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1.
Medicine (Baltimore) ; 102(1): e32586, 2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36607861

RESUMEN

The aim of this study was to investigate the clinical features and risk factors of intrahepatic cholestasis of pregnancy (ICP) and its effect on pregnancy outcomes. The data from 300 pregnant women with ICP and 300 pregnant women without ICP admitted from July 2015 to December 2016 at Changsha Maternal and Child Health Hospital were collected. The factors associated with ICP were examined. The family history of ICP, twin pregnancies, number of births, hypertensive disorder of pregnancy (HDP), gestational diabetes, hyperlipidemia, hepatitis virus infection, and in vitro fertilization and embryo transfer, differed significantly between the 2 groups (all P < .05). The multivariable analysis showed that body mass index at delivery, number of births, HDP, gestational diabetes, hyperlipidemia, and hepatitis virus infection were associated with ICP (all P < .05). The incidence of abnormal amniotic fluid and premature births in the ICP group were significantly higher than in the control group (all P < .05). ICP is associated with BMI at delivery, number of births, HDP, gestational diabetes, hyperlipidemia, and hepatitis virus infection. ICP greatly influences pregnancy outcomes.


Asunto(s)
Colestasis Intrahepática , Diabetes Gestacional , Hepatitis , Preeclampsia , Complicaciones del Embarazo , Virosis , Niño , Embarazo , Femenino , Lactante , Humanos , Diabetes Gestacional/epidemiología , Estudios Retrospectivos , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Colestasis Intrahepática/complicaciones , Colestasis Intrahepática/epidemiología , Virosis/complicaciones , Hepatitis/complicaciones
2.
J Am Anim Hosp Assoc ; 59(1): 1-6, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36584317

RESUMEN

A 7 yr old castrated male Cavalier King Charles spaniel presented for evaluation of liver enzyme elevations. Abdominal ultrasound revealed a small liver with mixed echogenicity, small hypoechoic nodules, and an irregular surface. Histologic examination and copper quantification of the liver obtained by laparoscopy diagnosed copper-associated hepatitis. One month later the dog developed hyperkeratosis of all four foot pads and ulcerations of feet, legs, and rectum. Punch biopsies confirmed superficial necrolytic dermatitis. After a total of 2 mo of chelation with no changes to medications, skin lesions began to improve, continuing over the following 6 wk to almost complete resolution. At this point the skin lesions returned and had minimal response to four amino acids infusions. The dog was switched from penicillamine to trientine. Zinc acetate was initiated 6 wk after the switch to trientine, and skin improvement was noted soon thereafter. At the time of death, skin lesions were improving and the dog was clinically comfortable. Copper-associated hepatitis should be considered as a possible etiology for superficial necrolytic dermatitis. Treatment of superficial necrolytic dermatitis is often unrewarding, and copper chelation, when copper-associated hepatitis has been confirmed, represents another therapeutic option.


Asunto(s)
Dermatitis , Enfermedades de los Perros , Hepatitis , Enfermedades de la Piel , Perros , Masculino , Animales , Dermatitis/tratamiento farmacológico , Dermatitis/veterinaria , Dermatitis/diagnóstico , Cobre , Trientina/uso terapéutico , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/diagnóstico , Enfermedades de la Piel/veterinaria , Hepatitis/complicaciones
3.
J Gen Virol ; 103(11)2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36367762

RESUMEN

Over the past few months there have been reports of severe acute hepatitis in several hundred, otherwise healthy, immunocompetent young children. Several deaths have been recorded and a relatively large proportion of the patients have needed liver transplants. Most of the cases, so far, have been seen in the UK and in North America, but it has also been reported in many other European countries, the Middle East and Asia. Most common viruses have been ruled out as a causative agent; hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) were not detected, nor were Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) in many cases. A small proportion of the children had been infected with SARS-CoV-2 but these seem to be in a minority; similarly, almost none of the children had been vaccinated against COVID-19. Significantly, many of the patients were infected with adenovirus 41 (HAdV-F41). Previously, HAdV-41 had not been linked to hepatitis and is usually considered to cause gastroenteritis in both immunocompetent and immunocompromised patients. In two most recent studies, adeno-associated virus 2 (AAV2) was detected in almost all patients, together with species C and F HAdVs and human herpesvirus 6B (HHV6B). Here, I discuss the possibility that a change in tropism of HAdV-41 and changes in AAV2 may be responsible for their links to acute hepatitis.


