Colestasis, delirium y nocardiosis pulmonar en un varón con lupus eritematoso sistémico de inicio tardío / Cholestasis, delirium and pulmonary nocardiosis in a man with systemic lupus erythematosus of late onset

Resumen Se presenta el caso de un varón de 64 años que fue internado por delirium asociado a ictericia con patrón de colestasis en el hepatograma, y una masa en el pulmón derecho en el contexto de pérdida de peso y síndro me constitucional de 8 meses de evolución. Se realizó punción de la masa pulmonar cuyo cultivo desarrolló colonias blanquecinas identificadas como Nocardia cyria cigeorgica por espectrometría de masas (MALDI-TOF MS). Se llegó al diagnóstico de lupus eritematosos sistémico (LES) por presentar 8 de los criterios de acuerdo con el grupo SLICC 2012 y 24 puntos de acuerdo a los criterios EULAR/ACR 2019. La biopsia hepática mostró leve y variable infiltrado inflamatorio mixto en espacios porta, con ausencia de hepatitis de interfase y presencia de reacción ductular periférica. Se interpretaron estos hallazgos como vincu lados a hepatopatía por LES. El delirium fue interpretado como afectación neuroló gica por LES en base al descarte de otras enfermedades. Recibió tratamiento antibiótico y tras constatarse reducción del tamaño de la masa pulmonar se adminis traron pulsos de ciclofosfamida intravenosa. Evolucionó favorablemente, con normalización del hepatograma y el estado de conciencia, y recuperación del peso en forma progresiva. Al año se lo encontró en buen estado de salud. Justifica el reporte del caso la rara forma de presenta ción del LES de comienzo tardío, así como la nocardiosis pulmonar concomitante sin tratamiento inmunosupre sor previo.

Abstract A case is presented of a 64-year-old male patient who was admitted because of delirium, jaundice, a pattern of cholestasis in the liver profile and a right lung mass in the context of a constitutional syndrome and weight loss in the last eight months. The lung mass was punctured and the culture of the obtained material developed white colonies, identified by mass spectrometry (MALDI-TOF) as Nocardia cyriacigeorgica. Regarding the clinical diagnosis, it was considered as systemic lupus erythematosus (SLE), on the basis of fulfilling 8 criteria according to SLICC 2012 group, and 24 points according to EULAR/ACR 2019. The liver biopsy showed a mixt cellular infiltrate in portal spaces, with absence of interphase hepatitis and presence of peripheral ductular reaction. These findings were interpreted as liver compromise relate to SLE. Delirium was also considered as a neurological mani festation related to SLE on the basis of ruling out other causes. After being treated with antibiotics and documenting a reduction in the size of the lung mass he received cy clophosphamide in intravenous pulses, achieving normal ization of his liver profile and his state of consciousness, and a progressively weight recovering. A year after he was in good health. The report of this case is justified because of the rare presenting form of late onset SLE, as well as the concomi tant pulmonary nocardiosis in the absence of previous immunosuppressant treatment.

Case report on failed Kasai-portoenterostomy for extrahepatic biliary atresia with neonatal cholestasis in one-month-old infant

Biliary atresia is a neonatal onset, obstructive cholangiopathy of the intrahepatic or extrahepatic biliary system, leading to the build-up of bile in the liver. This case discusses a one-month-old infant who was previously diagnosed with jaundice, presenting the symptoms of yellowish eyes and skin, pale stools, and palpable liver. The infant and her mother抯 liver enzyme levels were found to be higher and her histopathology studies evidenced atretic gall bladder. The liver biopsy revealed mild periportal ductular reaction and diffuse hepatocanalicular cholestasis. She was diagnosed with neonatal cholestasis- extrahepatic biliary atresia (EHBA) and underwent Kasai-portoenterostomy. She was stable and discharged with gallstone dissolution agents, antibiotics, vitamin supplements, and a barbiturates-liver enzyme inducer. After six months, she presented hepatosplenomegaly with ascites and was found to have transaminitis. She was then diagnosed with EHBA- failed Kasai, probable cholangitis, and planned for living donor liver transplantation. Antibiotics, antiviral, antifungal, anticoagulants, and immunosuppressants were prescribed on discharge. The Doppler study of allograft was performed to check the blood flow after transplantation. Acute graft rejection was monitored on day 5 with liver transplant pack reports. One year later, the infant's condition had shown improvement, evidenced by enhanced food intake, absence of symptoms, and the return of liver function tests to normal levels.

