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2.
Artigo em Inglês | MEDLINE | ID: mdl-32046867

RESUMO

Despite advances in research, the pathophysiology of food allergy has not yet been fully elucidated. IL-10 has both a pro- and anti-inflammatory effect on the development of food allergy and in order to understand its different immune-modulatory effects the factors that influence the inflammatory microenvironment need to be taken into account. Specific single nucleotide polymorphisms of the IL-10 gene seem to confer an increased risk of developing food allergy, but to date there is a substantial lack of genome- wide association studies regarding the genetic and epigenetic underpinnings of the disease. Special interest has been drawn to the development of allergen-specific regulatory CD4+CD25+ T-cells secreting IL-10 in the immunotherapy of allergic diseases. In addition, a distinct population of human tolerogenic dendritic cells (DC), DC-10 seems to hold great potential and could potentially serve as a therapeutic tool to improve the management of food allergy.

3.
Expert Rev Gastroenterol Hepatol ; 14(3): 185-196, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32098516

RESUMO

Introduction: Hepatocyte transplantation (HT) is a promising alternative to liver transplantation for the treatment of liver-based metabolic diseases and acute liver failure (ALF). However, shortage of good-quality liver tissues, early cell loss post-infusion, reduced cell engraftment and function restricts clinical application.Areas covered: A comprehensive literature search was performed to cover pre-clinical and clinical HT studies. The review discusses the latest developments to address HT limitations: cell sources from marginal/suboptimal donors to neonatal livers, differentiating pluripotent stem cells into hepatocyte-like cells, in vitro expansion, prevention of immune response to transplanted cells by encapsulation or using innate immunity-inhibiting agents, and enhancing engraftment through partial hepatectomy or irradiation.Expert opinion: To date, published data are highly encouraging specially the alginate-encapsulated hepatocyte treatment of children with ALF. Hepatocyte functions can be further improved through co-culturing with mesenchymal stromal cells. Moreover, ex-vivo genetic correction will enable the use of autologous cells in future personalized medicine.

4.
J Pediatr ; 218: 121-129.e3, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31955873

RESUMO

OBJECTIVES: To report baseline features and long-term medical/social outcomes of juvenile autoimmune liver disease, including autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), managed in a single tertiary center. STUDY DESIGN: Retrospective study of children diagnosed in 2000-2004 with AIH/ASC followed up to date. Patients with abnormal cholangiogram were classified as ASC. Presentation and outcome features were compared. RESULTS: Eighty-three children were included (42 female, median age 12.1 years [8.5-14.1 years], AIH = 54, ASC = 29). Most (65%) had antinuclear and/or anti-smooth muscle autoantibodies; 6% presented with acute liver failure; 29% had histologic evidence of cirrhosis. The 1999 and simplified International Autoimmune Hepatitis Group criteria failed to diagnose up to 26% of patients with AIH and 48% with ASC, and the proposed the European Society for Pediatric Gastroenterology, Hepatology and Nutrition criteria were accurate. Response to treatment was excellent with 95% achieving normal transaminase levels. During follow-up, 31% had at least 1 relapse episode; 3 patients with AIH developed cholangiopathy and 5 patients with ASC developed progressive bile duct injury. At last follow-up (median of 14.5 years, 10.4-16.8), 99% were alive, 11 underwent transplantation and 1 is listed for transplant. Five-, 10-, and 15-year transplant-free survival rates were 95%, 88%, and 83%; patients with ASC and those relapsing being more likely to require transplant. Social outcome was excellent with 93% in employment/education. CONCLUSIONS: Seamless management of juvenile autoimmune liver disease leads to excellent clinical and social outcomes. Despite good response to immunosuppressive treatment, patients with ASC have a worse prognosis than those with AIH. Diagnostic models developed for adults are unsatisfactory to correctly diagnose juvenile autoimmune liver disease.

