World Journal of Hepatology最新文献

In this article, we discuss the recently published study by Wang et al, which investigated the therapeutic potential of levodopa, a well-known drug used to treat Parkinson's disease, for the treatment of liver diseases. The study revealed that levodopa, a dopamine precursor, exerts therapeutic effects by modulating dopamine receptor D1 signaling and activating Hippo/Yes-associated protein 1 pathway, which plays an important role in liver fibrosis. Furthermore, given that dysregulation of the brain-liver axis, including the dopaminergic reward circuit, has been implicated in the progression of liver diseases, particularly those exacerbated by stress, the purpose of this article is to make a further investigation on the potential of levodopa in regulating metabolic dysfunction and addressing maladaptive eating behaviors. Considering the important role of dopamine in regulating lipid metabolism, inflammation, and fibrosis in the liver, levodopa may present as a promising therapeutic candidate for chronic liver diseases characterized by altered dopamine sensitivity.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) may progress to cirrhosis and lead to serious complications. Lipid accumulation, hepatocellular ballooning, and sinusoidal endothelial dysfunction increase intrahepatic vascular resistance, resulting in early clinically significant portal hypertension (CSPH). Although hepatic venous pressure gradient (HVPG) remains the gold standard, decompensated cirrhosis may yield deceptively low values. Transient elastography and platelet count provide supportive diagnostic evidence, yet obesity can overestimate disease severity. This report highlights the diagnostic challenge of CSPH, especially MAFLD in geriatric patients.

Case summary: A 78-year-old woman with class I obesity, type 2 diabetes mellitus, and dyslipidemia presented with hematemesis and melena for a three-day period. A prior computed tomography scan revealed moderate diffuse hepatic steatosis, splenic vein dilatation, and splenomegaly. On admission, she presented with pallor, epigastric tenderness, splenomegaly, and mild ascites. Laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia, and hyperglycemia. Abdominal ultrasound confirmed chronic liver disease with splenomegaly. Esophagogastroduodenoscopy demonstrated grade II-III esophageal varices and portal hypertensive gastropathy. Noninvasive fibrosis assessments (non-alcoholic fatty liver disease fibrosis score, aspartate transaminase-to-platelet ratio index, fibrosis-4 index, and FibroScan: E = 28 kPa, controlled attenuation parameter = 191 dB/m) indicated advanced hepatic fibrosis. HVPG measurement was not performed, however due to the Baveno VII criteria (transient elastography ≥ 25 kPa and platelet count < 150 × 10⁹/L), confirmed the diagnosis of CSPH. The patient received endoscopic variceal ligation, a nonselective beta-blocker, a proton pump inhibitor, insulin, a sodium-glucose cotransporter 2 inhibitor, and lifestyle modification, resulting in clinical improvement.

Conclusion: Early and precise evaluation of CSPH in geriatric MAFLD requires an integrated clinical assessment to optimize diagnosis, management, and improve outcomes.

Background: Primary biliary cholangitis (PBC) is a rare, nonsuppurative cholestatic disease that affects the small intrahepatic bile ducts. If not adequately managed, it may progress to liver cirrhosis and hepatocellular carcinoma. Only a few studies have explored the impact of cardiometabolic risk factors on liver fibrosis progression in PBC. Relevant data on the role of adipokines in these processes are also limited.

Aim: To compare leptin and adiponectin levels in PBC patients stratified by the presence of metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic syndrome (MetS), fibrosis, and biochemical response.

Methods: We conducted a cross-sectional study involving 81 PBC patients diagnosed according to European Association for the Study of the Liver guidelines, all followed at a tertiary care center in Košice, Slovakia. Patients were included consecutively from the patient database in hepatology clinic in a prospective manner. Data on biochemical, clinical and anthropometric variables and their associations with MASLD, MetS, fibrosis, and biochemical response were evaluated using statistical methods including logistic regression and receiver operating characteristic analysis.

