World Journal of Hepatology最新文献

Drug-induced liver injury (DILI) is an important but often underrecognized complication in the management of inflammatory bowel disease (IBD), particularly in patients receiving long-term immunomodulatory or biologic therapies. Agents such as thiopurines, methotrexate, anti-tumor necrosis factor agents, and newer small molecules including tofacitinib and upadacitinib have all been implicated in hepatotoxicity, with clinical manifestations ranging from asymptomatic elevations in liver enzymes to severe hepatic injury. Differentiating DILI from hepatobiliary disorders commonly associated with IBD, such as primary sclerosing cholangitis, metabolic dysfunction-associated steatotic liver disease, and autoimmune hepatitis, remains a significant diagnostic challenge. The absence of standardized monitoring protocols, coupled with the variable latency and heterogeneous presentation of DILI, further complicates early recognition and management. In this narrative review, we synthesize current evidence on the epidemiology, pathophysiological mechanisms, and clinical spectrum of DILI in IBD. We also outline diagnostic strategies, including the role and limitations of causality assessment tools, and propose practical considerations for baseline evaluation, longitudinal monitoring, and therapeutic decision-making.

Background: Hepatic ischemia reperfusion (HIR) injury is a major complication affecting various major liver surgeries, including liver transplantation. Aprepitant (APRE), a neurokinin-1 receptor antagonist, is commonly used as an antiemetic to prevent chemotherapy-induced nausea and vomiting.

Aim: To assess the potential protective effect of APRE against HIR-induced liver injury via targeting the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing receptor 3/interleukin (IL)-1beta signaling pathway.

Methods: Six groups of adult male Wistar albino rats were divided as follows: Sham group, Sham/APRE10 group (APRE 10 mg/kg), HIR group, HIR/APRE5 group (APRE 5 mg/kg), HIR/APRE10 group (APRE 10 mg/kg), and HIR/APRE20 group (APRE 20 mg/kg). Serum alanine transaminase, aspartate transaminase, liver malondialdehyde, total antioxidant capacity levels, as well as IL-6, sirtuin 1 (Sirt1), caspase-3, cleaved caspase-3, and tumor necrosis factor alpha biomarkers, were evaluated. Hepatic specimens were examined histopathologically and immunohistochemically for nuclear factor erythroid-2-related factor 2 (Nrf2) immunoexpression.

Results: HIR resulted in hepatic damage, as evidenced by histopathological changes and a significant increase in serum alanine transaminase, aspartate transaminase, hepatic malondialdehyde, caspase-3, and tumor necrosis factor alpha levels. Additionally, there were significant increases in hepatic total antioxidant capacity and reductions in IL-6 and cleaved caspase-3 protein levels, as demonstrated by Western blot analysis, along with enhanced immunoexpression of Sirt1 and Nrf2. APRE has significantly reduced various parameters of oxidative stress, inflammation, and apoptosis, and a significant increase in liver Nrf2 immunoexpression, leading to a significant improvement in the histopathological changes.

Conclusion: In conclusion, targeting the Sirt1/Nrf2 signaling pathway, as demonstrated by APRE in our model, could present a promising therapeutic target to protect against HIR-induced liver injury during major liver surgeries.

Metabolic-associated steatotic liver disease (MASLD) has become the leading cause of chronic liver disease worldwide, yet reliable tools for prognostication remain limited. Fibrosis-based indices such as the fibrosis-4 and nonalcoholic fatty liver disease fibrosis score are widely used but primarily reflect structural damage rather than functional decline. The albumin-bilirubin (ALBI) score, originally established to assess hepatic reserve in patients with hepatocellular carcinoma, provides a simple and objective measure of liver function derived from routine laboratory parameters. Recent validation and meta-analytic studies have shown that ALBI predicts liver-related outcomes and all-cause mortality across diverse chronic liver disease populations, including MASLD, and offers complementary prognostic information beyond fibrosis-based models. Its simplicity, cost-effectiveness, and compatibility with automated reporting systems make it feasible for integration into clinical workflows and population-level risk stratification. However, interpretation of ALBI should consider potential confounders such as renal dysfunction, inflammation, and Gilbert syndrome, and threshold calibration across ethnic groups remains necessary. The ALBI score represents a promising functional biomarker that could enhance risk prediction and care pathways in MASLD, although prospective, multiethnic, and longitudinal studies remain needed to confirm its prognostic value and define clinically meaningful cut-offs.

