Long-Term Safety and Effectiveness of Rituximab Biosimilar RTXM83: A Retrospective Extension Study in Brazilian Patients with Diffuse Large B-Cell Lymphoma.

INTRODUCTION: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. METHODS: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. RESULTS: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. CONCLUSION: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered".

Real-World Study of Adjuvant Biosimilar Trastuzumab-dkst for HER2-Positive Breast Cancer Treatment in a Brazilian Population.

INTRODUCTION: Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. METHODS: We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. RESULTS: Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9-98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. CONCLUSION: Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. GOV REGISTRATION: NCT03892655.

WFUMB Guideline/Guidance on Liver Multiparametric Ultrasound: Part 1. Update to 2018 Guidelines on Liver Ultrasound Elastography.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.

WFUMB Guidelines/Guidance on Liver Multiparametric Ultrasound. Part 2: Guidance on Liver Fat Quantification.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance on the use of the available tools for the quantification of liver fat content with ultrasound. These are attenuation coefficient, backscatter coefficient, and speed of sound. All of them use the raw data of the ultrasound beam to estimate liver fat content. This guidance has the aim of helping the reader in understanding how they work and interpret the results. Confounding factors are discussed and a standardized protocol for measurement acquisition is suggested to mitigate them. The recommendations were based on published studies and experts' opinion but were not formally graded because the body of evidence remained low at the time of drafting this document.

Psoriasis and steatotic liver disease: Are PNPLA3 and TM6SF2 polymorphisms suitable for the hepato-dermal axis hypothesis?

INTRODUCTION AND OBJECTIVES: A high prevalence of steatotic liver disease has been described in psoriasis. However, the influence of genetic polymorphisms has yet to be investigated in this scenario. This study aims to determine the frequency of steatosis, advanced liver fibrosis and PNPLA3/TM6SF2 genotypes in individuals with psoriasis and to evaluate the impact of genetic polymorphisms, metabolic parameters and cumulative methotrexate dose on steatosis and fibrosis. MATERIALS AND METHODS: Cross-sectional study that prospectively included psoriasis outpatients, submitted to clinical and laboratory analysis, transient elastography (FibroScan®, Fr) and PNPLA3/TM6SF2 genotyping. Steatosis was defined by CAP ≥275 dB/m and advanced liver fibrosis as transient elastography ≥10 kPa. Logistic regression analysis evaluated the independent variables related to steatosis and fibrosis; p-value< 0.05 was considered significant. RESULTS: One hundred and ninety-nine patients were enrolled (age 54.6 ± 12.6 years, 57.3% female). Metabolic syndrome (MetS), steatosis and advanced liver fibrosis prevalence were 55.8%, 54.8% and 9%, respectively. PNPLA3 and TM6SF2 genotypes frequencies were CC 42.3%/CG 49.5%/GG 8.2% and CC 88.7%/ CT 11.3%/ TT 0%. MetS (OR3.01 95%CI 1.51-5.98; p = 0.002) and body mass index (OR1.17 95%CI 1.08-1.26; p < 0.01) were independently associated with steatosis. Diabetes Mellitus (T2DM) (OR10.76 95%CI 2.42-47.87; p = 0.002) and harboring at least one PNPLA3 G allele (OR5.66 95%CI 1.08-29.52; p = 0.039) were associated with advanced fibrosis, but not TM6SF2 polymorphism or cumulative MTX dose. CONCLUSIONS: MetS and T2DM confer higher odds for steatosis and advanced fibrosis in individuals with psoriasis. PNPLA3 G allele, but not TM6SF2 polymorphism, impacts a 5-fold odds of advanced liver fibrosis.

Factors Associated with Disagreement of Fibrosis Stages between 2D-Shear Wave Elastography and Transient Elastography in Chronic Hepatitis B.

