Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil.

Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

THE ROLE OF ELASTOGRAPHY IN CLINICALLY SIGNIFICANT PORTAL HYPERTENSION.

• In compensated cirrhosis, using non-invasive methods would exempt the patient from the need of an endoscopy. • The Baveno VII presented the "rule of 5" for Vibration-Controlled Transient Elastography; liver stiffness measurement ≤15 kPa and platelets >150.000/mm3 exclude clinically significant portal hypertension (CSPH), while when ≥25 kPa is highly suggestive of CSPH. • Spleen stiffness measurement has been proposed as a more specific technique to predict the presence of CSPH. • Elastography has gained prestige in the non-invasive evaluation of patients with advanced chronic liver disease by allowing prophylactic measures to be taken when suggesting the presence of CSPH. This is a narrative review that aims to discuss the importance of elastographic methods in the evaluation of clinically significant portal hypertension (CSPH) in cirrhotic patients, where the authors propose an algorithm for evaluating these patients. In compensated advanced chronic liver disease, the goal is to prevent the development of CSPH and, in those already with CSPH, prevent the appearance of gastroesophageal varices (GEV) and other complications of portal hypertension. In compensated cirrhosis, the prevalence of GEV is 30-40%, of which 10-20% are at risk of bleeding. Therefore, using non-invasive methods would exempt the patient from the need of an endoscopy. Hepatic Elastography is a non-invasive, safe, reproducible method, available through many techniques: Vibration-Controlled Transient Elastography (VCTE), Shear Wave Elastography (SWE) and Magnetic Resonance Elastography (MRE). The Baveno VII presented the "rule of 5" for VCTE: liver stiffness measurement (LSM) ≤15 kPa and platelets >150.000/mm3 exclude CSPH, while an LSM ≥25 kPa is highly suggestive of CSPH. Also, the "rule of 4" for SWE has been proposed: patients with ≥17 kPa could be considered as having CSPH. At last, spleen stiffness measurement (SSM) has been proposed as a more specific technique to predict the presence of CSPH. In conclusion, elastography has gained prestige in the non-invasive evaluation of patients with advanced chronic liver disease by allowing prophylactic measures to be taken when suggesting the presence of CSPH.

O papel da elastografia na hipertensão portal clinicamente significativa / The role of elastography in clinically significant portal hypertension

ABSTRACT This is a narrative review that aims to discuss the importance of elastographic methods in the evaluation of clinically significant portal hypertension (CSPH) in cirrhotic patients, where the authors propose an algorithm for evaluating these patients. In compensated advanced chronic liver disease, the goal is to prevent the development of CSPH and, in those already with CSPH, prevent the appearance of gastroesophageal varices (GEV) and other complications of portal hypertension. In compensated cirrhosis, the prevalence of GEV is 30-40%, of which 10-20% are at risk of bleeding. Therefore, using non-invasive methods would exempt the patient from the need of an endoscopy. Hepatic Elastography is a non-invasive, safe, reproducible method, available through many techniques: Vibration-Controlled Transient Elastography (VCTE), Shear Wave Elastography (SWE) and Magnetic Resonance Elastography (MRE). The Baveno VII presented the "rule of 5" for VCTE: liver stiffness measurement (LSM) ≤15 kPa and platelets >150.000/mm3 exclude CSPH, while an LSM ≥25 kPa is highly suggestive of CSPH. Also, the "rule of 4" for SWE has been proposed: patients with ≥17 kPa could be considered as having CSPH. At last, spleen stiffness measurement (SSM) has been proposed as a more specific technique to predict the presence of CSPH. In conclusion, elastography has gained prestige in the non-invasive evaluation of patients with advanced chronic liver disease by allowing prophylactic measures to be taken when suggesting the presence of CSPH.

RESUMO Trata-se de uma revisão narrativa que visa discutir a importância dos métodos elastográficos na avaliação da hipertensão portal clinicamente significativa (HPCS) em pacientes cirróticos, onde os autores propõem um algoritmo para avaliação desses pacientes. Na doença hepática crônica avançada compensada, o objetivo é prevenir o desenvolvimento de HPCS, e naqueles já com HPCS prevenir o aparecimento de varizes gastroesofágicas (VGE) e outras complicações da hipertensão portal. Na cirrose compensada, a prevalência de VGE é de 30-40% e 10-20% são varizes com risco de sangramento, portanto o uso de métodos não invasivos dispensaria o paciente de endoscopia. A elastografia hepática é um método não invasivo, seguro e reprodutível, disponível através de várias técnicas: elastografia transitória (VCTE), onda de cisalhamento (SWE) e elastografia por ressonância magnética. O Baveno VII apresentou a "regra dos 5" para VCTE: medida da rigidez hepática (LSM) ≤15 kPa e plaquetas >150.000/mm3 excluem HPCS enquanto um LSM ≥25 kPa é altamente sugestivo de HPCS. Além disso, foi proposta a "regra dos 4" para SWE: pacientes com ≥17 kPa podem ser considerados como portadores de HPCS. Por fim, a medição da rigidez do baço (SSM) foi proposta como uma técnica mais específica para prever a presença de HPCS. Em conclusão, a elastografia ganhou prestígio na avaliação não invasiva de pacientes com doença hepática crônica avançada, ao permitir a adoção de medidas profiláticas ao sugerir a presença de HPCS.

