Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B

COVID-19; Hepatitis B; TenofovirCOVID-19; Hepatitis B; TenofovirCOVID-19; Hepatitis B; TenofovirBackground and Aims HIV-positive patients on tenofovir hydroxyl fumarate (TDF)/emtricitabine have a lower risk of COVID-19 and hospitalization than those given other treatments. Our aim was to analyze the severity of COVID-19 in patients with chronic hepatitis B (CHB) on TDF or entecavir (ETV). Methods Spanish hospital databases (n = 28) including information regarding adult CHB patients on TDF or ETV for the period February 1st to November 30th 2020 were searched for COVID-19, defined as a positive SARS-CoV-2 polymerase chain reaction, and for severe COVID-19. Results Of 4736 patients, 117 had COVID-19 (2.5%), 67 on TDF and 50 on ETV. Compared to patients on TDF, those on ETV showed (p < 0.05) greater rates of obesity, diabetes, ischemic cardiopathy, and hypertension. COVID-19 incidence was similar in both groups (2.3 vs. 2.6%). Compared to TDF, patients on ETV more often (p < 0.01) had severe COVID-19 (36 vs. 6%), required intensive care unit (ICU) (10% vs. 0) or ventilatory support (20 vs. 3%), were hospitalized for longer (10.8 ± 19 vs. 3.1 ± 7 days) or died (10 vs. 1.5%, p = 0.08). In an IPTW propensity score analysis adjusted for age, sex, obesity, comorbidities, and fibrosis stage, TDF was associated with a sixfold reduction in severe COVID-19 risk (adjusted-IPTW-OR 0.17, 95%CI 0.04–0.67, p = 0.01). Conclusion Compared to ETV, TDF seems to play a protective role in CHB patients with SARS-CoV-2 whereby the risk of severe COVID-19 is lowered.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. No funding sources needed

Early predictors of corticosteroid response in acute severe autoimmune hepatitis: a nationwide multicenter study

Early predictors; Corticosteroid; Autoimmune hepatitisPredictors primerencs; Corticosteroides; Hepatitis autoimmunePredictores tempranos; Corticosteroide; Hepatitis autoinmuneBackground and Aims To assess whether corticosteroids improve prognosis in patients with AS-AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids. Methods This was a retrospective cohort study including all patients with AS-AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan–Meier and Cox regression methods were used for data analysis. Results Of 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90-day transplant-free survival was 61.6% (95% confidence interval [CI] 55.4–67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2–0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C-index 0.82; [95% CI 0.8–0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non-responders. MELD on day 7 with a cut-off of 25 (sensitivity 62.5%[95% CI: 47.0–75.8]; specificity 95.2% [95% CI: 89.9–97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3–2.1). Conclusion Older patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided.This study was supported in part by grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, number PI20/01302, awarded to Agustín Albillos and number PI 21/01310, awarded to Luis Téllez. CIBEREHD is funded by the Instituto de Salud Carlos III using grants cofinanced by the European Development Regional Fund “A way to achieve Europe” (EDRF). María Carlota Londoño received support from the Plan Nacional de I+D+I co-funded by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER-"Una manera de Hacer Europa") (PI17/00955). Laura Patricia Llovet received the Resident Award “Clínic-La Pedrera” granted by the Hospital Clínic de Barcelona, Research, Innovation and Education Department

Rituximab is a safe and effective alternative treatment for patients with autoimmune hepatitis : Results from the ColHai registry

Small series suggest that rituximab could be effective as treatment for autoimmune hepatitis (AIH), although data are scarce. We aimed to evaluate the efficacy and safety of rituximab in different cohorts of patients with AIH. Methods: Multicentre retrospective analysis of the 35 patients with AIH and its variant forms treated with rituximab and included in the ColHai registry between 2015 and 2023. Most patients were female (83%), 10 (29%) had cirrhosis and four (11.4%) variant forms of AIH. Indication for rituximab were as follows: 14(40%) refractory AIH, 19(54%) concomitant autoimmune or haematological disorder, 2(6%) intolerance to prior treatments. In three (9%) subjects with a concomitant disorder, rituximab was the first therapy for AIH. Overall, 31 (89%) patients achieved or maintained complete biochemical response (CBR), including the three in first-line therapy. No difference in CBR was observed according to rituximab indication (refractory AIH 86% vs. concomitant disorders 90%, p =.824) or cirrhosis (80% vs. 92%, p =.319). Rituximab was associated with a significant reduction in corticosteroids (median dose: prior 20 vs. post 5 mg, p <.001) and the discontinuation of ≥1 immunosuppressant in 47% of patients. Flare-free rate at 1st, 2nd and 3rd year was 86%, 73% and 62% respectively. Flares were not associated with the development of liver failure and were successfully managed with repeated doses of rituximab and/or increased corticosteroids. Three (9%) patients experienced infusion-related adverse events (1 anaphylaxis and 2 flu-like symptoms) and five (14%) infections. Rituximab is safe and effective in patients with refractory AIH and those treated due to concomitant autoimmune or haematological disorders

Clinical Utility of a Risk-Adapted Protocol for the Evaluation of Coronary Artery Disease in Liver Transplant Recipients

