Liver PDFF estimation using a multi-decoder water-fat separation neural network with a reduced number of echoes.

OBJECTIVE: To accurately estimate liver PDFF from chemical shift-encoded (CSE) MRI using a deep learning (DL)-based Multi-Decoder Water-Fat separation Network (MDWF-Net), that operates over complex-valued CSE-MR images with only 3 echoes. METHODS: The proposed MDWF-Net and a U-Net model were independently trained using the first 3 echoes of MRI data from 134 subjects, acquired with conventional 6-echoes abdomen protocol at 1.5 T. Resulting models were then evaluated using unseen CSE-MR images obtained from 14 subjects that were acquired with a 3-echoes CSE-MR pulse sequence with a shorter duration compared to the standard protocol. Resulting PDFF maps were qualitatively assessed by two radiologists, and quantitatively assessed at two corresponding liver ROIs, using Bland Altman and regression analysis for mean values, and ANOVA testing for standard deviation (STD) (significance level: .05). A 6-echo graph cut was considered ground truth. RESULTS: Assessment of radiologists demonstrated that, unlike U-Net, MDWF-Net had a similar quality to the ground truth, despite it considered half of the information. Regarding PDFF mean values at ROIs, MDWF-Net showed a better agreement with ground truth (regression slope = 0.94, R2 = 0.97) than U-Net (regression slope = 0.86, R2 = 0.93). Moreover, ANOVA post hoc analysis of STDs showed a statistical difference between graph cuts and U-Net (p < .05), unlike MDWF-Net (p = .53). CONCLUSION: MDWF-Net showed a liver PDFF accuracy comparable to the reference graph cut method, using only 3 echoes and thus allowing a reduction in the acquisition times. CLINICAL RELEVANCE STATEMENT: We have prospectively validated that the use of a multi-decoder convolutional neural network to estimate liver proton density fat fraction allows a significant reduction in MR scan time by reducing the number of echoes required by 50%. KEY POINTS: • Novel water-fat separation neural network allows for liver PDFF estimation by using multi-echo MR images with a reduced number of echoes. • Prospective single-center validation demonstrated that echo reduction leads to a significant shortening of the scan time, compared to standard 6-echo acquisition. • Qualitative and quantitative performance of the proposed method showed no significant differences in PDFF estimation with respect to the reference technique.

Acute Liver Injury Among Pediatric Liver Transplantation Recipients With Coronavirus Disease 2019: An International Collaborative Study.

ABSTRACT: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic. The occurrence of acute liver injury (ALI) has been reported in liver transplant (LT) recipients; however, the findings on children remain controversial. This is the first extensive, worldwide report on the impact of COVID-19 on pediatric LT recipients. Our online survey reported 110 pediatric LT recipients with severe acute respiratory syndrome coronavirus 2 infection. Of these, 37 were symptomatic and 20 out of them (54%) had complicated COVID-19, which included ALI and acute liver graft rejection. No mortality was reported. Pediatric LT recipients who had undergone transplantation less than 6 months before contracting COVID-19 had a greater number of hospital admissions and a higher ALI frequency (P = 0.013 and P = 0.033, respectively) than those who had undergone transplantation more than 6 months prior. Our study found that COVID-19 cases among pediatric LT recipients demonstrated a high complication rate. We propose that these patients must be followed up strictly.

Beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

BACKGROUND: Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including haemorrhage from oesophageal and gastrointestinal varices. Variceal haemorrhage commonly occurs in children with chronic liver disease or portal vein thrombosis. Therefore, prevention is important. Band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding in children. However, primary prophylaxis is not the current standard of care in paediatric patients because it is unknown whether those treatments are of benefit or harm when used for primary prophylaxis in children and adolescents. OBJECTIVES: To determine the benefits and harms of beta-blockers compared with placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, LILACS, and Science Citation Index Expanded (April 2020). We screened the reference lists of the retrieved publications and manually searched the main paediatric gastroenterology and hepatology conference (NASPGHAN and ESPGHAN) abstract books from 2008 to December 2019. We searched clinicaltrials.gov, the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) for ongoing clinical trials. We imposed no language or document type restrictions on our search. SELECTION CRITERIA: We planned to include randomised clinical trials, irrespective of blinding, language, or publication status to assess benefits and harms. We included observational studies, retrieved with the searches for randomised clinical trials, for a narrative report of harm. DATA COLLECTION AND ANALYSIS: We planned to summarise data from randomised clinical trials by standard Cochrane methodologies. We planned to asses risk of bias and use GRADE to assess the certainty of evidence. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and health-related quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We planned to use intention-to-treat principle. We planned to analyse data with RevMan Analysis. MAIN RESULTS: We found no randomised clinical trials that assessed beta-blockers compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. We found four observational studies that reported on harms. As a systematic search for observational studies was not planned, we only listed the reported harms in a table. AUTHORS' CONCLUSIONS: Randomised clinical trials assessing the benefits or harms of beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are lacking. Therefore, trials with adequate power and proper design, assessing the benefits and harms of beta-blockers versus placebo on patient-relevant clinical outcomes, such as mortality, quality of life, failure to control variceal bleeding, and adverse events are needed. Unless such trials are conducted and the results become published, we cannot make any conclusions regarding the benefits or harms of the two interventions.

Band ligation versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis.

