analysis validated its direct binding to the RAC3 promoter region. These findings suggest that RAC3 drives HCC progression through E2F1-mediated cell-cycle dysregulation. CONCLUSION: This study identified RAC3 as a key HCC oncogenic driver; its overexpression links to poor prognosis/resistance. Targeting the RAC3/E2F1 axis offers a new therapy, which highlights RAC3 as a biomarker/target.
Liver stiffness measurements in patients with metabolic dysfunction-associated steatotic liver disease: Updates on the method effectiveness and perspectives.
Sukocheva O, Ow TW, Harding D … +2 more , Le Mire M, Tse E
World J Hepatol · 2025 Jul · PMID 40747230 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most widespread chronic liver disease signified by serious life-threatening conditions. The prevalence of MASLD increases along the growing prevalen...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most widespread chronic liver disease signified by serious life-threatening conditions. The prevalence of MASLD increases along the growing prevalence in obesity and metabolic syndrome. To minimize costs and complications, non-invasive diagnostic tools, including transient elastography (TE), were introduced for assessment of MASLD. TE measures liver stiffness (LS), a clinical marker for the diagnosis of liver fibrosis and cirrhosis. LS measurements are based on ultrasound wave imaging and quantification. Vibration-controlled TE, including FibroScan, is commonly used TE methods which can accurately identify the degree of liver fibrosis and cirrhosis progression. TE was reported to predict the progression towards hepatocellular carcinoma, portal hypertension, and varices. However, the accuracy of LS diagnostics alone in patients with MASLD remains controversial. TE measurements have several limitations, including inadequate precision due to focal liver lesions, cholestasis, inflammation, and other pathological and anatomical factors which can lead to the stiffness variability. Overestimations of TE readings were reported in obese patients with body mass index (BMI) over 30 kg/m, and older patients with ascites, diabetes, or hypertension. Not all MASLD patients have high BMI. The prevalence of obesity among MASLD patients varies worldwide, indicating the urgent need for comprehensive diagnostic tools. In patients with MASLD, improved diagnostic accuracy has been demonstrated by combining LS measurements with other blood test-based scores and simple clinical parameters (agile scores based on age, sex, platelet count, aminotransferases, and diabetes). This study reviews the limitations of TE-based diagnostics and discusses the combined scoring algorithm. In conclusion, the sequence of LS measurements along assessment of other important clinical markers is an effective, low-cost, reliable tool to identify and monitor fibrosis progression in MASLD.
Molecular tumor boards in pancreatic cancer with liver metastasis: A case report.
Yan Y, Ren ZZ, Wang WY … +2 more , Tang J, Zhang YW
World J Hepatol · 2025 Jul · PMID 40747229 · Full text
BACKGROUND: Pancreatic cancer has limited treatment options and poor prognosis owing to late diagnosis and aggressive biology. Current therapies include surgery, chemotherapy, and radiation; however, the outcomes remain...
BACKGROUND: Pancreatic cancer has limited treatment options and poor prognosis owing to late diagnosis and aggressive biology. Current therapies include surgery, chemotherapy, and radiation; however, the outcomes remain suboptimal. Molecular tumor boards (MTB) enhance personalized treatment by analyzing genomic data to identify targetable mutations and recommend precise therapies. CASE SUMMARY: A 45-year-old male presented with jaundice in December 2022. Initial investigations revealed a pancreatic head mass and liver metastases; a liver biopsy confirmed moderately differentiated adenocarcinoma. The patient received multimodal therapies, including gemcitabine, albumin-bound paclitaxel, nimotuzumab, and proton radiotherapy, which initially resulted in significant shrinkage of the pancreatic lesion and a reduction in liver metastases. However, the disease eventually progressed, prompting further evaluation at our MTB clinic. Genetic testing revealed a homologous recombination deficiency (HRD) score of 58 (HRD-positive) and a pathogenic BRCA2 mutation (p.T3033fs), suggesting sensitivity to PARP inhibitors and platinum-based therapies. Based on these findings, the patient was administered olaparib, which, combined with immunotherapy (tislelizumab, atezolizumab) and hepatic arterial infusion chemotherapy (5-fluorouracil + leucovorin + oxaliplatin regimen), led to further stabilization and partial reduction of liver metastases. This case underscores the positive role of the MTB model in interpreting genetic profiles and guiding personalized treatment strategies for such patients. CONCLUSION: The patient's clinical course highlights the potential of MTB in providing significant benefits for advanced pancreatic cancer with liver metastases.