Transjugular intrahepatic portosystemic shunt in decompensated cirrhotic patients in a tertiary hospital in southern Brazil.

OBJECTIVE: The aim of the present study was to evaluate the outcomes of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt. METHODS: A retrospective longitudinal observational study was carried out evaluating 38 cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt. The outcomes were evaluated in an outpatient follow-up period of 3 months. The assumed significance level was 5%. RESULTS: The indications for transjugular intrahepatic portosystemic shunt were refractory ascites in 21 (55.3%), variceal hemorrhage in 13 (34.2%), and hydrothorax in 4 (10.5%) patients. There was development of hepatic encephalopathy in 10 (35.7%) patients after transjugular intrahepatic portosystemic shunt. From the 21 patients with refractory ascites, resolution was observed in 1 (3.1%) patient, and in 16 (50.0%) patients, there was ascites control. Regarding transjugular intrahepatic portosystemic shunt after variceal bleeding, 10 (76.9%) patients remained without new bleeding or hospitalizations in the follow-up period. The global survival in the follow-up period in patients with and without hepatic encephalopathy was 60 vs. 82%, respectively (p=0.032). CONCLUSION: Transjugular intrahepatic portosystemic shunt can be considered in decompensated cirrhotic patients; however, the development of hepatic encephalopathy which can shorten survival should be focused.

Hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis.

Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma (HCC), but in non-alcoholic fatty liver disease (NAFLD), up to 50% of patients with HCC had no clinical or histological evidence of cirrhosis. It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis, and each patient should be evaluated on a case-by-case basis based on the profile of specific risk factors identified. For HCC screening in NAFLD, a valid precision-based screening is needed. Currently, when evaluating this population of patients, the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program. Hence, the objective of the present study is to review the epidemiology, the pathophysiology, the histopathological aspects, the current recommendations, and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.

Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil

ABSTRACT Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

There is no correlation between stages of nafld assessed by liver biopsy and the diagnostic criteria for sarcopenia in active populations: a cross-sectional study / Não há correlação entre os estágios da dhgna avaliados por biópsia hepática e os critérios diagnósticos para sarcopenia em populações ativas: um estudo transversal / No existe correlación entre las etapas de ehgna evaluadas mediante biopsia hepática y los criterios diagnósticos de sarcopenia en poblaciones activas: un estudio transversal

Objective: To demonstrate the correlations of the diagnostic criteria for sarcopenia and the levels of Non-alcoholic Fat Liver Disease (NAFLD) assessed by liver biopsy in a physically active population. Methods: Cross-sectional study. Individuals aged >18 years, with NAFLD confirmed by liver biopsy, physically active. Sarcopenia assessment followed EWGSOP2: muscle strength by handgrip, Skeletal Muscle Mass by Bioimpedance, and physical performance by usual gait speed. Statistical Analysis: To test differences between groups in continuous variables, Student's T or Mann-Whitney U Test for independent samples. Pearson and Spearman tests were used for correlations. A 5% significance was considered (p<0.05). Results: 52 patients with NAFLD included, consisting of 35 women and 15 men. There was no difference in age or anthropometric variables. Were found difference statically significant in platelets (higher in women), basal insulin, HOMA-IR and Quick (higher in men). In sarcopenia, the handgrip strength showed difference in favors of men. There was no statistically significant correlation between the sarcopenia and NAFLD levels. Discussion: sarcopenia has been reported as an independent risk factor for NAFLD and its progressions. The physical exercise is one of the most recommended and more effective treatment for both conditions, so is expected that a non-sedentary individual can reduce both indicators. However, there is no consensus about the best method. Also, the both conditions share heterogeneity in diagnosis, prognosis, reason for develop and risk factors across the literature. Conclusion: For populations where most individuals are physically active, it is not possible to find correlation between sarcopenia diagnostic criteria and the stages of NAFLD.

