Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

Impact of Brazilian expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a multicenter study.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the main indications for orthotopic liver transplantation (OLT). In Brazil, selection criteria for HCC is an expanded version of the Milan Criteria (MC), the so-called "Brazilian Milan Criteria" (BMC). Our aims were to evaluate post-OLT outcomes in patients with HCC and analyze the BMC performance. MATERIALS AND METHODS: We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,059 liver transplant recipients with HCC. Tumor was staged according to MC and BMC and correlated with overall survival (OS) and disease-free survival (DFS). We compared the ability of MC and BMC to predict OS and DFS using Delta C-statistic. RESULTS: Post-OLT OS were 63% in five years and HCC recurrence was observed in 8% of patients. At diagnosis, 85% of patients were within MC. Patients within MC at diagnosis and in the explant showed a higher OS and DFS than patients outside MC and within BMC and patients outside both criteria (p < 0.001). Patients outside MC in the explant had an increased risk of tumor recurrence (HR: 3.78; p < 0.001) and poor survival (HR:1.77; p = 0.003). The BMC presented a lower performance than MC in properly classifying patients regarding recurrence risk. CONCLUSIONS: In a large Brazilian cohort of HCC patients submitted to liver transplantation, we observed satisfactory overall survival and recurrence rates. However, patients transplanted within the Brazilian expanded criteria had lower OS and DFS when compared to patients within MC, which may generate future discussions regarding the criteria currently used.

Hepatocellular carcinoma recurrence after liver transplantation in a Brazilian multicenter study: clinical profile and prognostic factors of survival.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. PATIENTS AND METHODS: We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. RESULTS: OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified α-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. CONCLUSION: In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis.

Nonalcoholic steatohepatitis in posttransplantation liver: Review article.

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) associated or not with cirrhosis is the third leading indication for liver transplantation (LT) around the world. After transplants, NASH has a high prevalence and occurs as both recurrent and de novo manifestations. De novo NASH can also occur in allografts of patients transplanted for non-NASH liver disease. OBJECTIVE: To evaluate recurrent or de novo NASH in post-LT patients. METHOD: A literature review was performed using search engines of indexed scientific material, including Medline (by PubMed), Scielo and Lilacs, to identify articles published in Portuguese and English until August 2016. Eligible studies included: place and year of publication, prevalence, clinical characteristics, risk factors and survival. RESULTS: A total of 110 articles were identified and 63 were selected. Most of the studies evaluated recurrence and survival after LT. Survival reached 90-100% in 1 year and 52-100% in 5 years. Recurrence of NAFLD (steatosis) was described in 15-100% and NASH, in 4-71%. NAFLD and de novo NASH were observed in 18-67% and 3-17%, respectively. Metabolic syndrome, diabetes mellitus, dyslipidemia and hypertension were seen in 45-58%, 18-59%, 25-66% and 52-82%, respectively. CONCLUSION: After liver transplants, patients present a high prevalence of recurrent and de novo NASH. They also show a high frequence of metabolic disorders. Nevertheless, these alterations seem not to influence patient survival.

Drought stress and tree size determine stem CO2 efflux in a tropical forest.

CO2 efflux from stems (CO2_stem ) accounts for a substantial fraction of tropical forest gross primary productivity, but the climate sensitivity of this flux remains poorly understood. We present a study of tropical forest CO2_stem from 215 trees across wet and dry seasons, at the world's longest running tropical forest drought experiment site. We show a 27% increase in wet season CO2_stem in the droughted forest relative to a control forest. This was driven by increasing CO2_stem in trees 10-40 cm diameter. Furthermore, we show that drought increases the proportion of maintenance to growth respiration in trees > 20 cm diameter, including large increases in maintenance respiration in the largest droughted trees, > 40 cm diameter. However, we found no clear taxonomic influence on CO2_stem and were unable to accurately predict how drought sensitivity altered ecosystem scale CO2_stem , due to substantial uncertainty introduced by contrasting methods previously employed to scale CO2_stem fluxes. Our findings indicate that under future scenarios of elevated drought, increases in CO2_stem may augment carbon losses, weakening or potentially reversing the tropical forest carbon sink. However, due to substantial uncertainties in scaling CO2_stem fluxes, stand-scale future estimates of changes in stem CO2 emissions remain highly uncertain.

