RESUMO
BACKGROUND AND AIMS: Spontaneous ruptured hepatocellular carcinoma is an uncommon complication, and there are scarce data about non-cirrhotic patients. Tumor treatment is not standardized and the risk of peritoneal dissemination is unclear. AIM: we analyzed the treatment and survival in patients with rHCC on non-cirrhotic liver. METHODS: One hundred and forty-one non-cirrhotic patients with hepatocellular carcinoma diagnosed by histology were included in a multicenter prospective registry (2018-2022). Seven of them (5%) presented with hemoperitoneum due to spontaneous rupture. RESULTS: Liver disease was associated in three patients (42.9%). A single nodule was detected in three cases (42.9%). One patient had vascular invasion and none extrahepatic spread. Initial hemostatic therapy and sequential treatment was individualized. Patients with single nodule were treated: resection (one case) with recurrence at 4 months treated with TACE and sorafenib. TACE/TAE followed by surgery (two cases) one in remission 43 months later, the other had liver recurrence at 18 months and was transplanted. Patients with multiple lesions were treated: TAE/emergency surgery and subsequent systemic therapy (two cases), one received lenvatinib (1-year survival) and the other sorafenib (5-month survival). TAE and surgery with subsequent systemic therapy (one case). Initial hemostatic surgery, dying on admission (one case). No patient developed intraperitoneal metastasis. All patients with multiple lesions died by tumor. The 3-year survival rate was 42.9%. CONCLUSIONS: Initial hemostasis was achieved in all patients by TAE/TACE or surgery. Subsequent treatment was individualized, based on tumor characteristics, regardless of rupture. Long-time remission could be achieved in single nodule patients.
RESUMO
There is uncertainty regarding Wilson's disease (WD) management. OBJECTIVES: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. METHODS: Data on WD patients followed at 32 Spanish hospitals were collected. RESULTS: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. CONCLUSIONS: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored.
Assuntos
Degeneração Hepatolenticular , Humanos , Feminino , Masculino , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , Estudos Retrospectivos , Quelantes/uso terapêutico , Zinco , Cobre , Penicilamina/uso terapêuticoRESUMO
Introducción. Durante la aplicación del método Ponseti (MP), el niño puede mostrar incomodidad, tensión muscular o movimientos corporales que hacen del procedimiento una experiencia desagradable y estresante para pacientes, familiares y personal de salud.Objetivos. Describir los desenlaces de la aplicación de técnicas no farmacológicas (TNF) para el favorecer el estado emocional durante la atención estándar de pacientes con pie equino varo congénito (PEVC) tratados con el MP, el nivel de satisfacción del paciente y su familia con la atención recibida y la calidad de la atención en salud, y evaluar los posibles factores asociados al éxito de la aplicación de las TNF. Metodología. Estudio observacional descriptivo realizado en una cohorte de 21 niños atendidos en una clínica Ponseti de Bogotá (Colombia) entre febrero y noviembre de 2021. Las TNF se aplicaron en dos esquemas diferenciados por los sentidos estimulados. Los datos se describen usando medidas de tendencia central y de dispersión (prueba de Shapiro-Wilk), y la asociación exploratoria entre tener éxito en los esquemas de TNF y las variables se determinó con la prueba de chi-cuadrado (p≥0,05).Resultados. La mediana de edad fue 4,5 meses y el primer esquema de TNF fue exitoso en el 66,67% de los pacientes (97 consultas). El nivel de satisfacción de los cuidadores fue alto (86,07%). El equipo sanitario reportó que el procedimiento fue "extremadamente fácil" o "muy fácil" (86,07%-88,52%). Se identificaron como posibles factores asociados explor-atoriamente al éxito del primer esquema de TNF el sexo, antecedente de tratamiento con MP, y nivel de satisfacción del cuidador con la atención recibida.Conclusión. Las TNF mejoran el estado psicoemocional del niño, facilitando la aplicación del MP y aumentando la satisfacción del cuidador y del equipo sanitario con las sesiones de tratamiento