Results: Patients with PBC/MASLD had significantly lower adiponectin levels (1698.24 pg/mL vs 2042.08 pg/mL, P = 0.015) and higher leptin levels (1.89 ng/mL vs 0.62 ng/mL, P < 0.001) compared with those without MASLD. The leptin-to-adiponectin (L/A) ratio was also significantly elevated (1.63 vs 0.27, P < 0.001). Similar patterns were observed in patients with MetS: Adiponectin (1208.41 pg/mL vs 2086.10 pg/mL, P = 0.002), leptin (1.51 ng/mL vs 0.79 ng/mL, P = 0.002), and L/A ratio (1.28 vs 0.41, P = 0.009). By contrast, no significant differences in adipokine levels were observed between patients with and without advanced fibrosis or complete biochemical response (all P > 0.05).

Conclusion: Adipokines reflect metabolic status in PBC. The L/A ratio is promising biomarker for MASLD. No significant association between leptin and adiponectin levels and advanced fibrosis was detected within the limited sample size of this study.

Acute-on-chronic liver failure (ACLF) is a swiftly deteriorating condition characterized by profound systemic inflammation and failure of multiple organ systems, leading to high early mortality. There remains a critical need for more effective biomarkers to facilitate timely and accurate risk assessment. Recent findings by Zhu and Yan demonstrated that evaluating temporal changes in the C-reactive protein to albumin ratio (CAR), especially the 7-day variation, offers superior prediction of 28-day mortality compared with single baseline measurements. By integrating the 7-day variation of CAR with the model for end-stage liver disease sodium score and the grade of hepatic encephalopathy, the Chinese Group on Study of Severe Hepatitis B (COSSH)-CAR model was created, which surpassed traditional prognostic tools such as the Child-Pugh, model for end-stage liver disease, and COSSH-ACLF. This comment highlights the importance of using dynamic biomarker trajectories rather than static values for prognostic evaluation. CAR is biologically compelling because it captures both the inflammatory burden and the patient's nutritional/physiological reserve. While the COSSH-CAR model is promising and based on routinely obtainable laboratory data, its widespread adoption will depend on validation in larger, diverse, and non-hepatitis B virus-related cohorts. Future work should examine CAR kinetics in prospective and interventional studies and consider how they may support individualized management strategies. Collectively, these observations suggest that the CAR could represent an important addition to current ACLF prognostic frameworks.

Background: Anticoagulation therapy is recommended during the acute or subacute stage for patients with pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome (PA-HSOS). Transjugular intrahepatic portosystemic shunts (TIPS) is suggested as a step-up treatment when patients do not respond to anticoagulants. However, more evidence of the efficacy of TIPS is needed.

Aim: To evaluate the effect of TIPS in these patients.

Methods: Between January 2013 and September 2020, we retrospectively enrolled patients with PA-HSOS who did not respond to short-term anticoagulation therapy at four hospitals. The patients were divided into a TIPS treatment group and an anticoagulation therapy group. Baseline information and clinical characteristics were collected and recorded. Survival in both groups was the primary study endpoint and the risk factors for patient death were further analyzed.

Results: A total of 99 patients were enrolled according to the inclusion and exclusion criteria (63 in the TIPS group and 36 in the anticoagulation therapy group). There were 17 deaths during the median follow-up time of 32.5 months. Treatment, age, aspartate aminotransferase, and serum total bilirubin were independent risk factors for predicting death. The survival of patients in the TIPS group was significantly greater than that of patients in the continuing anticoagulation therapy group (P = 0.028). When stratified by the Drum-Tower Severity Scoring, in the TIPS group, mild and moderate patients had better outcomes than severe patients.

Conclusion: TIPS can improve the transplant-free survival rate in patients with PA-HSOS who do not respond to short-term anticoagulation therapy, and patients with mild and moderate Drum-Tower Severity Scoring grade can benefit from TIPS.

Background: Dynamic alterations in lymphocyte subsets demonstrate significant correlations with clinical disease severity in patients with coronavirus disease 2019 (COVID-19). As the most prevalent chronic liver disease globally, non-alcoholic fatty liver disease (NAFLD) exhibits distinct chronic inflammatory and immunometabolic disturbances that may substantially affect immune response patterns in COVID-19 patients. Nevertheless, the characteristics of lymphocyte subset dynamics and their clinical implications in COVID-19-NAFLD remain to be fully elucidated.

