Objectives: Methotrexate (MTX) is a potent antineoplastic and immunosuppressive drug; nevertheless, its therapeutic use is limited by hepatotoxicity, mostly driven by oxidative stress (OS). This research sought to examine the possible preventive impact of vinpocetine (VPC) against MTX-induced liver injury in rats.
Methods: Thirty-two female Wistar albino rats were randomly allocated into four groups: Control, MTX (20 mg/kg, single dose, intraperitoneally), VPC (10 mg/kg/day, intraperitoneally for 7 days), and MTX+VPC. Upon conclusion of the experiment, liver tissues and serum samples were obtained. Hepatic OS indicators, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), were assessed. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed. Histopathological evaluation focused on sinusoidal dilation and congestion.
Results: The treatment of MTX markedly elevated liver levels of MDA, TOS, and OSI, while concurrently diminishing SOD, CAT, GPx, and TAS values, signifying substantial OS. VPC co-administration markedly reduced MTX-induced oxidative imbalance, as shown by decreased MDA and OSI levels and a partial recovery of antioxidant enzyme activity. Serum AST and ALT levels exhibited no significant differences among the groups. Histopathological examination revealed that MTX caused considerable sinusoidal dilatation, which was somewhat reduced by VPC, but this reduction did not achieve statistical significance.
Conclusion: VPC offers partial protection against MTX-induced hepatic OS and early histopathological changes without influencing serum transaminase levels. These data indicate that VPC may function as a possible supplementary treatment to alleviate MTX-induced hepatotoxicity.

Objectives: Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide. Despite the availability of systemic therapies, treatment resistance and tumor progression remain major challenges in HCC management. Increasing evidence indicates that aberrant activation of the fibroblast growth factor receptor 4 (FGFR4) axis and the phosphoinositide 3-kinase (PI3K) signaling pathway plays a critical role in hepatocarcinogenesis, tumor proliferation, and therapeutic resistance. Drug repositioning strategies offer an efficient approach for identifying new therapeutic applications for widely used non-oncologic drugs. This study aimed to investigate the potential inhibitory interactions of commonly prescribed drugs—atorvastatin, metformin, and celecoxib—against FGFR4 and PI3Kα through molecular docking analysis and to compare their binding profiles with sorafenib, a reference drug used in HCC treatment.
Methods: The crystal structures of FGFR4 and PI3Kα were retrieved from the Protein Data Bank and prepared using AutoDockTools. The three-dimensional structures of atorvastatin, metformin, celecoxib, and sorafenib were obtained from the PubChem database. Molecular docking simulations were performed using AutoDock 4 employing the Lamarckian Genetic Algorithm. The docking protocol was validated by redocking the co-crystallized ligand into the ATP-binding pocket, and root mean square deviation (RMSD) values below 2.0 Å were considered acceptable. Binding energies (ΔG), ligand–protein interaction profiles, and pharmacokinetic properties were analyzed using SwissADME.
Results: Docking simulations revealed that atorvastatin exhibited the strongest binding affinity toward both FGFR4 (-9.94 kcal/mol) and PI3Kα (-9.10 kcal/mol), demonstrating binding energies comparable to or stronger than the reference inhibitor. Celecoxib also showed notable binding affinity toward PI3Kα (-8.79 kcal/mol), whereas sorafenib demonstrated moderate binding interactions. In contrast, metformin exhibited relatively weak binding energies for both targets. Interaction analysis revealed that atorvastatin formed stabilizing hydrogen bonds and hydrophobic contacts with key residues within the ATP-binding pockets of FGFR4 and PI3Kα. ADMET prediction indicated that all investigated compounds satisfied Lipinski’s rule of five and displayed generally acceptable pharmacokinetic properties.
Conclusion: These findings suggest that atorvastatin may interact strongly with both FGFR4 and PI3Kα signaling proteins, highlighting its potential as a dual-target modulator in hepatocellular carcinoma. The results provide preliminary in silico evidence supporting the repositioning of commonly prescribed drugs in HCC therapy, warranting further experimental and clinical validation.

