Amyloidosis: a rare cause of severe acute liver failure.

Gastrointestinal amyloidosis can be primary, more associated with monoclonal plasma cell dyscrasia, or secondary, usually secondary to a tissue-destructive, chronic inflammatory process (such as inflammatory bowel disease, for example) and long-term dialysis. The rare presentation of severe acute liver failure in systemic amyloidosis can make this diagnosis/ management more difficult. Hepatomegaly with signs of diffuse infiltrative disease and periportal involvement associated with thoracic and other abdominal radiological findings in the appropriate clinical context may constitute a diagnostic imaging clue in this challenge.

Corrigendum to "Metabolic dysfunctions promoted by AIN-93G standard diet compared with three obesity-inducing diets in C57BL/6J mice" [Curr. Res. Physiol. (2022) 436-444].

[This corrects the article DOI: 10.1016/j.crphys.2022.11.001.].

Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19

ABSTRACT COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

Metabolic dysfunctions promoted by AIN-93G standard diet compared with three obesity-inducing diets in C57BL/6J mice.

Researchers from different fields have studied the causes of obesity and associated comorbidities, proposing ways to prevent and treat this condition by using a common animal model of obesity to create a profound energy imbalance in young adult rodents. However, to confirm the harmful effects of consuming a high-fat and hypercaloric diet, it is common to include normolipidic and normocaloric control groups in the experimental protocols. This study compared the effect of three experimental diets described in the literature - namely, a high-fat diet, a high-fat and high-sucrose diet, and a high-fat and high-fructose diet - to induce obesity in C57BL/6 J mice with the standard AIN-93G diet as a control. We hypothesize that the AIN diet formulation is not a good control in this type of experiment because this diet promotes weight gain and metabolic dysfunctions similar to the hypercaloric diet. The metabolic data of animals fed the AIN-93G diet were similar to those of the high-calorie groups (development of steatosis and hyperlipidemia). However, it is important to emphasize that the group fed a high-fat diet had a higher percentage of total fat (p = 0.0002) and abdominal fat (p = 0.013) compared to the other groups. Also, the high-fat group responded poorly to glucose and insulin tolerance tests, showing a picture of insulin resistance. As expected, the intake of the AIN-93G diet promotes metabolic alterations in the animals like the high-fat formulations. Therefore, although this diet continues to be used as the gold standard for growth and maintenance, it warrants a reassessment of its composition to minimize the metabolic changes observed in this study, thus updating its fitness as a normocaloric model of a standard rodent diet.

Clinical impact of the Model for End Liver Disease (MELD) score on the presence of microvascular invasion and on the postoperative outcome in patients undergoing liver transplantation.

OBJECTIVE: to correlate clinical and epidemiological data with the pathological analysis of liver explants from patients undergoing liver transplantation for hetapocarcinoma in the UNICAMP HC and to verify whether the MELD and MELD-Na scores are reliable factors to predict a worse post-transplant prognosis. METHODS: we studied liver transplants carried out between May 2010 and November 2017. After excluding 38 patients, we included 87, analyzing clinical and laboratory data for correlation with the outcome Microvascular Invasion (MVI). Subsequently, we computed the MELD and MELD-Na scores and performed a descriptive analysis of clinical and laboratory data and, finally, calculated ROC curves to assess the association between these laboratory parameters and mortality in these patients. RESULTS: most patients were male (78.30%), with an average age of 58.53 years. Most liver diseases were caused by HCV (53.26%). We found no predictors for MVI among the laboratory parameters. The ROC curves for death identified the MELD score as the cutoff point with the highest combined sensitivity (90.91%) and specificity (37.50%), with a value of 10 points, whereas in the MELD-Na the cutoff point was 7 points, with a sensitivity of 90.91% and a specificity of 33.33%, both scores being significant. CONCLUSIONS: there were no reliable predictors of MVI between clinical, laboratory, and epidemiological variables. The MELD-Na score is more sensitive than the MELD one for predicting mortality in patients undergoing liver transplantation.

High Expression of SOD2 Protein Is a Strong Prognostic Factor for Stage IIIB Squamous Cell Cervical Carcinoma.

