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BACKGROUND AND AIMS: The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients. APPROACH AND RESULTS: Multicenter study enrolling 388 patients with PBC-cirrhosis from the Spanish ColHai registry. Biopsy (20%), ultrasound (59%), or transient elastography (21%) defined cirrhosis, and the presence of varices and splenomegaly defined clinically significant portal hypertension (CSPH). Paris-II and PBC OCA international study of efficacy criteria determined the response to ursodeoxycholic acid (UDCA), fibrates (n=93), and OCA (n=104). The incidence of decompensated cirrhosis decreased for UDCA versus OCA or fibrates in the real-world population, but they were similar considering the propensity score-matched cohort (UDCA 3.77 vs. second-line therapy 4.5 100 persons-year, respectively), as patients on second-line therapy exhibited advanced liver disease. Consequently, GGT, albumin, platelets, clinically significant portal hypertension, and UDCA response were associated with a decompensating event. OCA response (achieved in 52% of patients) was associated with bilirubin (OR 0.21 [95% CI: 0.06-0.73]) and AST (OR 0.97 [95% CI: 0.95-0.99]), while fibrate response (achieved in 55% of patients) with AST [OR 0.96 (95% CI: 0.95-0.98]). In patients treated with OCA, drug response (sHR 0.23 [95% CI: 0.08-0.64]), diabetes (sHR 5.62 [95% CI: 2.02-15.68]), albumin (sHR 0.34 [95% CI: 0.13-0.89]), and platelets (sHR 0.99 [95% CI: 0.98-1.00]) were related to decompensation. In patients treated with fibrate, drug response (sHR 0.36 (95% CI: 0.14-0.95]), albumin (sHR 0.36 (95% CI: 0.16-0.81]), and clinically significant portal hypertension (sHR 3.70 (95% CI: 1.17-11.70]) were associated with decompensated cirrhosis. CONCLUSIONS: Advanced PBC, rather than OCA and fibrates, was found to be associated with decompensating events. Therefore, biochemical and clinical variables should be considered when making decisions about the management of these drugs. Moreover, a positive response to OCA and fibrates reduced the risk of decompensation.
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BACKGROUND AND AIMS: In patients with non-severe acute or chronic autoimmune hepatitis (AIH) without cirrhosis, clinical practice guidelines recommend indistinct use of prednisone or budesonide. However, budesonide is infrequently used in clinical practice. We aimed to describe its use and compare its efficacy and safety with prednisone as first-line options. APPROACH AND RESULTS: This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone. Efficacy was assessed using logistic regression and validated using inverse probability of treatment weighting propensity score. The median time to biochemical response (BR) was 3.1 months in patients treated with budesonide and 4.9 months in those with prednisone. The BR rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). The probability of achieving BR, assessed using the inverse probability of treatment weighting propensity score, was significantly lower in the budesonide group (OR = 0.20; 95% CI: 0.11-0.38) at any time during follow-up, and at 6 (OR = 0.51; 95% CI: 0.29-0.89) and 12 months after starting treatment (0.41; 95% CI: 0.23-0.73). In patients with transaminases <2 × upper limit of normal, BR was similar in both treatment groups. Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%, p = 0.047). CONCLUSIONS: In the real-life setting, the use of budesonide as first-line treatment is low, and it is generally prescribed to patients with perceived less disease activity. Budesonide was inferior to prednisone as a first-line drug but was associated with fewer side effects.
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Budesonida , Hepatite Autoimune , Humanos , Budesonida/efeitos adversos , Prednisona/uso terapêutico , Hepatite Autoimune/tratamento farmacológico , Estudos Retrospectivos , Glucocorticoides/efeitos adversosRESUMO
BACKGROUND AND AIMS: 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. RESULTS: 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. CONCLUSION: Rituximab is safe and effective in patients with refractory AIH and those treated due to concomitant autoimmune or haematological disorders.
