AIM:To explore differences in biochemical indices between neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and that with other etiologies. METHODS:Patients under 6 mo of age who were referred for ...AIM:To explore differences in biochemical indices between neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and that with other etiologies. METHODS:Patients under 6 mo of age who were referred for investigation of conjugated hyperbiliru-binaemia from June 2003 to December 2010 were eligible for this study. After excluding diseases affecting the extrahepatic biliary system, all patients were screened for the two most common SLC25A13 mutations; the coding exons of the entire SLC25A13 gene was sequenced and Western blotting of citrin protein performed in selected cases. Patients in whom homo-zygous or compound heterozygous SLC25A13 mutation and/or absence of normal citrin protein was detected were defined as having NICCD. Cases in which no specific etiological factor could be ascertained after a com-prehensive conjugated hyperbilirubinaemia work-up were defined as idiopathic neonatal cholestasis (INC). Thirty-two NICCD patients, 250 INC patients, and 39 infants with cholangiography-confirmed biliary atresia (BA) were enrolled. Laboratory values at their first visit were abstracted from medical files and compared. RESULTS:Compared with BA and INC patients, the NICCD patients had significantly higher levels of total bile acid (TBA) [all measures are expressed as median (inter-quartile range):178.0 (111.2-236.4) μmol/L in NICCD vs 112.0 (84.9-153.9) μmol/L in BA and 103.0 (70.9-135.3) μmol/L in INC, P = 0.0001]. The NICCD patients had significantly lower direct bilirubin [D-Bil 59.6 (43.1-90.9) μmol/L in NICCD vs 134.0 (115.9-151.2) μmol/L in BA and 87.3 (63.0-123.6) μmol/L in INC, P = 0.0001]; alanine aminotransferase [ALT 34.0 (23.0-55.0) U/L in NICCD vs 108.0 (62.0-199.0) U/L in BA and 84.5 (46.0-166.0) U/L in INC, P = 0.0001]; aspartate aminotransferase [AST 74.0 (53.5-150.0) U/L in NICCD vs 153.0 (115.0-239.0) U/L in BA and 130.5 (81.0-223.0) U/L in INC, P = 0.0006]; albumin [34.9 (30.7-38.2) g/L in NICCD vs 38.4 (36.3-42.2) g/L in BA and 39.9 (37.0-42.3) g/L in INC, P = 0.0001]; glucose [3.2 (2.0-4.4) mmol/L in NICCD vs 4.1 (3.4-5.1) mmol/L in BA and 4.0 (3.4-4.6) mmol/L in INC, P = 0.0014] and total cholesterol [TCH 3.33 (2.97-4.00) mmol/L in N ICCD vs 4.57 (3.81-5.26) mmol/L in BA and 4.00 (3.24-4.74) mmol/L in INC, P = 0.0155] levels. The D-Bil to total bilirubin (T-Bil) ratio was significantly lower in NICCD patients [all measures are expressed as median (inter-quartile range):0.54 (0.40-0.74)] than that in BA patients [0.77 (0.72-0.81), P = 0.001] and that in INC patients [0.74 (0.59-0.80), P = 0.0045]. A much higher AST/ALT ratio was found in NICCD patients [2.46 (1.95-3.63)] compared to BA patients [1.38 (0.94-1.97), P = 0.0001] and INC patients [1.48 (1.10-2.26), P = 0.0001]. NICCD patients had significantly higher TBA/D-Bil ratio [3.36 (1.98-4.43) vs 0.85 (0.72-1.09) in BA patients and 1.04 (0.92-1.14) in INC patients, P = 0.0001], and TBA/TCH ratio [60.7 (32.4-70.9) vs 24.7 (19.8-30.2) in BA patients and 24.2 (21.4-26.9) in INC patients, P = 0.0001] compared to the BA and INC groups. CONCLUSION:NICCD has significantly different bio- chemical indices from BA or INC. TBA excretion in NICCD appeared to be more severely disturbed than that of bilirubin and cholesterol.展开更多
AIM: To investigate the differences in the mutation spectra of the SLC25A13 gene mutations from specific regions of China. METHODS: Genetic analyses of SLC25A13 mutations were performed in 535 patients with neonatal i...AIM: To investigate the differences in the mutation spectra of the SLC25A13 gene mutations from specific regions of China. METHODS: Genetic analyses of SLC25A13 mutations were performed in 535 patients with neonatal intrahepatic cholestasis from our center over eight years. Unrelated infants with at least one mutant allele were enrolled to calculate the proportion of SLC25A13 mutations in different regions of China. The boundary between northern and southern China was drawn at the historical border of the Yangtze River.RESULTS: A total of 63 unrelated patients (about 11% of cases with intrahepatic cholestasis) from 16 provinces or municipalities in China had mutations in the SLC25A13 gene, of these 16 (25%) were homozygotes, 28 (44%) were compound heterozygotes and 19 (30%) were heterozygotes. In addition to four well described common mutations (c.851_854del, c.1638_1660dup23, c.615+5G>A and c.1750+72_17514dup17insNM_138459.3:2667 also known as IVS16ins3kb), 13 other mutation types were identified, including three novel mutations: c.985_986insT, c.287T>C and c.1349A>G. According to the geographical division criteria, 60 mutant alleles were identified in patients from the southern areas of China, 43 alleles were identified in patients from the border, and 4 alleles were identified in patients from the northern areas of China. The proportion of four common mutations was higher in south region (56/60, 93%) than that in the border region (34/43, 79%, χ 2 = 4.621, P = 0.032) and the northern region (2/4, 50%, χ 2 = 8.288, P = 0.041). CONCLUSION: The SLC25A13 mutation spectra among the three regions of China were different, providing a basis for the improvement of diagnostic strategies and interpretation of genetic diagnosis.展开更多
Wilson disease is an autosomal recessive disorder of copper metabolism that can cause fatal neurological and hepatic disease if not diagnosed and treated. The youngest child with normal liver function reported so far ...Wilson disease is an autosomal recessive disorder of copper metabolism that can cause fatal neurological and hepatic disease if not diagnosed and treated. The youngest child with normal liver function reported so far is an 8-mo-old Japanese boy with low ceruloplasmin levels, and the youngest child with elevated aminotransferase ever reported so far is a 9-mo-old Korean boy with confirmed by genetic testing. Here we report an 8-mo-old Chinese boy presented with elevated liver enzymes, and low serum ceruloplasmin level. Genetic analysis of ATP7 B gene detected two heterozygous disease causing mutations(c.2621C>T/p.A874 V and c.3809A>G/p.N1270S), and parental origins were determined. Persistent elevation of serum aminotransferase in this infant was normalized after zinc therapy. To our best knowledge, this is the youngest patient with elevated liver enzymes ever reported worldwide. We hope that this will raise awareness among pediatricians, leading to earlier diagnosis, timely treatment, and better clinical outcome.展开更多