Asunto(s)
Infecciones por Adenoviridae , COVID-19 , Infecciones por Virus de Epstein-Barr , Hepatitis , Parvovirinae , Niño , Humanos , Preescolar , Adenoviridae , Herpesvirus Humano 4 , SARS-CoV-2 , Hepatitis/complicaciones
4.
J Med Case Rep ; 16(1): 422, 2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36329514

RESUMEN

BACKGROUND: Recently, an unknown hepatitis outbreak among children has concerned many individuals worldwide. These cases are frequently reported, mainly from Europe and other countries. In this study, we present two similar patients, who, to the best of our knowledge, are the first cases reported in the Middle East (Shiraz, Fars Province, Iran). Unlike in similar cases reported up until 30 April 2022, our patients' hepatitis eventually resulted in aplastic anemia. CASE PRESENTATION: In this study, we present cases of two Iranian boys aged 13 and 8 years with hepatitis of unknown origin who developed aplastic anemia in the course of hospitalization. CONCLUSIONS: Hepatitis-associated aplastic anemia is a well-known immune-mediated form of aplastic anemia that we detected in our patients and treated with immunosuppressive therapy. One patient established a satisfactory response to the treatment, but unfortunately, the other was declared brain dead.


Asunto(s)
Anemia Aplásica , Hepatitis , Niño , Masculino , Humanos , Anemia Aplásica/complicaciones , Irán/epidemiología , Hepatitis/complicaciones , Brotes de Enfermedades , Terapia de Inmunosupresión
5.
Immun Inflamm Dis ; 10(11): e728, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36301029

RESUMEN

BACKGROUND: CCAAT/enhancer-binding protein ß (C/EBPß) is a transcription factor known to be involved in macrophage differentiation and function, steatohepatitis and liver fibrosis. METHODS: Immune restricted C/EBPß deficient and control mice were investigated in steady-state and in the CDA-HFD steatohepatitis model. Mice were assessed for weight change, liver biochemical profile, histology and hepatic phagocytes composition. RESULTS: Flow cytometry analysis of hepatic nonparenchymal cells revealed reduced numbers of hepatic monocytes and Kupffer cells and an increase in hepatic MHC class II positive myeloid cells in immune cells restricted C/EBPß deficient mice. Immune-restricted C/EBPß deficiency resulted in decreased weight gain and appearance of mild spontaneous liver inflammation. Nevertheless, In the CDA-HFD steatohepatitis model, immune restricted C/EBPß deficient and proficient mice exhibit similar grade of hepatic steatosis, liver enzymes levels and fibrosis stage. CONCLUSIONS: Immune-restricted C/EBPß deficiency leads to significant alteration in hepatic mononuclear phagocytes composition associated with spontaneous mild hepatitis. Steatohepatitis associated fibrosis is not dependent on C/EBPß expression by immune cells.


Asunto(s)
Hígado Graso , Hepatitis , Ratones , Animales , Hígado Graso/complicaciones , Cirrosis Hepática/complicaciones , Hepatitis/complicaciones , Regulación de la Expresión Génica
7.
PLoS One ; 17(9): e0274582, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36107926

