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1.
Proc Natl Acad Sci U S A ; 117(12): 6717-6725, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32139604

RESUMO

Most hepatocellular carcinomas (HCCs) develop in patients with chronic hepatitis, which creates a microenvironment for the growth of hepatic progenitor cells (HPCs) at the periportal area and subsequent development of HCCs. We investigated the signal from the inflammatory liver for this pathogenic process in the hepatic conditional ß-catenin knockout mouse model. Senescent ß-catenin-depleted hepatocytes in aged mice create an inflammatory microenvironment that stimulates periportal HPC expansion but arrests differentiation, which predisposes mice to the development of liver tumors. The release of complement C1q from macrophages in the inflammatory niche was identified as the unorthodox signal that activated the ß-catenin pathway in periportal HPCs and was responsible for their expansion and de-differentiation. C1q inhibitors blocked the ß-catenin pathway in both the expanding HPCs and the liver tumors but spared its orthodox pathway in pericentral normal hepatocytes. This mechanism has been validated in human liver specimens from patients with chronic hepatitis. Taken together, these results demonstrate that C1q- mediated activation of ß-catenin pathway in periportal HPCs is a previously unrecognized mechanism for replenishing hepatocytes in the inflammatory liver and, if unchecked, for promoting hepatocarcinogenesis. C1q may become a new target for blocking carcinogenesis in patients with chronic hepatitis.


Assuntos
Carcinoma Hepatocelular/etiologia , Complemento C1q/metabolismo , Hepatite Crônica/complicações , Neoplasias Hepáticas/etiologia , Fígado/patologia , Células-Tronco/patologia , beta Catenina/fisiologia , Animais , Carcinogênese , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Diferenciação Celular , Senescência Celular , Humanos , Fígado/imunologia , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Transdução de Sinais , Células-Tronco/imunologia , Células-Tronco/metabolismo , Microambiente Tumoral
2.
Gastroenterol. hepatol. (Ed. impr.) ; 42(6): 362-371, jun.-jul. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-183787

RESUMO

Introducción: La infección crónica por el virus de la hepatitis C (VHC) es un factor de riesgo para desarrollar placas de ateroma, aunque se desconoce el posible efecto al eliminar el virus. Nuestro objetivo fue analizar si tras 12 meses de la erradicación del VHC por antivirales de acción directa (AAD) mejoraba la ateromatosis subclínica y existía modificación en la composición de las placas. Materiales y métodos: Estudio prospectivo que incluyó 85 pacientes con infección crónica por VHC en diferentes estadios de fibrosis, sometidos a AAD. Se excluyeron pacientes con antecedentes cardiovasculares, diabetes y enfermedad renal. Se realizó ecografía arterial (carótidas y femorales) para diagnosticar placa de ateroma (definida como grosor íntima-media≥1,5mm) y se analizó su composición (porcentaje de lípidos, fibrosis y calcio con software HEMODYN4) al inicio del estudio y tras 12 meses de finalizar la terapia. Resultados: Tras el seguimiento no se detectaron cambios en el grosor íntima-media (0,65mm vs. 0,63mm, p=0,240) ni en la presencia de placas (65,9%vs. 71,8%, p=0,063). Tampoco hubo modificación significativa en la composición de las mismas ni del territorio vascular afecto, observándose un aumento del perfil lipídico en sangre (p<0,001) tras 12 meses del tratamiento. Estos resultados se confirmaron en subgrupos por gravedad de enfermedad hepática. Discusión: La erradicación del VHC por AAD no mejora las placas de ateroma ni varía su composición, independientemente de la fibrosis hepática. Se precisan más estudios prospectivos que evalúen el riesgo residual cardiovascular tras la erradicación viral


