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BACKGROUND AND AIMS: Identifying patients with steatotic liver disease who are at a high risk of developing HCC remains challenging. We present a deep learning (DL) model to predict HCC development using hematoxylin and eosin-stained whole-slide images of biopsy-proven steatotic liver disease. APPROACH AND RESULTS: We included 639 patients who did not develop HCC for ≥7 years after biopsy (non-HCC class) and 46 patients who developed HCC <7 years after biopsy (HCC class). Paired cases of the HCC and non-HCC classes matched by biopsy date and institution were used for training, and the remaining nonpaired cases were used for validation. The DL model was trained using deep convolutional neural networks with 28,000 image tiles cropped from whole-slide images of the paired cases, with an accuracy of 81.0% and an AUC of 0.80 for predicting HCC development. Validation using the nonpaired cases also demonstrated a good accuracy of 82.3% and an AUC of 0.84. These results were comparable to the predictive ability of logistic regression model using fibrosis stage. Notably, the DL model also detected the cases of HCC development in patients with mild fibrosis. The saliency maps generated by the DL model highlighted various pathological features associated with HCC development, including nuclear atypia, hepatocytes with a high nuclear-cytoplasmic ratio, immune cell infiltration, fibrosis, and a lack of large fat droplets. CONCLUSIONS: The ability of the DL model to capture subtle pathological features beyond fibrosis suggests its potential for identifying early signs of hepatocarcinogenesis in patients with steatotic liver disease.
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AIM: To evaluate the use of donor-derived cell-free DNA (dd-cfDNA) in diagnosing graft injuries in Japanese liver transplantation (LTx), including family-related living donors. METHODS: A total of 321 samples from 10 newly operated LTx recipients were collected to monitor the early dynamics of dd-cfDNA levels after LTx. Fifty-five samples from 55 recipients were collected during protocol biopsies (PB), whereas 36 samples from 27 recipients were collected during event biopsies, consisting of 11 biopsy-proven acute rejection (AR), 20 acute dysfunctions without rejection (ADWR), and 5 chronic rejections. The levels of dd-cfDNA were quantified using a next-generation sequencer based on single nucleotide polymorphisms. RESULTS: The dd-cfDNA levels were elevated significantly after LTx, followed by a rapid decline to the baseline in patients without graft injury within 30 days post-LTx. The dd-cfDNA levels were significantly higher in the 11 samples obtained during AR than those obtained during PB (p < 0.0001), which decreased promptly after treatment. The receiver operator characteristic curve analysis of diagnostic ability yielded areas under the curve of 0.975 and 0.897 for AR (rejection activity index [RAI] ≥3) versus PB and versus non-AR (ADWR + PB). The dd-cfDNA levels during AR were elevated earlier and correlated more strongly with the RAI (r = 0.740) than aspartate aminotransferase/alanine aminotransferase. The dd-cfDNA levels were neither associated with graft fibrosis based on histology nor the status of donor-specific antibodies in PB samples. CONCLUSIONS: Donor-derived cell-free DNA serves as a sensitive biomarker for detecting graft injuries in LTx. Further large-scale cohort studies are warranted to optimize its use in differentiating various post-LTx etiologies.
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BACKGROUND: Patients with intestinal failure (IF) often present with abnormal body composition characterized by high fat mass. However, the distribution of fat and its association with the development of IF-associated liver disease (IFALD) remain unclear. This study aims to investigate the body composition and its relationship with IFALD in older children and adolescents with IF. METHODS: This retrospective case-control study enrolled patients with IF receiving parenteral nutrition (PN) at Keio University Hospital who initiated PN before the age of 20 years (cases). The control group included patients with abdominal pain, with available computed tomography (CT) scan and anthropometric data. CT scan images of the third lumbar vertebra (L3) were used for body composition analysis and compared between the groups. Liver histology was compared with CT scan findings in IF patients who underwent biopsy. RESULTS: Nineteen IF patients and 124 control patients were included. To account for age distribution, 51 control patients were selected. The median skeletal muscle index was 33.9 (29.1-37.3) in the IF group and 42.1 (39.1-45.7) in the control group (P < 0.01). The median visceral adipose tissue index (VATI) was 9.6 (4.9-21.0) in the IF group and 4.6 (3.0-8.3) in the control group (P = 0.018). Among the 13 patients with IF who underwent liver biopsies, 11 (84.6%) had steatosis, and there was a tendency for fibrosis to correlate with VATI. CONCLUSION: Patients with IF exhibit low skeletal muscle mass and high visceral fat, which may be related to liver fibrosis. Routine monitoring of body composition is recommended.