RESUMEN

Non-alcoholic fatty liver disease (NAFLD), represents an unmet medical need that can progress to non-alcoholic steatohepatitis (NASH), which, without intervention, can result in the development of cirrhosis and hepatocellular carcinoma (HCC). Inflammation is a pathological hallmark of NASH, and targeting key inflammatory mediators of NASH may lead to potential therapeutics for the disease. Herein, we aimed to investigate the role of IL-23 signaling in NASH progression in murine models. We showed that recombinant IL-23 can promote IL-17 producing cell expansion in the liver and that these cells are predominately γδ T cells and Mucosal Associated Invariant T cells (MAITs). Reciprocally, we found that IL-23 signaling is necessary for the expansion of γδ T cells and MAIT cells in the western diet (WD) diet induced NASH model. However, we did not observe any significant differences in liver inflammation and fibrosis between wild type and Il23r-/- mice in the same NASH model. Furthermore, we found that Il23r deletion does not impact liver inflammation and fibrosis in the choline-deficient, L-amino acid-defined and high-fat diet (CDA-HFD) induced NASH model. Based on these findings, we therefore propose that IL-23 signaling is not necessary for NASH pathogenesis in preclinical models and targeting this pathway alone may not be an effective therapeutic approach to ameliorate the disease progression in NASH patients.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Aminoácidos/uso terapéutico , Animales , Carcinoma Hepatocelular/patología , Colina , Modelos Animales de Enfermedad , Hepatitis/complicaciones , Mediadores de Inflamación , Interleucina-17/genética , Interleucina-23 , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/patología
8.
World J Gastroenterol ; 28(26): 3243-3257, 2022 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-36051336

RESUMEN

BACKGROUND: Sodium glucose cotransporter-2 inhibitors (SGLT2-I) are the most recently approved drugs for type 2 diabetes (T2D). Recent clinical trials of these compounds reported beneficial cardiovascular (CV) and renal outcomes. A major cause of vascular dysfunction and CV disease in diabetes is hyperglycemia associated with inflammation and oxidative stress. Pre-clinical studies demonstrated that SGLT2-I reduce glucotoxicity and promote anti-inflammatory effects by lowering oxidative stress. AIM: To investigate the effects of SGLT2-I on markers of oxidative stress, inflammation, liver steatosis, and fibrosis in patients of T2D with non-alcoholic fatty liver disease (NAFLD). METHODS: We referred fifty-two consecutive outpatients treated with metformin monotherapy and exhibiting poor glycemic control to our centre. We introduced the outpatients to an SGLT2-I (dapagliflozin, empagliflozin, or canagliflozin; n = 26) or a different hypoglycemic drug [other glucose-lowering drugs (OTHER), n = 26]. We evaluated circulating interleukins and serum hydroxynonenal (HNE)- or malondialdehyde (MDA)-protein adducts, fatty liver index (FLI), NAFLD fibrosis score, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST-to-platelet-ratio index (APRI), and fibrosis-4 on the day before (T0) and following treatment for six months (T1). We also performed transient elastography at T0 and T1. RESULTS: Add-on therapy resulted in improved glycemic control and reduced fasting blood glucose in both groups. Of note, following treatment for six months, a reduction of FLI and APRI, as well as of the FibroScan result, was reported in patients treated with SGLT2-I, but not in the OTHER group; furthermore, in the SGLT2-I group, we reported lower circulating levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor, vascular endothelial growth factor, and monocyte chemoattractant protein-1, and higher levels of IL-4 and IL-10. We did not observe any modification in circulating interleukins in the OTHER group. Finally, serum HNE- and MDA-protein adducts decreased significantly in SGLT2-I rather than OTHER patients and correlated with liver steatosis and fibrosis scores. CONCLUSION: The present data indicate that treatment with SGLT2-I in patients with T2D and NAFLD is associated with improvement of liver steatosis and fibrosis markers and circulating pro-inflammatory and redox status, more than optimizing glycemic control.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hepatitis , Enfermedad del Hígado Graso no Alcohólico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hepatitis/complicaciones , Humanos , Hipoglucemiantes/uso terapéutico , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Oxidación-Reducción , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/metabolismo
9.
J Med Case Rep ; 16(1): 294, 2022 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-35907896