Efficacy analysis of blood inflammation and liver function indexes in ICP diagnosis and delivery mode prediction / 重庆医学

Objective To observe the changes of laboratory blood indexes in patients with intrahepatic cholestasis of pregnancy(ICP),and analyze the value of blood inflammation indexes and liver function indexes in the diagnosis of ICP and the prediction of delivery mode.Methods A total of 251 patients diagnosed with ICP in this hospital from January 2021 to December 2022 were selected as the ICP group,and another 200 healthy pregnant women were selected as the control group.The patients with ICP were further divided into the severe ICP group(n=47)and the mild ICP group(n=204),the vaginal delivery group(n=113)and the cesarean section group(n=138)according to the severity of ICP and delivery mode.Mann-Whitney U test was used for comparison of parameters between groups,and Spearman method was used for correlation analy-sis.Receiver operating characteristic(ROC)curves were used to evaluate the efficacy of laboratory indicators in diagnosing ICP and predicting delivery mode.Results Neutrophil/lymphocyte ratio(NLR)[6.01(4.45,8.37)vs.3.36(4.12,3.51)]and aspartate transaminase(AST)level[20.00(16.00,33.00)U/L vs.15.00(13.00,18.00)U/L]in the ICP group were significantly higher than those in the control group(P＜0.05),and NLR in the severe ICP group was significantly higher than that in the mild ICP group[4.93(3.87,7.35)vs.4.14(3.12,5.17),P＜0.05].Correlation analysis showed that NLR was positively correlated with AST level(r=0.279,P＜0.001)and ICP severity(r=0.139,P=0.028)in patients with ICP.The area under ROC curve(AUC)of NLR combined with AST for ICP diagnosis was 0.882(95％CI:0.851-0.913).In ad-dition,cholinesterase(CHE)[6 020.00(5 499.50,6 703.50)U/L vs.5 341.50(4 651.75,6 259.25)U/L]and prealbumin(PA)[199.00(177.71,225.20)mg/Lvs.169.17(139.18,204.40)mg/L]levels in the va-ginal delivery group were significantly higher than those in the cesarean section group(P＜0.05),and the AUC of CHE combined with PA for predicting vaginal delivery in ICP patients was 0.727(95％CI:0.664-0.789).Conclusion NLR and AST have potential value in the diagnosis of ICP,and CHE and PA have poten-tial value in predicting delivery mode of ICP patients.

Paricalcitol inhibition of oxidative stress alleviates the damage of hepatocyte tight junction in mice / 基础医学与临床

Objective To explore the impact of paricalcitol(Pal)on the oxidative stress-induced tight junction dam-age of mouse hepatocytes and its mechanism.Methods A model of cholestatic liver injury was created by routine bile duct ligation.The mice were randomly divided into control group(control),model group(BDL)and treatment group(BDL+Pal).HE staining microscopy was used to observe the morphological changes of liver tissues.The human hepa-toma cell line HepG2 was cultured and divided into blank group,model group(400 μmol/L H2O2)and treatment group(400 μmol/L H2O2+20 nmol/L Pal).Western blot was used to examine the level of tight junction protein 1(ZO-1),occludin,phosphorylated p65(p-p65),phosphorylated ERK(p-ERK)and phosphorylated myosin II regulated light chain(p-MLC)protein were checked in each group.Results Compared with the control group,the level of p-p65,p-ERK and p-MLC in the model group was significantly increased(P＜0.000 1 or P＜0.01 or P＜0.001).The protein expression of ZO-1 and occludin was significantly decreased(P＜0.01).HE staining mi-croscopy showed an increased hepatocyte necrosis and inflammatory cell infiltration.In contrast,the above levels in the treatment group showed an opposite trend relative to the model group.Conclusions Pal is able to alleviate the damage of hepatocyte tight junctions by inhibiting oxidative stress in cholestatic mice and HepG2 cells.Its mecha-nism is potentially related to the inhibition of reactive oxygen species and NF-κB/p65 and ERK signaling pathways.

Construction and validation of Alignment Diagram model for risk of parenteral nutrition-associated cholestasis in extremely/ultra-low birth weight infants / 中国小儿急救医学

Objective:To explore the high-risk factors for parenteral nutrition associated cholestasis（PNAC）in extremely/ultra-low birth weight infants，and establish a risk Alignment Diagram prediction model.Methods:We retrospectivly analyzed the clinical data of hospitalized extremely/ultra-low birth weight infants admitted to Neonatology Department at Quanzhou Children's Hospital from January 2019 to December 2020，using multivariate Logistic regression analysis to screen for independent risk factors for the occurrence of PNAC.An Alignment Diagram model prediction model for PNAC was constructed by using R software，and the performance of the model was evaluated through receiver operating characteristic curves.Results:A total of 203 extremely/ultra-low birth weight infants were included，with a median gestational age of 29.14（28.00，30.86）weeks and a median birth weight of 1　170（1　000,1　300）g.Among them，26（12.81%）cases developed PNAC.Multivariate Logistic regression analysis showed that the duration of parenteral nutrition（ OR=1.015 ，95% CI 1.003-1.034），the cumulative amount of glucose（ OR=1.014 ，95% CI 1.001-1.028），small for gestational age（ OR=3.455 ，95% CI 1.127-10.589），and neonatal sepsis（ OR=3.142 ，95% CI 1.039-9.503）were independent risk factors for PNAC（ P＜0.05）；The four independent risk factors mentioned above were introduced into R software to construct an Alignment Diagram model，the area under the receiver operating characteristic curve was 0.835（95% CI 0.842-0.731），and the results of the Hosmer Limeshow goodness of fit test show that：χ 2=5.34，degree of freedom=8， P=0.72.A calibration curve indicated good consistency between the predicted probability of the model and the actual occurrence rate，with good accuracy. Conclusion:The Alignment Diagram model constructed based on four independent risk factors of the duration of parenteral nutrition，glucose accumulation，small for gestational age infants，and neonatal sepsis exhibits high predictive ability，and is expected to provide an intuitive and convenient visualization tool for preventing or reducing the occurrence of PNAC in extremely/ultra-low birth weight infants