Objetivo: Demonstrar as correlações dos critérios diagnósticos de sarcopenia e dos níveis de doença hepática gordurosa não alcoólica (DHGNA) avaliados por biópsia hepática em uma população fisicamente ativa. Métodos: Estudo transversal. Indivíduos com idade >18 anos, com DHGNA confirmada por biópsia hepática, fisicamente ativos. A avaliação da sarcopenia seguiu o EWGSOP2: força muscular por preensão manual, massa muscular esquelética por bioimpedância e performance física por velocidade usual de marcha. Análise Estatística: Para testar diferenças entre grupos nas variáveis contínuas, teste T de Student ou Teste U de Mann-Whitney para amostras independentes. Os testes de Pearson e Spearman foram utilizados para correlações. Foi considerada significância de 5% (p<0,05). Resultados: Foram incluídos 52 pacientes com DHGNA, sendo 35 mulheres e 15 homens. Não houve diferença na idade ou nas variáveis antropométricas. Foram encontradas diferenças estatisticamente significativas em plaquetas (maior em mulheres), insulina basal, HOMA-IR e Quick (maior em homens). Na sarcopenia, a força de preensão manual apresentou diferença em favor dos homens. Não houve correlação estatisticamente significativa entre os níveis de sarcopenia e DHGNA. Discussão: a sarcopenia tem sido relatada como fator de risco independente para DHGNA e suas progressões. O exercício físico é um dos tratamentos mais recomendados e mais eficazes para ambas as condições, pelo que se espera que um indivíduo não sedentário consiga reduzir ambos os indicadores. No entanto, não há consenso sobre o melhor método. Além disso, ambas as condições compartilham heterogeneidade no diagnóstico, prognóstico, razão de desenvolvimento e fatores de risco em toda a literatura. Conclusão: Para populações onde a maioria dos indivíduos é fisicamente ativo, não é possível encontrar correlação entre os critérios diagnósticos de sarcopenia e os estágios da DHGNA.

Objetivo: demostrar las correlaciones de los criterios diagnósticos de sarcopenia y los niveles de enfermedad del hígado graso no alcohólico (EHGNA) evaluados mediante biopsia hepática en una población físicamente activa. Métodos: Estudio transversal. Individuos mayores de 18 años, con EHGNA confirmada mediante biopsia hepática, físicamente activos. La evaluación de la sarcopenia siguió el EWGSOP2: fuerza muscular mediante agarre manual, masa muscular esquelética mediante bioimpedancia y rendimiento físico mediante velocidad de marcha habitual. Análisis estadístico: Para probar diferencias entre grupos en variables continuas, prueba T de Student o U de Mann-Whitney para muestras independientes. Para las correlaciones se utilizaron las pruebas de Pearson y Spearman. Se consideró una significancia del 5% (p<0,05). Resultados: Se incluyeron 52 pacientes con EHGNA, 35 mujeres y 15 hombres. No hubo diferencia en la edad ni en variables antropométricas. Se encontraron diferencias estadísticamente significativas en plaquetas (mayor en mujeres), insulina basal, HOMA- IR y Quick (mayor en hombres). En la sarcopenia, la fuerza de prensión manual mostró diferencia a favor de los hombres. No hubo correlación estadísticamente significativa entre la sarcopenia y los niveles de NAFLD. Discusión: la sarcopenia ha sido reportada como un factor de riesgo independiente para NAFLD y sus progresiones. El ejercicio físico es uno de los tratamientos más recomendados y efectivos para ambas afecciones, por lo que se espera que una persona no sedentaria pueda reducir ambos indicadores. Sin embargo, no hay consenso sobre cuál es el mejor método. Además, ambas afecciones comparten heterogeneidad en el diagnóstico, pronóstico, motivo de desarrollo y factores de riesgo en la literatura. Conclusión: Para poblaciones donde la mayoría de las personas son físicamente activas, no es posible encontrar correlación entre los criterios de diagnóstico de sarcopenia y las etapas de NAFLD.

Transjugular intrahepatic portosystemic shunt in decompensated cirrhotic patients in a tertiary hospital in southern Brazil

SUMMARY OBJECTIVE: The aim of the present study was to evaluate the outcomes of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt. METHODS: A retrospective longitudinal observational study was carried out evaluating 38 cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt. The outcomes were evaluated in an outpatient follow-up period of 3 months. The assumed significance level was 5%. RESULTS: The indications for transjugular intrahepatic portosystemic shunt were refractory ascites in 21 (55.3%), variceal hemorrhage in 13 (34.2%), and hydrothorax in 4 (10.5%) patients. There was development of hepatic encephalopathy in 10 (35.7%) patients after transjugular intrahepatic portosystemic shunt. From the 21 patients with refractory ascites, resolution was observed in 1 (3.1%) patient, and in 16 (50.0%) patients, there was ascites control. Regarding transjugular intrahepatic portosystemic shunt after variceal bleeding, 10 (76.9%) patients remained without new bleeding or hospitalizations in the follow-up period. The global survival in the follow-up period in patients with and without hepatic encephalopathy was 60 vs. 82%, respectively (p=0.032). CONCLUSION: Transjugular intrahepatic portosystemic shunt can be considered in decompensated cirrhotic patients; however, the development of hepatic encephalopathy which can shorten survival should be focused.

Cardiac abnormalities in patients with nonalcoholic fatty liver disease.

