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.

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.

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.

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.

RECOMMENDATIONS FOR INVASIVE PROCEDURES IN PATIENTS WITH DISEASES OF THE LIVER AND BILIARY TRACT: REPORT OF A JOINT MEETING OF THE BRAZILIAN SOCIETY OF HEPATOLOGY (SBH), BRAZILIAN SOCIETY OF DIGESTIVE ENDOSCOPY (SOBED) AND BRAZILIAN SOCIETY OF INTERVENTIONAL RADIOLOGY AND ENDOVASCULAR SURGERY (SOBRICE).

Liver and biliary tract diseases are common causes of morbidity and mortality worldwide. Invasive procedures are usually performed in those patients with hepatobiliary diseases for both diagnostic and therapeutic purposes. Defining proper indications and restraints of commonly used techniques is crucial for proper patient selection, maximizing positive results and limiting complications. In 2018, the Brazilian Society of Hepato-logy (SBH) in cooperation with the Brazilian Society of Interventional Radiology and Endovascular surgery (SOBRICE) and the Brazilian Society of Digestive Endoscopy (SOBED) sponsored a joint single-topic meeting on invasive procedures in patients with hepatobiliary diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to guide clinicians, gastroenterologists, hepatologists, radiologists, and endoscopists for the proper use of invasive procedures for management of patients with hepatobiliary diseases.

Albumin for cirrhotic patients with extraperitoneal infections: A meta-analysis.

BACKGROUND AND AIM: Bacterial infections are among the main causes of death in patients with cirrhosis. While there are unquestionable benefits of using albumin in patients with spontaneous bacterial peritonitis, the benefits of albumin are controversial for those with extraperitoneal infections. The aim was to compare the use of albumin associated to antibiotics and antibiotics alone in cirrhotic patients with extraperitoneal infections. METHODS: A systematic review was performed using MEDLINE and Embase databases. Randomized controlled trials comparing albumin associated to antibiotics and antibiotics alone in cirrhotic patients with extraperitoneal infections were considered eligible, as long as at least one of the following outcomes was evaluated: mortality and renal dysfunction. Meta-analysis was performed using the random effects model, through the Mantel-Haenszel method. The study protocol was registered at PROSPERO platform (CRD42018107191). RESULTS: The literature search yielded 812 references. Three randomized controlled trials fulfilled the selection criteria and were included in this meta-analysis. There was no evidence of significant difference between the groups regarding mortality in 30 days (risk ratio [RR] = 1.62, 95% confidence interval [CI]: 0.92-2.84, P = 0.09, I2 = 0%) or in 90 days (RR = 1.27, 95% CI: 0.89-1.83, P = 0.19, I2 = 0%). Regarding renal dysfunction, there was also no evidence of significant difference between the groups (RR = 0.55, 95% CI: 0.25-1.19, P = 0.13, I2 = 0%). CONCLUSION: There is no evidence of significant benefits of using albumin for cirrhotic patients with extraperitoneal infections regarding mortality or renal dysfunction.

RECOMMENDATIONS OF THE BRAZILIAN SOCIETY OF HEPATOLOGY FOR THE MANAGEMENT OF ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS.

Acute kidney injury is a common complication of cirrhosis, occurring in up to 20% of patients hospitalized with cirrhosis. This field is rapidly changing, with significant advances in classification, biomarkers and therapy over the last few years. On the behalf of the Brazilian Society of Hepatology, a panel of experts in Hepatology and Nephrology reviewed published evidence to integrate findings and develop the recommendations presented in this manuscript.

Tratamento antissecretor da doença do refluxo gastroesofágico pediátrica - uma revisão sistemática / Antisecretory treatment for pediatric gastroesophageal reflux disease - a systematic review