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Enfermedades Intestinales , Insuficiencia Intestinal , Hepatopatías , Fallo Hepático , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Estudios de Casos y Controles , Estudios Retrospectivos , Hepatopatías/complicaciones , Enfermedades Intestinales/terapia , Fallo Hepático/complicaciones , Nutrición ParenteralRESUMEN
We present the case of an 85-year-old male patient diagnosed with human herpesvirus 8 (HHV8)-negative effusion-based lymphoma (EBL) that developed from long-lasting pleural effusion (PE) induced by dasatinib treatment for chronic myeloid leukemia (CML). After the onset of this disorder, dasatinib treatment was discontinued and drainage was performed to regress the effusion. The major molecular response (MMR) was thus lost. The patient did not tolerate nilotinib treatment, but bosutinib was successful in restoring MMR. During these clinical courses, the patient suffered from a recurrence of EBL, which was treated with rituximab-based chemotherapy. The PE sample just before the 3rd cycle of chemotherapy revealed the proliferation of CD57-positive T cells, along with the disappearance of lymphoma cells. Anti-tumor immunity may have been activated following the immunochemotherapy in the undisturbed immunological environment when both EBL and CML almost regressed. After four cycles of R-CVP therapy, the patient has been in remission for 16 months and no longer requires drainage.
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Herpesvirus Humano 8 , Leucemia Mielógena Crónica BCR-ABL Positiva , Linfoma , Derrame Pleural , Masculino , Humanos , Anciano de 80 o más Años , Dasatinib/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Derrame Pleural/inducido químicamente , Derrame Pleural/tratamiento farmacológicoRESUMEN
Histiocytic neoplasms, such as Langerhans cell histiocytosis (LCH) and disseminated juvenile xanthogranuloma (JXG), can involve the liver and sometimes cause liver failure. We aimed to classify non-LCH histiocytic proliferating disorders that do not exhibit typical disseminated JXG histology. We examined four pediatric patients who presented with liver failure and splenomegaly. Two patients with liver cirrhosis without cholestasis underwent liver transplantation (LT). The other two patients presented with giant cell hepatitis causing neonatal/infantile acute liver failure (ALF). The infantile ALF patient also underwent LT. Liver dysfunction developed after LT in all three transplant cases and the grafts exhibited massive sinusoidal infiltration of histiocytes with hemophagocytosis, similar to the native liver. The neonatal ALF patient was treated with an LCH-type chemotherapy regimen, and is alive and well at 18 months. Infiltrating histiocytes were positive for CD68 and CD163, and negative for CD1a, CD207, and S-100 protein. The BRAF V600E mutation was not present. Liver histological findings were not consistent with conventional disseminated JXG or LCH, although the histological findings in other organs overlapped those of well-known histiocytic neoplasms. The histological and immunohistochemical findings of infiltrating histiocytes suggest that these four cases constituted a disseminated JXG-like systemic disease.
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Histiocitosis de Células de Langerhans , Fallo Hepático , Xantogranuloma Juvenil , Niño , Histiocitos/metabolismo , Histiocitos/patología , Humanos , Xantogranuloma Juvenil/diagnóstico , Xantogranuloma Juvenil/metabolismo , Xantogranuloma Juvenil/patologíaRESUMEN
Approximately 0.17-2% of mature cystic teratomas undergo malignant transformation, of which squamous cell carcinoma (SCC) is the most common, accounting for 80% of these cases. Urothelial malignant transformation is extremely rare. The present study involves a 58-year-old patient who visited the hospital with discomfort in the lower abdomen. USG and pelvic MRI showed a left ovarian mature cystic teratoma. Left salpingo-oophorectomy was performed, and pathological examination revealed urothelial carcinoma transformation of the mature cystic teratoma morphologically and immunohistochemically. No metastasis to other organs was identified by CT after the surgery. Additional surgery, including total hysterectomy, right salpingo-oophorectomy, omentectomy, and dissection of pelvic and para-aortic lymph nodes, was performed without complications. No tumors were identified elsewhere, and the patient's stage was confirmed as IA. She had an uneventful postoperative course and was discharged 10 days later. CT showed no metastasis or recurrence six months later.
