RESUMO
BACKGROUND: Simvastatin administration to decompensated cirrhosis patients improved Child-Pugh (CP) at the end of a safety trial (EST). AIM: To evaluate whether simvastatin reduces cirrhosis severity through a secondary analysis of the safety trial. METHODS: Thirty patients CP class (CPc) CPc A (n = 6), CPc B (n = 22), and CPc C (n = 2) received simvastatin for one year. PRIMARY ENDPOINT: cirrhosis severity. Secondary endpoints: health-related quality of life (HRQoL) and hospitalizations for cirrhosis complications. RESULTS: Cirrhosis severity decreased baseline versus EST only across CP score (7.3 ± 1.3 versus 6.7 ± 1.7, P = 0.041), and CPc: 12 patients lessened from CPc B to CPc A, and three patients increased from CPc A to CPc B (P = 0.029). Due to cirrhosis severity changes and differences in clinical outcomes, 15 patients completed the trial as CPc AEST and another 15 as CPc B/C. At baseline, CPc AEST showed greater albumin and high-density lipoprotein cholesterol concentrations than CPc B/C (P = 0.036 and P = 0.028, respectively). Comparing EST versus baseline, only in CPc AEST, there was a reduction in white-cell blood (P = 0.012), neutrophils (P = 0.029), monocytes (P = 0.035), and C-reactive protein (P = 0.046); an increase in albumin (P = 0.011); and a recovery in HRQoL (P < 0.030). Finally, admissions for cirrhosis complications decreased in CPc AEST versus CPc B/C (P = 0.017). CONCLUSIONS: Simvastatin would reduce cirrhosis severity only in CPc B at baseline in a suitable protein and lipid milieu, possibly due to its anti-inflammatory effects. Furthermore, only in CPc AEST would improve HRQoL and reduce admissions by cirrhosis complications. However, as these outcomes were not primary endpoints, they require validation.
Assuntos
Qualidade de Vida , Sinvastatina , Humanos , Albuminas , Inflamação/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/tratamento farmacológico , Sinvastatina/uso terapêuticoRESUMO
This review summarizes the safety and efficacy of statins in patients with cirrhosis. Due to concerns about the safety of statins in patients with impaired liver function, they have recently been investigated as a potential treatment option in cirrhosis. The most clinically significant adverse event is statin-related myopathy, and this may be related to the high serum statin concentrations in the setting of severely impaired liver function. Rhabdomyolysis is the most serious and potentially life-threatening manifestation. It has recently been demonstrated that the recommended dose of simvastatin in patients with decompensated cirrhosis would be 20 mg/d because higher values, such as 40 mg/d, are associated with many adverse events, especially muscle injury. Likewise, simvastatin should not be administered to patients with Model for End-stage Liver Disease score > 12 and/or Child-Pugh class C because of the high risk of severe muscle injury. Due to the pleiotropic effects, the focus on statins has shifted from being considered harmful to something useful. Through these effects, statins could prevent liver-related morbidity and mortality in cirrhotic patients. Observational studies in large populations of patients with cirrhosis have shown that treatment with statins to decrease high cholesterol levels was associated with a reduced risk of hepatic decompensation, hepatocellular carcinoma development and death. The few randomized controlled trials in patients with cirrhosis and portal hypertension showed that statins lower portal pressure, quite likely through a reduction in hepatic resistance. Another large randomized controlled trial in patients with variceal bleeding showed that simvastatin in addition to standard of care did not prevent rebleeding but improved survival rate. Despite these encouraging outcomes, the quality of the evidence regarding the use of statins is low or very low due to the observational characteristics of most of the studies involved. Therefore, it is advisable to perform further randomized controlled trials on a large series of patients with hard clinical endpoints, using different statin types and varying doses. The objectives would be to prevent liver-related morbidity and mortality rather than treating cirrhosis complications to take additional information that makes it possible to add statins to the standard of care of these patients.