BACKGROUND: Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal and gastrointestinal varices. Variceal bleeding commonly occurs in children and adolescents with chronic liver disease or portal vein thrombosis. Prevention is, therefore, important. Randomised clinical trials have shown that non-selective beta-blockers and endoscopic variceal band ligation decrease the incidence of variceal bleeding in adults. In children and adolescents, band ligation, beta-blockers, and sclerotherapy have been proposed as primary prophylaxis alternatives for oesophageal variceal bleeding. However, it is unknown whether these interventions are of benefit or harm when used for primary prophylaxis in children and adolescents. OBJECTIVES: To assess the benefits and harms of band ligation compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, and two other databases (April 2020). We scrutinised the reference lists of the retrieved publications, and we also handsearched abstract books of the two main paediatric gastroenterology and hepatology conferences from January 2008 to December 2019. We also searched clinicaltrials.gov, the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) for ongoing clinical trials. We imposed no language or document type restrictions on our search. SELECTION CRITERIA: We aimed to include randomised clinical trials irrespective of blinding, language, or publication status, to assess the benefits and harms of band ligation versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. If the search for randomised clinical trials retrieved quasi-randomised and other observational studies, then we read them through to extract information on harm. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to perform this systematic review. We used GRADE to assess the certainty of evidence for each outcome. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We used the intention-to-treat principle. We analysed data using Review Manager 5. MAIN RESULTS: One conference abstract, describing a feasibility multi-centre randomised clinical trial, fulfilled our review inclusion criteria. We judged the trial at overall high risk of bias. This trial was conducted in three hospital centres in the United Kingdom. The aim of the trial was to determine the feasibility and safety of further larger randomised clinical trials of prophylactic band ligation versus no active treatment in children with portal hypertension and large oesophageal varices. Twelve children received prophylactic band ligation and 10 children received no active treatment. There was no information on the age of the children included, or about the diagnosis of any child included. All children were followed up for at least six months. Mortality was 8% (1/12) in the band ligation group versus 0% (0/10) in the no active intervention group (risk ratio (RR) 2.54, 95% confidence interval (CI) 0.11 to 56.25; very low certainty of evidence). The abstract did not report when the death occurred, but we assume it happened between the six-month follow-up and one year. No child (0%) in the band ligation group developed adverse events (RR 0.28, 95% CI 0.01 to 6.25; very low certainty of evidence) but one child out of 10 (10%) in the no active intervention group developed idiopathic thrombocytopaenic purpura. One child out of 12 (8%) in the band ligation group underwent liver transplantation versus none in the no active intervention group (0%) (RR 2.54, 95% CI 0.11 to 56.25; very low certainty of evidence). The trial reported no other serious adverse events or liver-related morbidity. Quality of life was not reported. Oesophageal variceal bleeding occurred in 8% (1/12) of the children in the band ligation group versus 30% (3/10) of the children in the no active intervention group (RR 0.28, 95% CI 0.03 to 2.27; very low certainty of evidence). No adverse events considered non-serious were reported. Two children were lost to follow-up by one-year. Ten children in total completed the trial at two-year follow-up. There was no information on funding.  We found two observational studies on endoscopic variceal ligation when searching for randomised trials. One found no harm, and the other reported E nterobacter cloacae septicaemia in one child and mild, transient, upper oesophageal sphincter stenosis in another. We did not assess these studies for risk of bias. We did not find any ongoing randomised clinical trials of interest to our review. AUTHORS' CONCLUSIONS: The evidence, obtained from only one feasibility randomised clinical trial at high risk of bias, is very scanty. It is very uncertain about whether prophylactic band ligation versus sham or no (active) intervention may affect mortality, serious adverse events and liver-related morbidity, or oesophageal variceal bleeding in children and adolescents with portal hypertension and large oesophageal varices. We have no data on quality of life. No adverse events considered non-serious were reported. The results presented in the trial need to be interpreted with caution. In addition, the highly limited data cover only part of our research question; namely, children with portal hypertension and large oesophageal varices. Data on children with portal vein thrombosis are lacking. Larger randomised clinical trials assessing the benefits and harms of band ligation compared with sham treatment for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis are needed. The trials should include important clinical outcomes such as death, quality of life, failure to control bleeding, and adverse events.

Early Obesity: Risk Factor for Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), defined as fat accumulation greater than 5% in hepatocytes, may progress to fibrosis or cirrhosis later in life. NAFLD prevalence in adolescents has increased significantly in direct relation with obesity prevalence. Fatty liver has become the most frequent indication for liver transplantation in adults. OBJECTIVE: The aim of the study was to identify anthropometric variables during the first 10 years of life associated to the risk of developing NAFLD in adolescence. METHODS: Longitudinal cohort study 'Growth and Obesity Chilean Cohort Study' (GOCS) consisting of 513 children born in 2002 to 2003, with yearly anthropometric data collected over a 10-year period. The presence of intrahepatic fat in the livers of subjects 14 to 16 years of age was determined using abdominal ultrasound. In addition, elastography was performed on all participants with ultrasound evidence of NAFLD. RESULTS: 9.7% of the participants presented findings compatible with NAFLD. After 2 years of age, obesity significantly and progressively increased the probability of NAFLD occurrence in adolescence. Obesity at 5 years of age was associated with the highest OR for NAFLD, reaching values of 8.91 (95% CI 3.03-16.11). Among participants with NAFLD, those with altered liver elasticity (≥7 kPa) had greater weight, BMI z-score, waist and hip circumference, and altered liver enzymes (P < 0.05). CONCLUSION: The risk of developing NAFLD in adolescence increases progressively with early obesity starting at age 2 years.