High superoxide dismutase 2 (SOD2) expression is associated with a poor prognosis at many cancer sites, the presence of metastases, and more advanced cervical cancer. This study aims to determine whether SOD2 protein expression is associated with the prognosis of stage IIIB cervical carcinoma. METHODS: sixty-three patients with stage IIIB squamous cell cervical carcinoma were included. The evaluation of SOD2 expression by immunohistochemistry was based on a positive cell ratio score and the staining intensity score. Taking disease recurrence and death as endpoints, receiver operating characteristic curves were used to discriminate between high and low SOD2 expression. RESULTS: high SOD2 expression was associated with recurrence (p = 0.001), distant recurrence (p = 0.002), and death (p = 0.005). A multivariate analysis showed that patients with high SOD2 expression had a threefold increased risk for recurrence (HR = 3.16; 1.33-7.51) and death (HR = 2.98; 1.20-7.40) compared with patients who had low SOD2 expression. Patients with high SOD2 expression had shorter disease-free survival (p = 0.001) and overall survival (p = 0.003) than patients with low SOD2 expression. CONCLUSION: high SOD2 expression is a strong prognostic factor for stage IIIB squamous cell carcinoma of the cervix and could be used as a prognostic marker in women with cervical carcinoma.

Clinical impact of the Model for End Liver Disease (MELD) score on the presence of microvascular invasion and on the postoperative outcome in patients undergoing liver transplantation / Impacto clínico do Model For End Liver Disease (MELD) na presença de invasão microvascular e no desfecho pós-operatório em pacientes submetidos a transplante hepático

ABSTRACT Objective: to correlate clinical and epidemiological data with the pathological analysis of liver explants from patients undergoing liver transplantation for hetapocarcinoma in the UNICAMP HC and to verify whether the MELD and MELD-Na scores are reliable factors to predict a worse post-transplant prognosis. Methods: we studied liver transplants carried out between May 2010 and November 2017. After excluding 38 patients, we included 87, analyzing clinical and laboratory data for correlation with the outcome Microvascular Invasion (MVI). Subsequently, we computed the MELD and MELD-Na scores and performed a descriptive analysis of clinical and laboratory data and, finally, calculated ROC curves to assess the association between these laboratory parameters and mortality in these patients. Results: most patients were male (78.30%), with an average age of 58.53 years. Most liver diseases were caused by HCV (53.26%). We found no predictors for MVI among the laboratory parameters. The ROC curves for death identified the MELD score as the cutoff point with the highest combined sensitivity (90.91%) and specificity (37.50%), with a value of 10 points, whereas in the MELD-Na the cutoff point was 7 points, with a sensitivity of 90.91% and a specificity of 33.33%, both scores being significant. Conclusions: there were no reliable predictors of MVI between clinical, laboratory, and epidemiological variables. The MELD-Na score is more sensitive than the MELD one for predicting mortality in patients undergoing liver transplantation.

RESUMO Objetivo: correlacionar dados clínicos e epidemiológicos com a análise patológica dos explantes hepáticos dos pacientes submetidos ao transplante hepático por hetapocarcinoma no HC da UNICAMP e verificar se os scores MELD e MELD-Na apresentam diferenças estatísticas para predizer pior prognóstico pós-transplante. Métodos: considerando os transplantes hepáticos ocorridos entre maio/2010 e novembro/2017, após excluir 38, 87 pacientes foram incluídos, analisando-se dados clínicos e laboratoriais desses pacientes para verificar se há independência entre esses e desfecho Invasão Microvascular (IMV). Posteriormente, realizou-se o cálculo do MELD e MELD-Na, a análise descritiva dos dados clínicos e laboratoriais e, por fim, curvas ROC para avaliar a associação entre esses parâmetros laboratoriais e o desfecho óbito nestes pacientes. Resultados: a maior parte dos pacientes foi do sexo masculino (78,30%), com idade, em média, de 58,53 anos. A maior parte das hepatopatias foi causada pelo VHC (53,26%). Não foi encontrado preditores para o desfecho IMV entre os parâmetros laboratoriais. As curvas ROC para o desfecho óbito identificaram o score MELD como ponto de corte de maior sensibilidade (90,91%) e especificidade (37,50%) simultâneas com o valor de 10 pontos, ao passo que no MELD-Na o ponto de corte foi 7 pontos, com sensibilidade de 90,91% e especificidade de 33,33%, sendo ambas as escalas significativas. Conclusões: não foram encontrados preditores para IMV entre critérios clínicos, laboratoriais e epidemiológicos. O score MELD-Na é mais sensível que o MELD para predizer mortalidade nos pacientes submetidos a transplante hepático.