Introduction: Chronic infection with hepatitis C virus is a risk factor for developing atheromatous plaques, although the possible effect of virus clearance is unknown. Our aim was to determine whether or not subclinical atheromatosis improved and there was any modification in the composition of the plaques 12 months after eradication of hepatitis C virus by direct-acting antiviral agents. Materials and methods: Prospective study that included 85 patients with chronic hepatitis C virus infection in different stages of fibrosis who were on direct-acting antiviral agents. Patients with a cardiovascular history, diabetes and kidney disease were excluded. An arterial ultrasound (carotid and femoral) was performed to diagnose atheromatous plaques (defined as intima-media thickness ≥1.5mm) and the composition (percentage of lipids, fibrosis and calcium with HEMODYN4 software) was analysed at the beginning of the study and 12 months after stopping the therapy. Results: After follow-up no changes were detected in the intima-media thickness (0.65mm vs. 0.63mm, P=.240) or in the presence of plaques (65.9% vs 71.8%, P=.063). There was also no significant change in their composition or affected vascular territory, with an increase in blood lipid profile (P<.001) after 12 months of treatment. These results were confirmed in subgroups by severity of liver disease. Discussion: The eradication of hepatitis C virus by direct-acting antiviral agents does not improve the atheroma plaques and nor does it vary their composition, regardless of liver fibrosis. More prospective studies are needed to evaluate residual cardiovascular risk after virus eradication


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Hepatite Crônica/complicações , Hepatite Crônica/diagnóstico , Hepatite C/complicações , Aterosclerose/complicações , Artérias Carótidas/diagnóstico por imagem , Placa Aterosclerótica/complicações , Estudos Prospectivos , Antropometria , Hepatite Crônica/sangue , Análise Estatística , Antivirais/uso terapêutico , Fatores de Risco , Placa Aterosclerótica/diagnóstico
3.
Dtsch Med Wochenschr ; 144(8): 520-527, 2019 04.
Artigo em Alemão | MEDLINE | ID: mdl-30986859

RESUMO

Chronic viral hepatitis can remain unrecognized but may nevertheless lead to liver cirrhosis and hepatocellular carcinoma. Thus, patients with elevated liver enzymes as well as risk groups need to be screened and treated for viral hepatitis. These groups include, in particular, migrants from countries with high HBV or HCV prevalence, persons with previous or current intravenous drug use, and homosexual men. For HBV- or HCV-associated diseases, such as panarteriitis nodosa, cryoglobulinemic vasculitis or B-cell lymphoma, antiviral therapy may lead to remission. Prior to high-dose immunosuppressive therapy, especially with regimes containing rituximab, chronic or resolved HBV infection must be ruled out or antiviral prophylaxis may be required to avoid a potentially fatal HBV reactivation.


Assuntos
Hepatite Crônica/diagnóstico , Hepatite Viral Humana/diagnóstico , Doença Aguda , Hepatite Crônica/complicações , Hepatite Crônica/terapia , Hepatite Viral Humana/complicações , Hepatite Viral Humana/terapia , Humanos
4.
Cient. dent. (Ed. impr.) ; 16(1): 17-25, ene.-abr. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-183377

RESUMO

La enfermedad o disfunción hepática puede deberse a numerosas causas como infecciones adquiridas, patologías congénitas o el abuso de drogas. Cuando esta disfunción y el daño hepático se prolongan a lo largo del tiempo, puede desembocar en una cirrosis hepática, cuadro irreversible y de graves repercusiones para el enfermo. Las dos patologías hepáticas más frecuentes y principales causas de la cirrosis son la hepatitis o inflamación hepática, la cual se puede deber a numerosos factores siendo el más frecuente las infecciones por virus, y la enfermedad hepática alcohólica, provocada por el abuso de alcohol continuado durante un largo período de tiempo. El manejo odontológico de un paciente con alteraciones hepáticas supone un verdadero reto, ya que el hígado juega un papel vital en numerosas funciones metabólicas, como la secreción de bilis o la excreción de bilirrubina procedente del metabolismo de la hemoglobina. Un fallo en la función hepática puede suponer alteraciones en el metabolismo de aminoácidos, amoníaco, proteínas, hidratos de carbono y triglicéridos. Un paciente con patología hepática tendrá un metabolismo alterado de numerosos fármacos empleados habitualmente por el dentista, tendrá un mayor riesgo de hemorragia debido a anomalías en la síntesis de diferentes factores de coagulación, siendo además un paciente con mayor riesgo de infecciones. La gran repercusión de la enfermedad hepática, así como el notable desconocimiento de muchos profesionales odontólogos en su manejo, justifican este artículo donde se talla tanto las generalidades más importantes de esta entidad como sus principales manifestaciones orales y consideraciones en el manejo odontológico


