Livers

Background/Objectives: The ¹³C-Methacetin Breath Test (MBT) is a non-invasive tool to evaluate hepatic microsomal function via exhaled ¹³CO₂, reflecting cytochrome P450 1A2 (CYP1A2)-mediated metabolism. Despite decades of evidence demonstrating its utility in diagnosing cirrhosis, stratifying liver disease severity, and predicting outcomes, MBT adoption remains limited due to methodological inconsistencies and variable diagnostic thresholds. This review aimed to summarize MBT data in adults and assess its diagnostic and prognostic performance. Methods: A literature review was conducted using PubMed, Web of Science, and Scopus. Eligible studies included those applying oral or intravenous methacetin with defined reference values or diagnostic cutoffs. Outcomes of interest were percent dose recovery (PDR), cumulative PDR (cPDR), and LiMAx^® values. Due to heterogeneity in protocols, units, and endpoints, results were synthesized narratively. Results: Healthy individuals typically demonstrated rapid metabolism (e.g., cPDR30 10–15%), whereas cirrhotic patients showed significantly reduced values (e.g., cPDR30 ≈ 1%). Diagnostic cutoffs varied widely (<0.35% to <8%), reflecting methodological and population differences. MBT reliably identified advanced liver disease but showed inconsistent sensitivity for early-stage fibrosis and metabolic dysfunction-associated steatotic liver disease. Variability in dosing, timing, measurement duration, and analytic technique limited cross-study comparability. Conclusions: MBT is a validated, dynamic marker of liver function with both diagnostic and prognostic relevance. However, inconsistent protocols and thresholds hinder its clinical implementation. Standardization of MBT procedures, reference ranges, and reporting metrics is essential. A harmonized protocol (“MBT-60”), supported by multicenter validation, demographic stratification, and direct comparison with structural and serologic liver tests, is recommended to facilitate MBT integration into routine hepatology practice. Full article

Background: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis due to late-stage presentation and ineffective systemic therapies. Targeting the tumor microenvironment (TME) in ICC offers new therapeutic possibilities, particularly through tumor-associated macrophages (TAM), which can both promote and inhibit tumor progression. The current study utilized multi-omics analysis to characterize the gene signature of TAM and explore its therapeutic potential in ICC. Methods: Public GEO datasets provided the basis for analysis. Single-cell RNA sequencing (scRNA-seq) data from five ICCs, three adjacent non-tumorous tissues (ANTs), and four healthy liver samples were examined with Python. To validate scRNA-seq findings, bulk RNA-seq data from 27 ICC and 27 matched ANT samples were assessed using R. Differentially expressed genes were identified with adjusted p-values <0.01 and log2-fold changes >1 or <−1. CIBERSORT pipeline analyzed 22 immune cell subtypes in bulk RNA-seq data. STRING database analyzed the contribution of unique TAM-related genes to networks of protein–protein interactions. Results: TAM population demonstrated phenotypic heterogeneity exhibiting partial gene signatures of inflammatory (MS1) and anti-inflammatory (MS2) macrophages. Unique TAM-associated markers, TREM2, CD9, and PRMT10, showed variable expression within the TAM subpopulation. Bulk RNAseq analysis confirmed the scRNA-seq results, highlighting overexpression of TREM2 and CD9 in most ICC samples versus ANT. Immune cell deconvolution revealed decreased MS1 and MS2 macrophages in ICC, and alterations in adaptive immune profile, suggesting immunotolerant TME. STRING database defined TREM2-LGALS3 axis as a potential target for anti-tumor therapies. Conclusions: TAM represents a unique heterogenous population which is primarily found in ICC TME versus ANT or healthy liver tissue The non-uniform expression of unique gene signature demonstrates additional heterogeneity in the TAM subpopulation and suggests that TREM2+ TAM may be desirable targets for anti-TREM2-LGALS3 immunotherapy. Full article