ABSTRACT BACKGROUND: Proton pump inhibitors and histamine H2 receptor antagonists are two of the most commonly prescribed drug classes for pediatric gastroesophageal reflux disease, but their efficacy is controversial. Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux, even that causal relation is not proven. OBJECTIVE: To evaluate the use of proton pump inhibitors and histamine H2 receptor antagonists in pediatric gastroesophageal reflux disease through a systematic review. METHODS: A systematic review was performed, using MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. The search was limited to studies published in English, Portuguese or Spanish. There was no limitation regarding date of publication. Studies were considered eligible if they were randomized-controlled trials, evaluating proton pump inhibitors and/or histamine H2 receptor antagonists for the treatment of pediatric gastroesophageal reflux disease. Studies published only as abstracts, studies evaluating only non-clinical outcomes and studies exclusively comparing different doses of the same drug were excluded. Data extraction was performed by independent investigators. The study protocol was registered at PROSPERO platform (CRD42016040156). RESULTS: After analyzing 735 retrieved references, 23 studies (1598 randomized patients) were included in the systematic review. Eight studies demonstrated that both proton pump inhibitors and histamine H2 receptor antagonists were effective against typical manifestations of gastroesophageal reflux disease, and that there was no evidence of benefit in combining the latter to the former or in routinely prescribing long-term maintenance treatments. Three studies evaluated the effect of treatments on children with asthma, and neither proton pump inhibitors nor histamine H2 receptor antagonists proved to be significantly better than placebo. One study compared different combinations of omeprazole, bethanechol and placebo for the treatment of children with cough, and there is no clear definition on the best strategy. Another study demonstrated that omeprazole performed better than ranitidine for the treatment of extraesophageal reflux manifestations. Ten studies failed to demonstrate significant benefits of proton pump inhibitors or histamine H2 receptor antagonists for the treatment of unspecific manifestations attributed to gastroesophageal reflux in infants. CONCLUSION: Proton pump inhibitors or histamine H2 receptor antagonists may be used to treat children with gastroesophageal reflux disease, but not to treat asthma or unspecific symptoms.

RESUMO CONTEXTO: Inibidores de bomba de prótons e antagonistas dos receptores H2 da histamina são duas das mais comumente prescritas classes de medicações para a doença do refluxo gastroesofágico pediátrica, mas sua eficácia é controversa. Muitos pacientes são tratados com essas drogas por manifestações atípicas atribuídas ao refluxo gastroesofágico, mesmo que uma relação causal não esteja comprovada. OBJETIVO: Avaliar os inibidores da bomba de prótons e os antagonistas dos receptores H2 da histamina na doença do refluxo gastroesofágico pediátrica através de uma revisão sistemática. MÉTODOS: Realizou-se uma revisão sistemática, utilizando as bases de dados MEDLINE, EMBASE e Cochrane Central Register of Controlled Trials. A pesquisa foi limitada a estudos publicados em inglês, português e espanhol. Não houve limitação quanto à data de publicação. Os estudos foram considerados elegíveis se fossem ensaios controlados randomizados que avaliassem inibidores da bomba de prótons e/ou antagonistas dos receptores H2 da histamina para o tratamento da doença do refluxo gastroesofágico pediátrica. Estudos publicados apenas como resumos, estudos que não avaliassem desfechos clinicamente relevantes e estudos que comparassem exclusivamente diferentes doses do mesmo fármaco foram excluídos. A extração de dados foi realizada por pesquisadores independentes. O protocolo do estudo foi registrado na plataforma PROSPERO (CRD42016040156). RESULTADOS: Após a análise das 735 referências identificadas, 23 estudos (1598 pacientes randomizados) foram incluídos na revisão sistemática. Oito estudos demonstraram que tanto os inibidores da bomba de prótons como os antagonistas dos receptores H2 da histamina eram eficazes contra as manifestações típicas da doença de refluxo gastroesofágico e que não havia evidências de benefício na combinação dessas classes de drogas ou na prescrição rotineira de tratamentos de manutenção de longo prazo. Três estudos avaliaram o efeito dos tratamentos em crianças com asma e, nem os inibidores da bomba de prótons, nem os antagonistas dos receptores H2 da histamina se mostraram significativamente melhores do que o placebo. Um estudo comparou diferentes combinações de omeprazol, betanecol e placebo para o tratamento de crianças com tosse, e não há uma definição clara sobre a melhor estratégia terapêutica. Outro estudo demonstrou que o omeprazol apresentou melhor desempenho do que a ranitidina para o tratamento de manifestações extraesofágicas da doença do refluxo gastroesofágico. Dez estudos não tiveram sucesso em demonstrar benefícios significativos dos inibidores da bomba de prótons ou dos antagonistas dos receptores H2 da histamina para o tratamento de manifestações inespecíficas atribuídas ao refluxo gastroesofágico em crianças menores de 1 ano de idade. CONCLUSÃO: Inibidores da bomba de prótons ou antagonistas dos receptores H2 da histamina podem ser utilizados para tratar crianças com doença de refluxo gastroesofágico, mas não para tratar asma ou sintomas inespecíficos.