Liver disease or dysfunction may be due to numerous causes such as acquired infections, congenital pathologies or drug abuse. When this dysfunction and liver damage are prolonged overtime, it can lead to hepatic cirrhosis, an irreversible condition and serious repercussions for the patient. The two most frequent liver diseases and major causes of cirrhosis are hepatitis or hepatic inflammation, which may be due to numerous factors being the most frequent virus infections, and alcoholic liver disease, caused by alcohol abuse continued during A long period of time. The dental management of a patient with liver disorders is a real challenge, since the liver plays a vital role in many metabolic functions, such as bile secretion or excretion of bilirubin from hemoglobin metabolism. A failure in liver function can lead to alterations in the metabolismof amino acids, ammonia, proteins, carbohydrates and triglycerides. A patient with liver disease will have an altered metabolism of numerous drugs commonly used by the dentist, will have a greater risk of hemorrhage due to abnormalities in the synthesis of different coagulation factors, being also a patient with a higher risk of infections. The great repercussion of liver disease, as well as the remarkable lack of knowledge of many dental professionals in its management, justify this article where it is detailed both the most important generalities of this entity as its main oral manifestations and considerations in dental management


Assuntos
Humanos , Hepatite Viral Humana/complicações , Hepatite Crônica/complicações , Hepatopatias Alcoólicas/complicações , Doenças da Boca/complicações , Doenças da Boca/terapia , Assistência Odontológica para Doentes Crônicos/métodos , Doenças Dentárias/complicações , Doenças Dentárias/terapia
5.
J Ultrasound Med ; 38(1): 9-14, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30444274

RESUMO

Nowadays, shear wave elastographic techniques have brought a substantial reduction of liver biopsies performed to stage liver fibrosis in patients with chronic hepatitis. The availability of accurate noninvasive methods for the assessment of liver fibrosis was an important breakthrough and prompted ultrasound federations of societies as well as clinical and radiologic societies to issue international guidelines or consensus statements on the clinical applications of shear wave elastographic techniques. This article reviews the guidelines that have been published as of today.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite Crônica/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Hepatite Crônica/complicações , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/complicações
6.
Basic Clin Pharmacol Toxicol ; 124(5): 607-614, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30471199

RESUMO

Glycyrrhizin is used to treat chronic hepatitis, but it also plays an important role in pseudoaldosteronism. Multidrug resistance-associated protein 2 is important for glycyrrhizin excretion. Dysfunction of this transporter increases the serum levels of direct bilirubin, glycyrrhizin and its metabolites. Hence, elevated direct-bilirubin levels could predict the risk of pseudoaldosteronism. This study aimed to evaluate the relationship between elevated direct-bilirubin levels and hypokalaemia, which is the most sensitive marker of pseudoaldosteronism. This retrospective cohort study was conducted in a Japanese university hospital. The occurrence of hypokalaemia is defined as a serum potassium level of ≤3.5 mEq/L after the administration of a glycyrrhizin-containing medication, and a further decline of ≥0.5 mEq/L or an increase of ≥0.5 mEq/L after discontinuing the glycyrrhizin-containing medication was examined in patients with chronic hepatitis between January 2009 and December 2015. This analysis involved 1392 patients, including 596 women. Hepatitis C virus infections were the most common cause of chronic hepatitis in this study. Seventy-nine patients received glycyrrhizin (exposed group; mean age: 60.5 ± 14.2) and 1313 did not receive glycyrrhizin (control group; mean age: 58.3 ± 15.8 years). Synergistic effects of glycyrrhizin-containing medications and elevated direct-bilirubin levels were associated with hypokalaemia. Elevated direct-bilirubin levels and hypoalbuminaemia were associated with hypokalaemia in the exposed group. Older age, female sex, high daily glycyrrhizin dosage, longer duration of glycyrrhizin intake, and potassium-lowering medications were not associated with hypokalaemia after the model adjustment. Elevated direct-bilirubin levels and hypoalbuminaemia may predict pseudoaldosteronism caused by glycyrrhizin.