Background/Objectives: Vitamin D is recognized as a key modulator of metabolic diseases, including metabolic-dysfunction-associated steatotic liver disease (MASLD), in which its deficiency contributes to both disease onset and progression. Despite the widespread and often prolonged use of vitamin D supplementation, optimal serum levels in individuals with MASLD remain unclear and warrant further investigation. Methods: In this study, hepatic steatosis was induced in male and female Wistar rats over a 45-day period. The animals were then divided into five groups (control, 2500, 7000, 14,000, and 21,000 IU/kg/week of cholecalciferol). After four weeks of treatment, the animals were euthanized, and blood samples were collected for biochemical, hormonal, inflammatory, oxidative stress analyses and liver architecture evaluation. Results: High-dose vitamin D supplementation in rats with MASLD induced dose-dependent metabolic, inflammatory, and oxidative changes, with some sex-specific differences. Urea and alanine aminotransferase levels increased at higher doses in both sexes, suggesting potential nephrotoxic and hepatotoxic effects, while creatinine and aspartate aminotransferase remained stable. Adiponectin levels decreased consistently, and leptin levels rose across all doses, indicating a shift toward a pro-adipogenic profile. Pro-inflammatory molecules (IL-1β, IL-6, IL-8, TNF, C-reactive protein) increased progressively with dose, while IL-10 followed a U-shaped curve. Oxidative stress markers showed elevated protein carbonylation only at the highest dose, a slight reduction in TBARS, and a peak in total antioxidant status at 7000 IU/kg/week. Conclusions: High-dose vitamin D triggers antioxidant responses but drives harmful inflammatory and metabolic shifts in MASLD. Full article

Metabolic-associated steatotic liver disease is currently one of the most common causes of liver disease in the world, affecting a large portion of the global population; these patients are at risk of developing advanced liver fibrosis and cirrhosis. Noninvasive tests (NITs), including lab tests such as FIB-4, NAFLD Fibrosis Score and the Aspartate Aminotransferase-to-Platelet Ratio Index, are widely used for fibrosis risk stratification, but their accuracy across various racial, ethnic, and age groups remains poorly characterized. This review examines disparities in NIT performance across these populations and the need for tailored screening strategies. A comprehensive, narrative literature review highlighted significant variability in NIT performance, with studies in African American, Hispanic and Asian patients all revealing mixed results when the performance of NITs was used to assess fibrosis levels. Additionally, the age of patients may influence fibrosis testing, as older adults tend to have higher false-positive rates due to age-based biases. Although imaging modalities like VCTE and MRE may offer superior accuracy in the noninvasive assessment of hepatic fibrosis, they face accessibility limitations and have rarely been validated in specific racial groups. This review concludes that current NITs for MASLD risk stratification needs to be recalibrated with population-specific and age-adjusted thresholds, and future research should focus on inclusive validation studies and integrating clinical judgment to improve screening accuracy. Full article

Background: The National Surgical Quality Improvement Program (NSQIP) database provides one of the largest repositories of surgical outcome data—guiding local, national, and international quality improvement and research. We aim to describe a model to estimate Clavien–Dindo complication (CDC) rates from NSQIP data to enable comprehensive outcome measurement, allowing an NSQIP-based surrogate measure for longer-term outcomes. Methods: This is a validation study of a model to estimate CDCs from NSQIP data for pancreaticoduodenectomy (PD) and hepatic resection (HR). The primary objective of this study is to evaluate whether our method to estimate CDCs ≥ 3 outcomes from NSQIP data results in similar serious complication rates to large benchmark studies on outcomes following PD and HR. Secondary outcomes evaluate whether specific NSQIP outcomes provide adequate information to estimate CDC grades I-V following PD and HR. Results: We evaluated 20,575 patients undergoing PD, with 71.3% having pancreatic ductal adenocarcinoma. Comparing CDCs ≥ 3 complications for NSQIP and benchmark PD patients, we estimated a 23.2% rate with our model, which was significantly lower than the reported 27.6% in the benchmark study (p < 0.001). Additionally, the benchmark reported higher complication rates for every CDC grade compared to our estimates using NSQIP PD patients (p < 0.001). Further, we evaluated 29,809 patients within NSQIP undergoing HR, where most patients with a diagnosis listed had colorectal cancer metastases (30.8%). Compared to the benchmark HR study (n = 2159), the NSQIP patients were less likely to have hepatic resection for malignancy (57.7% vs. 84.0%; p < 0.001). Comparing CDCs ≥ 3 complications following HR demonstrated that rates were clinically similar (13.0% vs. 15.8%) but statistically different between the benchmark study and NSQIP data (p < 0.001). Additionally, the NSQIP patients had lower rates of estimated complications for nearly all CDC grades (p < 0.001). Conclusions: This is the first reported method to estimate aggregate morbidity from NSQIP data. Results demonstrate that despite differences in this and comparator cohorts, this model may underestimate CDC grade 1–2 complications but provide similar rates of CDCs ≥ 3 complications compared to benchmark studies. Future studies to validate or modify this estimation method are warranted and may allow extrapolation of short-term NSQIP measures to oncologic, quality of life, and long-term outcomes. Full article

