Progressive Familial Intrahepatic Cholestasis Type 2 and Recurrence After Liver Transplantation: A Case Report.

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a rare autosomal recessive disorder caused by mutations in the ABCB11 gene. Clinical manifestations include cholestasis with low γ-glutamyltransferase (GGT), hepatosplenomegaly, and severe pruritus. Liver transplantation is required for individuals with progressive liver disease or failure of the bypass procedure and has been considered curative. However, in the case of PFIC2, although bile salt excretory pump (BSEP) deficiency is a liver-specific condition rather than a systemic disease, evidence of recurrent BSEP disease has been shown in a small proportion of allografts. We describe an unusual case of a 21-year-old individual with PFIC2 and evidence of recurrent BSEP disease after liver transplantation, with clinical and laboratory improvement after pulse therapy with methylprednisolone for 3 days and adjustment of oral immunosuppression. This case report highlights the recurrence of PFIC2 in patients post liver transplant. It also emphasizes the importance of clinical suspicion, which should be considered in cases of posttransplant cholestasis in PFIC2 patients, especially those with low γ-glutamyltransferase (GGT) and without signs of acute graft rejection. Having knowledge of the condition favors a targeted diagnostic approach and contributes to early therapeutic management and a higher success rate.

Liver Transplant and Active Ulcerative Colitis: A Case Report.

BACKGROUND: The association between ulcerative colitis (UC) and primary sclerosing cholangitis has been described for several years and can be classified as having a distinct disease phenotype from inflammatory bowel diseases (IBD). The simultaneous occurrence of decompensated liver disease requiring liver transplant and active IBD is a management challenge, considering that these patients may be at increased risk of infections, thromboembolic events, bleeding, and drug hepatotoxicity. CASE PRESENTATION: We describe a case of a 37-year-old patient with UC and sclerosing cholangitis presenting with severe decompensated rectocolitis complicated with thromboembolic phenomena and severe liver dysfunction who underwent liver transplant while using biological therapy to control bowel disease. CONCLUSIONS: This case highlights the evolution of sclerosing cholangitis to liver transplant in patients with decompensated UC. Despite the risk of recurrence, primary sclerosing cholangitis has excellent results after liver transplant. Despite the use of immunosuppression after liver transplant, biological therapy may be necessary to control IBD.

Liver Transplantation After Acute Portal Vein Thrombosis: Case Report.

BACKGROUND: Portal vein thrombosis is a relatively frequent complication in patients with liver cirrhosis. Its detection and management are essential to avoid worsening portal hypertension or liver function complications. This complication can also negatively impact or even preclude liver transplant. CASE PRESENTATION: We report the case of a patient who presented with acute portal vein thrombosis, which allowed the diagnosis of liver cirrhosis and hepatocarcinoma within the Milan criteria. Chemical thrombolysis was performed with a mechanical aspiration of the thrombus, and in a second moment, the patient was submitted to a liver transplant. CONCLUSIONS: Advances in the therapeutic approach to portal vein thrombosis and surgical techniques have allowed the condition to no longer be an absolute contraindication to liver transplantation. Diagnosis in the acute phase is associated with greater therapeutic success, aiming to avoid the extension of thrombosis and achieve portal vein recanalization.

Performance of High Mobility Protein Group 1 and Interleukin-6 as Predictors of Outcomes Resulting from Variceal Bleeding in Patients with Advanced Chronic Liver Disease.