Assuntos
Hepatite Crônica/complicações , Hepatite Crônica/tratamento farmacológico , Síndrome de Liddle/induzido quimicamente , Síndrome de Liddle/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Bilirrubina/sangue , Efeito de Coortes , Feminino , Ácido Glicirrízico/efeitos adversos , Ácido Glicirrízico/uso terapêutico , Hepatite Crônica/sangue , Humanos , Hipopotassemia/sangue , Hipopotassemia/induzido quimicamente , Síndrome de Liddle/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
8.
J Med Case Rep ; 12(1): 260, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30170627

RESUMO

BACKGROUND: Dengue fever is the commonest mosquito-borne illness in the tropics and subtropics. Renal transplantation is one of the ever expanding modes of treatment of end-stage renal disease. Hepatitis B is a common infection in South and East Asia, but rare in Sri Lanka. Here we describe a recipient of a renal transplant with a stable graft, on antiviral treatment for hepatitis B infection, developing dengue superinfection and entering a complex clinical course. To the best of our knowledge this is the first report of such a case. CASE PRESENTATION: A 59-year-old Sri Lankan woman developed acute renal failure and needed dialysis support; she had upper gastrointestinal bleeding that needed transfusions, pancytopenia, and a prolonged phase of thrombocytopenia. She eventually recovered from illness, and her renal functions returned to baseline levels. The differences in presentation, signs, symptoms, and mortality of renal transplant recipients infected with dengue fever from the general population are discussed, with possible reasons for altered presentation. CONCLUSIONS: Dengue superinfection in transplant recipients with hepatitis B infection can lead to management difficulties. The recovery can be slow as seen from this case, with prolonged thrombocytopenia.


Assuntos
Dengue/diagnóstico , Hepatite B/tratamento farmacológico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Antivirais/uso terapêutico , Dengue/complicações , Dengue/tratamento farmacológico , Feminino , Hepatite B/complicações , Hepatite Crônica/complicações , Hepatite Crônica/tratamento farmacológico , Humanos , Falência Renal Crônica/complicações , Pessoa de Meia-Idade , Qualidade de Vida , Superinfecção/diagnóstico , Superinfecção/terapia , Trombocitopenia/etiologia , Trombocitopenia/terapia
9.
Magn Reson Imaging ; 54: 71-76, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30130549

RESUMO

PURPOSE: To assess the value of susceptibility-weighted imaging (SWI) for staging of liver fibrosis (F), necroinflammatory activity (A), and steatosis (S) of chronic hepatitis. METHODS: 100 Sprague-Dawley (SD) male rats were randomly divided into a chronic hepatitis model group (n = 88) and a control group (n = 12). The chronic hepatitis model rats were induced by intraperitoneal injection of 40% (v/v) of carbon tetrachloride (CCl4) diluted in olive oil. All rats were examined by magnetic resonance imaging (MRI) and then killed immediately to detect pathologic staging as liver fibrosis (F), necroinflammatory activity (A), and steatosis (S). Liver-to-muscle signal intensity ratios (SIRs) of SWI were analyzed and associated with histopathologic findings. RESULTS: There were ultimately 11 normal control rats and 60 chronic hepatitis model rats. Statistical data were as follows: F0 (n = 11), F1 (n = 18), F2 (n = 16), F3 (n = 13), F4 (n = 13); A0 (n = 11), A1 (n = 29), A2 (n = 21), A3 (n = 10); S0 (n = 11), S1 (n = 12), S2 (n = 12), S3 (n = 18), and S4 (n = 18). The liver-to-muscle SIR of the SWI was related to hepatic fibrosis (P < 0.05) and liver steatosis (P < 0.05) but not to necroinflammatory activity (P > 0.05). By partial correlation analysis, a significant negative correlation was shown between the liver-to-muscle SIR and staging of liver fibrosis (r = -0.68, P < 0.05) as well as a low correlation with liver steatosis (r = 0.30, P < 0.05). Except for F0-F1 and F1-F2, there were statistical differences between each of the stages of hepatic fibrosis (P < 0.05), with an area under the ROC of 0.87 for F3 or above and of 0.96 for F4. CONCLUSION: SWI can be a reliable method for staging hepatic fibrosis.