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BACKGROUND: Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of congenital neonatal systemic juvenile xanthogranuloma with atypical skin appearance that made the diagnosis difficult. CASE PRESENTATION: A preterm Japanese female neonate with prenatally diagnosed fetal hydrops in-utero was born with purpuric lesions involving the trunk and face. Since birth, she had hypoxemic respiratory failure, splenomegaly, anemia, thrombocytopenia, coagulopathy, and was transfusion dependent for red blood cells, fresh frozen plasma, and platelets. Multiple cystic lesions in her liver, part of them with vascular, were detected by ultrasound. A liver biopsy was inconclusive. A skin lesion on her face similar to purpura gradually changed to a firm and solid enlarged non-yellow nodule. Technically, the typical finding on skin biopsy would have been histiocytic infiltration (without Touton Giant cells) and immunohistochemistry results which then would be consistent with a diagnosis of systemic juvenile xanthogranuloma, and chemotherapy improved her general condition. CONCLUSIONS: This case report shows that skin biopsies are necessary to detect neonatal systemic juvenile xanthogranuloma when there are organ symptoms and skin eruption, even if the skin lesion does not have a typical appearance of yellow papules or nodules.
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Púrpura , Xantogranuloma Juvenil , Biopsia , Edema , Femenino , Humanos , Recién Nacido , Piel , Xantogranuloma Juvenil/complicaciones , Xantogranuloma Juvenil/diagnósticoRESUMEN
PURPOSE: STING-associated vasculopathy with onset in infancy (SAVI) is a type-I interferonopathy, characterized by systemic inflammation, peripheral vascular inflammation, and pulmonary manifestations. There are three reports of SAVI patients developing liver disease, but no report of a SAVI patient requiring liver transplantation. Therefore, the relevance of liver inflammation is unclear in SAVI. We report a SAVI patient who developed severe liver disorder following liver transplantation. METHODS: SAVI was diagnosed in a 4-year-old girl based on genetic analysis by whole-exome sequencing. We demonstrated clinical features, laboratory findings, and pathological examination of her original and transplanted livers. RESULTS: At 2 months of age, she developed bronchitis showing resistance to bronchodilators and antibiotics. At 10 months of age, she developed liver dysfunction with atypical cholangitis, which required liver transplantation at 1 year of age. At 2 years of age, multiple biliary cysts developed in the transplanted liver. At 3.9 years of age, SAVI was diagnosed by whole-exome sequencing. Inflammatory cells from the liver invaded the stomach wall directly, leading to fatal gastrointestinal bleeding unexpectedly at 4.6 years of age. In pathological findings, there were no typical findings of liver abscess, vasculitis, or graft rejection, but biliary cysts and infiltration of inflammatory cells, including plasmacytes around the bile duct area, in the transplanted liver were noted, which were findings similar to those of her original liver. CONCLUSION: Although further studies to clarify the mechanisms of the various liver disorders described in SAVI patients are needed, inflammatory liver manifestations may be amplified in the context of SAVI.
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Hepatopatías/terapia , Trasplante de Hígado/efectos adversos , Proteínas de la Membrana/genética , Enfermedades Vasculares/terapia , Preescolar , Femenino , Mutación con Ganancia de Función , Humanos , Hígado/patología , Hepatopatías/genética , Hepatopatías/patología , Enfermedades Vasculares/genética , Enfermedades Vasculares/patologíaRESUMEN
INTRODUCTION: Of the 23 cases of spinal intradural-extramedullary ependymomas which have been reported to date, 11 were diagnosed as anaplastic. Here we present a very rare case of a thoracic intradural-extramedullary (not intramedullary) anaplastic ependymoma in an adult along with a literature review. CASE PRESENTATION: A 29-year-old man presented with rapidly progressive gait disturbance, a sensory-deficit below the trunk and urination disorders that had begun a few months earlier. Magnetic resonance imaging of his thoracic spine revealed a dorsal-located intradural-extramedullary tumor at T4-5. The rapid deterioration of his symptoms within several months led him to refer to our department for surgery. Within one month the size of tumor increased to involve the T4-6 level, consequently worsening his gait disturbance. He underwent surgery and tumor mass was resected. However, there was leptomeningeal dissemination of the tumor cells on the surface of cord. A near-total resection was therefore achieved. Histopathology revealed the resected specimen had immunoreactivity for EMA/Vimentin/CD56/CD99/S-100/GFAP, with a Ki-67 index of ~35%. These factors led to the diagnosis of anaplastic ependymoma. Seven weeks postoperatively he received adjuvant radiotherapy to the whole brain and the whole spinal cord. He recovered as an independent ambulator without recurrence 1 year postoperatively. DISCUSSION: Because of their rarity, there are no clear treatment or adjuvant therapy guidelines for spinal anaplastic ependymoma. Adjuvant radiotherapy to the whole brain and spinal cord was necessarily indicated after near-total resection. Although the patient's condition has not recurred 1 year after surgery, careful and serial follow-up is necessary for this individual.