Deciphering the role of in liver diseases: Mechanisms, clinical relevance, and emerging therapeutic opportunities.
Boonto T, Ariyachet C
World J Hepatol · 2025 Jul · PMID 40747228 · Full text
Liver diseases are progressive conditions driven by multiple factors, including molecular regulators such as nonprotein-coding RNAs, which orchestrate genetic and epigenetic processes across various biological levels. Lo...
Liver diseases are progressive conditions driven by multiple factors, including molecular regulators such as nonprotein-coding RNAs, which orchestrate genetic and epigenetic processes across various biological levels. Long noncoding RNAs (lncRNAs), RNA molecules longer than 200 nucleotides, have been identified as key modulators in both cancerous and noncancerous liver diseases. Among them, (TUG1), one of the earliest discovered lncRNAs, has emerged as a tumor promoter in hepatocellular carcinoma. Functionally, TUG1 exerts its regulatory effects primarily through microRNA sponging as a competing endogenous RNA while also exhibiting protein-binding capabilities that suggest additional roles in both transcriptional and posttranscriptional regulation. Furthermore, evidence suggests that dysregulation of TUG1 is closely linked to the development and progression of liver diseases. This review explores the key characteristics, mechanisms, and signaling pathways through which TUG1 affects liver disease, offering fresh insights into potential therapeutic directions and new avenues for future TUG1-related research.
Are we standing on the shifting sands of post-transplant metabolic-associated steatotic liver disease?
Zatta R, da Silva LS, Felga G … +1 more , Pimentel CF
World J Hepatol · 2025 Jul · PMID 40747227 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the predominant global cause of chronic liver disease and represents a major indication for liver transplantation. Post-transplant MASLD manifests a...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the predominant global cause of chronic liver disease and represents a major indication for liver transplantation. Post-transplant MASLD manifests as recurrent disease in nearly all recipients by five years post-transplantation, while de novo MASLD shows variable incidence (18%-78%). Although histologically similar, recurrent MASLD follows a more aggressive trajectory, with accelerated fibrosis and cirrhosis. Metabolic disturbances, immunosuppression regimens, donor-related factors, and chronic inflammation synergistically contribute to disease pathogenesis. The disorder not only compromises graft function but is also associated with elevated cardiovascular and overall morbidity, and malignancy risk. Despite advancements in noninvasive diagnostics, histopathology remains essential for definitive diagnosis and prognostic stratification. Management should prioritize metabolic optimization, lifestyle intervention, and tailored immunosuppressive regimens. Glucagon-like peptide-1 receptor agonists represent a promising therapeutic avenue. However, the absence of standardized, transplant-specific guidelines is a significant limitation. Further research is necessary to define diagnostic criteria, risk stratification, and targeted therapy to improve graft survival and patient outcomes.
Tumor necrosis factor alpha-induced protein 3: A key biomarker for response to ursodeoxycholic acid in primary biliary cholangitis.
Zang B, Li JX, Liu QX … +8 more , Yao Y, Li H, Wang Y, Wang JG, Yang YF, Liang RW, Xin XR, Liu B
World J Hepatol · 2025 Jul · PMID 40747226 · Full text
BACKGROUND: The pathogenesis of primary biliary cholangitis (PBC) remains unclear. Ursodeoxycholic acid (UDCA) is the only first-line clinical treatment, but approximately 40% of patients exhibit a poor response. AIM: To...
