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 ≥6) and 81% sensitivity and 99% specificity (cutoff ≥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. (HEPATOLOGY 2008.)
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. (Hepatology 2014;59:592–600)
Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this ...cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of
and
genera were increased depending on patients' age at diagnosis.
was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of
in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.
Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations.
To describe ...the diagnostic features and response to treatment in our cohort of WD patients.
This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams,
genotyping, and response to treatment.
Symptoms occurred at an average age of 17.4 (7-49) years, and patients were followed up for an average of 9.6 (0-45) years. Patients presented mainly with hepatic (36.3%), neurologic (34.7%), and neuropsychiatric (8.3%) forms. Other presentations were hematologic, renal, or musculoskeletal, and 16.8% of the patients were asymptomatic. Kayser-Fleischer rings occurred in 78.3% of the patients, hypoceruloplasminemia in 98.3%, and elevated cupruria/24h in 73.0%, with an increase after D-penicillamine in 54.0%. Mutations of the
gene were detected in 84.4% of alleles. Brain magnetic resonance imaging showed abnormalities in the basal ganglia in 77.7% of patients. D-penicillamine was the first choice in 93.6% of the 245 patients, and 21.1% of these patients were switched due to adverse effects. The second-line therapies were zinc and trientine. The therapeutic response did not differ significantly between the drugs (
= 0.2). Nine patients underwent liver transplantation and 82 died.
Wilson disease is diagnosed at a late stage, and therapeutic options are limited. In people under 40 years of age with compatible manifestations, WD could be considered earlier in the differential diagnosis. There is a need to include
genotyping and therapeutic alternatives in clinical practice.
The objective of this study was to evaluate the health-related quality of life in children and adolescents with autoimmune hepatitis.
A cross-sectional assessment with the Pediatric Quality of Life ...Inventory 4.0 (PedsQL 4.0) was completed for 80 patients with autoimmune hepatitis and 45 healthy controls. Demographic data, prednisone dose, disease remission state, disease severity, and abdominal pain were also evaluated.
Based on the child self-reports, physical, emotional, school, and total scores were significantly lower in autoimmune hepatitis patients when compared with controls (p<0.05). Based on the parental reports, only the physical and total scores were significantly lower in autoimmune hepatitis patients versus controls (p<0.05). Further analysis in autoimmune hepatitis patients with abdominal pain in the last month revealed significantly lower physical, social, and total median scores (p<0.05). No differences were observed based on disease remission state or disease severity (p>0.05). Autoimmune hepatitis patients who received a prednisone dose below 0.16mg/kg/day at the time of the interview showed significantly higher physical scores than those who received a dose similar to or above 0.16mg/kg/day (87.5 50–100 vs. 75 15.63–100, p=0.006).
Reduced scores in the physical, emotional, and school domains were observed in pediatric autoimmune hepatitis patients compared to control patients. Abdominal pain and corticosteroid dose negatively influenced the health-related quality of life in children and adolescents with autoimmune hepatitis.
Avaliar a qualidade de vida relacionada à saúde em crianças e adolescentes com hepatite autoimune (HAI).
Foi concluída uma avaliação transversal com o Inventário Pediátrico de Qualidade de Vida 4.0 (PedsQL 4.0) para 80 pacientes com hepatite autoimune e 45 controles saudáveis. Os dados demográficos, a dose de prednisona, o estado de remissão da doença, a gravidade da doença e dor abdominal também foram avaliados.
Com base nos autorrelatos das crianças, os escores físico, emocional, escolar e total foram significativamente menores em pacientes com hepatite autoimune em comparação com os controles (p < 0,05). Com base nos relatos dos pais, apenas os escores físico e total foram significativamente menores em pacientes com hepatite autoimune em comparação com os controles (p < 0,05). Uma análise adicional em pacientes com hepatite autoimune com dor abdominal no mês passado revelou escores médios físico, social e total significativamente menores (p < 0,05). Nenhuma diferença foi observada com base no estado de remissão da doença ou na gravidade da doença (p > 0,05). Os pacientes com hepatite autoimune que receberam uma dose de prednisona abaixo de 0,16mg/kg/dia no momento da entrevista mostraram escores físicos significativamente maiores que os que receberam uma dose semelhante ou acima de 0,16mg/kg/dia 87,5 (50-100) em comparação com 75 (15,63-100), p = 0,006.
Escores reduzidos nos domínios físico, emocional e escolar foram observados em pacientes pediátricos com hepatite autoimune em comparação com pacientes do grupo de controle. Dor abdominal e dose de corticosteroide influenciaram negativamente a qualidade de vida relacionada à saúde em crianças e adolescentes com hepatite autoimune.