ANTISECRETORY TREATMENT FOR PEDIATRIC GASTROESOPHAGEAL REFLUX DISEASE - A SYSTEMATIC REVIEW.

BACKGROUND: Proton pump inhibitors and histamine H2 receptor antagonists are two of the most commonly prescribed drug classes for pediatric gastroesophageal reflux disease, but their efficacy is controversial. Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux, even that causal relation is not proven. OBJECTIVE: To evaluate the use of proton pump inhibitors and histamine H2 receptor antagonists in pediatric gastroesophageal reflux disease through a systematic review. METHODS: A systematic review was performed, using MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. The search was limited to studies published in English, Portuguese or Spanish. There was no limitation regarding date of publication. Studies were considered eligible if they were randomized-controlled trials, evaluating proton pump inhibitors and/or histamine H2 receptor antagonists for the treatment of pediatric gastroesophageal reflux disease. Studies published only as abstracts, studies evaluating only non-clinical outcomes and studies exclusively comparing different doses of the same drug were excluded. Data extraction was performed by independent investigators. The study protocol was registered at PROSPERO platform (CRD42016040156). RESULTS: After analyzing 735 retrieved references, 23 studies (1598 randomized patients) were included in the systematic review. Eight studies demonstrated that both proton pump inhibitors and histamine H2 receptor antagonists were effective against typical manifestations of gastroesophageal reflux disease, and that there was no evidence of benefit in combining the latter to the former or in routinely prescribing long-term maintenance treatments. Three studies evaluated the effect of treatments on children with asthma, and neither proton pump inhibitors nor histamine H2 receptor antagonists proved to be significantly better than placebo. One study compared different combinations of omeprazole, bethanechol and placebo for the treatment of children with cough, and there is no clear definition on the best strategy. Another study demonstrated that omeprazole performed better than ranitidine for the treatment of extraesophageal reflux manifestations. Ten studies failed to demonstrate significant benefits of proton pump inhibitors or histamine H2 receptor antagonists for the treatment of unspecific manifestations attributed to gastroesophageal reflux in infants. CONCLUSION: Proton pump inhibitors or histamine H2 receptor antagonists may be used to treat children with gastroesophageal reflux disease, but not to treat asthma or unspecific symptoms.

Razão da contagem de plaquetas ao quadrado/diâmetro do baço-aspartato aminotransferase: avaliação de um novo método não-invasivo para a predição de varizes esofágicas / Platelet count squared/spleen diameter-aspartate aminotransferase ratio: non-invasive method to predict esophageal varices

ABSTRACT BACKGROUND - Variceal bleeding has a high mortality among cirrhotics, and screening with endoscopy is indicated at the diagnosis of cirrhosis. Screening with endoscopy implies discomfort, risks and considerable costs. OBJECTIVE - To evaluate platelet count squared/spleen diameter-aspartate aminotransferase ratio (PS/SA), as a non-invasive predictor of esophageal varices in cirrhotics. METHODS - This cross-sectional study evaluated cirrhotics for PS/SA and presence of esophageal varices. Outpatient records of cirrhotic patients were reviewed for the abovementioned data. Sensitivity, specificity, negative and positive predictive values of PS/SA were calculated. After the univariate analysis, variables with P<0.10 were submitted to a logistic regression. RESULTS - The study included 164 cirrhotics, 59.70% male, with a mean age of 56.7 years. Hepatitis C was the most frequent cause of cirrhosis, being present in 90 patients. Patients were classified as Child-Pugh A in 52.44% and as Child-Pugh B or C in 47.56%. Esophageal varices were present in 72.56% of the patients at endoscopy. PS/SA, with a cutoff of 3x108, had a sensitivity of 95.80% (confidence interval of 95% - 95%CI=0.92-0.99), a specificity of 22.70% (95%CI=0.10-0.35), a positive predictive value of 77.20% (95%CI=0.70-0.84) and a negative predictive value of 66.70% (95%CI=0.42-0.91). In the logistic regression, only platelet count and Child-Pugh score were associated to esophageal varices (P<0.05). CONCLUSION - PS/SA has an excellent sensitivity to predict esophageal varices, allowing almost one fourth of patients without esophageal varices to spare endoscopy. Nevertheless, PS/SA is not independently associated to esophageal varices.

