Resumen Introdución: La pandemia del coronavirus 2019 (COVID-19) representa un desafío a la salud mental de los profesionales de la salud que trabajan en la atención directa al paciente. Se necesitan datos de investigación para apoyar la implementación de las intervenciones e las medidas de protección. Objetivo: Evaluar la prevalencia y factores relacionados con la ansiedad, depresión y estrés en el equipo de salud de un hospital de referencia en la atención de pacientes con COVID-19 cuatro meses después del primer caso confirmado en Brasil. Método: Se trata de un estudio transversal, descriptivo y cuantitativo con enfermeros, técnicos de enfermería, fisioterapeutas y médicos. Se utilizó un cuestionario sociodemográfico y los aspectos profesionales relacionados a la COVID-19. Se utilizó la escala DASS-21 para evaluar la ansiedad, depresión y el estrés. Resultados: Participaron de la investigación 112 personas, de las cuales el 52,68% presentaron síntomas de depresión, el 57,14% de ansiedad y el 78,57% de stress. Hubo asociación de depresión con el puesto de enfermero, con el hecho de estar bajo acompañamiento psicológico previo a la pandemia, con la ausencia de participación en capacitaciones para la asistencia. La ansiedade presentó asociacion con el sexo feminino y con el miedo a enfermarse. El estrés se asoció a una edad más joven, de 30 a 39 años y al estado civil casado o en unión estable. Conclusión: Durante la fase inicial del brote de COVID-19 hubo una alta prevalencia de trastornos mentales entre los profesionales de la asistencia directa al paciente y los síntomas de depresión, ansiedad y estrés se manifestaron en la mayoría de los participantes de manera moderada y severa.

Abstract Introduction: The 2019 coronavirus pandemic (COVID-19) represented a challenge to the mental health of health professionals working in direct paciente care. Research data is important to assist with the implementation of interventions and protective measures. Objective: To assess the prevalence and factors related to anxiety, depression and stress in the health team of a referral hospital in the care of patients with COVID-19 four months after the first confirmed case in Brazil. Method: This is a cross-sectional, descriptive and quantitative study with nurses, nursing technicians, physiotherapist and physicians. A sociodemographic and profesional aspects related to COVID-19 questionnaire were used. To assess anxiety, depression and stress the DASS-21 scale was used. Results: 112 people participated in the study, of which 52,68% had depression symptoms, 57,14% of anxiety and 78,57% of stress. There was an association of depression with the position of nurse, with being under psychological monitoring prior the pandemic, with absence of participation in care training. Anxiety was associated with female gender and the fear of falling ill. Stress was associated with the younger age, 30 to 39 years, and with marital status, married or in stable union. Conclusion: during the initial phase of COVID-19 outbreak there was a high prevalence of mental disorders among professionals directly assisting patients and symptoms of depression, anxiety and stress were manifested in most participants in a moderated or severe manner.

Resumo Introdução: A pandemia de coronavírus 2019 (COVID-19) representa um desafio à saúde mental dos profissionais de saúde que atuam na assistência direta ao paciente. Dados de pesquisas são necessários para auxiliar a implementação de intervenções e medidas de proteção. Objetivo: Avaliar a prevalência e os fatores relacionados à ansiedade, depressão e estresse na equipe de saúde de um hospital de referência no atendimento a pacientes com COVID-19 quatro meses após o primeiro caso confirmado no Brasil. Métodos: Trata-se de um estudo transversal, correlacional e quantitativo com enfermeiros, técnicos de enfermagem, fisioterapeutas e médicos. Foi utilizado um questionário sociodemográfico e sobre os aspectos profissionais relacionados a COVID-19. Para a avaliação da ansiedade, depressão e estresse foi utilizada a escala DASS-21. Resultados: Participaram do estudo 112 pessoas, das quais 52,68% apresentaram sintomas de depressão, 57,14% de ansiedade e 78,57% de estresse. Houve associação da depressão com o cargo de enfermeiro, com o fato de estar em acompanhamento psicológico anterior a pandemia, com a ausência de participação em treinamento para assistência. A ansiedade apresentou associação com o sexo feminino e com o medo de adoecer. O estresse foi associado a idade mais jovem, 30 a 39 anos e ao estado civil casado ou em união estável. Conclusão: Durante a fase inicial do surto de COVID-19 houve uma alta prevalência de transtornos mentais nos profissionais de assistência direta ao paciente e os sintomas de depressão, ansiedade e estresse se manifestaram na maioria dos participantes de forma moderada e grave.