Assuntos
Doença Hepática Terminal , Varizes Esofágicas e Gástricas , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão Portal , Neoplasias Hepáticas , Hemorragia Gastrointestinal , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Índice de Gravidade de DoençaRESUMO
BACKGROUND & AIMS: It is not clear how often patients who are on gluten-free diets (GFDs) for treatment of celiac disease still are exposed to gluten. We studied levels of gluten immunogenic peptides (GIP) in fecal and urine samples, collected over 4 weeks, from patients with celiac disease on a long-term GFD. METHODS: We performed a prospective study of 53 adults with celiac disease who had been on a GFD for more than 2 years (median duration, 8 y; interquartile range, 5-12 y) in Argentina. At baseline, symptoms were assessed by the celiac symptom index questionnaire. Patients collected stool each Friday and Saturday and urine samples each Sunday for 4 weeks. We used a commercial enzyme-linked immunosorbent assay to measure GIP in stool and point-of-care tests to measure GIP in urine samples. RESULTS: Overall, 159 of 420 stool and urine samples (37.9%) were positive for GIP; 88.7% of patients had at least 1 fecal or urine sample that was positive for GIP (median, 3 excretions). On weekends (urine samples), 69.8% of patients excreted GIP at least once, compared with 62.3% during weekdays (stool). The number of patients with a sample that was positive for GIP increased over the 4-week study period (urine samples in week 1 vs week 4: P < .05). Patients with symptoms had more weeks in which GIP was detected in stool than patients without symptoms (P < .05). The number of samples that were positive for GIP correlated with titers of deamidated gliadin peptide IgA in patients' blood samples, but not with levels of tissue transglutaminase. CONCLUSIONS: Patients with celiac disease on a long-term GFD still frequently are exposed to gluten. Assays to detect GIP in stool and urine might be used to assist dietitians in assessment of GFD compliance.
Assuntos
Doença Celíaca , Gliadina , Adulto , Dieta Livre de Glúten , Glutens , Humanos , Peptídeos , Estudos ProspectivosRESUMO
BACKGROUND: The high mortality rate of decompensated cirrhosis underlines the need for new treatments. Experimental models of cirrhosis and its reported relationship with atherosclerotic cardiovascular disease have provided data supporting the rational use of statins in these patients. However, little is known about the safety of statins in this setting. AIM: We evaluate the safety of chronic simvastatin treatment in patients with decompensated cirrhosis. METHODS: We conducted a prospective, open, uncontrolled, phase 2a trial in 30 patients with Child-Pugh class A (n = 6), B (n = 22), and C (n = 2) decompensated cirrhosis. The patients received standard treatment throughout the trial plus simvastatin 20 mg/day for 2 weeks and thereafter simvastatin 40 mg/day up to 1 year. RESULTS: Sixteen out of 30 patients (53.3%) showed adverse events, including gastrointestinal toxicity (36.7%), muscle injury (MI) (36.7%), and headache (13.3%). No liver injury was registered. Due to MI alone, simvastatin dosage was reduced in 23.4% of cases and transiently interrupted in 13.3%. Once these adverse events were overcome, simvastatin was resumed until the end of the trial. MI was associated with baseline MELD score > 12 (p = 0.035) and with baseline Child-Pugh class C. No MI was associated with final Child-Pugh score ≤ 6 (p = 0.030) or final Child-Pugh class A (p = 0.020). CONCLUSIONS: Chronic treatment with simvastatin 40 mg/day in patients with decompensated cirrhosis was associated with several adverse events, being MI the only clinically significant one, which appears to be related to the simvastatin dosage and the degree of cirrhosis severity. Noticeably, no liver injury was recorded.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Cirrose Hepática , Fígado/efeitos dos fármacos , Sinvastatina , Argentina/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Progressão da Doença , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Cefaleia/induzido quimicamente , Cefaleia/diagnóstico , Cefaleia/epidemiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Mialgia/induzido quimicamente , Mialgia/diagnóstico , Mialgia/epidemiologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Índice de Gravidade de Doença , Sinvastatina/administração & dosagem , Sinvastatina/efeitos adversosRESUMO
Resumen En los primeros años del siglo XX, no existía en México un hospital que tuviera la capacidad de atender los problemas de salud de la niñez mexicana, lo que hacía necesaria la construcción de una institución moderna para atenderlos. En 1933, esta situación llevó a un grupo de médicos, encabezados por el Dr. Federico Gómez Santos, a solicitar y conseguir que el presidente de la República, Abelardo L. Rodríguez, reconociera la imperiosa necesidad de contar con un hospital de niños y aprobara el proyecto para su construcción. Luego de diez años de lucha en el campo político, social y económico, y con el apoyo de los presidentes Lázaro Cárdenas y Manuel Ávila Camacho, el 30 de abril de 1943 se inauguró el Hospital Infantil de México. Hoy, después de 75 años de su creación, el hospital ha resistido la prueba del tiempo y mantiene incólume sus principios de asistencia, enseñanza e investigación, emergiendo como la cuna de la pediatría mexicana y latinoamericana.