Mechanism of bis（2-ethylhexyl） phthalate in inducing cholestasis and liver injury in mice / 临床肝胆病杂志

ObjectiveTo investigate the mechanism of bis（2-ethylhexyl） phthalate （DEHP） in inducing cholestasis and liver injury in mice. MethodsIn the in vivo experiment， adult female ICR mice were randomly divided into control group （corn oil） and DEHP group （200 mg/kg/d）， and a model of cholestasis was established by intragastric administration for 4 weeks. After blood and liver tissue samples were collected from all mice， a biochemical analyzer was used to measure the level of total bile acid （TBA） in serum and the liver， and a microplate reader was used to measure alkaline phosphatase （ALP） and gamma-glutamyl transpeptidase （GGT）； HE staining was used to observe the pathological changes of the liver； RT-PCR was used to measure the mRNA expression levels of the inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the liver； liquid chromatography/triple quadrupole mass spectrometry was used to measure the bile acid profile in the liver of mice. In the in vitro experiment， AML-12 mouse hepatocytes were cultured and treated with DEHP （250 µmol/L）， DCA （125 µmol/L）， and CDCA （125 µmol/L） for 24 hours， and RT-PCR was used to measure the mRNA expression levels of the inflammatory cytokines IL-1β， IL-6， and TNF-α. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the LSD-t test was used for further comparison between two groups. ResultsThe in vivo experiment showed that compared with the control group， the DEHP group had significant increases in the serum levels of TBA， ALP， and GGT and the level of TBA in the liver （the t values are respectively -4.396， -5.109， -8.504， -3.792 and -7.974， all P<0.05，）. Compared with the control group， the DEHP group had significant increases in cholic acid， chenodeoxycholic acid， taurocholic acid， deoxycholic acid， and ursodeoxycholic acid （the t values are respectively -2.802， -3.177， -2.633， -2.874 and -2.311， all P<0.05）. HE staining of the liver showed that the mice in the DEHP group had enlargement of the portal area， bile duct deformation， inflammatory cell infiltration around the bile duct， and significant increases in the mRNA expression levels of the inflammatory factors IL-1β， IL-6， and TNF-α in the liver （the t values are respectively -2.539， -2.823 and -4.636， all P<0.05）. The in vitro experiment showed that the actual difference in hepatocyte viability after 0-1 000 µmol/L DEHP treatment does not exceed 15%， but there were significant increases in the mRNA expression levels of the inflammatory cytokines IL-1β， IL-6， and TNF-α after treatment with DEHP at different concentrations of 125 µmol/L， 250 µmol/L， and 500 µmol/L （all P<0.05）. Compared with DEHP stimulation alone， the combined stimulation of CDCA and DEHP upregulates the cytokine in hepatocyte IL-1β mRNA levels （P<0.01）； the combined stimulation of DCA and DEHP can significantly increase the cytokine in hepatocyte IL-1β and IL-6 mRNA levels （all P<0.01）. ConclusionDEHP exposure can cause cholestasis and induce liver inflammation in mice， possibly by promoting the production of toxic bile acids and the secretion of inflammatory factors.

Role of apical sodium-dependent bile acid transporter in hepatobiliary diseases / 临床肝胆病杂志

Apical sodium-dependent bile acid transporter （ASBT） is a key transporter responsible for intestinal reabsorption of bile acid and plays an important role in maintaining bile acid and cholesterol homeostasis， and its expression is regulated by various factors including transcription factors， nuclear receptors， and intestinal microflora. The abnormal expression and function of ASBT can lead to disorders in the metabolism of bile acid and cholesterol， causing a variety of hepatobiliary diseases. At present， ASBT has attracted wide attention as a therapeutic target. This article elaborates on the biological characteristics and expression regulation mechanism of ASBT and reviews the role of ASBT in hepatobiliary diseases， in order to provide a new direction for the treatment of related diseases.