OBJECTIVE: This study aimed to evaluate the correlation between Nonalcoholic fatty liver disease and cardiac abnormalities. METHODS: Patients with Nonalcoholic fatty liver disease who attended an outpatient clinic in Southern Brazil were prospectively evaluated. Patients should be older than 18 years and have steatosis. RESULTS: A total of 174 patients were evaluated. The mean age was 63±12 years, 65% were women, 71% white, 82.2% hypertensive, 52.3% diabetic, 56.3% obese, and 30% dyslipidemic. There was no association between Nonalcoholic fatty liver disease and cardiac abnormalities, even after adjusting for age, sex, and metabolic syndrome. CONCLUSIONS: The present study did not show a direct correlation between Nonalcoholic fatty liver disease and cardiac abnormalities, regardless of metabolic syndrome.

Cardiac abnormalities in patients with nonalcoholic fatty liver disease

SUMMARY OBJECTIVE: This study aimed to evaluate the correlation between Nonalcoholic fatty liver disease and cardiac abnormalities. METHODS: Patients with Nonalcoholic fatty liver disease who attended an outpatient clinic in Southern Brazil were prospectively evaluated. Patients should be older than 18 years and have steatosis. RESULTS: A total of 174 patients were evaluated. The mean age was 63±12 years, 65% were women, 71% white, 82.2% hypertensive, 52.3% diabetic, 56.3% obese, and 30% dyslipidemic. There was no association between Nonalcoholic fatty liver disease and cardiac abnormalities, even after adjusting for age, sex, and metabolic syndrome. CONCLUSIONS: The present study did not show a direct correlation between Nonalcoholic fatty liver disease and cardiac abnormalities, regardless of metabolic syndrome.

Relationship between phase angle, steatosis, and liver fibrosis in patients coinfected with human immunodeficiency virus/hepatitis C virus.

BACKGROUND: Malnutrition, lipodystrophy, and dyslipidemia are prevalent characteristics in patients with human immunodeficiency virus (HIV) infection with or without previous treatment. Such a clinical condition can lead to the hypothesis of the presence of hepatic steatosis with possible progression to fibrosis and the risk of hepatocellular carcinoma. Notably, a low phase angle (PA), evaluated by bioelectrical impedance analysis (BIA), is an independent prognostic marker of clinical progression and survival in HIV-infected patients. AIM: To evaluate the relationship between PA and body composition with steatosis and hepatic fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: A retrospective observational study by convenience sampling of coinfected HIV/HCV patients, in which all patients underwent transient elastography (Fibroscan) and BIA evaluation. Student's t test was used for group comparisons, and Spearman's or Pearson's correlation test was used when appropriate. The significance level was set at 5%, and analyses were performed using SPSS version 21.0. RESULTS: Forty-three patients who received antiretroviral therapy met the inclusion criteria, and 23 (53.5%) were under treatment with protease inhibitors (PIs). There was no difference in PA between those who used PIs and those who did not (P = 0.635). There was no correlation between fibrosis grade and PA (P = 0.355) or lean mass (P = 0.378). There was a significant inverse correlation between the controlled attenuation parameter (CAP) and lean mass (P = 0.378), positive correlation between PA and lean mass (P = 0.378), and negative correlation between PA and fatty mass (P = 0.378), although the CAP and PA were not correlated. When evaluated by sex, no significant correlations were found. CONCLUSION: PA determines the muscle function of HIV/HCV-coinfected patients, and the CAP values reinforce the association with lean mass, suggesting that patients require early nutritional interventions.

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.

Nonalcoholic fatty liver disease: scintigraphy in the diagnosis of steatohepatitis.

OBJECTIVE: Nonalcoholic fatty liver disease is the most prevalent cause of chronic liver disease worldwide. Nonalcoholic steatohepatitis is associated with increased mortality rates due to the liver and cardiovascular diseases. The gold standard for discriminating nonalcoholic fatty liver disease activity and staging is the anatomopathological examination, which is an invasive method. In this regard, noninvasive methods, such as scintigraphy, have been under investigation. This study investigated the role of scintigraphy in the diagnosis of nonalcoholic steatohepatitis in obese patients with nonalcoholic fatty liver disease undergoing bariatric surgery. METHODS: Patients undergoing bariatric surgery and liver biopsy were prospectively included. 99mTc-phytate scintigraphy was performed to assess liver/spleen, spleen/heart, and liver/heart uptake ratios, while 99mTc-isonitrile scintigraphy assessed liver/heart ratio. To evaluate the presence of nonalcoholic steatohepatitis, the results of 99mTc-phytate scintigraphy and 99mTc-isonitrile scintigraphy were compared with the anatomopathological examination. RESULTS: Sixty-one patients with nonalcoholic fatty liver disease were allocated into two groups, namely, nonalcoholic steatohepatitis (n=49) and non-nonalcoholic steatohepatitis (n=12). The results of scintigraphic images obtained after the infusion of radiopharmaceutical 99mTc-phytate in liver/spleen, spleen/heart, liver/heart ratios and 99mTc-isonitrile liver/heart ratio presented no difference between groups with and without nonalcoholic steatohepatitis with an accuracy of 47.5, 37.7, 50.8, and 52.5%, respectively. CONCLUSION: Scintigraphy was not proven to be a useful method to differentiate patients with and without nonalcoholic steatohepatitis.