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Ependimoma , Neoplasias de la Médula Espinal , Adulto , Ependimoma/radioterapia , Ependimoma/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Radioterapia Adyuvante , Neoplasias de la Médula Espinal/radioterapia , Neoplasias de la Médula Espinal/cirugía , Columna VertebralRESUMEN
Tumor flare reaction (TFR) is a unique immune-mediated tumor recognition phenomenon presenting as rapid enlargement of the tumor, which mimics disease progression, developing in the early stage of treatment using immunomodulatory drugs or immune checkpoint inhibitors. A 59-year-old man with follicular lymphoma had residual tumor burden in the left hilar lymph nodes after R-CHOP therapy, and received lenalidomide and rituximab (R2) therapy. He developed respiratory distress on day 11 of R2 therapy. Chest X-ray and CT demonstrated left lung atelectasis due to left hilar lymph node swelling. We performed transbronchial lung biopsy on day 20 of R2 therapy. The biopsied left bronchus tissue exhibited extensive necrosis, which had a B-cell phenotype consistent with that of follicular lymphoma. Neither NK cells nor cytotoxic T cells were detected. It was unclear whether the immune effector cells disappeared at the time of transbronchial lung biopsy. Atelectasis in our patient improved by continuing R2 therapy beyond TFR.
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Factores Inmunológicos/efectos adversos , Lenalidomida/efectos adversos , Ganglios Linfáticos/patología , Neoplasias/complicaciones , Atelectasia Pulmonar/diagnóstico , Atelectasia Pulmonar/etiología , Protocolos de Quimioterapia Combinada Antineoplásica , Biopsia , Ciclofosfamida , Doxorrubicina , Humanos , Factores Inmunológicos/uso terapéutico , Lenalidomida/uso terapéutico , Linfoma Folicular/complicaciones , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prednisona , Radiografía Torácica , Rituximab , VincristinaRESUMEN
In deceased donor liver transplantation, a donor liver with moderate (>30%) macrosteatosis used to be considered inappropriate for grafting. We examined the outcomes of children who underwent living donor liver transplantation (LDLT) at the National Center for Child Health and Development whose donor livers had moderate-to-severe macrosteatosis. Twelve children were enrolled who had received a moderate-to-severe macrosteatotic liver graft and underwent liver biopsy soon after LDLT. The primary diseases were biliary atresia in 7 patients, acute liver failure in 3 patients, glycogen storage disease type 1 in 1 patient, and primary sclerosing cholangitis in 1 patient. Median age was 11 months. There were 4 recipients who received grafts from their fathers, and 8 received grafts from their mothers. Median donor age was 35.5 years. We compared the degree of donor liver steatosis with the results of graft liver biopsies that were collected 4-105 days after LDLT. The levels of donor liver macrovesicular steatosis were moderate (34%-66%) in 9 patients and severe (>66%) in 3 patients. The nonalcoholic fatty liver disease activity score was 3 in 7 patients and 4 in 5 patients. Shortly after LDLT, 11 of 12 patients showed improvement in steatosis compared with the donor livers. One biopsy specimen taken 22 days after LDLT showed 60% macrosteatosis, which was the same as that in the donor liver. However, this patient was alive and well 6 years after LDLT. One patient died after LDLT because of infection and respiratory failure. The levels of steatosis of the donor liver grafts improved soon after LDLT in children, and the outcomes of children receiving a moderate-to-severe macrosteatotic liver from their parents were excellent.