Este estudio, en el cual el solicitante es autor senior (útimo autor), estuvo encaminado a determinar si un protocolo de evaluación de enfermedad coronaria adaptado al riesgo basal en pacientes receptores de trasplante hepático, era capaz de atenuar el riesgo de enfermedad coronaria y en la supervivencia de pacientes trasplantados. El resultado fundamental de este estudio prospectivo fue que este protocolo (que comprende una evaluacion escalonada de la anatomía coronaria con intervenciones terapéuticas adaptadas) iguala la probabilidad de eventos cardiovasculares postrasplante con respecto a los pacientes de bajo riesgo. La aplicabilidad de este estudio es grande puesto que permite de forma protocolizada y adaptada a cada paciente la valoracion precisa del riesgo coronario, evitando exploraciones agresivas.The prevalence and management of coronary artery disease (CAD) in liver transplantation (LT) candidates are not well characterized. The aims of this study were to evaluate the impact on clinical outcomes of a specifically designed protocol for the management of asymptomatic CAD in LT candidates and to investigate noninvasive risk profiles for obstructive and nonobstructive CAD for 202 LT candidates. Those with high baseline cardiovascular risk (CVR; defined by the presence of classic CVR factors and/or decreased ejection fraction) received coronary angiography and significant arterial stenosis and were treated with percutaneous stents. Patients were followed up after LT until death or coronary event (CE). There were 78 patients who received coronary evaluation (62 direct angiography, 14 computed tomography coronary angiography, and 2 both). Of them, 39 (50%) patients had CAD of any severity, and 6 (7.7%) had significant lesions (5 were amenable to be treated with stents, whereas 1 patient had diffuse lesions which contraindicated the LT). Insulin-dependent diabetes was the only factor related to CAD of any severity (odds ratio, 3.44; 95% confidence interval [CI], 1.00-11.97). A total of 69 patients (46 with coronary evaluation) received LT. The incidence of CEs and overall survival after LT were similar between patients with and without coronary evaluation. Furthermore, no differences occurred between these groups in a multivariate competing risk model (subhazard ratio, 0.84; 95% CI, 0.27-2.61; P = 0.76). In conclusion, the application of an angiographic screening protocol of CAD in a selected high-risk Mediterranean population is safe and effective. The short- and medium-term incidence rates of CEs and death after LT in this population are similar to that observed in low-risk patients.Depto. de MedicinaFac. de MedicinaTRUEpu

Noninvasive prediction of outcomes in autoimmune hepatitis-related cirrhosis

The value of noninvasive tools in the diagnosis of autoimmune hepatitis (AIH)-related cirrhosis and the prediction of clinical outcomes is largely unknown. We sought to evaluate (1) the utility of liver stiffness measurement (LSM) in the diagnosis of cirrhosis and (2) the performance of the Sixth Baveno Consensus on Portal Hypertension (Baveno VI), expanded Baveno VI, and the ANTICIPATE models in predicting the absence of varices needing treatment (VNT). A multicenter cohort of 132 patients with AIH-related cirrhosis was retrospectively analyzed. LSM and endoscopies performed at the time of cirrhosis diagnosis were recorded. Most of the patients were female (66%), with a median age of 54 years. Only 33%-49% of patients had a LSM above the cutoff points described for the diagnosis of AIH-related cirrhosis (12.5, 14, and 16 kPa). Patients with portal hypertension (PHT) had significantly higher LSM than those without PHT (15.7 vs. 11.7 kPa; P = 0.001), but 39%-52% of patients with PHT still had LSM below these limits. The time since AIH diagnosis negatively correlated with LSM, with longer time being significantly associated with a lower proportion of patients with LSM above these cutoffs. VNT was present in 12 endoscopies. The use of the Baveno VI, expanded Baveno VI criteria, and the ANTICIPATE model would have saved 46%-63% of endoscopies, but the latter underpredicted the risk of VNT. Conclusions: LSM cutoff points do not have a good discriminative capacity for the diagnosis of AIH-related cirrhosis, especially long-term after treatment initiation. Noninvasive tools are helpful to triage patients for endoscopy

Early predictors of corticosteroid response in acute severe autoimmune hepatitis: a nationwide multicenter study

Background and aims: To assess whether corticosteroids improve prognosis in patients with AS-AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids. Methods: This was a retrospective cohort study including all patients with AS-AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan-Meier and Cox regression methods were used for data analysis. Results: Of 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90-day transplant-free survival was 61.6% (95% confidence interval [CI] 55.4-67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2-0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C-index 0.82; [95% CI 0.8-0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non-responders. MELD on day 7 with a cut-off of 25 (sensitivity 62.5%[95% CI: 47.0-75.8]; specificity 95.2% [95% CI: 89.9-97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3-2.1). Conclusion: Older patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided.This study was supported in part by grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, number PI20/01302, awarded to Agustín Albillos and number PI 21/01310, awarded to Luis Téllez. CIBEREHD is funded by the Instituto de Salud Carlos III using grants cofinanced by the European Development Regional Fund “A way to achieve Europe” (EDRF). María Carlota Londoño received support from the Plan Nacional de I+D+I co-funded by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER-"Una manera de Hacer Europa") (PI17/00955). Laura Patricia Llovet received the Resident Award “Clínic-La Pedrera” granted by the Hospital Clínic de Barcelona, Research, Innovation and Education Department