Assuntos
Fígado Gorduroso/diagnóstico por imagem , Hepatite Crônica/complicações , Cirrose Hepática/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Animais , Tetracloreto de Carbono , Diagnóstico Diferencial , Modelos Animais de Doenças , Estudos de Avaliação como Assunto , Fígado Gorduroso/etiologia , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
10.
Nutrition ; 54: 83-88, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29753174

RESUMO

OBJECTIVES: The effect of skeletal muscle fat deposition on the prognosis of patients with chronic liver disease remains unclear. Skeletal muscle fat deposition can be estimated by attenuation of skeletal muscle in Hounsfield units (HU) on computed tomography (CT). The aim of this retrospective cohort study was to investigate the association between skeletal muscle fat deposition assessed by skeletal muscle attenuation (SMA), and hepatocellular carcinoma (HCC). METHODS: We enrolled 288 patients with chronic liver disease (139 men, 149 women; mean age 67.5 ± 10.4 y; hepatitis C virus, 239; hepatitis B virus, 17; without viral infection, 32; chronic hepatitis, 227; and cirrhosis, 61) who underwent liver biopsy and CT scanning between January 2013 and February 2017. The patients were divided into two groups based on SMA levels, with the cutoff value of 31 HU. We analyzed the effect of SMA on HCC development. RESULTS: During the study follow-up period (median, 2.50 y; range, 0.5-4.7 y), HCC was identified in 19 patients (7%). The cumulative incidence of HCC in patients with lower SMA (<31 HU) was significantly higher than in patients with SMA ≥31 HU (P = 0.007). Cox proportional hazards regression analysis confirmed cirrhosis (hazard ratio [HR], 6.626; 95% confidence interval [CI], 2.57-17.12; P <0.001) and lower SMA (HR, 3.502; 95% CI, 1.25-9.83; P = 0.017) as significant independent factors associated with HCC development in patients with chronic liver disease. CONCLUSIONS: Patients with cirrhosis and skeletal muscle fat deposition assessed by SMA had a higher risk for developing HCC.


Assuntos
Tecido Adiposo/patologia , Carcinoma Hepatocelular/etiologia , Doença Hepática Terminal/patologia , Neoplasias Hepáticas/etiologia , Músculo Esquelético/patologia , Tecido Adiposo/diagnóstico por imagem , Idoso , Carcinoma Hepatocelular/epidemiologia , Doença Hepática Terminal/complicações , Feminino , Seguimentos , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Hepatite Crônica/complicações , Hepatite Crônica/patologia , Humanos , Incidência , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos
11.
J Clin Neurosci ; 53: 218-220, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29724648

RESUMO

Cystic dilatation of synovial sheath, one of the targets of extra-hepatic manifestations associated with liver disease, is a main pathologic finding of lumbar synovial cyst (LSC). However, LSCs are not well documented in correlation with chronic viral hepatitis. In this case series, three patients with chronic viral hepatitis presented with radiating pain in the unilateral lower extremities. On magnetic resonance imaging of the lumbar spine, all had unilateral LSCs at the facet joint of the lumbar spine. Two did not have definite spinal instability at the LSC level. Ultimately, all three showed clinical improvements following epidural spine interventions.