Nonalcoholic steatohepatitis in posttransplantation liver: Review article / Esteato-hepatite não alcoólica no pós-transplante de fígado: artigo de revisão

Summary Introduction: Nonalcoholic steatohepatitis (NASH) associated or not with cirrhosis is the third leading indication for liver transplantation (LT) around the world. After transplants, NASH has a high prevalence and occurs as both recurrent and de novo manifestations. De novo NASH can also occur in allografts of patients transplanted for non-NASH liver disease. Objective: To evaluate recurrent or de novo NASH in post-LT patients. Method: A literature review was performed using search engines of indexed scientific material, including Medline (by PubMed), Scielo and Lilacs, to identify articles published in Portuguese and English until August 2016. Eligible studies included: place and year of publication, prevalence, clinical characteristics, risk factors and survival. Results: A total of 110 articles were identified and 63 were selected. Most of the studies evaluated recurrence and survival after LT. Survival reached 90-100% in 1 year and 52-100% in 5 years. Recurrence of NAFLD (steatosis) was described in 15-100% and NASH, in 4-71%. NAFLD and de novo NASH were observed in 18-67% and 3-17%, respectively. Metabolic syndrome, diabetes mellitus, dyslipidemia and hypertension were seen in 45-58%, 18-59%, 25-66% and 52-82%, respectively. Conclusion: After liver transplants, patients present a high prevalence of recurrent and de novo NASH. They also show a high frequence of metabolic disorders. Nevertheless, these alterations seem not to influence patient survival.

Resumo Introdução: A doença hepática gordurosa não alcoólica (DHGNA) é a terceira causa de transplante hepático no mundo. Tem elevada prevalência após transplante hepático (TH) e é representada pela recorrência da esteato-hepatite (NASH), ou por NASH de novo, que ocorre em pacientes transplantados por outra etiologia. Objetivo: Realizar uma revisão da literatura para avaliar a relevância da recorrência ou do NASH de novo em pacientes transplantados de fígado. Método: Realizada revisão da literatura através de artigos indexados no Medline, Scielo e Lilacs até 2016 publicados em inglês e português. Foram considerados elegíveis estudos que incluíram local e ano de publicação, prevalência e características clínicas dos pacientes. Resultados: Foram identificados 110 artigos e selecionados 63, que avaliaram a recorrência de NASH, NASH de novo e sobrevida após o TH. A sobrevida foi de 90% a 100% em um ano e de 52-100% em 5 anos. A recorrência de esteatose variou de 15-100% e a de NASH de 4-71%, enquanto esteatose e NASH de novo variaram de 18-67% e 3-17%, respectivamente. A frequência de síndrome metabólica, diabetes, dislipidemia e hipertensão variaram de 45-58%, 18-59%, 25-66% e 52-82%, respectivamente. Conclusão: No pós-transplante de fígado, os pacientes apresentam elevada prevalência de recorrência, de NASH de novo e de distúrbios metabólicos. Entretanto, essas alterações parecem não influenciar a sobrevida dos pacientes.

New Onset Diabetes and Non-Alcoholic Fatty Liver Disease after Liver Transplantation.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is an emerging cause of graft dysfunction after liver transplantation (LT) frequently related to the development of new onset diabetes after LT (NODAT). This study was undertaken to evaluate the frequencies of NODAT and NAFLD after LT, to investigate their major risk factors and the impact of de novo or recurrent NAFLD in graft function. MATERIAL AND METHODS: 119 patients submitted to LT were prospectively evaluated. RESULTS: After 4 ± 1 years, NODAT, recurrent and de novo NAFLD were observed in 31%, 56% and 43% of the subjects, respectively. Only 3 patients had non-alcoholic steatohepatitis (NASH) without fibrosis. Other risk factors for NAFLD such as arterial hypertension (AHT), metabolic syndrome (MS), hypertriglyceridemia and obesity were seen in 51%, 50%, 35% and 24% of the subjects, respectively. In addition, insulin resistance (IR), assessed by HOMA-IR and ß-cell dysfunction, determined by HOMA-ß, were observed in 16% and 94% of the patients, respectively. Occurrence of NODAT was associated with male gender, higher waist circumference, higher HOMA-IR and lower HOMA-ß values. No correlation was found between NAFLD and NODAT, MS, hypertriglyceridemia, obesity and HOMAIR and HOMA-ß levels. CONCLUSIONS: NODAT, recurrent and de novo NAFLD are common after LT but are not associated with signs of graft dysfunction, possibly due to the low frequency of IR and NASH. No correlation is observed between NAFLD and NODAT, MS, hypertriglyceridemia, obesity and IR. ß-cell dysfunction and diabetes, however, are seen in most of the patients, possibly due to calcineurin inhibitor toxicity.