Variceal bleeding is a serious complication in cirrhotic patients and is related to increased expression of inflammatory mediators that accentuate circulatory dysfunction. The study aims to evaluate the performance of high mobility protein group 1 (HMG1) and interleukin-6 (IL-6) as predictors of acute kidney injury (AKI), infection and death in these patients. Fifty patients who were diagnosed with advanced chronic liver disease with variceal bleeding were included. The mean age was 52.8 ± 10.8 years, and 33 (66%) were male. Twenty-one (42%) patients were classified as Child-Pugh C, 21 (42%) Child-Pugh B and 8 (16%) Child-Pugh A. The mean HMG1 serum level was 2872.36 pg/mL ± 2491.94, and the median IL-6 serum level was 47.26 pg/mL (0-1102.4). In AKI, the serum level of HMG1 that performed best on the ROC curve was 3317.9 pg/mL. The IL-6 serum level was not associated with AKI. HMG1 and IL-6 cut-off values that better predicted infection were 3317.9 pg/mL and 72.9 pg/mL, and for mortality, the values were 2668 pg/mL and 84.5 pg/mL, respectively. In multivariate analysis, the variables that were associated with AKI and infection outcomes were model for end-stage liver disease and HMG1. Infections were related to the risk of death. Clinical and laboratory variables related to the outcomes were identified. Serum levels of HMG1 were associated with AKI and infection and had good performance in the ROC curve. IL-6 levels were not maintained in logistic regression outcomes but had good performance in infection and death outcomes. Such data will be useful for comparisons and possible future validations.

INFLAMMATORY BOWEL DISEASE CARE IN BRAZIL: HOW IT IS PERFORMED, OBSTACLES AND DEMANDS FROM THE PHYSICIANS' PERSPECTIVE.

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic inflammatory affections of recurrent nature whose incidence and prevalence rates have increased, including in Brazil. In long term, they are responsible for structural damage that impacts quality of life, morbidity and mortality of patients. OBJECTIVE: To describe the profile of physicians who treat IBD patients as well as the characteristics of IBD care, unmet demands and difficulties. METHODS: A questionnaire containing 17 items was prepared and sent to 286 physicians from 101 Brazilian cities across 21 states and the Federal District, selected from the register of the State Commission of the "Study Group of Inflammatory Bowel Disease of Brazil" (GEDIIB). RESULTS: The majority of the physicians who answered the questionnaire were gastroenterologists and colorectal surgeons. More than 60% had up to 20 years of experience in the specialty and 53.14% worked at three or more locations. Difficulties in accessing or releasing medicines were evident in this questionnaire, as was referrals to allied healthy professionals working in IBD-related fields. More than 75% of physicians reported difficulties in performing double-balloon enteroscopy and capsule endoscopy, and 67.8% reported difficulties in measuring calprotectin. With regard to the number of patients seen by each physician, it was shown that patients do not concentrate under the responsibility of few doctors. Infliximab and adalimumab were the most commonly used biological medicines and there was a higher prescription of 5-ASA derivatives for ulcerative colitis than for Crohn's disease. Steroids were prescribed to a smaller proportion of patients in both diseases. The topics "biological therapy failure" and "new drugs" were reported as those with higher priority for discussion in medical congresses. In relation to possible differences among the country's regions, physicians from the North region reported greater difficulty in accessing complementary exams while those from the Northeast region indicated greater difficulty in accessing or releasing medicines. CONCLUSION: The data obtained through this study demonstrate the profile of specialized medical care in IBD and are a useful tool for the implementation of government policies and for the Brazilian society as a whole.

Atendimento da doença inflamatória intestinal no Brasil: como é feito, os entraves e as demandas sob a ótica dos médicos / Inflammatory bowel disease care in brazil: how it is performed, obstacles and demands from the physicians' perspective

