International Journal Of Hepatology[JOURNAL]
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200 papers
Shock in Adult-Onset Still's Disease Complicated by Macrophage Activation Syndrome: Clinical Characteristics and Prognosis of 14 Patients.
Li D, Cheng L, Zhang Y … +1 more , Qian L
Int J Hepatol · 2025 · PMID 41255953 · Full text
BACKGROUND: Shock is a rare life-threatening complication in patients with adult-onset Still's disease (AOSD) complicated by macrophage activation syndrome (MAS). This study aims to summarize the clinical characteristics...
BACKGROUND: Shock is a rare life-threatening complication in patients with adult-onset Still's disease (AOSD) complicated by macrophage activation syndrome (MAS). This study aims to summarize the clinical characteristics and prognosis of this condition. METHODS: We performed a retrospective study of 14 patients hospitalized from January 2017 to December 2023 who experienced shock secondary to AOSD complicated by MAS. RESULTS: Among the 14 patients, 11 presented with a progressive rash, and 10 exhibited a remittent fever prior to shock onset. Compared to levels at admission, serum ferritin (SF), lactate dehydrogenase (LDH), and procalcitonin levels were significantly elevated, while serum albumin (ALB) levels were significantly decreased, both at the time of MAS diagnosis and at the onset of shock. Shock resolved in nine patients, and five died. All the improved patients were treated with high-dose glucocorticoids (equivalent prednisolone dose ≥ 1 mg/kg/day) prior to MAS diagnosis, and received glucocorticoid pulse therapy. Among them, five (55.6%) received combination therapy with low-dose etoposide and cyclosporine, one (11.1%) received etoposide alone, one (11.1%) received a combination of cyclosporine and tocilizumab, and two (22.2%) receive no additional immunosuppressive therapy. Of the five patients who died, four (80%) received glucocorticoids therapy (two before MAS diagnosis), and only two received a combination of cyclosporine. None of the deceased patients received tocilizumab or etoposide. Compared to patients who died, the patients who improved had significantly higher rates of early glucocorticoid therapy (100% vs. 40%, = 0.027) and etoposide use (66.7% vs. 0%, = 0.028). CONCLUSION: Shock is a life-threatening condition secondary to AOSD with MAS. The early combined use of high-dose glucocorticoids and etoposide may be key to improving outcomes in this critical condition.
Minimal Criteria to Screen for Wilson Disease: A Delphi Consensus in the United States.
Bronstein JM, Gonzalez-Peralta RP, Lorincz M … +3 more , Medici V, Diaz-Mendoza S, Pantiri K
Int J Hepatol · 2025 · PMID 41210890 · Full text
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 time...
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.
Anti-Inflammatory Drugs for Alcoholic Liver Disease: A Systematic Review on Survival and Adverse Events.
Zulfatim HS, Afrina V, d'Arqom A … +3 more , Sutantyo QE, Amornsupak K, Nualkaew T
Int J Hepatol · 2025 · PMID 41199753 · Full text
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...
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.
Studying the Effect of Hepatic Steatosis on Liver Stiffness Measurement (LSM) in HBV Patients With and Without Therapy.
Lak E, Jasemi Zergani F, Shokati Eshkiki Z … +3 more , Hajiani E, Talebi V, Mohamadi S
Int J Hepatol · 2025 · PMID 41194966 · Full text
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. Sin...
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).
Results of a Randomized Controlled Trial Evaluating the Impact of Conversion to LCP Tacrolimus on Neurologic Toxicities in Liver Transplant Recipients.
Coffman KS, Revuelta GJ, DeTurk N … +10 more , Palmer C, Culpepper H, Overstreet M, Fleming J, Terry K, Patel N, McGillicuddy J, Nagaraju S, Rice TC, Taber DJ
Int J Hepatol · 2025 · PMID 41089174 · Full text
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-ce...
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], = 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 ( = 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.
Radiological Response and Characteristics of Patients Diagnosed With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: An Observational Study.
Brito VA, Aroucha DCBL, Arruda AM … +6 more , Furtado LCC, Fonseca VP, Oliveira-Filho PCR, Branco ELPC, Brito MFBL, Pereira LMMB
Int J Hepatol · 2025 · PMID 41025044 · Full text
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...
