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.

Abstract With the emergence of new variants of SARS-CoV-2, questions about transmissibility, vaccine efficacy, and impact on mortality are important to support decision-making in public health measures. Modifications related to transmissibility combined with the fact that much of the population has already been partially exposed to infection and/or vaccination, have stimulated recommendations to reduce the isolation period for COVID-19. However, these new guidelines have raised questions about their effectiveness in reducing contamination and minimizing impact in work environments. Therefore, a collaborative task force was developed to review the subject in a non-systematic manner, answering questions about SARS-CoV-2 variants, COVID-19 vaccines, isolation/quarantine periods, testing to end the isolation period, and the use of masks as mitigation procedures. Overall, COVID-19 vaccines are effective in preventing severe illness and death but are less effective in preventing infection in the case of the Omicron variant. Any strategy that is adopted to reduce the isolation period should take into consideration the epidemiological situation of the geographical region, individual clinical characteristics, and mask for source control. The use of tests for isolation withdrawal should be evaluated with caution, due to results depending on various conditions and may not be reliable.

RESUMO Contexto - Na doença hepática crônica os níveis plasmáticos de oligoelementos normalmente apresentam-se baixos, mas a causa específica e implicações funcionais desta anormalidade ainda não estão bem esclarecidas. Estes elementos podem estar diminuídos em consequência da função hepática alterada em pacientes com cirrose e/ou desnutrição. Objetivo - Avaliar o estado nutricional e o perfil de oligoelementos plasmáticos dos pacientes com cirrose hepática em lista para transplante e correlacionar com a gravidade da doença. Métodos - Trata-se de um estudo transversal, no qual foram avaliados 31 pacientes do sexo masculino com diagnóstico de cirrose hepática compensada em lista de espera para transplante de fígado. O estado nutricional foi avaliado objetivamente por medidas antropométricas através do escore de Mendenhall e classificado segundo Blackburn, subjetivamente por um questionário sistematizado por Detsky e a gravidade da doença pelo escore MELD e CTP. Os oligoelementos plasmáticos (Zn, Se, Cu, Ca, Fe, Mg e Mn) foram analisados pelo método de espectrometria de massas com fonte de plasma indutivamente acoplado (ICP-MS). Para análise estatística foi utilizado o Teste de Mann-Whitney. Resultados - De acordo com a avaliação nutricional 19 (61,3%) estavam com desnutrição e 12 (38,7%) com sobrepeso. Em relação à gravidade da doença 12 (39%) foram classificados como Child A, 17 (55%), Child B e 2 (6%) Child C, sendo 46,9% dos pacientes com o escore MELD >17. Na análise dos oligoelementos 31 (100%) apresentaram níveis de Mn acima dos valores de referência, 23 (74,2%) níveis baixos de Cu, 29 (93,5%) com deficiência de Se, e 31 (100%) níveis baixos de Ca e Mg. Em relação à gravidade da doença não houve diferença estatística entre os oligoelementos estudados, já em relação ao estado nutricional o grupo desnutrido apresentou níveis maiores de Mn (P=0,01) e Fe (P=0,01) e níveis diminuídos de Zn (P=0,03) quando comparado ao grupo sobrepeso. Conclusão - Os resultados mostraram que os oligoelementos estão alterados na doença hepática crônica, sem associação significativa com a gravidade da doença, mas sim com o estado nutricional. A desnutrição está presente nos pacientes estudados, porém um novo cenário com aumento na prevalência de sobrepeso foi verificado independente do grau de descompensação hepática.

ABSTRACT Background - In chronic liver disease, trace element levels in plasma are usually low. However, the specific cause and functional implications of this abnormality are yet not well understood. These element levels may decrease as a result of abnormal liver function in patients with cirrhosis and/or malnutrition. Objective - To evaluate the nutritional status and the profile of trace elements in plasma of patients with cirrhosis on a liver transplant list and to correlate them with disease severity. Methods - This cross-sectional study evaluated 31 male patients diagnosed with compensated liver cirrhosis on a waiting list for liver transplant. Nutritional status was objectively evaluated through anthropometry using Mendenhall score and Blackburn classification, subjectively through the Detsky questionnaire and severity of the disease by MELD and CTP score. Trace elements (Zn, Se, Cu, Ca, Fe, Mg and Mn) in plasma were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Statistical analysis was performed using Mann-Whitney test. Results - According to the nutritional assessment 19 (61.3%) were malnourished and 12 (38.7%) were overweight. Regarding disease severity 12 (39%) were classified as Child A, 17 (55%), Child B and 2 (6%) Child C, with 46.9% of patients with MELD score >17. The trace element analysis indicated that 31 (100%) had Mn levels above the reference range, 23 (74.2%) low levels of Cu, 29 (93.5%) with deficiency of Se, and 31 (100%) low levels of Ca and Mg. Disease severity did not show statistical difference between the studied trace elements, in contrast to the nutritional status, in which the malnourished group showed higher levels of Mn (P=0.01) and Fe (P=0.01) and low levels of Zn (P=0.03) when compared to the overweight group. Conclusion - The results showed that the trace elements in plasma are altered in chronic liver disease; without significant correlation to disease severity, but correlated to nutritional status. Malnutrition is present in the patients studied, nonetheless a new scenario with an increase in the prevalence of overweight was verified regardless of the degree of hepatic decompensation.