ABSTRACT BACKGROUND: Inflammatory bowel diseases (IBD) are chronic inflammatory affections of recurrent nature whose incidence and prevalence rates have increased, including in Brazil. In long term, they are responsible for structural damage that impacts quality of life, morbidity and mortality of patients. OBJECTIVE: To describe the profile of physicians who treat IBD patients as well as the characteristics of IBD care, unmet demands and difficulties. METHODS: A questionnaire containing 17 items was prepared and sent to 286 physicians from 101 Brazilian cities across 21 states and the Federal District, selected from the register of the State Commission of the "Study Group of Inflammatory Bowel Disease of Brazil" (GEDIIB). RESULTS: The majority of the physicians who answered the questionnaire were gastroenterologists and colorectal surgeons. More than 60% had up to 20 years of experience in the specialty and 53.14% worked at three or more locations. Difficulties in accessing or releasing medicines were evident in this questionnaire, as was referrals to allied healthy professionals working in IBD-related fields. More than 75% of physicians reported difficulties in performing double-balloon enteroscopy and capsule endoscopy, and 67.8% reported difficulties in measuring calprotectin. With regard to the number of patients seen by each physician, it was shown that patients do not concentrate under the responsibility of few doctors. Infliximab and adalimumab were the most commonly used biological medicines and there was a higher prescription of 5-ASA derivatives for ulcerative colitis than for Crohn's disease. Steroids were prescribed to a smaller proportion of patients in both diseases. The topics "biological therapy failure" and "new drugs" were reported as those with higher priority for discussion in medical congresses. In relation to possible differences among the country's regions, physicians from the North region reported greater difficulty in accessing complementary exams while those from the Northeast region indicated greater difficulty in accessing or releasing medicines. CONCLUSION: The data obtained through this study demonstrate the profile of specialized medical care in IBD and are a useful tool for the implementation of government policies and for the Brazilian society as a whole.

RESUMO CONTEXTO: As doenças inflamatórias intestinais (DII) são afecções inflamatórias crônicas de caráter recorrente, cujas taxas de incidência e prevalência têm aumentado, inclusive no Brasil. A longo prazo, são responsáveis por danos estruturais que impactam na qualidade de vida, morbidade e mortalidade dos pacientes. OBJETIVO: Avaliar o perfil dos médicos que atendem pacientes com DII, assim como as características deste atendimento, demandas não atendidas e dificuldades. MÉTODOS: Um questionário contendo 17 variáveis foi elaborado e enviado para médicos, selecionados a partir do cadastro da Comissão das Estaduais do Grupo de Estudos da Doença Inflamatória Intestinal do Brasil (GEDIIB), totalizando 286 médicos de 101 cidades brasileiras distribuídas por 21 estados e Distrito Federal. RESULTADOS: A maioria dos médicos que respondeu o questionário foram Gastroenterologistas e Coloproctologistas. Mais de 60% tinham até 20 anos de atuação na especialidade e 53,14% trabalhavam em três locais ou mais. A dificuldade no acesso ou liberação de medicamentos ficou evidenciada neste questionário, assim como a dificuldade no encaminhamento para profissionais não médicos que atuam em DII. Mais de 75% dos médicos relataram dificuldades para realização de enteroscopia por duplo balão e cápsula endoscópica, e 67,8% para realização da calprotectina. Em relação ao número de pacientes atendidos por cada médico, foi evidenciado que não há uma concentração de pacientes sob a responsabilidade de poucos médicos. O infliximabe e o adalimumabe foram os biológicos mais utilizados e ficou evidenciada prescrição maior de derivados de 5-ASA para retocolite ulcerativa quando comparada à doença de Crohn. Os corticoides foram prescritos para uma parcela menor de pacientes em ambas doenças. Os temas "falha a terapia biológica" e "novas drogas" foram referidos como aqueles com maior prioridade para discussão em eventos científicos. Em relação às possíveis diferenças entre cada região e o restante do país, os médicos da região Norte relataram maior dificuldade no acesso a exames complementares e os médicos da região Nordeste, maior dificuldade no acesso ou liberação de medicamentos. CONCLUSÃO: Os dados obtidos por meio deste estudo mostram o perfil do atendimento médico especializado em DII e podem se constituir em ferramenta útil para para elaboração de políticas governamentais e para sociedade brasileira como um todo.