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. To identify factors associated with the response to TACE by modified Response Evaluation Criteria in Solid Tumors (mRECIST) in patients with HCC. 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%. 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 ( < 0.001) compared to the nonresponding group, resulting in lesion enlargement ( = 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 ( < 0.001). Hepatitis C virus (HCV) etiology was associated with a higher chance of treatment response ( = 0.032). Initial disease staging was characterized by single tumors, while intermediate staging presented larger tumors after TACE. 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.
Adverse Reactions of First-Line Tyrosine Kinase Inhibitors in Advanced Hepatocellular Carcinoma Treatment: A Descriptive Analysis From WHO-VigiAccess.
Sui WF, Duan YX, Cai ZF … +3 more , Xia YM, Li JY, Fu JH
Int J Hepatol · 2025 · PMID 40980823 · Full text
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 (WH...
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. 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. A total of 63,375 ADR reports were analyzed for two first-line TKIs used in advanced HCC treatment: lenvatinib ( = 28,419) and sorafenib ( = 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. 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.
Efficacy of Sofosbuvir-Velpatasvir-Ribavirin Regimen for Retreatment of Chronic Hepatitis C in Patients With Prior DAA Failure: A Retrospective Study From a National Treatment Center.
Singh S, Sengupta S, Kumar D … +4 more , Mukherjee K, Hasan AMD, Sadhukhan P, Ahammed SM
Int J Hepatol · 2025 · PMID 40948725 · Full text
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 DA...
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. 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). 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. 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.
Identification of Key Gene Related to Matrisome in HBV-Associated Liver Cirrhosis via Bioinformatics Analysis.
Chaulagain RP, Shrestha Y, Dinislam K … +1 more , Jin S
Int J Hepatol · 2025 · PMID 40901642 · Full text
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...
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. 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 < 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 (: 91%, : 90%), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Among 14,470 analyzed genes, 2125 were upregulated and 3689 downregulated in cirrhotic tissues. Upregulated genes (, ) were linked to metabolic reprogramming, while downregulated genes (, ) implicated immune dysregulation. A subset of 274 ECM-related DEGs (178 upregulated, 96 downregulated) was identified, including , , , and . Pathway analysis highlighted dysregulation of Ras/MAPK and ERBB signaling pathways associated with fibrogenesis and tumorigenesis. 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.
Clinical and Histopathological Correlation of Quantitative HBsAg Levels in Chronic Hepatitis B.
Yılmaz T, Özdemir E, Düzenci D … +1 more , Bahçecioğlu İH
Int J Hepatol · 2025 · PMID 40761436 · Full text
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, l...
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. 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. 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 ( = 0.014 and = 0.025, respectively). Among CHB patients, HBeAg-positive patients had significantly lower qHBsAg levels than HBeAg-negative patients (1805 vs. 4028 IU/mL, < 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 ( = -0.388, = 0.015). 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 in the Pathogenesis of Liver Diseases: A Review.
Nowicka AA, Gomułkiewicz A, Serafińska S … +2 more , Simon KA, Dzięgiel P
Int J Hepatol · 2025 · PMID 40755507 · Full text
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 response...
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.
Alcohol Consumption After Listing for Liver Transplantation Is Associated With Increased Risk of Alcohol Consumption After Transplantation.
Abrial L, Erard D, Tron L … +8 more , Radenne S, Bonadona A, Barthelon J, Antonini T, Hilleret MN, Decaens T, Dumortier J, Costentin C
Int J Hepatol · 2025 · PMID 40611916 · Full text
Alcohol abstinence is required before liver transplantation (LT) for alcohol-related liver disease (ALD). However, some patients may have alcohol intake during the pretransplant period. Describe the prevalence of alcoho...