Introduction: Children may show discomfort, muscle tension or body movements while using the Ponseti method (PM), making the procedure an unpleasant and stressful experience for patients, family members, and health care personnel. Objectives: To describe the outcomes achieved following the use of non-pharmacological techniques (NPT) for emotional support when providing standard care to patients with congenital talipes equinovarus (CTEV) treated with the PM, as well as the level of patient and family satisfaction with the care received and the quality of health care, and to evaluate the possible factors associated with the success of the use of NPT.Methodology: Descriptive observational study conducted in a cohort of 21 children treated in a Ponseti clinic in Bogotá (Colombia) between February and November 2021. NPT were implemented in two schemes differentiated by the senses stimulated. Data are described using measures of central tendency and dispersion (Shapiro-Wilk test), and the exploratory association between having success with the NPT schemes and the variables was determined using the chi-square test (p≥0.05). Results: The median age was 4.5 months, and the first NPT scheme was successful in 66.67% of patients (97 consultations). The level of caregiver satisfaction was high (86.07%). The healthcare team reported that the procedure was "extremely easy" or "very easy" (86.07%-88.52%). Possible factors exploratorily associated with the success of the first NPT scheme were identified as gender, history of treatment with the PM, and level of caregiver satisfaction with the care received.Conclusion: NPT improve the psychoemotional state of the child, facilitating PM implementation, and increasing caregiver and healthcare team satisfaction with the treatment sessions
RESUMO
OBJECTIVE: To inform the update of the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and the Cochrane Library searched up to 13 May 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of three or more weeks investigating the effect of diets with low glycaemic index (GI)/glycaemic load (GL) in diabetes. OUTCOME AND MEASURES: The primary outcome was glycated haemoglobin (HbA1c). Secondary outcomes included other markers of glycaemic control (fasting glucose, fasting insulin); blood lipids (low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, apo B, triglycerides); adiposity (body weight, BMI (body mass index), waist circumference), blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), and inflammation (C reactive protein (CRP)). DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias. Data were pooled by random effects models. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess the certainty of evidence. RESULTS: 29 trial comparisons were identified in 1617 participants with type 1 and 2 diabetes who were predominantly middle aged, overweight, or obese with moderately controlled type 2 diabetes treated by hyperglycaemia drugs or insulin. Low GI/GL dietary patterns reduced HbA1c in comparison with higher GI/GL control diets (mean difference −0.31% (95% confidence interval −0.42 to −0.19%), P<0.001; substantial heterogeneity, I2=75%, P<0.001). Reductions occurred also in fasting glucose, LDL-C, non-HDL-C, apo B, triglycerides, body weight, BMI, systolic blood pressure (dose-response), and CRP (P<0.05), but not blood insulin, HDL-C, waist circumference, or diastolic blood pressure. A positive dose-response gradient was seen for the difference in GL and HbA1c and for absolute dietary GI and SBP (P<0.05). The certainty of evidence was high for the reduction in HbA1c and moderate for most secondary outcomes, with downgrades due mainly to imprecision. CONCLUSIONS: This synthesis suggests that low GI/GL dietary patterns result in small important improvements in established targets of glycaemic control, blood lipids, adiposity, blood pressure, and inflammation beyond concurrent treatment with hyperglycaemia drugs or insulin, predominantly in adults with moderately controlled type 1 and type 2 diabetes. The available evidence provides a good indication of the likely benefit in this population. STUDY REGISTRATION: ClinicalTrials.gov NCT04045938.
Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Índice Glicêmico , Carga Glicêmica , Fatores de Risco Cardiometabólico , Dieta para Diabéticos , Controle Glicêmico , HumanosRESUMO
We propose and experimentally demonstrate a modular microring laser (MML) cavity for sensing applications. The proposed MML permits much more design freedom compared with a traditional simple ring cavity by decoupling the performance parameters into several regions in the cavity. Thus, the different biosensor performance parameters can be optimized semi-independently limiting the need for trade-offs on the design of the biosensing device. The first generation MML has been fabricated and tested. A fiber-to-fiber slope efficiency of up to 1.2%, a temperature coefficient of 1.35 GHz/K and a 3σ limit of detection (LOD) of 3.1 × 10-7 RIU without averaging and 6.0 × 10-8 RIU with a 60 s averaging, has been measured for the MML sensor, which is a record-low LOD in on-chip ring cavity optical sensors. Further optimization is possible, capitalizing on the key advantage of the MML concept, namely the potential for designing the laser cavity to achieve the desired optimization goals.