Band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

BACKGROUND: Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including haemorrhage from oesophageal and gastrointestinal varices. Variceal haemorrhage commonly occurs in children with chronic liver disease or portal vein obstruction. Prevention is therefore important. In adults, numerous randomised clinical trials have demonstrated benefits of non-selective beta-blockers and endoscopic variceal ligation as primary prevention in decreasing the risk of variceal haemorrhage. In children, band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding. However, primary prophylaxis is not the current standard of care in children because it is unknown whether those treatments are of benefit or cause harm when used for primary prophylaxis of oesophageal variceal bleeding in children and adolescents. OBJECTIVES: To determine the benefits and harms of band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, LILACS, and Science Citation Index Expanded (27 April 2020). We scrutinised the reference lists of retrieved publications, and performed a manual search from the main paediatric gastroenterology and hepatology conferences (NASPGHAN and ESPGHAN) abstract books from 2008 to 2019. We searched ClinicalTrials.gov, FDA, EMA, and WHO for ongoing clinical trials. There were no language or document type restrictions. SELECTION CRITERIA: We planned to include randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. If the search for randomised clinical trials retrieved quasi-randomised and observational studies, then we read them through to extract information on harms. DATA COLLECTION AND ANALYSIS: We planned to summarise data from randomised clinical trials by standard Cochrane methodologies. We planned to assess risk of bias and use GRADE to assess the certainty of evidence per outcome. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We planned to analyse data with intention-to-treat. We planned to use Review Manager 5 to analyse the data. MAIN RESULTS: We found no randomised clinical trials assessing band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. AUTHORS' CONCLUSIONS: Randomised clinical trials assessing the benefits or harms of band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are lacking. Therefore, trials with adequate power and proper design, assessing the benefits and harms of band ligation versus sclerotherapy on patient-relevant clinical outcomes such as mortality, quality of life, failure to control variceal bleeding, and adverse events are needed. Unless such trials are conducted and the results become published, we cannot make any conclusions regarding the benefits or harms of these two interventions.

Sclerotherapy versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

BACKGROUND: Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal and gastrointestinal varices. Variceal bleeding commonly occurs in children with chronic liver disease or portal vein obstruction. Therefore, prevention is important. Primary prophylaxis of variceal bleeding in adults is the established standard of care because of the results of numerous randomised clinical trials demonstrating the efficacy of non-selective beta-blockers or endoscopic variceal ligation in decreasing the incidence of variceal bleeding. In children, band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding. However, it is unknown whether those treatments are of benefit or harm when used for primary prophylaxis in children. OBJECTIVES: To assess the benefits and harms of sclerotherapy compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase Elsevier, and two other registers in February 2019. We scrutinised the reference lists of the retrieved publications, and performed a manual search of the main paediatric gastroenterology and hepatology conference (NASPGHAN and ESPGHAN) abstracts from January 2008 to December 2018. We searched four registries for ongoing clinical trials. There were no language or document type restrictions. SELECTION CRITERIA: We included randomised clinical trials irrespective of blinding, language, or publication status assessing sclerotherapy versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to perform this systematic review. We used the intention-to-treat principle to analyse outcome data, and GRADE to assess the certainty of evidence per outcome. MAIN RESULTS: We found only one randomised clinical trial that fulfilled our inclusion criteria. The trial was at high risk of bias. The trial included 108 Brazilian children with median age of 4.3 years (range 11 months to 13 years). Fifty-six children were randomised to prophylactic sclerotherapy (ethanolamine oleate 2%) and 52 children to no intervention (control). Children were followed up for a median of 4.5 years. Eight children (six from the sclerotherapy group versus two from the control group) dropped out before the end of the trial. The follow-up was from 18 months to eight years. Mortality was 16% (9/56 children) in the sclerotherapy group versus 15% (8/52 children) in the control group (risk ration (RR) 1.04, 95% confidence interval (CI) 0.44 to 2.50; very low-certainty evidence). Upper gastrointestinal bleeding occurred in 21% (12/56) of the children in the sclerotherapy group versus 46% (24/52) in the control group (RR 0.46, 95% CI 0.26 to 0.83; very low-certainty evidence). There were more children with congestive hypertensive gastropathy in the sclerotherapy group than in the control group (14% (8/56) versus 6% (3/52); RR 2.48, 95% CI 0.69 to 8.84; very low-certainty evidence). The incidence of gastric varices was similar between the sclerotherapy group and the control group (11% (6/56) versus 10% (5/52); RR 1.11, 95% CI 0.36 to 3.43; very low-certainty evidence). The incidence of bleeding from gastric varices was higher in the sclerotherapy group than in the control group (4% (3/56) versus 0% (0/52); RR 6.51, 95% CI 0.34 to 123.06; very low-certainty evidence). The study did not assess health-related quality of life. Oesophageal variceal bleeding occurred in 5% (3/56) of the children in the sclerotherapy group versus 40% (21/52) of the children in the control group (RR 0.13, 95% CI 0.04 to 0.42; very low-certainty evidence). The most prevalent complications (defined as non-serious) were pain and fever after the procedure, which promptly resolved with analgesics. However, numerical data on the frequency of these adverse events and their occurrences in the two groups were lacking. No funding information was provided. We found no ongoing trials. AUTHORS' CONCLUSIONS: The evidence, obtained from one randomised clinical trial at high risk of bias, is very uncertain on whether sclerotherapy has an influence on mortality and if it may decrease first upper gastrointestinal or oesophageal variceal bleeding in children. The evidence is very uncertain on whether sclerotherapy has an influence on congestive hypertensive gastropathy, incidence on gastric varices, and incidence of bleeding from gastric varices. Health-related quality of life was not measured. There were no serious events caused by sclerotherapy, and analysis of non-serious adverse events could not be performed due to lack of numerical data. The GRADE assessment of each outcome showed a very low-certainty evidence. The results of the trial need to be interpreted with caution. Larger randomised clinical trials, following the SPIRIT and CONSORT statements, assessing the benefits and harms of sclerotherapy compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are needed. The trials should include important clinical outcomes such as death, failure to control bleeding, and adverse events.

Sclerotherapy versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis.