Assuntos
Hepatite Crônica/complicações , Cisto Sinovial/virologia , Articulação Zigapofisária/patologia , Idoso , Humanos , Vértebras Lombares/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Cisto Sinovial/patologia , Articulação Zigapofisária/virologia
12.
Sci Rep ; 8(1): 2008, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29386646

RESUMO

Gilbert's syndrome (GS) patients present with remittent unconjugated hyperbilirubinemia. In this study, we investigated the correlation between polymorphisms in the gene encoding UDP-glucuronosyltransferase, UGT1A1, and the development of unconjugated hyperbilirubinemia in clinical GS and post-hepatitis hyperbilirubinemia. Blood samples were collected from 285 patients, including 85 patients who were clinically diagnosed with GS, 70 patients who had indirect hyperbilirubinemia during the recovery period of chronic liver diseases, 109 patients with normal hepatic function and 21 chronic active hepatitis patients. All samples were tested for the presence of the *28/*6 UGT1A1 genotype by pyrosequencing. Compared with the GS-control group, a significant difference in variations of the UGT1A1*28/*6 allele gene was found in GS patients. The post-hepatitis group showed a significant difference in the UGT1A1*28/*6 allele gene frequency distribution relative to that in the hepatitis control group. There were no significant differences between the GS group and post-hepatitis group in the distribution of the UGT1A1*28/*6 allele gene frequency and UGT1A1 diplotypes. UGT1A1*28/*6 gene polymorphisms in patients who had indirect hyperbilirubinemia while recovering from chronic liver diseases presented similar patterns as those seen for GS patients. These findings suggest that a "Gilbert's-like" syndrome might be part of the spectrum of persistent unconjugated hyperbilirubinemia in post-chronic hepatitis patients.


Assuntos
Doença de Gilbert/genética , Hepatite Crônica/genética , Hiperbilirrubinemia/genética , Adulto , Feminino , Frequência do Gene , Doença de Gilbert/patologia , Glucuronosiltransferase/genética , Hepatite Crônica/complicações , Hepatite Crônica/patologia , Humanos , Hiperbilirrubinemia/etiologia , Hiperbilirrubinemia/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único
14.
J Hepatol ; 68(3): 519-525, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29162389

RESUMO

BACKGROUND & AIMS: We hypothesized that patients currently diagnosed with cryptogenic cirrhosis (CC) have truly 'cryptogenic' liver disease, which is unlikely to have evolved from NASH. The aim of this study is to characterize patients with CC, and compare their characteristics to patients with cirrhosis of other etiologies. METHODS: To investigate this, we compared the clinical characteristics of adults with CC (n = 7,999) to those with cirrhosis caused by non-alcoholic steatohepatitis (NASH) (n = 11,302), alcohol (n = 21,714) and autoimmune hepatitis (n = 3,447), using the UNOS database from 2002-16. We performed an age, gender and year of listing matched comparison of CC and NASH (n = 7,201 in each group), and also stratified patients by the presence of obesity or diabetes mellitus (DM). RESULTS: From 2002 to 2016, patients listed with a diagnosis of NASH increased from about 1% to 16% while CC decreased from 8% to 4%. A logistic regression model using the entire United Network for Organ Sharing data (n = 138,021) suggested that the strongest predictors of NASH were type 2 DM, obesity, age ≥60 years, female gender and white race. Type 2 DM was more common in patients with NASH (53%) than those with CC (29%), alcoholic cirrhosis (16%) and autoimmune hepatitis (16%), and obesity was more common in NASH (65.3%) compared to the other three groups (33-42%). There were more white individuals (82.3%) in the NASH group and a lower prevalence of black, Hispanic and Asian individuals, compared to the other three groups. Hepatocellular carcinoma was more commonly seen in NASH (19% vs. 9-13% in the other groups) and this is not influenced by obesity and type 2 DM. The differences between CC and NASH remained unchanged even when two groups were matched for age, gender and year of listing, or when stratified by the presence or absence of obesity or type 2DM. CONCLUSIONS: Based on risk perspectives, CC should not be equated with the term 'NASH cirrhosis'. LAY SUMMARY: We hypothesized that cryptogenic cirrhosis is a distinct condition from cirrhosis caused by non-alcoholic steatohepatitis (NASH). By comparing cryptogenic cirrhosis with cirrhosis of other causes, we found clear clinical differences. Therefore, cryptogenic cirrhosis should not be considered the same as NASH cirrhosis. Further investigations are required to identify unknown causes of cirrhosis.