Citrin deficiency typically presents as neonatal intrahepatic cholestasis and resolves in late infancy.Here we report a case of citrin deficiency that presented as acute liver failure in late infancy in an apparently ...Citrin deficiency typically presents as neonatal intrahepatic cholestasis and resolves in late infancy.Here we report a case of citrin deficiency that presented as acute liver failure in late infancy in an apparently healthy child. The full-term male infant weighed3400 g at birth, and exhibited normal development for eight months, at which time he contracted bronchial pneumonia. The infant developed jaundice and laboratory tests indicated elevated bilirubin and ammonia levels and an abnormal coagulation profile.Plasma amino acid analysis showed elevated levels of tyrosine, methionine, citrulline, and arginine. Citrin deficiency was suspected, and genomic DNA analysis revealed a mutation(IVS16ins3kb) in SLC25A13, which encodes a mitochondrial aspartate-glutamate carrier protein. The infant was immediately put on a lactosefree,medium-chain-triglyceride-enriched formula with ursodeoxycholic acid and lipid-soluble vitamins.However, cholestasis and abnormal laboratory indices persisted, and the infant died at the age of 11.5 mo,two days before a scheduled liver transplantation. This case demonstrates that citrin deficiency can present in late infancy as acute liver failure triggered by infection,and may require liver transplantation.展开更多
Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (OMIM 208085) is an autosomal recessive disorder that is caused by mutations in 2 interacting genes VPS33B and VIPAS39. Mutations in VPS33B gene account...Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (OMIM 208085) is an autosomal recessive disorder that is caused by mutations in 2 interacting genes VPS33B and VIPAS39. Mutations in VPS33B gene account for most cases of ARC. As low or normal gamma-glutamyl transpeptidase (GGT) activity has been described in all patients with ARC syndrome identified so far, ARC syndrome is a possible diagnosis for low GGT cholestasis. Here we describe a Chinese patient with neonatal cholestasis and a high GGT level in three consecutive tests. She had other typical manifestations of ARC syndrome, including arthrogryposis multiplex congenita, renal involvement and ichthyosis. Genetic study of the VPS33B gene further confirmed the diagnosis by identification of compound heterozygosity of two known disease-causing mutations, c.403+2T > A and c.1509-1510insG. The mechanism of high GGT in this patient is unclear. Nevertheless, this case indicates that ARC syndrome cannot be excluded from the differential diagnosis of neonatal cholestasis even if high GGT activity is found.展开更多
Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase defici...Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase deficiency patients in China's Mainland diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis.A high proportion of atypical 3-oxo-4-bile acids in the urine indicated a deficiency in 4-3-oxosteroid 5β-reductase.All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents.One patient exhibited compound heterozygous mutations:c.396C>A and c.722A>T,while the other was heterozygous for the mutation c.797G>A.Based on these mutations,a diagnosis of primary 4-3-oxosteroid 5β-reductase deficiency could be confirmed.With ursodeoxycholic acid treatment and fat-soluble vitamin supplements,liver function tests normalized rapidly,and the degree of hepatomegaly was markedly reduced in both patients.展开更多
BACKGROUND Disorders of primary bile acid synthesis may be life-threatening if undiagnosed,or not treated with primary bile acid replacement therapy. To date, there are few reports on the management and follow-up of p...BACKGROUND Disorders of primary bile acid synthesis may be life-threatening if undiagnosed,or not treated with primary bile acid replacement therapy. To date, there are few reports on the management and follow-up of patients with Δ4-3-oxosteroid 5β-reductase(AKR1 D1) deficiency. We hypothesized that a retrospective analysis of the responses to oral bile acid replacement therapy with chenodeoxycholic acid(CDCA) in patients with this bile acid synthesis disorder will increase our understanding of the disease progression and permit evaluation of this treatment regimen as an alternative to the Food and Drug Administration(FDA) approved drug cholic acid, which is currently unavailable in China.AIM To evaluate the therapeutic responses of patients with AKR1 D1 deficiency to oral bile acid therapy, specifically CDCA.METHODS Twelve patients with AKR1 D1 deficiency, confirmed by fast atom bombardment ionization-mass spectrometry analysis of urine and by gene sequencing for mutations in AKR1 D1, were treated with differing doses of CDCA or ursodeoxycholic acid(UDCA). The clinical and biochemical responses to therapy were monitored over a period ranging 0.5-6.4 years. Dose adjustment, to optimize the therapeutic dose, was based on changes in serum biochemistry parameters,notably liver function tests, and suppression of the urinary levels of atypical hepatotoxic 3-oxo-Δ4-bile acids measured by mass spectrometry.RESULTS Physical examination, serum biochemistry parameters, and sonographic findings improved in all 12 patients during bile acid therapy, except one who underwent liver transplantation. Urine bile acid analysis confirmed a significant reduction in atypical hepatotoxic 3-oxo-Δ4 bile acids concomitant with clinical and biochemical improvements in those patients treated with CDCA. UDCA was ineffective in down-regulating endogenous bile acid synthesis as evidenced from the inability to suppress the urinary excretion of atypical 3-oxo-Δ4-bile acids. The dose of CDCA required for optimal clinical and biochemical responses varied from 5.5-10 mg/kg per day among patients based on maximum suppression of the atypical bile acids and improvement in serum biochemistry parameters, and careful titration of the dose was necessary to avoid side effects from CDCA.CONCLUSION The primary bile acid CDCA is effective in treating AKR1 D1 deficiency but the therapeutic dose requires individualized optimization. UDCA is not recommended for long-term management.展开更多
Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a rare genetic disorder and has not been described in China. We present a female infant with neonatal intrahepatic cholestasis from a Chinese family ...Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a rare genetic disorder and has not been described in China. We present a female infant with neonatal intrahepatic cholestasis from a Chinese family with ARC syndrome. All 23 coding exons and flanking introns of the VPS33B gene were amplified and sequenced using peripheral lymphocyte genomic DNA of the patient and her parents. Genetic testing revealed two novel mutations (c.1033delA and c.1567C>T) in the VPS33B gene. The patient is a compound heterozygote and her parents were heterozygous for each of the mutations.展开更多
Interstitial lung and liver disease(ILLD) is caused by biallelic mutations in the methionyl-tRNA synthetase(MARS) gene. To date, no genetic changes other than missense variants were reported in the literature. Here, w...Interstitial lung and liver disease(ILLD) is caused by biallelic mutations in the methionyl-tRNA synthetase(MARS) gene. To date, no genetic changes other than missense variants were reported in the literature. Here, we report a five-month old female infant with typical ILLD(failure to thrive, developmental delay, jaundice, diffuse interstitial lung disease, hepatomegaly with severe steatosis, anemia, and thrombocytosis) showing novel phenotypes such as kidney stones, acetabular dysplasia, prolonged fever, and extreme leukocytosis. Whole exome sequencing revealed a novel truncating variant(c.2158 C>T/p.Gln720 Stop) together with a novel tri-nucleotide insertion(c.893_894 insTCG that caused the insertion of an arginine at amino acid position 299) in the MARS gene.展开更多
Steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and...Steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307(p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid(UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid(CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.展开更多
BACKGROUND Acute liver failure(ALF)can be a primary presentation of Wilson disease(WD).Mortality rates are high in WD with ALF(WDALF).Predictions of mortality in WDALF vary by model and are sometimes contradictory,per...BACKGROUND Acute liver failure(ALF)can be a primary presentation of Wilson disease(WD).Mortality rates are high in WD with ALF(WDALF).Predictions of mortality in WDALF vary by model and are sometimes contradictory,perhaps because few patients are studied or WD diagnoses are questionable.AIM To determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.METHODS We reviewed the medical records of our pediatric WDALF patients(n=41 over 6-years-old,single-center retrospective study)and compared seven prognostic models(King’s College Hospital Criteria,model for end-stage liver disease/pediatric end-stage liver disease scoring systems,Liver Injury Unit[LIU]using prothrombin time[PT]or international normalized ratio[INR],admission LIU using PT or INR,and Devarbhavi model)with one another.RESULTS Among the 41 Han Chinese patients with ALF,WD was established by demonstrating ATP7B variants in 36.In 5 others,Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis.Three died during hospitalization and three underwent liver transplantation(LT)within 1 mo of presentation and survived(7.3%each);35(85.4%)survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis.Parameters significantly correlated with mortality included encephalopathy,coagulopathy,and gamma-glutamyl transpeptidase activity,bilirubin,ammonia,and serum sodium levels.Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.CONCLUSION WDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis,even after enlisting for LT.展开更多
BACKGROUND Pediatric recurrent acute liver failure(RALF) with recovery between episodes is rare. Causes include autoimmune disease, which may flare and subside;intermittent exposure to toxins, as with ingestions; and ...BACKGROUND Pediatric recurrent acute liver failure(RALF) with recovery between episodes is rare. Causes include autoimmune disease, which may flare and subside;intermittent exposure to toxins, as with ingestions; and metabolic disorders,among them the fever-associated crises ascribed to biallelic mutations in SCYL1,with RALF beginning in infancy. SCYL1 disease manifest with RALF, as known to date, includes central and peripheral neurologic and muscular morbidity(hepatocerebellar neuropathy syndrome). Primary ventilatory and skeletal diseases also have been noted in some reports.CASE SUMMARY We describe a Han Chinese boy in whom fever-associated RALF began at age 14 mo. Bilateral femoral head abnormalities and mild impairment of neurologic function were first noted aged 8 years 6 mo. Liver biopsy after the third RALF episode(7 years) and during resolution of the fourth RALF episode(8 years 6 mo) found abnormal architecture and hepatic fibrosis, respectively. Whole-exome sequencing revealed homozygosity for the novel frameshift mutation c.92_93 insGGGCCCT, p.(H32 Gfs~*20) in SCYL1(parental heterozygosity confirmed).CONCLUSION Our findings expand the mutational and clinical spectrum of SCYL1 disease. In our patient a substantial neurologic component was lacking and skeletal disease was identified relatively late.展开更多