5.
Liver Transpl ; 26(3): 419-430, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31715057

RESUMO

Liver transplantation (LT) for patients with propionic acidemia (PA) is an emerging therapeutic option. We present a retrospective review of patients with PA who underwent LT at a tertiary liver center between 1995 and 2015. A total of 14 children were identified (8 males) with median age at initial presentation of 3 days (range, 0-77 days). Pretransplant median protein restriction was 1 g/kg/day (range, 0.63-1.75 g/kg/day), 71% required supportive feeding, and 86% had developmental delay. Frequent metabolic decompensations (MDs) were the main indication for LT with a median age at transplantation of 2.4 years (range, 0.8-7.1 years). Only 1 graft was from a living donor, and 13 were from deceased donors (4 auxiliary). The 2-year patient survival was 86%, and overall study and graft survival was 79% and 69%, respectively. Three patients died after LT: at 43 days (biliary peritonitis), 225 days (acute-on-chronic rejection with multiorgan failure), and 13.5 years (posttransplant lymphoproliferative disease). Plasma glycine and propionylcarnitine remained elevated but reduced after transplant. Of 11 survivors, 5 had at least 1 episode of acute cellular rejection, 2 sustained a metabolic stroke (with full recovery), and 3 developed mild cardiomyopathy after LT. All have liberalized protein intake, and 9 had no further MDs: median episodes before transplant, 4 (range, 1-30); and median episodes after transplant, 0 (range, 0-5). All survivors made some developmental progress after LT, and none worsened at a median follow-up of 5.8 years (range, 2-23 years). LT in PA significantly reduces the frequency of MDs, can liberalize protein intake and improve quality of life, and should continue to be considered in selected cases.

6.
Lancet ; 395(10219): 226-239, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31791690

RESUMO

This final report of the Lancet Commission into liver disease in the UK stresses the continuing increase in burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions which are worsening in deprived areas. Only with comprehensive food and alcohol strategies based on fiscal and regulatory measures (including a minimum unit price for alcohol, the alcohol duty escalator, and an extension of the sugar levy on food content) can the disease burden be curtailed. Following introduction of minimum unit pricing in Scotland, alcohol sales fell by 3%, with the greatest effect on heavy drinkers of low-cost alcohol products. We also discuss the major contribution of obesity and alcohol to the ten most common cancers as well as measures outlined by the departing Chief Medical Officer to combat rising levels of obesity-the highest of any country in the west. Mortality of severely ill patients with liver disease in district general hospitals is unacceptably high, indicating the need to develop a masterplan for improving hospital care. We propose a plan based around specialist hospital centres that are linked to district general hospitals by operational delivery networks. This plan has received strong backing from the British Association for Study of the Liver and British Society of Gastroenterology, but is held up at NHS England. The value of so-called day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and, in particular, schemes to allow general practitioners to refer patients directly for elastography assessment. New funding arrangements for general practitioners will be required if these proposals are to be taken up more widely around the country. Understanding of the harm to health from lifestyle causes among the general population is low, with a poor knowledge of alcohol consumption and dietary guidelines. The Lancet Commission has serious doubts about whether the initiatives described in the Prevention Green Paper, with the onus placed on the individual based on the use of information technology and the latest in behavioural science, will be effective. We call for greater coordination between official and non-official bodies that have highlighted the unacceptable disease burden from liver disease in England in order to present a single, strong voice to the higher echelons of government.


Assuntos
Alcoolismo/epidemiologia , Hepatopatias/epidemiologia , Hepatopatias/prevenção & controle , Obesidade/epidemiologia , Bebidas Alcoólicas/economia , Alcoolismo/complicações , Alcoolismo/terapia , Comércio , Redes Comunitárias/organização & administração , Comorbidade , Efeitos Psicossociais da Doença , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Legislação sobre Alimentos , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Transplante de Fígado/estatística & dados numéricos , Obesidade/complicações , Pacotes de Assistência ao Paciente , Escócia , Reino Unido/epidemiologia
7.
J Hepatol ; 72(5): 877-884, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31843649

RESUMO

BACKGROUND & AIMS: Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis. METHODS: Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT. RESULTS: Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions. CONCLUSION: The results demonstrate the feasibility and safety of an HMB infusion in children with ALF. LAY SUMMARY: Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure.