Serum procalcitonin as a marker of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD)

Abstract Background Neonatal Intrahepatic Cholestasis (NICCD), as the early-age stage of Citrin deficiency involving liver dysfunction, lacks efficient diagnostic markers. Procalcitonin (PCT) has been identified as a biomarker for infection as well as various organ damage. This study aimed to explore the potential of PCT as a biomarker for NICCD. Methods In a single-center retrospective case-control study. Serum PCT concentrations before and after treatment of 120 NICCD patients, as the study group, were compared to the same number of cholestatic hepatitis patients, as the control group. The potential value of PCT to discriminate NICCD from control disease was further explored using Receiver Operating Characteristic (ROC) curve analysis and compared to those of other inflammatory markers. Results There was a significantly higher level of PCT in NICCD patients than in the control group. PCT concentrations were only weakly correlated with neutrophil counts and CRP levels (p ˂ 0.05). At a cut-off value of 0.495 ng/mL, PCT exhibited a significantly higher diagnostic value compared to other inflammatory markers for discriminating NICCD from the control, with a sensitivity of 90.8 % and specificity of 98.3 %. Conclusion PCT might be used as an initial biomarker to discriminate children with NICCD from another hepatitis disease.

Factors associated with cholestasis in newborns with gastroschisis / Fatores associados à colestase em recém-nascidos com gastrosquise

ABSTRACT Objective: To describe the incidence and to analyze risk factors associated with cholestasis in neonates with gastroschisis. Methods: This is a retrospective cohort study in a tertiary single center analyzing 181 newborns with gastroschisis between 2009 and 2020. The following risk factors associated with cholestasis were analyzed: gestational age, birth weight, type of gastroschisis, silo closure or immediate closure, days of parenteral nutrition, type of lipid emulsion, days of fasting, days to reach a full diet, days with central venous catheter, presence of infections, and outcomes. Results: Among the 176 patients evaluated, 41 (23.3%) evolved with cholestasis. In the univariate analysis, low birth weight (p=0.023), prematurity (p<0.001), lipid emulsion with medium-chain triglycerides and long-chain triglycerides (p=0.001) and death (p<0.001) were associated with cholestasis. In the multivariate analysis, patients who received lipid emulsion with fish oil instead of medium chain triglycerides/long chain triglycerides (MCT/LCT) emulsion had a lower risk of cholestasis. Conclusions: Our study shows that lipid emulsion with fish oil is associated with a lower risk of cholestasis in neonates with gastroschisis. However, this is a retrospective study and a prospective study should be performed to confirm the results.

RESUMO Objetivo: Analisar a incidência e os fatores de risco associados à colestase em recém-nascidos com gastrosquise. Métodos: Estudo de coorte retrospectivo em um único centro terciário, que analisou 181 recém-nascidos com gastrosquise entre 2009 e 2020. Foram examinados os seguintes fatores de risco associados à colestase: idade gestacional, peso ao nascer, tipo de gastrosquise, fechamento com silo ou fechamento imediato, dias de uso nutrição parenteral, tipo de emulsão lipídica, dias de jejum, dias para atingir a dieta completa, dias com cateter venoso central, presença de infecções e desfechos. Resultados: Dos 176 pacientes avaliados, 41 (23,3%) evoluíram com colestase. Baixo peso ao nascer (p=0,023), prematuridade (p<0,001), emulsão lipídica com triglicerídeos de cadeia média e triglicerídeos de cadeia longa (p=0,001) e óbito (p<0,001) foram associados à colestase. Na análise multivariada, os pacientes que receberam emulsão lipídica com óleo de peixe em vez da emulsão diária de triglicérides de cadeia média/triglicérides de cadeia longa (MCT/LCT) apresentaram menor risco de colestase. Conclusões: Nosso estudo mostra que a emulsão lipídica com óleo de peixe está associada a menor risco de colestase em neonatos com gastrosquise, porém este é um estudo retrospectivo, e um estudo prospectivo deve ser realizado para confirmar os resultados.

Antioxidant effect of Rosa pimpinellifolia L. fruit extract on cholestatic liver injury: an experimental study

SUMMARY BACKGROUND: Antioxidants have been considered a rational curative strategy to prevent and cure liver diseases involving oxidative stress. An acute obstructive jaundice rat model was established to investigate the in vivo hepatoprotective efficacy of Rosa pimpinellifolia L. METHODS: The experimental jaundice model was performed by binding the main bile duct in 25 male Sprague-Dawley rats. All rats were randomly divided into five groups: first group: laparotomy-sham-only, second group: biliary tract binding (control), and third, fourth, and fifth groups: treatment groups with 250, 500, and 750 mg/kg fruit extracts daily, respectively. RESULTS: Considering dosage, although there was no significant therapeutic effect in the 250 mg/kg of Rosa pimpinellifolia L. group, the best results were found in the 500 mg/kg dose group, while results in the 750 mg/kg dose group showed consistent correlation with proinflammatory response. With regard to biochemical parameters, lipid hydroperoxide level in the rat serum and liver tissue was significantly decreased in all treatment groups. Amadori products, which are one of the early markers of glycol-oxidative stress, showed statistical significance in the treatment. CONCLUSION: It was revealed that the antioxidant effect of Rosa pimpinellifolia L. was more prominent in the early stages of hepatic injury secondary to oxidative stress.