Assuntos
Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Idoso , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Progressão da Doença , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Masculino , Prednisolona/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
Older patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥ 65 years) were categorized according to age: "young" (< 65 years); "young-old" (65-74 years); "middle-old" (75-84 years); and "oldest-old" (≥ 85 years). All elderly groups had an increasingly higher comorbidity burden (P < 0.001) and polypharmacy (P < 0.001). There was a relationship between jaundice and hospitalization (P < 0.001), and both were more prevalent in the older age groups, especially in the oldest-old (88% and 69%, respectively), and the DILI episode was more severe (P = 0.029). The proportion of females decreased across age groups from the young to the middle-old, yet in the oldest-old there was a distinct female predominance. Pattern of liver injury shifted towards cholestatic with increasing age among top culprit drugs amoxicillin-clavulanate, atorvastatin, levofloxacin, ibuprofen, and ticlopidine. The best cutoff point for increased odds of cholestatic DILI was 65 years. Older patients had increased non-liver-related mortality (P = 0.030) as shown by the predictive capacity of the Model for End-Stage Liver Disease score (odds ratio (OR) = 1.116; P < 0.001), and comorbidity burden (OR = 4.188; P = 0.001) in the 6-month mortality. Older patients with DILI exhibited an increasingly predominant cholestatic phenotype across a range of culprit drugs, other than amoxicillin-clavulanate, with increased non-liver-related mortality and require a different approach to predict outcome. The oldest DILI patients exhibited a particular phenotype with more severe DILI episodes and need to be considered when stratifying older DILI populations.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimedicação , Índice de Gravidade de Doença , Fatores Sexuais , Espanha/epidemiologia , Adulto JovemRESUMO
KY(WO4)2 is a promising material for on-chip laser sources. Deep etching of small KY(WO4)2 samples in combination with various thin film deposition techniques is desirable for the manufacturing of such devices. There are, however, several difficulties that need to be overcome before deep etching of KY(WO4)2 can be realized in small samples in a reproducible manner. In this paper, we address the problems of (i) edge bead formation when using thick resist on small samples, (ii) sample damage during lithography mask touchdown, (iii) resist reticulation during prolonged argon-based inductively coupled plasma reactive ion etching (ICP-RIE), and (iv) redeposited material on the feature sidewalls. We demonstrate the etching of 6.5 µm deep features and the removal of redeposited material using a wet etch procedure. This process will enable the realization of waveguides both in ion-irradiated KY(WO4)2 as well as thin KY(WO4)2 membranes transferred onto glass substrate by bonding and subsequent polishing.
RESUMO
Rare-earth ion-doped potassium yttrium double tungstate, RE:KY(WO4)2, is a promising candidate for small, power-efficient, on-chip lasers and amplifiers. Thin KY(WO4)2onglass layers with thicknesses ranging between 0.9 and 1.6 ïm are required to realize on-chip lasers based on high refractive index contrast waveguides operating between 1.55 and 3.00 µm. The crystalline nature of KY(WO4)2 makes the growth of thin, defect-free layers on amorphous glass substrates impossible. Heterogeneous integration is one of the promising approaches to achieve thin KY(WO4)2onglass layers. In this process, crystal samples, with a thickness of 1 mm, are bonded onto a glass substrate and thinned down with an extensive lapping and polishing procedure to the desired final thickness. In this study, a lapping and polishing process for KY(WO4)2 was developed toward the realization of integrated active optical devices in this material.
RESUMO
Nanophotonic waveguide enhanced Raman spectroscopy (NWERS) is a sensing technique that uses a highly confined waveguide mode to excite and collect the Raman scattered signal from molecules in close vicinity of the waveguide. The most important parameters defining the figure of merit of an NWERS sensor include its ability to collect the Raman signal from an analyte, i.e. "the Raman conversion efficiency" and the amount of "Raman background" generated from the guiding material. Here, we compare different photonic integrated circuit (PIC) platforms capable of on-chip Raman sensing in terms of the aforementioned parameters. Among the four photonic platforms under study, tantalum oxide and silicon nitride waveguides exhibit high signal collection efficiency and low Raman background. In contrast, the performance of titania and alumina waveguides suffers from a strong Raman background and a weak signal collection efficiency, respectively.