INTRODUCTION AND OBJECTIVES: The agreement of elastography techniques in chronic Hepatitis B (CHB) needs evaluation. We aimed to evaluate, in CHB, the agreement between transient elastography (TE) and two-dimensional shear wave elastography (2D-SWE), analyzing the factors related to the disagreement of measures. MATERIALS AND METHODS: CHB patients underwent liver stiffness measures with both TE and 2D-SWE on the same day. For concordance analysis, we defined liver fibrosis as F0/1 vs. F ≥ 2, F0/1-F2 vs. F ≥ 3 and F0/1-F2-F3 vs. F4 for both methods. Logistic regression analysis was used to identify the variables independently associated with the disagreement between methods. RESULTS: A total of 150 patients were enrolled. Liver fibrosis categorization according to TE was: F0-F1 = 73 (50.4%), F ≥ 2 = 40 (27.6%), F ≥ 3 = 21 (14.5%) and F4 = 11 (7.6%), and according to 2D-SWE was: F0/F1 = 113 (77.9%), F ≥ 2 = 32 (22.1%), F≥ 3 = 25 (17.2%) and F4 = 11 (7.6%). It was observed that 20.0% of the sample had steatosis (CAP≥ 275 dB/m). TE and SD-SWE estimated equal fibrosis stages in 79.3% of cases. Spearman's correlation coefficient was 0.71 (p < 0.01). Kappa values for F ≥ 2, F ≥ 3 and F = 4 were: 0.78, p < 0.001; 0.73, p < 0.001; and 0.64, p < 0.001, respectively. Diabetes mellitus (DM) (OR 5.04; 95%CI: 1.89-13.3; p < 0.001) and antiviral treatment (OR 6.79; 95%CI: 2.33-19.83; p < 0.001) were independently associated with discordance between both methods. CONCLUSIONS: In CHB, there is strong correlation and good agreement between TE and 2D-SWE in identifying fibrosis stages. Diabetes mellitus and antiviral therapy may impact the agreement of stiffness measures obtained with these elastographic methods.

Coerência em narrativas escritas de crianças com dificuldades escolares ou quecoixas mportamentais: o papel das variáveis linguísticas e a influência da escolaridade / Coherence in written narratives of children with school difficulties or behavioral complaints: the role of linguistic variables and the influence of schooling / Coherencia en narrativas escritas de niños con dificultades escolares o quejas de conducta: el papel de las variables lingüísticas y la influencia de la educación

Introdução: A narrativa escrita deve articular a ideia principal através da relação entre tema, perso-nagens e desfecho, sendo responsabilidade de quem escreve relacionar esses componentes para levá-los à coerência. A coerência consiste de uma dependência de relações macro-linguísticas (associação do tema do texto às estruturas que o compõem) e micro-linguísticas (conectivos que trarão coesão à narrativa), a fim de proporcionar ao texto o poder de interpretação. Objetivo: analisar quais variáveis linguísticas estavam relacionadas ao melhor desempenho em coerência nas narrativas escritas de escolares do ensino fundamental. Métodos: a amostra foi composta por 37 crianças (idade entre 7 ­ 11 anos) sem deficiência intelectual e/ou deficiência auditiva. Cada criança teve sua elaboração escrita classificada em adequada (coerência nível III e IV segundo instrumento utilizado) ou inadequada (coerência nível I ou II). Poste-riormente, foi analisado um conjunto de variáveis que poderiam estar relacionadas ao desempenho da narrativa, a saber: compreensão oral, vocabulário, consciência fonológica, consciência morfossintática, memória de trabalho ­ alça fonológica, leitura e escrita. Todas essas variáveis foram avaliadas através de testes padronizados. Para a análise estatística utilizou-se modelo de regressão logística. Resultados:dentre todas as habilidades linguísticas avaliadas, consciência morfossintática (p = 0,02) foi a variável significativa. Somada a estas, temos também a escolaridade (p = 0,01), porém a consciência morfossin-tática apresentou coeficiente negativo enquanto a escolaridade apresentou coeficiente positivo. Conclu-são: crianças que apresentam alteração em consciência morfossintática apresentam maiores chances de elaborarem narrativas escritas incoerentes. Já as crianças com maior grau de escolaridade, são as que possuem textos mais adequados.