Assuntos
Hepatite Autoimune , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Adulto , Fatores Etários , Idoso , Diabetes Mellitus/epidemiologia , Diagnóstico Diferencial , Feminino , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Hepatite Crônica/complicações , Hepatite Crônica/diagnóstico , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade/epidemiologia , Medição de Risco , Fatores de Risco , Fatores Sexuais
16.
Medicine (Baltimore) ; 96(39): e7915, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28953614

RESUMO

RATIONALE: Acute hepatitis E virus (HEV) infections are usually self-limiting in immunocompetent patients. HEV persistence has been described only in immunosuppressed patients such as solid-organ transplant recipients, patients with hematological diseases, or patients with human immunodeficiency virus (HIV) infection. PATIENT CONCERNS: A 61-year-old patient was admitted in hospital for jaundice and asthenia. DIAGNOSES: The patient had underlying cirrhosis and developed a chronic HEV infection. INTERVENTION: Ribavirin therapy was initiated. OUTCOMES: Ribavirin therapy for 12 months allowed the clearance of the virus and HEV viral load remained undetectable thereafter. This patient had taken no immunosuppressive drugs, was not suffering from any autoimmune disease and was not infected with HIV. We studied the patient's anti-HEV immune response months after the viral clearance. His peripheral blood mononuclear cells (PBMC) were stimulated in vitro by HEV peptides. The patient had a mild T lymphopenia, but polyclonal stimulation of PBMC showed a robust T cell response. The response of his anti-HEV specific interferon-γ producing T cells was low. LESSONS: Other studies are now needed to identify the population with a chronic evolution of HEV infection despite no apparent immunodepression.


Assuntos
Antivirais/uso terapêutico , Hepatite E/complicações , Hepatite E/tratamento farmacológico , Cirrose Hepática/complicações , Ribavirina/uso terapêutico , ELISPOT , Hepatite E/imunologia , Hepatite Crônica/complicações , Hepatite Crônica/tratamento farmacológico , Hepatite Crônica/imunologia , Humanos , Interferon gama/sangue , Cirrose Hepática/imunologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade
17.
Int J Infect Dis ; 64: 4-8, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28847760

RESUMO

OBJECTIVES: To determine the seroprevalence of hepatitis E virus (HEV) infection in patients with chronic hepatitis and/or hepatocellular carcinoma (HCC) and to assess its potential consequences for disease progression. METHODS: We conducted a prospective case-control study on patients with HCC hepatitis B or C related and non-HCC patients including patients with CLD and patients without clinical evidence of liver disease. Anti-HEV IgG and IgM were tested by ELISA using commercially available kits. Liver damage was assessed by alanine aminotransferase, aspartate aminotransferase, platelets and prothrombin measurements. RESULTS: We observed a significant anti-HEV IgG carriage in HCC patients compared to non-HCC subjects with CLD (41.8% vs 12.6%; P=9.1 E-6; OR=4.8, 95%CI: 2.3-10.6). HCC patients with HEV infection display more profound alterations of circulating liver enzymes, platelets count and prothrombin time than HCC patients without sero-reactivity to HEV. CONCLUSION: Overall, this study indicates a high prevalence of HEV infection in Cameroonian patients with CLD and HCC. These data suggest either that patients with liver tumors are more susceptible to hepeviral infection or that, in a tropical context, HEV might promote the progression of liver diseases towards tumor.


Assuntos
Carcinoma Hepatocelular/virologia , Vírus da Hepatite E , Hepatite E/complicações , Adulto , Camarões/epidemiologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Anticorpos Anti-Hepatite , Hepatite B/complicações , Hepatite E/epidemiologia , Vírus da Hepatite E/imunologia , Hepatite Crônica/complicações , Humanos , Neoplasias Hepáticas , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Estudos Soroepidemiológicos , Adulto Jovem
18.
Rev Recent Clin Trials ; 12(3): 162-167, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28606043

