Abstract Background Metabolic dysfunction-associated steatotic liver disease ( MASLD) is the leading cause of chronic liver disease, which may progress to cirrhosis and liver cancer. Even though hepatic biopsy is the benchmark for diagnosis, non-invasive techniques are becoming more popular for MASLD diagnosis, progression tracking, and treatment monitoring. Recently, hepatic injury and fibrosis have been linked to liver fatty acid-binding protein (L-FABP). This study assesses the diagnostic utility of L-FABP in Egyptian patients with MASLD. Methods This case-control study included 80 participants: 20 age- and sex-matched healthy controls and 60 patients with MASLD. Patients from Menoufia University Hospitals were enrolled between October 2024 and June 2025. Each patient underwent clinical evaluation, laboratory testing, and measurement of serum L-FABP by enzyme-linked immunosorbent assay (ELISA). Fibroscan with controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), as well as abdominal ultrasonography, were performed. Fibrosis-4 Index (FIB-4), NAFLD fibrosis score, and aspartate aminotransferase to platelet ratio index (APRI) were calculated. Results Patients with MASLD had significantly greater serum levels of L-FABP than controls (p < 0.001). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), APRI, FIB-4, and Nonalcoholic Fatty Liver Disease (NAFLD) fibrosis scores were significantly correlated with L-FABP. L-FABP levels and steatosis grade, however, did not significantly correlate. An L-FABP cut-off of 4.05 ng/mL was shown to have acceptable diagnostic accuracy for MASLD (AUC = 0.90, 95% sensitivity). An L-FABP cut-off of 6.5 ng/mL demonstrated excellent accuracy (AUC = 0.963) for the prediction of liver fibrosis. Multivariate logistic regression analysis identified serum L-FABP as an independent factor associated with the presence of liver fibrosis (p = 0.043). Conclusion Serum L-FABP is a potential noninvasive biomarker for the diagnosis of MASLD and for evaluating liver fibrosis. It correlates well with the degree of liver injury and fibrosis but not with the degree of steatosis.
Hepatocellular carcinoma (HCC) is a worldwide health issue and the third most common cause of cancer-related fatalities globally. The Ras association domain family 1 isoform (RASSF1A) is a tumor suppressor gene; it plays a role in maintaining microtubule stability, cell cycle progression, and induction of apoptosis. The carcinogenic impact of methylation, an important epigenetic alteration, is well recognized in HCC. Therefore, we aimed to evaluate the significance of plasma concentration of methylated RASSF1A in patients with post-hepatitis C virus (HCV) cirrhosis as a non-invasive diagnostic indicator for HCC. The levels of methylated RASSF1A were measured in the plasma of 120 individuals divided into three groups (40 individuals each): HCC patients with chronic HCV infection, cirrhotic patients after hepatitis C without HCC, and a healthy control group matched for age and sex. Methylation-sensitive restriction enzyme digestion and real-time quantitative polymerase chain reaction techniques were used to assess the RASSF1A expression levels. patients with HCC showed markedly elevated levels of circulating hypermethylated RASSF1A compared to post-hepatitis C patients and control groups. Moreover, a statistically significant association between RASSF1A and various clinico-pathological parameters was noted. The plotted receiver operating characteristic (ROC) curves indicated that plasma RASSF1A significantly differentiated between HCC and cirrhotic patients. Circulating hypermethylated RASSF1A may serve as a non-invasive diagnostic marker to differentiate HCC in post-HCV cirrhotic patients and to assess their progression.
