International Journal of Hepatology最新文献

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.

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 m² 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.

Aim: 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). Methods: 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). Results: 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. Conclusion: 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.

Background and Aims: 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. Methods: 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. Results: 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, p < 0.001). Conclusions: 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.

Background: 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. Methods: 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. Results: 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 (p < 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 × 10⁹/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. Conclusion: PLT < 314.5 × 10⁹/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.

Background and Aims: 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). Patients and Methods: 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. Results: Time-zero biopsies of 60 liver allografts revealed no or minimal to mild IRI (n = 38, 63.3%) (Group 1) versus moderate to severe IRI (n = 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 (p = 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. Conclusion: Time-zero biopsies with moderate to severe IRI upon biopsy can predict adverse clinical outcomes following LT.

Background and aims: Focal liver lesions (FLL) are one of the most common indications for hepatology and hepatobiliary surgery consultation. In this retrospective study, we aim to assess if contrast-enhanced ultrasound (CEUS) can address diagnostic dilemmas in the evaluation of indeterminate liver lesions by identifying characteristics of indeterminate FLL on CEUS and correlating these with cross-sectional imaging and pathology findings. Methods: We retrospectively reviewed all patients who underwent CEUS evaluation for liver lesions over a 28-month period (Oct 2020 to Jan 2023) at the University of Kentucky. To assess the relationship between CEUS results and the corresponding CT, MRI, and/or pathologic findings, the McNemar-Bowker tests were performed. Results: Twenty-nine patients were included (after two exclusions from a total n of 31). Mean age was 54 years, 62% were female, and 48% had underlying cirrhosis. Of the 29 patients with initial cross-sectional imaging, the initial results showed malignancy or likely malignant lesion in 6 patients and benign or likely benign lesion in 6 patients. The remaining 17 patients had inconclusive/indeterminate results. CEUS clarified an "indeterminate" CT/MRI result 15 times out of 17 (88.2%), moving the diagnosis to "benign" 11 times while suggesting "malignant" only four times. When aggregating indeterminate cross-sectional results with either benign or malignant categories suggested by CEUS, CEUS never reversed a benign CT/MRI diagnosis but often reversed a malignant CT/MRI diagnosis. Conclusion: CEUS provided a definitive diagnosis of indeterminate liver lesions in approximately 90% of patients and avoided the need for biopsy in most patients. In cases where the liver lesions were biopsied, CEUS accurately distinguished malignant versus benign lesions as confirmed by biopsy findings. CEUS, therefore, has the potential to provide a precise diagnosis for the majority of indeterminate lesions.