Herpesvirus reactivation is common after liver transplantation.OBJECTIVE:Analyze the presence of cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6) DNA in liver donor biopsies, seeking to better understand issues involving human donor leukocyte antigens (HLA)-A, B and DR, as well as correlations with acute cellular rejection.METHODS:Fifty-nine liver transplantation patients were investigated for the presence of HCMV and HHV-6 DNA in liver donor biopsies, using the Nested-PCR technique. The clinical donor information and HLA matches were obtained from the São Paulo State Transplant System. The recipients' records regarding acute cellular rejection were studied.RESULTS:Seven (11.8%) biopsies were positive for HCMV DNA and 29 (49%) were positive for HHV-6 DNA. In 14 donors with HLA-DR 15 nine had HHV-6 DNA positive liver biopsy with a tendency for significant association (p=0.09), 22 recipients developed acute cellular rejection and 9/22 were positive for HLA-DR 15 (p=0.03; χ2=4.51), which was statistically significant in univariate analysis and showed a tendency after multivariate analysis (p=0.08).CONCLUSION:HHV-6 DNA was prevalent in liver donors studied as well as HLA-DR 15. These findings suggest that patients with HLA-DR 15 in liver donor biopsies develop more rejection after liver transplantation.

RACIONAL: Utiliza-se o escore MELD (Model End-Stage Liver Disease) para o prognóstico da mortalidade em lista de espera para transplante de fígado e, em alguns estudos, para predição da sobrevida pós-operatória a longo prazo. OBJETIVO: Verificar a aplicação do escore MELD como predição da sobrevida após o transplante. MÉTODOS: Por intermédio de dados coletados prospectivamente efetuou-se um estudo de coorte longitudinal retrospectivo em 232 pacientes. Excluíram-se os retransplantes, insuficiência hepática aguda, crianças e enxertos duplos ou reduzidos. Avaliaram-se os dados dos doadores: idade, sexo, peso, creatinina, bilirrubina, sódio, aspartato aminotransferase, antecedentes pessoais, causa da morte, presença de esteatose, número de critérios expandidos do doador e índice de risco do doador. Em relação aos receptores, analisaram-se as variáveis: sexo, idade, peso, doença hepática, pontos de Child-Turcotte-Pugh, escore MELD, depuração de creatinina, sódio, tempos de isquemia e de hospitalização, quantidade de hemoderivados transfundidos, presença e grau de disfunção do enxerto. A análise estatística foi efetuada usando-se a análise de regressão univariada e/ou múltipla, estatística 'c', teste exato de Fisher, método de Kaplan-Meier (teste log-rank) para sobrevida, e análise de regressão de Cox para risco de óbito ajustado para as condições clínicas. RESULTADOS: O ponto de corte MELD para sobrevida foi 20 e de Child-Turcotte-Pugh foi 11,5. Para escore MELD maior ou igual a 20, os fatores preditivos de sobrevida foram: volume de sangue transfundido, disfunção do enxerto e o sódio do doador. Para os hiponatrêmicos os fatores preditivos de sobrevida foram: volume de sangue transfundido, disfunção do enxerto e sódio do doador. A sobrevida estimada para pacientes com escore MELD >25 foi menor ao final de 12 meses (68,86% vs 39,13%). A sobrevida estimada para os pacientes sem hiponatremia foi maior (65,16% vs 44,44%). A sobrevida aos 5 e 10 anos também seguiu o mesmo padrão. O uso de doadores limítrofes não alterou a sobrevida, mas quando se utilizou o índice de risco do doador observou-se que a sobrevida foi maior para pacientes com índice de risco do doador menor que 1,7 (63,62% vs 53,70%). A associação deste índice com o escore MELD não mostrou diferença estatística em relação à sobrevida. Observou-se que a falência e disfunção do enxerto foram associadas ao número crescente de critérios expandidos do doador. Os receptores de doadores maiores de 50 anos tiveram menor sobrevida (65,58% vs 38,40%) e o escore delta-MELD não discriminou a sobrevida. CONCLUSÃO: A sobrevida dos receptores a curto e longo prazo é associada a escores MELD acima de 25, ao volume de sangue transfundido, à disfunção do enxerto, à hiponatremia, à idade do doador acima de 50 anos e àqueles doadores com índice de risco do doador acima de 1,7.