RESUMO CONTEXTO - A hemorragia varicosa tem elevada mortalidade entre cirróticos, e o rastreamento endoscópico de varizes está indicado no momento do diagnóstico da cirrose. O rastreamento endoscópico implica desconforto, riscos e custos consideráveis. OBJETIVO - Avaliar a razão da contagem de plaquetas ao quadrado/diâmetro do baço-aspartato aminotransferase (PQ/BA) como preditor não-invasivo de varizes esofágicas em cirróticos. MÉTODOS - Este estudo transversal avaliou cirróticos quanto ao PQ/BA e à presença de varizes esofágicas. Prontuários ambulatoriais de cirróticos foram revisados quanto a tais dados. Sensibilidade, especificidade e valores preditivos negativo e positivo do PQ/BA foram calculados. Após a análise univariada, variáveis com P<0,10 foram submetidas à regressão logística. RESULTADOS - O estudo incluiu 164 cirróticos, 59,70% masculinos, com média de idade de 56,7 anos. Hepatite C foi a mais frequente causa de cirrose, estando presente em 90 pacientes. Os pacientes foram classificados como Child-Pugh A em 52,44% e em Child-Pugh B ou C em 47,56%. As varizes esofágicas estiveram presentes à endoscopia em 72,56% dos pacientes. PQ/BA, com um ponto de corte de 3x108, teve sensibilidade de 95,80% (intervalo de confiança de 95% - IC95%=0,92-0,99), especificidade de 22,70% (IC95%=0,10-0,35), valor preditivo positivo de 77,20% (IC95%=0,70-0,84) e valor preditivo negativo de 66,70% (IC95%=0,42-0,91). Na regressão logística, apenas a contagem de plaquetas e o escore de Child-Pugh associaram-se às varizes esofágicas (P<0,05). CONCLUSÃO - PQ/BA apresentou excelente sensibilidade para predizer varizes esofágicas, permitido que cerca de um quarto dos pacientes sem varizes esofágicas evitasse a endoscopia. Entretanto, PQ/BA não se associou de maneira independente às varizes esofágicas.

PLATELET COUNT SQUARED/SPLEEN DIAMETER-ASPARTATE AMINOTRANSFERASE RATIO: NON-INVASIVE METHOD TO PREDICT ESOPHAGEAL VARICES.

BACKGROUND: - Variceal bleeding has a high mortality among cirrhotics, and screening with endoscopy is indicated at the diagnosis of cirrhosis. Screening with endoscopy implies discomfort, risks and considerable costs. OBJECTIVE: - To evaluate platelet count squared/spleen diameter-aspartate aminotransferase ratio (PS/SA), as a non-invasive predictor of esophageal varices in cirrhotics. METHODS: - This cross-sectional study evaluated cirrhotics for PS/SA and presence of esophageal varices. Outpatient records of cirrhotic patients were reviewed for the abovementioned data. Sensitivity, specificity, negative and positive predictive values of PS/SA were calculated. After the univariate analysis, variables with P<0.10 were submitted to a logistic regression. RESULTS: - The study included 164 cirrhotics, 59.70% male, with a mean age of 56.7 years. Hepatitis C was the most frequent cause of cirrhosis, being present in 90 patients. Patients were classified as Child-Pugh A in 52.44% and as Child-Pugh B or C in 47.56%. Esophageal varices were present in 72.56% of the patients at endoscopy. PS/SA, with a cutoff of 3x108, had a sensitivity of 95.80% (confidence interval of 95% - 95%CI=0.92-0.99), a specificity of 22.70% (95%CI=0.10-0.35), a positive predictive value of 77.20% (95%CI=0.70-0.84) and a negative predictive value of 66.70% (95%CI=0.42-0.91). In the logistic regression, only platelet count and Child-Pugh score were associated to esophageal varices (P<0.05). CONCLUSION: - PS/SA has an excellent sensitivity to predict esophageal varices, allowing almost one fourth of patients without esophageal varices to spare endoscopy. Nevertheless, PS/SA is not independently associated to esophageal varices.