Tubulovillous adenoma of the duodenal papilla: radiological-endoscopic and anatomopathological correlation in the surgical proposal.

Tubulovillous adenomas of the duodenal ampulla are rare neoplasms. The present report describes a case with radiological-endoscopic and pathological correlation in which the patient underwent duodenal pancreatectomy with good postoperative progression. With advanced imaging methods, especially magnetic resonance and endoscopic ultrasound, locoregional aspects and extraluminal, lymphovascular, and metastatic invasion have been increasingly discussed as contributors to therapeutic decision making. This progression improves lesion staging and is especially useful in selecting eligible candidates for endoscopic treatment.

Tubulovillous adenoma of the duodenal papilla: radiological-endoscopic and anatomopathological correlation in the surgical proposal

SUMMARY Tubulovillous adenomas of the duodenal ampulla are rare neoplasms. The present report describes a case with radiological-endoscopic and pathological correlation in which the patient underwent duodenal pancreatectomy with good postoperative progression. With advanced imaging methods, especially magnetic resonance and endoscopic ultrasound, locoregional aspects and extraluminal, lymphovascular, and metastatic invasion have been increasingly discussed as contributors to therapeutic decision making. This progression improves lesion staging and is especially useful in selecting eligible candidates for endoscopic treatment.

RESUMO Os adenomas túbulo-vilosos da ampola duodenal são neoplasias raras. Neste trabalho apresentamos um caso com correlação radiológico-endoscópica e patológica, tendo a paciente sido submetida à duodenopancreatectomia com boa evolução pós-operatória. Com os avanços dos métodos de imagem, em especial da ressonância magnética e ultrassonografia endoscópica, aspectos locorregionais, além da invasão extraluminal, linfovascular e metastática, têm sido discutidos de maneira crescente como contribuintes na decisão terapêutica. Essa evolução contribui para o melhor estadiamento destas lesões e é especialmente útil para selecionar candidatos elegíveis ao tratamento endoscópico.

The value of morphofunctional magnetic resonance imaging with hepatospecific contrast agent in the characterization of hepatocellular carcinoma in a non-cirrhotic patient with hepatitis C.

Hepatocellular carcinoma in patients with hepatitis C in the absence of cirrhosis is uncommon. We demonstrate the importance of morphofunctional magnetic resonance imaging (MRI) with a hepatospecific contrast agent by describing an asymptomatic female patient with HCV, who presented with a nodule detected on ultrasound. She underwent inconclusive computed tomography, presenting no signs of chronic liver disease. MRI with hepatospecific contrast providing functional information combined with the superior tissue contrast inherent to this method stands out for its greater accuracy with the possibility of not resorting to invasive diagnostic methods. With increasing experience and the dissemination of this new diagnostic modality in the medical field, its use and other potential benefits of morphofunctional MRI with hepatospecific contrast agents may be established, benefiting patients with challenging focal liver lesions.

Efeito da infusão da solução M& G na proteção do tecido renal de ratos Wistar submetidos a isquemia e reperfusão programada / Effect of infusion of M& G solution for protection of renal tissue in Wistar rats subjected to programmed ischemia-reperfusion

Resumo Contexto A isquemia e reperfusão (I/R) renal está envolvida diretamente com insuficiência renal aguda, ocorrendo em casos como infarto por embolização ou trombose, quadros de septicemia e transplante renal. Esse processo é complexo, envolvendo respostas imunes inatas e adaptativas, presença de infiltrado celular, produção e liberação de citocinas e quimiocinas. Também desencadeia respostas celulares e liberação de espécies reativas de oxigênio, além de resultar em apoptose e, em alguns casos, necrose celular. Nesse contexto, é imprescindível a avaliação dos mecanismos de proteção ao tecido renal. Objetivos O objetivo foi testar a solução desenvolvida M&G, avaliando sua capacidade protetora no rim por meio de análise morfométrica e presença e expressão de citocinas inflamatórias (TNF-alfa, VEGF, HIF e IL-8). Métodos Foram selecionados 18 ratos Wistar, divididos em três grupos: Sham (S), Controle (C) e Estudo (E). O grupo S foi submetido ao processo cirúrgico sem o clampeamento arterial. No grupo C, foi clampeada a aorta acima e abaixo da artéria renal esquerda, sem a infusão de solução preservadora. No grupo E, além do clampeamento, realizou-se a punção da aorta e a infusão contínua da solução M&G por 20 minutos a 15 °C. Realizou-se a avaliação morfológica e imuno-histoquímica com os marcadores. Resultados Identificaram-se diferenças morfológicas entre o grupo S comparado aos grupos C e E. Na análise dos marcadores, houve redução na intensidade de expressão do TNF e na expressão do VEGF no grupo E. Não houve diferenças com HIF e IL-8 entre os grupos. Conclusões A solução M&G apresentou redução da presença e expressão de TNF-alfa e tendência de redução do VEGF.