RESUMEN

BACKGROUND: Liver involvement in adults with acute myeloid leukemia is uncommon. Most of the case reports describe acute liver failure or obstructive jaundice, while acute hepatitis is rarely mentioned. We report a patient with acute myeloid leukemia who presented with clinical, biochemical, and radiological signs of acute hepatitis that totally regressed after chemotherapy. CASE PRESENTATION: A 38-year-old Caucasian man presented with fever, cough, and mild fatigue. Laboratory workup showed anemia, thrombocytopenia, severe leukocytosis, transaminitis, and hyperbilirubinemia. Imaging of the abdomen (ultrasound and magnetic resonance) showed hepatomegaly, splenomegaly, upper limits portal veins diameters, increased thickness of the gallbladder wall, and significant abdominal lymph nodes. Peripheral blood smear and bone marrow evaluation were consistent with acute myeloid leukemia, and liver biopsy showed massive sinusoidal and portal infiltration by leukemic cells. After remission-inducing chemotherapy, there was complete normalization of liver function tests, and liver, spleen, and portal vein size. CONCLUSIONS: This case highlights the importance of taking acute myeloid leukemia into account as a possible cause of liver damage to make a rapid diagnosis and start appropriate treatment that may lead to hematological remission and hepatic dysfunction resolution.


Asunto(s)
Colestasis , Subunidad beta del Factor de Unión al Sitio Principal , Hepatitis , Leucemia Mieloide Aguda , Cadenas Pesadas de Miosina , Enfermedad Aguda , Adulto , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Colestasis/complicaciones , Colestasis/tratamiento farmacológico , Colestasis/patología , Hepatitis/complicaciones , Hepatitis/diagnóstico , Hepatitis/tratamiento farmacológico , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/patología , Hígado/fisiología , Hígado/fisiopatología , Masculino
10.
Ann Hematol ; 101(8): 1815-1823, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35739427

RESUMEN

Hepatitis-associated aplastic anemia (HAAA), a rare subtype of aplastic anemia (AA), is defined as bone marrow failure occurring after acute hepatitis. Severe HAAA requires immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT) as lifesaving treatment. The outcomes of HAAA patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) have not been systematically evaluated. We retrospectively compared the characteristics of 15 patients with HAAA and 60 non-hepatitis-associated aplastic anemia (non-HAAA) patients, all 75 of whom underwent haplo-HSCT in our hospital between January 2006 and October 2021. The median ages of the patients were 18 years old (range, 3-36) for HAAA patients and 13 years (range, 2-45) for non-HAAA patients (p = 0.693). The median time for neutrophil engraftment was 14 days (range, 11-22) in the HAAA group and 12 days (range, 10-21) in the non-HAAA group (p = 0.363). At the time of analysis, 15 HAAA patients and 58 non-HAAA patients were alive, and their median follow-up times were 37 (range, 3-87) months and 31 (range, 2-110) months (p = 0.347), respectively. There were no significant differences in the three-year overall survival (OS) rates (100% vs. 96.7 ± 0.33%, P = 0.638) or liver event-free survival (LEFS) (80.0 ± 0.17% vs. 76.7 ± 0.19%, P = 0.747) between the two groups. Despite the small number of HAAA patients due to the rarity of the disease, these results, such as the similar incidence rates of 3-year OS and fewer liver events than expected, suggest that haplo-HSCT is a feasible treatment for HAAA a when there are no human leukocyte antigen (HLA)-matched donors available and has a low risk of transplant-related mortality and complications.


Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Hepatitis A , Hepatitis , Adolescente , Adulto , Niño , Preescolar , Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hepatitis/complicaciones , Hepatitis/terapia , Humanos , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Adulto Joven
11.
J Med Food ; 25(6): 652-659, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35708629

RESUMEN

Cholestatic liver disease, or cholestasis, is a condition characterized by liver inflammation and fibrosis following a bile duct obstruction and an intrahepatic accumulation of bile acids. Inhibiting inflammation is a promising therapeutic strategy for cholestatic liver diseases. Acer tegmentosum Maxim extract (ATE) is best known for its anti-inflammatory and antioxidative properties. In this study, we investigated the effects of ATE on liver injury and fibrosis in mice with bile duct ligation (BDL)-induced cholestasis through analysis of gene expression, cytokines, and histological examination. Oral administration of ATE (20 or 50 mg/kg) for 14 days significantly attenuated hepatocellular necrosis compared to vehicle-treated BDL mice, which was accompanied by the reduced level of serum bile acids and bilirubin. We determined that ATE treatment reduced liver inflammation, oxidative stress, and fibrosis. These beneficial effects of ATE were concurrent with the decreased expression of genes involved in the NF-κB pathway, suggesting that the anti-inflammatory effect of ATE could be a possible mechanism against cholestasis-associated liver injury. Our findings substantiate ATE's role as an alternative therapeutic agent for cholestasis-induced liver injury and fibrosis.