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with poor clinical prognosis and high mortality, despite the advances related to therapeutic options for HCC. Therefore, exploring alternative therapeutic options and their associated mechanisms is relevant and urgently needed. Natural products may be an important source of novel anti-cancer compounds. Coffee consumption is associated with protective effects against liver diseases, but the molecular mechanisms underlying these benefits remain poorly understood. Objectives: In this study, we evaluated the in vitro effects of green (GC) and roasted coffee (RC) extracts, alongside chlorogenic acid (CGA), on the proliferation of HepG2 hepatocellular carcinoma cells. Results: Both coffee extracts and CGAs significantly reduced HepG2 cell viability and cell proliferation in a dose-dependent manner. GC at 500 µg/mL and CGA at 400 and 800 µM significantly induced caspase-3 activity. In addition, HepG2 cells treated with coffee extracts (500 and 1000 µg/mL) resulted in dose-dependent membrane permeabilization, leading to an increased number of necrotic cells. Despite these anti-proliferative effects, TOP/FOP luciferase assays revealed minimal activation of the Wnt/β-catenin signaling pathway. Among canonical Wnt target genes, only c-Myc expression was notably downregulated after treatment. Moreover, β-catenin protein levels and subcellular localization remained largely unchanged. Conclusions: These findings suggest that coffee extracts and chlorogenic acids inhibit HepG2 cell proliferation, highlighting their hepatoprotective properties, even in cells containing mutations that constitutively activate Wnt signaling. Full article

Background: Liver cancer, either primary or metastatic, is a leading cause of cancer-related deaths and in many cases is presented in stages requiring major hepatectomy. Adequate future liver remnant (FLR) volume is essential before any major hepatectomy. Portal vein embolization (PVE) has long been the standard technique for preoperative liver hypertrophy, but liver venous deprivation (LVD) has emerged as a novel method, potentially offering faster and superior results. The aim of this study is to compare FLR hypertrophy outcomes between LVD and PVE in patients undergoing major hepatectomy for liver malignancy. Methods: A systematic literature search was conducted across PubMed, Cochrane library, and clinicaltrials.gov for studies assessing FLR volume changes after LVD or PVE in patients with primary or secondary liver tumors undergoing liver resection. Data extraction was performed independently by two reviewers. The study protocol was registered in PROSPERO and was prepared according to the PRISMA guidelines. Results: Twelve retrospective cohort studies were included in this systematic review. Liver venous deprivation consistently demonstrated superior FLR hypertrophy, with a faster and higher percentage increase compared to PVE. Time to resection was also shorter in the LVD groups in most studies. Safety outcomes were comparable, with no consistent difference in post-procedural complications or mortality. Conclusions: Liver venous deprivation may potentially be a safe and effective alternative to PVE, offering more robust and rapid FLR hypertrophy with similar morbidity and mortality rates. While current evidence supports its superiority in selected patients, future validation with larger prospective clinical trials is essential before it can be adopted as standard management of patients with insufficient FLR volume. Full article

Ascites and renal dysfunction are among the most frequent and severe complications of decompensated advanced chronic liver disease (dACLD), often representing two interrelated manifestations of a shared pathophysiological continuum. Recurrent ascites and refractory ascites pose significant therapeutic challenges and are frequently associated with kidney impairment, particularly hepatorenal syndrome. Recent advances have reshaped the understanding of the underlying mechanisms, moving beyond the classical paradigm of peripheral arterial vasodilation to encompass systemic inflammation, gut dysbiosis, and cirrhosis-associated immune dysfunction (CAID). These insights have prompted a shift from uniform treatment protocols toward personalized, multidisciplinary strategies. Therapeutic innovations such as long-term albumin infusion, a transjugular intrahepatic portosystemic shunt, and the Alfapump^® system offer promising options, though each requires careful patient selection. Emerging approaches—including fecal microbiota transplantation and peritoneal dialysis—further expand the therapeutic landscape. Ultimately, early risk stratification, the integration of non-invasive tools, and individualized care models are essential to improving outcomes in this high-risk population. This review synthesizes current evidence and highlights future directions for the tailored management of dACLD patients with ascites and renal dysfunction. Full article