Introduction: The written narrative must articulate the main idea through the relation between theme, characters and outcome, being the responsibility of those who write to relate these components to bring them to coherence. Consistency consists of a dependence on macro-linguistic relations (association of the theme of the text with the structures that make it up) and micro-linguistic (connectives that will bring cohesion to the narrative), in order to provide the text with the power of interpretation. Objective: to analyze which linguistic variables are related to the best coherence performance in the written narrati-ves of elementary schoolchildren. Methods: the sample consisted of 37 children aged 7-11 years with no intellectual or hearing deficiency. The written elaboration of each child was classified as adequate (level III and IV coherence according to the instrument used) or inadequate (level I or II coherence). A set of variables that might be related to the performance of the narrative was then analyzed, such as oral comprehension, vocabulary, phonological awareness, morphosyntactic awareness, working memory ­ phonological loop, reading, and writing. All of these variables were evaluated using standardized tests and statistical analysis was performed using a logistic regression model. Results: among all the linguistic skills evaluated, morphosyntactic awareness (p = 0.02) was the significant variable. In addition to these there was also schooling (p = 0.01), although morphosyntacic awareness showed a negative coefficient while schooling showed a positive coefficient. Conclusion: children with changes in morphosyntactic awareness have a greater chance to elaborate incoherent written narratives, whereas children with higher schooling elaborate more adequate texts.

Introducción: La narrativa escrita debe articular la idea principal a través de la relación entre tema, personajes y desenlace, siendo responsabilidad de quienes escriben relacionar estos componentes para llevarlos a la coherencia. La coherencia consiste en una dependencia de relaciones macrolingüísticas y microlingüísticas, para dotar al texto de poder de interpretación. Objetivo: analizar qué variables lingüísticas se relacionaron con un mejor desempeño en coherencia en las narrativas escritas de estudiantes de primaria. Metodos: la muestra estuvo formada por 37 niños (de 7 a 11 años). Cada niño tenía su elabo-ración escrita clasificada como adecuada (nivel de coherencia III y IV, según el instrumento utilizado) o inadecuada (nivel de coherencia I o II). Posteriormente, se analizaron un conjunto de variables que podrían estar relacionadas con el desempeño de la narrativa, a saber: escucha, vocabulario, conciencia fonológica, conciencia morfosintáctica, memoria de trabajo - bucle fonológico, lectura y escritura. Todas estas variables se evaluaron mediante pruebas estandarizadas. Para el análisis estadístico se utilizó un modelo de regresión logística. Resultados: entre todas las habilidades lingüísticas evaluadas, la conciencia morfosintáctica (p = 0,02) fue la variable significativa. Sumado a estos, también tenemos la educación (p = 0.01), pero la conciencia morfosintáctica tuvo un coeficiente negativo mientras que la educación tuvo un coeficiente positivo. Conclusión: los niños con alteración de la conciencia morfosintáctica son más propensos a desarrollar narrativas escritas incoherentes. Los niños con mayor nivel educativo, en cambio, son los que tienen los textos más adecuados.

Staging Fibrosis in Chronic Viral Hepatitis.

Staging fibrosis accurately has always been a challenge in viral hepatitis and other liver diseases. Liver biopsy is an imperfect gold standard due to its intra and interobserver agreement limitations and additional characteristics such as its safety and cost. Hence, non-invasive tests have been developed to stage liver fibrosis. In addition to serological biomarkers, physical tests with reasonable accuracy are available and adopted in the daily clinic regarding viral hepatitis fibrosis staging. In this review, we discuss the published data regarding the staging of liver fibrosis in chronic hepatitis B and C, emphasizing non-invasive markers of fibrosis, both serological and physical. Moreover, we also discuss a persistent central gap, the evaluation of liver fibrosis after HCV cure.

Açai supplementation (Euterpe oleracea Mart.) attenuates cardiac remodeling after myocardial infarction in rats through different mechanistic pathways.

Myocardial infarction has a high mortality rate worldwide. Therefore, clinical intervention in cardiac remodeling after myocardial infarction is essential. Açai pulp is a natural product and has been considered a functional food because of its antioxidant/anti-inflammatory properties. The aim of the present study was to analyze the effect of açai pulp supplementation on cardiac remodeling after myocardial infarction in rats. After 7 days of surgery, male Wistar rats were assigned to six groups: sham animals fed standard chow (SA0, n = 14), fed standard chow with 2% açai pulp (SA2, n = 12) and fed standard chow with 5% açai pulp (SA5, n = 14), infarcted animals fed standard chow (IA0, n = 12), fed standard chow with 2% açai pulp (IA2, n = 12), and fed standard chow with 5% açai pulp (IA5, n = 12). After 3 months of supplementation, echocardiography and euthanasia were performed. Açai pulp supplementation, after myocardial infarction, improved energy metabolism, attenuated oxidative stress (lower concentration of malondialdehyde, P = 0.023; dose-dependent effect), modulated the inflammatory process (lower concentration of interleukin-10, P<0.001; dose-dependent effect) and decreased the deposit of collagen (lower percentage of interstitial collagen fraction, P<0.001; dose-dependent effect). In conclusion, açai pulp supplementation attenuated cardiac remodeling after myocardial infarction in rats. Also, different doses of açai pulp supplementation have dose-dependent effects on cardiac remodeling.