Abstract In the early years of the 20th century, no hospital in Mexico held the capacity to address the health problems of Mexican children, making it necessary to build a modern institution to take care of these issues. This situation mobilized a group of doctors led by Dr. Federico Gómez Santos to seek the acknowledgement of the President, Abelardo L. Rodríguez, of the urgent need of a children's hospital. Later, the President approved the project for its construction in 1933. After 10 years of struggle in the political, social and economic fields, and with the support of presidents Lázaro Cárdenas and Manuel Ávila Camacho, the Hospital Infantil de México was inaugurated on April 30th, 1943. Today, 75 years after its creation, the hospital has withstood the test of time maintaining intact its principles of assistance, teaching and research, and emerging as the cradle of Mexican and Latin American pediatrics.
Assuntos
Criança , História do Século XX , História do Século XXI , Humanos , Hospitais Pediátricos/história , MéxicoRESUMO
In the early years of the 20th century, no hospital in Mexico held the capacity to address the health problems of Mexican children, making it necessary to build a modern institution to take care of these issues. This situation mobilized a group of doctors led by Dr. Federico Gómez Santos to seek the acknowledgement of the President, Abelardo L. Rodríguez, of the urgent need of a children's hospital. Later, the President approved the project for its construction in 1933. After 10 years of struggle in the political, social and economic fields, and with the support of presidents Lázaro Cárdenas and Manuel Ávila Camacho, the Hospital Infantil de México was inaugurated on April 30th, 1943. Today, 75 years after its creation, the hospital has withstood the test of time maintaining intact its principles of assistance, teaching and research, and emerging as the cradle of Mexican and Latin American pediatrics.
En los primeros años del siglo XX, no existía en México un hospital que tuviera la capacidad de atender los problemas de salud de la niñez mexicana, lo que hacía necesaria la construcción de una institución moderna para atenderlos. En 1933, esta situación llevó a un grupo de médicos, encabezados por el Dr. Federico Gómez Santos, a solicitar y conseguir que el presidente de la República, Abelardo L. Rodríguez, reconociera la imperiosa necesidad de contar con un hospital de niños y aprobara el proyecto para su construcción. Luego de diez años de lucha en el campo político, social y económico, y con el apoyo de los presidentes Lázaro Cárdenas y Manuel Ávila Camacho, el 30 de abril de 1943 se inauguró el Hospital Infantil de México. Hoy, después de 75 años de su creación, el hospital ha resistido la prueba del tiempo y mantiene incólume sus principios de asistencia, enseñanza e investigación, emergiendo como la cuna de la pediatría mexicana y latinoamericana.
Assuntos
Hospitais Pediátricos/história , Criança , História do Século XX , História do Século XXI , Humanos , MéxicoRESUMO
BACKGROUND: Life-long removal of gluten from the diet is currently the only way to manage celiac disease (CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides (GIP) in stool and urine have been developed. Their utility, in comparison with conventional dietary and analytical follow-up strategies, has not been fully established. AIM: To assess the performance of enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (PoCTs) for GIP excretion in CeD patients on gluten-free diet (GFD). METHODS: We conducted an observational, prospective, cross-sectional study in patients following a GFD for at least two years. Using the Gastrointestinal Symptom Rating Scale questionnaire, patients were classified at enrollment as asymptomatic or symptomatic. Gluten consumption was assessed twice by 3-d dietary recall and GIP excretion (by ELISA in stool and PoCTs (commercial kits for stool and urine) in two consecutive samples. These samples and dietary reports were obtained 10 day apart one from the other. Patients were encouraged to follow their usual GFD during the study period. RESULTS: Forty-four patients were enrolled, of which 19 (43.2%) were symptomatic despite being on a GFD. Overall, 83 sets of stool and/or urine samples were collected. Eleven out of 44 patients (25.0%) had at least one positive GIP test. The occurrence of at least one positive test was 32% in asymptomatic patients compared with 15.8% in symptomatic patients. GIP was concordant with dietary reports in 65.9% of cases (Cohen´s kappa: 0.317). PoCT detected dietary indiscretions. Both ELISA and PoCT in stool were concordant (concomitantly positive or negative) in 67 out of 74 (90.5%) samples. Excretion of GIP was detected in 7 (8.4%) stool and/or urine samples from patients considered to be strictly compliant with the GFD by dietary reports. CONCLUSION: GIP detects dietary transgressions in patients on long-term GFD, irrespective of the presence of symptoms. PoCT for GIP detection constitutes a simple home-based method for self-assessment of dietary indiscretions.