Alcohol abstinence is required before liver transplantation (LT) for alcohol-related liver disease (ALD). However, some patients may have alcohol intake during the pretransplant period. Describe the prevalence of alcohol consumption on list and impact on the LT project. All patients listed for ALD, in two French transplant centers, between January 2014 and December 2018 were included retrospectively. Documented alcohol consumption (DAC) on list was defined by any alcohol intake during the waiting period elicited by patient interview and/or by biology. Four hundred and twenty-six patients were included. DAC on list was observed in 41 patients (9.6%), with a median delay of 6.2 months (IQR 2.8; 11.4) after listing. Addiction counseling was proposed to 30 patients (73%), and 28 (68%) were placed or maintained in temporary contraindication. DAC on list was associated with the waiting time length (OR 1.07, 95% CI 1.04; 1.1; < 0.001), occupation ("intermediate occupation" OR 6.39, 95% CI 1.93; 22.74, = 0.003 and "employee": OR 5.83, 95% CI 1.79; 20.68, = 0.004 compared to "Craftsman" category) and less likely in former smokers (OR 0.23, 95% CI 0.07; 0.77; = 0.02). We observed a higher risk of alcohol consumption after LT (OR 6.36, 95% CI 1.61-26.93; = 0.009) in patient with DAC on list, but no impact on 5-year posttransplant survival. Alcohol consumption on the list was documented in 9.6% of the patients, associated with an increased risk of alcohol consumption after LT. These results support systematic screening of alcohol consumption and active addiction counseling before transplant. Importantly, 5-year overall survival since listing was not statistically different between patients with or without DAC during the waiting time period.
Metabolic-Associated Steatotic Liver Disease: From Molecular Mechanisms to Novel Therapies.
Cooper J, Patel P, Tristeza J … +1 more , Yang A
Int J Hepatol · 2025 · PMID 40589542 · Full text
Metabolic-associated steatotic liver disease (MASLD) is a burgeoning worldwide burden and is currently the leading indication for a liver transplant. Despite the growing burden of disease, there are few pharmacological t...
Metabolic-associated steatotic liver disease (MASLD) is a burgeoning worldwide burden and is currently the leading indication for a liver transplant. Despite the growing burden of disease, there are few pharmacological treatments available. The underlying molecular mechanisms of the development of MASLD are still being elucidated. In this review, we will summarize the known molecular mechanisms in the development of MASLD along with past, current, and future pharmacologic clinical trials.
Clinical Evaluation of the Progression of Liver Disease in Patients Coinfected With HBV and HDV in the Western Amazon Region of Brazil.
Ton JT, Passos-Silva AM, Ton ET … +6 more , de Castro Silva E, Santos AO, Araújo A, Vieira D, Salcedo JMV, Vasconcelos MPA
Int J Hepatol · 2025 · PMID 40520348 · Full text
Worldwide, an estimated 296 million individuals are chronic carriers of hepatitis B virus (HBV), with approximately 5% also coinfected with hepatitis delta virus (HDV). In Brazil, HBV and HDV are endemic in the states of...
Worldwide, an estimated 296 million individuals are chronic carriers of hepatitis B virus (HBV), with approximately 5% also coinfected with hepatitis delta virus (HDV). In Brazil, HBV and HDV are endemic in the states of the Western Amazon. This study is aimed at characterizing a cohort of patients coinfected with HBV and HDV and comparing their clinical and epidemiological profiles with those of HBV monoinfected individuals. The study involved a retrospective clinical analysis of individuals monoinfected with HBV and coinfected with HDV, conducted between 2017 and 2018 in Rondônia, Brazil. A total of 324 patients were enrolled in the study, comprising 302 individuals with HBV monoinfection and 22 with HBV-HDV coinfection. Patients with HDV exhibited significantly more clinical signs of advanced liver disease. Using APRI and FIB-4 scores with cut-off values established for HBV, over 40% of HDV-infected patients had values indicative of advanced liver fibrosis, compared to 5%-10% in the HBV monoinfected group. Across all evaluated parameters of liver disease, HDV patients displayed more severe characteristics, with 45.5% already showing signs of advanced liver disease at the time of enrollment. Our study underscores the importance of the clinical analysis of hepatitis delta as a more aggressive disease model compared to hepatitis B in the population of the Western Brazilian Amazon, highlighting its significance as a public health concern in the region.
Reduced Mastication Is Associated With Dynapenia Markers in Patients With Cirrhosis: A Cross-Sectional Study.