Background: We have previously demonstrated that the function and expression of the Na⁺/taurocholate cotransporting polypeptide (NTCP) and the organic cation transporter 1 (OCT1) are affected by increasing free or unesterified cholesterol in the plasma membrane by an acute incubation with cholesterol for 30 min. In the current study we wanted to extend these findings to a more chronic condition to mimic what would be seen in obese patients. Methods: We incubated HEK293 cells that stably express NTCP or OCT1 for 24 h with 0.05 mM cholesterol and determined their function by measuring uptake of radioactive taurocholate or MPP⁺. Expression at the plasma membrane was quantified with a biotinylation assay combined with Western blots. Results: Incubation with cholesterol increased the cholesterol content of the cells by about 2-fold. Transport mediated by NTCP and OCT1 was decreased. Membrane expression for both transporters showed a slight decrease, and when kinetics were normalized for the membrane expression, the V_max for NTCP-mediated taurocholate uptake slightly decreased, but the V_max and the capacity (V_max/K_m) for OCT1-mediated MPP⁺ uptake increased by 2.5-fold and 3-fold, respectively. Acyl-Coenzyme A acyltransferase inhibitors enhanced the decrease in transport function, potentially due to retention of more free cholesterol in the plasma membrane. Conclusions: Chronic increases in free cholesterol in the plasma membrane can result in increased or decreased transporter function and expression. In the case of OCT1, which is involved in the uptake of the anti-diabetic drug metformin into hepatocytes, the 3-fold increase in transport capacity might affect drug therapy. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with liver metastases (CRLM) representing a common and often incurable manifestation. While surgical resection combined with chemotherapy remains the standard for resectable disease, a significant subset of patients presents with unresectable CRLM. Recent advances have positioned liver transplantation (LT) as a promising therapeutic option for select patients with unresectable CRLM. This review synthesizes current evidence from landmark studies—including the SECA and TRANSMET trials—and emerging data from North American cohorts, highlighting the evolution of patient selection criteria, prognostic indicators such as the Oslo score and metabolic tumor volume, and the role of living-donor and extended-criteria grafts. Outcomes from recent studies demonstrate that LT can achieve 5-year overall survival rates exceeding 70% in well-selected patients, rivaling those of traditional transplant indications. Ongoing trials such as SECA-III and SOULMATE aim to refine indications and address organ allocation challenges. Collectively, these findings suggest that LT can offer long-term survival benefits comparable to traditional transplant indications, marking a paradigm shift in the management of metastatic CRC. Full article

Irritable Bowel Syndrome (IBS) and Metabolic dysfunction-associated fatty liver disease (MAFLD) have traditionally been viewed as disorders of distinct organ systems. IBS is a gut–brain axis disorder characterized by abdominal pain, altered bowel habits, and psychological comorbidities. MAFLD, recently redefined to emphasize its metabolic underpinnings, is the hepatic manifestation of systemic metabolic dysfunction. Growing evidence suggests that these conditions share overlapping pathophysiological mechanisms linked through disruption of the gut–liver–brain axis (GLBA), including psychological stress, gut dysbiosis, impaired intestinal permeability, systemic inflammation, and altered neuroendocrine signaling. Neuroimaging studies further reveal functional alterations in brain regions responsible for interoception, emotional regulation, and stress responsiveness in both disorders. This narrative review explores how psychological distress influences the onset and progression of IBS and MAFLD via GLBA dysfunction and stress-induced epigenetic reprogramming. A targeted literature search of major biomedical databases, supplemented by manual screening, identified relevant observational, clinical, neuroimaging, and molecular studies. Findings indicate that chronic psychological distress activates the hypothalamic–pituitary–adrenal (HPA) axis, elevates cortisol, disrupts gut microbiota, and reduces vagal tone; amplifying intestinal permeability and microbial translocation. These changes promote hepatic inflammation and gastrointestinal symptoms. Stress-related epigenetic modifications further impair GLBA communication, while psychological and lifestyle interventions may reverse some of these molecular imprints. Recognizing the shared neuromodulation and epigenetic mechanisms that link IBS and MAFLD opens promising avenues for integrated therapeutic strategies targeting the GLBA to improve outcomes across both conditions. Full article