Refractory autoimmune hepatitis (AIH) is defined as intolerance of or unresponsiveness to standard immunosuppression and occurs in 10%-20% of children with AIH. Lack of response or slower than expected response to induction of remission with steroids, despite good compliance, might be the first clue to refractory AIH. Refractoriness to treatment is associated with an 11.7 times higher risk for liver transplantation or death due to liver disease. The first and foremost consideration for the management is to assess compliance with treatment. It is then important to re-evaluate the diagnosis, assess alternative aetiologies which can mimic the clinical, serological, and histological features of AIH, and address the presence of extra-hepatic co-morbidities. It is important to consider the specific clinical situations, previous therapy, and prior adverse effects before deciding on the most appropriate treatment regimen in refractory AIH. Consideration also should be given to compliance with previous therapy, need for drug level monitoring, growth potential, available formulations, route of administration of medication, and children's and families' preferences before deciding on the therapy. Treatment should be decided and monitored only in specialized hepatology centers.

Background: The global incidence of hyperlipidemia has been increasing on an annual basis, concomitant with improvements in living standards and dietary changes. Hyperlipidemia is closely associated with the development of numerous diseases, and in clinical cases, drug-induced cholestasis may lead to elevated serum cholesterol and triglyceride levels, a phenomenon known as secondary hyperlipidemia. Hyperlipidemia is recognized as a significant risk factor for the development of cardiovascular disease. Therefore, effective monitoring and control of lipid levels is crucial in the management of patients diagnosed with drug-induced cholestatic liver disease.

Case summary: We present a special case of refractory hyperlipidemia associated with cholestatic liver disease in a 49-year-old woman.

Conclusion: In the treatment of clinical cases of drug-induced cholestatic liver disease and hyperlipidemia, it is essential for medical professionals to consider the patient's overall condition, formulate an individualized treatment plan, and closely monitor the patient's biochemical indices and clinical symptoms to ensure treatment efficacy and prognosis.

The study by Devan et al presents an ultrasound-based protocol for monitoring tumor growth in a syngeneic orthotopic rat model of hepatocellular carcinoma (HCC). This approach is commendable for its reproducibility, cost-effectiveness, and alignment with ethical imperatives, particularly in reducing the need for invasive assessments. The strong correlation of ultrasound-based volumes with histology and therapeutic response highlights its translational promise. However, certain considerations merit further discussion. Ultrasound imaging, while accessible, is inherently operator-dependent, and its accuracy may decline with irregular or heterogeneous tumor morphology. Moreover, the exclusive reliance on the rat hepatoma cell line (N1S1) cells raises questions about generalizability to other HCC models with differing immune interactions. Future refinements should standardize training protocols, incorporate multimodal validation, and explore diverse tumor settings. Despite these limitations, the study provides a useful approach, and its broader integration could democratize preclinical oncology research, especially in resource-constrained environments.

Background: Advanced chronic liver disease is a progressive condition associated with high morbidity and mortality, leading to complications such as decompensation and hepatocellular carcinoma. Although prognostic scores such as the Child-Pugh score (which combines clinical assessment and laboratory parameters) and laboratory-based models, including Model for End-Stage Liver Disease (MELD) 3.0, albumin-bilirubin (ALBI) grade, and fibrosis-4 (FIB-4), are often used, their accuracy is limited by subjective assessments and variability in laboratory results. The Functional Liver Imaging Score (FLIS), a semi-quantitative magnetic resonance imaging (MRI) measure of liver function, may also be influenced by observer variability. This emphasizes the need for objective, reproducible tools to improve risk stratification and support treatment decision-making.

Aim: To evaluate the prognostic value of hepatic enhancement (HE) and signal intensity measured by gadoxetate disodium-enhanced MRI.

Methods: In this retrospective cohort study, 100 patients with advanced chronic liver disease underwent gadoxetate-enhanced MRI. HE and signal intensity were measured quantitatively in liver segments III, VI, VIII, and the caudate lobe, and global values were calculated by averaging segmental measurements. Correlations were assessed with FLIS, Child-Pugh, MELD 3.0, ALBI, FIB-4, liver stiffness (FibroScan), and hepatic venous pressure gradient. Cox regression and receiver operating characteristic analysis were used to evaluate associations with hepatic decompensation, mortality, and hepatocellular carcinoma (HCC) occurrence during follow-up.

Results: Global HE showed a significant correlation with FLIS (r = 0.797), Child-Pugh (r = -0.589), MELD 3.0 (r = -0.658), ALBI (r = -0.599), FIB-4 (r = -0.308), liver stiffness (r = -0.470), and hepatic venous pressure gradient (r = -0.340). Lower HE was significantly associated with a higher risk of decompensation and mortality in univariate Cox regression. After adjustment for MELD 3.0, etiology, and prior HCC, segment VI HE remained independently predictive of mortality. At 12 months, HE improved risk stratification for mortality and reduced unnecessary interventions by 11 per 100 patients at a 10% threshold in the decision curve analysis. HE had an area under the receiver operating characteristic curve of 0.74 for predicting decompensation and 0.74 for predicting mortality. HE was higher in patients who developed or experienced recurrence of HCC during follow-up, but this was not statistically significant (P = 0.1).

