SPONTANEOUS REGRESSION OF HEPATOCELLULAR CARCINOMA: FOCUSING IN THE ASSOCIATED RISK FACTORS.

BACKGROUND: Spontaneous regression (SR) is defined as the partial or complete disappearance of a tumor, in the absence of a specific treatment. Evidence of the SR in hepatocellular carcinoma (HCC) is rare. OBJECTIVE: The authors aimed to review all the cases of SR of HCC in two reference centers of Southern Brazil, highlighting the main characteristics. METHODS: Data of all patients with HCC were retrospectively reviewed looking for the occurrence of SR in patients from two tertiary centers in Southern Brazil, in the last five years. The diagnosis of cirrhosis was established according to clinical, laboratory and imaging data, as well as upper endoscopy or histopathological examination when necessary. The diagnosis of HCC was based on typical findings according to radiologic criteria (LIRADS) or histopathological examination. Spontaneous regression was defined as a partial or complete involution of a HCC in the absence of a specific therapy. RESULTS: From all cases of HCC in the last 5 years (n=433), there were five cases of SR. Three (60%) were men, the mean age was 62.6 (50.0-76.0) years, and the etiology was HCV in 3 (60%). Complete regression was observed in three patients (60%), one patient (20%) presented partial regression, and one (20%) relapesed and died. The time of follow-up varied between 12 and 21 months. In this presentation, it was highlighted one case of SR observed after COVID-19 infection in a patient with cirrhosis. The possible mechanisms involved in this situation were reviewed, emphasizing the most common like hypoxia and immunological. There were also one patient submitted to a surgical procedure as a possible fator involved and three patients without obvious risk factors. CONCLUSION: This phenomenon will possibly contribute to a better understanding of the pathophysiological mechanisms of HCC.

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.

Results of transarterial chemoembolization of hepatocellular carcinoma as a bridging therapy to liver transplantation / Resultados da quimioembolização transarterial do carcinoma hepatocelular como terapia ponte para transplante de fígado

Abstract Objective: To evaluate the degree of tumor necrosis after transarterial chemoembolization (TACE), used as a bridging therapy in patients awaiting liver transplantation, and its effect on survival. Materials and Methods: This was a retrospective cohort study involving 118 patients submitted to TACE prior to liver transplantation, after which the degree of tumor necrosis in the explant and post-transplant survival were evaluated. Results: Total necrosis of the neoplastic nodule in the explant was observed in 76 patients (64.4%). Of the patients with total necrosis in the explanted liver, 77.8% had presented a complete response on imaging examinations. Drug-eluting bead TACE (DEB-TACE), despite showing a lower rate of complications than conventional TACE, provided a lower degree of total necrosis, although there was no statistical difference between the two. By the end of the study period, 26 of the patients had died. Survival was longer among the patients with total necrosis than among those with partial or no necrosis (HR = 2.24 [95% CI: 0.91-5.53]; p = 0.078). Conclusion: In patients undergoing TACE as a bridging therapy, total tumor necrosis appears to be associated with improved patient survival.

Resumo Objetivo: Avaliar os resultados da necrose tumoral após quimioembolização transarterial (TACE) como terapia ponte e seu reflexo na sobrevida dos pacientes. Materiais e Métodos: Estudo de coorte retrospectivo, com 118 pacientes que realizaram TACE, em que foram avaliados o grau de necrose tumoral no explante e a sobrevida pós-transplante. Resultados: Necrose total do nódulo neoplásico no explante foi observada em 76 pacientes (64,4%). Observou-se que 77,8% dos pacientes com necrose total no explante hepático tinham apresentado resposta completa nos exames de imagem. A DEB-TACE, apesar de ter demonstrado menor taxa de intercorrências, proporcionou menor grau de necrose total em relação à TACE convencional, a despeito de não haver diferença estatística. Ao final do seguimento do estudo, o número de óbitos foi de 26. A sobrevida foi maior nos pacientes que tiveram necrose total quando comparada com grau de necrose parcial ou ausência de necrose [HR = 2,24 (IC 95%: 0,91-5,53); p = 0,078]. Conclusão: Necrose completa do tumor nos pacientes submetidos a TACE como terapia ponte parece estar associada com melhora da sobrevida.

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.

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.

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.