BACKGROUND: The pathogenesis of primary biliary cholangitis (PBC) remains unclear. Ursodeoxycholic acid (UDCA) is the only first-line clinical treatment, but approximately 40% of patients exhibit a poor response. AIM: To identify novel biomarkers for PBC to predict the efficacy of UDCA and enhance treatment. METHODS: Microarray expression profiling datasets were downloaded from the Gene Expression Omnibus and analyzed to identify differentially expressed genes between PBC patients and healthy controls. Immunohistochemistry was performed to validate key genes in liver tissues of the participants. Logistic regression was employed to evaluate prognostic risk factors, receiver operating characteristic curves were used to assess predictive performance, and correlations between key genes and clinicopathological characteristics were analyzed. RESULTS: By bioinformatic analysis, 13 genes primarily associated with the progression of PBC were identified, and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) was selected for further investigation. Then expression of TNFAIP3 in PBC patients was significantly elevated compared to healthy controls on immunohistochemistry ( < 0.0001). Multivariate Cox regression analysis indicated that both TNFAIP3 and fatigue were independent risk factors for response to UDCA in PBC patients ( < 0.05). The area under the curve for TNFAIP3 and fatigue were 0.691 and 0.704, respectively, while their combination showed a significantly higher area under the curve of 0.848. The expression of TNFAIP3 was also correlated with age, albumin, total bilirubin, alkaline phosphatase and splenomegaly ( < 0.05). CONCLUSION: TNFAIP3 and fatigue are independent risk factors for response to UDCA in Chinese patients with PBC. TNFAIP3 may be a potential biomarker or therapeutic target for PBC. These findings offer new insights into the pathogenesis of PBC.
Challenges of infections post-liver transplantation: Insights and future directions.
Li J, Wang W
World J Hepatol · 2025 Jul · PMID 40747225 · Full text
infections (KPIs), particularly carbapenem-resistant (CRKP), pose significant challenges in liver transplantation (LT) recipients, with high morbidity and mortality. Guo 's study highlights risk factors, such as elevate...
infections (KPIs), particularly carbapenem-resistant (CRKP), pose significant challenges in liver transplantation (LT) recipients, with high morbidity and mortality. Guo 's study highlights risk factors, such as elevated day-one alanine aminotransferase levels and prolonged catheterization, and identifies polymyxin B and ceftazidime/avibactam as effective treatments. However, limitations like the absence of pre-transplant colonization data and host-pathogen interaction insights highlight the need for enhanced strategies. Future directions should include routine CRKP colonization surveillance, immune and genomic profiling, and the development of novel therapeutics. By integrating these approaches, we can improve the prevention, diagnosis, and treatment of KPIs in LT patients.
New hope in treating progressive familial intrahepatic cholestasis in children.
Mkarem LE, Batika MAH, Bitar R
World J Hepatol · 2025 Jul · PMID 40747224 · Full text
Progressive familial intrahepatic cholestasis (PFIC) is a group of rare, inherited cholestatic liver disorders presenting in infants and children and are associated with impaired bile flow (, cholestasis), pruritus and p...
Progressive familial intrahepatic cholestasis (PFIC) is a group of rare, inherited cholestatic liver disorders presenting in infants and children and are associated with impaired bile flow (, cholestasis), pruritus and progressive liver disease. Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive. The impaired bile flow within the liver, leads to accumulation in the liver and inflammation. Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive. A potential for reducing pathologic bile accumulation in the liver is surgical biliary diversion, with an aim to interrupt the enterohepatic circulation. These procedures have demonstrated a positive effect in PFIC by normalizing serum bile acids, reducing pruritus and liver injury and improving the patient quality of life. Nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter (IBAT). IBAT inhibition has demonstrated efficacy in reducing serum bile acids and pruritus. We aim to present the 13 types of PFIC and the current evidence on the use of IBAT inhibitors in treating children with PFIC.
Evolving therapeutic landscape of primary biliary cholangitis: A review.
Mitchell NE, Chan SY, Jerez Diaz D … +3 more , Ansari N, Lee J, Twohig P
World J Hepatol · 2025 Jul · PMID 40747223 · Full text
Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction, leading to fibrosis, cirrhosis, and eventual liver failure. Over the past two decade...
Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction, leading to fibrosis, cirrhosis, and eventual liver failure. Over the past two decades, significant advancements have paved the way for novel therapeutic strategies. Ursodeoxycholic acid (UDCA) has been the cornerstone of PBC management, improving survival and delaying disease progression in most patients. However, up to 40% of patients demonstrate an inadequate response to UDCA, necessitating additional treatment options. Obeticholic acid (OCA), a farnesoid X receptor agonist, has emerged as a second-line therapy, showing efficacy in reducing alkaline phosphatase levels and improving liver biochemistry. Beyond UDCA and OCA, a new wave of therapeutic agents are reshaping the PBC landscape. These include fibrates, peroxisome proliferator-activated receptor agonists and novel immunomodulatory drugs aimed at reducing autoimmune-mediated liver injury. Bile acid transport inhibitors, anti-fibrotic agents, and gut microbiome-targeted therapies are also under investigation, offering hope for personalized treatment approaches. This review highlights the evolution of PBC therapy, emphasizing the unmet needs of patients with refractory disease and the potential of emerging therapies to improve outcomes. As the therapeutic landscape continues to expand, optimizing treatment strategies through precision medicine holds the promise of transforming the management of PBC.
Microbiome dysbiosis and immune checkpoint inhibitors: Dual targets in Hepatocellular carcinoma management.
Pamungkas KMN, Lesmana Dewi PIS, Alamsyah AZ … +4 more , Dewi NLPY, Dewi NNGK, Mariadi IK, Sindhughosa DA
World J Hepatol · 2025 Jul · PMID 40747222 · Full text
Hepatocellular carcinoma (HCC), a primary malignancy of the liver and leading cause of cancer-related mortality worldwide, poses substantial therapeutic challenges, particularly in advanced and unresectable stages. Immun...
Hepatocellular carcinoma (HCC), a primary malignancy of the liver and leading cause of cancer-related mortality worldwide, poses substantial therapeutic challenges, particularly in advanced and unresectable stages. Immune checkpoint inhibitors (ICIs) have emerged as critical therapeutic agents, targeting immune checkpoint pathways to restore antitumor immune responses. Combinations such as atezolizumab (anti-programmed cell death ligand 1 with bevacizumab (anti-vascular endothelial growth factor), as well as antibodies directed against cytotoxic T-lymphocyte associated protein 4 and programmed cell death protein 1 (, ipilimumab and nivolumab), have demonstrated improved clinical outcome in selected patients. However, the overall efficacy of ICIs remains hindered by variable response rate and primary or acquired resistance. Recent evidence suggests that the gut microbiome plays a pivotal role in modulating host immune responses and may significantly influence the therapeutic efficacy of ICIs. Dysbiosis within the gut-liver axis has been implicated not only in pathogenesis and progression of HCC but also diminishing immunotherapy effectiveness. Emerging studies highlight the potential of microbiome-targeted interventions including dietary modulation, prebiotics, probiotics, and fecal microbiota transplantation to enhance ICIs responsiveness. This review explores the evolving interplay between the gut microbiota and immunotherapy in HCC, with a focus on microbiome-based strategies aimed at optimizing clinical outcomes.
Three-year outcomes of tumor necrosis factor alpha inhibitor therapy in rheumatoid arthritis patients with elevated liver enzymes.
Duggal S, Kattamuri L, Sairam S
World J Hepatol · 2025 Jul · PMID 40747221 · Full text
BACKGROUND: Elevated liver enzymes in rheumatoid arthritis (RA) are often attributed to multiple factors including disease activity and treatment-related adverse effects. Tumor necrosis factor inhibitors (TNFi) have show...
BACKGROUND: Elevated liver enzymes in rheumatoid arthritis (RA) are often attributed to multiple factors including disease activity and treatment-related adverse effects. Tumor necrosis factor inhibitors (TNFi) have shown mixed effects on liver function, with varying safety profiles among agents. AIM: To evaluate the hepatic safety of TNFi therapy-etanercept and adalimumab-in RA patients with elevated liver enzymes. METHODS: A retrospective chart review was conducted for RA patients with elevated liver enzymes receiving TNFi at a single center between January 1, 2019, and September 30, 2024. Out of the patients screened, 9 met the inclusion criteria. Trends in liver enzymes, fibrosis-4 (FIB-4) score, and changes in the Child-Pugh class were analyzed at 1-year and 3-year follow-up periods. RESULTS: Among 9 patients (4 on adalimumab, 5 on etanercept), the median age was 56 years [interquartile range (IQR): 49.5-64.5 years], 77.8% were female, and the median body mass index was 36.99 kg/m² (IQR: 30.95-43.43 kg/m²). Median baseline FIB-4 was 1.25 (IQR: 1.02-1.65), with no cirrhosis observed at baseline. Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels declined consistently, with significant reductions from baseline to 3 years ( = 0.003). FIB-4 scores also significantly decreased ( = 0.003), while albumin, bilirubin, and Child-Pugh class remained stable at the 3-year follow-up. At 3 years, 66.7% achieved RA remission ( = 0.03). CONCLUSION: TNFi therapy (adalimumab or etanercept) was associated with significant improvement in liver enzymes and FIB-4 without hepatic decompensation, supporting its safety in our cohort of RA patients with liver involvement. Larger prospective studies are warranted to further validate these findings.