Conclusion: Lower HE in segment VI improved prognostic classification of high-risk patients. These patients align with Baveno VII criteria for intensified management, supporting the potential role of HE in risk-adapted surveillance.

Background: Direct acting antivirals have revolutionized hepatitis C virus (HCV) treatment. However, the high price of the brand forms is a barrier for their use in resource limited countries as Egypt.

Aim: To assess the safety and efficacy of the generic sofosbuvir (SOF)/ledipasvir (LED) in Egyptian HCV-infected children and to compare the results with the brand form.

Methods: This analytical retrospective study included HCV infected children and adolescents aged 12-18 years or weighing > 35 kg. Collected data included: Age, sex, risk factors of HCV acquisition, comorbidities, liver functions, HCV viral load, degree of hepatic fibrosis, sustained virologic response (SVR) and frequency of treatment adverse effects. Patients who received the generic form of SOF/LED (Ledisbuvir) were compared to patients who received the brand form (Harvoni^®) regarding SVR and frequency of adverse events.

Results: The study included 43 patients who received Ledisbuvir and 73 who received Harvoni^®. All patients achieved SVR. Treatment side effects were mild, transient and comparable in both groups.

Conclusion: The use of generic SOF/LED in HCV infected children is safe and effective. It is comparable to the brand form at a reduced price and represents an affordable and effective alternative.

Background: Laparoscopic hepatectomy has been widely accepted for the treatment of liver tumors. Compared with open surgery, it provides a reduced hospital stay, less intraoperative blood loss, less trauma, and fewer incisional infections, without affecting tumor outcomes. However, lesions in the right lobe of the liver are deep and obstructed by the ribs, making exposure difficult and increasing the degree of surgical difficulty; thus, liver tumors in the deep right lobe pose technical challenges in standard laparoscopic surgery.

Aim: To investigate the safety and efficacy of laparoscopic retroperitoneal partial hepatectomy for liver tumors.

Methods: The clinical data of 72 patients who underwent laparoscopic retroperitoneal partial hepatectomy for liver tumors between January 2018 and December 2024 at the First People's Hospital of Yunnan Province were analyzed. Of the 72 patients included, 34 were male and 38 were female, with ages ranging from 34 years to 72 years (median age, 45 years). The tumors were all located in the right lobe of the liver, with 30 cases in segment S6, 27 cases in segment S7, and 15 cases in segment S8; the mean tumor diameter was 7.5 ± 3.4 cm. The postoperative tumor indices, liver function, and postoperative complications were analyzed to evaluate the clinical efficacy of laparoscopic partial hepatectomy via the retroperitoneal approach.

Results: The surgeries were successfully completed in all patients, and conversion to open surgery was required in 10 patients. The mean operative time, blood loss, drain retention time, and length of postoperative hospital stay were 140 ± 30 minutes, 150 ± 46 mL, 3.8 ± 1.2 days, and 8.3 ± 5.3 days, respectively. Liver function tests returned to normal in all patients within two weeks of surgery. Fifteen patients developed atelectasis and pleural effusion and were managed with incision and drainage and antibiotics. Two patients developed uncomplicated minimal ascites, and the remaining patients had no perioperative complications, such as abdominal hemorrhage, infection, liver failure, bile leakage, and other adverse events. All patients were successfully treated.

Conclusion: Laparoscopic retroperitoneal partial hepatectomy is a safe and effective approach for right hepatic space-occupying lesions, particularly in segments S6, S7, and S8, with fewer postoperative complications, less trauma, and faster recovery times. This procedure provides a new surgical access for resection of deep tumors in the right lobe of the liver and has clear clinical implications.

Background: Cerebrospinal fluid (CSF) pseudocysts are uncommon complications of ventriculoperitoneal (VP) shunts, usually occurring within 3 weeks to 10 years of insertion. We report a perihepatic CSF pseudocyst presenting over 27 years after shunt placement, representing an exceptionally long interval compared with prior reports. This case highlights the importance of maintaining diagnostic openness when investigating unexplained ascites, and demonstrates the role of fluid beta-2 transferrin in confirming a rare diagnosis.

Case summary: A 42-year-old man with spina bifida and prior VP shunt insertion was admitted for urinary tract infection, later developing recurrent symptomatic perihepatic fluid collections. Extensive hepatic, cardiac, and surgical evaluations were unremarkable, and repeated percutaneous drainages failed. The possibility of CSF origin was raised after clinical reappraisal, and beta-2 transferrin testing of the drained fluid confirmed a CSF pseudocyst. The patient underwent VP shunt exploration and revision with relocation to the pleural space, leading to resolution of the abdominal collections and symptoms.

Conclusion: Persistent diagnostic uncertainty requires broad clinical suspicion and selective testing to identify rare causes of ascites.