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Hepatite Autoimune , Sistema de Registros , Rituximab , Humanos , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Feminino , Hepatite Autoimune/tratamento farmacológico , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , Resultado do Tratamento , Fatores Imunológicos/uso terapêutico , Fatores Imunológicos/efeitos adversos , Adulto JovemRESUMO
INTRODUCTION AND OBJECTIVES: Different patterns of liver injury have been reported in association with the SARS-CoV-2 vaccines. The aim of this study was to describe a nationwide cohort of patients with SARS CoV-2 vaccine-induced liver injury, focusing on treatment and the evolution after further booster administration. PATIENTS AND METHODS: multicentre, retrospective-prospective study, including subjects who developed abnormal liver tests within 90 days after administration of SARS-CoV-2 vaccination. RESULTS: 47 cases were collected: 17 after prime dose and 30 after booster. Age was 57 years, 30 (63.8 %) were female, and 7 (14.9 %) had a history of prior autoimmune hepatitis (AIH). Most cases were non-severe, though 9 (19.1 %) developed acute liver injury or failure (ALF). Liver injury tended to be more severe in those presenting after a booster (p=0.084). Pattern of liver injury was hepatocellular (80.9 %), mixed (12.8 %) and 3 (6.4 %) cholestatic. Liver biopsy was performed on 33 patients; 29 showed findings of AIH. Forty-one (87.2 %) patients received immunosuppressants, mostly corticosteroids (35/41). One required liver transplantation and another died due to ALF. Immunosuppression was discontinued in 6/41 patients without later rebound. Twenty-five subjects received at least one booster and 7 (28.0 %) relapsed from the liver injury, but all were non-severe. Recurrence was less frequent among patients on immunosuppressants at booster administration (28.6 % vs. 88.9 %, p=0.007). CONCLUSIONS: SARS CoV-2 vaccine-induced liver injury is heterogeneous but mostly immune-mediated. Relapse of liver injury after re-exposure to vaccine is frequent (28.0 %) but mild. Immunosuppression at booster administration is associated with a lower risk of liver injury.
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Vacinas contra COVID-19 , COVID-19 , Recidiva , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Vacinas contra COVID-19/efeitos adversos , Estudos Retrospectivos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Estudos Prospectivos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , SARS-CoV-2 , Idoso , Adulto , Imunização Secundária , Fatores de Risco , Transplante de Fígado , Imunossupressores/efeitos adversosRESUMO
The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2 % to 40 %, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.
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Colite , Gastroenteropatias , Humanos , Colite/induzido quimicamente , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Fígado , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.
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Colite , Gastroenteropatias , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Gastroenteropatias/induzido quimicamente , Colite/induzido quimicamente , Colite/tratamento farmacológico , Fígado , PrognósticoRESUMO
BACKGROUND & AIMS: Liver injury related to immunotherapy is a relatively frequent immune-related adverse event that requires permanent discontinuation of immune checkpoint inhibitors (ICIs) in severe cases. We present the outcome of a cohort of patients who were retreated with immunotherapy after resolution of severe immune-related hepatitis. METHODS: We performed a prospective, multicenter, noninterventional study that included all consecutive patients with cancer and previous grade 3 or 4 immune-related hepatitis who were retreated with ICIs in 3 academic hospitals. RESULTS: Twenty-three patients who developed severe immune-related hepatitis were included: 20 of 23 (87.0%) received a single ICI and 3 of 23 (13.0%) received anti-programmed cell death protein-1 plus an anti-cytotoxic T-lymphocyte-associated antigen. The most frequent cancers were lung cell and urinary tract (7 and 6 cases, respectively). Immunotherapy was discontinued in all cases. Nineteen patients (82.6%) also received corticoids. Patients mainly were retreated with the same ICI (18 of 23; 78.3%) after a median time of 10 weeks (range, 1-54 wk) from the severe immune-related hepatitis. Fifteen patients (65.2%) did not have recurrence of the immune-related hepatitis after retreatment. Among the 8 (34.8%) subjects with recurrence, 5 of 8 were grade 3 and 3 of 8 were grade 4. Six (75%) had either an underlying autoimmune disease or antinuclear antibodies ≥1/80 (75% vs 26.7%; P = .037). None of the patients with previously grade 4 hepatitis had a recurrence, and those patients who had a recurrence tended to present with a better oncological prognosis. Overall, 19 (82.6%) subjects required permanent discontinuation of ICIs, with cancer progression the main reason for discontinuation (9 of 19; 47.8%). CONCLUSIONS: Retreatment with ICIs is a feasible option after a severe immune-related hepatitis, even with the same ICIs, without recurrence of the liver injury retreatment in up to 65% of patients.
