ABSTRACT
BACKGROUND: Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is the recommended rescue therapy for patients with chronic hepatitis C infection who fail direct-acting antivirals (DAAs). Data are limited on the effectiveness of this treatment after the current first-line therapies. Our aim was to analyse the effectiveness and safety of SOF/VEL/VOX among patients failing sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). METHODS: Retrospective multicentre study (26 Spanish hospitals), including chronic hepatitis C patients unsuccessfully treated with SOF/VEL or GLE/PIB, and retreated with SOF/VEL/VOX ± ribavirin for 12 weeks between December 2017 and December 2022. RESULTS: In total, 142 patients included: 100 (70.4%) had failed SOF/VEL and 42 (29.6%) GLE/PIB. Patients were mainly men (84.5%), White (93.9%), with hepatitis C virus genotype (GT) 3 (49.6%) and 47.2% had liver cirrhosis. Sustained virological response (SVR) was evaluated in 132 patients who completed SOF/VEL/VOX and were followed 12 weeks after end of treatment; 117 (88.6%) achieved SVR. There were no significant differences in SVR rates according to initial DAA treatment (SOF/VEL 87.9% vs. GLE/PIB 90.2%, p = 0.8), cirrhosis (no cirrhosis 90% vs. cirrhosis 87.1%, p = 0.6) or GT3 infection (non-GT3 91.9% vs. GT3 85.5%, p = 0.3). However, when considering the concurrent presence of SOF/VEL treatment, cirrhosis and GT3 infection, SVR rates dropped to 82.8%. Ribavirin was added in 8 (6%) patients, all achieved SVR. CONCLUSION: SOF/VEL/VOX is an effective rescue therapy for failures to SOF/VEL or GLE/PIB, with an SVR of 88.6%. Factors previously linked to lower SVR rates, such as GT3 infection, cirrhosis and first-line therapy with SOF/VEL were not associated with lower SVRs.
Subject(s)
Aminoisobutyric Acids , Antiviral Agents , Benzimidazoles , Carbamates , Cyclopropanes , Hepatitis C, Chronic , Heterocyclic Compounds, 4 or More Rings , Proline , Quinoxalines , Sofosbuvir , Sulfonamides , Sustained Virologic Response , Humans , Male , Female , Hepatitis C, Chronic/drug therapy , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Antiviral Agents/therapeutic use , Sofosbuvir/therapeutic use , Carbamates/therapeutic use , Middle Aged , Retrospective Studies , Sulfonamides/therapeutic use , Benzimidazoles/therapeutic use , Quinoxalines/therapeutic use , Proline/analogs & derivatives , Proline/therapeutic use , Cyclopropanes/therapeutic use , Aged , Pyrrolidines/therapeutic use , Lactams, Macrocyclic/therapeutic use , Drug Combinations , Leucine/analogs & derivatives , Leucine/therapeutic use , Drug Therapy, Combination , Treatment Outcome , Hepacivirus/genetics , Hepacivirus/drug effects , BenzopyransABSTRACT
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.
Subject(s)
Hepatitis, Alcoholic , Recurrence , Registries , Humans , Male , Female , Middle Aged , Hepatitis, Alcoholic/mortality , Risk Factors , Adult , Spain/epidemiology , Registries/statistics & numerical data , Severity of Illness Index , Incidence , Prognosis , AgedABSTRACT
Objetivos: Analizar la evolución analítica, clínica y de la fibrosis en pacientes F3-F4 curados con antivirales de acción directa (AAD). Pacientes y métodos: Estudio unicéntrico, observacional y prospectivo. Se incluyeron todos los pacientes con hepatitisC F3-F4 curados con AAD del 1 de noviembre de 2014 al 31 de agosto de 2019. Se realizó una visita basal (VB) y a las 12semanas (12s), 1, 2, 3 y 4años tras finalizar el tratamiento. Se recogieron variables demográficas, analíticas, medición no invasiva de la fibrosis, marcadores indirectos de hipertensión portal, presencia de varices esofágicas, descompensaciones de la cirrosis y hepatocarcinoma. Resultados: Se trataron 169 pacientes: 123 (72,8%) hombres, edad 57,5±12 años; 117 (69,2%) presentaban cirrosis, 99 (84,6%) ChildA. El 96,4% consiguieron respuesta virológica sostenida (RVS). La mediana de seguimiento fue de 46,14 (2,89-62,55) meses. Durante el seguimiento se observó precozmente un aumento significativo de plaquetas (155×103/μl [VB]; 163×103/μl [12s]), colesterol (158mg/dl [VB]; 179mg/dl [12s]) y albúmina (4,16g/dl [VB]; 4,34g/dl [12s]), y un descenso significativo de GPT (82UI/l [VB]; 23UI/l [12s]), GOT (69UI/l [VB]; 26UI/l [12s]), GGT (118UI/l [VB]; 48UI/l [12s]), y bilirrubina (0,9mg/dl [VB]; 0,7mg/dl [12s]). La fibrosis disminuyó, también inicialmente, tanto con métodos serológicos como Fibroscan (19,9KPa [VB]; 14,8KPa [12s]); p<0,05). El 8,1% de los pacientes con cirrosis compensada presentaron alguna descompensación. El 4,5% desarrollaron varices esofágicas. Nueve (5,52%) pacientes presentaron hepatocarcinoma de novo; seis (3,68%) lo presentaban basalmente, y el 40% sufrieron recidiva. Durante el seguimiento la mortalidad fue del 9,2%. Conclusiones: Existe mejoría de los parámetros analíticos y de la fibrosis hepática medida por métodos no invasivos en los pacientes F3-F4 curados con AAD.(AU)
Aims: To analyze laboratory parameters, clinical and fibrosis evolution in F3-F4 patients cured with direct-acting antivirals (DAA). Patients and methods: Unicenteric, observational and prospective study. All F3F4 hepatitis C patients cured with DAA from 01/11/2014 to 31/08/2019 were included. A basal visit (BV) was performed and at 12 weeks (12w), 1, 2, 3 and 4 years after treatment. Demographic and laboratory variables, fibrosis measured by non-invasive tests, indirect markers of portal hypertension, the presence of esophageal varices, cirrhosis decompensation and hepatoceullar carcinoma were collected. Results: 169 patients were treated: 123 (72.8%) men, age 57.5±12 years; 117 (69.2%) with cirrhosis, 99 (84.6%) ChildA. 96,4% achieved SVR. The study was conducted for a median follow-up of 46.14 (2.89-62.55) months. It was observed a significant increase in platelets [155×103/μL (BV); 163×103/μL (12w)], cholesterol [158mg/dL (BV); 179mg/dL (12w)] and albumin [4.16g/dL (BV); 4.34g/dL (12w)] and a significant decrease in ALT [82UI/L (BV); 23UI/L (12w], AST [69UI/L (BV); 26UI/L (12w)], GGT [118UI/L (BV); 48UI/L (12w)] and bilirrubin [0.9mg/dL (BV); 0.7mg/dL (12w)]. Fibrosis also improved early in follow-up, both by serological methods and Fibroscan [19.9kPa (BV); 14.8kPa (12w; P<.05]. 8.1% of compensated cirrhosis patients had some decompensation. 4.5% developed esophageal varices. Nine patients (5.52%) had de novo hepatocellular carcinoma; 6 (3.68%) had hepatoceullar carcinoma in BV and 40% had a recurrence. During follow-up mortality was 9.2%. Conclusions: There is an improvement in laboratory parameters and fibrosis measured by non-invasive methods in F3-F4 patients cured with DAA. However, the risk of decompensation and the incidence/recurrence of hepatocellular carcinoma still remain, so there is a need to follow these patients.(AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Infections , Hepatitis C , Fibrosis , Clinical Evolution , Antiviral Agents , Sustained Virologic Response , Carcinoma, Hepatocellular , Prospective Studies , Gastroenterology , Gastrointestinal DiseasesABSTRACT
Objetivo: Evaluar el resultado del cribado de hepatitis B y C en pacientes ingresados con COVID-19.Pacientes y métodos: Estudio transversal, prospectivo, realizado en dos hospitales españoles de tercer nivel. Se estudiaron marcadores de hepatitis B (HBsAg, anti-HBc) y C (anti-VHC, ARN VHC) a todos los pacientes hospitalizados con COVID-19 del 1 de marzo al 31 de diciembre de 2020.Resultados: En este periodo ingresaron 4662 pacientes con COVID-19: 56,3% fueron varones, la edad mediana fue 76 (0-104) años. Se realizó serología de hepatitis B a 2915 (62,5%) pacientes; 253 (8,75%) presentaban anti-HBc+y 11 (0,38%) HBsAg+. De los 11 pacientes, 4 desconocían el diagnóstico, 7 recibieron esteroides y uno recibió profilaxis. Hubo un caso de reactivación del VHB. Se determinaron anticuerpos anti-VHC a 2895 (62%) pacientes; 24 (0,83%) fueron positivos. De ellos, 13 pacientes estaban diagnosticados: 10 habían recibido tratamiento, uno se había curado espontáneamente y dos no habían sido tratados. De los 11 restantes, 10 tenían ARN VHC indetectable. En total, solo 3 (0,10%) pacientes tenían carga viral detectable. Sin embargo, ninguno recibió tratamiento (2> 90 años con comorbilidades, uno falleció por COVID-19).Conclusiones: El cribado de hepatitis C en pacientes ingresados por COVID-19 en nuestro medio ha mostrado menor utilidad de la esperada. La baja prevalencia de infección activa tras los tratamientos antivirales y la alta edad mediana de nuestra población limitan la detección de potenciales candidatos a tratamiento. El cribado de hepatitis B debería dirigirse a prevenir la reactivación en pacientes que precisen tratamientos inmunosupresores.(AU)