Validation and Performance of FibroScan®-AST (FAST) Score on a Brazilian Population with Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIM: FAST score has a good performance for diagnosing the composite of NASH + NAS ≥ 4 + F ≥ 2. However, it has not been evaluated in Latin American individuals with nonalcoholic fatty liver disease (NAFLD). We aimed to analyze the performance of the FAST score in a Brazilian NAFLD population. METHODS: Cross-sectional study was held in ≥ 18 years NAFLD patients diagnosed by ultrasonography and submitted to liver biopsy (LB). Liver stiffness (LSM) and CAP measurements were performed with FibroScan®, using M (BMI < 32 kg/m2) or XL probes. Area under receiver operating characteristic (AUROC) curves were calculated as well as sensitivity (S), specificity (Spe), positive predictive value (VPP) and negative predictive value (NPV) for the previously established FAST score cut-offs. RESULTS: Among 287 patients included (75% female; mean age 55 ± 10 years), NASH + NAS ≥ 4 + F ≥ 2 was reported in 30% of LB. For the FAST cut-off of 0.35, the S and NPV to rule out NASH + NAS ≥ 4 + F ≥ 2 were 78.8% and 87.8%, respectively. Regarding the cut-off of 0.67, the Spe and PPV to rule-in NASH + NAS ≥ 4 + F ≥ 2 were 89.1%, 61.8%, respectively. The AUROC of FAST for all included patients was 0.78 (95% CI 0.72-0.84) and for those with ≥ 32 kg/m2 was 0.81 (95% CI 0.74-0.88). CONCLUSION: FAST score has a good performance in a Brazilian NAFLD population, even in patients with higher BMI when the XL probe is adopted. Therefore, FAST can be used as a noninvasive screening tool mainly for excluding the diagnosis of progressive NASH, reducing the number of unnecessary liver biopsies.

Diabetes influences liver stiffness in chronic hepatitis C patients with and without virological cure: A longitudinal study.

OBJECTIVES: The aim was to prospectively assess the variation in liver stiffness (LS) and the associated factors for LS progression in a cohort of naïve, non-responder (NR), and sustained virological response (SVR) chronic hepatitis C (CHC) patients. METHODS: This was a longitudinal study on CHC patients prospectively followed with serial elastography (Fibroscan®). The LS progression rate was determined, and the associated factors for progression were assessed using multiple linear regression analysis. RESULTS: A total of 406 patients were followed up for 44 (35-53) months [naïve (29%), NR (24%), and SVR (47%)]. At the end of the follow-up period, the SVR group had a significant decrease in LS [11.8 (9.2) vs. 8.8 (8.4) kPa (p<0.001)], the NR group had a significant increase in LS [6.6 (5.2) vs. 7.1 (4.5) kPa (p=0.069)], and the naïve group had no change in LS [6.3 (3.0) vs. 6.0 (3.8) kPa (p=0.22)]. The related factors for LS progression were lack of SVR (p=0.002) and diabetes (p=0.05). In the non-diabetic SVR group, a negative rate of progression (-0.047 kPa/month) was observed, whereas in the diabetic SVR group, a positive rate of progression (+0.037 kPa/month) was observed. The highest rate of progression was observed in NR with diabetes at the rate of +0.044 kPa/month. CONCLUSION: LS in diabetes patients progresses despite SVR, suggesting the need for a close follow-up of this group post-treatment considering the risk of progression of liver disease even after SVR.

Biosimilar Use in Breast Cancer Treatment: A National Survey of Brazilian Oncologists' Opinions, Practices, and Concerns.