Objectives: Morbid obesity is strongly associated with non-alcoholic fatty liver disease (NAFLD), and hepatic steatosis is highly prevalent among candidates for bariatric surgery. Given the invasive nature of liver biopsy, there is a growing need for reliable non-invasive methods to assess hepatic steatosis. This study aimed to compare the diagnostic performance of insulin resistance–based indices (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] and Quantitative Insulin Sensitivity Check Index [QUICKI]) and biochemical scores (Hepatic Steatosis Index [HSI] and NAFLD Liver Fat Score [NAFLD-LFS]) in predicting ultrasonographically detected hepatic steatosis in patients with morbid obesity.
Methods: In this single-center retrospective observational study, 206 patients with morbid obesity who underwent primary laparoscopic sleeve gastrectomy between March 2024 and February 2026 and had available preoperative laboratory and abdominal ultrasonography data were included. Insulin resistance indices (HOMA-IR, QUICKI) and composite scores (HSI and NAFLD-LFS) were calculated. Hepatic steatosis was graded ultrasonographically as grade 1–3 and categorized as mild (grade 1) and moderate-to-severe (grade ≥2) for diagnostic performance analyses. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic accuracy.
Results: Hepatic steatosis was classified as grade 1 in 28.2%, grade 2 in 59.2%, and grade 3 in 12.6% of patients. Steatosis grade showed positive correlations with HOMA-IR (r=0.244), HSI (r=0.354), NAFLD-LFS (r=0.297), HbA1c (r=0.274), transaminases, and glucose/insulin levels, and a negative correlation with QUICKI. In ROC analysis, HSI demonstrated the highest diagnostic performance (AUC=0.716), followed by HbA1c (AUC=0.656) and NAFLD-LFS (AUC=0.645). In multivariable analysis, age (OR=1.04), BMI (OR=1.23), and NAFLD-LFS (OR=1.42) were identified as independent predictors, while female sex was associated with lower risk (OR=0.34).
Conclusion: In patients with morbid obesity, hepatic steatosis is significantly associated with metabolic parameters and insulin resistance. Among non-invasive indices, HSI demonstrated the highest diagnostic performance. HSI and NAFLD-LFS may serve as practical tools in the preoperative assessment of bariatric surgery candidates.

Congenital extrahepatic portosystemic shunt (CEPS), also known as Abernethy malformation, is a rare vascular anomaly characterized by diversion of portal venous blood away from the liver into the systemic circulation. Type 1 malformations are defined by the complete absence of intrahepatic portal venous flow and require liver transplantation as definitive treatment. We report two pediatric patients diagnosed with Abernethy type 1B malformation. The first patient presented with progressive cholestasis, growth retardation, and impaired liver synthetic function. Due to clinical deterioration and absence of intrahepatic portal flow, living donor liver transplantation was performed with portal vein reconstruction using an interposition graft. The second patient presented with hyperammonemia and neurocognitive impairment. Imaging confirmed type 1B CEPS, along with a focal hepatic lesion consistent with a benign regenerative nodule. The patient underwent successful living donor liver transplantation with standard portal reconstruction. Both patients had uneventful postoperative courses. During follow-up (18 and 24 months), liver function normalized and growth parameters improved, with no vascular complications observed. Liver transplantation remains the only definitive treatment for Abernethy type 1B malformation. Early diagnosis and meticulous surgical planning, particularly regarding portal inflow reconstruction, are essential for optimal outcomes.

Advanced hepatocellular carcinoma (HCC) with extrahepatic metastases has a poor prognosis. Immune checkpoint inhibitors have recently become an important treatment option for certain types of cancer. A 58-year-old Kyrgyz male patient with a history of hepatitis B virus (HBV)-related liver cirrhosis for five years was referred to our hospital for liver transplant evaluation. However, a PET-CT (positron emission tomography-computed tomography) scan performed prior to evaluation revealed metastases in the lungs and lymph nodes in different parts of the body. Dynamic liver MRI (magnetic resonance imaging) was consistent with multicentric hepatocellular carcinoma (HCC). The patient had no history of variceal bleeding, hepatic encephalopathy, or ascites. Liver function tests were not elevated, and the baseline AFP (alpha-fetoprotein) level was 463 ng/mL, with a Child-Pugh score of 6 (A). Due to the presence of extrahepatic disease, the patient was not eligible for liver transplantation, and systemic treatment was planned. Systemic treatment was initiated with nivolumab 3 mg/kg + ipilimumab 1 mg/kg at 21-day intervals. These doses were started due to toxicity concerns. The first response evaluation showed an 80% reduction in intrahepatic disease burden and a marked reduction in the size and activity of other metastatic lesions. No side effects beyond grade 1 were observed in the patient. Thus, treatment was continued. In the second treatment response evaluation, although there was an increase in the metabolic activity of some extrahepatic lesions, the reduction in liver lesions was 50% less than the previous one. The patient's general condition was good, and he had no symptoms. The dual therapy started in July 2025 was continued in January 2026 with nivolumab 240 mg every two weeks. This case highlights an extraordinary response to dual immune checkpoint inhibition in metastatic HCC and demonstrates the potential of immunotherapy without compromising efficacy, with some dose adjustments to account for toxicity in selected patients with advanced disease.