RESUMO

BACKGROUND: Despite the high prevalence of viral hepatic cirrhosis all over the world, the characteristic motor features of related Parkinsonism (extrapyramidal manifestations) are not well described. The current study aimed to characterize such disorder in a sample of Egyptian patients with chronic viral liver disease (CLD), and their clinical correlates. METHODS: Ninety-six (96) patients with CLD were examined for the presence of extrapyramidal signs. Parkinsonism was assessed using the UPDRS-III scale and its sub scores. Ataxia and dystonia were also assessed by related scales. Patients with Parkinsonism were compared to other patients and correlations with clinical features of CLD were done. RESULTS: The clinical diagnosis of extrapyramidal manifestations was justified in 57 patients (59.4%) with predominant akinetic rigid syndrome (ARS) (87.7%). Bradykinesia and axial features were the most frequent signs (89.5% and 70.2%, respectively). 38.6% of patients had postural tremors, whereas only 3.5% had rest tremors. Gait and postural abnormalities were detected in 38.6% and 36.8% respectively. Parkinsonism was associated with advanced hepatic cirrhosis (p=0.02) and increased episodes of hepatic encephalopathy (HE) (p=0.006). Severity of parkinsonian features was correlated to patients' age, age of onset of CLD and rapid progression, while impaired speech and gait were rather correlated to a number of episodes of HE. CONCLUSION: Advanced viral cirrhosis is associated with high prevalence of parkinsonism that is characterized by symmetrical ARS with frequent axial features, postural tremor, gait and postural impairment. Severity of these signs is correlated to age, age of onset, rapid progression and frequency of HE.


Assuntos
Hepatite Crônica/complicações , Hepatite Viral Humana/complicações , Degeneração Hepatolenticular/etiologia , Cirrose Hepática/complicações , Adulto , Idoso , Estudos Transversais , Egito/epidemiologia , Feminino , Hepatite Crônica/epidemiologia , Hepatite Viral Humana/epidemiologia , Degeneração Hepatolenticular/epidemiologia , Humanos , Incidência , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Taxa de Sobrevida/tendências
19.
Liver Int ; 37(11): 1651-1659, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28508586

RESUMO

BACKGROUND & AIMS: We previously found that hepatic stellate cell activation induced by autophagy maintains the liver architecture to prevent collapse during acute liver failure. Nitric oxide has shown to induce hepatic stellate cell apoptosis. Whether and how nitric oxide is involved in acute liver failure and autophagy remains unclear. METHODS: Acute liver failure patients were recruited to investigate the correlation between plasma nitric oxide levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from acute liver failure patients who had undergone liver transplantation. The expression of nitric oxide synthases and hepatic stellate cell activation (alpha-SMA), and autophagic activity (LC3) were investigated by immunohistochemistry. Autophagy and apoptosis were investigated by immunoblot analysis, confocal microscopy, and flow cytometry in hepatic stellate cells treated with nitric oxide donors. RESULTS: Plasma nitric oxide level was significantly increased in patients with acute liver failure compared to those with cirrhosis (53.60±19.74 µM vs 19.40±9.03 µM, Z=-7.384, P<.001) and positively correlated with MELD-Na score (r=.539, P<.001), implicating nitric oxide in acute liver failure. At least some Nitric oxide was produced by overexpression of inducible nitric oxide synthases and endothelial nitric oxide synthases, but not neuronal nitric oxide synthases in the liver tissue. In vivo observation revealed that autophagy was inhibited in hepatic stellate cells based on decreased LC3 immunostaining, and in vitro experiments demonstrated that Nitric oxide can inhibit autophagy. Moreover, nitric oxide promoted hepatic stellate cell apoptosis, which was rescued by an autophagy inducer. CONCLUSIONS: Increased nitric oxide synthases/ nitric oxide promotes apoptosis through autophagy inhibition in hepatic stellate cells during acute liver failure, providing a novel strategy for the treatment of patients with acute liver failure.


Assuntos
Apoptose , Autofagia , Células Estreladas do Fígado/citologia , Falência Hepática Aguda/sangue , Óxido Nítrico/sangue , Adulto , Animais , Feminino , Hepatite Crônica/complicações , Humanos , Fígado/patologia , Cirrose Hepática/complicações , Falência Hepática Aguda/patologia , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase/metabolismo
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