Brunetto B, Saraiva L, Callegari-Jacques SM … +6 more , Ferri H, Lizott HB, Valões R, Fernandes SA, Hoppe L, Fornari F
Int J Hepatol · 2025 · PMID 40365525 · Full text
Dental diseases are common in patients with cirrhosis. In these patients, reduced mastication might interfere with protein intake and contribute to malnutrition. We addressed the relationship between reduced mastication...
Dental diseases are common in patients with cirrhosis. In these patients, reduced mastication might interfere with protein intake and contribute to malnutrition. We addressed the relationship between reduced mastication and dynapenia in patients with cirrhosis. This cross-sectional study involved patients with cirrhosis treated in a Brazilian center. Trained dentists performed oral examinations and tested the patients for nutritional parameters such as handgrip strength (HGS) and gait speed test (GST). Reduced mastication was presumed when a patient had molar edentulism (≥ 3 teeth), bad dental occlusion, or ill-fitting denture. Associations between mastication status and malnutrition were evaluated using multivariate linear regression analysis for continuous measures and adjusted prevalence ratio (PR (95% confidence interval)) for binary measures. We included 149 patients with cirrhosis (60 ± 13 years old, 76% men, 64% Child A, 60% due to alcoholism only). Reduced mastication affected 107 patients (72%), low muscle strength (decreased HGS) occurred in 45 (30%), and decreased GST was observed in 58 (41%, among 143 patients able to walk). Thirty-one out of 143 (22%) presented decreased HGS and GST, characterizing dynapenia. Reduced mastication was associated either with decreased HGS [PR = 2.28 (1.08-4.81), = 0.030; reduced mastication decreases the HGS mean by 12.5 kg for men ( < 0.001) and 8.1 kg for women ( = 0.065)] or with decreased GST [PR 1.97 (1.09-3.55), = 0.024; reduced mastication increased the time of GST by 1.1 s on average ( = 0.005)], adjusting for age, alcoholic etiology, and Child-Pugh classification. Reduced mastication is associated with dynapenia markers in patients with cirrhosis. Further studies are needed to assess whether oral rehabilitation can change the curse of malnutrition in this population.
Virological and Biochemical Effects of Tenofovir Alafenamide in Different Patient Groups With Chronic Hepatitis B Virus Infection in Real-World Cohort.
Bektas E, Yilmaz A, Kikili CI … +10 more , Nuriyev K, Istemihan Z, Senkal IV, Imanov Z, Cavus B, Cifcibasi Ormeci A, Akyuz F, Demir K, Besisik SF, Kaymakoglu S
Int J Hepatol · 2025 · PMID 40265082 · Full text
Hepatitis B virus (HBV) infection is an important health concern worldwide. HBV infection can lead to acute hepatitis, cirrhosis, hepatocellular carcinoma, liver failure, and death. Nucleos(t)ide analogs (NAs) form the c...
Hepatitis B virus (HBV) infection is an important health concern worldwide. HBV infection can lead to acute hepatitis, cirrhosis, hepatocellular carcinoma, liver failure, and death. Nucleos(t)ide analogs (NAs) form the core of the HBV treatment. The safety and efficacy of NAs in long-term follow-up are still critical issues. We enrolled 225 consecutive patients with at least 12 months of longitudinal follow-up using tenofovir alafenamide (TAF), including 39 antiviral naïve and 186 antiviral experienced patients. In the treatment-experienced group, the main reasons for switching from other NAs to TAF were renal dysfunction and osteoporosis. Renal outcome, lipid profile, virological response, and ALT normalization under the TAF treatment were evaluated. Age > 60 years, liver transplant recipients, and patients with decompensated cirrhosis were evaluated separately, as well as the total cohort. Phosphorus levels increased especially in hypophosphatemic individuals, eGFR levels also increased slightly but statistically significantly, and the remarkable improvement in eGFR stages was observed in the eGFR < 60 mL/min/1.73 m group. A minimal increase in LDL-c levels occurred after TAF treatment, which did not reach statistical significance. Total cholesterol and HDL-c levels increased significantly, while triglyceride levels remained unchanged. In the total cohort, HBV-DNA was strongly suppressed in either treatment-naïve or experienced patients. ALT and AST levels decreased with the TAF treatment, but ALT normalization rate did not change significantly. No serious adverse events associated with TAF occurred, and discontinuation was not required in the total cohort. Our findings support that TAF treatment is well-tolerated and effective in patients with chronic HBV infection.