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Antineoplásicos Imunológicos , Hepatite , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico , Estudos Prospectivos , Neoplasias/tratamento farmacológico , Retratamento , Estudos RetrospectivosRESUMO
BACKGROUND AND AIMS: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly 3α,7α,12α-trihydroxy-5ß-cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration. METHODS AND RESULTS: Among 33 patients with unexplained hypertransaminasemia from 11 hospitals and 13 of their relatives, seven individuals with abnormally high C27-BA levels (>50% of total BAs) were identified by high-performance liquid chromatography-mass spectrometry. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in two patients and three family members. Two additional nonrelated patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In patients with ADAH, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized aminotransferase levels. Incubation of HuH-7 hepatoma cells with THCA, which was efficiently taken up, but not through BA transporters, increased reactive oxygen species production (flow cytometry), endoplasmic reticulum stress biomarkers (GRP78, CHOP, and XBP1-S/XBP1-U ratio), and BAXα expression (reverse transcription followed by quantitative polymerase chain reaction and immunoblot), whereas cell viability was decreased (tetrazolium salt-based cell viability test). THCA-induced cell toxicity was higher than that of major C24-BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site-directed mutagenesis) and expressed in HuH-7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH. CONCLUSIONS: Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a noninvasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.
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Ácidos e Sais Biliares , Ácido Ursodesoxicólico , Humanos , Ácido Ursodesoxicólico/farmacologia , Ácido Ursodesoxicólico/uso terapêutico , Acil-CoA Oxidase/genética , Espécies Reativas de Oxigênio , Transaminases , Sais de Tetrazólio , OxirredutasesRESUMO
OBJECTIVE: The study aimed to establish recommendations and quality criteria to enhance the healthcare process of PBC. PATIENTS AND METHODS: It was conducted using qualitative techniques, preceded by a literature review. A consensus conference involving five specialists in the field was held, followed by a Delphi process developed in two waves, in which 30 specialist physicians in family and community medicine, digestive system and internal medicine were invited to participate. RESULTS: Seven recommendations and 15 sets of quality criteria, indicators and standards were obtained. Those with the highest consensus were «Know the impact on the patient's quality of life. Consider their point of view and agree on recommendations and care¼ and «Evaluate possible fibrosis at the time of diagnosis and during PBC follow-up, assessing the evolution of factors associated with poor disease prognosis: noninvasive fibrosis (elastography > 2.1 kPa/year), GGT, ALP and bilirubin annually¼, respectively. CONCLUSIONS: The implementation of the consensus recommendations and criteria would provide better patient care. The need for multidisciplinary follow-up and an increased role of primary care is emphasized.
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Budesonide is a glucocorticoid characterized by its local action, with a low systemic bioavailability. Since the original trial comparing budesonide with prednisone in 2010, it is recommended as an effective alternative for the treatment of non-severe acute or chronic autoimmune hepatitis. In this document, we review the general pharmacologic properties of glucocorticoids, the available evidence for the use of budesonide as first line option for autoimmune hepatitis as well as the safety profile of the drug.