Biliary acids is a critical laboratory value in pregnant women: a case report as an opportunity to improve the quality of care

Biliary acids (BA) levels were found greatly increased to 72.1 µM/l in a pregnant woman. Bambino Gesù Children’s Hospital had not established critical alarm values for BA, so communication of the result was overpassed. After 30 hours, the patient referred to the emergency room of another hospital for the assessment of the pregnancy course and BA re-evaluation, which in turn resulted normal. BA levels in our sample were re-analyzed in both laboratories and high levels were confirmed. We utilized an enzymatic cycling colorimetric method measuring primary, secondary and tertiary BA. The patient was on therapy with ursodeoxycholic acid (UDCA) explaining total BA results difference reported in the two different blood samples. BA accumulation maybe leads to fetal complications or loss and a quick communication of the result to clinician could potentially be life-saving for the baby. We implemented corrective actions to avoid adverse events by the introduction of a note on the report, warning of UDCA therapy interference in BA dosage and recommending the suspension of therapy 24 hours before blood sampling; furthermore, in order to provide high level of health care, we introduced an alarm value for fertile women in our critical values list.

A case report of intrahepatic cholestasis of pregnancy with acute pancreatitis

Cholestasis is a condition that impairs the release of a digestive fluid called bile from liver cells. As a result, bile builds up in the in the liver, impairing liver function. The problems with bile release occur within the liver (intrahepatic), the condition is described as intrahepatic cholestasis. Intrahepatic cholestatsis of pregnancy usually becomes apparent in the third trimester of pregnancy. Bile flow returns to normal after delivery of the baby, and the signs and symptoms of the condition disappear. However, they can return during later pregnancies. Intrahepatic cholestasis of pregnancy can cause problems for the unborn baby. The condition is associated with an increased risk of premature delivery and stillbirth. Additionally, some infants born to mothers with intrahepatic cholestasis of pregnancy have a slow heart rate and a lack of oxygen during delivery (fetal distress). Acute pancreatitis is defined as the sudden inflammation of pancreas manifested clinically by abdominal pain, nausea of dehydration that is usually self-limiting but occasionally can progress to severe disease and even death. Most cases of acute pancreatitis in pregnancy are caused by gallstone disease. It is thought with the weight and hormonal changes induced by pregnancy, gallstones are more likely to form and thus travel down the common bile duct to obstruct the pancreatic duct outflow. Another proposed mechanism for acute pancreatitis in pregnancy is high fat levels in the blood called triglycerides. Again, the hormonal changes of pregnancy can predispose certain women to developing this condition. When the triglycerides levels become too high, oxygen cannot adequately travel to the pancreas via bloodstream, and pancreatitis can ensue. Acute fatty liver of pregnancy (AFLP) is a rare but life-threatening complication that typically occurs in the third trimester of pregnancy. Extant studies show the low incidence of AFLP ranging from 1/7000 to 1/20000. Maternal mortality is 10% to 15%, and fetal mortality is up to 20% . The severity of this disease underscores the need for early diagnosis and management. The clinical diagnosis of AFLP is challenging, and the differential diagnoses includes other peripartum conditions such as severe viral hepatitis, pre-eclampsia, hemolysis, elevated liver enzymes, and a low platelet count (HELLP) syndrome or thrombotic microangiopathies. The primary treatment for AFLP includes rapid pregnancy termination and symptomatic therapy. Liver transplantation has been considered a last resort. We reported the case of 20-year-old primigravida at 36 weeks of gestation who developed IHCP mimicking Acute fatty liver of pregnancy with Acute Pancreatitis, however with multidisciplinary team approach she had a good feto-maternal outcome.