Abstract Background Renal ischemia-reperfusion (I/R) is directly associated with acute renal failure and can occur in conditions such as infarction caused by embolization or thrombosis, septicemia, and kidney transplantation. The process is complex, involving innate and adaptive immune responses, presence of cellular infiltrate, and production and release of cytokines and chemokines. It also triggers cell responses and release of reactive oxygen species, in addition to causing apoptosis and, in some cases, cell necrosis. Against this background, evaluation of renal tissue protection mechanisms is essential. Objectives The objective of this study was to test the M&G solution, developed in prior research, evaluating its capacity to protect the kidneys using morphometric analysis and by assaying the presence and expression of inflammatory cytokines (TNF-alpha, VEGF, HIF, and IL-8). Methods Eighteen Wistar rats were divided into three groups: Sham (S), Control (C), and Experimental (E). The S group underwent the surgical operation, but without arterial clamping. In group C, the aorta was clamped above and below the left renal artery, without infusion of the preservation solution. In group E, in addition to clamping, the aorta was punctured and M&G solution was infused continuously for 20 minutes at 15o C. Morphological analysis and immunohistochemical assessment of markers were then conducted. Results Morphological differences were identified in group S compared with groups C and E. Analysis of markers revealed reduced intensity of expression of TNF and of VEGF in group E. There were no differences in HIF or IL-8 between groups. Conclusions The M&G solution was associated with a reduction in presence and expression of TNF-alpha and a trend to reduced VEGF.

The value of morphofunctional magnetic resonance imaging with hepatospecific contrast agent in the characterization of hepatocellular carcinoma in a non-cirrhotic patient with hepatitis C

SUMMARY Hepatocellular carcinoma in patients with hepatitis C in the absence of cirrhosis is uncommon. We demonstrate the importance of morphofunctional magnetic resonance imaging (MRI) with a hepatospecific contrast agent by describing an asymptomatic female patient with HCV, who presented with a nodule detected on ultrasound. She underwent inconclusive computed tomography, presenting no signs of chronic liver disease. MRI with hepatospecific contrast providing functional information combined with the superior tissue contrast inherent to this method stands out for its greater accuracy with the possibility of not resorting to invasive diagnostic methods. With increasing experience and the dissemination of this new diagnostic modality in the medical field, its use and other potential benefits of morphofunctional MRI with hepatospecific contrast agents may be established, benefiting patients with challenging focal liver lesions.

RESUMO O surgimento de carcinoma hepatocelular em pacientes portadores de hepatite C na ausência de cirrose é de ocorrência pouco comum. Demonstramos a importância da ressonância magnética (RM) morfofuncional com contraste hepatoespecífico por meio da descrição de uma paciente do sexo feminino, assintomática, portadora do vírus da hepatite C (VHC), que se apresentou com nódulo detectado na ultrassonografia. Realizou tomografia computadorizada inconclusiva, sem sinais de hepatopatia crônica. A RM com contraste hepatoespecífico, ao proporcionar informações funcionais, somado ao superior contraste tecidual inerente ao método, destaca-se pela maior acurácia, com a possiblidade de não se recorrer a métodos diagnósticos invasivos. Com o acúmulo de experiência e divulgação dessa nova modalidade diagnóstica no meio médico, sua utilização e outros potenciais benefícios da RM morfofuncional com contraste hepatoespecífico podem vir a se estabelecer, beneficiando pacientes com lesões hepáticas focais desafiadoras.

Microvascular invasion in hepatocellular carcinoma: is it predictable with quantitative computed tomography parameters? / Invasão microvascular no carcinoma hepatocelular: é possível predizer pelos parâmetros quantitativos da tomografia computadorizada?