Asprosin is an adipokine increased in diabetes and fatty liver disease, two metabolic comorbidities frequently present in chronic hepatitis C virus (HCV) infection. Moreover, low serum asprosin levels were found in cirrhosis. However, its association with liver fibrosis stages in chronic HCV remains unclear. This study examined whether serum asprosin reflects liver disease severity in patients with chronic HCV. Serum asprosin levels were measured by enzyme-linked immunosorbent assay before direct-acting antiviral (DAA) therapy, during treatment, and at sustained virological response 12 weeks after treatment (SVR12). Associations with liver fibrosis, cirrhosis, body mass index, sex, diabetes, hepatic steatosis, HCV viral load, genotype, and circulating lipids were analyzed. Higher serum asprosin in obese men, but not in obese women, was observed in chronic HCV. After exclusion of obese patients, women had higher serum asprosin levels than men. Serum asprosin did not differ in patients with or without diabetes and/or hepatic steatosis, irrespective of obesity status. It was not associated with liver fibrosis assessed by shear-wave elastography or fibrosis-4 score. Patients with ultrasound-defined cirrhosis had serum asprosin levels comparable to those without cirrhosis. Serum asprosin was also unrelated to liver function markers, the Model for End-Stage Liver Disease score, HCV viral load, or genotype. DAA therapy did not alter serum asprosin levels, which were 1.38 (0.32–4.61) ng/ml before therapy, 1.30 (0.16–2.27) ng/ml at 12 weeks of therapy, and 1.32 (0.40–3.75) ng/ml at SVR12. Females had modestly higher serum asprosin levels than males at therapy end and SVR12. Serum asprosin correlated positively with phosphatidylinositol and phosphatidylcholine before and after therapy. Serum asprosin levels in chronic HCV show sex-specific differences. In contrast, it does not reflect metabolic comorbidities, liver fibrosis, cirrhosis, or virological features and remains stable during DAA therapy. Its positive relationship with circulating phospholipids before and after treatment suggests a role in lipid metabolism that merits further study.
Abstract Cholangiocarcinomas (CCAs) are a broad category of lethal cancers that arise in the biliary tree. After hepatocellular carcinoma (HCC), CCA is the second most common primary hepatic malignancy, making up 15% of all primary liver tumors. Their prognosis is poor because they are frequently diagnosed in advanced stages. The inability to achieve full resection is still a challenge. There are already many distinct CCA molecular subtypes, each with its own treatment response and prognosis. Another limitation for popular treatment approaches is the high heterogeneity and chemoresistance of CCAs. To enhance knowledge of CCA and draw attention to current gaps, we provide a summary of the latest advancements in the field, emphasizing cells of origin, classification, genetic landscape, epigenetic changes, novel biomarkers, artificial intelligence (AI) integration and treatment lines including liver transplantation.
Abstract Background Cholangiocarcinoma (CCA) is a rare, aggressive, insidious, and increasingly prevalent cancer characterized by late-stage diagnosis and resistance to chemotherapy. The expression levels of the long non-coding RNA HOTAIR are associated with various pathological processes, including metabolic disorders, autoimmune diseases, and developmental abnormalities. Their involvement in development and progression of multiple malignancies, including CCA, makes them a promising target for therapeutic intervention against this silent killer. Aim To evaluate the association between two single-nucleotide polymorphisms (SNPs), rs4759314 and rs920778 of LncRNA-HOTAIR, and the susceptibility to CCA. Method This cross-sectional study included three groups (totaling 150 participants): 50 patients with cholangiocarcinoma (mean age 55.66 ± 8.92 years; 70% males and 30% females), 50 patients with nonmalignant biliary obstruction (mean age 53.82 ± 8.63 years; 68% males and 32 females), and 50 healthy individuals serving as the control group (mean age 52.20 ± 6.79 years; 54% males and 46% females). The rs4759314 and rs920778 were genotyped using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). Clinical data, including CA19.9 levels, were recorded. Result Regarding the clinical characteristics of the cholangiocarcinoma (CCA) patients, our analysis revealed that 82% of cases exhibited focal liver lesions, while 72% presented with lymph node metastasis. Furthermore, the majority of the study population showed normal spleen size (92%) and absence of ascites (56%). Concerning the HOTAIR rs4759314 polymorphism, the AA genotype was the most frequent across all study groups. However, the GG genotype was notably more frequent in the CCA group compared to other study groups. Similarly, the G allele demonstrated a higher frequency in the CCA group than other groups. Statistical analysis indicated that the GG genotype was associated with an increased risk of CCA compared with the AA genotype (OR = 4.18, 95% CI: 1.19–14.60, p = 0.025). Regarding the HOTAIR rs920778 polymorphism, the CT genotype was the most frequent among all groups, with no statistically significant association observed regarding CCA susceptibility. Conclusion The findings suggest that the HOTAIR rs4759314 polymorphism may have a potential association with an increased susceptibility to cholangiocarcinoma, indicating that the G allele could serve as a potential genetic biomarker. Further research is warranted to validate its clinical utility.