8.
J Gen Virol ; 100(11): 1491-1500, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31592753

RESUMO

Hepatitis E virus (HEV) is a zoonotic infection, with consumption of processed pork products thought to be the major route of transmission in England. The clinical features of HEV infection range from asymptomatic infection to mild hepatitis to fulminant liver failure. Persistent, chronic hepatitis is increasingly recognized in immunocompromised patients. Infection via HEV-containing blood components and organs has been reported and measures to reduce this transmission risk were introduced into the blood service in England in 2016. We report here the sequence and phylogenetic findings from investigations into a transmission event from an HEV-infected donor to two recipients. Phylogenetic analysis of HEV genome sequence fragments obtained by Sanger sequencing showed that, whilst most of the sequences from both recipients' samples grouped with the sequence from the blood donor sample, the relationship of five sequences from recipient 2 were unresolved. Analysis of Illumina short-read deep sequence data demonstrated the presence of two divergent viral populations in the donor's sample that were also present in samples from both recipients. A clear phylogenetic relationship was established, indicating a probable transmission of both populations from the donor to each of the immunocompromised recipients. This study demonstrates the value of the application of new sequencing technologies combined with bioinformatic data analysis when Sanger sequencing is not able to clarify a proper phylogenetic relationship in the investigation of transmission events.

9.
J Pediatr Gastroenterol Nutr ; 69(6): 648-654, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31503215

RESUMO

OBJECTIVE: Mother-to-infant transmission (MIT) is the leading cause of hepatitis B virus (HBV) infections globally. The aim of this international study was to assess the impediments to prevention of (MIT) of HBV. METHODS: A cross-sectional survey was developed by the Federation of the International Societies for Pediatric Gastroenterology, Hepatology and Nutrition. (FISPGHAN) The survey was sent to HBV experts of the 5-member societies of FISPGHAN, and 63 of 91 countries/regions responded. Main outcome measures include percentage of countries having vaccine programs, timing of the first dose of HBV vaccine, availability of HBV vaccine for outborn neonates, payment of HBV vaccine and hepatitis B immune globulin, screening HBV markers during pregnancy, and antivirals to highly infectious pregnant mothers. RESULTS: Among the participating countries/regions, 11% did not implement infant HBV immunization programs. The first dose of vaccine was given >24 hours in 36% of the total countries and 100% of African countries. The recommended birth dose was unavailable for outborn neonates in 45% of the total countries, including 92% of African and 50% of Latin American countries/regions. During pregnancy, 44% countries do not screen maternal viral markers, and 46% do not provide third trimester antiviral therapy for highly viremic pregnant mothers. CONCLUSIONS: Our study demonstrated multiple obstacles to achieving the goal of preventing MIT of HBV. Comprehensive public health programs to enhance vaccine coverage rate, supply HBV vaccine for out-born neonates, screening maternal HBV markers, treating highly viremic pregnant mothers are proposed to overcome these obstacles and achieve the goal of preventing MIT of HBV.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31495946