Abstract Objective: To investigate whether quantitative computed tomography (CT) measurements can predict microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Materials and Methods: This was a retrospective analysis of 200 cases of surgically proven HCCs in 125 consecutive patients evaluated between March 2010 and November 2017. We quantitatively measured regions of interest in lesions and adjacent areas of the liver on unenhanced CT scans, as well as in the arterial, portal venous, and equilibrium phases on contrast-enhanced CT scans. Enhancement profiles were analyzed and compared with histopathological references of MVI. Univariate and multivariate logistic regression analyses were used in order to evaluate CT parameters as potential predictors of MVI. Results: Of the 200 HCCs, 77 (38.5%) showed evidence of MVI on histopathological analysis. There was no statistical difference between HCCs with MVI and those without, in terms of the percentage attenuation ratio in the portal venous phase (114.7 vs. 115.8) and equilibrium phase (126.7 vs. 128.2), as well as in terms of the relative washout ratio, also in the portal venous and equilibrium phases (15.0 vs. 8.2 and 31.4 vs. 26.3, respectively). Conclusion: Quantitative dynamic CT parameters measured in the preoperative period do not appear to correlate with MVI in HCC.

Resumo Objetivo: O objetivo deste estudo foi investigar se parâmetros quantitativos da tomografia computadorizada (TC) podem predizer invasão microvascular (IMV) no carcinoma hepatocelular (CHC). Materiais e Métodos: Foram analisados, retrospectivamente, 200 CHCs comprovados de 125 pacientes submetidos consecutivamente a transplante ou ressecção hepática entre março/2010 e novembro/2017. Foram realizadas medidas quantitativas da densidade das lesões e do parênquima hepático adjacente pré-contraste e nas fases arterial, portal e de equilíbrio das TCs. Parâmetros de impregnação foram comparados com a presença de IMV nos laudos anatomopatológicos. Regressões logísticas univariadas e multivariadas foram utilizadas para avaliar os parâmetros da TC como potenciais preditores de IMV. Resultados: Dos 200 CHCs, 77 (38,5%) tinham IMV no anatomopatológico. Não houve diferença estatística na razão de atenuação entre CHCs com IMV e os sem IMV na fase portal (114,7 para IMV positiva e 115,8 para IMV negativa) ou de equilíbrio (126,7 para IMV positiva e 128,2 para IMV negativa), nem na razão de washout relativa nas fases portal e de equilíbrio (15,0 para IMV positiva e 8,2 para IMV negativa na fase portal, e 31,4 para IMV positiva e 26,3 para IMV negativa na fase de equilíbrio). Conclusão: Não houve relação entre os parâmetros quantitativos da TC pré-operatória e IMV dos CHCs.

Multiple hepatic metastases of cardiac angiosarcoma

The differential diagnosis of hepatic focal lesions is challenging because the etiology can be inflammatory, infectious, and even neoplastic. A rare cause of metastatic liver nodules is cardiac angiosarcoma. We report a case of this tumor, which was diagnosed only after autopsy. A 26-year-old Caucasian man was admitted for progressive dyspnea and cough over the past 3 weeks. Physical examination showed only hypophonetic heart sounds. Laboratory analysis demonstrated anemia and elevated inflammatory markers, despite normal biochemical parameters and liver function. Transthoracic echocardiography revealed massive pericardial effusion. Abdomen computed tomography (CT) showed multiple hepatic nodules, the largest of which measured 3 cm, but the percutaneous biopsy revealed only lobular necrosis and perisinusoidal fibrosis without granulomas or neoplastic cells. During hospitalization, the patient had fever and night sweats with weight loss, and empiric treatment for extrapulmonary tuberculosis associated with corticosteroids was initiated. The outpatient follow-up revealed complete improvement of the pericardial effusion, but maintenance of the liver lesions. After 2 months of hospital discharge, the patient was readmitted with hemorrhagic shock due to bleeding liver lesions, which were evidenced by CT. Embolization of the right hepatic artery was performed, but the patient soon died. The autopsy revealed a primary cardiac angiosarcoma with multiple hepatic metastases, rupture of the Glisson's capsule and laceration of the liver. The case shows how important and difficult the diagnosis of focal liver lesions is, since it may result in an unexpected fatal outcome.