International Journal of Hepatology最新文献

Background: The objective was to develop consensus on minimal screening criteria for Wilson disease (WD) diagnosis in US gastroenterology and neurology settings for implementation in clinical practice to support the timely diagnosis of WD.

Methods: A modified Delphi panel with three rounds was conducted. The first round survey was developed with input from a steering committee of four clinical experts in WD who set the analysis rules (consensus: ≥ 80%). Other US gastroenterologists/hepatologists or neurologists with experience treating WD were recruited using purposive sampling, and 32 were invited to participate.

Results: Eleven panelists completed the three rounds. Consensus was reached for 94/126 (74.6%) statements. All panelists agreed that hepatomegaly, splenomegaly, or stigmata of liver disease are suggestive of WD in patients with a neuropsychiatric manifestation; a neurologic exam, 24-h urine copper, ceruloplasmin, and Kayser-Fleischer (KF) ring examination should be performed; and liver biopsy and liver copper determination can be a useful final stage to confirm WD diagnosis. Panelists agreed that noninvasive testing should be performed prior to invasive testing and that the absence of KF rings does not exclude a diagnosis of WD. Panelists agreed that it is important to collaborate in a multidisciplinary team.

Conclusions: This study identified minimal criteria to raise suspicion of WD, minimal tests to confirm or rule out a WD diagnosis, and areas with poor consensus to be explored in future research. These results can complement clinical practice guidance and support cross-specialty collaboration.

Aim: Alcoholic liver disease (ALD) is a major global health burden, with alcoholic hepatitis (AH) and severe alcoholic hepatitis (SAH) contributing significantly to mortality. Inflammation plays a central role in disease progression, and various anti-inflammatory therapies, particularly corticosteroids, have been employed to improve survival. However, clinical outcomes across different treatments vary. This systematic review is aimed at evaluating the effectiveness of anti-inflammatory pharmacological therapies compared to corticosteroids in improving short-term survival at 1, 3, and 6 months and to assess the incidence of adverse events in patients with ALD.

Methods: The review followed PRISMA guidelines. A comprehensive literature search was conducted in PubMed, Scopus, ScienceDirect, and Clarivate Web of Science using MeSH terms. Inclusion criteria consisted of full-text, open-access, English articles (2014-2024) that reported survival outcomes and adverse events in patients with ALD treated with corticosteroids versus alternative or adjunctive anti-inflammatory therapies. Studies lacking a corticosteroid comparator were excluded.

Results: Nine randomized controlled trials (RCTs) involving patients with AH and SAH were included. The interventions compared to corticosteroids included pentoxifylline, anakinra, metadoxine, S-adenosylmethionine (SAMe), granulocyte colony-stimulating factor (G-CSF), rifaximin, and fecal microbiota transplantation (FMT) as monotherapies or combination regimens. Among anti-inflammatory therapies, combination therapy with corticosteroids and metadoxine significantly improves 3- and 6-month survival rates in patients with ALD. Similarly, corticosteroids combined with SAMe demonstrate efficacy in enhancing 1- and 6-month survival rates. Notably, the metadoxine-based combination regimen exhibited a superior safety profile, with fewer adverse events compared to other anti-inflammatory therapies evaluated in this review.

Conclusions: Even though corticosteroids remain the current standard of care for severe AH, this review suggests that certain combination therapies, particularly those involving metadoxine or SAMe, may offer some survival benefits. FMT also shows promise by potentially improving survival while maintaining a favorable safety profile. Among these, the metadoxine-based regimen has been explored as a promising therapeutic strategy in some contexts. However, these findings must be interpreted with caution. The evidence is limited by significant study heterogeneity and a lack of high-quality RCTs. These limitations underscore the critical need for well-powered, rigorous RCTs with standardized survival and safety outcomes.

Introduction: The issue of fatty liver disease is becoming more widely acknowledged as a global health concern. This disorder manifests as inflammation brought on by varied degrees of fat buildup in the liver tissue. Since studies have shown that fatty liver is a major factor affecting the prognosis of patients with chronic hepatitis, the coexistence of viral hepatitis and fatty liver is noteworthy. Transient elastography is a useful technique for identifying and measuring the degree of steatosis. The liver stiffness measurement (LSM) index might be a good substitute for these patients if it shows a high diagnostic value in identifying hepatic steatosis.