BACKGROUND Mannosyl-oligosaccharide glucosidase(MOGS)deficiency is an extremely rare type of congenital disorder of glycosylation(CDG),with only 12 reported cases.Its clinical,genetic,and glycomic features are still e...BACKGROUND Mannosyl-oligosaccharide glucosidase(MOGS)deficiency is an extremely rare type of congenital disorder of glycosylation(CDG),with only 12 reported cases.Its clinical,genetic,and glycomic features are still expanding.Our aim is to update the novel clinical and glycosylation features of 2 previously reported patients with MOGS-CDG.CASE SUMMARY We collected comprehensive clinical information,and conducted the immunoglobulin G1 glycosylation assay using nano-electrospray ionization source quadruple time-of-flight mass spectrometry.Novel dysmorphic features included an enlarged tongue,forwardly rotated earlobes,a birth mark,overlapped toes,and abnormal fat distribution.Novel imaging findings included pericardial effusion,a deep interarytenoid groove,mild congenital subglottic stenosis,and laryngomalacia.Novel laboratory findings included peripheral leukocytosis with neutrophil predominance,elevated C-reactive protein and creatine kinase,dyslipidemia,coagulopathy,complement 3 and complement 4 deficiencies,decreased proportions of T lymphocytes and natural killer cells,and increased serum interleukin 6.Glycosylation studies showed a significant increase of hypermannosylated glycopeptides(Glc3Man7GlcNAc2/N2H10 and Man5GlcNAc2/N2H5)and hypersialylated glycopeptides.A compensatory glycosylation pathway leading to an increase in Man5GlcNAc2/N2H5 was indicated with the glycosylation profile.CONCLUSION We confirmed abnormal glycomics in 1 patient,expanding the clinical and glycomic spectrum of MOGS-CDG.We also postulated a compensatory glycosylation pathway,leading to a possible serum biomarker for future diagnosis.展开更多
It has been more than 3 years since the novel coronavirus(SARS-CoV-2)pandemic raged globally.The coronavirus disease 2019(COVID-19)has greatly influenced human society.According to data from the World Health Organizat...It has been more than 3 years since the novel coronavirus(SARS-CoV-2)pandemic raged globally.The coronavirus disease 2019(COVID-19)has greatly influenced human society.According to data from the World Health Organization(WHO),there were over 656 million confirmed cases of COVID-19 in the world as of January 1,2023,including over 6.6 million deaths[1].展开更多
Background and Aims:We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bi...Background and Aims:We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid(tauro-THBA)in cholestasis.Methods:Serum bile acid profiles were evaluated in 13 ABCB4-mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry(UPLC/MRM-MS).The concentration of tauro-THBA was compared between ABCB4-mutated patients with different prognoses.The areas under the curve(AUCs)of tauro-THBA were compared between ABCB11-mutated patients with native liver survival and those who died or underwent liver transplantation before 3 years of age by receiver operating characteristic curve(ROC),with another patient cohort for further verification.Results:The overall hydrophobicity indices of bile acids in ABCB4-mutated patients(12.99±3.25 m)were significantly lower than those of healthy controls(14.02±1.74 m,p<0.000).That was due to markedly increased bile acid modifications including conjugation,sulfation,and ketonization.Differences in the tauro-THBA concentration in ABCB4-mutated patients with different prognoses were not significant.ROC analysis indicated that levels of tauro-THBA of<60 nM yielded an AUC of 0.900 with a sensitivity of 80%and specificity of 87.5%for ABCB11-mutated patients with different prognoses(p=0.0192).Of the 15 patients with good prognosis,14 were classified correctly and four of the five patients with a poor prognosis were classified correctly(14:15 vs.1:5,p=0.005)with tauro-THBA as a classifier.Conclusions:Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gammaglutamyl transferase intrahepatic cholestasis patients.展开更多
Background The liver manifestations of Alagille syndrome(ALGS)are highly variable,and factors affecting its prognosis are poorly understood.We asked whether the composition of bile acids in ALGS patients with good cli...Background The liver manifestations of Alagille syndrome(ALGS)are highly variable,and factors affecting its prognosis are poorly understood.We asked whether the composition of bile acids in ALGS patients with good clinical outcomes differs from that in patients with poor outcomes and whether bile acids could be used as prognostic biomarkers.Methods Blood for bile acid profiling was collected from genetically confirmed JAG1-associated ALGS patients before one year of age.A good prognosis was defined as survival with native liver and total bilirubin(TB)<85.5 μmol/L,while a poor prognosis was defined as either liver transplantation,death from liver failure,or TB ≥ 85.5 μmol/L at the last follow-up.Results We found that the concentrations of two poly-hydroxylated bile acids,tauro-2β,3α,7α,12α-tetrahydroxylated bile acid(THBA)and glyco-hyocholic acid(GHCA),were significantly increased in patients with good prognosis compared to those with poor prognosis[area under curve(AUC)=0.836 and 0.782,respectively]in the discovery cohort.The same trend was also observed in the molar ratios of GHCA to glyco-chenodeoxycholic acid(GCDCA)and tetrahydroxylated bile acid(THCA)to tauro-chenodeoxycholic acid(TCDCA)(both AUC=0.836).A validation cohort confirmed these findings.Notably,tauro-2β,3α,7α,12α-THBA achieved the highest prediction accuracy of 88.00%(92.31%sensitivity and 83.33%specificity);GHCA at>607.69 nmol/L was associated with native liver survival[hazard ratio:13.03,95%confidence interval(CI):(2.662-63.753),P=0.002].Conclusions We identified two poly-hydroxylated bile acids as liver prognostic biomarkers of ALGS patients.Enhanced hydroxylation of bile acids may result in better clinical outcomes.展开更多
