Assuntos
Prestação Integrada de Cuidados de Saúde , Doença Hepática Terminal/cirurgia , Transplante de Fígado , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos , Adulto , Idoso , Prestação Integrada de Cuidados de Saúde/economia , Prestação Integrada de Cuidados de Saúde/organização & administração , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/economia , Doença Hepática Terminal/epidemiologia , Feminino , Custos de Cuidados de Saúde , Humanos , Cooperação Internacional , Kuweit/epidemiologia , Transplante de Fígado/economia , Doadores Vivos/provisão & distribuição , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Fatores de Tempo , Obtenção de Tecidos e Órgãos/economia , Obtenção de Tecidos e Órgãos/organização & administraçãoAssuntos
Rejeição de Enxerto/induzido quimicamente , Transplante de Fígado/efeitos adversos , Fósforo/intoxicação , Rodenticidas/intoxicação , Adolescente , Adulto , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Disfunção Primária do Enxerto/induzido quimicamente , Disfunção Primária do Enxerto/patologia , Adulto JovemRESUMO
BACKGROUND: Crigler Najjar type 1 is a rare autosomal recessive condition caused by the absence of UDPGT enzyme due to mutations in the UGT1A1 gene. This enzyme is responsible for elimination of unconjugated bilirubin from the body by glucuronidation. Affected individuals are at risk for kernicterus and require lifelong phototherapy. Liver transplant is the only definitive treatment. CASE PRESENTATION: Here we report a case of a 6 month old Sudanese female infant with CN1 whose molecular analysis revealed a novel homozygous 22 base pair duplication (c.55_76dup) in the coding exon 1 of the UGT1A1 gene. This 22 bp duplication causes a frame shift leading to a premature stop codon. She underwent a successful liver transplant at 7 months of age and is doing well at 1 year follow-up. CONCLUSION: This study shows that molecular diagnosis helps in precise diagnosis of CN1 and in prognosis, prompt medical intervention and appropriate therapy. This particular 22 bp duplication within the coding region of UGT1A1 can be a founder mutation in the Sudanese population.
Assuntos
Síndrome de Crigler-Najjar/genética , Duplicação Gênica , Glucuronosiltransferase/genética , Consanguinidade , Síndrome de Crigler-Najjar/cirurgia , Éxons , Feminino , Humanos , Lactente , Transplante de Fígado , Linhagem , SudãoRESUMO
PURPOSE: Auxiliary partial orthotopic liver transplantation (APOLT) in metabolic liver disease (MLD) has the advantage of correcting the metabolic defect, preserving the native liver for gene therapy in the future with the possibility of withdrawal of immunosuppression. METHODS: Retrospective analysis of safety and efficacy of APOLT in correcting the underlying defect and its impact on neurological status of children with MLD. RESULTS: A total of 13 APOLT procedures were performed for MLD during the study period. The underlying aetiologies being propionic acidemia (PA)-5, citrullinemia type 1 (CIT1)-3 and Crigler-Najjar syndrome type 1 (CN1)-5 cases respectively. Children with PA and CIT1 had a median of 8 and 4 episodes of decompensation per year, respectively, before APOLT and had a mean social developmental quotient (DQ) of 49 (<3 standard deviations) as assessed by Vineland Social Maturity Scale prior to liver transplantation. No metabolic decompensation occurred in patients with PA and CIT1 intraoperatively or in the immediate post-transplant period on protein-unrestricted diet. Patients with CN1 were receiving an average 8-15 h of phototherapy per day before APOLT and had normal bilirubin levels without phototherapy on follow-up. We have 100% graft and patient survival at a median follow-up of 32 months. Progressive improvement in neurodevelopment was seen in children within 6 months of therapy with a median social DQ of 90. CONCLUSIONS: APOLT is a safe procedure, which provides good metabolic control and improves the neurodevelopment in children with selected MLD.
RESUMO
BACKGROUND: The aim of this study was to study the determinants of nonadherence to immunosuppressant drugs in liver transplant (LT) recipients using personalised interview and questionnaire methods. METHODS: The study was conducted on adult LT recipients (deceased donor liver transplant [DDLT] and living donor liver transplant [LDLT]) from the Indian subcontinent, at post-LT clinic visit between July and December 2016. Recipient details included baseline demography, comorbidity, psychological status, details of addiction, indication and type of transplant. Details on financial support for transplantation, admissions for rejection, infection and posttransplant complications were obtained from the hospital records. An adherence questionnaire was completed by direct interview and using a questionnaire. RESULTS: Sixty-seven LT recipients (56 males, median age 48.17 years) constituted the study group. Overall, 11 patients (16.47%) were nonadherent to treatment. LDLT recipients were more adherent than DDLT recipients. Nonadherent recipients were believers in alternative systems of medicine. Medication-related factors such as improper dosing, meagre drug knowledge difficulty in remembering drug dose and timings and economic constraints in continuing medical treatment were statistically significant in nonadherent recipients. Although variation in the tacrolimus levels were significantly more common in the nonadherent group, acute cellular rejection and infection were not statistically different. CONCLUSIONS: The prevalence of nonadherence was 16.5%. Determinants of nonadherence were DDLT, belief in alternative medications, high regimen complexity, poor knowledge about medications and cost issues with long-term medications.
RESUMO
BACKGROUND AND AIM: Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C. MATERIAL AND METHODS: We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival. RESULTS: Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLCC. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p < 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p < 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p < 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted. CONCLUSION: TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Feminino , Humanos , Índia , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Sorafenibe , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
BACKGROUND: Gallstones (GS) in south India (SI) are predominantly pure pigment or mixed, while in North India (NI), these are either pure cholesterol or mixed. While cholesterol rich gallbladder (GB) bile predicts cholesterol GS, constituent of bile in primary pigment GS is not known. We compared the composition of GB bile from healthy liver donors and patients with GS from north and south India. METHODS: Gallbladder bile from healthy liver donors from north (10) and south India (8) served as controls. Cases were patients from north (21) and south India (17) who underwent cholecystectomy for GS disease. Gallbladder bile from both cases and controls was analyzed for cholesterol, lecithin (phospholipid), and bile salts. Gallstones were classified as cholesterol, mixed, and pigment based on morphology and biochemical analysis. RESULTS: The median cholesterol concentration in control bile from north was significantly high compared to south (p<0.001) with no difference in lecithin and bile salts (p NS). Except for one sample each from north and south, the cholesterol solubility of controls was within the critical micellar zone. Mixed GS were most frequent in north India (61.9 %) while pigment GS dominated in south (61.9 %). The median cholesterol concentration in bile samples of cholecystectomy patients from north India was significantly high GS (p < 0.00001) with significant lowering of bile salts and lecithin (p < 0.00001). In south India, patients with mixed GS had high cholesterol content in bile compared to controls and patients with pigment GS; bile in latter had significantly higher concentration of bile salt compared to controls and mixed GS. The ternary plot confirmed the composition of GB bile from north and south India. CONCLUSIONS: Gallbladder bile in controls and patients with GS from north India had significantly high cholesterol concentration. In south India, patients with mixed GS had cholesterol rich bile while pigment GS had higher concentrations of bile salts.