Evaluation of the Biomarkers HMGB1 and IL-6 as Predictors of Mortality in Cirrhotic Patients with Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) affects from 20% to 50% of cirrhotic patients, and the one-month mortality rate is 60%. The main cause of AKI is bacterial infection, which worsens circulatory dysfunction through the release of HMGB1 and IL-6. OBJECTIVES: To evaluate HMGB1 and IL-6 as biomarkers of morbidity/mortality. METHODS: Prospective, observational study of 25 hospitalised cirrhotic patients with AKI. Clinical and laboratory data were collected at the time of diagnosis of AKI, including serum HMGB1 and IL-6. RESULTS: The mean age was 55 years; 70% were male. Infections accounted for 13 cases. The 30-day and three-month mortality rates were 17.4% and 30.4%, respectively. HMGB1 levels were lower in survivors than in nonsurvivors at 30 days (1174.2 pg/mL versus 3338.5 pg/mL, p = 0.035), but not at three months (1540 pg/mL versus 2352 pg/mL, p = 0.243). Serum IL-6 levels were 43.3 pg/mL versus 153.3 pg/mL (p = 0.061) at 30 days and 35.8 pg/mL versus 87.9 pg/mL (p = 0.071) at three months, respectively. The area under the ROC curve for HMGB1 was 0.842 and 0.657, and that for IL-6 was 0.803 and 0.743 for discriminating nonsurvivors at 30 days and three months, respectively. In multivariate analysis, no biomarker was independently associated with mortality. CONCLUSION: HMGB1 levels were associated with decreased survival in cirrhotics. Larger studies are needed to confirm our results.

Manifestações clínicas e diagnóstico da doença de Whipple: relato de caso / Clinical manifestations and diagnosis of Whipple?s disease:case report

A doença de Whipple é uma infecção multissistêmica rara, cujo agentecausal é um bacilo Gram-positivo, Tropheryma whippelii. Caracteriza-se por fase prolongada de sintomatologia inespecífica, o que faz postergar o seu diagnóstico. A doença evolui com boa resposta à antibioticoterapia, com boa evolução clínica e laboratorial, mas se não tratada adequadamente pode ser grave e fatal. Este relato descreve umcaso de doença de Whipple, com manifestações sistêmicas. Relato de caso: paciente masculino, 60 anos de idade, há um ano com perda de 15 kg, diarreia, anorexia, poliartralgia e palidez cutaneomucosa. Seu peso era de 45 kg e o índice de massa corpóreo de 18,7. A propedêutica completa revelou: hemoglobina de 8,12 g/dL, sorologias virais e marcadores de doença celíaca negativos; tomografia de abdome: linfonodomegaliaem cadeias mesentéricas e paraórticas; endoscopia digestiva alta revelou áreas de pangastrite enantematosa e biópsia com histopatológico compatível com doença de Whipple, colonoscopia sem alterações. Iniciado tratamento com ceftriaxone seguido por sulfametoxazol-trimetoprim. Evoluiu com melhora, mantendo acompanhamento em ambulatório. Conclusão: a doença de Whipple pode ser fatal se não diagnosticadae tratada de maneira correta. A resposta terapêutica é boa e ocorre nas duas primeiras semanas de tratamento com antibiótico.

Whipple?s disease is a rare multisystemic infection whose causative agent is the Gram-positive bacillus Tropheryma whippelii. It is characterized by a prolonged phase of nonspecific symptoms that delays diagnosis. The disease evolves with good response to antibiotic therapy, good clinical and laboratory evolution, however, if not properly treated it can be serious and fatal. This report describes a case of Whipple?s disease withsystemic manifestations. Case report: male patient, 60 years of age, 15 kg weight loss in one year, diarrhea, anorexia, poly arthralgia, and cutaneous-mucosa pallor. His weight was 45 kg with 18.7 body mass index. The complete propaedeutics revealed: 8.12 g/dL hemoglobin, negative viral serology and celiac disease markers; CT scan of abdomen:lymphadenopathy in mesenteric and para-aortic chains; upper gastrointestinal endoscopy revealed areas of enanthematous pangastritis and biopsy with histopathologic findings compatible with Whipple?s disease, colonoscopy without alterations. Treatment wasstarted with ceftriaxone and followed by sulfamethoxazole-trimethoprim. Patient evolved with improvement maintaining ambulatory monitoring. Conclusion: the Whipple?s disease can be fatal if not diagnosed and treated properly. The therapeutic response is good and occurs in the first two weeks of treatment with antibiotics.