Monkeypox is a zoonotic disease.Since the first human monkeypox case was detected in 1970,it has been prevalent in some countries in central and western Africa.Since May 2022,monkeypox cases have been reported in more...Monkeypox is a zoonotic disease.Since the first human monkeypox case was detected in 1970,it has been prevalent in some countries in central and western Africa.Since May 2022,monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide.As of September 14,2022,there have been more than 58,200 human monkeypox cases,and there is community transmission.The cessation of smallpox vaccination in 1980,which had some cross-protection with monkeypox,resulted in a general lack of immunity to monkeypox,which caused global concern and vigilance.As of Sep-tember 14,2022,there are four monkeypox cases in China,including three in Taiwan province and one in Hong Kong city.Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians'understanding of monkeypox and achieve early detection,early diagno-sis,early treatment,and early disposal,we have organized national authoritative experts in pediatric infection,respiratory,dermatology,critical care medicine,infectious diseases,and public health and others to formulate this expert consensus,on the basis of the latest"Clinical management and infection prevention and control for monkeypox"released by The World Health Organization,the"guidelines for diagnosis and treatment of monkeypox(version 2022)"issued by National Health Commission of the People's Republic of China and other relevant documents.During the development of this consensus,multidisciplinary experts have repeatedly demonstrated the etiology,epidemiology,transmission,clinical manifestations,laboratory examinations,diagnosis,differential diagnosis,treatment,discharge criteria,prevention,disposal process,and key points of prevention and control of suspected and confirmed cases.展开更多
基金Supported by National Science Foundation of China, No. 30973230 and No. 81070281
文摘AIM:To explore differences in biochemical indices between neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and that with other etiologies. METHODS:Patients under 6 mo of age who were referred for investigation of conjugated hyperbiliru-binaemia from June 2003 to December 2010 were eligible for this study. After excluding diseases affecting the extrahepatic biliary system, all patients were screened for the two most common SLC25A13 mutations; the coding exons of the entire SLC25A13 gene was sequenced and Western blotting of citrin protein performed in selected cases. Patients in whom homo-zygous or compound heterozygous SLC25A13 mutation and/or absence of normal citrin protein was detected were defined as having NICCD. Cases in which no specific etiological factor could be ascertained after a com-prehensive conjugated hyperbilirubinaemia work-up were defined as idiopathic neonatal cholestasis (INC). Thirty-two NICCD patients, 250 INC patients, and 39 infants with cholangiography-confirmed biliary atresia (BA) were enrolled. Laboratory values at their first visit were abstracted from medical files and compared. RESULTS:Compared with BA and INC patients, the NICCD patients had significantly higher levels of total bile acid (TBA) [all measures are expressed as median (inter-quartile range):178.0 (111.2-236.4) μmol/L in NICCD vs 112.0 (84.9-153.9) μmol/L in BA and 103.0 (70.9-135.3) μmol/L in INC, P = 0.0001]. The NICCD patients had significantly lower direct bilirubin [D-Bil 59.6 (43.1-90.9) μmol/L in NICCD vs 134.0 (115.9-151.2) μmol/L in BA and 87.3 (63.0-123.6) μmol/L in INC, P = 0.0001]; alanine aminotransferase [ALT 34.0 (23.0-55.0) U/L in NICCD vs 108.0 (62.0-199.0) U/L in BA and 84.5 (46.0-166.0) U/L in INC, P = 0.0001]; aspartate aminotransferase [AST 74.0 (53.5-150.0) U/L in NICCD vs 153.0 (115.0-239.0) U/L in BA and 130.5 (81.0-223.0) U/L in INC, P = 0.0006]; albumin [34.9 (30.7-38.2) g/L in NICCD vs 38.4 (36.3-42.2) g/L in BA and 39.9 (37.0-42.3) g/L in INC, P = 0.0001]; glucose [3.2 (2.0-4.4) mmol/L in NICCD vs 4.1 (3.4-5.1) mmol/L in BA and 4.0 (3.4-4.6) mmol/L in INC, P = 0.0014] and total cholesterol [TCH 3.33 (2.97-4.00) mmol/L in N ICCD vs 4.57 (3.81-5.26) mmol/L in BA and 4.00 (3.24-4.74) mmol/L in INC, P = 0.0155] levels. The D-Bil to total bilirubin (T-Bil) ratio was significantly lower in NICCD patients [all measures are expressed as median (inter-quartile range):0.54 (0.40-0.74)] than that in BA patients [0.77 (0.72-0.81), P = 0.001] and that in INC patients [0.74 (0.59-0.80), P = 0.0045]. A much higher AST/ALT ratio was found in NICCD patients [2.46 (1.95-3.63)] compared to BA patients [1.38 (0.94-1.97), P = 0.0001] and INC patients [1.48 (1.10-2.26), P = 0.0001]. NICCD patients had significantly higher TBA/D-Bil ratio [3.36 (1.98-4.43) vs 0.85 (0.72-1.09) in BA patients and 1.04 (0.92-1.14) in INC patients, P = 0.0001], and TBA/TCH ratio [60.7 (32.4-70.9) vs 24.7 (19.8-30.2) in BA patients and 24.2 (21.4-26.9) in INC patients, P = 0.0001] compared to the BA and INC groups. CONCLUSION:NICCD has significantly different bio- chemical indices from BA or INC. TBA excretion in NICCD appeared to be more severely disturbed than that of bilirubin and cholesterol.
基金Supported by National Natural Science Foundation of China, No. 30973230 and No. 81070281
文摘AIM: To investigate the differences in the mutation spectra of the SLC25A13 gene mutations from specific regions of China. METHODS: Genetic analyses of SLC25A13 mutations were performed in 535 patients with neonatal intrahepatic cholestasis from our center over eight years. Unrelated infants with at least one mutant allele were enrolled to calculate the proportion of SLC25A13 mutations in different regions of China. The boundary between northern and southern China was drawn at the historical border of the Yangtze River.RESULTS: A total of 63 unrelated patients (about 11% of cases with intrahepatic cholestasis) from 16 provinces or municipalities in China had mutations in the SLC25A13 gene, of these 16 (25%) were homozygotes, 28 (44%) were compound heterozygotes and 19 (30%) were heterozygotes. In addition to four well described common mutations (c.851_854del, c.1638_1660dup23, c.615+5G>A and c.1750+72_17514dup17insNM_138459.3:2667 also known as IVS16ins3kb), 13 other mutation types were identified, including three novel mutations: c.985_986insT, c.287T>C and c.1349A>G. According to the geographical division criteria, 60 mutant alleles were identified in patients from the southern areas of China, 43 alleles were identified in patients from the border, and 4 alleles were identified in patients from the northern areas of China. The proportion of four common mutations was higher in south region (56/60, 93%) than that in the border region (34/43, 79%, χ 2 = 4.621, P = 0.032) and the northern region (2/4, 50%, χ 2 = 8.288, P = 0.041). CONCLUSION: The SLC25A13 mutation spectra among the three regions of China were different, providing a basis for the improvement of diagnostic strategies and interpretation of genetic diagnosis.