BACKGROUND: Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal and gastrointestinal varices. Variceal bleeding commonly occurs in children with chronic liver disease or portal vein obstruction. Prevention is therefore important. Primary prophylaxis of variceal bleeding in adults is the established standard of care because of the results of numerous randomised clinical trials demonstrating the efficacy of non-selective beta-blockers or endoscopic variceal ligation in decreasing the incidence of variceal bleeding. However, sclerotherapy is the only endoscopic prophylactic option currently available in infants weighing less than 10 kg of bodyweight due to the size of the endoscopic ligator. OBJECTIVES: To assess the benefits and harms of sclerotherapy versus any type of beta-blocker for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase Elsevier, LILACS (Bireme), and Science Citation Index Expanded (Web of Science) in February 2019. We scrutinised the reference lists of the retrieved publications and performed a manual search from the main paediatric gastroenterology and hepatology conferences (NASPGHAN and ESPGHAN) abstract books from January 2008 to December 2018. We searched ClinicalTrials.gov, FDA, EMA, and WHO, for ongoing clinical trials. There were no language or document type restrictions. SELECTION CRITERIA: We planned to include randomised clinical trials irrespective of blinding, language, or publication status, assessing sclerotherapy versus any type of beta-blocker for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. We planned to include quasi-randomised and other observational studies retrieved with the searches for randomised clinical trials for report of harm. DATA COLLECTION AND ANALYSIS: We planned to collect and summarise data from randomised clinical trials as described in our protocol, using standard Cochrane methodologies. MAIN RESULTS: We found no randomised clinical trials assessing sclerotherapy versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. AUTHORS' CONCLUSIONS: Randomised clinical trials assessing the benefits or harms of sclerotherapy versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis are lacking. Therefore, trials with adequate power and proper design, assessing the benefits and harms of sclerotherapy versus beta-blockers on patient-relevant clinical outcomes such as mortality, failure to control bleeding, and adverse events are needed. Unless such trials are conducted and the results become published, we cannot make any conclusions regarding the benefits or harms of the two interventions.

[Current situation of pediatric liver transplantation in Chile. Inequities associated with the MELD/PELD prioritization system]. / Situación actual del trasplante hepático pediátrico por hepatopatías crónicas en Chile: Inequidades asociadas a la priorización por sistema MELD/PELD.

BACKGROUND: The Chilean allocation system for liver transplantation (LT) uses the MELD/PELD score to prioritize candidates on the waiting list. AIM: To assess if the Chilean allocation system for LT is equitable for pediatric candidates compared to their adult counterparts. MATERIAL AND METHODS: We used the Public Health Institute's registry between October 2011 and December 2017. We analyzed candidates with chronic hepatic diseases listed for LT. The primary outcome was the cadaveric liver transplantation (CLT) rate. Secondary outcomes were death or disease progression in the waiting list and living donor liver transplant (LDLT) rate. RESULTS: We analyzed 122 pediatric and 735 adult candidates. Forty one percent of pediatric candidates obtained a CLT compared to 48% of adults (p = NS). Among patients aged under two years of age, the access to CLT on the waiting list there was 28% of CLT, compared to 48% in adults (p = 0.001). Fifty-seven percent of candidates aged under two years were listed for cholestatic diseases, obtaining a CLT in 18% and requiring a LDLT in 49%. The median time in the waiting list for CLT was 5.9 months in pediatric candidates and 5.1 in adults, while the median time to death in the waiting list was 2.8 and 5.6 months, respectively. The mortality rate at one year in candidates under two years old was 38.1% compared to 32.5% in adults. CONCLUSIONS: Pediatric candidates with chronic liver diseases, especially under two years of age, have greater access difficulties to CLT than adults. Half of the pediatric candidates die on the waiting list before three months. The mortality among candidates under two years of age in the waiting list is excessively high.

[Adaptation to the reality of Latin America of the NASPGHAN/ESPGHAN 2016 Guidelines on the Diagnosis, Prevention and Treatment of Helicobacter pylori Infection in Pediatrics]. / Adaptación a la realidad de Latinoamérica de la Guía Clínica NASPGHAN/ESPGHAN 2016 sobre Diagnóstico, Prevención y Tratamiento de Infección por Helicobacter pylori en Pediatría.

INTRODUCTION: The latest joint H. pylori NASPGHAN and ESPGHAN clinical guidelines published in 2016, contain 20 statements that have been questioned in practice regarding their applicability in Latin America (LA); in particular in relation to gastric cancer prevention. METHODS: We conduc ted a critical analysis of the literature, with special emphasis on LA data and established the level of evidence and level of recommendation of the most controversial claims in the Joint Guidelines. Two rounds of voting were conducted according to the Delphi consensus technique and a Likert scale (from 0 to 4) was used to establish the "degree of agreement" among a panel of SLAGHNP ex perts. RESULTS: There are few studies regarding diagnosis, treatment effectiveness and susceptibility to antibiotics of H. pylori in pediatric patients of LA. Based on these studies, extrapolations from adult studies, and the clinical experience of the participating expert panel, the following recom mendations are made. We recommend taking biopsies for rapid urease and histology testing (and samples for culture or molecular techniques, when available) during upper endoscopy only if in case of confirmed H. pylori infection, eradication treatment will be indicated. We recommend that selected regional centers conduct antimicrobial sensitivity/resistance studies for H. pylori and thus act as reference centers for all LA. In case of failure to eradicate H. pylori with first-line treatment, we recommend empirical treatment with quadruple therapy with proton pump inhibitor, amoxi cillin, metronidazole, and bismuth for 14 days. In case of eradication failure with the second line scheme, it is recommended to indicate an individualized treatment considering the age of the pa tient, the previously indicated scheme and the antibiotic sensitivity of the strain, which implies performing a new endoscopy with sample extraction for culture and antibiogram or molecular resistance study. In symptomatic children referred to endoscopy who have a history of first or se cond degree family members with gastric cancer, it is recommended to consider the search for H. pylori by direct technique during endoscopy (and eradicate it when detected). CONCLUSIONS: The evidence supports most of the general concepts of the NASPGHAN/ESPGHAN 2016 Guidelines, but it is necessary to adapt them to the reality of LA, with emphasis on the development of regional centers for the study of antibiotic sensitivity and to improve the correct selection of the eradication treatment. In symptomatic children with a family history of first or second degree gastric cancer, the search for and eradication of H. pylori should be considered.

Portal Angiogenesis in Chronic Liver Disease Patients Correlates with Portal Pressure and Collateral Formation.