RESUMO
Whispering gallery mode resonator lasers hold the promise of an ultralow intrinsic limit of detection. However, the widespread use of these devices for biosensing applications has been hindered by the complexity and lack of robustness of the proposed configurations. In this work, we demonstrate biosensing with an integrated microdisk laser. Al2O3doped with Yb3+ was utilized because of its low optical losses as well as its emission in the range 1020-1050 nm, outside the absorption band of water. Single-mode laser emission was obtained at a wavelength of 1024 nm with a linewidth of 250 kHz while the microdisk cavity was submerged in water. A limit of detection of 300 pM (3.6 ng/ml) of the protein rhS100A4 in urine was experimentally demonstrated, showing the potential of the proposed devices for biosensing.
Assuntos
Óxido de Alumínio/química , Técnicas Biossensoriais/instrumentação , Dispositivos Lab-On-A-Chip , Lasers , Itérbio/químicaRESUMO
We report on the optical-gain properties of channel waveguides patterned into lattice-matched KGdxLuyEr1-x-y(WO4)2 layers grown onto undoped KY(WO4)2 substrates by liquid phase epitaxy. A systematic investigation of gain is performed for five different Er3+ concentrations in the range of 0.75 to 10at.% and different pump powers and signal wavelengths. In pump-probe-beam experiments, relative internal gain, i.e., signal enhancement minus absorption loss of light propagating in the channel waveguide, is experimentally demonstrated, with a maximum value of 12 ± 5 dB/cm for signals at the peak-emission wavelength of 1534.7 nm.
RESUMO
OBJECTIVE: To describe and analyse predictive and prognostic factors of overall survival (OS) in high-grade gliomas at our institution. MATERIAL AND METHOD: All patients diagnosed with grade iii (GIII) or grade iv (GIV) gliomas (excluding oligodendrogliomas, oligoastrocytomas or infratentorial gliomas) were prospectively included from November 2010 to August 2014. All were treated with surgery followed by adjuvant radiochemotherapy. The Kaplan-Meier method was used for the statistical analysis, considering a P value Ë.05 to be significant. RESULTS: 89 patients were studied (18 GIII and 71 GIV). The average age was 60 years and 55% were men. The mean Karnofsky score was 80%. The most common location was the frontal lobe (38%). A total of 65% were partial resections. Complete chemotherapy was administered to 74% and complete RT to 83% of patients. Mean OS was 26.8±8.3 months for GIII and 12.5±1 month for GIV. 72 had died by the end of this study. A total of 40% of patients had MGMT methylation, 7% IDH1 mutation and 47% EGFR amplification. Statistically significant variables for OS were: GIII (P=.020), age Ë70 years (P=.040), Ë65 years (P=.013) and Ë60 years (P=.003), Karnofsky ≥70% (P=.029), complete radiotherapy (P=.000), complete resection (P=.001), MGMT methylation (P=.042), IDH1 mutation (P=.007) and EGFR non-amplification (P=.034). Additionally, GIII and GIV subgroups were independently analysed. In GIII, the only significant biomarker for OS was IDH1 mutation, while in GIV, MGMT methylation (P=.023) was significant. Age ≥70 years old was a significant factor in the GIII-subgroup (P=.040) but not for GIV (P=.166). CONCLUSIONS: Data are in line with previous studies, with the exception of age, which does not appear to be significant in GIV.
Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Feminino , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Taxa de SobrevidaRESUMO
A low-loss, broadband and high fabrication tolerant optical coupler for the monolithic integration of Si3N4 and polymer waveguides is designed and experimentally demonstrated. The coupler is based on the adiabatic vertical tapering of the Si3N4 waveguides. Low-loss operation is experimentally verified at both 976 and 1460-1635 nm wavelengths. Measured losses per coupler are as low as 0.12 and 0.14 dB at 976 and 1550 nm, respectively, and below 0.2 dB at both wavelengths for lateral misalignments between the Si3N4 and polymer waveguides up to 1.0 µm.