RESUMO

BACKGROUND AND AIM: Crigler-Najjar syndrome (CNS) results from biallelic mutations of UGT1A1 causing partial or total loss of uridine 5'-diphosphate glucuronyltransferase activity leading to unconjugated hyperbilirubinemia and its attendant risk for irreversible neurological injury (kernicterus). CNS is exceedingly rare and has been only partially characterized through relatively small studies, each comprising between two and 57 patients. METHODS: A systematic literature review was conducted to consolidate data on the patient, caregiver, and societal burden of CNS. RESULTS: Twenty-eight articles on clinical aspects of CNS were identified, but no published data on its humanistic or economic burden were found. In patients with complete UGT1A1 deficiency (type 1 CNS [CNS-I]), unconjugated bilirubin levels increase 3-6 mg/dL/day during the newborn period and reach neurologically dangerous levels between 5 and 14 days of age. Phototherapy is the mainstay of treatment but poses significant challenges to patients and their families. Despite consistent phototherapy, patients with CNS-I have worsening hyperbilirubinemia with advancing age. Liver transplantation is the only definitive therapy for CNS-I and is increasingly associated with excellent long-term survival but also incurs high costs, medical and surgical morbidities, and risks of immunosuppression. CONCLUSIONS: Crigler-Najjar syndrome is associated with a substantial burden, even with existing standards of care. The development of novel disease-modifying therapies has the potential to reduce disease burden and improve the lives of CNS patients and their families.

11.
Liver Transpl ; 25(10): 1561-1570, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31379050

RESUMO

Liver transplantation (LT) for small infants remains challenging because of the demands related to graft selection, surgical technique, and perioperative management. The aim of this study was to evaluate the short-term and longterm outcomes of LT regarding vascular/biliary complications, renal function, growth, and patient/graft survival in infants ≤3 months compared with those of an age between >3 and 6 months at a single transplant center. A total of 64 infants ≤6 months underwent LT and were divided into 2 groups according to age at LT: those of age ≤3 months (range, 6-118 days; XS group, n = 37) and those of age >3 to ≤6 months (range, 124-179 days; S group, n = 27) between 1989 and 2014. Acute liver failure was the main indication for LT in the XS group (n = 31, 84%) versus S (n = 7, 26%). The overall incidence of hepatic artery thrombosis and portal vein thrombosis/stricture were 5.4% and 10.8% in the XS group and 7.4% and 11.1% in the S group, respectively (not significant). The overall incidence of biliary stricture and leakage were 5.4% and 2.7% in the XS group and 3.7% and 3.7% in the S group, respectively (not significant). There was no significant difference between the 2 groups in terms of renal function. No significant difference was found between the 2 groups for each year after LT in terms of height and weight z score. The 1-, 5-, and 10-year patient survival rates were 70.3%, 70.3%, and 70.3% in the XS group compared with 92.6%, 88.9%, and 88.9% in the S group, respectively (not significant). In conclusion, LT for smaller infants has acceptable outcomes despite the challenges of surgical technique, including vascular reconstruction and graft preparation, and perioperative management.

12.
Clin Transplant ; 33(10): e13698, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31436896

RESUMO

BACKGROUND AND AIMS: This multicenter trial compared immediate-release tacrolimus (IR-T) vs prolonged-release tacrolimus (PR-T) in de novo kidney, liver, and heart transplant recipients aged <16 years. Each formulation had similar pharmacokinetic (PK) profiles. Follow-up efficacy and safety results are reported herein. MATERIALS AND METHODS: Patients, randomized 1:1, received once-daily, PR-T or twice-daily, IR-T within 4 days of surgery. After a 4-week PK assessment, patients continued randomized treatment for 48 additional weeks. At Year 1, efficacy assessments included the number of clinical acute rejections, biopsy-confirmed acute rejection (BCAR) episodes (including severity), patient and graft survival, and efficacy failure (composite of death, graft loss, BCAR, or unknown outcome). Adverse events were assessed throughout. RESULTS: The study included 44 children. At Year 1, mean ± standard deviation tacrolimus trough levels were 6.6 ± 2.2 and 5.4 ± 1.6 ng/mL, and there were 2 and 7 acute rejection episodes in the PR-T and IR-T groups, respectively. No cases of graft loss or death were reported during the study. The overall efficacy failure rate was 18.2% (PR-T n = 1; IR-T n = 7). CONCLUSIONS: In pediatric de novo solid organ recipients, the low incidence of BCAR and low efficacy failure rate suggest that PR-T-based immunosuppression is effective and well tolerated to 1-year post-transplantation.