PURPOSE: Breast cancer is the most common malignancy in Brazilian women, with 66,280 new cases in 2020 (with 20% overexpressing human epidermal growth factor receptor 2 [HER2]). The trastuzumab biosimilar was the first oncology biosimilar approved in Brazil for HER2-positive breast cancer treatment. This study aimed to assess the current level of knowledge of biosimilars, comfort of use, extrapolation indications, and switching of practices among oncologists in Brazil. METHODS: A 24-question survey was developed using an online platform that sought information regarding responders' characteristics and use of biosimilars. The survey analyzed the basic knowledge of biosimilars, trastuzumab biosimilars, level of comfort with extrapolation, switching treatment regimens, and opinions concerning the cost of HER2-positive breast cancer therapy. Data were collected between July and September 2019 and included 144 oncologists from five Brazilian regions. RESULTS: In total, 95% of respondents could identify the most appropriate definition of biosimilars and 96% felt comfortable prescribing trastuzumab biosimilars. Although 63% of respondents would use the biosimilar in all settings wherein the reference biologic was approved, 35% would use the biosimilar for cases involving metastatic disease. Although 82% of oncologists were in favor of switching from a reference biologic to a biosimilar, 18% would avoid switching regimens. The lack of studies detailing switching to other regimens and the correct timing to switch was the major concern. The cost of HER2 therapy was a significant concern for most oncologists. CONCLUSION: Oncologists demonstrated a high level of knowledge of biosimilars and encouraging levels of prescriber use; however, extrapolation and switching treatment regimens are barriers to the effective use of biosimilars in cancer treatment. Efforts should be concentrated on strategies involving medical education programs on biosimilars.

Current management of NAFLD/NASH.

NAFLD is the most common cause of liver disease worldwide, and its prevalence is significantly increasing. Studies have shown that it is associated with comorbidities such as diabetes, metabolic syndrome and obesity. Early diagnosis and management are highly important and could modify the prognosis of the disease. Evaluating the possibility of multiple aetiologies and recognizing the additional causes of liver disease should be a part of the patient's initial assessment. There are no approved drug treatments as yet, so the main management strategies should involve lifestyle changes such as physical activity and dietary re-education.

Brazilian Society of Hepatology and Brazilian College of Radiology practice guidance for the use of elastography in liver diseases.

In 2015 the European Association for the Study of Liver Diseases (EASL) and the Asociación Latinoamericana para el Estudio del Hígado (ALEH) published a guideline for the use of non-invasive markers of liver disease. At that time, this guideline focused on the available data regarding ultrasonic-related elastography methods. Since then, much has been published, including new data about XL probe use in transient elastography, magnetic resonance elastography, and non-invasive liver steatosis evaluation. In order to draw evidence-based guidance concerning the use of elastography for non-invasive assessment of fibrosis and steatosis in different chronic liver diseases, the Brazilian Society of Hepatology (SBH) and the Brazilian College of Radiology (CBR) sponsored a single-topic meeting on October 4th, 2019, at São Paulo, Brazil. The aim was to establish specific recommendations regarding the use of imaging-related non-invasive technology to diagnose liver fibrosis and steatosis based on the discussion of evidence-based topics by an organizing committee of experts. It was submitted online to all SBH and CBR members. The present document is the final version of the manuscript that supports the use of this new technology as an alternative to liver biopsy.

Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis.

BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis. METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284. FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m2), 530 (23%) were overweight (BMI ≥25 to <30 kg/m2), and 1080 (47%) were obese (BMI ≥30 kg/m2). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low. INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard. FUNDING: The German Federal Ministry of Education and Research and Echosens.

Diabetes influences liver stiffness in chronic hepatitis C patients with and without virological cure: A longitudinal study