Herbal and dietary supplements (HDS) are used by over half of American adults and represent a multi-billion-dollar industry. More recently, they have gained popularity, in part due to promotion on multiple social media platforms. However, the Food and Drug Administration (FDA) does not regulate these products rigorously, and up to 20% of acute liver injuries are attributed to HDS. The true incidence of HDS hepatotoxicity is unknown but thought to be underreported. According to the World Health Organization (WHO), HDS-induced liver injuries are now the fifth most common cause of liver disease–associated death. The most common type of supplements associated with liver injury are bodybuilding and weight loss supplements. This study represents a comprehensive literature review of HDS-induced liver injury with a focus on the two most common culprits: bodybuilding supplements and weight loss supplements. Future strategies recommended to mitigate hepatotoxicity include strengthening regulatory oversight through mandatory product listing, enhancing post-market surveillance with standardized reporting and registries, improving product quality via ingredient verification and contaminant testing and, possibly, implementing standardized risk labeling. Full article

Background: As the growing global population continues to age, the risk of chronic metabolic diseases, including cardiovascular disease, neurodegenerative disorders, type 2 diabetes mellitus, and fatty liver disease, increases considerably. Driven largely by lifestyle factors and metabolic dysfunction, this escalating health crisis is placing mounting pressure on healthcare systems and contributing to significant economic costs. Insulin resistance and hyperinsulinaemia are major drivers of these disorders, emphasising the need for early detection and intervention. Changes in liver enzymes, such as alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), commonly assessed in routine laboratory testing, can serve as biomarkers of early-stage insulin resistance, offering a potentially underutilised window for intervention and disease prevention. Correspondingly, low-carbohydrate ketogenic diets have shown to be effective in reversing insulin resistance, metabolic disease, and liver disease. Objectives: We chose to explore the relationship between suppressing ketosis and changes in liver enzymes in the Ketosis Suppression and Ageing cohort. Methods: Ten lean (BMI 20.5 kg/m² ± 1.4), healthy young women (age 32.3 ± 8.9 years) who habitually followed a ketogenic diet maintaining nutritional ketosis (NK) for an average of 3.9 years (±2.3) were exposed to a higher carbohydrate diet, in line with standard healthy eating guidelines for a 21-day phase and then transitioned back to a ketogenic diet. Results: Carbohydrate challenge and suppression of ketosis increased insulin resistance score HOMA-IR by 2.13-fold (p = 0.0008), GKI by 22.28-fold (p = 0.0024), and liver markers ALT by 1.85-fold (p = 0.0010), GGT, 1.29-fold (p = 0.0087) and the ALT/AST, 1.30-fold (p = 0.0266), reflecting an adverse pattern suggestive of hepatic insulin resistance. Conclusions: These results support the clinical utility of liver markers as early and directional signs of hyperinsulinaemia. Full article

Background: Perihilar cholangiocarcinoma (pCCA), especially the periductal-infiltrating subtype, is notoriously difficult to diagnose due to subtle imaging findings and the absence of a mass. Case Presentation: We describe a 56-year-old man with morbid obesity and deep vein thrombosis (DVT), admitted for severe cholestatic jaundice. Initial ultrasound and two ERCPs were inconclusive, with only mild hilar duct dilation on CT. MRI was not possible due to the severe weight of the patient. Only at the 3rd ERCP with digital cholangioscopy were irregular mucosa and tumor infiltration observed, and a biopsy confirmed moderately to poorly differentiated adenocarcinoma. The patient deteriorated rapidly after discharge, returning in septic shock. Despite laparoscopy excluding cholecystitis and cirrhosis, he died from multiorgan failure. Autopsy revealed diffuse hilar tumor infiltration, nodal metastases, and fatal pulmonary tumor embolism (Bismuth IV). Conclusions: This case highlights the necessity of early escalation to cholangioscopy in unresolved cholestasis, the importance of recognizing paraneoplastic thrombosis, and the value of autopsy in clarifying cause of death. Full article