Asunto(s)
Acer , Colestasis , Hepatitis , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/farmacología , Ácidos y Sales Biliares/uso terapéutico , Conductos Biliares/metabolismo , Conductos Biliares/cirugía , Colestasis/tratamiento farmacológico , Colestasis/metabolismo , Colestasis/patología , Fibrosis , Hepatitis/complicaciones , Hepatitis/tratamiento farmacológico , Hepatitis/patología , Inflamación/tratamiento farmacológico , Hígado/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Ratones , Extractos Vegetales/farmacología
12.
United European Gastroenterol J ; 10(8): 795-804, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35773246

RESUMEN

There is increasing global concern of severe acute hepatitis of unknown etiology in young children. In early 2022, our center for liver transplantation in the Netherlands treated five children who presented in short succession with indeterminate acute liver failure. Four children underwent liver transplantation, one spontaneously recovered. Here we delineate the clinical course and comprehensive diagnostic workup of these patients. Three of five patients showed a gradual decline of liver synthetic function and had mild neurological symptoms. Their clinical and histological findings were consistent with hepatitis. These three patients all had a past SARS-CoV-2 infection and two of them were positive for adenovirus DNA. The other two patients presented with advanced liver failure and encephalopathy and underwent dialysis as a bridge to transplantation. One of these children spontaneously recovered. We discuss this cluster of patients in the context of the currently elevated incidence of severe acute hepatitis in children.


Asunto(s)
COVID-19 , Hepatitis , Fallo Hepático Agudo , Niño , Preescolar , Hepatitis/complicaciones , Humanos , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/epidemiología , Fallo Hepático Agudo/etiología , Países Bajos/epidemiología , Estudios Retrospectivos , SARS-CoV-2
13.
Eur J Med Res ; 27(1): 45, 2022 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-35313994

RESUMEN

BACKGROUND: Hepatitis-associated aplastic anemia (HAAA) is a specific type of aplastic anemia, and hematopoietic stem-cell transplantation (HSCT) is recommended as the first-line. Acute rhabdomyolysis (AR) during hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication, with only 10 cases reported in the world so far. CASE PRESENTATION: Herein, we present a case of AR developing during HLA-haploidentical HSCT in a 55-year-old man who suffered from HAAA. On day 7 after stem cell transfusion, the patient reported a muscle pull in thigh and complained of muscle swelling, pain and change in urine color. Despite the timely diagnosis (based on the levels of myoglobin and creatine kinase, and muscle MRI findings, etc.) and rapid hydration and alkalization, the situation progressed dramatically, and the patient died of multi-organ failure during the preparation for continuous renal replacement therapy (CRRT). Five days after his death, the whole-exome sequencing result confirmed that the patient had a germline missense mutation in SCN4A I 1545 V and ACTN3 R577X. CONCLUSION: AR is a rare but threatening complication during HSCT, especially in cases with kidney dysfunction. The creatine kinase level may not truly and completely reflect the severity and prognosis for cases with localized lesion. We suggest that genetic analysis should be performed for better understanding the pathological changes of AR during HSCT, especially for patients with bone marrow failure.


Asunto(s)
Anemia Aplásica/complicaciones , Anemia Aplásica/fisiopatología , Anemia Aplásica/terapia , Hepatitis/complicaciones , Rabdomiólisis/etiología , Rabdomiólisis/fisiopatología , Rabdomiólisis/terapia , Anemia Aplásica/etiología , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Células Madre/métodos , Trasplante Homólogo/métodos , Resultado del Tratamiento
14.
BMJ Case Rep ; 15(3)2022 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-35318201

RESUMEN

Hepatitis-associated aplastic anaemia (HAAA) is a rare condition characterised by onset of acute hepatitis which is followed by development of severe pancytopenia due to bone marrow failure within 6 months. This syndrome can be precipitated by acute viral infections, but the aetiology remains unknown in the majority. Drug-induced HAAA is extremely rare and has been reported with nutritional and dietary supplements in current literature. We report the first cases of ayurvedic herbal and homeopathic remedies-associated HAAA in two patients which proved fatal in both. Evaluation of patients with acute hepatitis and severe pancytopenia must include a detailed evaluation for complementary and alternative medicine use.