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Budesonida , Hepatite Autoimune , Budesonida/uso terapêutico , Glucocorticoides/uso terapêutico , Hepatite Autoimune/tratamento farmacológico , Humanos , Prednisona/uso terapêuticoRESUMO
Safety of regorafenib in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been recently demonstrated. We aimed to assess the survival benefit of regorafenib compared with best supportive care (BSC) in LT patients after sorafenib discontinuation. This observational multicenter retrospective study included LT patients with HCC recurrence who discontinued first-line sorafenib. Group 1 comprised regorafenib-treated patients, whereas the control group was selected among patients treated with BSC due to unavailability of second-line options at the time of sorafenib discontinuation and who were sorafenib-tolerant progressors (group 2). Primary endpoint was overall survival (OS) of group 1 compared with group 2. Secondary endpoints were safety and OS of sequential treatment with sorafenib + regorafenib/BSC. Among 132 LT patients who discontinued sorafenib included in the study, 81 were sorafenib tolerant: 36 received regorafenib (group 1) and 45 (group 2) received BSC. Overall, 24 (67%) patients died in group 1 and 40 (89%) in group 2: the median OS was significantly longer in group 1 than in group 2 (13.1 versus 5.5 months; P < 0.01). Regorafenib treatment was an independent predictor of reduced mortality (hazard ratio, 0.37; 95% confidence interval [CI], 0.16-0.89; P = 0.02). Median treatment duration with regorafenib was 7.0 (95% CI, 5.5-8.5) months; regorafenib dose was reduced in 22 (61%) patients for adverse events and discontinued for tumor progression in 93% (n = 28). The median OS calculated from sorafenib start was 28.8 months (95% CI, 17.6-40.1) in group 1 versus 15.3 months (95% CI, 8.8-21.7) in group 2 (P < 0.01). Regorafenib is an effective second-line treatment after sorafenib in patients with HCC recurrence after LT.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Piridinas , Estudos Retrospectivos , Sorafenibe/uso terapêuticoRESUMO
BACKGROUND: Information regarding impact on healthcare systems of relapsed or refractory (R/R) FLT3 mutated (FLT3mut) acute myeloid leukemia (AML) is scarce. OBJECTIVE: To assess the time and reimbursement associated with hospitalizations of patients with R/R FLT3mut AML in a tertiary Spanish hospital. METHODS: Retrospective review of medical charts identified patients aged ≥ 18 years with R/R FLT3mut AML between 1998 and 2018. Data were collected from the date of first diagnosis of R/R FLT3mut AML (index) until death or loss to follow-up. The primary end point was duration and frequency of hospitalization, use of outpatient resources and transfusion burden. Reimbursement associated with hospitalizations (including associated chemotherapy) was also assessed. RESULTS: Thirty-eight patients were eligible for inclusion. Their median age was 52 years, and 30 (79%) received intensive salvage chemotherapy; FLAG-IDA-based regimens were the most frequent (24 patients, 63%). Overall, there were 150 hospitalizations (mean 3.9/patient; mean duration 21 days). Patients spent a mean of 24% of the study period in hospital. Total mean reimbursement was 108 293 per patient; the majority (89 834) attributable to inpatient stays (22 576 /hospitalization). During chemotherapy period (prior to first alloHSCT), there were 73 hospitalizations (mean duration 22 days); mean reimbursement was 19 776 per hospitalization and 49 819 per patient. AlloHSCT (n = 16) involved 77 hospitalizations (mean duration 21 days), mean reimbursement 25 231/hospitalization and 131 515 per patient. CONCLUSION: Data from this study suggest that there is a substantial healthcare resource utilization and cost burden on R/R FLT3mut AML patients in Spain receiving active treatments.
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Recursos em Saúde , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Mutação , Aceitação pelo Paciente de Cuidados de Saúde , Tirosina Quinase 3 Semelhante a fms/genética , Adulto , Resistencia a Medicamentos Antineoplásicos , Feminino , Custos de Cuidados de Saúde , Hospitalização , Humanos , Reembolso de Seguro de Saúde , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Recidiva , Estudos Retrospectivos , Espanha/epidemiologia , Centros de Atenção TerciáriaRESUMO
OBJECTIVES: Liver Imaging Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) diagnosis in high-risk patients is a dynamic system, which was lastly updated in 2018. We aimed to evaluate the accuracy for HCC diagnosis of LI-RADS v2018 with magnetic resonance imaging (MRI) with extracellular contrast for solitary nodules ≤ 20 mm detected during ultrasound (US) surveillance in cirrhotic patients, with particular interest in those observations categorized as LI-RADS 3. METHODS: Between November 2003 and February 2017, we included 262 consecutive cirrhotic patients with a newly US-detected solitary ≤ 20-mm nodule. A LI-RADS (LR) v2018 category was retrospectively assigned. The diagnostic accuracy for each LR category was described, and the main MRI findings associated with HCC diagnosis were analyzed. RESULTS: Final diagnoses were as follows: 