RESULTS OF IMMUNOHISTOCHEMISTRY IN THE DIFFERENTIAL DIAGNOSIS OF EARLY HEPATOCELLULAR CARCINOMA AND NODULES WITH HIGH-GRADE DYSPLASIA IN PATIENTS WITH CIRRHOSIS.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver and cirrhosis is considered a pre-malignant disease. In this context, the evolutionary sequence from low grade dysplastic nodule and high grade dysplastic nodule (HGDN) to early HCC and advanced HCC has been studied. The differential diagnosis between HGDN and early HCC is still a challenge, especially in needle biopsies. OBJECTIVE: To evaluate an immunohistochemistry panel to differentiate dysplastic nodules and HCC. METHODS: Patients with cirrhosis who underwent surgical resection or liver transplantation were included. The sensitivity, specificity and accuracy for the diagnosis of neoplasia were analyzed by evaluating five markers: heat shock protein 70, glypican 3, glutamine synthetase, clathrin heavy chain and beta-catenin. P≤0.05 was considered statistically significant. RESULTS: One hundred and fifty-six nodules were included; of these, 57 were HCC, 14 HGDN, 18 low grade dysplastic nodules and 67 regenerative macronodules. Sensitivity of HCC diagnosis was 64.9% for glypican 3 and 77.2% for glutamine syntetase, while specificity was 96.0% and 96.0% respectively. When the panel of four markers was considered (excluding beta catenin), the specificity ranged from 87.9% for one positive marker to 100% for at least three markers. The best accuracy for HCC diagnosis was obtained with at least two positive markers, which was associated with a sensitivity of 82.5% and specificity of 99%. CONCLUSION: Differential diagnosis of dysplastic nodules and HCC by morphological criteria can be challenging. Immunomarkers are useful and should be used for the differential diagnosis between HCC and HGDN.

Papel da imunohistoquímica no diagnóstico diferencial do carcinoma hepatocelular precoce e dos nódulos com displasia de alto grau em pacientes com cirrose / Results of immunohistochemistry in the differential diagnosis of early hepatocellular carcinoma and nodules with high-grade dysplasia in patients with cirrhosis

ABSTRACT BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver and cirrhosis is considered a pre-malignant disease. In this context, the evolutionary sequence from low grade dysplastic nodule and high grade dysplastic nodule (HGDN) to early HCC and advanced HCC has been studied. The differential diagnosis between HGDN and early HCC is still a challenge, especially in needle biopsies OBJECTIVE: To evaluate an immunohistochemistry panel to differentiate dysplastic nodules and HCC. METHODS: Patients with cirrhosis who underwent surgical resection or liver transplantation were included. The sensitivity, specificity and accuracy for the diagnosis of neoplasia were analyzed by evaluating five markers: heat shock protein 70, glypican 3, glutamine synthetase, clathrin heavy chain and beta-catenin. P≤0.05 was considered statistically significant. RESULTS: One hundred and fifty-six nodules were included; of these, 57 were HCC, 14 HGDN, 18 low grade dysplastic nodules and 67 regenerative macronodules. Sensitivity of HCC diagnosis was 64.9% for glypican 3 and 77.2% for glutamine syntetase, while specificity was 96.0% and 96.0% respectively. When the panel of four markers was considered (excluding beta catenin), the specificity ranged from 87.9% for one positive marker to 100% for at least three markers. The best accuracy for HCC diagnosis was obtained with at least two positive markers, which was associated with a sensitivity of 82.5% and specificity of 99%. CONCLUSION: Differential diagnosis of dysplastic nodules and HCC by morphological criteria can be challenging. Immunomarkers are useful and should be used for the differential diagnosis between HCC and HGDN.