Autoimmune hepatitis with syncytial giant cells in chronic lymphocytic leukemia: A case report and literature review.
Giacomelli M, Carotti S, Vozella F … +7 more , Pagliei F, Taffon C, Baiocchini A, Gambaro FL, Picardi A, Vespasiani-Gentilucci U, Galati G
World J Hepatol · 2025 Jul · PMID 40747220 · Full text
BACKGROUND: Hepatic manifestations in chronic lymphocytic leukemia (CLL) are common: Elevation of liver enzymes frequently occurs, and differential diagnosis is often challenging. Liver infiltration by leukemic cells, pr...
BACKGROUND: Hepatic manifestations in chronic lymphocytic leukemia (CLL) are common: Elevation of liver enzymes frequently occurs, and differential diagnosis is often challenging. Liver infiltration by leukemic cells, primary and secondary hepatic malignancies, drug-induced hepatotoxicity, immunological disorders, and infections have been reported. Nevertheless, syncytial giant cell hepatitis (GCH) as a manifestation of autoimmune hepatitis in patients with CLL is an extremely rare condition, currently reported only in anecdotal cases. CASE SUMMARY: Here, we report the case of a 62-year-old Caucasian woman affected by CLL, who developed GCH with peculiar histopathological features. The patient was evaluated for abnormal liver test results. Liver histology revealed significant inflammatory lymphomononuclear infiltrates with a plasma cell component, widespread syncytial changes in the hepatocytes with gigantocellular features, hepatocyte rosettes, and the typical feature of emperipolesis, consistent with a diagnosis of GCH. The patient was treated with corticosteroids and mycophenolate mofetil, resulting in a complete biochemical response. CONCLUSION: Early histological diagnosis of GCH is crucial in patients with CLL, with mycophenolate mofetil representing a promising treatment option.
Link between type 2 diabetes mellitus and hepatocellular carcinoma.
Giri S, Mukhuty A, Mondal SA … +4 more , Sahoo J, Roy A, Kamalanathan S, Naik D
World J Hepatol · 2025 Jul · PMID 40747219 · Full text
Type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC) have a strong bidirectional relationship. T2DM increases the risk of developing HCC, mainly through the nonalcoholic steatohepatitis pathway, but a signi...
Type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC) have a strong bidirectional relationship. T2DM increases the risk of developing HCC, mainly through the nonalcoholic steatohepatitis pathway, but a significant proportion of patients develop HCC without developing cirrhosis. The identification of HCC in T2DM patients is difficult considering the low incidence of HCC and the high prevalence of T2DM. However, considering the alarming increase in the incidence of diabetes mellitus in the global population, effective strategies are urgently needed to identify patients at high risk. Nonetheless, various classes of drugs, such as sodium-glucose cotransporter-2 inhibitors and incretin analogs, may be promising for reducing the risk of nonalcoholic steatohepatitis and HCC development in T2DM patients in the future. In this review, we discuss all these facets of the relationship between HCC and T2DM, and we summarize future directions.
Role of mac-2 binding protein glycosylation isomer in predicting fibrosis in patients with metabolic dysfunction-associated steatotic liver disease.
Pham TTT, Ho DT, Pham C … +6 more , Phan H, Phu B, Nguyen T, Nguyen D, Phan HT, Nguyen KM
World J Hepatol · 2025 Jul · PMID 40747218 · Full text
BACKGROUND: Mac-2 binding protein glycosylation isomer (M2BPGi) serves as a marker of activated hepatic stellate cells and as such holds potential as a biomarker for liver fibrosis. In Viet Nam, metabolic dysfunction-ass...