Cardiotoxicidade induzida por quimioterápicos: [revisão] / Chemotherapy induced cardiotoxicity: [review]

A sobrevida dos pacientes com câncer aumentou consideravelmente nos últimos 20 anos e, com ela,o número de eventos adversos associados aos quimioterápicos. A cardiotoxicidade crônica induzida pelos agentes antineoplásicos pode comprometer a sobrevida e a qualidade de vida dos pacientes, independentemente de seu prognóstico oncológico. Inúmeros fármacos foram associados a eventos adversos cardiovasculares, e até o momento não há protocolos bem estabelecidos para se detectar precocemente a toxicidade cardíaca. Alguns métodos auxiliam o diagnóstico, como o ecocardiograma, a dosagem de marcadores bioquímicos como a troponina I e o peptídeo natriurético, e a biópsia endomiocárdica. A cardiotoxicidade induzida por quimioterápicos tem se mostrado irreversível e ,uma vez estabelecida a disfunção miocárdica, seu tratamento independe do agente associado à indução da lesão. Estudos recentes sugerem o papel de agentes específicos como o dexrazoxane, a eritropoietina, a trombopoietina e os inibidores da enzima conversora de angiotensina na prevenção do desenvolvimento de cardiotoxicidade relacionada à quimioterapia.

Life expectancy of cancer patients has considerably increased in the last 20 years, but adverseevents associated to chemotherapy have also been more frequent. Chronic cardiactoxicity of antineoplastic agents can compromise survival and quality of life, independentof the oncological prognosis. A wide range of chemotherapy drugs have been associatedto cardiovascular adverse events, and until nowadays there are no well establishedprotocols for early detection of cardiac toxicity. Some methods help in identifying initialcardiomyopathy, such as the echocardiogram, the biochemical markers troponin I andnatriuretic peptide, and endomiocardial biopsy. Chemotherapy induced cardiotoxicityseems to be irreversible, and once myocardial dysfunction is established, the treatmentis not dependent of the causative drug. Recent studies suggest a role for specific agentssuch as dexrazoxan, eritropoietin, thrombopoietin and angiotensin converting enzymeinhibitors in preventing chemotherapy induced cardiotoxicity.

Choque cardiogênico na miocardiopatia induzida por agentes antineoplásicos: relato de caso / Cardiogenic shock in cardiomyopathy induced by antineoplastic agents: a case report

No Brasil, a principal etiologia da insuficiência cardíaca (IC) é a cardiopatia isquêmica crônica associada à hipertensão arterial. A IC pode se manifestar como doença crônica estável ou descompensada. A IC descompensada pode se apresentar como edema agudo de pulmão ou choque cardiogênico no atendimento de urgência. Este trabalho descreve a evolução de paciente admitida em unidade de pronto-socorro com choque cardiogênico secundário à miocardiopatia induzida por agentes antineoplásicos, manifesta quatro anos após a quimioterapia para câncer de mama.

The main cause of heart failure (HF) in Brazil is ischemic cardiomyopathy associated to arterial hypertension. HF can present as a chronic stable or as a decompensated disease. Decompensated HF can manifest as acute pulmonary edema and cardiogenic shock in the emergency unit. We describe here a patient admitted to an emergency room with cardiogenic shock secondary to cardiomyopathy induced by antineoplastic agents, 4 years after chemotherapy for breast cancer.