RESUMO CONTEXTO: O carcinoma hepatocelular (CHC) é o câncer primário do fígado mais frequente e a cirrose é considerada uma doença pré-maligna. Nesse contexto, a sequência evolutiva do nódulo displásico de baixo grau e nódulo displásico de alto grau (NDAG) para CHC precoce e CHC avançado tem sido estudada. O diagnóstico diferencial entre NDAG e CHC precoce ainda é um desafio, principalmente em biópsias por agulha. OBJETIVO: Avaliar um painel de imunohistoquímica para diferenciar nódulos displásicos de CHC. MÉTODOS: Foram incluídos pacientes com cirrose submetidos à ressecção cirúrgica ou transplante de fígado. A sensibilidade, especificidade e acurácia para o diagnóstico da neoplasia foram analisadas avaliando cinco marcadores: proteína de choque térmico 70kDa, glipican 3, glutamina sintetase, clatrina de cadeia pesada e beta-catenina. P≤0,05 foi considerado estatisticamente significativo. RESULTADOS: Cento e cinquenta e seis nódulos foram incluídos; destes, 57 eram CHC, 14 NDAG, 18 nódulos displásicos de baixo grau e 67 macronódulos regenerativos. A sensibilidade do diagnóstico de CHC foi de 64,9% para glipican 3 e 77,2% para glutamina sintetase, enquanto a especificidade foi de 96,0% e 96,0%, respectivamente. Quando o painel de quatro marcadores foi considerado (excluindo beta catenina), a especificidade variou de 87,9% para um marcador positivo a 100% para pelo menos três marcadores. A melhor acurácia para o diagnóstico de CHC foi obtida com pelo menos dois marcadores positivos, o que foi associado a uma sensibilidade de 82,5% e especificidade de 99%. CONCLUSÃO: O diagnóstico diferencial de nódulos displásicos e CHC por critérios morfológicos pode ser desafiador. Imunomarcadores são úteis e devem ser usados para o diagnóstico diferencial entre CHC e NDAG.

BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF HEPATOCELLULAR CARCINOMA.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

Muscle depletion in cirrhotic patients assessed using computed tomography: a cross-sectional study.

BACKGROUND: Sarcopenia is a common complication in patients with cirrhosis and may lead to increased morbidity and mortality. OBJECTIVE: To investigate the prevalence of sarcopenia and its association with disease severity scores, among patients with cirrhosis. DESIGN AND SETTING: Observational and retrospective cohort study carried out in a tertiary-care hospital in southern Brazil. METHODS: This study was conducted among patients with chronic liver disease who were followed up at the gastroenterology and hepatology outpatient clinic of a tertiary-care hospital in southern Brazil and who underwent computed tomography scans of the abdomen through any indication. RESULTS: We included 83 patients in the study. In the population evaluated, there was a predominance of males (57.80%) and the mean age was 56 years. Hepatitis B or C virus was present in the genesis of the disease in 34.9% of the cases, followed by an etiology of alcohol abuse (30.1%). Sarcopenia was diagnosed in 41 (49.4%) of the patients when the cutoff point for cirrhotic patients was used. There was no significant correlation between the Child-Pugh and MELD severity scores and the occurrence of sarcopenia. CONCLUSION: Sarcopenia presents high prevalence among patients with chronic liver disease, without any association with predictors of severity.

Muscle depletion in cirrhotic patients assessed using computed tomography: a cross-sectional study

ABSTRACT BACKGROUND: Sarcopenia is a common complication in patients with cirrhosis and may lead to increased morbidity and mortality. OBJECTIVE: To investigate the prevalence of sarcopenia and its association with disease severity scores, among patients with cirrhosis. DESIGN AND SETTING: Observational and retrospective cohort study carried out in a tertiary-care hospital in southern Brazil. METHODS: This study was conducted among patients with chronic liver disease who were followed up at the gastroenterology and hepatology outpatient clinic of a tertiary-care hospital in southern Brazil and who underwent computed tomography scans of the abdomen through any indication. RESULTS: We included 83 patients in the study. In the population evaluated, there was a predominance of males (57.80%) and the mean age was 56 years. Hepatitis B or C virus was present in the genesis of the disease in 34.9% of the cases, followed by an etiology of alcohol abuse (30.1%). Sarcopenia was diagnosed in 41 (49.4%) of the patients when the cutoff point for cirrhotic patients was used. There was no significant correlation between the Child-Pugh and MELD severity scores and the occurrence of sarcopenia. CONCLUSION: Sarcopenia presents high prevalence among patients with chronic liver disease, without any association with predictors of severity.

Atualização das recomendações da Sociedade Brasileira de Hepatologia para o diagnóstico e tratamento do carcinoma hepatocellular / Brazilian society of hepatology updated recommendations for diagnosis and treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2015 suas primeiras recomendações sobre a abordagem do CHC. Desde então, novas evidências sobre o diagnóstico e tratamento do CHC foram relatadas na literatura médica, levando a diretoria da SBH a promover uma reunião monotemática sobre câncer primário de fígado em agosto de 2018 com o intuito de atualizar as recomendações sobre o manejo da neoplasia. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização baseada em evidências científicas visando que pudesse nortear a prática clínica multidisciplinar do CHC. O texto resultante foi submetido a avaliação e aprovação de todos membros da SBH através de sua homepage. O documento atual é a versão final que contêm as recomendações atualizadas e revisadas da SBH.

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.