BACKGROUND: Mac-2 binding protein glycosylation isomer (M2BPGi) serves as a marker of activated hepatic stellate cells and as such holds potential as a biomarker for liver fibrosis. In Viet Nam, metabolic dysfunction-associated steatotic liver disease (MASLD) is rising in prevalence and there is an urgent need for better clinical management, particularly in early detection methods that will improve overall prognosis. AIM: To examine M2BPGi cut-off values for staging liver fibrosis in patients with MASLD and risk factors associated with disease progression. METHODS: A total of 301 individuals with ultrasound-confirmed or FibroScan-confirmed diagnosis of fatty liver were enrolled in the study. The participants were stratified according to fibrosis stage, measured magnetic resonance elastography. M2BPGi, Fibrosis-4 (FIB-4) Index score, and routine parameters of liver function were assessed to statistically investigate the correlation of M2BPGi levels in various fibrosis stages and to identify risk factors associated with fibrosis severity. RESULTS: M2BPGi levels positively correlated with fibrosis stages, with cut-off indexes of 0.57 for F0-1, 0.68 for F2-3, and 0.78 for F4. M2BPGi levels in the F0-1 group were significantly different from those in both the F2-3 group ( = 0.038) and the F4 group ( = 0.0051); the F2-3 and F4 groups did not show a significant difference ( = 0.39). Females exhibited significantly higher M2BPGi levels than males for all fibrosis stages, particularly in the F2-3 group ( = 0.01) and F4 group ( = 0.0006). In the F4 (cirrhosis) group, individuals with diabetes had significantly higher M2BPGi levels than those without. M2BPGi, hemoglobin A1c, and FIB-4 score were identified as independent risk factors for greater fibrosis and cirrhosis. CONCLUSION: M2BPGi levels varied significantly throughout fibrosis progression, from early MASLD to cirrhosis, with sex correlation. M2BPGi holds promise as an early biomarker for fibrosis characterization in MASLD adult patient populations.
Heart rate variability in the clinical assessment of patients with chronic liver disease.
Bustos N, Giubergia F, Mora C … +6 more , Lara C, Urzúa Á, Cattaneo M, Poniachik J, Vera DB, Gajardo AI
World J Hepatol · 2025 Jul · PMID 40747217 · Full text
Autonomic dysfunction (AD) is frequently observed in cirrhotic patients and is associated with poor clinical outcomes and prognoses. Heart rate variability (HRV), a noninvasive tool for assessing autonomic nervous system...
Autonomic dysfunction (AD) is frequently observed in cirrhotic patients and is associated with poor clinical outcomes and prognoses. Heart rate variability (HRV), a noninvasive tool for assessing autonomic nervous system balance, has been extensively studied in a variety of conditions, including chronic liver disease (CLD); however, no recent reviews have focused on its role in CLD. This article examines the mechanisms of AD in CLD and the foundation for HRV assessment, highlighting its diagnostic, prognostic, and therapeutic applications in CLD, including liver transplantation (LT). Changes in HRV, particularly in patients with cirrhotic complications, and its prognostic significance throughout the natural history of CLD are summarized. We show that HRV is consistently reduced in CLD patients, reflecting AD, and is inversely correlated with liver disease severity. Also, low HRV is associated with complications such as hepatic encephalopathy, ascites, and portal hypertension. Moreover, evidence indicates that reduced HRV is an independent risk factor for mortality and circulatory instability in CLD. Furthermore, treatment with beta-blockers and LT improves HRV, underscoring its potential role in patient management. While further studies are needed, HRV emerges as a promising tool for the comprehensive evaluation and clinical management of patients with CLD, offering insights into disease progression and therapeutic response.
Advancing therapeutic vaccines for chronic hepatitis B: Integrating reverse vaccinology and immunoinformatics.
Naully PG, Tan MI, El Khobar KE … +2 more , Sukowati CHC, Giri-Rachman EA
World J Hepatol · 2025 Jul · PMID 40747216 · Full text
Current treatments for chronic hepatitis B (CHB) are lifelong, often accompanied by side effects and the risk of drug resistance, highlighting the urgent need for alternative therapies such as therapeutic vaccines. Howev...