Acute liver failure (ALF) in children is a life‐threatening condition that often leads to urgent liver transplantation (LT). The aim of the present investigation was to describe the experience in ...Brazil in treating pediatric ALF, with an emphasis on the role of living donor liver transplantation (LDLT) in treating this condition. All children with ALF who fulfilled the criteria for an urgent LT were admitted to the intensive care unit. Patients were divided into 2 groups based on the moment of admission: before and after June 2007, when the LDLT program for ALF was started. Statistical analyses were performed to identify prognostic factors of patients with ALF. For the study, 115 children with ALF were admitted. All patients had some degree of encephalopathy. Among the patients, 26% of them required intracranial pressure monitoring (IPM), 12.8% of the patients required hemodialysis, and 79 patients underwent transplantation (50 deceased donors and 29 living donors) corresponding to 12.4% of all pediatric LTs. Only 9 children recovered without LT. The need for IPM and nonperformance of LT were related to a higher mortality. The mortality rate of patients who underwent LT was significantly lower than that of children with ALF who did not undergo a LT (48.1% versus 75%; P = 0.02). The incidences of primary nonfunction and mortality were statistically higher among deceased donor liver transplantations than LDLTs. Finally, it was verified that the overall survival rate of transplanted patients was increased after the introduction of LDLT (P = 0.02). In conclusion, ALF in children continues to be a severe and devastating condition, and a LT should be performed promptly. The introduction of LDLT could increase the survival rate of patients in Brazil. Liver Transplantation 22 1006–1013 2016 AASLD
Abstract To assess the impact of oral conditions on the oral health-related quality of life (OHRQoL) of pediatric liver transplant candidates. This cross-sectional study included 60 children aged 13 ...to 48 months who were liver transplant candidates that attended the AC Camargo Cancer Center, São Paulo, Brazil. On the day of oral examinations, the children’s mothers were invited to answer two questionnaires; one related to children’s OHRQoL using the B-ECOHIS and another related to socioeconomic/demographic characteristics. Thereafter, a single, adequately trained dentist carried out children’s oral examinations for gingival inflammation (Silness-Löe index), dental plaque (Green-Vermillion Simplified index), dental caries (dmft index), developmental defects of enamel (DDE index), tooth discoloration, oral mucosal/lip alterations. The data collected also included socioeconomic/demographic characteristics and liver disease. The adjusted Poisson regression model was used to associate children’s socioeconomic/demographic characteristics and clinical conditions to the outcome. The adjusted regression model showed that children with untreated caries lesions (RR = 3.35, p < 0.0001) and tooth discoloration (RR = 1.74, p = 0.04) had poorer total B-ECOHIS scores. Dental discoloration and untreated caries lesions had a negative impact on the OHRQoL in pediatric liver transplant candidates.
Lysosomal acid lipase deficiency in Brazilian children: a case series Benevides, Gabriel Nuncio; Miura, Irene Kazue; Person, Natalia Canale ...
Jornal de pediatria,
September-October 2019, 2019 Sep - Oct, 2019-09-00, 20190901, 2019-09-01, Letnik:
95, Številka:
5
Journal Article
Recenzirano
Odprti dostop
To describe the demographic, clinical, laboratory and molecular characteristics of patients with lysosomal acid lipase deficiency.
A retrospective review of the medical records of children with the ...disease.
Seven children with lysosomal acid lipase deficiency (5 male; 2 female); 6 were mixed race, and 1 was black. The mean ages at the first onset of symptoms and at diagnosis were 5.0 years (4 months to 9 years) and 6.9 years (3–10 years), respectively. Symptom manifestations at onset were: 3 patients had abdominal pain, one had bone/joint pain due to rickets, and 1 had chronic diarrhea and respiratory insufficiency due to interstitial pneumonitis. One was asymptomatic, and clinical suspicion arose due to hepatomegaly. Six patients had hepatomegaly, and none had splenomegaly. Two patients were siblings. Enzymatic assay and molecular analysis confirmed the diagnoses. Genetic analysis revealed a rare pathogenic variant (p.L89P) in three patients, described only once in medical literature and never described in Brazil. None of those patients were related to each other. Lysosomal acid lipase deficiency was previously described as an autosomal recessive disease, but three patients were heterozygous and undoubtedly had the disease (low enzyme activity, suggestive lab findings and clinical symptoms).
This case series supports that lysosomal acid lipase deficiency can present with highly heterogeneous signs and symptoms among patients, but it should be considered in children presenting with gastrointestinal symptoms associated with dyslipidemia. We describe a rare variant in three non-related patients that may suggest a Brazilian genotype for lysosomal acid lipase deficiency.
Descrever as características demográficas, clínicas, laboratoriais e moleculares de pacientes com deficiência de lipase ácida lisossomal.
Análise retrospectiva dos prontuários médicos de crianças com a deficiência de lipase ácida lisossomal.
Sete crianças com deficiência de lipase ácida lisossomal (5M:2F); seis eram pardas e uma negra. As faixas etárias no início dos sintomas e no diagnóstico foram 5 anos (4 meses a 9 anos) e 6,9 anos (3 a 10 anos), respectivamente. As manifestações dos sintomas no início foram as que seguem: três pacientes apresentaram dor abdominal, um apresentou dor nos ossos/articulações devido a raquitismo e um apresentou diarreia crônica e insuficiência respiratória devido à pneumonite intersticial. Os outros não apresentaram sintomas e a suspeita clínica surgiu devido à hepatomegalia. Seis pacientes apresentaram hepatomegalia e um apresentou esplenomegalia. Dois pacientes eram irmãos. O ensaio enzimético e a análise molecular confirmaram os diagnósticos. A análise genética revelou uma variante patogênica rara (p.L89P) em três pacientes, descrita uma única vez na literatura médica e nunca descrita no Brasil. Nenhum desses pacientes tinha parentesco com os outros. A deficiência de lipase ácida lisossomal foi anteriormente descrita como uma doença recessiva autossômica, porém três pacientes eram heterozigotos e, sem dúvida, apresentaram a doença (atividade enzimática baixa, achados laboratoriais sugestivos e sintomas clínicos).
Esta casuística afirma que a deficiência de lipase ácida lisossomal pode se manifestar com sinais e sintomas altamente heterogêneos entre os pacientes, porém deve ser considerada em crianças que apresentam sintomas gastrointestinais associados à dislipidemia. Descrevemos uma variante rara em três pacientes não relacionados que pode sugerir um genótipo brasileiro para deficiência de lipase ácida lisossomal.
Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic ...hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified.
Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment.
The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc).
Delta infection is also part of the guideline, since it is an important infection in some parts of the country.
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