Drug-induced liver injury and COVID-19: A review for clinical practice.

Coronavirus disease 2019 (COVID-19) consists of a systemic disease that can present many complications. The infection presents broad clinical symptoms and a high rate of transmissibility. In addition to severe acute respiratory syndrome, the patients manifest complications beyond the respiratory system. The frequency of liver damage in COVID-19 patients ranges from 14.8% to 53% of patients. One should pay attention to drug-induced liver injury (DILI) in patients with COVID-19, especially considering the off-label use of drugs in prophylactic and therapeutic regimens applied on large scales. This review aims to present relevant information on the medication used so far in COVID-19 patients and its possible hepatotoxicity. We reviewed liver damage in patients with COVID-19 on PubMed and Virtual Health Library to investigate DILI cases. Four studies were selected, involving the medicines remdesivir, tocilizumab and a pharmacovigilance analysis study. The hepatotoxicity profile of drugs presented in the literature considers use in accordance to usual posology standards for treatment. However, drugs currently used in the management of COVID-19 follow different dosages and posology than those tested by the pharmaceutical industry. The deficiency of uniformity and standardization in the assessment of hepatotoxicity cases hinders the publication of information and the possibility of comparing information among healthcare professionals. It is suggested that severe liver injury in COVID-19 patients should be reported in pharmacovigilance institutions, and physicians should pay attention to any considerable abnormal liver test elevation as it can demonstrate unknown drug hepatotoxicity. Liver disorders in COVID-19 patients and the use of several concomitant off-label medications - with a potential risk of further damaging the liver - should at least be a warning sign for rapid identification and early intervention, thus preventing liver damage from contributing to severe impairment in patients.

PERFORMACE OF TRIGLYCERIDE-GLUCOSE INDEX ON DIAGNOSIS AND STAGING OF NAFLD IN OBESE PATIENTS.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the world, and its prevalence is increasing alongside obesity. In United States, NAFLD is already the second leading cause of liver transplantation. The spectrum of the disease ranges from simple steatosis, which has a benign course, to steatohepatitis, which may progress to cirrhosis and its complications. The rising of noninvasive methods for diagnosing and staging non-alcoholic steatohepatitis (NASH) and fibrosis decreases the need of liver biopsy, as well as the costs and the occurrence of complications related to it. OBJECTIVE: To analyze the performance of the triglyceride-glucose index to evaluate steatosis, NASH and liver fibrosis in obese patients with NAFLD. METHODS: This is a retrospective cross-sectional study. Every medical record of patients who were candidates for bariatric surgery at a leading hospital in Southern Brazil were analyzed. The triglyceride-glucose index (TyG Index), a method composed only of two simple laboratory tests (serum triglycerides and fasting glucose levels), was performed prior to surgery. The TyG Index performance regarding the anatomopathological findings was evaluated, and the AUROC curve was calculated to evaluate the best cut-off point for diagnosing steatosis, non-alcoholic steatohepatitis and liver fibrosis grade. Also, the NAFLD fibrosis Score (NFS) was evaluated. RESULTS: A total of 423 patients were evaluated. The TyG Index with a cut-off point of 8.76 excluded significant simple steatosis (grade 2-3) in obese patients, with 67.6% sensitivity, 65.1% specificity, 46.3% positive predictive value (PPV), 81.8% negative predictive value (NPV), 65.8% accuracy and 0.66 AUROC (P=0.005). In the evaluation of NASH, the TyG Index with a cut-off point of 8.82 excluded significant NASH (grade 2-3) with 57.3% sensitivity, 58.6% specificity, 33.7% PPV, 78.8% NPV, 58.2% accuracy and 0.58 AUROC (P=0.022). When evaluating liver fibrosis, the TyG Index with a cut-off point of 8.91 showed a sensitivity of 61.8%, a specificity of 62.5%, a PPV of 13.8 and a NPV of 94.4% for exclusion of advanced fibrosis (F3-4), with a 62.4% accuracy and 0.69 AUROC (P<0.001). When analyzing the performance of NFS in the diagnosis of advanced fibrosis, the cut-off point <-1.455 excluded advanced fibrosis with sensitivity of 59.4%, specificity of 51%, PPV of 11%, NPV of 92.4% and accuracy of 51.7%. However, the cut-off point of 0.676 to diagnose advanced fibrosis presented sensitivity of 21.9%, specificity of 83%, PPV of 11.7%, NPV of 91.2% and 77.3% accuracy. The AUROC was 0.54 (P=0.480). CONCLUSION: TyG Index did not perform well in the diagnosis of significant steatosis and NASH. However, it was able to exclude advanced fibrosis in obese patients who are candidates for bariatric surgery.