基金Supported by National Natural Science Foundation of China,No.81070281
文摘Wilson disease is an autosomal recessive disorder of copper metabolism that can cause fatal neurological and hepatic disease if not diagnosed and treated. The youngest child with normal liver function reported so far is an 8-mo-old Japanese boy with low ceruloplasmin levels, and the youngest child with elevated aminotransferase ever reported so far is a 9-mo-old Korean boy with confirmed by genetic testing. Here we report an 8-mo-old Chinese boy presented with elevated liver enzymes, and low serum ceruloplasmin level. Genetic analysis of ATP7 B gene detected two heterozygous disease causing mutations(c.2621C>T/p.A874 V and c.3809A>G/p.N1270S), and parental origins were determined. Persistent elevation of serum aminotransferase in this infant was normalized after zinc therapy. To our best knowledge, this is the youngest patient with elevated liver enzymes ever reported worldwide. We hope that this will raise awareness among pediatricians, leading to earlier diagnosis, timely treatment, and better clinical outcome.
基金Supported by National Natural Science Foundation of China,No.813111071Key projects of Shanghai Municipal Health Bureau,No.2013-27
文摘Citrin deficiency typically presents as neonatal intrahepatic cholestasis and resolves in late infancy.Here we report a case of citrin deficiency that presented as acute liver failure in late infancy in an apparently healthy child. The full-term male infant weighed3400 g at birth, and exhibited normal development for eight months, at which time he contracted bronchial pneumonia. The infant developed jaundice and laboratory tests indicated elevated bilirubin and ammonia levels and an abnormal coagulation profile.Plasma amino acid analysis showed elevated levels of tyrosine, methionine, citrulline, and arginine. Citrin deficiency was suspected, and genomic DNA analysis revealed a mutation(IVS16ins3kb) in SLC25A13, which encodes a mitochondrial aspartate-glutamate carrier protein. The infant was immediately put on a lactosefree,medium-chain-triglyceride-enriched formula with ursodeoxycholic acid and lipid-soluble vitamins.However, cholestasis and abnormal laboratory indices persisted, and the infant died at the age of 11.5 mo,two days before a scheduled liver transplantation. This case demonstrates that citrin deficiency can present in late infancy as acute liver failure triggered by infection,and may require liver transplantation.
基金Supported by National Natural Science Foundation of China,No.81070281
文摘Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (OMIM 208085) is an autosomal recessive disorder that is caused by mutations in 2 interacting genes VPS33B and VIPAS39. Mutations in VPS33B gene account for most cases of ARC. As low or normal gamma-glutamyl transpeptidase (GGT) activity has been described in all patients with ARC syndrome identified so far, ARC syndrome is a possible diagnosis for low GGT cholestasis. Here we describe a Chinese patient with neonatal cholestasis and a high GGT level in three consecutive tests. She had other typical manifestations of ARC syndrome, including arthrogryposis multiplex congenita, renal involvement and ichthyosis. Genetic study of the VPS33B gene further confirmed the diagnosis by identification of compound heterozygosity of two known disease-causing mutations, c.403+2T > A and c.1509-1510insG. The mechanism of high GGT in this patient is unclear. Nevertheless, this case indicates that ARC syndrome cannot be excluded from the differential diagnosis of neonatal cholestasis even if high GGT activity is found.
基金Supported by National Natural Science Foundation of China, No.81070281
文摘Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase deficiency patients in China's Mainland diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis.A high proportion of atypical 3-oxo-4-bile acids in the urine indicated a deficiency in 4-3-oxosteroid 5β-reductase.All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents.One patient exhibited compound heterozygous mutations:c.396C>A and c.722A>T,while the other was heterozygous for the mutation c.797G>A.Based on these mutations,a diagnosis of primary 4-3-oxosteroid 5β-reductase deficiency could be confirmed.With ursodeoxycholic acid treatment and fat-soluble vitamin supplements,liver function tests normalized rapidly,and the degree of hepatomegaly was markedly reduced in both patients.
基金Supported by the National Natural Science Foundation of China,No.81570468 and No.81741056Jinshan Science and Technology Commission,No.2014-3-07
文摘BACKGROUND Disorders of primary bile acid synthesis may be life-threatening if undiagnosed,or not treated with primary bile acid replacement therapy. To date, there are few reports on the management and follow-up of patients with Δ4-3-oxosteroid 5β-reductase(AKR1 D1) deficiency. We hypothesized that a retrospective analysis of the responses to oral bile acid replacement therapy with chenodeoxycholic acid(CDCA) in patients with this bile acid synthesis disorder will increase our understanding of the disease progression and permit evaluation of this treatment regimen as an alternative to the Food and Drug Administration(FDA) approved drug cholic acid, which is currently unavailable in China.AIM To evaluate the therapeutic responses of patients with AKR1 D1 deficiency to oral bile acid therapy, specifically CDCA.METHODS Twelve patients with AKR1 D1 deficiency, confirmed by fast atom bombardment ionization-mass spectrometry analysis of urine and by gene sequencing for mutations in AKR1 D1, were treated with differing doses of CDCA or ursodeoxycholic acid(UDCA). The clinical and biochemical responses to therapy were monitored over a period ranging 0.5-6.4 years. Dose adjustment, to optimize the therapeutic dose, was based on changes in serum biochemistry parameters,notably liver function tests, and suppression of the urinary levels of atypical hepatotoxic 3-oxo-Δ4-bile acids measured by mass spectrometry.RESULTS Physical examination, serum biochemistry parameters, and sonographic findings improved in all 12 patients during bile acid therapy, except one who underwent liver transplantation. Urine bile acid analysis confirmed a significant reduction in atypical hepatotoxic 3-oxo-Δ4 bile acids concomitant with clinical and biochemical improvements in those patients treated with CDCA. UDCA was ineffective in down-regulating endogenous bile acid synthesis as evidenced from the inability to suppress the urinary excretion of atypical 3-oxo-Δ4-bile acids. The dose of CDCA required for optimal clinical and biochemical responses varied from 5.5-10 mg/kg per day among patients based on maximum suppression of the atypical bile acids and improvement in serum biochemistry parameters, and careful titration of the dose was necessary to avoid side effects from CDCA.CONCLUSION The primary bile acid CDCA is effective in treating AKR1 D1 deficiency but the therapeutic dose requires individualized optimization. UDCA is not recommended for long-term management.