Asunto(s)
Anemia Aplásica , Enfermedad Hepática Inducida por Sustancias y Drogas , Gymnema sylvestre , Hepatitis , Materia Medica , Anemia Aplásica/inducido químicamente , Anemia Aplásica/terapia , Enfermedad Hepática Inducida por Sustancias y Drogas/complicaciones , Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Hepatitis/complicaciones , Humanos , Materia Medica/efectos adversos
15.
Medicine (Baltimore) ; 101(8): e28953, 2022 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-35212305

RESUMEN

RATIONALE: Hepatitis-associated aplastic anemia (HAAA) is a rare illness that results in bone marrow failure following hepatitis development. The etiological agent remains unknown in most HAAA cases. However, clinical features of the disease and immunotherapy response indicate that immune-mediated factors play a central role in the pathogenesis of HAAA. Activation of cytotoxic T cells and increase in CD8 cells could exert cytotoxic effects on the myelopoietic cells in the bone marrow. PATIENT CONCERNS: A 15-month-old boy was brought to our hospital with complaints of generalized petechiae and purpura observed a week prior to hospitalization. His liver was palpated 3 cm below the costal margin, platelet count was 0 × 104/µL, and alanine aminotransferase level was 1346 IU/L. A blood test indicated cytomegalovirus infection, and 3 bone marrow examinations revealed progressive HAAA. As the disease progressed to the 3rd, 6th, and 9th week after onset, CD4+ T cells were markedly decreased, CD8+ T cells were markedly increased, and the CD4/CD8 ratio was significantly decreased. The number of B cells and natural killer cells decreased with time, eventually reaching 0.0%. DIAGNOSIS: HAAA. INTERVENTIONS: Rabbit antithymocyte globulin and eltrombopag olamine (a thrombopoietin receptor agonist) were administered. OUTCOMES: The patient's platelet count returned to normal, and bone marrow transplantation was avoided. The peripheral blood lymphocytes (PBLs) improved as the patient's general condition recovered. LESSONS: This case demonstrates that HAAA induced by cytomegalovirus infection features decreasing CD4+ and increasing CD8+ PBLs as the bone marrow hypoplasia progresses. The PBLs return to their normal levels with the recovery from the disease. Our case findings thus support the involvement of immunological abnormality in HAAA.


Asunto(s)
Médula Ósea/patología , Infecciones por Citomegalovirus/complicaciones , Hepatitis/complicaciones , Linfocitos/patología , Anemia Aplásica/complicaciones , Benzoatos , Humanos , Hidrazinas , Lactante , Células Asesinas Naturales , Subgrupos Linfocitarios , Masculino , Pirazoles , Receptores de Trombopoyetina/agonistas
16.
Int J Mol Sci ; 23(2)2022 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-35054960

RESUMEN

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.


Asunto(s)
Biomarcadores , Susceptibilidad a Enfermedades , Hígado Graso Alcohólico/etiología , Hígado Graso Alcohólico/metabolismo , Hepatitis/complicaciones , Hepatitis/metabolismo , Estrés Oxidativo , Transducción de Señal , Animales , Susceptibilidad a Enfermedades/inmunología , Etanol/efectos adversos , Etanol/metabolismo , Hígado Graso/complicaciones , Hígado Graso/etiología , Hígado Graso/metabolismo , Hígado Graso Alcohólico/patología , Regulación de la Expresión Génica , Hepatitis/etiología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Inmunidad Innata , Redes y Vías Metabólicas , MicroARNs/genética , Oxidación-Reducción
17.
Hematol Oncol Stem Cell Ther ; 15(2): 8-12, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33197413