Aspectos clínicos, laboratoriais e evolutivos de pacientes pediátricos com doença hepática por deficiência de alfa 1-antitripsina / Clinical, laboratorial and evolutionary aspects of pediatric patients with liver disease due to alpha 1-antitrypsin deficiency

ABSTRACT Background: Alpha 1-antitrypsin deficiency (AATD) is a hereditary codominant autosomal disease. This liver disease ranges from asymptomatic cases to terminal illness, which makes early recognition and diagnosis challenging. It is the main cause of pediatric liver transplantation after biliary atresia. Objective: To describe the clinical characteristics, as well as those of histologic and laboratory tests, phenotypic and/or genetic evaluation and evolution of a cohort of pediatric patients with AATD. Methods: This is a retrospective observational study of 39 patients with confirmed or probable AATD (without phenotyping or genotyping, but with suggestive clinical features, low serum alpha 1-antitrypsin (AAT) level and liver biopsy with PAS granules, resistant diastasis). Clinical, laboratory and histological varia­bles, presence of portal hypertension (PH) and survival with native liver have been analyzed. Results: A total of 66.7% of 39 patients were male (26/39). The initial manifestation was cholestatic jaundice in 79.5% (31/39). Liver transplantation was performed in 28.2% (11/39) of patients. Diagnosis occurred at an average of 3.1 years old and liver transplantation at 4.1 years of age. 89.2% (25/28) of the patients with confirmed AATD were PI*ZZ or ZZ. The average AAT value on admission for PI*ZZ or ZZ patients was 41.6 mg/dL. All transplanted patients with phenotyping or genotyping were PI*ZZ (or ZZ). Those who were jaundiced on admission were earlier referred to the specialized service and had higher levels of GGT and platelets on admission. There was no significant difference in the survival curve when comparing cholestatic jaundiced to non-cholestatic jaundiced patients on admission. Comparing patients who did or did not progress to PH, higher levels of AST and APRI score at diagnosis (P=0.011 and P=0.026, respectively) were observed and in the survival curves patients with PH showed impairment, with 20.2% survival with native liver in 15 years. Conclusion: Jaundice is an important clinical sign that motivates referral to a specialist, but it does not seem to compromise survival with native liver. Patients progressing to PH had higher AST, APRi score on admission and significantly impaired survival with native liver. It is important to pay attention to these signs in the follow-up of patients with AATD.

RESUMO Contexto: Deficiência de alfa 1-antitripsina (DAAT) é uma doença hereditária, de caráter autossômico codominante. A apresentação da doença hepática varia desde casos assintomáticos até doença terminal, o que dificulta reconhecimento e diagnóstico precoces. É a principal causa de transplante hepático pediátrico após atresia de vias biliares. Objetivo: Descrever as características clínicas, de exames laboratoriais, histológicos, avaliação fenotípica e/ou genética e sobrevida de uma coorte de pacientes pediátricos com DAAT. Métodos: Estudo observacional retrospectivo de 39 pacientes com diagnóstico de DAAT confirmada ou provável (sem fenotipagem ou genotipagem, mas com clínica sugestiva, baixo nível sérico de alfa 1-antitripsina (A1AT) e biópsia hepática com grânulos PAS, diástase resistentes). Variáveis clínicas, laboratoriais, histológicas, presença de hipertensão portal (HP) e sobrevida com fígado nativo foram analisadas. Resultados: Dos 39 pacientes, 66,7% eram do sexo masculino (26/39). A manifestação inicial foi icterícia colestática em 79,5% (31/39). Em 28,2% (11/39) houve necessidade de transplante hepático. O diagnóstico ocorreu com uma idade média de 3,1 anos e, o transplante hepático, 4,1 anos. Dos pacientes com DAAT confirmada, 89,2% (25/28) eram PI*ZZ ou ZZ. O valor médio de A1AT na admissão de pacientes PI*ZZ ou ZZ foi 41,6 mg/dL. Todos os transplantados com fenotipagem ou genotipagem eram PI*ZZ (ou ZZ). Os ictéricos à admissão foram referenciados mais cedo ao serviço especializado e apresentaram níveis mais elevados de GGT e plaquetas à admissão. Não houve diferença significativa na curva de sobrevida ao compararmos icterícia colestática ou não à admissão. Ao comparar os pacientes que progrediram ou não para HP, observou-se níveis mais elevados de AST e APRI escore ao diagnóstico (P=0,011 e P=0,026, respectivamente) e, nas curvas de sobrevida, pacientes com HP apresentaram comprometimento, com 20,2% de sobrevida com fígado nativo em 15 anos. Conclusão: Icterícia é um sinal clínico importante que motiva o encaminhamento ao especialista, mas parece não comprometer a sobrevida com fígado nativo. Pacientes com evolução para HP tiveram AST e escore APRi mais elevados à admissão e comprometimento significativo da sobrevida com fígado nativo. Importante atentar a esses sinais no seguimento de pacientes com DAAT.

Intrahepatic cholestasis of pregnancy- case series done in a tertiary care hospital

Intrahepatic cholestasis of pregnancy (ICP) also known as obstetric cholestasis is a liver disorder of pregnancy which is characterised by maternal pruritus usually in the third trimester, raised serum bile acids and increased incidence of adverse fetal outcomes and usually complete resolution of symptoms post-delivery. The etiology of ICP is complex and multifactorial as is the mechanism by which fetal complications occur which is yet not completely understood. The introduction of ursodeoxycholic acid in the management of ICP has provided significant improvement in maternal symptoms as well as fetal outcome. We present a case series of 5 cases of obstetric cholestasis which presented in our tertiary care hospital which could possibly help and guide obstetricians in the future who are dealing with dilemma in diagnosis and management of this condition.