Transient Elastography vs Aspartate Aminotransferase to Platelet Ratio Index in Hepatitis C: A Meta-Analysis

ABSTRACT Background and rationale. Many different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. Material and methods. A systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. Results. Eight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71- 186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. Conclusion. In conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.

TERLIPRESSIN VERSUS NORADRENALINE FOR HEPATORENAL SYNDROME. Economic evaluation under the perspective of the Brazilian Public Health System.

BACKGROUND: - Terlipressin and noradrenaline are the best studied treatments for hepatorenal syndrome, and there is no evidence of superiority of one over the other regarding to efficacy. While the former drug is more costly, the latter requires admission into an intensive care unit. OBJECTIVE: - The aim of this study was to perform an economic evaluation, comparing treatments for hepatorenal syndrome with terlipressin and noradrenaline. METHODS: - For the economic evaluation, a cost-minimization analysis was performed. Direct medical costs of the two treatment strategies were compared under the perspective of the Brazilian Public Health System as the third-party payer. A probabilistic sensitivity analysis was performed. RESULTS: - The costs of treatments with terlipressin or noradrenaline were 287.77 and 2,960.45 International Dollars (Int$) respectively. Treatment using terlipressin would save Int$2,672.68 for the Public Health System for each hospital admission related to hepatorenal syndrome. In the probabilistic sensitivity analysis, it was verified that the cost of the treatment with noradrenaline could vary between Int$2,326.53 and Int$3,644.16, while costs related to the treatment using terlipressin are not variable. CONCLUSION: - The treatment strategy using terlipressin was more economical than that using noradrenaline under the perspective of the Brazilian Public Health System as the third-party payer.

Analysis of the survival of cirrhotic patients enlisted for liver transplantation in the pre- and post-MELD era in southern Brazil.

CONTEXT: Transplantation is the only cure for decompensated cirrhosis. Model for End-Stage Liver Disease (MELD) is used in liver allocation. OBJECTIVES: Comparing survival of enlisted populations in pre- and post-MELD eras and estimating their long-term survival. METHODS: This is a retrospective study of cirrhotics enlisted for transplantation during pre- and post-MELD eras. Survival curves were generated using Kaplan-Meier's model. Cox's model was used to determine risk factors for mortality. Exponential, Weibull's, normal-log and Gompertz's models were used to estimate long-term survival. RESULTS: The study included 162 patients enlisted in pre-MELD era and 184 in post-MELD period. Kaplan-Meier's survival curve of patients enlisted in post-MELD era was better than that of pre-MELD period (P = 0.009). This difference remained for long-term estimates, with a survival of 53.54% in 5 years and 44.64% in 10 years for patients enlisted in post-MELD era and of 43.17% and 41.75% for pre-MELD period. Era in which patients had been enlisted (P = 0.010) and MELD score at enlistment (P<0.001) were independently associated to survival with hazard ratios of 0.664 (95% CI-confidence interval = 0.487-0.906) and 1.069 (95% CI = 1.043-1.095). CONCLUSIONS: MELD-based transplantation policy is superior to chronology-based one, promoting better survival for enlisted patients, even in long-term.