EVALUATION OF REST ENERGY EXPENDITURE IN PATIENTS WITH NON ALCOHOLIC FATTY LIVER DISEASE.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is currently considered a global public health problem, with changes in lifestyle being the effective way to treat the disease. To date, there is no recommended standard of assessment to determine the resting energy expenditure (REE) of patients with NAFLD, so that dietary therapy can be properly guided. OBJECTIVE: To evaluate the REE of patients with NAFLD through indirect calorimetry and compare with different predictive formulas of REE and with REE by electrical bioimpedance analysis (BIA). Assess body composition through BIA, with NAFLD staging and the presence of comorbidities. METHODS: They were evaluated in patients with NAFLD over 18 years of age treated at the Gastroenterology outpatient clinic of a tertiary level hospital in southern Brazil. NAFLD staging was performed using liver biopsy or a non-invasive method. Weight, height and body mass index (BMI) were determined in all patients. The short version of the International Physical Activity Questionnaire was used to assess physical activity. Comorbidities as arterial hypertension, diabetes mellitus and dyslipidemia were evaluated. To estimate energy expenditure at rest, Harris-Benedict, Jeor Mifflin-St, World Health Organization and Schofield formulas were used. BIA was used to assess resting metabolic rate (RMR) and body mass, and to measure RMR, indirect calorimetry was also used. Associations between categorical variables were tested with Pearson's χ2 test and between groups with McNemar's test. The level of significance assumed was 5%. The degree of agreement between the REE measurement methods was assessed using the Blan-Altman test. RESULTS: A total of 67 patients were evaluated, 70.5% male, with a mean age of 59 years and a mean BMI of 33.08 kg/m2 ±5.13. The average RMR per CI was 1,753 kcal ±614.58. When comparing the RMR estimate by different formulas with indirect calorimetry, only the Jeor Mifflin-St formula showed a statistically significant difference (P=0.0001), with a difference of +318.49 kcal. BIA and Harris Benedict's formula presented values closer to CI, 1,658 and 1,845 kcal respectively. CONCLUSION: We suggest that the Jeor Mifflin-St formula should not be used to estimate the RMR in patients with NAFLD. In the absence of indirect calorimetry, some alternatives can be used safely in this population, such as BIA and the predictive formulas of Harris Benedict, Schofield and the World Health Organization.

Avaliação do gasto energético de repouso em pacientes com doença hepática gordurosa não alcoólica / Evaluation of rest energy expenditure in patients with non alcoholic fatty liver disease

ABSTRACT BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is currently considered a global public health problem, with changes in lifestyle being the effective way to treat the disease. To date, there is no recommended standard of assessment to determine the resting energy expenditure (REE) of patients with NAFLD, so that dietary therapy can be properly guided. OBJECTIVE: To evaluate the REE of patients with NAFLD through indirect calorimetry and compare with different predictive formulas of REE and with REE by electrical bioimpedance analysis (BIA). Assess body composition through BIA, with NAFLD staging and the presence of comorbidities. METHODS: They were evaluated in patients with NAFLD over 18 years of age treated at the Gastroenterology outpatient clinic of a tertiary level hospital in southern Brazil. NAFLD staging was performed using liver biopsy or a non-invasive method. Weight, height and body mass index (BMI) were determined in all patients. The short version of the International Physical Activity Questionnaire was used to assess physical activity. Comorbidities as arterial hypertension, diabetes mellitus and dyslipidemia were evaluated. To estimate energy expenditure at rest, Harris-Benedict, Jeor Mifflin-St, World Health Organization and Schofield formulas were used. BIA was used to assess resting metabolic rate (RMR) and body mass, and to measure RMR, indirect calorimetry was also used. Associations between categorical variables were tested with Pearson's χ2 test and between groups with McNemar's test. The level of significance assumed was 5%. The degree of agreement between the REE measurement methods was assessed using the Blan-Altman test. RESULTS: A total of 67 patients were evaluated, 70.5% male, with a mean age of 59 years and a mean BMI of 33.08 kg/m2 ±5.13. The average RMR per CI was 1,753 kcal ±614.58. When comparing the RMR estimate by different formulas with indirect calorimetry, only the Jeor Mifflin-St formula showed a statistically significant difference (P=0.0001), with a difference of +318.49 kcal. BIA and Harris Benedict's formula presented values closer to CI, 1,658 and 1,845 kcal respectively. CONCLUSION: We suggest that the Jeor Mifflin-St formula should not be used to estimate the RMR in patients with NAFLD. In the absence of indirect calorimetry, some alternatives can be used safely in this population, such as BIA and the predictive formulas of Harris Benedict, Schofield and the World Health Organization.