Methods: This pilot study presents an analytical cross-sectional analysis of 53 hepatitis B patients (26 men and 27 women) who sought care at Aria Hospital in Ahvaz, Iran, between April 2023 and November 2024. Participants were divided into two groups: 34 patients in the treatment group and 19 patients in the nontreatment group. The subjects' prevalence of hepatic fibrosis was evaluated using transient elastography and the LSM index. Further comparisons between treatment-receiving and nonreceiving patients were conducted using LSM.

Results: The prevalence of steatosis was found to be 25% in the untreated group and 26.7% in the treatment group. In the treatment group, the incidence of fibrosis was 58.8%, while in the untreated group, it was 57.9%. In both the treatment-treated and nontreated groups of hepatitis B patients, the associations between the study variables and the LSM index were evaluated. Every correlation that was found was not statistically significant. Additionally, the LSM's diagnostic value for hepatic steatosis was evaluated. In the treatment group, the test showed limited diagnostic value, while in the untreated group, it showed satisfactory diagnostic value.

Conclusions: In patients with hepatitis B, the LSM derived from transient elastography does not show a statistically significant correlation with factors such as age, gender, body mass index (BMI), or degree of hepatic steatosis. According to this study, the LSM number is not a reliable indicator for identifying hepatic steatosis in patients with hepatitis B when compared to the CAP score (AUC = 0.69 and 0.74).

Background/aims: Neurotoxicity is commonly seen in liver transplant (LT) patients receiving tacrolimus. We sought to determine the impact of LCP tacrolimus on neurologic toxicity in LT recipients.

Methods: This single-center, semiblinded, parallel group randomized controlled trial compared neurotoxicity burden in LT patients receiving immediate-release (IR) tacrolimus versus LCP tacrolimus. Thirty LT recipients transplanted between January 2020 and February 2022 were enrolled between 15 and 364 days posttransplant and followed for 6 months postrandomization. The primary endpoint was change from baseline to 6 months in composite Patient Global Impression of Improvement (PGI-I) score. Select secondary endpoints included change in Fahn-Tolosa-Marin (FTM) Tremor Rating Scale, IMAB-Q10, SF-12, and Medical Symptom Validity Test (MSVT) scores.

Results: No significant differences were seen in composite PGI scores, though all patients saw improvement in overall PGI scores (IR -5 [-13.5 to -0.25] vs. LCP -4 [-9.5 to -0.5], p = 0.78). Other tests examining neurotoxicities showed no difference between groups but an overall trend toward improvement in symptoms between baseline and end of study. One episode of moderate rejection (rejection activity index [RAI] score of 6) was reported in the LCP group, with no episodes in the IR group (p = 0.31). No graft loss or mortality occurred in either group.

Conclusions: Our study showed LCP tacrolimus had similar rates of neurotoxicity in LT recipients compared to IR without increasing the risk of rejection, graft loss, or mortality; these results suggest LCP tacrolimus can be a safe alternative in LT recipients.

Trial registration: ClinicalTrials.gov identifier: NCT03823768.

Introduction: Hepatocellular carcinoma (HCC), commonly associated with cirrhosis and factors such as viral hepatitis and metabolic disorders, is often diagnosed at advanced stages, influencing survival. Transarterial chemoembolization (TACE) is a primary therapeutic approach aimed at prolonging survival or serving as a link to liver transplantation. Objective: To identify factors associated with the response to TACE by modified Response Evaluation Criteria in Solid Tumors (mRECIST) in patients with HCC. Materials and Methods: This is a retrospective cohort study conducted at a Liver Institute in Brazil, including patients with HCC at Stages A and B treated with TACE from January 2011 to December 2021. Data were collected from electronic or digitized physical medical records and included demographic, clinical-laboratory, and tumor-related variables. Radiological response was assessed using mRECIST criteria. Statistical analysis encompassed various tests, with a significance level of 5%. Results: Seventy-six patients were evaluated, the majority being male (67.1%), with a median age of 62 years (57.0-70.0). Patients who responded to TACE showed a significant reduction in lesion size (p < 0.001) compared to the nonresponding group, resulting in lesion enlargement (p = 0.047). Only 38.2% of patients showed an objective response after the first TACE, with a trend towards a higher response in patients with stable disease (p < 0.001). Hepatitis C virus (HCV) etiology was associated with a higher chance of treatment response (p = 0.032). Initial disease staging was characterized by single tumors, while intermediate staging presented larger tumors after TACE. Conclusion: The association between HCV-induced cirrhosis and a better response to TACE underscores the importance of assessing liver function status in determining therapeutic response. No association was identified between pre-TACE alpha-fetoprotein levels and a higher likelihood of radiological response.