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Trasplante de Hígado , Donadores Vivos , Adulto , Niño , Supervivencia de Injerto , Humanos , Lactante , Hígado/cirugía , Trasplante de Hígado/efectos adversos , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Although poor long-term graft survival in LT in AYA is recognized, detailed epidemiological data are still lacking. L-TCMR may have poor outcomes. This study aimed to provide a detailed, epidemiological assessment of the association between AYA age and rejection. L-TCMR was defined in this study as TCMR with central vein or perivenular inflammation occurring later than 3 months after LT. A total of 342 patients who survived for at least 3 months after LT between 2005 and 2015 were enrolled. The AYA group (10-24 years) was compared with the C group (less than 10 years), and the incidence and outcomes of L-TCMR were analyzed. In total, 342 patients had LT; 38 of these were AYA with the mean follow-up period of 6.7 years. A total of 304 patients in C group had a mean follow-up period of 6.3 years (P = .28). The incidence of L-TCMR in AYA group was significantly higher than in C group (15.8% vs 4.6%, P = .006). The time to L-TCMR after LT was significantly shorter in AYA group (P = .01). Neither patient survival nor the incidence of non-adherence differed significantly between the groups (P = .18 and P = .89). The number of additional immunosuppressants after L-TCMR was significantly higher in the AYA group (P = .04). A high incidence of L-TCMR was observed in AYA group irrespective of non-adherence. AYA patients with L-TCMR should be followed carefully due to the poor results of post-treatment biopsy and the need for intensive immunosuppressive therapy.
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Rechazo de Injerto/inmunología , Trasplante de Hígado , Linfocitos T/inmunología , Adolescente , Niño , Preescolar , Femenino , Rechazo de Injerto/epidemiología , Humanos , Lactante , Masculino , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: Central perivenulitis can occur in association with T-cell-mediated rejection and can sometimes require strong immunosuppressant therapy as refractory rejection. Furthermore, patients with central perivenulitis are more likely to have subsequent episodes of T-cell-mediated rejection and develop chronic rejection than those without central perivenulitis. We retrospectively analyzed clinical data of pediatric patients with episodes of T-cell-mediated rejection according to severity of central perivenulitis and monitored HLA-DR-positive CD8-positive T cells and recent thymic emigrants during treatment for T-cell-mediated rejection. MATERIALS AND METHODS: We identified biopsy-proven T-cell-mediated rejection in 50 liver transplant recipients (45 with living-related donors, 5 with deceased donors) between September 2014 and August 2018. Lymphocyte subsets in peripheral blood samples were analyzed. RESULTS: Of 50 pediatric patients, 30 were boys and 20 were girls (median age at transplant of 1.1 y; interquartile range, 0.6-6.2 y). Central perivenulitis was found in 46 patients (92%), which was mild in 13, moderate in 16, and severe in 17. Antithymocyte globulin was more frequently administered to patients with severe central perivenulitis than others (P < .05). Patients with antithymocyte globulin treatment were less likely to have subsequent episodes of T-cell-mediated rejection than those without this treatment (P < .05). The absolute number of CD8-positive HLA-DR-positive T cells in patients during treatment was significantly higher than in control patients (P < .05). The absolute number of recent thymic emigrants in patients with active infection was significantly lower than in patients without infection (P < .05). CONCLUSIONS: Our results suggest the efficacy and safety of antithymocyte globulin for treating T-cell-mediated rejection with severe central perivenulitis in pediatric liver transplant recipients and suggest that antithymocyte globulin can prevent subsequent episodes of T-cell-mediated rejection. Analyzing lymphocyte subsets during treatment for rejection may help highlight viable therapeutic strategies for achieving a good outcome.
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Suero Antilinfocítico/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Inmunosupresores/uso terapéutico , Trasplante de Hígado/efectos adversos , Linfocitos T/efectos de los fármacos , Factores de Edad , Suero Antilinfocítico/efectos adversos , Niño , Preescolar , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/mortalidad , Rechazo de Injerto/patología , Humanos , Inmunofenotipificación , Inmunosupresores/efectos adversos , Lactante , Trasplante de Hígado/mortalidad , Masculino , Fenotipo , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Linfocitos T/inmunología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Congenital hepatic fibrosis (CHF) often accompanies autosomal recessive polycystic kidney disease (ARPKD), which stems from a PKHD1 gene mutation. The aim of this study was to clarify the prognosis of children with CHF who received living donor liver transplantation (LDLT) from donors who might be heterozygous carriers of a hepatorenal fibrocystic disease. Fourteen children with CHF who underwent LDLT at our center were enrolled. Eight and two patients had ARPKD and nephronophthisis, respectively. Eight of the donors were the recipients' fathers, and six donors were their mothers. We examined the histological and radiological findings of the donor livers and complications in the recipients following the liver transplantation. Seven of the donor livers presented morphological abnormalities of the bile ducts. Abdominal computed tomography revealed liver cysts in eight donors. One recipient underwent re-LT for graft failure due to rejection. Three patients presented with rejection, and one presented with sepsis. The overall survival rate was 100% and the original graft survival rate was 93%. In conclusion, the prognosis of recipients who received a LDLT from their parents for CHF was excellent. However, the morphology of half the donor livers was abnormal. Careful follow-up is needed to ensure long-term graft survival.