RESUMO CONTEXTO: A doença hepática gordurosa não alcoólica (DHGNA) é considerada, atualmente, um problema de saúde pública global, sendo a mudança no estilo de vida a forma efetiva de tratar a doença. Até o momento não há um padrão de avaliação recomendado para determinar o gasto energético de repouso (GER) de pacientes com DHGNA, para que se possa nortear adequadamente a conduta dietoterápica. OBJETIVO: Avaliar o GER de pacientes com DHGNA através da calorimetria indireta (CI) e comparar com diferentes fórmulas preditivas do GER e com GER através da bioimpedância elétrica (BIA). Avaliar a composição corporal através da BIA, com o estadiamento da DHGNA e com a presença de comorbidades. MÉTODOS: Foram avaliados em pacientes com DHGNA maiores de 18 anos de idade atendidos no ambulatório de Gastroenterologia de um Hospital de nível terciário do Sul do Brasil. O estadiamento da DHGNA foi realizado através de biópsia hepática ou método não invasivo. Peso, altura e índice de massa corporal (IMC) foram determinados em todos os pacientes. Para avaliação da atividade física foi utilizada a versão curta do International Physical Activity Questionnaire. Foram avaliadas as comorbidades hipertensão arterial, diabetes mellitus e dislipidemia. Para a estimativa do gasto energético de repouso utilizou-se as fórmulas de Harris-Benedict, de Jeor Mifflin-St, da Organização Mundial de Saúde e de Schofield. A BIA foi utilizada para avaliação do GER e da massa corporal, e para aferição do GER também se utilizou a CI. Associações entre variáveis categóricas foram testadas com teste χ2 de Pearson e entre grupos com teste de McNemar. O nível de significância assumido foi de 5%. O grau de concordância entre os métodos de mensuração do GER foi aferido pelo teste de Blan-Altman. RESULTADOS: Foram avaliados 67 pacientes, sendo 70,5% do sexo masculino, com média de idade de 59 anos e média de IMC 33,08 kg/m2 ±5,13. O GER médio por CI foi de 1.753 kcal ±614,58. Ao comparar a estimativa do GER por diferentes fórmulas com a calorimetria indireta, apenas a fórmula de Jeor Mifflin-St apresentou diferença estatisticamente significativa (P=0,0001), com uma diferença de +318,49 kcal. A BIA e a fórmula de Harris Benedict apresentaram valores mais próximos à CI, 1.658 e 1.845 kcal respectivamente. CONCLUSÃO: Sugerimos que a fórmula de Jeor Mifflin-St não deva ser utilizada para estimativa do GER em pacientes com DHGNA. Na ausência da CI algumas alternativas podem ser utilizadas com segurança nesta população, como a BIA e as fórmulas preditivas de Harris Benedict, de Schofield e da Organização Mundial de Saúde.

Avaliação do desempenho do índice triglicerídeo-glicose no diagnóstico e estadiamento da DHGNA em pacientes obesos / Performace of triglyceride-glucose index on diagnosis and staging of nafld in obese patients

ABSTRACT BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the world, and its prevalence is increasing alongside obesity. In United States, NAFLD is already the second leading cause of liver transplantation. The spectrum of the disease ranges from simple steatosis, which has a benign course, to steatohepatitis, which may progress to cirrhosis and its complications. The rising of noninvasive methods for diagnosing and staging non-alcoholic steatohepatitis (NASH) and fibrosis decreases the need of liver biopsy, as well as the costs and the occurrence of complications related to it. OBJECTIVE: To analyze the performance of the triglyceride-glucose index to evaluate steatosis, NASH and liver fibrosis in obese patients with NAFLD. METHODS: This is a retrospective cross-sectional study. Every medical record of patients who were candidates for bariatric surgery at a leading hospital in Southern Brazil were analyzed. The triglyceride-glucose index (TyG Index), a method composed only of two simple laboratory tests (serum triglycerides and fasting glucose levels), was performed prior to surgery. The TyG Index performance regarding the anatomopathological findings was evaluated, and the AUROC curve was calculated to evaluate the best cut-off point for diagnosing steatosis, non-alcoholic steatohepatitis and liver fibrosis grade. Also, the NAFLD fibrosis Score (NFS) was evaluated. RESULTS: A total of 423 patients were evaluated. The TyG Index with a cut-off point of 8.76 excluded significant simple steatosis (grade 2-3) in obese patients, with 67.6% sensitivity, 65.1% specificity, 46.3% positive predictive value (PPV), 81.8% negative predictive value (NPV), 65.8% accuracy and 0.66 AUROC (P=0.005). In the evaluation of NASH, the TyG Index with a cut-off point of 8.82 excluded significant NASH (grade 2-3) with 57.3% sensitivity, 58.6% specificity, 33.7% PPV, 78.8% NPV, 58.2% accuracy and 0.58 AUROC (P=0.022). When evaluating liver fibrosis, the TyG Index with a cut-off point of 8.91 showed a sensitivity of 61.8%, a specificity of 62.5%, a PPV of 13.8 and a NPV of 94.4% for exclusion of advanced fibrosis (F3-4), with a 62.4% accuracy and 0.69 AUROC (P<0.001). When analyzing the performance of NFS in the diagnosis of advanced fibrosis, the cut-off point <-1.455 excluded advanced fibrosis with sensitivity of 59.4%, specificity of 51%, PPV of 11%, NPV of 92.4% and accuracy of 51.7%. However, the cut-off point of 0.676 to diagnose advanced fibrosis presented sensitivity of 21.9%, specificity of 83%, PPV of 11.7%, NPV of 91.2% and 77.3% accuracy. The AUROC was 0.54 (P=0.480). CONCLUSION: TyG Index did not perform well in the diagnosis of significant steatosis and NASH. However, it was able to exclude advanced fibrosis in obese patients who are candidates for bariatric surgery.

