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Background and Aims: Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described., Approach and Results: A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7-36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8-29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p <0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11-2.18])., Conclusions: RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH., (Copyright © 2024 American Association for the Study of Liver Diseases.)

The epicardial space (ES) is the anatomic region located between the myocardium and the pericardium. This space includes the visceral pericardium and the epicardial fat that contains the epicardial coronary arteries, cardiac veins, lymphatic channels, and nerves. The epicardial fat represents the main component of the ES. This fat deposit has been a focus of research in recent years owing to its properties and relationship with coronary gossypiboma plaque and atrial fibrillation. Although this region is sometimes forgotten, a broad spectrum of lesions can be found in the ES and can be divided into neoplastic and nonneoplastic categories. Epicardial neoplastic lesions include lipoma, paraganglioma, metastases, angiosarcoma, and lymphoma. Epicardial nonneoplastic lesions encompass inflammatory infiltrative disorders, such as immunoglobulin G4-related disease and Erdheim-Chester disease, along with hydatidosis, abscesses, coronary abnormalities, pseudoaneurysms, hematoma, lipomatosis, and gossypiboma. Initial imaging of epicardial lesions may be performed with echocardiography, but CT and cardiac MRI are the best imaging modalities to help characterize epicardial lesions. Due to the nonspecific onset of signs and symptoms, the clinical history of a patient can play a crucial role in the diagnosis. A history of malignancy, multisystem diseases, prior trauma, myocardial infarction, or cardiac surgery can help narrow the differential diagnosis. The diagnostic approach to epicardial lesions should be made on the basis of the specific location, characteristic imaging features, and clinical background. © RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Background & Aims: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality., Methods: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year., Results: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death., Conclusion: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients., Impact and Implications: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis., Methods: Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD., Results: The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH., Conclusions: Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Abnormal liver function tests (A-LFTs) during admission for coronavirus disease-19 (COVID-19) are frequent, but its evolution after COVID-19 resolution remains unexplored. We evaluated factors related to A-LFTs during COVID-19 and assessed the liver outcome after patients' discharge. This is a observational study including: (1) retrospective analysis of variables related to A-LFTs during COVID-19; and (2) follow-up evaluation with blood test, transient elastography and liver biopsy in those with persistent A-LFTs. A-LFTs were defined according to CTCAEv4.0. Among 595 patients, 366 (61.5%) showed A-LFTs. The ratio of partial pressure of oxygen and inspired oxygen fraction (P/F) below 200, ferritin ≥1000 ng/mL, male gender and antibiotic and immunomodulatory treatments were related to A-LFTs. Follow-up evaluation was performed in 153 individuals. Persistent A-LFTs at follow-up was similar in patients with/without A-LFTs during admission (14.1% vs. 4.9%, p = 0.104). Fifteen (93%) and 58 (39%) patients with/without A-LFTs at follow-up showed metabolic fatty liver disease criteria (p < 0.001), which were histologically confirmed. In conclusion, A-LFTs during COVID-19 were related to infection severity. Abnormalities remitted at follow-up in >80% of patients, and no correlation between A-LFTs at admission and at follow-up was found. Most patients with A-LFTs at follow-up had non-invasive and histologically proven fatty liver disease., (© 2022 John Wiley & Sons Ltd.)

Background: Nucleos(t)ide analogues withdrawal may improve HBsAg loss rates. However, conditions to select patients are not well established., Aims: to evaluate the impact of HBsAg kinetics before treatment interruption on post-treatment response., Methods: Longitudinal, ambispective study in non-cirrhotic chronic hepatitis B HBeAg-negative patients, analysing on-treatment and post-treatment HBsAg kinetics. On-treatment HBsAg kinetics diagnostic accuracy (AUROC) to identify HBsAg loss was evaluated., Results: 52 HBeAg-negative patients stopped treatment after 8.2 years, and 6 (11.5%) achieved HBsAg loss one year after withdrawal. Multivariate analysis showed that on-treatment HBsAg kinetics was related to HBsAg loss (OR=0.10; 95%CI=0.016-0.632; p = 0.014) with a high diagnostic accuracy (AUROC=0.935). A significant HBsAg decline ≥1 log10 IU/mL showed a positive and negative predictive value of 50% and of 97.6%, respectively. After treatment interruption, HBsAg decline speed (log10 IU/mL/year) accelerated in patients treated >6 years (from -0.06 to -0.20, p<0.05) and remained stable in treated <6 years (from -0.12 to -0.12 p=ns)., Conclusions: On-treatment HBsAg kinetics can predict post-treatment HBsAg loss rate. Half of patients with a significant HBsAg decline can eliminate HBsAg the first year after withdrawal. Post-treatment HBsAg decline is faster not only in patients who lost the HBsAg but also in those who remain HBsAg-positive., Competing Interests: Conflict of interest None declared., (Copyright © 2022. Published by Elsevier Ltd.)

Background & Aims: Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort., Methods: This was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end-stage liver disease (MELD). We evaluated bacterial infections, liver-related complications, mortality and liver function tests after 90 days., Results: Twenty-one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute-on-chronic liver failure (ACLF) linked to infections within the treatment group. Liver-related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment., Conclusions: Rifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)