Brazilian society of hepatology recommendations for the diagnosis and treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB). All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript containing the recommendations of the Brazilian Society of Hepatology.

RESUMO O carcinoma hepatocelular é uma neoplasia de importância global e associada a altos índices de mortalidade. Recentes avanços no diagnóstico e tratamento da doença tornaram necessárias que se atualizassem as recomendações sobre o manejo da doença. Para definir as recomendações sobre o diagnóstico e tratamento do carcinoma hepatocelular, a Sociedade Brasileira de Hepatologia organizou uma reunião monotemática em João Pessoa (PB). Todos expositores foram solicitados a fazer uma revisão sistemática da literatura e apresentar os temas relacionados a fatores de risco para o desenvolvimento de carcinoma hepatocelular, métodos para rastreamento, diagnóstico radiológico e sistemas de estadiamento da doença, tratamentos curativos e paliativos e carcinoma hepatocelular em fígado não cirrótico. Após o encontro, todos os expositores se reuniram para discussão dos tópico e elaboração dessas recomendações. O texto resultante foi ainda submetido a avaliação e aprovação por todos membros da Sociedade através de sua homepage. O documento atual é a versão final que contêm as recomendações da Sociedade Brasileira de Hepatologia.

Brazilian society of hepatology recommendations for the diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB). All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript containing the recommendations of the Brazilian Society of Hepatology.

Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis.

UNLABELLED: Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001). CONCLUSION: With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity.

Prevalence of non-organ-specific autoantibodies in a rural community from northeastern Brazil: a population-based study.

Non-organ-specific autoantibodies (NOSA) are well-recognized diagnostic markers of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but can also be observed in patients with viral hepatitis as well as in healthy subjects. The aim of this study was to evaluate the prevalence of NOSA in subjects living in a rural community in Brazil and to correlate their occurrence with the presence of liver disease. Seven hundred twenty-five apparently healthy subjects were randomly selected for assessment of antinuclear (ANA), anti-smooth muscle (SMA), antimitochondrial (AMA), anti-liver/kidney microsome type 1, and anti-liver cytosol type 1 antibodies. Subjects with those NOSA were evaluated for the presence of AIH, PBC, and viral hepatitis. Reactivities for all NOSA, SMA, ANA, and AMA were detected, respectively, in 14, 10, 4, and 0.1% of subjects, with a mean titer of 1:40. NOSA-positive subjects were significantly older and more frequently females. No correlation was observed between the occurrence of NOSA and PBC, AIH, or viral hepatitis. The prevalence of NOSA in Brazilians was 14%. They were usually low titer. NOSA were more frequently observed in females and older subjects and their presence was not correlated with the presence of AIH, PBC, or viral hepatitis.

Hemorragia digestiva alta varicosa: relatório do 1º consenso da Sociedade Brasileira de Hepatologia / Varicel bleeding: consensus meeting report from the brazilian society of hepatology

Nas últimas duas décadas, foi observada redução importante na mortalidade associada ao primeiro sangramento varicoso, que vem sendo atribuída à melhoria na assistência ao paciente cirrótico e à abordagem multidisciplinar do paciente com hemorragia digestiva alta varicosa (HDAV), particularmente por emergencistas, hepatologistas, gastroenterologistas, endoscopistas e intensivistas. Visando estabelecer recomendações para o manejo da HDAV, a Sociedade Brasileira de Hepatologia (SBH) realizou reunião de consenso para elaboração de documento a ser utilizado como orientação de conduta médica. Dentro da sistemática utilizada, foi criada pela SBH uma comissão organizadora composta por quatro membros que escolheram 27 pesquisadores, representando as diversas regiões do país, para serem moderadores ou expositores dos tópicos relacionados à prevenção, diagnóstico e tratamento da HDAV. Todos os tópicos foram abordados de acordo com o grau de evidência científica disponível. As recomendações foram elaboradas em reunião após ampla discussão com os membros da comissão organizadora, expositores, moderadores e participantes da reunião do consenso, ficando a cargo da comissão organizadora a redação do documento final. A reunião do consenso ocorreu em Salvador em 06 de maio de 2009 e esta publicação exibe as principais conclusões do consenso organizadas sob a forma de resumo da literatura médica seguido pelas recomendações da SBH.