Aims: To determine the safety of first-line tyrosine kinase inhibitors (TKIs) in advanced hepatocellular carcinoma (HCC) treatment by assessing the adverse drug reactions (ADRs) as reported in the World Health Organization (WHO)-VigiAccess database. Methods: We compiled ADR reports for two first-line TKIs from WHO-VigiAccess with retrospective descriptive analysis, gathering data on the disease systems and symptoms associated with ADRs, as well as population and geographic characteristics of advanced HCC patients. Results: A total of 63,375 ADR reports were analyzed for two first-line TKIs used in advanced HCC treatment: lenvatinib (N = 28,419) and sorafenib (N = 34,956). Gender distribution revealed male predominance for sorafenib (67.62%), whereas lenvatinib had more female reporters (53.40%). Among the 27 system organ classes, gastrointestinal disorders had the highest number of ADR reports for lenvatinib (15,683, 55.18%) and sorafenib (21,423, 61.29%). Based on gastrointestinal disorders, lenvatinib and sorafenib had similar reporting odds ratio (ROR) of 0.94 (0.96-0.92) and 0.96 (0.98-0.94) and proportional reporting ratio (PRR) of 0.95 (0.97-0.94) and 0.97 (0.98-0.95). The highest proportions of adverse reactions of diarrhea reported for the two drugs were 12% for lenvatinib and 15.74% for sorafenib. Conclusion: While gastrointestinal toxicities were class-wide concerns, agent-specific risks necessitate tailored monitoring. These findings emphasized the need for vigilant monitoring and personalized management in clinical practice.

Introduction: Direct-acting antivirals (DAAs) are highly effective in treating HCV infection, but a small subset of patients may fail to achieve SVR12 and require further intervention. In resource-limited settings where second-line DAAs (such as SOF/VEL/VOX) may be unavailable, optimizing first-line treatments is essential. This study evaluated the efficacy (SVR12) of a retreatment regimen based on first-line DAAs (SOF/VEL) with ribavirin. Method: This retrospective study screened all viremic patients who attended the apex treatment center (ATC) between January 2019 and December 2023 and received DAAs as per the National Viral Hepatitis Control Program (NVHCP) guidelines. Patients who failed to achieve SVR12 were subsequently retreated with the available first-line regimen (SOF/VEL plus ribavirin). Results: A total of 1814 viremic patients attended the ATC. One thousand two hundred and sixty-two patients completed therapy. One thousand one hundred ninety-eight (94.9%) patients achieved SVR12, and 64 patients (5.1%) failed to achieve SVR12. Additionally, 41 patients with DAA failure were referred from the treatment center (TC) and model treatment center (MTC) for evaluation. After further exclusions, 36 patients were enrolled, and 30 of them were offered retreatment. The majority of patients were male (64.5%) with a median age of 45 years (IQR, 19-68). Five patients were cirrhotic, while the remainder was noncirrhotic. Baseline HCV RNA levels before the retreatment regimen were 87,882 IU/mL (IQR, 9870-484,902). Most patients (96.6%) had Genotype 3 HCV infection. Prior to retreatment, 27 patients had received a 12-week regimen of sofosbuvir and daclatasvir, while only three had been treated with the sofosbuvir-velpatasvir regimen. After retreatment with sofosbuvir, velpatasvir, and ribavirin, 22 patients (73%) achieved SVR12. None of the patients experienced any adverse event. Conclusion: First-line DAAs are highly effective to treat naïve patients. In the absence of second-line options, retreatment with first-line DAAs (SOF/VEL plus ribavirin) is a viable alternative.