BACKGROUND/AIMS: One hallmark of chronic liver disease in patients with portal hypertension is the formation of portal-systemic collaterals in which angiogenesis has a fundamental role. We studied patients with chronic liver disease undergoing liver transplantation to correlate levels of circulating angiogenic factors in portal and peripheral circulation with portal pressure and portal-systemic collaterals. METHODS: Sixteen patients who underwent liver transplantation were enrolled. During transplant surgery, we determined portal venous pressure and portal-systemic collateral formation. We determined angiogenics mediator levels in systemic and portal plasma. Peripheral plasma from healthy donors was measured as controls. RESULTS: Vascular endothelial growth factor (VEGF)-R1 and 2, Ang-1 and 2, Tie2, FGF- 1 and 2, CD163, PDGFR-ß, PDGFsRα, PDGF-AB and BB, CD163, TGF-ß VASH-1 levels were significantly different in the controls in comparison to cases. Significantly decreased portal venous levels of Ang-1, FGF-1, PDGF-AB/BB, and CC were observed in patients with higher portal pressure. Peripheral VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation. While peripheral VEGF-R1 was higher in patients with severe collateral formation. For portal circulation, VEGF, Ang-1, -pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation Conclusions: Angiogenesis factors correlated with portal pressure and collateral formation and different patterns of circulating angiogenesis mediators were found in peripheral and portal blood of patients with chronic liver disease. These results support the importance of angiogenic pathways in cirrhosis and portal hypertension and highlight areas for further study to identify clinically useful noninvasive markers of portal pressure and collateral formation.

Band ligation versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

BACKGROUND: Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including haemorrhage from oesophageal and gastrointestinal varices. Variceal haemorrhage commonly occurs in children with chronic liver disease or portal vein obstruction. Prevention is therefore important. Following numerous randomised clinical trials demonstrating efficacy of non-selective beta-blockers and endoscopic variceal ligation in decreasing the incidence of variceal haemorrhage, primary prophylaxis of variceal haemorrhage in adults has become the established standard of care. Hence, band ligation and beta-blockers have been proposed to be used as primary prophylaxis of oesophageal variceal bleeding in children. OBJECTIVES: To determine the benefits and harms of band ligation compared with any type of beta-blocker for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (February 2019), CENTRAL (December 2018), PubMed (December 2018), Embase Ovid (December 2018), LILACS (Bireme; January 2019), and Science Citation Index Expanded (Web of Science; December 2018). We scrutinised the reference lists of the retrieved publications and performed a manual search from the main paediatric gastroenterology and hepatology conferences (NASPGHAN and ESPGHAN) abstract books from 2009 to 2018. We searched ClinicalTrials.gov for ongoing clinical trials. There were no language or document type restrictions. SELECTION CRITERIA: We planned to include randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. We planned to also include quasi-randomised and other observational studies retrieved with the searches for randomised clinical trials for report of harm. DATA COLLECTION AND ANALYSIS: We planned to summarise data from randomised clinical trials using standard Cochrane methodologies. MAIN RESULTS: We found no randomised clinical trials assessing band ligation versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. AUTHORS' CONCLUSIONS: Randomised clinical trials assessing the benefits or harms of band ligation versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are lacking. There is a need for well-designed, adequately powered randomised clinical trials to assess the benefits and harms of band ligation versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. Those randomised clinical trials should include patient-relevant clinical outcomes such as mortality, failure to control bleeding, and adverse events.

[Liver transplantation: development, learning curve and results after the first 300 cases]. / Trasplante hepático: evolución, curva de aprendizaje y resultados después de los primeros 300 casos.

BACKGROUND: Liver transplantation (LT) is an option for people with liver failure who cannot be cured with other therapies and for some people with liver cancer. AIM: To describe, and analyze the first 300 LT clinical results, and to establish our learning curve. MATERIAL AND METHODS: Retrospective cohort study with data obtained from a prospectively collected LT Program database. We included all LT performed at a single center from March 1994 to September 2017. The database gathered demographics, diagnosis, indications for LT, surgical aspects and postoperative courses. We constructed a cumulative summation test for learning curve (LC-CUSUM) using 30-day post-LT mortality. Mortality at 30 days, and actuarial 1-, and 5-year survival rate were analyzed. RESULTS: A total of 281 patients aged 54 (0-71) years (129 women) underwent 300 LT. Ten percent of patients were younger than 18 years old. The first, second and third indications for LT were non-alcoholic steatohepatitis, chronic autoimmune hepatitis and alcoholic liver cirrhosis, respectively. Acute liver failure was the LT indication in 51 cases (17%). The overall complication rate was 71%. Infectious and biliary complications were the most common of them (47 and 31% respectively). The LC-CUSUM curve shows that the first 30 patients corresponded to the learning curve. The peri-operative mortality was 8%. Actuarial 1 and 5-year survival rates were 82 and 71.4%, respectively. CONCLUSIONS: Outcome improvement of a LT program depends on the accumulation of experience after the first 30 transplants and the peri-operative mortality directly impacted long-term survival.

[Diagnostic validity of fecal occult blood test in infants with food protein-induced allergic proctocolitis]. / Estudio de validez diagnóstica de la prueba de hemorragia oculta fecal en lactantes con proctocolitis alérgica inducida por proteína alimentaria.

INTRODUCTION: Food protein-induced allergic proctocolitis (FPIAP) is the most frequent presenta tion of non-IgE mediated food allergy (FA). The diagnosis is made by oral food challenge, however, non-invasive diagnostic tests are not available. In Chile, the fecal occult blood test (FOBT) is fre quently used to confirm FPIAP, however, there are no studies that support this practice. OBJECTIVE: To establish the diagnostic validity of FOBT in the evaluation of infants with FPIAP. PATIENTS AND METHOD: Case-control study with prospective recruitment of infants with rectal bleeding and suspicion of FPIAP, and controls were healthy infants, in whom the FOBT was conducted. All cases underwent an elimination diet, after which the diagnosis of FPIAP was confirmed by oral food cha llenge. RESULTS: 25 cases and 29 controls were included without significant differences in age, gen der, type of delivery, feeding, and maternal age. The cases had higher rates of allergic comorbidities, medication use, and family history of allergy. The FOBT was positive in 84% of cases and in 34% of controls (p < 0.001). The sensitivity of the FOBT for the diagnosis of FPIAP was 84%, specificity was 66%, positive predictive value 68%, and the negative predictive value 83%. The area under the ROC curve was 0.75 (CI 95% 0.61-0.88). CONCLUSIONS: Although the FOBT has an adequate sensitivity to diagnose FPIAP in infants with rectal bleeding, this test had abnormal results in more than a third of healthy infants. Therefore, the routine use of FOBT is not recommended for the diagnosis of FPIAP.

Platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices in people with chronic liver disease or portal vein thrombosis.

BACKGROUND: Current guidelines recommend screening of people with oesophageal varices via oesophago-gastro-duodenoscopy at the time of diagnosis of hepatic cirrhosis. This requires that people repeatedly undergo unpleasant invasive procedures with their attendant risks, although half of these people have no identifiable oesophageal varices 10 years after the initial diagnosis of cirrhosis. Platelet count, spleen length, and platelet count-to-spleen length ratio are non-invasive tests proposed as triage tests for the diagnosis of oesophageal varices. OBJECTIVES: Primary objectives To determine the diagnostic accuracy of platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices of any size in paediatric or adult patients with chronic liver disease or portal vein thrombosis, irrespective of aetiology. To investigate the accuracy of these non-invasive tests as triage or replacement of oesophago-gastro-duodenoscopy. Secondary objectives To compare the diagnostic accuracy of these same tests for the diagnosis of high-risk oesophageal varices in paediatric or adult patients with chronic liver disease or portal vein thrombosis, irrespective of aetiology.We aimed to perform pair-wise comparisons between the three index tests, while considering predefined cut-off values.We investigated sources of heterogeneity. SEARCH METHODS: The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register, the Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), and Science Citation Index - Expanded (Web of Science) (14 June 2016). We applied no language or document-type restrictions. SELECTION CRITERIA: Studies evaluating the diagnostic accuracy of platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices via oesophago-gastro-duodenoscopy as the reference standard in children or adults of any age with chronic liver disease or portal vein thrombosis, who did not have variceal bleeding. DATA COLLECTION AND ANALYSIS: Standard Cochrane methods as outlined in the Cochrane Handbook for Diagnostic Test of Accuracy Reviews. MAIN RESULTS: We included 71 studies, 67 of which enrolled only adults and four only children. All included studies were cross-sectional and were undertaken at a tertiary care centre. Eight studies reported study results in abstracts or letters. We considered all but one of the included studies to be at high risk of bias. We had major concerns about defining the cut-off value for the three index tests; most included studies derived the best cut-off values a posteriori, thus overestimating accuracy; 16 studies were designed to validate the 909 (n/mm3)/mm cut-off value for platelet count-to-spleen length ratio. Enrolment of participants was not consecutive in six studies and was unclear in 31 studies. Thirty-four studies assessed enrolment consecutively. Eleven studies excluded some included participants from the analyses, and in only one study, the time interval between index tests and the reference standard was longer than three months. Diagnosis of varices of any size. Platelet count showed sensitivity of 0.71 (95% confidence interval (CI) 0.63 to 0.77) and specificity of 0.80 (95% CI 0.69 to 0.88) (cut-off value of around 150,000/mm3 from 140,000 to 150,000/mm3; 10 studies, 2054 participants). When examining potential sources of heterogeneity, we found that of all predefined factors, only aetiology had a role: studies including participants with chronic hepatitis C reported different results when compared with studies including participants with mixed aetiologies (P = 0.036). Spleen length showed sensitivity of 0.85 (95% CI 0.75 to 0.91) and specificity of 0.54 (95% CI 0.46 to 0.62) (cut-off values of around 110 mm, from 110 to 112.5 mm; 13 studies, 1489 participants). Summary estimates for detection of varices of any size showed sensitivity of 0.93 (95% CI 0.83 to 0.97) and specificity of 0.84 (95% CI 0.75 to 0.91) in 17 studies, and 2637 participants had a cut-off value for platelet count-to-spleen length ratio of 909 (n/mm3)/mm. We found no effect of predefined sources of heterogeneity. An overall indirect comparison of the HSROCs of the three index tests showed that platelet count-to-spleen length ratio was the most accurate index test when compared with platelet count (P < 0.001) and spleen length (P < 0.001). Diagnosis of varices at high risk of bleeding. Platelet count showed sensitivity of 0.80 (95% CI 0.73 to 0.85) and specificity of 0.68 (95% CI 0.57 to 0.77) (cut-off value of around 150,000/mm3 from 140,000 to 160,000/mm3; seven studies, 1671 participants). For spleen length, we obtained only a summary ROC curve as we found no common cut-off between studies (six studies, 883 participants). Platelet count-to-spleen length ratio showed sensitivity of 0.85 (95% CI 0.72 to 0.93) and specificity of 0.66 (95% CI 0.52 to 0.77) (cut-off value of around 909 (n/mm3)/mm; from 897 to 921 (n/mm3)/mm; seven studies, 642 participants). An overall indirect comparison of the HSROCs of the three index tests showed that platelet count-to-spleen length ratio was the most accurate index test when compared with platelet count (P = 0.003) and spleen length (P < 0.001). DIagnosis of varices of any size in children. We found four studies including 277 children with different liver diseases and or portal vein thrombosis. Platelet count showed sensitivity of 0.71 (95% CI 0.60 to 0.80) and specificity of 0.83 (95% CI 0.70 to 0.91) (cut-off value of around 115,000/mm3; four studies, 277 participants). Platelet count-to-spleen length z-score ratio showed sensitivity of 0.74 (95% CI 0.65 to 0.81) and specificity of 0.64 (95% CI 0.36 to 0.84) (cut-off value of 25; two studies, 197 participants). AUTHORS' CONCLUSIONS: Platelet count-to-spleen length ratio could be used to stratify the risk of oesophageal varices. This test can be used as a triage test before endoscopy, thus ruling out adults without varices. In the case of a ratio > 909 (n/mm3)/mm, the presence of oesophageal varices of any size can be excluded and only 7% of adults with varices of any size would be missed, allowing investigators to spare the number of oesophago-gastro-duodenoscopy examinations. This test is not accurate enough for identification of oesophageal varices at high risk of bleeding that require primary prophylaxis. Future studies should assess the diagnostic accuracy of this test in specific subgroups of patients, as well as its ability to predict variceal bleeding. New non-invasive tests should be examined.