Colangiopatía hipertensiva portal por transformación portal cavernomatosa de origen no cirrótica: a propósito de un caso

La colangiopatía portal hace referencia a anomalías colangiográficas que se producen en pacientes con cavernomatosis portal, siendo progresiva, cursando con enfermedad biliar sintomática y anomalías graves de las vías biliares. Y, representa una complicación infrecuente de la hipertensión portal. Se describe el caso de un hombre de 53 años, con historia de larga data de hipertensión portal nocirrótica y cavernomatosis portal, quien presentó un episodio de enfermedad biliar obstructiva sintomática, y en estudios se documentó tejido fibrótico de extensión periportal ascendente con compresión extrínseca del colédoco distal y dilatación de la vía biliar extra e intrahepática. Por lo que se procedió a colangiopancreatografía retrógrada endoscópica, realizándose tratamiento paliativo, con papilotomía pequeña y colocación de endoprótesis biliar plástica, siendo exitoso por ausencia de complicaciones procedimentales, y mejoría clínica y parámetros bioquímicos. Finalmente, recibiendo de alta con indicación de seguimiento prioritario para recambios periódicos de endoprótesis biliares, y valoración por hepatología. La colangiopatía portal es una entidad rara que debe sospecharse en sujetos con hipertensión portal de origen no-cirrótico, con hallazgos imagenológicos de estenosis, angulaciones o dilataciones segmentarias, su tratamiento debe ser individualizado, y la terapia endoscópica es de elección en enfermedad biliar sintomática.

Portal cholangiopathy refers to cholangiographic abnormalities occurring in patients with portal cavernomatosis, being progressive, presenting with symptomatic biliary disease and severe biliary tract abnormalities. And, it represents an infrequent complication of portal hypertension. We describe the case of a 53-year-old man with a long history of non-cirrhotic portal hypertension and portal cavernomatosis, who presented an episode of symptomatic obstructive biliary disease, and studies documented fibrotic tissue of ascending periportal extension with extrinsic compression of the distal common bile duct and dilatation of the extra and intrahepatic biliary tract. Therefore, endoscopic retrograde cholangiopancreatography was performed, and palliative treatment with small papillotomy and placement of a plastic biliary endoprosthesis was successful due to the absence of procedural complications, and clinical improvement and biochemical parameters. Finally, the patient was discharged with indication of priority follow-up for periodic replacement of biliary stents, and evaluation by hepatology. Portal cholangiopathy is a rare entity that should be suspected in subjects with portal hypertension of non-cirrhotic origin, with imaging findings of stenosis, angulations or segmental dilatations, its treatment should be individualized, and endoscopic therapy is of choice in symptomatic biliary disease.

Biliary atresia: a review

Bile duct atresia (BA) is a severe, progressive cholangiopathy characterized by fibrous and inflammatory obliteration of the intrahepatic and extrahepatic bile ducts. It leads to liver failure, scarring, and end-stage cirrhosis if timely treatment is not achieved. It represents the number one indication for pediatric liver transplantation as a single disease worldwide. Various etiological factors have been associated with BA, such as structural malformations, viral, immune-mediated, and genetic infections. The incidence of BA varies around the world. Untreated BA patients have a 2-year mortality of nearly 100%. The clinical picture is characterized by jaundice, acholia, and jaundice that persists beyond the first 2 weeks of life. Direct or conjugated bilirubin remains the primary screening laboratory test for BA; elevated values ??occur within the first 2 days of life. Currently, the primary treatment of choice is the Kasai portoenterostomy; the success of surgery has been based on the restoration of bile flow and the elimination of jaundice. However, more than 70% of patients develop liver cirrhosis secondary to persistent liver inflammation, which will require liver transplantation. The following review of the literature aims to collect relevant information from what has been published in recent years on bile duct atresia; focused on the study of etiology, pathophysiology, advances in genetics and immunology. As well as the results associated with surgical treatment and the requirement for liver transplantation.