RESUMO
We study the spectroscopic properties of thin films of potassium ytterbium gadolinium double tungstates, KYb0.57Gd0.43(WO4)2, and potassium ytterbium lutetium double tungstates, KYb0.76Lu0.24(WO4)2, specifically at the central absorption line near 981 nm wavelength, which is important for amplifiers and lasers. The absorption cross-section of both thin films is found to be similar to those of bulk potassium rare-earth double tungstates, suggesting that the crystalline layers retain their spectroscopic properties albeit having >50 at.% Yb3+ concentration. The influence of sample temperature is investigated and found to substantially affect the measured absorption cross-section. Since amplifiers and lasers typically operate above room temperature due to pump-induced heating, the temperature dependence of the peak-absorption cross-section of the KYb0.57Gd0.43(WO4)2 is evaluated for the sample being heated from 20 °C to 170 °C, resulting in a measured reduction of peak-absorption cross-section at the transitions near 933 nm and 981 nm by ~40% and ~52%, respectively. It is shown that two effects, the change of Stark-level population and linewidth broadening due to intra-manifold relaxation induced by temperature-dependent electron-phonon interaction, contribute to the observed behavior. The effective emission cross-sections versus temperature have been calculated. Luminescence-decay measurements show no significant dependence of the luminescence lifetime on temperature.
RESUMO
BACKGROUND & AIMS: Chronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity. METHODS: 298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or ⩾1year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition. RESULTS: Out of 298 patients enrolled 273 (92%) resolved ⩽1year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p=0.011], dyslipidemia [OR: 4.26, p=0.04] and severe DILI [OR: 14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001). Main drug classes involved in chronicity were statins (24%) and anti-infectives (24%). Histological examination in chronic patients demonstrated two cases with ductal lesion and seven with cirrhosis. CONCLUSIONS: One year is the best cut-off point to define chronic DILI or prolonged recovery, with risk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery. LAY SUMMARY: Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Alanina Transaminase , Seguimentos , Humanos , Estudos Prospectivos , Fatores de RiscoRESUMO
The characterization of the inclusion complex between 2-hydroxybenzophenone (2OHBP) and ß-cyclodextrin (ßCD) in the solid state was performed using Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM). The apparent formation constant of the complex was determined by phase solubility diagrams and liquid chromatography (HPLC) at different temperatures. The formation of the inclusion complex induced slight shifts in the FTIR spectrum while by PXRD a new crystalline phase was observed. TEM studies revealed that the complex forms aggregates of nanometric size. The inclusion complex showed a higher solubility in the tested dissolution media than free 2OHBP. Moreover, the freeze-dried solid complex exhibits a higher thermal stability than the solid free drug. The thermodynamic analysis allowed us to conclude that the encapsulation process is endothermic in water and exothermic in methanol-water.
Assuntos
Benzofenonas/química , beta-Ciclodextrinas/química , Varredura Diferencial de Calorimetria , Cromatografia Líquida de Alta Pressão , Entropia , Ligação de Hidrogênio , Metanol/química , Microscopia Eletrônica de Transmissão , Modelos Moleculares , Estrutura Molecular , Solubilidade , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Água/química , Difração de Raios XRESUMO
BACKGROUND & AIMS: The current definition of the pattern of liver injury in hepatotoxicity (DILI) is given by the R (ratio) value, dividing alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in upper limits of normal at DILI onset. We aimed to explore the validity of using aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) as biomarkers of hepatocelullar and cholestatic damage, respectively, when calculating the R value. METHODS: Clinical, laboratory and histological data from 588 DILI episodes included in the Spanish DILI Registry were analyzed. Linear regression analysis was performed to establish the most appropriate cut-off points for hepatocellular and cholestatic patterns when calculating R with AST and GGT. RESULTS: The overall agreement between ALT/ALP and AST/ALP was 76%, with 96%, 61% and 41% agreement in the hepatocellular (R ≥ 5), cholestatic (R ≤ 2) and mixed groups respectively (P < 0.001). Classified by the causative drug, the agreement was higher (87-95%) among drug classes that mainly present with hepatocellular damage and lower (48-58%) for those in which cholestatic-mixed injury predominate (P < 0.001)). The overall agreement between ALT/ALP and ALT/GGT was weak (59%), except for in hepatocellular cases that showed a good agreement (94%) (P = 0.001). Pattern of injury according to liver histology demonstrated 65%, 68% and 47% agreement for ALT/ALP, AST/ALP and ALT/GGT ratios respectively. CONCLUSIONS: AST can reliably replace ALT when calculating pattern of liver injury in DILI, while GGT can only substitute ALP when the R value scores as hepatocellular. The biochemical signature of causative drugs does influence the validity of the ratios with AST or GGT.