Background: Hepatitis B virus (HBV)-associated liver cirrhosis, characterized by progressive fibrosis and regenerative nodule formation, remains a critical public health concern due to its high risk of progression to hepatocellular carcinoma (HCC). The matrisome-comprising extracellular matrix (ECM) components such as collagens, laminins, fibronectin, glycoproteins, and proteoglycans-plays a pivotal role in disease pathogenesis. Previous studies have shown that HBV infection modulates ECM composition and activates fibrogenic responses through hepatic stellate cells, contributing to cirrhosis and eventual HCC development. However, key ECM-related genes driving HBV-induced cirrhosis remain poorly understood. Methods: Bulk RNA-seq data from 30 normal and 30 HBV-related cirrhotic liver tissues were analyzed. Differentially expressed genes (DEGs) were identified using the Limma package based on thresholds of p < 0.01 and |log2 fold change| > 1. ECM-related genes were curated from the Molecular Signatures Database (MsigDB). Functional significance was assessed via random forest classification (accuracy: 91%, recall: 90%), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Results: Among 14,470 analyzed genes, 2125 were upregulated and 3689 downregulated in cirrhotic tissues. Upregulated genes (COX6B1, RPS10) were linked to metabolic reprogramming, while downregulated genes (PLCG2, ARHGEF12) implicated immune dysregulation. A subset of 274 ECM-related DEGs (178 upregulated, 96 downregulated) was identified, including CTSA, CRELD2, MAPK10, and ITGA1. Pathway analysis highlighted dysregulation of Ras/MAPK and ERBB signaling pathways associated with fibrogenesis and tumorigenesis. Conclusions: This bioinformatics study delineates key matrisome-associated genes and pathways in HBV-related cirrhosis, offering novel insights into potential biomarkers and therapeutic targets. Further validation in larger cohorts is warranted to confirm clinical relevance.

Objective: This study is aimed at comparing different clinical forms of chronic hepatitis B (CHB) infection (HBeAg-negative chronic HBV infection and HBeAg-positive and HBeAg-negative CHB patients) and evaluate their demographic, laboratory, virological, and histopathological characteristics, as well as investigate the relationship between quantitative HBsAg (qHBsAg) levels and these parameters. Materials and Methods: This prospective study included a total of 307 patients, comprising 142 HBeAg-negative chronic HBV infection and 165 CHB patients (39 HBeAg-positive and 126 HBeAg-negative). Patient data, including age, sex, ALT, AST, GGT, ALP, total bilirubin, HBV DNA, and qHBsAg levels, were recorded. Additionally, liver biopsy was performed in 111 cases (31 HBeAg-positive and 80 HBeAg-negative), and histological activity index (HAI) and fibrosis staging (ISHAK score) were evaluated. Results: No significant differences were observed between HBeAg-negative chronic HBV infection and CHB patients in age and sex distribution. In the CHB group, ALT and HBV DNA levels were significantly higher (p = 0.014 and p = 0.025, respectively). Among CHB patients, HBeAg-positive patients had significantly lower qHBsAg levels than HBeAg-negative patients (1805 vs. 4028 IU/mL, p < 0.001). Histopathological evaluations showed no significant association between qHBsAg levels and fibrosis severity (ISHAK score > 2) or necroinflammatory activity (HAI > 6). ROC analysis confirmed the limited diagnostic value of qHBsAg for advanced fibrosis (AUC 0.511, 95% CI 0.454-0.569). In HBeAg-positive patients, a weak negative correlation was found between qHBsAg and HBV DNA levels (r = -0.388, p = 0.015). Discussion: Our study demonstrated variability in laboratory findings across different forms of CHB. Notably, HBeAg-positive patients exhibited high HBV DNA levels alongside low qHBsAg levels. The limited efficacy of qHBsAg as a fibrosis marker suggests caution in its clinical use. These findings underscore the importance of considering multiple parameters in assessing liver damage.

Metallothioneins (MTs) are primarily known for maintaining cellular metal homeostasis and protecting against metal toxicity, but they also play critical roles in mitigating oxidative stress and modulating immune responses. Reduced MTs expression is associated with disease progression in several chronic hepatic disorders. In metabolic dysfunction-associated steatotic liver disease (MASLD), MT1 downregulation has been linked to the transition from simple steatosis to steatohepatitis. Additionally, evidence suggests that individuals with low MTs expression may be more susceptible to obesity, which is one of the key drivers in the development of MASLD. In chronic viral hepatitis, in vivo MTs downregulation contrasts with acute-phase in vitro upregulation, suggesting an effect of persistent inflammation. MTs downregulation in hepatocellular carcinoma (HCC) correlates with poor prognosis, positioning MTs as potential biomarkers and therapeutic targets. In contrast, increased MTs expression may play a protective or diagnostically informative role in other conditions. In alcoholic hepatitis, MT1 overexpression contributes to defense against oxidative stress and inflammation. In Wilson's disease, MTs demonstrates prominent hepatic expression and may offer diagnostic value alongside traditional markers such as rhodanine staining. In cholestatic liver diseases like PBC and PSC, MTs expression correlates with disease progression. This review highlights the emerging role of MTs in liver disease pathogenesis and positions them as promising molecular tools that may inform future strategies for diagnosis, prognosis, and treatment of liver diseases.