RESUMEN

Hepatitis-associated aplastic anemia (HAAA) is a rare illness, characterized by onset of pancytopenia with a hypoplastic bone marrow that traditionally occurs within 6 months of an increase in serum aminotransferases. HAAA is observed in 1% to 5% of all newly diagnosed cases of acquired aplastic anemia. Several hepatitis viruses have been linked to the disease, but in many cases no specific virus is detected. The exact pathophysiology is unknown; however, immune destruction of hematopoietic stem cells is believed to be the underlying mechanism. HAAA is a potentially lethal disease if left untreated. Management includes immunosuppression with antithymocyte globulin and cyclosporine and allogeneic hematopoietic stem cell transplantation.


Asunto(s)
Anemia Aplásica , Hepatitis , Humanos , Anemia Aplásica/complicaciones , Anemia Aplásica/terapia , Suero Antilinfocítico , Hepatitis/complicaciones , Hepatitis/terapia , Terapia de Inmunosupresión , Ciclosporina/uso terapéutico
19.
J Pediatr Hematol Oncol ; 44(1): e223-e226, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34669357

RESUMEN

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were <3 to 5×upper limit of normal (ULN) in 2 patients, <5 to 10×ULN in 2 patients, and >10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed.


Asunto(s)
Anemia Aplásica , Trasplante de Células Madre Hematopoyéticas , Hepatitis , Fallo Hepático Agudo , Adolescente , Alanina Transaminasa/sangre , Aloinjertos , Anemia Aplásica/sangre , Anemia Aplásica/etiología , Anemia Aplásica/mortalidad , Anemia Aplásica/terapia , Aspartato Aminotransferasas/sangre , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Hepatitis/sangre , Hepatitis/complicaciones , Hepatitis/mortalidad , Hepatitis/terapia , Humanos , Fallo Hepático Agudo/sangre , Fallo Hepático Agudo/complicaciones , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/terapia , Masculino , Estudios Retrospectivos , Tasa de Supervivencia
20.
Scand J Gastroenterol ; 57(3): 311-318, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34846975

RESUMEN

BACKGROUND: Hypoxic hepatitis (HH) is an important clinical entity in patients in the intensive care unit (ICU). The aims of the study were to assess the etiology, clinical characteristics and outcomes of HH in the ICU of a tertiary hospital. Secondary aim was to analyze the effects of concomitant ischemia in other organs than the liver. METHODS: All patients with HH, 2011-2018, in a university hospital ICU were included. Data were collected on etiology, relevant clinical data and outcome. HH was defined by an increase in aminotransferases ≥10 times the upper limit of normal within 48 h from a clinical event of cardiac, circulatory or respiratory failure. Other causes of liver cell necrosis were excluded. RESULTS: Of 9,931 patients hospitalized in the ICU, 159 (1.6%) fulfilled criteria for HH. In-hospital mortality occurred in 85 (53%) and 60 (38%) survived one year. Median ICU stay was five days (interquartile range (IQR) 3-10) and median hospital stay 16 days (IQR 7-32). Shock (48%), cardiac arrest (25%) and hypoxia (13%) were the most common causes of HH. Acute kidney injury (81%), rhabdomyolysis (50%), intestinal ischemia (6%) and ischemic pancreatitis (3%) occurred concomitantly. Age (odds ratio (OR) 1.05 (95% CI 1.02-1.09)), serum lactate (OR 2.61 (95% CI 1.23-5.50)) and lactate dehydrogenase (OR 1.14 (95% CI 1.02-1.27)) were predictors of mortality. CONCLUSIONS: Hypoxic hepatitis was related to shock in approximately 50% of cases and associated with high in-hospital mortality. HH was commonly associated with ischemia in other organs. In-hospital mortality was associated with age, lactate and LD.


Asunto(s)
Enfermedad Crítica , Hepatitis , Hepatitis/complicaciones , Hepatitis/epidemiología , Mortalidad Hospitalaria , Humanos , Hipoxia/complicaciones , Hipoxia/epidemiología , Unidades de Cuidados Intensivos , Prevalencia
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