14.
J Mol Med (Berl) ; 97(4): 563-577, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30820592

RESUMO

For patients with non-cirrhotic liver-based metabolic disorders, hepatocyte transplantation can be an effective treatment. However, long-term function of transplanted hepatocytes following infusion has not been achieved due to insufficient numbers of hepatocytes reaching the liver cell plates caused by activation of the instant blood-mediated inflammatory reaction (IBMIR). Our aim was to determine if the natural immune modulator, alpha-1 antitrypsin (AAT), could improve engraftment of transplanted hepatocytes and investigate its mechanism of action. A tubing loop model was used to analyse activation of the IBMIR when human hepatocytes were in contact with ABO-matched blood and 4 mg/ml AAT. Platelet and white cell counts, complement and cytokine expression were analysed. To determine if AAT could improve short-term engraftment, female rats underwent tail vein injection of AAT (120 mg/kg) or water (control) prior to the intrasplenic transplantation of 2 × 107 male hepatocytes. At 48 h and 1 week, livers were collected for analysis. In our loop model, human hepatocytes elicited a significant drop in platelet count with thrombus formation compared to controls. Loops containing AAT and hepatocytes showed no platelet consumption and no thrombus formation. Further, AAT treatment resulted in reduced IL-1ß, IL-6 and IFN-γ and increased IL-1RA compared to untreated loops. In vivo, AAT significantly improved engraftment of rat hepatocytes compared to untreated at 48 h. AAT infusion may inhibit the IBMIR, thus improving short-term engraftment of donor hepatocytes and potentially improve the outcomes for patients with liver-based metabolic disease. KEY MESSAGES: • Alpha-1 antitrypsin (AAT) acts as an immune modulator to improve the efficacy of hepatocyte transplantation. • Treatment with AAT decreased thrombus formation and pro-inflammatory cytokine expression in a tubing loop model. • AAT significantly improved engraftment of donor hepatocytes within the first 48 h post transplantation.

15.
J Pediatr Gastroenterol Nutr ; 69(1): 102-107, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30908388

RESUMO

OBJECTIVES: Our objective was to test the hypothesis that children with end-stage chronic liver disease (ESCLD) are hypermetabolic when compared to healthy children, and that this hypermetabolism persists for at least 6 months after liver transplant. METHODS: Seventeen patients with end-stage chronic liver disease and 14 healthy controls had their resting energy expenditure measured (mREE) by indirect calorimetry. Weight, height, and body mass index were converted to standard deviation (SD) scores. Children older than 5 years had air displacement plethysmography and patients older than 5 years also had whole body dual-energy X-ray absorptiometry with characterization of fat mass (FM), fat-free mass (FFM), and bone-free fat free (lean) mass. RESULTS: When compared to the prediction equation 44% of the patients and 50% of the healthy controls were hypermetabolic. The younger patients (0-5 years) had a lower mREE than the healthy controls but were significantly lighter and shorter than their healthy counterparts. mREE correlated strongly for all children with age, weight, height, and FFM. There was a strong negative correlation between age and mREE/kg in both patients (rs = -0.94, P < 0.01) and controls (rs = -0.91, P < 0.01). Almost 84% of the variance in mREE was explained by age (P < 0.001). There were no significant differences between resting energy expenditure (REE)/FFM between the 2 groups. mREE/kg before liver transplant correlated with mREE/kg after transplant (Pearson r = 0.83, P < 0.01). CONCLUSIONS: REE mostly reflected the size of the child. The patients were not hypermetabolic when compared to the healthy children. The main determinant of REE/kg after transplant was REE/kg before transplant.

