International Journal of Hepatology最新文献

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.

Background: 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. Objectives: Describe the prevalence of alcohol consumption on list and impact on the LT project. Methods: 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. Results: 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; p < 0.001), occupation ("intermediate occupation" OR 6.39, 95% CI 1.93; 22.74, p = 0.003 and "employee": OR 5.83, 95% CI 1.79; 20.68, p = 0.004 compared to "Craftsman" category) and less likely in former smokers (OR 0.23, 95% CI 0.07; 0.77; p = 0.02). We observed a higher risk of alcohol consumption after LT (OR 6.36, 95% CI 1.61-26.93; p = 0.009) in patient with DAC on list, but no impact on 5-year posttransplant survival. Conclusion: 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 (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.

Background: 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. Methods: The study involved a retrospective clinical analysis of individuals monoinfected with HBV and coinfected with HDV, conducted between 2017 and 2018 in Rondônia, Brazil. Results: 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. Conclusion: 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.

Background and Aim: 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. Methods: 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. Results: 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), p = 0.030; reduced mastication decreases the HGS mean by 12.5 kg for men (p < 0.001) and 8.1 kg for women (p = 0.065)] or with decreased GST [PR 1.97 (1.09-3.55), p = 0.024; reduced mastication increased the time of GST by 1.1 s on average (p = 0.005)], adjusting for age, alcoholic etiology, and Child-Pugh classification. Conclusions: 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.