Analysis of thessurvival of cirrhotic patients nlisted for liver transplantatiion in the pre- and post-meld era in southern Brazil / Análise da sobrevida de pacientes cirróticos listados para transplante ortotópico de fígado nas eras pré e pós MELD no Sul do Brasil

Context Transplantation is the only cure for decompensated cirrhosis. Model for End-Stage Liver Disease (MELD) is used in liver allocation. Objectives Comparing survival of enlisted populations in pre- and post-MELD eras and estimating their long-term survival. Methods This is a retrospective study of cirrhotics enlisted for transplantation during pre- and post-MELD eras. Survival curves were generated using Kaplan-Meier’s model. Cox’s model was used to determine risk factors for mortality. Exponential, Weibull’s, normal-log and Gompertz’s models were used to estimate long-term survival. Results The study included 162 patients enlisted in pre-MELD era and 184 in post-MELD period. Kaplan-Meier’s survival curve of patients enlisted in post-MELD era was better than that of pre-MELD period (P = 0.009). This difference remained for long-term estimates, with a survival of 53.54% in 5 years and 44.64% in 10 years for patients enlisted in post-MELD era and of 43.17% and 41.75% for pre-MELD period. Era in which patients had been enlisted (P = 0.010) and MELD score at enlistment (P<0.001) were independently associated to survival with hazard ratios of 0.664 (95% CI-confidence interval = 0.487-0.906) and 1.069 (95% CI = 1.043-1.095). Conclusions MELD-based transplantation policy is superior to chronology-based one, promoting better survival for enlisted patients, even in long-term. .

Contexto O transplante é a única cura para a cirrose descompensada. O Model for End-Stage Liver Disease (MELD) é usado na alocação de órgãos. Objetivos Comparar a sobrevida da população listada para transplante nas eras pré e pós-MELD e estimar sua sobrevida a longo prazo. Métodos Este é um estudo retrospectivo, de cirróticos listados para transplante nas eras pré e pós-MELD. Curvas de sobrevida foram criadas através do modelo de Kaplan-Meier. O modelo de Cox foi utilizada para determinar fatores de risco para mortalidade. Os modelos exponencial, Weibull, log-normal e Gompertz foram usados para estimar sobrevida de longo prazo. Resultados Incluíram-se 162 pacientes listados na era pré-MELD e 184 listados na pós-MELD. A curva de Kaplan-Meier para os pacientes listados na era pós-MELD foi melhor que a da pré-MELD (P = 0,009). Esta diferença permaneceu nas estimativas de longo prazo, com sobrevida de 53,54% em 5 anos e de 44,64% em 10 anos para pacientes listados na era pós-MELD e de 43,17% e 41,75% no período pré-MELD. A era em que os pacientes eram listados (P = 0,010) e o MELD de inscrição (P<0,001) estiveram associados de maneira independente à sobrevida, com razão de riscos de 0,664 (intervalo de confiança-IC 95% = 0,487-0,906) e de 1,069 (IC 95% = 1,043-1,095). Conclusões A política de transplantes baseada no escore MELD é superior à baseada no tempo de espera em lista, promovendo melhor sobrevida, mesmo em longo prazo. .

Aspartate aminotransferase-to-platelet ratio index (APRI) for the non-invasive prediction of esophageal varices.

BACKGROUND & AIMS: Variceal bleeding is a dramatic and common complication of cirrhosis, and, therefore, endoscopy is recommended for the screening of EV (esophageal varices) in every cirrhotic. This study evaluates the capacity of APRI (aspartate aminotransferase-to-platelet ratio index) in non-invasively predicting EV. MATERIAL AND METHODS: This cross-sectional study evaluated cirrhotics for their APRI value and the presence of EV, with a cutoff point of 1, 3; platelet count, spleen diameter, PC/SD (platelet count/ spleen diameter ratio), aspartate aminotransferase/alanine aminotransferase ratio, Child-Pugh score and MELD (model for end-stage liver disease) score were also studied. RESULTS: The study included 164 cirrhotics, 59.7% male, with a mean age of 56.7 years. APRI demonstrated a sensitivity of 64.7% (95% confidence interval-95%CI = 0.56-0.73), specificity of 72.7% (95%CI = 0.59-0.86), positive predictive value of 86.5% (95%CI = 0.79-0.94), negative predictive value of 43.2% (95%CI = 0.32-0.55). In the univariate analysis, platelet count, spleen diameter, Child and MELD scores, PC/SD and APRI were related to EV (p < 0.05). In the logistic regression, only platelet count and Child score were associated to EV (p < 0.05). CONCLUSION: APRI is not an independent factor for the prediction of EV. Its sensitivity, specificity and predictive values are insufficient for the index to be used for the screening of EV in cirrhotics.