16.
J Hepatol ; 71(1): 71-77, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30876944

RESUMO

BACKGROUND & AIMS: In patients with biliary atresia (BA), the rate of native liver survival (NLS) to adulthood has been reported as 14-44% worldwide. Complications related to portal hypertension (PHT) and cholangitis are common in adulthood. For those requiring liver transplantation (LT), the timing can be challenging. The aim of this study was to identify variables that could predict whether young people with BA would require LT when they are >16 years of age. METHODS: This study was a single-centre retrospective analysis of 397 patients who underwent Kasai portoenterostomy (KP) between 1980-96 in the UK. After KP, 111/397 (28%) demonstrated NLS until 16 years of age. At final follow-up, 67 showed NLS when >16 years old (Group 1) and 22 required LT when >16 years old (Group 2). Laboratory, clinical and radiological parameters were collected for both groups at a median age of 16.06 years (13.6-17.4 years). RESULTS: The need for LT when >16 years old was associated with higher total bilirubin (hazard ratio 1.03, p = 0.019) and lower creatinine (hazard ratio 0.95, p = 0.040), at 16 years, on multivariate analysis. Receiver-operating characteristic curve analysis demonstrated that a total bilirubin level of ≥21 µmol/L at 16 years old (AUROC = 0.848) predicted the need for LT when >16 years old, with 85% sensitivity and 74% specificity. Cholangitis episode(s) during adolescence were associated with a 5-fold increased risk of needing LT when >16 years old. The presence of PHT or gastro-oesophageal varices in patients <16 years old was associated with a 7-fold and 8.6-fold increase in the risk of needing LT, respectively. CONCLUSIONS: BA in adulthood requires specialised management. Adult liver disease scoring models are not appropriate for this cohort. Bilirubin ≥21 µmol/L, PHT or gastro-oesophageal varices at 16 years, and cholangitis in adolescence, can predict the need for future LT in young people with BA. Low creatinine at 16 years also has potential prognostic value. LAY SUMMARY: Patients with biliary atresia commonly require liver transplantation before reaching adulthood. Those who reach adulthood with their own liver are still at risk of needing a transplant. This study aimed to identify tests that could help clinicians predict which patients with biliary atresia who reach the age of 16 without a transplant will require one in later life. The study found that the presence of bilirubin ≥21 µmol/L, lower creatinine levels, and a history of portal hypertension or gastro-oesophageal varices at 16 years, as well as cholangitis in adolescence, could predict the future likelihood of needing a liver transplant for young people with biliary atresia.

17.
J Clin Exp Hepatol ; 9(1): 74-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30765941

RESUMO

Clinical practice guidelines for Wilson's disease (WD) have been published by the American Association for the Study of Liver Diseases and European Association for the Study of the Liver in 2008 and 2012, respectively. Their focus was on the hepatic aspects of the disease. Recently, a position paper on pediatric WD was published by the European Society of Pediatric Gastroenterology Hepatology and Nutrition. A need was felt to harmonize guidelines for the hepatic, pediatric, and neurological aspects of the disease and contextualize them to the resource-constrained settings. Therefore, experts from national societies from India representing 3 disciplines, hepatology (Indian National Association for Study of the Liver), pediatric hepatology (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition), and neurology (Movement Disorders Society of India) got together to evolve fresh guidelines. A literature search on retrospective and prospective studies of WD using MEDLINE (PubMed) was performed. Members voted on each recommendation, using the nominal voting technique. The Grades of Recommendation, Assessment, Development and Evaluation system was used to determine the quality of evidence. Questions related to diagnostic tests, scoring system, and its modification to a version suitable for resource-constrained settings were posed. While ceruloplasmin and 24-h urine copper continue to be important, there is little role of serum copper and penicillamine challenge test in the diagnostic algorithm. A new scoring system - Modified Leipzig score has been suggested with extra points being added for family history and serum ceruloplasmin lower than 5 mg/dl. Liver dry copper estimation and penicillamine challenge test have been removed from the scoring system. Differences in pharmacological approach to neurological and hepatic disease and global monitoring scales have been included. Rising bilirubin and worsening encephalopathy are suggested as indicators predicting need for liver transplant but need to be validated. The clinical practice guidelines provide recommendations for a comprehensive management of WD which will be of value to all specialties.