Colestasis intrahepática drepanocítica a propósito de un casoy revisión de la literatura / Sickle cell intrahepatic cholestasis regarding a case and reviewof the literature

La enfermedad de células falciformes (ECF) o anemia drepanocítica, es el trastorno hereditario más frecuente en los glóbulos rojos, y la enfermedad con más complicaciones en diferentes órganos, lo que provoca múltiples presentaciones de una misma enfermedad., se hace revisión literatura sobre ECF y colestasis intrahepática drepanocítica, y se describe un caso presentado en el Hospital General y de Especialidades Nuestra Señora de la Altagracia de Higüey Republica Dominicana en el año 2022. Es un varón de 24 años, con diagnóstico de ECF, que se complicó con una colestasis intrahepática drepanocítica muy severa que se manejó con hemodiálisis. El objetivo de publicar este caso es revisar la información respecto a la incidencia y la morbimortalidad de esta complicación, teniendo en cuenta que fue tratado por un equipo multidisciplinario usando la hemodiálisis como alternativa terapéutica(AU)

Sickle cell disease (SCD) or sickle cell anemia is the most common hereditary disorder in red blood cells, and the disease with the most complications in different organs, which causes multiple presentations of the same disease. Literature review on SCD is made and sickle cell intrahepatic cholestasis,and a case presented at the Hospital General y de Especialidades Nuestra Señora de la Altagracia de Higüey in the Dominican Republic in 2022 is described. Very severe sickle cell intrahepatic disease that was managed with hemodialysis. The purpose of publishing this case is to review the information regarding the incidence and morbidity and mortality of this complication,taking into account that it was treated by a multidisciplinary team using hemodialysis as a therapeutic alternative(AU)

Evaluation of bile acid and deranged liver function test in obstetrics cholestasis in pregnancy in fetal and perinatal outcome

Background: Pregnancy-related intrahepatic cholestasis is most prevalent hepatic disorder intense pruritus that affects the entire body including palm and sole. It is typically detected during second or third trimester. Pruritus frequently exacerbates at night, marked on the palms and soles of the feet and hands. Aim of this study was to evaluate bile acid and deranged liver function test in obstetrics cholestasis in pregnancy and to determine maternal fetal and outcomes.Methods: This prospective case series study was conducted in the Department of Obstetrics and Gynaecology, Muzaffarnagar Medical College. The present study was conducted in 50 women, who were selected from outpatient department of antenatal care from tertiary care, taken written permission before study. The medical records of all women with obstetrics cholestasis who delivered between December 2021and August 2022.Results: Subjects with IHCP has mean age of 30.11±5.03 year, found SGOT 40% in 100-200 and SGPT 44 % I (0-100) range and total bilirubin levels is 33 % in IHCP patients. In study found that LSCS due to 24% in fetal distress, 36% in MSL, 16% in IUGR, 14% preterm. Participants have 22% birth weight <2.5kg and 39 (78%) are under >2.5kg babies in IHCP patients and 24 % were underwent fetal distress and 24 % preterm delivery and 6 % got IUD . and no stillborn and 12% meconium.Conclusions: It causes maternal pruritus with impaired LFT and raised serum bile acids. Maternal morbidity is increased in terms of increased LSCS rates and discomfort due to pruritus.

Clinical, laboratory, and etiological profile of three infants with neonatal cholestasis and review of literature

Neonatal cholestasis occurs due to failure of the excretion of bile. This happens due to defects in intrahepatic bile production, defects in transmembrane transport of bile, or mechanical obstruction to the flow of bile. Etiology varies from biliary atresia, choledochal cyst, inborn errors of metabolism, neonatal hepatitis, progressive familial intrahepatic cholestasis, congenital infections, etc. Our 3 patients presented with hepatomegaly, splenomegaly, pale stools, and dark urine. We hereby report all these Indian infants presented with cholestasis and discussed in detail regarding clinical, laboratory, and etiological profiles of all.

Colestasis intrahepática por Treponema pallidum en paciente inmunocompetente / Intrahepatic cholestasis due to Treponema pallidum in an immunocompetent patient

La hepatitis por Treponema pallidum es una entidad poco frecuente y su diagnóstico representa un reto clínico. Treponema pallidum debe considerarse como etiología presuntiva en todo paciente con enfermedad hepática aguda, en el cual se hayan descartado otras causas más frecuentes. Se presenta el caso de un paciente joven, inmunocompetente, quien presentó elevación de los valores de las pruebas hepáticas con patrón colestásico y lesiones maculopapulares en palmas y plantas. Dado su cuadro clínico, las pruebas diagnósticas y la respuesta a la terapia antimicrobiana instaurada, se estableció el diagnóstico de colestasis por una sífilis secundario sifilítiao. Es importante incluir la sífilis secundaria entre las posibles causas de enfermedad hepática aguda.

Hepatitis due to Treponema pallidum is a rare entity and its diagnosis represents a clinical challenge. Treponema pallidum should be considered as a presumptive etiology in all patients with acute liver disease, when other frequent causes have been ruled out. We present the case of a young, immunocompetent patient with elevated values in his liver tests, a cholestatic pattern, and maculopapular lesions on his palms and soles. Given his clinical picture, diagnostic tests, and response to the antimicrobial therapy, a diagnosis of cholestasis due to secondary syphilis has been established. It is important to include secondary syphilis within the possible causes of acute liver disease.