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Aloinjertos/patología , Enfermedades Genéticas Congénitas/cirugía , Cirrosis Hepática/cirugía , Trasplante de Hígado/métodos , Donadores Vivos , Adolescente , Adulto , Niño , Preescolar , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
AIM: It has been reported that the long-term outcome for children with metabolic disorders after liver transplantation (LT) is excellent. However, there are several reports citing LT patients with metabolic disorders developing liver dysfunction early after LT. We examined the pathogenesis of liver dysfunction observed after LT in recipients with metabolic disorders at the National Center for Child Health and Development. METHODS: Of 106 children (aged <18 years) with metabolic disorders who underwent LT at our center, 36 patients who underwent liver biopsy within 60 days after LT were enrolled. The underlying diseases were urea cycle disorders (14 patients), methylmalonic acidemia (11 cases), Wilson's disease (3 patients), mitochondrial hepatopathy (3 patients), and others (5 patients). The median age was 1 year 2 months at LT. The reasons for biopsy were liver dysfunction (31 patients) and ascites (5 patients). RESULTS: The main findings of graft liver biopsy were diffuse steatosis (21 patients), rejection (8 patients), infection (3 patients), and others (4 patients). Of 21 patients who received graft biopsy showing steatosis, all the donor livers originally showed no steatosis or only mild steatosis. The liver function improved immediately after biopsy in 18 of 21 patients that showed diffuse steatosis. CONCLUSIONS: The major cause of liver dysfunction after LT in recipients with metabolic disorders was steatosis and the risk of rejection was low. It is important to take a liver biopsy and examine the cause of liver dysfunction to avoid administration of excess immunosuppressant, and select the right therapy for recipients with metabolic disorders.
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Enfermedad Hepática en Estado Terminal/cirugía , Enterocolitis Necrotizante/cirugía , Intestinos/trasplante , Trasplante de Hígado/métodos , Síndrome del Intestino Corto/cirugía , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/etiología , Enterocolitis Necrotizante/complicaciones , Humanos , Lactante , Trasplante de Hígado/normas , Donadores Vivos , Masculino , Índice de Severidad de la Enfermedad , Síndrome del Intestino Corto/etiología , Factores de Tiempo , Obtención de Tejidos y Órganos/normas , Resultado del TratamientoRESUMEN
Glycogen storage disease (GSD) type 1b (Online Mendelian Inheritance in Man [OMIM] 232220) is an autosomal recessive inborn error of carbohydrate metabolism caused by defects in glucose-6-phosphate translocase. GSD1b patients have severe hypoglycemia with several clinical manifestations of hepatomegaly, obesity, a doll-like face, and neutropenia. Liver transplantation (LT) has been indicated for severe glucose intolerance, poor metabolic control (PMC), and poor growth (PG). We retrospectively reviewed 11 children with GSD1b who underwent living donor liver transplantation (LDLT) at the National Center for Child Health and Development in Tokyo, Japan. Between November 2005 and December 2018, 495 children underwent LDLT with an overall 10-year patient and graft survival of 90.6% and 88.9%, respectively. Of these, LT was indicated for 11 patients with GSD1b. All patients are doing well with the stabilization of glucose intolerance and decreased hospitalization for infectious complications. Demand for granulocyte colony-stimulating factor significantly decreased. However, although LT stabilized the blood glucose level, the platelet function was not improved. The posttransplant developmental quotient (DQ) remained similar to the pretransplant DQ without deterioration. LDLT is a feasible procedure for GSD1b patients with regard to the longterm prognosis. LT should be considered for patients with severe glucose intolerance to protect the cognitive function against hypoglycemic encephalopathy and to ameliorate PMC and PG.