Aim: To characterize the dynamic changes in lymphocyte subsets among COVID-19 patients with NAFLD, in order to delineate their immunological profiles and inform clinical management strategies.

Methods: The cohort study compared lymphocyte subpopulations in 858 COVID-19 patients and 670 COVID-19-NAFLD patients at admission, discharge, and 2-week/4-week post-discharge follow-ups.

Results: Compared to COVID-19 patients without NAFLD, NAFLD-comorbid patients demonstrated persistently elevated CD3+CD4+ counts as well as lymphocyte counts and percentages at admission and at the 2-week and 4-week follow-ups post-discharge (all P < 0.05). Among COVID-19-NAFLD patients, those aged ≥ 60 years had significantly lower CD3+ counts, CD3+CD4+ counts, CD3+CD8+ counts, lymphocyte counts and percentages, and CD19+ counts and percentages at all assessed time points (all P < 0.05); significant liver fibrosis correlated with reduced CD3+CD4+ counts, CD3+CD8+ counts, and lymphocyte counts and percentages across all time points (all P < 0.05); multimorbidity (≥ 3 comorbidities) exacerbated immune imbalance, marked by elevated CD3+CD4+ percentages and CD56+ counts at admission, increased CD3+CD4+ counts, lymphocyte counts, and CD19+ counts and percentages at discharge, as well as sustained increases in CD3+CD4+ counts at the 2-week follow-up and higher CD3+CD4+ percentages at the 4-week post-discharge follow-up (all P < 0.05); and obesity and elevated liver enzymes were independently linked to higher CD3+CD4+ counts, CD19+ counts, and lymphocyte counts at all post-admission evaluations (from discharge through the 4-week follow-up) (all P < 0.05).

Conclusion: Age, liver fibrosis, comorbidities, obesity, liver enzyme abnormalities, vaccination status, low-density lipoprotein cholesterol, and hemoglobin A1c significantly modulate immune responses in COVID-19-NAFLD patients, warranting targeted clinical attention. Furthermore, patients with uncomplicated NAFLD (including lean NAFLD) also require particular clinical attention to mitigate risks of immune imbalance.

Background: Extracorporeal shock wave lithotripsy (ESWL) and laser lithotripsy (LL) are established alternatives for the management of difficult common bile duct (CBD) stones. However, there is limited evidence regarding the efficacy and safety of the latest-generation Dornier Delta III lithotripter. In particular, evidence on the clinical performance of the Dornier Delta III lithotripter is scarce.

Aim: To evaluate and compare the efficacy and safety of ESWL performed with the Dornier Delta III and of LL using a single-operator cholangioscope with specific focus on stone clearance rates, number of treatment sessions, and procedure-related adverse events in a large patient cohort.

Methods: We conducted a retrospective analysis of a prospectively maintained database at AIG Hospitals, Hyderabad, covering the period from January 2019 to December 2022. A total of 458 patients with difficult bile duct stones underwent either ESWL or LL based on clinical discretion. ESWL was performed using the Dornier Delta III lithotripter, whereas LL was carried out with a single-operator cholangioscope in combination with an yttrium-aluminum-garnet laser.

Results: The 387 patients with difficult bile duct stones (mean age 53.8 ± 15.7 years, 58.7% male) underwent ESWL. A single CBD stone was noted in 46.8% of patients while 53.2% patients had multiple stones. Complete duct clearance was achieved in 95.1% of patients, with 68.7% requiring two or more ESWL sessions. Adverse events included cholangitis in 3 patients and post-sphincterotomy bleeding in 4 patients; All were managed conservatively. Seventy-one patients (mean age 55 ± 15.4 years, 64.8% male) underwent LL. Complete duct clearance was achieved in 97.2% of patients with single-session clearance in 58 (81.7%) patients. The remaining 18.3% of patients required two or three sessions for fragmented stone removal. Adverse events included cholangitis in 2 patients and mild pancreatitis in 1 patient; all were managed conservatively. Patients with incomplete clearance were referred for surgery. There was no significant difference in efficacy between ESWL and LL (95.1% vs 97.2%, P = 0.4).