18.
Pediatr Transplant ; 23(2): e13339, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30597734

RESUMO

OBJECTIVES: Acute-on-chronic liver failure (ACLF) is an acute decompensation of cirrhosis complicated by other organ failure and is associated with increased mortality and morbidity. ACLF has not been studied in children with biliary atresia (BA), which is the commonest indication for pediatric liver transplantation (LT) worldwide. This study aims to evaluate ACLF and outcomes in children with BA while awaiting deceased donor LT. METHODS: This was a subanalysis of the dataset from a prospective cohort study of patients aged 0-18 years who underwent portoenterostomy for BA and were listed for LT at King's College Hospital, London, between 1999 and 2003. Outcomes included the development of ACLF, mortality, and complications. RESULTS: Ninety-nine (41 male) children were included, and follow-up was 10 [6.0-15.0] years. A total of 20/99 children developed ACLF. ACLF was associated with increased mortality while awaiting LT (20% vs 4%; P = 0.03). There were no associations between biochemical parameters at listing and death. Increased bilirubin levels 3 months post-portoenterostomy was predictive of development of ACLF (AUROC = 0.72, P < 0.01). Age at LT and time on the waiting list in the ACLF subgroup were both lower compared to the non-ACLF group (P > 0.05). Sepsis and gastrointestinal bleeding were the commonest precipitants of ACLF. Complications included ascites, hepatic encephalopathy, and hepatorenal syndrome; the ACLF subgroup required multisystem support and longer intensive care unit stay. CONCLUSIONS: ACLF in children with BA awaiting deceased donor LT carries increased mortality and morbidity. This warrants stratification of patients for earlier wait-listing and prioritization for LT.


Assuntos
Insuficiência Hepática Crônica Agudizada/etiologia , Atresia Biliar/complicações , Transplante de Fígado , Listas de Espera , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/epidemiologia , Adolescente , Atresia Biliar/mortalidade , Atresia Biliar/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Portoenterostomia Hepática , Prognóstico , Estudos Prospectivos , Fatores de Risco
20.
Transplantation ; 103(1): 68-70, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30335699

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has now become a common cause of chronic liver disease in children; however, unlike adults liver transplantation is rarely required as treatment. It is important that in children presenting with NAFLD, secondary causes of fatty liver particularly inherited metabolic defects should be excluded. METHODS: A pediatric working group comprised of 3 hepatologists and a liver transplant surgeon was tasked with a set of questions to address the current state of evidence and knowledge about NAFLD in children with particular focus on liver transplantation. A systematic review of the English literature regarding pediatric NAFLD (from birth to 18 years of age) published in the last 2 decades (2000-2018) was carried out. The evidence was evaluated by the subgroup members and further discussed with the wider workshop faculty leading to the recommendations for best practice. RESULTS: Given the paucity of literature on the subject good quality of evidence was only available on risk factors for NAFLD and medical treatment where the group could make recommendation with high/moderate strength. The evidence on natural history and indications for liver transplantation was poor hence group could not make any recommendations. CONCLUSIONS: Based on the existing literature and subgroups, collective experience NAFLD unlike in adults is a very rare indication for liver transplantation in children. No definitive recommendations could be made about the natural history, indications, and outcome of liver transplantation for NAFLD in children.


Assuntos
Conferências de Consenso como Assunto , Doença Hepática Terminal/cirurgia , Transplante de Fígado/normas , Hepatopatia Gordurosa não Alcoólica/cirurgia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Progressão da Doença , Doença Hepática Terminal/patologia , Medicina Baseada em Evidências/normas , Humanos , Lactente , Recém-Nascido , Hepatopatia Gordurosa não Alcoólica/patologia , Fatores de Risco , Resultado do Tratamento
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