[Follow up for a cohort of patients with biliary atresia: late surgery and development of biliary cysts]. / Seguimiento de pacientes con atresia biliar: cirugía tardía y desarrollo de lagunas biliares.

Since the introduction of Kasai’s hepatic portoenterostomy, the prognosis of patients with biliary atresia has improved. The presence of intrahepatic biliary cysts or bile lakes has been reported in some patients after the intervention. Bile lakes have been related to cholangitis and a poor outcome. OBJECTIVE: To describe the clinical features and prognosis of patients with biliary atresia after Kasai portoenterostomy, with special emphasis in those who developed biliary cysts. PATIENTS AND METHOD: Data from a retrospective cohort of 13 patients with biliary atresia with a Kasai portoenterostomy from 2008 to 2016 was analyzed. Demographic variables associated to Kasai portoenterostomy, hepatic transplant, biliary cysts and colangitis episodes were tabulated. Kaplan Meir and Log Rank test were used to evaluate colangitis-free and native liver survival. RESULTS: The mean age at Kasai was 85 months (SD 40.3, 42-193 months), six patients (46%) had a Kasai operation after 90 days of life. Four patients (31%) developed multiple biliary cysts; all of them had at least one episode of cholangitis. Cholangitis-free survival was significantly lower for those who developed bile lakes. Nine patients (69%) underwent liver transplant, 3 of them because of recurrent cholangitis. There were no differences in global survival or native liver survival between patients with or without biliary cysts. CONCLUSIONS: The incidence of biliary cysts after Kasai portoenterostomy in this series is similar to the reported. The results are consistent with the relationship proposed between the development of biliary cysts and cholangitis. Our patients, some already derived for evaluation and liver transplantation, underwent Kasai operation at an advanced age, which determines a poor prognosis.

Angiogenesis and portal-systemic collaterals in portal hypertension.

In patients with advanced liver disease with portal hypertension, portal-systemic collaterals contribute to circulatory disturbance, gastrointestinal hemorrhage, hepatic encephalopathy, ascites, hepatopulmonary syndrome and portopulmonary hypertension. Angiogenesis has a pivotal role in the formation of portal-systemic shunts. Recent research has defined many of the mediators and mechanisms involved in this angiogenic process, linking the central roles of hepatic stellate cells and endothelial cells. Studies of animal models have demonstrated the potential therapeutic impact of drugs to inhibit angiogenesis in cirrhosis. For example, inhibition of VEGF reduces portal pressure, hyperdynamic splanchnic circulation, portosystemic collateralization and liver fibrosis. An improved understanding of the role of other angiogenic factors provides hope for a novel targeted therapy for portal hypertension with a tolerable adverse effect profile.

Early endoscopic, laboratory and clinical predictors of poor disease course in paediatric ulcerative colitis.

OBJECTIVE: Data to support treatment algorithms in ambulatory paediatric UC are scarce. We aimed to explore the 1 year outcome in an inception cohort of paediatric UC patients and to identify early predictors of good outcome that might serve as short term treatment targets. DESIGN: A chart review of 115 children with new onset UC was performed (age 11 ± 4.1 years; 58 (50%) males; 86 (75%) extensive colitis; 70 (61%) moderate-severe disease; 63 (55%) received steroids at baseline). We assessed the Paediatric Ulcerative Colitis Activity Index (PUCAI) and laboratory variables at the time of diagnosis and at 3 months, and endoscopy at diagnosis. RESULTS: The 3 month PUCAI was the strongest predictor of 1 year sustained steroid free remission (SSFR) (area under the receiver operating characteristic curve (AUROC)=0.7 (95% CI 0.6 to 0.8) and colectomy by 2 years (AUROC=0.75 (0.6 to 0.89)). SSFR was achieved in 9/54 (17%) children who had active disease (PUCAI ≥ 10) at 3 months (negative predictive value (NPV)=83%) and by 4/46 (8.6%) of those with a PUCAI score >10; (NPV=91%, positive predictive value=52%; p<0.001), implying that PUCAI >10 at 3 months has a probability of 9% for achieving SSFR versus 48% with a PUCAI value of ≤10. None of the variables at baseline was predictive of SSFR or colectomy (endoscopic severity, disease extent, age, PUCAI or C reactive protein/erythrocyte sedimentation rate/albumin/haemoglobin; all AUROC<0.6, p>0.05) but baseline PUCAI predicted subsequent acute severe colitis and the need for salvage medical therapy. CONCLUSIONS: Completeness of the early response appears more important than baseline UC severity for predicting outcome in children, and supports using PUCAI<10 as a feasible treatment goal. Our data suggest that treatment escalation should be considered with a PUCAI value of ≥ 10 at 3 months.

Capsule endoscopy for the diagnosis of oesophageal varices in people with chronic liver disease or portal vein thrombosis.