Conclusion: ESWL using the latest generation lithotripter and LL provide equally effective and safe alternatives for managing difficult CBD stones, minimizing the need for surgery.

The prospective cohort study by Twohig et al evaluates the efficacy of a novel educational video module (EVM) in promoting treatment engagement and reducing alcohol use among hospitalized patients with alcohol-associated liver disease (ALD). Analyzing 42 patients, the study demonstrates that exposure to the EVM significantly increased rates of both pharmacologic (50% vs 22%) and psychosocial (73.8% vs 44%) treatment within 30 days of discharge, while markedly reducing the return to alcohol use (7.9% vs 35.6%) compared to a retrospective control cohort. These findings underscore the potential of a standardized, scalable educational intervention to bridge critical knowledge gaps in alcohol use disorder (AUD) management. While the study highlights the EVM as a powerful tool for patient empowerment and system-level quality improvement, its single-center design and limited sample size necessitate further validation through multicenter randomized trials. This article contextualizes these promising results within the broader challenge of AUD treatment, emphasizing the urgent need to integrate innovative, patient-centered education into standard clinical pathways to alleviate the growing burden of ALD.

Artificial intelligence (AI) is reshaping modern medicine, and gastroenterology and hepatology are among the specialties where its impact is becoming increasingly evident. AI has demonstrated the ability to process and analyze large amounts of clinical, radiological, endoscopic, and multi-omics data, offering unprecedented opportunities to enhance diagnostic accuracy, optimize therapeutic decision-making, and reduce variability in clinical practice. In endoscopy, computer-aided detection and diagnosis systems have shown consistent improvements in adenoma detection rates and real-time polyp characterization, while in hepatology, machine learning models outperform traditional scores for non-invasive assessment of liver fibrosis. Furthermore, multimodal approaches integrating genomics, microbiome, and imaging data are paving the way for precision medicine in inflammatory bowel disease and other complex digestive conditions. Despite these promising advances, significant barriers remain. The quality and heterogeneity of training data, the lack of rigorous external validation, and the opaque "black box" nature of many algorithms limit their clinical reliability. Ethical challenges, including accountability in case of diagnostic errors, protection of patient privacy, cost, and equitable access, also need to be addressed. This narrative review summarizes the current applications of AI in gastroenterology and hepatology, critically examines methodological and ethical challenges, and outlines future perspectives. Responsible, transparent, and equitable implementation will be essential for AI to transition from an emerging promise to a consolidated tool that improves outcomes and advances personalized digestive care.

In this editorial, we comment on the article by Wang et al, which investigates molecular and immune biomarkers predictive of response to sintilimab plus lenvatinib in hepatitis B virus-associated hepatocellular carcinoma (HCC). Yet, despite remarkable progress with immune-checkpoint and anti-angiogenic combinations, the biological heterogeneity of HCC continues to limit durable responses and individualized care. By integrating high-resolution transcriptomic, exomic, and immune-cell-profiling data, Wang et al identified a coherent triad - elevated LINC01554 expression, enrichment of CD4+ central-memory T cells, and solitary-tumour morphology - that independently predicted prolonged progression-free survival. This constellation links tumour-intrinsic transcriptional restraint, adaptive immune competence, and anatomical containment, illustrating how multi-omic profiling can clarify determinants of therapeutic benefit. These insights signify a shift from empiricism to biologically guided therapy, providing a scaffold for biologic stratification, longitudinal response monitoring, and rational sequencing of immunotherapeutic and anti-angiogenic agents. Collectively, they redefine HCC as a dynamic biological ecosystem rather than a uniform malignancy and highlight the imperative to embed multi-omic biomarker platforms within future clinical-trial design - marking a decisive step toward precision hepatology in inflammation-driven cancers.