基金Supported by National Natural Science Foundation of China,No.81070281
文摘Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a rare genetic disorder and has not been described in China. We present a female infant with neonatal intrahepatic cholestasis from a Chinese family with ARC syndrome. All 23 coding exons and flanking introns of the VPS33B gene were amplified and sequenced using peripheral lymphocyte genomic DNA of the patient and her parents. Genetic testing revealed two novel mutations (c.1033delA and c.1567C>T) in the VPS33B gene. The patient is a compound heterozygote and her parents were heterozygous for each of the mutations.
基金Supported by the National Natural Science Foundation of China,No.81570468
文摘Interstitial lung and liver disease(ILLD) is caused by biallelic mutations in the methionyl-tRNA synthetase(MARS) gene. To date, no genetic changes other than missense variants were reported in the literature. Here, we report a five-month old female infant with typical ILLD(failure to thrive, developmental delay, jaundice, diffuse interstitial lung disease, hepatomegaly with severe steatosis, anemia, and thrombocytosis) showing novel phenotypes such as kidney stones, acetabular dysplasia, prolonged fever, and extreme leukocytosis. Whole exome sequencing revealed a novel truncating variant(c.2158 C>T/p.Gln720 Stop) together with a novel tri-nucleotide insertion(c.893_894 insTCG that caused the insertion of an arginine at amino acid position 299) in the MARS gene.
基金the Guangdong Medical Research Foundation,No.A2018550
文摘Steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307(p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid(UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid(CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.
文摘BACKGROUND Acute liver failure(ALF)can be a primary presentation of Wilson disease(WD).Mortality rates are high in WD with ALF(WDALF).Predictions of mortality in WDALF vary by model and are sometimes contradictory,perhaps because few patients are studied or WD diagnoses are questionable.AIM To determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.METHODS We reviewed the medical records of our pediatric WDALF patients(n=41 over 6-years-old,single-center retrospective study)and compared seven prognostic models(King’s College Hospital Criteria,model for end-stage liver disease/pediatric end-stage liver disease scoring systems,Liver Injury Unit[LIU]using prothrombin time[PT]or international normalized ratio[INR],admission LIU using PT or INR,and Devarbhavi model)with one another.RESULTS Among the 41 Han Chinese patients with ALF,WD was established by demonstrating ATP7B variants in 36.In 5 others,Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis.Three died during hospitalization and three underwent liver transplantation(LT)within 1 mo of presentation and survived(7.3%each);35(85.4%)survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis.Parameters significantly correlated with mortality included encephalopathy,coagulopathy,and gamma-glutamyl transpeptidase activity,bilirubin,ammonia,and serum sodium levels.Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.CONCLUSION WDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis,even after enlisting for LT.
基金the National Natural Science Foundation of China,No.81570468
文摘BACKGROUND Pediatric recurrent acute liver failure(RALF) with recovery between episodes is rare. Causes include autoimmune disease, which may flare and subside;intermittent exposure to toxins, as with ingestions; and metabolic disorders,among them the fever-associated crises ascribed to biallelic mutations in SCYL1,with RALF beginning in infancy. SCYL1 disease manifest with RALF, as known to date, includes central and peripheral neurologic and muscular morbidity(hepatocerebellar neuropathy syndrome). Primary ventilatory and skeletal diseases also have been noted in some reports.CASE SUMMARY We describe a Han Chinese boy in whom fever-associated RALF began at age 14 mo. Bilateral femoral head abnormalities and mild impairment of neurologic function were first noted aged 8 years 6 mo. Liver biopsy after the third RALF episode(7 years) and during resolution of the fourth RALF episode(8 years 6 mo) found abnormal architecture and hepatic fibrosis, respectively. Whole-exome sequencing revealed homozygosity for the novel frameshift mutation c.92_93 insGGGCCCT, p.(H32 Gfs~*20) in SCYL1(parental heterozygosity confirmed).CONCLUSION Our findings expand the mutational and clinical spectrum of SCYL1 disease. In our patient a substantial neurologic component was lacking and skeletal disease was identified relatively late.
基金Supported by National Science and Technology Major Project,No.2014ZX09101046-004(to Chen L)National Natural Science Foundation of China,Nos.81873543 and 81570468(to Wang JS).
文摘BACKGROUND Mannosyl-oligosaccharide glucosidase(MOGS)deficiency is an extremely rare type of congenital disorder of glycosylation(CDG),with only 12 reported cases.Its clinical,genetic,and glycomic features are still expanding.Our aim is to update the novel clinical and glycosylation features of 2 previously reported patients with MOGS-CDG.CASE SUMMARY We collected comprehensive clinical information,and conducted the immunoglobulin G1 glycosylation assay using nano-electrospray ionization source quadruple time-of-flight mass spectrometry.Novel dysmorphic features included an enlarged tongue,forwardly rotated earlobes,a birth mark,overlapped toes,and abnormal fat distribution.Novel imaging findings included pericardial effusion,a deep interarytenoid groove,mild congenital subglottic stenosis,and laryngomalacia.Novel laboratory findings included peripheral leukocytosis with neutrophil predominance,elevated C-reactive protein and creatine kinase,dyslipidemia,coagulopathy,complement 3 and complement 4 deficiencies,decreased proportions of T lymphocytes and natural killer cells,and increased serum interleukin 6.Glycosylation studies showed a significant increase of hypermannosylated glycopeptides(Glc3Man7GlcNAc2/N2H10 and Man5GlcNAc2/N2H5)and hypersialylated glycopeptides.A compensatory glycosylation pathway leading to an increase in Man5GlcNAc2/N2H5 was indicated with the glycosylation profile.CONCLUSION We confirmed abnormal glycomics in 1 patient,expanding the clinical and glycomic spectrum of MOGS-CDG.We also postulated a compensatory glycosylation pathway,leading to a possible serum biomarker for future diagnosis.