197 HCC (75.2%), 5 cholangiocarcinoma (1.9%), 2 metastasis (0.8%), and 58 benign lesions (22.1%); 0/15 (0%) LR-1, 6/26 (23.1%) LR-2, 51/74 (68.9%) LR-3, 11/12 (91.7%) LR-4, 126/127 (99.2%) LR-5, and 3/8 (37.5%) LR-M were HCC. LR-5 category displayed a sensitivity and specificity of 64% (95% CI, 56.8-70.7) and 98.5% (95% CI, 91.7-100), respectively. Considering also LR-4 as diagnostic for HCC, the sensitivity slightly increased to 69.5% (95% CI, 62.6-75.9) with minor impact on specificity (96.2%; 95% CI, 89.3-99.6). Regarding LR-3 observations, 51 out of 74 were HCC, 2 were non-HCC malignancies, and 20 out of 21 LR-3 nodules > 15 mm (95.2%) were finally categorized as HCC. CONCLUSIONS: The high probability of HCC in US-detected LR-3 observations (68.9%) justifies triggering an active diagnostic work-up if intended to diagnose HCC at a very early stage. KEY POINTS: ⢠In cirrhotic patients with nodules ≤ 20 mm detected during US surveillance, 51 out of 74 (68.9%) of LR-3 nodules by MRI corresponded to an HCC. ⢠In LR-3 nodules, HCC diagnosis was closely related to baseline tumor size. All 5 nodules smaller than 1 cm were diagnosed as benign. Oppositely, 20 out of 21 LR-3 observations > 15 mm (95.2%) were diagnosed as HCC. ⢠The high probability of HCC in US-detected LR-3 observations justifies triggering an active diagnostic work-up if intended to diagnose HCC at a very early stage.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
GOALS: To describe the occurrence of malabsorption (MA) in hepatocellular carcinoma (HCC) patients under sorafenib, the potential relationship with pancreatic insufficiency (PI), and the role of pancreatic enzymes supplementation. BACKGROUND: With the increasing options of second-line systemic therapies for HCC, the recognition of drug intolerance using practical tools is crucial. It has been proposed that a MA syndrome could be due to sorafenib-induced pancreatic dysfunction. STUDY: All sorafenib-treated patients with suspicion of MA (defined as decreased stool consistency lasting >4 wk or presenting ≥10% body weight loss without HCC progression) were prospectively evaluated by serum markers, endoscopy, and imaging techniques. RESULTS: We evaluated 81 sorafenib-treated patients and 21 developed MA suspicion (85.7% male, 81.5% Child-Pugh A, 52.4% BCLC-B, and 47.6% BCLC-C) within a median 5.9 months after starting sorafenib. The median treatment duration, follow-up, and overall survival after MA suspicion were 5.9, 20.3, and 20.3 months, respectively. Nine of them (42.9%) presented hyperparathyroidism secondary to vitamin D deficiency and 8 with PI. A gradual decrease in pancreatic volume of up to 19% was observed among patients with PI. Six of the 8 patients with PI received pancreatic enzymes, with complete recovery from MA symptoms and stabilization of pancreatic volume. CONCLUSIONS: We validated the association between MA and PI in 10% of sorafenib-treated patients. Pancreatic enzymes supplementation successfully led to symptomatic recovery. Awareness of this adverse event can help in the management of sorafenib irrespective of cancer type and likely, of other tyrosine kinase inhibitors for HCC patients.
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Antineoplásicos , Carcinoma Hepatocelular , Insuficiência Pancreática Exócrina , Neoplasias Hepáticas , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Niacinamida/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Sorafenibe/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: This study assessed pharmacoeconomic costs associated with extracorporeal photopheresis (ECP) compared with other available second-line therapies for chronic graft-vs-host disease (cGvHD) in a tertiary Spanish institution. METHODS: Patients (≥18 years) diagnosed with steroid-refractory cGvHD were eligible. Data were collected retrospectively from index date until 1 year or relapse. Patients were distributed in two cohorts (ECP vs non-ECP), matched by age (≤ or > 40), hematopoietic stem cell transplant (HLA-identical sibling donor or other) and number of previous immunosuppressive lines (1, 2, or ≥ 3). Costs were assigned using the 2016 diagnosis-related group (DRG) system: DRG 579 (22 383) overnight stay due to major complication (ie, sepsis, pneumonia, parenteral nutrition, or respiratory failure), and DRG 875 (5154) if no major complication. The primary endpoint was healthcare resource utilization per patient. RESULTS: Forty patients (n = 20 per cohort) were included. Median age was 49, and 37.5% were female. Mean total cost per patient was 25 319 (95% CI: 17 049-33 590) across the two cohorts, with a slightly lower mean cost per ECP-treated patient (23 120) compared with the non-ECP cohort (27 519; P = .597). Twenty-seven inpatient hospitalizations occurred among ECP-treated patients, vs 33 in the non-ECP cohort. Day hospital and external consultations were more frequent in the ECP cohort. However, fewer inpatient admissions included DRG 579 compared with the non-ECP cohort (44% vs 58%). Inpatient length of stay was slightly shorter in the ECP cohort (30 vs 49 days; P = .298). CONCLUSIONS: ECP treatment may yield economic savings in Spain through resource savings and moving costs toward outpatient care.