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Enfermedad del Almacenamiento de Glucógeno Tipo I , Trasplante de Hígado , Niño , Enfermedad del Almacenamiento de Glucógeno Tipo I/cirugía , Factor Estimulante de Colonias de Granulocitos , Humanos , Japón , Trasplante de Hígado/efectos adversos , Donadores Vivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Intrapulmonary shunt (IPS) is recognized in 10% of chronic liver disease patients. Liver transplantation (LT) is associated with a high risk of morbidity and mortality in patients with IPS. PATIENTS AND METHODS: Of 519 pediatric LT cases between November 2005 and October 2018, 50 patients with IPS were enrolled in this study. The patients were divided into 3 groups, according to the shunt ratio, calculated by scintigraphy: mild (15%-20%, n = 26), moderate (20%-40%, n = 19), and severe (> 40%, n = 5). We compared the patients' characteristics before LT and the outcomes of LT between these groups. RESULTS: The major original disease resulting in LT in the mild and moderate groups was biliary atresia (73.1% and 52.6%, respectively), while that in the severe group was congenital portosystemic shunt (60%). The median ages at LT were 7.5, 6.1, and 8.3 years in the mild, moderate, and severe groups, respectively. All of the mild and moderate IPS patients lived; however, 3 patients with severe IPS (60.0%) died within 3 months. The shunt ratios of the mild and moderate IPS patients normalized within 2 years after LT, while the 2 surviving severe IPS patients showed a slight improvement. The autopsy findings of the lung in 1 deceased severe IPS patient showed medial hypertrophy and proliferation of intimal cells of the pulmonary arteries, suggesting a diagnosis of portopulmonary hypertension. CONCLUSIONS: LT can be safely performed for mild and moderate IPS patients; however, LT for severe IPS patients should be carefully indicated because concomitant portopulmonary hypertension may be masked by IPS.
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Síndrome Hepatopulmonar , Trasplante de Hígado , Adolescente , Atresia Biliar/complicaciones , Niño , Preescolar , Femenino , Síndrome Hepatopulmonar/complicaciones , Síndrome Hepatopulmonar/fisiopatología , Humanos , Trasplante de Hígado/estadística & datos numéricos , Pulmón/fisiopatología , Masculino , Pronóstico , Arteria Pulmonar/fisiopatologíaRESUMEN
Lipoprotein lipase (LPL) plays a central role in incorporating plasma lipids into tissues and regulates lipid metabolism and energy balance in the human body. Conversely, LPL expression is almost absent in normal adult livers. Therefore, its physiological role in the liver remains unknown. We aimed to elucidate the role of LPL in the pathophysiology of nonalcoholic steatohepatitis (NASH), a hepatic manifestation of obesity. Hepatic stellate cell (HSC)-specific LPL-knockout (LplHSC-KO ) mice, LPL-floxed (Lplfl/fl ) mice, or double-mutant toll-like receptor 4-deficient (Tlr4-/- ) LplHSC-KO mice were fed a high-fat/high-cholesterol diet for 4 weeks to establish the nonalcoholic fatty liver model or an high-fat/high-cholesterol diet for 24 weeks to establish the NASH model. Human samples, derived from patients with nonalcoholic fatty liver disease, were also examined. In human and mouse NASH livers, serum obesity-related factors, such as free fatty acid, leptin, and interleukin-6, dramatically increased the expression of LPL, specifically in HSCs through signal transducer and activator of transcription 3 signaling, as opposed to that in hepatocytes or hepatic macrophages. In the NASH mouse model, liver fibrosis was significantly reduced in LplHSC-KO mice compared with that in Lplfl/fl mice. Nonenzymatic LPL-mediated cholesterol uptake from serum lipoproteins enhanced the accumulation of free cholesterol in HSCs, which amplified TLR4 signaling, resulting in the activation of HSCs and progression of hepatic fibrosis in NASH. Conclusion: The present study reveals the pathophysiological role of LPL in the liver, and furthermore, clarifies the pathophysiology in which obesity, as a background factor, exacerbates NASH. The LPL-mediated HSC activation pathway could be a promising therapeutic target for treating liver fibrosis in NASH.
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Fluorescence-guided surgery with indocyanine green (ICG) for malignant hepatic tumors has been gaining more attention with technical advancements. Since hepatoblastomas (HBs) possess similar features to hepatocellular carcinoma, fluorescence-guided surgery can be used for HBs, as aggressive surgical resection, even for distant metastases of HBs, often contributes positively to R0 (complete) resection and subsequent patient survival. Despite a few caveats, fluorescence-guided surgery allows for the more sensitive identification of lesions that may go undetected by conventional imaging or be invisible macroscopically. This leads to precise resection of distant metastatic tumors as well as primary liver tumors.