In the last decades, several improvements in the management of variceal bleeding have resulted in a significant decrease in morbidity and mortality of cirrhotis with bleeding varices. Progress in the multidisciplinary approach to the patient with variceal blleding has led to a better management of this disease by critical care physicians, hepatologists, gastroenterologists, endoscopists, radiologists and surgeons. In this respect, the Brazilian Society of Hepatology has, recently, sponsored a consensus meeting in order to draw evidence-based recommendations on the management of these difficult-totreat subjects. An organizing committee comprised of four people was elected by the Governing Board and was responsible to invite 27 researchers from distinct regions of the country to make a systematic review of the subject and to present topics related to variceal bleeding, including prevention, diagnosis, management and treatment, accoding to evidence-based medicine. After the meeting, all participants were held together for discussion of the topics and the elaboration of the aforementioned recommendations. The organizing committee was responsible for writing the final document. The meeting was held at Salvador, May 6th, 2009 and the present manucrispt is the summary of the systematic review that was presented during the meeting organized in topics followed by the reccomendations of the Brazilian Society of Hepatology.

Simplified criteria for the diagnosis of autoimmune hepatitis.

UNLABELLED: Diagnosis of autoimmune hepatitis (AIH) may be challenging. However, early diagnosis is important because immunosuppression is life-saving. Diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) were complex and purely meant for scientific purposes. This study of the IAIHG aims to define simplified diagnostic criteria for routine clinical practice. Candidate criteria included sex, age, autoantibodies, immunoglobulins, absence of viral hepatitis, and histology. The training set included 250 AIH patients and 193 controls from 11 centers worldwide. Scores were built from variables showing predictive ability in univariate analysis. Diagnostic value of each score was assessed by the area under the receiver operating characteristic (ROC) curve. The best score was validated using data of an additional 109 AIH patients and 284 controls. This score included autoantibodies, immunoglobulin G, histology, and exclusion of viral hepatitis. The area under the curve for prediction of AIH was 0.946 in the training set and 0.91 in the validation set. Based on the ROC curves, two cutoff points were chosen. The score was found to have 88% sensitivity and 97% specificity (cutoff > or =6) and 81% sensitivity and 99% specificity (cutoff > or =7) in the validation set. CONCLUSION: A reliable diagnosis of AIH can be made using a very simple diagnostic score. We propose the diagnosis of probable AIH at a cutoff point greater than 6 points and definite AIH 7 points or higher.

Frequency of celiac disease and its serological markers in patients with autoimmune hepatitis

Transglutaminase (anti-tTG) and anti-endomysial (AEA) antibodies were reported to occur in patients with autoimmune hepatitis (AIH) as well as in subjects with advanced cirrhosis, but the prevalence of celiac disease (CD) in patients with AIH is either negligible or unknown. The frequency of IgA anti-tTG and IgA AEA was determined in 64 patients (54 females, mean age 19[5-67] years ) with AIH diagnosed according to international criteria. Patients with positive or intermediate results for those antibodies were submitted to duodenal biopsy and HLA-DQ2 or DQ8 typing. Anti-tTG and AEA were detected in 6 (9 por cento) and one patient (1.6 por cento) with AIH, respectively. Positive and borderline results for IgA anti-tTG were detected, respectively, in two (3 por cento) and four (6 por cento) patients. Only one patient with HLA-DQ2 and IgA anti-tTG and IgA AEA had CD on duodenal biopsy. Two patients with either positive or borderline results for IgA anti-tTG antibody and HLA-DQ2 had normal histology on duodenal biopsy. IgA anti-tTG antibody and/or AEA were observed in 9% of AIH patients, but CD was confirmed in only one of them. The occurrence of IgA anti-tTG antibody in the other patients could be ascribed to the presence of chronic liver disease or to latent or potential CD.

Cytotoxic T lymphocyte antigen-4 gene polymorphisms do not confer susceptibility to autoimmune hepatitis types 1 and 2 in Brazil.