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Doença Enxerto-Hospedeiro/tratamento farmacológico , Hospitais , Fotoferese/economia , Fotoferese/métodos , Esteroides/uso terapêutico , Adulto , Idoso , Doença Crônica , Farmacoeconomia , Feminino , Doença Enxerto-Hospedeiro/economia , Transplante de Células-Tronco Hematopoéticas/métodos , Hospitalização , Humanos , Imunossupressores , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Retrospectivos , Risco , Espanha/epidemiologia , Resultado do Tratamento , Adulto JovemRESUMO
The ways in which information is shared, regardless of its origin, are constantly undergoing major changes. These shifts affecting how people interact and exchange knowledge have been subject to disruptive changes in recent years, due to the possibilities created by social media. The SARS-CoV-2 pandemic has exponentially accelerated these changes and innovations. In health and biomedical settings, Twitter is a key tool. This document aims to depict and describe the nascent opportunities in the field of knowledge dissemination and research on hepatology.
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COVID-19 , Gastroenterologia , Disseminação de Informação/métodos , Pandemias , SARS-CoV-2 , Mídias Sociais , Congressos como Assunto , Previsões , Humanos , Publicações Periódicas como Assunto , Mídias Sociais/estatística & dados numéricos , Mídias Sociais/tendências , Rede Social , Sociedades Médicas , Sociedades CientíficasRESUMO
BACKGROUND & AIMS: Sorafenib and lenvatinib are the first-line treatments approved in hepatocellular carcinoma (HCC), but information is lacking about the relationships between their pharmacokinetics, patients pharmacogenetic profiles, adverse events (AE) and overall survival. We aimed to elucidate these relationships of tyrosine Kinase Inhibitors, such as sorafenib, in order to improve the design of trials testing it in combination with checkpoint inhibitors. METHODS: We assessed the pharmacokinetics of sorafenib and its N-oxide metabolite at day-0, day-7, day-30, day-60, day-90, day-120, day-150 and day-180 and nine single-nucleotide polymorphisms (SNP) in five genes related to sorafenib metabolism/transport to identify the best point for starting the combination between tyrosine kinases and checkpoint inhibitors. RESULTS: We prospectively included 49 patients (96% cirrhotic, 37% hepatitis-C, 82% Child-Pugh-A and 59% BCLC-C). Pharmacokinetic values peaked at day-7 and progressively declined until day-60. In the 16 patients without further dose modifications after day-60, pharmacokinetic values remained stable through day-180 (sorafenib P = .90; N-oxide P = .93). Pharmacokinetic values were higher in patients with early dermatological adverse events and lower in patients with early diarrhoea. Sorafenib and N-oxide pharmacokinetic values varied linearly with different alleles of MRP2*3972. CONCLUSIONS: Sorafenib's pharmacokinetics is heterogeneous across HCC patients. This heterogeneity affects adverse events development and must be taken into account in setting the dose and timing of its combination with checkpoint inhibitors.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Niacinamida/efeitos adversos , Farmacogenética , Compostos de Fenilureia/uso terapêutico , Sorafenibe/uso terapêuticoRESUMO
BACKGROUND & AIMS: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. METHODS: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. RESULTS: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges [IQR], 0.8-3.8), 10.8 months (IQR, 4.5-16.9), and 17.5 months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. CONCLUSIONS: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Europa (Continente) , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Diálise Renal , Sorafenibe/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the diagnostic accuracy and predictive value of gadoxetic acid liver MRI (Gd-EOB-DTPA MRI) alone or in combination with diffusion-weighted imaging (DWI) as a second-line tool for detecting early hepatocellular carcinoma (HCC) recurrence in cirrhotic patients with previous HCC treated with resection or ablation. METHODS: Between 2014 and 2017, we prospectively included 34 cirrhotic patients with complete response to resection and/or ablation of early HCC in whom a new focal lesion enhancing in the arterial phase without washout was detected during follow-up with EC-MRI. After signing the informed consent, all patients underwent DWI and Gd-EOB-DTPA MRI; two readers analyzed signal intensities on each phase of dynamic study and on DWI. The final diagnosis was established by histology or follow-up EC-MRI. We used cross-tabulation to calculate indices of diagnostic accuracy. RESULTS: We evaluated 34 patients (7 women; 73.5% with hepatitis C virus) with a total of 53 new arterial-phase-enhancing foci (median size, 10 [IQR 9-14] mm). The final diagnosis, reached by histopathology in 15 (35.7%) lesions and EC-MR follow-up in 27 (64.3%), was HCC in 42 (79.2%) and benign conditions in 11 (21.8%). Hepatobiliary-phase hypointensity on Gd-EOB-DTPA MRI plus hyperintensity on DWI yielded 54.8% sensitivity, 90.9% specificity, 95.8% positive predictive value, and 34.5% negative predictive value for diagnosing HCC recurrence. CONCLUSION: Among potential indices, combining hypointensity on hepatobiliary-phase Gd-EOB-DTPA MRI and hyperintensity on DWI has the highest specificity and positive predictive value to optimally detect HCC recurrence prior to confident diagnosis by conventional imaging criteria on EC-MRI in cirrhotic liver. KEY POINTS: ⢠In patients at risk of HCC recurrence, the use of gadoxetic acid liver MRI and DWI may improve the differentiation of unspecific new arterial-enhancing foci from early hypervascular HCC recurrence in patients with non-conclusive findings on extracellular liver MRI. ⢠Combined findings on hepatobiliary-phase gadoxetic acid-enhanced liver MRI and DWI had high specificity (90.9%) and positive predictive value (95.8%) for detecting early hypervascular HCC recurrence, but limited sensitivity. ⢠Combining hepatobiliary-phase hypointensity on gadoxetic acid MRI and hyperintensity on diffusion-weighted imaging allows early diagnosis of hypervascular hepatocellular carcinoma and may help select patients for salvage therapy.
Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Gadolínio DTPA/administração & dosagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To assess the effectiveness, safety, and overall survival (OS) of thermal ablation as upfront treatment of intrahepatic colangiocarcinoma (ICC) in patients with cirrhosis. MATERIALS AND METHODS: This was a retrospective analysis of all biopsy-confirmed ICC in cirrhotic patients treated in the authors' unit from 2001 to 2017. Baseline characteristics, ablation procedures, and complications were recorded, and time to recurrence (TTR) and OS were calculated. Twenty-seven patients were identified. Seventy percent had Child-Pugh A disease, and most had clinically significant portal hypertension. Median tumor size was 21 mm. Twenty-one cases were uninodular, and 10 were single ≤ 2 cm. RESULTS: Complete radiologic necrosis was achieved in 25 cases (92.6%). Median OS was 30.6 months (95% confidence interval [CI], 22.6-46.5), and recurrence was detected in 21 cases (77.8%) with a TTR of 10.1 months (95% CI, 7.7-20.9). In those patients with single ≤ 2-cm ICC, the OS was 94.5 months (95% CI, 11.7-not reached). Differences in OS were statistically significant between patients with single ICC ≤ 2 cm and patients with single ICC > 2 cm (P = .04) and between patients with single ICC > 2 cm and patients with multinodular ICC (P = .02). Only 1 patient had a treatment-related complication. CONCLUSIONS: Thermal ablation is a safe and effective treatment for ICC in patients with cirrhosis who are not candidates for surgery. The OS is similar to that reported in surgical series, but the initial treatment success is hampered by a high rate of tumor recurrence. Encouraging long-term survival after thermal ablation is achieved in patients with single ≤ 2-cm ICC.