Current treatments for chronic hepatitis B (CHB) are lifelong, often accompanied by side effects and the risk of drug resistance, highlighting the urgent need for alternative therapies such as therapeutic vaccines. However, challenges such as selecting appropriate antigens and addressing multiple hepatitis B virus (HBV) genotypes hinder the development of these vaccines. One approach to overcoming these challenges is reverse vaccinology (RV) combined with immunoinformatics. RV uses computational methods to identify antigens from pathogen genetic information, including genomic and proteomic data. These methods have helped researchers identify conserved epitopes across bacterial strains or viral species, including multiple HBV genotypes. Computational tools, such as epitope mapping algorithms, molecular docking analysis, molecular dynamics simulations, and immune response simulations, enable key epitope identification, predict vaccine candidates' binding potential to immune cell receptors, and forecast the immune response. Together, these approaches streamline therapeutic vaccine design for CHB, making it faster, more cost-effective, and accurate. This review aims to explore the potential role of RV and immunoinformatics in advancing therapeutic vaccine design for CHB.
Toward non-invasive assessment strategies in autoimmune hepatitis.
Jerez Diaz D, Twohig P
World J Hepatol · 2025 Jul · PMID 40747215 · Full text
In this article, we comment on the article by Peta . This study evaluates the diagnostic performance of FibroTest-Actitest, transient elastography, and the fibrosis-4 index against a histological reference. Using the Obu...
In this article, we comment on the article by Peta . This study evaluates the diagnostic performance of FibroTest-Actitest, transient elastography, and the fibrosis-4 index against a histological reference. Using the Obuchowski measure, the authors demonstrate that FibroTest and vibration-controlled transient elastography outperform the fibrosis-4 index in detecting fibrosis. Additionally, Actitest offers superior estimation of inflammatory activity compared to conventional biomarkers. Assessing liver fibrosis is crucial for managing autoimmune hepatitis (AIH), yet reliance on invasive liver biopsy remains higher than in other liver diseases. This is partly due to more complex diagnostic criteria for AIH, the lack of standardized scoring for non-invasive testing, and the presence of inflammation, which can lead to falsely elevated results with non-invasive tests. A Bayesian latent class model further supports the reliability of these non-invasive tests, highlighting their potential to complement biopsy, particularly for long-term disease monitoring. These findings underscore the importance of non-invasive diagnostics in optimizing AIH management.
Triglyceride-glucose-waist circumference index: A powerful tool for metabolic dysfunction-associated steatotic liver disease.
Priego-Parra BA, Román-Calleja BM, Gallego-Duran R … +3 more , Gracia-Sancho J, Velarde Ruiz-Velasco JA, Remes-Troche JM
World J Hepatol · 2025 Jul · PMID 40747214 · Full text
The search for reliable biomarkers to predict metabolic dysfunction-associated steatotic liver disease (MASLD) remains a key research focus. Traditional anthropometric parameters, such as triglycerides, glucose, and wais...
The search for reliable biomarkers to predict metabolic dysfunction-associated steatotic liver disease (MASLD) remains a key research focus. Traditional anthropometric parameters, such as triglycerides, glucose, and waist circumference (WC), have proven to be robust tools for diagnosing, stratifying, and predicting health outcomes. These measures facilitate early detection, personalized treatment strategies, and long-term risk assessment in metabolic health. The triglyceride-glucose (TyG) index and related parameters, particularly the TyG-WC index, are gaining recognition as reliable biomarkers for MASLD, with consistently high diagnostic accuracy across diverse populations. The TyG-WC index is associated with MASLD and an increased likelihood of all-cause, cardiovascular, and diabetes-related mortality, highlighting its importance in stratification and patient management. This opinion review summarizes key findings on the TyG-WC index across different MASLD populations and provides nutritional recommendations aimed at reducing this index. The TyG-WC index stands out as a practical and scalable biomarker for identifying and stratifying the risk of MASLD, particularly in resource-limited environments where access to advanced diagnostic tools is restricted. However, before the TyG-WC index can be integrated into routine clinical practice, rigorous, longitudinal studies involving ethnically diverse cohorts must validate its prognostic performance. It should be viewed as a complementary tool within a comprehensive metabolic risk assessment framework, supporting preventive strategies while awaiting formal endorsement in clinical guidelines.
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