Hepatocellular Carcinoma and Health-Related Quality of Life: A Systematic Review of Outcomes From Systemic Therapies.
Jayabalan D, Dhakal S, Raguragavan A … +5 more , Saxena A, Jeffrey GP, Calzadilla-Bertot L, Adams LA, Wallace MC
Int J Hepatol · 2025 · PMID 40230581 · Full text
Poor outcomes in advanced hepatocellular carcinoma (HCC) coupled with potential significant treatment side effects underpin a strong rationale to assess health-related quality of life (HRQOL) in those treated with system...
Poor outcomes in advanced hepatocellular carcinoma (HCC) coupled with potential significant treatment side effects underpin a strong rationale to assess health-related quality of life (HRQOL) in those treated with systemic therapies. This study is aimed at quantifying the effect of systemic therapies on HRQOL outcomes in HCC patients when compared to baseline or placebo, other systemic therapies, and transarterial radioembolisation (TARE). In May 2024, two independent reviewers searched PubMed, EMBASE, and Google Scholar for studies comparing postsystemic therapy HRQOL scores in adult patients with HCC to baseline or placebo, other systemic therapies, or to TARE. Narrative synthesis was used to synthesise results. Risk of bias was assessed using RoB 2 and ROBINS-I. This review was structured according to PRISMA guidelines and was prospectively registered in the PROSPERO register (CRD42024521699). Twenty-nine studies with 10,472 patients using eight HRQOL instruments were included. Compared to baseline, patients on atezolizumab/bevacizumab and sorafenib both experienced significant declines in HRQOL, and lenvatinib nonsignificantly decreased HRQOL. HRQOL remained unchanged in patients on pembrolizumab or nivolumab. Atezolizumab/bevacizumab and lenvatinib both significantly delayed HRQOL deterioration compared to sorafenib. Compared to TARE, atezolizumab/bevacizumab delayed time-to-deterioration in HRQOL, whereas sorafenib had significantly worse HRQOL. Despite worsening HRQOL outcomes compared to baseline, the first-line agents atezolizumab/bevacizumab and lenvatinib had superior HRQOL outcomes in comparison to sorafenib. Sorafenib significantly worsened HRQOL compared to TARE. As the majority of included studies included sorafenib, which has been largely superseded by newer therapies, further trials evaluating HRQOL with these newer therapies are required.
Ischemia-Reperfusion Injury at Time-Zero Biopsy as a Prognostic Factor in Predicting Liver Graft Outcome in Egyptian Living Donor Liver Transplanted Patients.
Sabry A, Zakaria H, Maher D … +2 more , Seddik RM, Nada A
Int J Hepatol · 2025 · PMID 40224292 · Full text
Ischemia-reperfusion injury (IRI) is believed to contribute to the early dysfunction of the graft as well as the survival of the patients following liver transplantation (LT). This study is aimed at ascertaining the role...
Ischemia-reperfusion injury (IRI) is believed to contribute to the early dysfunction of the graft as well as the survival of the patients following liver transplantation (LT). This study is aimed at ascertaining the role of time-zero biopsies in predicting early graft dysfunction and 5-year patient survival after living donor liver transplantation (LDLT). From February 2012 to August 2017, time-zero biopsies were obtained from 60 patients. Histological grading of time-zero biopsies was performed to identify the severity of IRI. Patients were divided into two groups: no or minimal to mild IRI versus moderate to severe IRI. Time-zero biopsies of 60 liver allografts revealed no or minimal to mild IRI ( = 38, 63.3%) (Group 1) versus moderate to severe IRI ( = 22, 36.7%) (Group 2). Group 2 recipients indicated a significant increase in serum bilirubin and a higher incidence of early graft dysfunction. There were significant survival differences between the two groups ( = 0.033), and the rate of death was higher in the moderate to severe IRI group. Recipient age, steatosis, and longer CIT were identified as independent predictors of moderate to severe IRI. Time-zero biopsies with moderate to severe IRI upon biopsy can predict adverse clinical outcomes following LT.