Chronic liver disease is a significant global cause of morbidity and mortality. While early-stage liver cirrhosis is often asymptomatic, it can progress to a decompensated phase known as end-stage liver disease (ESLD), resulting in a high symptom burden, diminished quality of life, and frequent hospitalizations. Palliative care is a form of specialized care aimed at addressing the needs of patients; however, it remains underutilized in ESLD patients. Globally, the integration of palliative care into ESLD is impeded by several barriers. Certain factors—such as advanced age, the presence of hepatocellular carcinoma (HCC), and transplant listing status—have been associated with higher rates of palliative care referral. This review provides a comprehensive analysis of the current literature, emphasizing the benefits of palliative care interventions in ESLD, including improved symptom control and enhanced quality of life. It also underscores the impact on caregivers and healthcare systems, notably in reducing hospital readmissions. We advocate for a paradigm shift toward proactive, patient-centered models that integrate symptom management, advance care planning, and psychosocial support alongside disease-specific treatments for patients with ESLD. Full article

Background: Alcoholic liver disease (ALD) contributes substantially to global liver-related morbidity and mortality. In conservative societies such as Oman, data on ALD are scarce due to stigma and legal constraints. This study aims to characterize the clinical spectrum, complications, and outcomes of ALD in Oman, providing the first detailed analysis from a tertiary care setting in the country. Methods: We retrospectively analyzed 131 Omani patients with documented unhealthy alcohol use from 2012 to 2018 at Sultan Qaboos University Hospital. ALD diagnosis was based on clinician judgment per EASL guidelines and DSM-5 criteria, where applicable. Data included demographics, clinical/laboratory findings, and radiologic/endoscopic features. Associations with complications and mortality were assessed using chi-square tests and logistic regression. Results: Of 131 patients, 84 (64.1%) were diagnosed with ALD: fatty liver (34.5%), alcoholic hepatitis (20.2%), cirrhosis (40.5%), and hepatocellular carcinoma (4.8%). Cirrhosis was significantly more prevalent in patients aged 50 years or older (OR = 2.53, 95% CI: 1.02–6.28; p = 0.048). Ascites and portal hypertension were strongly associated with mortality (OR = 5.20, CI: 1.85–14.6 and OR = 6.13, CI: 2.04–18.4, respectively; p < 0.01). Overall mortality in ALD was 28.6%, increasing to 44.1% in cirrhotics. Conclusion: ALD is a significant yet underrecognized problem in Oman, with high rates of late-stage presentation and mortality. Early detection and culturally tailored strategies are needed to improve care outcomes. Full article

Liver cirrhosis, a progressive and often irreversible condition, exerts widespread systemic effects, with the skin frequently serving as a visible window into the extent of hepatic dysfunction. Cutaneous manifestations, such as spider angiomas, palmar erythema, jaundice, and pruritus, not only reflect underlying pathophysiologic changes but also serve as important, non-invasive diagnostic and prognostic markers of disease severity. Early detection of such cutaneous findings may allow for early treatment, optimize patient management, and improve outcomes. This review addresses the various cutaneous manifestations of liver cirrhosis, their pathogenesis, and their prognostic and diagnostic importance, emphasizing the need for heightened clinical awareness of the improvement in patient care. Full article

Background: Early diagnosis of hepatocellular carcinoma (HCC) and monitoring of therapeutic results remain clinical challenges. Methods: In a prospective study, we evaluated the diagnostic capabilities of the serum level of glypican-3 in 70 patients with chronic advanced compensated liver disease: 40 cases with confirmed HCC and 30 cases with chronic viral hepatitis with bridging fibrosis or cirrhosis as a control group. The glypican-3 concentration was analyzed in the context of the disease characteristics. Results: The mean level of glypican-3 in HCC patients was 50.84 ± 75.98 ng/mL, significantly higher compared to the control group of 5.69 ± 10.43 ng/mL. A progressive increase in alpha-fetoprotein in accordance with the stage of neoplastic disease was observed, but this tendency was not assessed for glypican-3. Two cut-off levels can be suggested for glypican-3: 2.5 ng/mL to exclude HCC with an optimal sensitivity of 85%, and 33.7 ng/mL for confirmation of HCC, with a specificity of 96.7%. The diagnostic accuracy of serum glypican-3 was 80.0% for HCC, 82.1% for alpha-fetoprotein, and 87.4% for both tumor markers. Conclusions: This pilot study suggests a complementary role of glypican-3 with alpha-fetoprotein and better diagnostic performance when combining tumor biomarkers. Full article