RESUMO CONTEXTO: A doença hepática gordurosa não-alcoólica (DHGNA) é a doença hepática mais prevalente no mundo. Nos Estados Unidos, a DHGNA já é a segunda causa de transplante hepático. O espectro da doença abrange desde a esteatose simples, que apresenta curso benigno, até esteato-hepatite não-alcoólica (EHNA), que pode progredir para cirrose e suas complicações. O desenvolvimento de métodos não invasivos para o diagnóstico e estadiamento da EHNA e da fibrose hepática visa diminuir a necessidade de biópsia hepática, um procedimento invasivo e não raro associado a complicações. OBJETIVO: Analisar o desempenho do índice triglicerídeo-glicose (TyG Index) para o diagnóstico e estadiamento da DHGNA em pacientes obesos. MÉTODOS: Este é um estudo transversal retrospectivo. Foram analisados todos os prontuários de pacientes candidatos a cirurgia bariátrica em um hospital de referência do Sul do Brasil e calculado o TyG Index, um escore composto por dois exames laboratoriais (triglicerídeos e glicose de jejum), realizados previamente à cirurgia. O desempenho do TyG Index em relação aos achados anatomopatológicos hepáticos foi avaliado, e calculada a curva ROC para avaliação de esteatose simples, EHNA e fibrose hepática. O NAFLD Fibrosis Score (NFS) também foi avaliado. RESULTADOS: Foram avaliados 423 pacientes. O melhor ponto de corte do TyG Index para a exclusão de esteatose simples significativa (grau 2-3) foi de 8,76, com sensibilidade 67,6%, especificidade 65,1%, valor preditivo positivo (VPP) 46,3%, valor preditivo negativo (VPN) 81,8%, acurácia 65,8% e AUROC 0,66 (P=0,005). Na avaliação de EHNA significativa (grau 2-3), o melhor ponto de corte foi de 8,82 com sensibilidade 57,3%, especificidade 58,6%, VPP 33,7%, VPN 78,8%, acurácia 58,8% e AUROC 0,58 (P=0,022). Em relação à fibrose avançada (grau 3-4), o melhor ponto de corte do TyG Index foi de 8,91 com sensibilidade 61,8%, especificidade 62,5%, VPP 13,8%, VPN 94,4%, acurácia 62,4% e AUROC 0,69 (P<0,001). Ao analisarmos o desempenho do NFS no diagnóstico de fibrose avançada, o ponto de corte de <-1,455 excluiu fibrose avançada com sensibilidade 59,4%, especificidade 51%, VPP 11%, VPN 92,4% e acurácia 51,7%. Entretanto, o ponto de corte de 0,676 para fibrose avançada apresentou sensibilidade de 21,9%, especificidade 83%, VPP 11,7%, VPN 91,2% e acurácia 77,3%. A AUROC foi de 0,54 (P=0,480). CONCLUSÃO: O TyG Index não apresentou bom desempenho para o diagnóstico e estadiamento da esteatose simples e da EHNA. Entretanto, foi capaz de excluir fibrose avançada em pacientes obesos candidatos a cirurgia bariátrica.

Role of micronutrients in staging of nonalcoholic fatty liver disease: A retrospective cross-sectional study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) presents high incidence throughout the world and has been progressively increasing in prevalence. This disease has a heterogeneous natural history, including simple steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. The factors that determine its evolution to more severe forms of the disease are still poorly understood, and micronutrients with antioxidant potential may be involved in the pathophysiology of the disease. AIM: To evaluate the relationship between serum levels of micronutrients and the severity of NAFLD. METHODS: A retrospective, observational and cross-sectional study was conducted. This study included all patients undergoing bariatric surgery who experienced liver biopsy during the procedure, and had serum levels of micronutrients (vitamin D, vitamin B12, zinc, iron, and magnesium), which was assessed in a preoperative evaluation conducted at a reference center in southern Brazil. RESULTS: A total of 614 patients were analyzed, of which 93% had steatosis, 70.7% had NASH, and 49.3% had some degree of fibrosis. Serum levels of vitamin D were negatively correlated with the severity of steatosis and NASH, and serum levels of vitamin B12 were positively correlated with the severity of steatosis and fibrosis. The other micronutrients showed no association with NAFLD staging. CONCLUSION: Serum levels of vitamin D are inversely related to the severity of steatosis and NASH, and serum levels of vitamin B12 are higher in more advanced stages of simple steatosis and liver fibrosis. Serum levels of zinc, iron, and magnesium were not associated with NAFLD severity.