OBJECTIVES: The aim was to prospectively assess the variation in liver stiffness (LS) and the associated factors for LS progression in a cohort of naïve, non-responder (NR), and sustained virological response (SVR) chronic hepatitis C (CHC) patients. METHODS: This was a longitudinal study on CHC patients prospectively followed with serial elastography (Fibroscan®). The LS progression rate was determined, and the associated factors for progression were assessed using multiple linear regression analysis. RESULTS: A total of 406 patients were followed up for 44 (35-53) months [naïve (29%), NR (24%), and SVR (47%)]. At the end of the follow-up period, the SVR group had a significant decrease in LS [11.8 (9.2) vs. 8.8 (8.4) kPa (p<0.001)], the NR group had a significant increase in LS [6.6 (5.2) vs. 7.1 (4.5) kPa (p=0.069)], and the naïve group had no change in LS [6.3 (3.0) vs. 6.0 (3.8) kPa (p=0.22)]. The related factors for LS progression were lack of SVR (p=0.002) and diabetes (p=0.05). In the non-diabetic SVR group, a negative rate of progression (-0.047 kPa/month) was observed, whereas in the diabetic SVR group, a positive rate of progression (+0.037 kPa/month) was observed. The highest rate of progression was observed in NR with diabetes at the rate of +0.044 kPa/month. CONCLUSION: LS in diabetes patients progresses despite SVR, suggesting the need for a close follow-up of this group post-treatment considering the risk of progression of liver disease even after SVR.

Altered touch perception and associated risk factors in individuals with diabetes mellitus.

OBJECTIVE: To evaluate the prevalence of altered touch perception in the feet of individuals with diabetes mellitus and the associated risk factors. METHOD: Cross-sectional study with 224 individuals with diabetes mellitus conducted in an endocrinology clinic at a public hospital in Campina Grande, Paraíba. The evaluation used touch sensitivity and perception, and a descriptive and multivariate analysis with Poisson regression was performed. RESULTS: We found the prevalence of altered touch perception to be 53.1%. The risk factors that had a significant and joint impact on its occurrence were: female gender; previous ulcer; diabetes mellitus type 2; burning sensation, cracks, fissures, calluses, and Charcot foot. CONCLUSIONS: This study found a high prevalence of altered perception of touch, and this should support the planning of actions aimed at preventing the problem. The study showed the relevance of the phenomenon as a nursing diagnosis that could be included in NANDA-International.

New drugs for non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in Western countries. At present the safest and most effective first-line therapy for the management of non-alcoholic steatohepatitis (NASH) is lifestyle modification with diet and exercise. However, long-term adherence to lifestyle modification is rare in the target population, leading to progression of liver disease and its complications such as cirrhosis and hepatocellular carcinoma. Thus, new drugs that focus mainly on the pathogenesis of NASH to target inflammation and fibrogenesis are under investigation. This mini-review summarizes the results of pivotal finalized phase 2 studies, and provide an outline of ongoing phase 2 and phase 3 studies.

The performance of M and XL probes of FibroScan for the diagnosis of steatosis and fibrosis on a Brazilian nonalcoholic fatty liver disease cohort.

OBJECTIVES: Recently, controlled attenuation parameter (CAP) was incorporated for XL probe. However, its performance through M and XL probes has been scarcely evaluated in nonalcoholic fatty liver disease (NAFLD). The performance of probes regarding transient elastography by Fibroscan is still under debate. AIM: Compare the performance of CAP and transient elastography in NAFLD patients obtained through XL with M probes using histological analysis as gold standard. METHODS: NAFLD patients underwent liver biopsy and FibroScan/CAP with M and XL probes the same day. C-statistic evaluated CAP performance in the identification of moderate/severe (≥33%) and severe (≥66%) steatosis by both probes and transient elastography performance for identification of significant fibrosis (≥F2). RESULTS: Eighty-one patients (74% female; age 54.2 ± 9.9 years; BMI 32.8 ± 5.2/ BMI ≥ 25 92.6%; 96% metabolic syndrome; 60% diabetes mellitus) were included. Mean CAP with M and XL probes was 314 ± 39 and 325 ± 47 dB/m, respectively. The areas under receiver operating characteristic curves (AUROCs) of the M and XL probes for steatosis detection ≥33% were 0.75 (0.64-0.84) and 0.76 (0.65-0.84) (P = 0.95) and for steatosis ≥66% 0.83 (0.73-0.90) and 0.82 (0.71-0.89) (P = 0.73), respectively, with similar performances for both degrees of steatosis. Regarding transient elastography, AUROCs of M and XL probes for ≥F2 were 0.82 (0.71-0.93) and 0.80 (0.69-0.92) (P = 0.66). CONCLUSION: Performance of M and XL probes is similar for the diagnosis of moderate and severe steatosis and significant fibrosis even on a overweight population with NAFLD.