BACKGROUND: Current guidelines recommend performance of oesophago-gastro-duodenoscopy at the time of diagnosis of hepatic cirrhosis to screen for oesophageal varices. These guidelines require people to undergo an unpleasant invasive procedure repeatedly with its attendant risks, despite the fact that half of the people do not have identifiable oesophageal varices 10 years after the initial diagnosis of cirrhosis. Video capsule endoscopy is a non-invasive test proposed as an alternative method for the diagnosis of oesophageal varices. OBJECTIVES: To determine the diagnostic accuracy of capsule endoscopy for the diagnosis of oesophageal varices in children or adults with chronic liver disease or portal vein thrombosis, irrespective of the aetiology. To investigate the accuracy of capsule endoscopy as triage or replacement of oesophago-gastro-duodenoscopy. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register (October 2013), MEDLINE (Ovid SP) (1950 to October 2013), EMBASE (Ovid SP) (1980 to October 2013), ACP Journal Club (Ovid SP) (1991 to October 2013), Database of Abstracts of Reviews of Effects (DARE) (Ovid SP) (third quarter), Health Technology Assessment (HTA) (Ovid SP) (third quarter), NHS Economic Evaluation Database (NHSEED) (Ovid SP) (third quarter), and Science Citation Index Expanded (SCI-EXPANDED) (ISI Web of Knowledge) (1955 to October 2013). We applied no language or document type restrictions. SELECTION CRITERIA: Studies that evaluated the diagnostic accuracy of capsule endoscopy for the diagnosis of oesophageal varices using oesophago-gastro-duodenoscopy as the reference standard in children or adults of any age, with chronic liver disease or portal vein thrombosis. DATA COLLECTION AND ANALYSIS: We followed the available guidelines provided in the Cochrane Handbook for Diagnostic Test of Accuracy Reviews. We calculated the pooled estimates of sensitivity and specificity using the bivariate model due to the absence of a negative correlation in the receiver operating characteristic (ROC) space and of a threshold effect. MAIN RESULTS: The search identified 16 eligible studies, in which only adults with cirrhosis were included. In one study, people with portal thrombosis were also included. We classified most of the studies at high risk of bias for the 'Participants selection' and the 'Flow and timing' domains. One study assessed the accuracy of capsule endoscopy for the diagnosis of large (high-risk) oesophageal varices. In the remaining15 studies that assessed the accuracy of capsule endoscopy for the diagnosis of oesophageal varices of any size in people with cirrhosis, 936 participants were included; the pooled estimate of sensitivity was 84.8% (95% confidence interval (CI) 77.3% to 90.2%) and of specificity 84.3% (95% CI 73.1% to 91.4%). Eight of these studies included people with suspected varices or people with already diagnosed or even treated varices, or both, introducing a selection bias. Seven studies including only people with suspected but unknown varices were at low risk of bias; the pooled estimate of sensitivity was 79.7% (95% CI 73.1% to 85.0%) and of specificity 86.1% (95% CI 64.5% to 95.5%). Six studies assessed the diagnostic accuracy of capsule endoscopy for the diagnosis of large oesophageal varices, associated with a higher risk of bleeding; the pooled sensitivity was 73.7% (95% CI 52.4% to 87.7%) and of specificity 90.5% (95% CI 84.1% to 94.4%). Two studies also evaluated the presence of red marks, which are another marker of high risk of bleeding; the estimates of sensitivity and specificity varied widely. Two studies obtained similar results with the use of a modified device as index test (string capsule). Due to the absence of data, we could not perform all planned subgroup analyses. Interobserver agreement in the interpretation of capsule endoscopy results and any adverse event attributable to capsule endoscopy were poorly assessed and reported. Only four studies evaluated the interobserver agreement in the interpretation of capsule endoscopy results: the concordance was moderate. The participants' preferences for capsule endoscopy or oesophago-gastro-duodenoscopy were reported differently but seemed in favour of capsule endoscopy in nine of 10 studies. In 10 studies, participants reported some minor discomfort on swallowing the capsule. Only one study identified other significant adverse events, including impaction of the capsule due to previously unidentified oesophageal strictures in two participants. No adverse events were reported as a consequence of the reference standard. AUTHORS' CONCLUSIONS: We cannot support the use of capsule endoscopy as a triage test in adults with cirrhosis, administered before oesophago-gastro-duodenoscopy, despite the low incidence of adverse events and participant reports of being better tolerated. Thus, we cannot conclude that oesophago-gastro-duodenoscopy can be replaced by capsule endoscopy for the detection of oesophageal varices in adults with cirrhosis. We found no data assessing capsule endoscopy in children and in people with portal thrombosis.

[Severe acute pancreatitis secondary to hypertriglyceridemia as the onset of Type 1 Diabetes Mellitus in the pediatric age]. / Pancreatitis aguda grave secundaria a hipertrigliceridemia como debut de Diabetes Mellitus Tipo 1 en edad pediátrica.

Hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) secondary to insulin deficiency following the onset of type 1 diabetes mellitus (T1DM) is a rare but serious complication in children. OBJECTIVE: To describe the diagnosis and treatment of severe HTG and to emphasize the need for timely diagnosis of T1DM. CLINICAL CASE: A 15-year-old female adolescent with a history of overweight presented with a two-weeks history of fever, anorexia, and diffuse abdominal pain. Laboratory tests revealed triglycerides of 17,580 mg/dL, lipase of 723 U/L, and blood glucose of 200 mg/dL. An abdominal CT scan showed an enlarged and edematous pancreas. She was hospitalized with a diagnosis of AP and severe HTG, which progressed to acute necro-hemorrhagic pancreatitis. Treatment included continuous intravenous insulin infusion until triglyceride levels decreased. Upon discontinuation of insulin, fasting hyperglycemia (206 mg/dL) and metabolic acidosis recurred, therefore DM was suspected. Upon targeted questioning, a history of polydipsia, polyuria, and weight loss during the last 3 months stood out. Glycated hemoglobin was markedly elevated (14.7%). Insulin therapy was optimized, achieving stabilization of laboratory parameters after 15 days of treatment and complete anatomical resolution of pancreatic involvement at one year of follow-up. CONCLUSIONS: The presence of severe HTG in pediatrics compels us to consider its secondary causes, such as the onset of T1DM. It is crucial to improve the ability to diagnose T1DM early, as it may present with infrequent and high-risk presentations for the patient.