OBJECTIVE: Susceptibility to autoimmune hepatitis (AIH) has been linked to different HLA-DR antigens in distinct populations. Recently, an A-G polymorphism in exon 1 of the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene was associated with predisposition to AIH type 1 (AIH-1) in white individuals in North America. This polymorphism has been associated with several other autoimmune diseases, presumably because of its effect in the expression of CTLA-4, an adhesion molecule that downregulates peripheral T cell responses. The aims of this study were to assess the frequency of CTLA-4 genotypes in Brazilian patients with AIH-1 and AIH type 2 (AIH-1), as well as to investigate the influence of these genotypes in disease expression. METHODS: Determination of CTLA-4 genotypes was carried out in 106 patients with AIH-1, 26 subjects with AIH-2, and 67 healthy control subjects by polymerase chain reaction (PCR)-based techniques. RESULTS: No difference in the distribution of CTLA-4 genotypes was observed in subjects with AIH-1 and AIH-2 as compared to healthy controls. Patients with AIH-1 and AIH-2 with the GG genotype exhibited lower gamma-globulin and ALT levels, respectively. CONCLUSIONS: Susceptibility to AIH-1 and AIH-2 in Brazilian patients is not influenced by exon 1 CTLA-4 gene polymorphisms at position 49.

Clinical distinctions and pathogenic implications of type 1 autoimmune hepatitis in Brazil and the United States.

BACKGROUND/AIMS: Type 1 autoimmune hepatitis has a strong genetic predisposition that varies among different ethnic groups. Our aims were to determine if the clinical manifestations differed between patients with type 1 autoimmune hepatitis from Brazil and the United States and if classical disease could be associated with region-specific susceptibility markers. METHODS: The clinical manifestations and genetic risk factors of 161 patients from the United States were compared to those of 115 patients from Brazil. RESULTS: The patients from Brazil had earlier disease onset, lower frequency of concurrent immune diseases, higher serum levels of aspartate aminotransferase and gamma-globulin, greater occurrence of smooth muscle antibodies, and lower frequency of antinuclear antibodies than the patients from the United States. Human leukocyte antigen (HLA) DR13 and DRB1*1301 occurred more commonly in the Brazilian patients and HLA DR4 less often. Normal subjects from each country had similar frequencies of HLA DR13 and DR3. CONCLUSIONS: Type 1 autoimmune hepatitis in Brazil has different features at presentation than the disease in Caucasoid patients from the United States, and it is associated with HLA DR13. Background populations in each country have similar frequencies of HLA DR13 and DR3, and region-specific etiologic factors may determine the HLA association.

Diabetes mellitus-related autoantibodies in childhood autoimmune hepatitis.

OBJECTIVE: To determine the frequency and significance of diabetes mellitus (DM)-related autoantibodies in children with autoimmune hepatitis (AIH). RESEARCH DESIGN AND METHODS: Anti-islet cell antibodies (ICA), insulin autoantibodies (IAA), and anti-glutamic acid decarboxylase (GAD65) antibodies were assessed in 28 children (25 female) with AIH before and after 3-9 years of therapy with azathioprine and prednisone. RESULTS: There was biochemical and clinical remission of AIH activity in 76% of the children after 1 year of immunosuppressive therapy. Positive ICA and IAA were found in 60.7% and 18.5% of the patients, decreasing to 38.5% and 12% after 3-9 years of therapy. Anti-GAD autoantibodies were present in only one patient who had Graves' disease, high ICA titer, and developed type 1 DM after 3 years. After 3-9 years of follow up, all had normal fasting glycemia, glycosylated hemoglobin (HbA1c), and, with a single exception, normal responses to oral glucose tolerance testing. No increase in the frequencies of HLA antigens was observed in ICA- and IAA-positive patients compared to antibody-negative patients or a control population. The majority of the patients with HLA-DRB1*03 or DRB1*04, however, were positive for ICA (7/10), and three of them had IAA. The frequency of high risk HLA DQB1*0302 or DQB1*02 alleles was low and similar to control frequencies, indicating low-risk for DM despite the presence of DM-related autoimmunity markers. CONCLUSIONS: AIH in childhood is associated with high frequency of ICA and IAA, with less than expected rates of progression to DM. Immunosuppression reduced ICA and IAA frequency and titers.