BACKGROUND: The model for end-stage liver disease (MELD) was developed to predict short-term mortality in patients with cirrhosis. There are few reports studying the correlation between MELD and long-term posttransplantation survival. AIM: To assess the value of pretransplant MELD in the prediction of posttransplant survival. METHODS: The adult patients (age >18 years) who underwent liver transplantation were examined in a retrospective longitudinal cohort of patients, through the prospective data base. We excluded acute liver failure, retransplantation and reduced or split-livers. The liver donors were evaluated according to: age, sex, weight, creatinine, bilirubin, sodium, aspartate aminotransferase, personal antecedents, brain death cause, steatosis, expanded criteria donor number and index donor risk. The recipients' data were: sex, age, weight, chronic hepatic disease, Child-Turcotte-Pugh points, pretransplant and initial MELD score, pretransplant creatinine clearance, sodium, cold and warm ischemia times, hospital length of stay, blood requirements, and alanine aminotransferase (ALT >1,000 UI/L = liver dysfunction). The Kaplan-Meier method with the log-rank test was used for the univariable analyses of posttransplant patient survival. For the multivariable analyses the Cox proportional hazard regression method with the stepwise procedure was used with stratifying sodium and MELD as variables. ROC curve was used to define area under the curve for MELD and Child-Turcotte-Pugh. RESULTS: A total of 232 patients with 10 years follow up were available. The MELD cutoff was 20 and Child-Turcotte-Pugh cutoff was 11.5. For MELD score > 20, the risk factors for death were: red cell requirements, liver dysfunction and donor's sodium. For the patients with hyponatremia the risk factors were: negative delta-MELD score, red cell requirements, liver dysfunction and donor's sodium. The regression univariated analyses came up with the following risk factors for death: score MELD > 25, blood requirements, recipient creatinine clearance pretransplant and age donor >50. After stepwise analyses, only red cell requirement was predictive. Patients with MELD score < 25 had a 68.86%, 50,44% and 41,50% chance for 1, 5 and 10-year survival and > 25 were 39.13%, 29.81% and 22.36% respectively. Patients without hyponatremia were 65.16%, 50.28% and 41,98% and with hyponatremia 44.44%, 34.28% and 28.57% respectively. Patients with IDR > 1.7 showed 53.7%, 27.71% and 13.85% and index donor risk <1.7 was 63.62%, 51.4% and 44.08%, respectively. Age donor > 50 years showed 38.4%, 26.21% and 13.1% and age donor <50 years showed 65.58%, 26.21% and 13.1%. Association with delta-MELD score did not show any significant difference. Expanded criteria donors were associated with primary non-function and severe liver dysfunction. Predictive factors for death were blood requirements, hyponatremia, liver dysfunction and donor's sodium. CONCLUSION: In conclusion MELD over 25, recipient's hyponatremia, blood requirements, donor's sodium were associated with poor survival.

A determinação dos níveis de alanina aminostransferase (ALT) tem sido útil para o diagnóstico de hepatopatias. Ultimamente, a elevação dos níveis séricos de ALT em doadores de sangue, tem sido associada a um maior risco de hepatites pós-transfusionais. Este estudo busca identificar os fatores associados com elevados níveis de ALT entre doadores voluntários de sangue e avaliar as relações entre estes aumentos de ALT e o desenvolvimento de infecção pelo vírus da hepatite C. Assim, 116 doadores voluntários de sangue com níveis de ALT elevados, quando da primeira doação, foram estudados. Todos foram questionados sobre hepatopatias prévias, exposição a hepatites, exposição a produtos químicos, uso de drogas ou medicamentos, comportamento sexual, contacto com sangue ou secreções e consumo de álcool. A cada 3 meses foram medidos os níveis de AST, ALT, fosfatase alcalina, gama-glutamil transferase, colesterol, triglicérides e glicemia durante o período de 1-2 anos. Os níveis séricos de hormônios tireoidianos e a presença de auto-anticorpos também foram mensurados. Ultrassonografia abdominal foi realizada em todos os pacientes com elevação persistente dos níveis de AST ou ALT. Foi realizada biópsia hepática em 9 doadores sem diagnóstico definido após investigação clínica. A presença de anticorpos anti-HCV foi novamente pesquisada em 116 doadores no momento da primeira avaliação clínica. Ao final do follow-up (2 anos) 71 doadores foram re-testados para a presença do anti-HCV. Nenhum doador se tornou reagente para os marcadores dos virus da hepatite B ou hepatite C, durante o seguimento. Dos 116 doadores, 101 (87%) mantiveram níveis séricos de ALT persistentemente aumentados. Obesidade e alcoolismo foram as principais condições associadas à elevação dos níveis séricos de ALT em 91/101 (90,1%) doadores. Hipertrigliceridemia, hipercolesterolemia, hipotireoidismo e diabetes mellitus também se associaram a níveis aumentados de ALT. Somente 1/101 (0,9%) apresentou hepatite crônica ativa não A-G e 3/101 (2,9%) apresentaram biópsia hepática com diagnóstico de hepatite reacional. A determinação rotineira dos níveis de ALT, em bancos de sangue não foi útil para detectar doadores infectados com o vírus da hepatite C no Brasil no período que antecede a soroconversão para anti-vhc.

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.