Cirrhosis Is an Independent Risk Factor for Mortality in Ischemic Stroke-A Nationwide Analysis.
Ogunniyi KE, Alagbo HO, Tolu-Akinnawo OZ … +7 more , Ibrahim S, Adeleke OD, Mahtani A, Ugwendum DF, Padda I, Farid M, Awoyemi T
Int J Hepatol · 2025 · PMID 40144590 · Full text
Ischemic stroke remains a leading cause of preventable cardiovascular mortality worldwide, with emerging evidence suggesting an association between liver cirrhosis and both stroke occurrence and severity. However, the sp...
Ischemic stroke remains a leading cause of preventable cardiovascular mortality worldwide, with emerging evidence suggesting an association between liver cirrhosis and both stroke occurrence and severity. However, the specific impact of cirrhosis on stroke-related mortality remains incompletely understood. Elucidating this relationship is crucial for improving risk stratification and early recognition of high-risk individuals. : We conducted a retrospective cohort study comparing ischemic stroke patients with cirrhosis to those without, using the National Inpatient Sample database for 2021. Univariate and multivariate logistic regression analyses were performed to compare various outcomes. A total of 536,199 discharges for ischemic stroke were included, among which 4464 had a documented history of liver cirrhosis. Discharges with cirrhosis were predominantly male (58.2%) with a mean age of 67 years, which was 2.17 years younger than those without cirrhosis. In-hospital mortality was 7% (95% CI: 5.5%-8.99%) among discharges with cirrhosis versus 4.2% (95% CI: 4.0%-4.33%) in those without.. After adjusting for cofounders in multivariate logistic regression, it was revealed that cirrhosis is associated with 69% higher mortality risk in stroke discharges (OR = 1.69, 95% CI: 1.27-2.25, < 0.001). Our study identifies liver cirrhosis as an independent risk factor for mortality among patients hospitalized with ischemic stroke. These findings underscore the necessity of incorporating proactive management strategies for liver cirrhosis into stroke care and prevention protocols, potentially improving outcomes in this high-risk population.
The Risk Factors of Refractory Adult-Onset Still's Disease.
Cheng L, Zong H, Li D … +2 more , Zhang Y, Qian L
Int J Hepatol · 2025 · PMID 40134799 · Full text
Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology and pathogenesis. Some patients fail to respond to conventional glucocorticoids and immunosuppressant therapies, a condition...
Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology and pathogenesis. Some patients fail to respond to conventional glucocorticoids and immunosuppressant therapies, a condition known as refractory AOSD. The prognosis for patients with refractory AOSD is typically poor, significantly impacting their quality of life and overall health. This study retrospectively analyzes the predictive factors for refractory AOSD to provide new strategies and insights for clinical diagnosis and treatment. Overall, 105 AOSD patients hospitalized between January 2008 and October 2024 were selected, 41 of whom were classified as refractory. Multivariate logistic regression analysis was conducted to identify risk factors for refractory AOSD, and receiver operating characteristic (ROC) curves were used to evaluate the predictive power of these indicators. Patients with refractory AOSD were more likely to develop splenomegaly and MAS. Additionally, the neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase, serum ferritin (SF) levels, and AOSD system score were higher in refractory cases than in nonrefractory cases, while lymphocyte count and platelet (PLT) count were lower in the refractory AOSD group ( < 0.05). Multivariate logistic regression analysis identified PLT, NLR, and AOSD system scores as independent risk factors for predicting refractory AOSD. ROC curve analysis revealed that the area under the curve for PLT, NLR, and AOSD system scores were 0.659, 0.661, and 0.660, respectively. The optimal cutoff values for PLT, NLR, and AOSD system score in predicting refractory AOSD were 314.5 × 10/L, 10.555, and 5.5, respectively, with sensitivities of 80.5%, 53.7%, and 75.6% and specificities of 46.9%, 75.0%, and 50.0%, respectively. PLT < 314.5 × 10/L, NLR > 10.555, or an AOSD system score of > 5.5 before treatment may serve as independent risk factors for predicting refractory AOSD, providing clinicians with an early warning to identify disease progression.
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