Aims: To evaluate the results of a hepatitis B and C screening program in hospitalized COVID-19 patients.Method: Transversal prospective study conducted in two Spanish hospitals. Patients admitted from March 1st to December 31st 2020 with a diagnosis of COVID-19 were tested for markers of hepatitis B (HBsAg, anti-HBc) and C (anti-HCV, HCV RNA) infection.Results: In this period, 4662 patients with COVID-19 were admitted to our centers: 56.3% were male, median age was 76 (0104) years. Data regarding HBV infection was available in 2915 (62.5%) patients; 253 (8.75%) were anti-HBc+ and 11 (0.38%) HBsAg+. From these, 4 patients did not have a previous diagnosis of hepatitis B, 7 received corticosteroids and one received prophylaxis. There was one HBV reactivation. Anti-HCV was available in 2895 (62%) patients; 24 (0.83%) were positive. From these, 13 patients had a previous hepatitis C diagnosis: 10 patients had been treated with SVR, one achieved spontaneous cure and 2 did not receive treatment. From the 11 previously unknown anti-VHC+patients, 10 had a negative HCV RNA. Overall, only 3 (0.10%) patients tested RNA HCV+. However, none received HCV treatment (2 older than 90 years with comorbidities, 1 died from COVID-19).Conclusion: Screening of hepatitis C infection in hospitalized COVID-19 patients seems less useful than expected. The low prevalence of active infection after antiviral treatments and the high age of our population limit the detection of potential candidates for treatment. HBV screening should be aimed to prevent reactivation under immunosuppressive treatments.(AU)
Subject(s)
Humans , Male , Female , Mass Screening , Hepatitis B Antibodies , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Betacoronavirus , Prospective Studies , Gastroenterology , Cross-Sectional StudiesABSTRACT
La terlipresina es un análogo de la vasopresina, utilizado tanto en el tratamiento de la hemorragia por varices esofágicas como en el síndrome hepatorrenal. En general es un fármaco seguro, con efectos secundarios leves. Sin embargo, en ocasiones pueden ocurrir complicaciones isquémicas potencialmente graves, como la necrosis cutánea, que es necesario reconocer de forma precoz para realizar la retirada inmediata del fármaco. Presentamos el caso de una paciente que presentó necrosis cutánea extensa secundaria a la administración de terlipresina, y realizamos una revisión de los casos publicados, describiendo sus características, posibles factores de riesgo, localización de las lesiones, dosis recibida, forma de administración y posibles tratamientos (AU)
Terlipressin is a vasopressin analogue used in esophageal variceal bleeding and hepatorenal syndrome management. It is a safe drug with mild secondary effects. However, potentially serious ischemic complications may occur, such as cutaneous necrosis. It is useful to recognize these events early, in order to withdraw terlipressin and introduce other adjuvant drugs if needed. We report a detailed case of cutaneous necrosis secondary to terlipressin administration and present a case review of patients, describing their characteristics, risk factors, lesion locations, doses, methods of administration and possible treatments (AU)
Subject(s)
Humans , Female , Aged, 80 and over , Necrosis/chemically induced , Necrosis/complications , Drug-Related Side Effects and Adverse Reactions/complications , Deamino Arginine Vasopressin/adverse effects , Risk Factors , Biopsy , Dosage Forms , Abdominal Pain/etiologyABSTRACT
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