基金National Natural Science Foundation of China(72174138)High-level Public health Talents Training Program of Beijing Municipal Health Commission(2022-2-002).
文摘It has been more than 3 years since the novel coronavirus(SARS-CoV-2)pandemic raged globally.The coronavirus disease 2019(COVID-19)has greatly influenced human society.According to data from the World Health Organization(WHO),there were over 656 million confirmed cases of COVID-19 in the world as of January 1,2023,including over 6.6 million deaths[1].
基金funded by the National Key Research and Development Program of China(Grant No.2021YFC 2700800)(to JSW)the National Natural Science Foundation of China,Grants No.82201898(to TL),82171853(to JSW).+3 种基金supported by the Shanghai Sailing Program(20YF1402900 to TL)Health Industry Clinical Research Project of Shanghai Municipal Health Commission(20224Y0281 to TL)Chan-Xue-Yan Program of Fudan University(FDEKCXY17 to TL)the Canadian Institutes of Health Research(to VL&RW).
文摘Background and Aims:We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid(tauro-THBA)in cholestasis.Methods:Serum bile acid profiles were evaluated in 13 ABCB4-mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry(UPLC/MRM-MS).The concentration of tauro-THBA was compared between ABCB4-mutated patients with different prognoses.The areas under the curve(AUCs)of tauro-THBA were compared between ABCB11-mutated patients with native liver survival and those who died or underwent liver transplantation before 3 years of age by receiver operating characteristic curve(ROC),with another patient cohort for further verification.Results:The overall hydrophobicity indices of bile acids in ABCB4-mutated patients(12.99±3.25 m)were significantly lower than those of healthy controls(14.02±1.74 m,p<0.000).That was due to markedly increased bile acid modifications including conjugation,sulfation,and ketonization.Differences in the tauro-THBA concentration in ABCB4-mutated patients with different prognoses were not significant.ROC analysis indicated that levels of tauro-THBA of<60 nM yielded an AUC of 0.900 with a sensitivity of 80%and specificity of 87.5%for ABCB11-mutated patients with different prognoses(p=0.0192).Of the 15 patients with good prognosis,14 were classified correctly and four of the five patients with a poor prognosis were classified correctly(14:15 vs.1:5,p=0.005)with tauro-THBA as a classifier.Conclusions:Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gammaglutamyl transferase intrahepatic cholestasis patients.
基金Key Research and Development Program of China(No.2021YFC 2,700,800 to J-S W.National Natural Science Foundation of China(No.81741056 to WJS)National Natural Science Foundation of China(No.81873543 to WJS)Natural Science Foundation of Shanghai(20YF1402900 to T L).
文摘Background The liver manifestations of Alagille syndrome(ALGS)are highly variable,and factors affecting its prognosis are poorly understood.We asked whether the composition of bile acids in ALGS patients with good clinical outcomes differs from that in patients with poor outcomes and whether bile acids could be used as prognostic biomarkers.Methods Blood for bile acid profiling was collected from genetically confirmed JAG1-associated ALGS patients before one year of age.A good prognosis was defined as survival with native liver and total bilirubin(TB)<85.5 μmol/L,while a poor prognosis was defined as either liver transplantation,death from liver failure,or TB ≥ 85.5 μmol/L at the last follow-up.Results We found that the concentrations of two poly-hydroxylated bile acids,tauro-2β,3α,7α,12α-tetrahydroxylated bile acid(THBA)and glyco-hyocholic acid(GHCA),were significantly increased in patients with good prognosis compared to those with poor prognosis[area under curve(AUC)=0.836 and 0.782,respectively]in the discovery cohort.The same trend was also observed in the molar ratios of GHCA to glyco-chenodeoxycholic acid(GCDCA)and tetrahydroxylated bile acid(THCA)to tauro-chenodeoxycholic acid(TCDCA)(both AUC=0.836).A validation cohort confirmed these findings.Notably,tauro-2β,3α,7α,12α-THBA achieved the highest prediction accuracy of 88.00%(92.31%sensitivity and 83.33%specificity);GHCA at>607.69 nmol/L was associated with native liver survival[hazard ratio:13.03,95%confidence interval(CI):(2.662-63.753),P=0.002].Conclusions We identified two poly-hydroxylated bile acids as liver prognostic biomarkers of ALGS patients.Enhanced hydroxylation of bile acids may result in better clinical outcomes.
基金National Natural Science Foundation of China(72174138)High-level Public health Talents Training Program of Beijing Municipal Health Commission(2022-2-002).
文摘Monkeypox is a zoonotic disease.Since the first human monkeypox case was detected in 1970,it has been prevalent in some countries in central and western Africa.Since May 2022,monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide.As of September 14,2022,there have been more than 58,200 human monkeypox cases,and there is community transmission.The cessation of smallpox vaccination in 1980,which had some cross-protection with monkeypox,resulted in a general lack of immunity to monkeypox,which caused global concern and vigilance.As of Sep-tember 14,2022,there are four monkeypox cases in China,including three in Taiwan province and one in Hong Kong city.Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians'understanding of monkeypox and achieve early detection,early diagno-sis,early treatment,and early disposal,we have organized national authoritative experts in pediatric infection,respiratory,dermatology,critical care medicine,infectious diseases,and public health and others to formulate this expert consensus,on the basis of the latest"Clinical management and infection prevention and control for monkeypox"released by The World Health Organization,the"guidelines for diagnosis and treatment of monkeypox(version 2022)"issued by National Health Commission of the People's Republic of China and other relevant documents.During the development of this consensus,multidisciplinary experts have repeatedly demonstrated the etiology,epidemiology,transmission,clinical manifestations,laboratory examinations,diagnosis,differential diagnosis,treatment,discharge criteria,prevention,disposal process,and key points of prevention and control of suspected and confirmed cases.