ABSTRACT Introduction: This study aimed to characterize Staphylococcus aureus isolates from bloodstream infections in patients attending a teaching hospital, between 2011 and 2015. Methods: The minimum inhibitory concentration for daptomycin, linezolid, oxacillin, teicoplanin, vancomycin, and trimethoprim/sulfamethoxazole was accessed by broth microdilution. SCCmec type and clonal profile were determined by molecular tests. Vancomycin heteroresistance was evaluated using screening tests and by population analysis profile/area under the curve. Results: Among 200 S. aureus isolates, 55 (27.5%) were MRSA, carrying SCCmec II (45.5%) or IV (54.5%). The most frequent MRSA lineages were USA100 (ST5-II) (45.5%) and USA800 (ST5-IV) (30.9%). Six isolates were confirmed as vancomycin heteroresistant, showing area under the curve ratio 1.1, 1.2 or 1.3 (four USA100, one USA800 and one USA1100 isolates). Conclusions: Daptomycin and vancomycin non-susceptible MRSA clonal lineages were found in bloodstream infections over five years, highlighting the importance of continuous surveillance of multiresistant bacteria in hospitals.

ABSTRACT To characterize methicillin-resistant Staphylococcus aureus isolates from an intensive care unit of a tertiary-care teaching hospital, between 2005 and 2010. A total of 45 isolates were recovered from patients admitted to the intensive care unit in the study period. Resistance rates higher than 80% were found for clindamycin (100%), erythromycin (100%), levofloxacin (100%), azithromycin (97.7%), rifampin (88.8%), and gentamycin (86.6%). The SCCmec typing revealed that the isolates harbored the types III (66.7%), II (17.8%), IV (4.4%), and I (2.2%). Four (8.9%) isolates carried non-typeable cassettes. Most (66.7%) of the isolates were related to the Brazilian endemic clone from CC8/SCCmec III, which was prevalent (89.3%) between 2005 and 2007, while the USA100/CC5/SCCmec II lineage emerged in 2007 and was more frequent in the last few years. The study showed high rates of antimicrobial resistance among methicillin-resistant S. aureus isolates and the replacement of Brazilian clone, a well-established hospital lineage, by the USA100 in the late 2000s, at the intensive care unit under study.

PURPOSE: To evaluate the underlying mechanisms by which sevoflurane protects the liver against ischemia/reperfusion injury evaluate the mechanism by which sevoflurane exerts this protective effect. METHODS: Twenty-six rats were subjected to partial ischemia/reperfusion injury for 1h: one group received no treatment, one group received sevoflurane, and sham group of animals received laparotomy only. Four hours after reperfusion, levels of alanine and aspartate aminotransferases, tumor necrosis factor-a, and interleukins 6 and 10 were measured. Analyses of mitochondrial oxidation and phosphorylation, malondialdehyde content, histology, and pulmonary vascular permeability were performed. RESULTS: Serum levels of alanine and aspartate aminotransferases were significantly lower in the sevoflurane group compared to untreated controls (p<0.05). The sevoflurane group also showed preservation of liver mitochondrial function compared to untreated controls (p<0.05). Sevoflurane administration did not alter increases in serum levels of tumor necrosis factor-a, and interleukins 6 and 10. Sevoflurane treatment significantly reduced the coagulative necrosis induced by ischemia/reperfusion (p<0.05). Pulmonary vascular permeability was preserved in the sevoflurane group compared to untreated controls. CONCLUSION: Sevoflurane administration protects the liver against ischemia/reperfusion injury, via preservation of mitochondrial function, and also preserves lung vascular permeability.

Staphylococcus aureus is an important cause of infections and HIV-infected individuals are frequently susceptible to this pathogen. The aim of this study was to perform a systematic review to identify both the risk factors associated with colonization/infection by methicillin-resistant S. aureus in HIV patients and the methods used for characterization of isolates. An electronic search of articles published between January 2001 and December 2013 was first conducted. Among 116 studies categorized as being at a quality level of A, B or C, only 9 studies were considered to have high methodological quality (level A). The majority of these studies were retrospective (4/9 studies). The risk factors associated with colonization/infection by S. aureus were use of antimicrobials (4/9 studies), previous hospitalization (4/9 studies) and low CD4+ T lymphocyte counts (<200 cells/μl) (3/9 studies). Culture in mannitol salt agar (3/9 studies) and the latex agglutination test (5/9 studies) were the main methods used for bacterial phenotypic identification. Genotypic profiles were accessed by pulsed-field gel electrophoresis (6/9 studies) and USA300 was the most prevalent lineage (5/9 studies). Most isolates were resistant to erythromycin (3/9 studies) and susceptible to vancomycin (4/9 studies). Ultimately, use of antimicrobials and previous hospitalization were the main risk factors for colonization/infection by methicillin-resistant S. aureus in HIV-infected individuals. However, the numbers of evaluated patients, the exclusion and inclusion criteria and the characterization of the S. aureus isolates were not uniform, which made it difficult to establish the characteristics associated with HIV patients who are colonized/infected by S. aureus.

OBJECTIVE: To investigate the pathogenesis of bloodstream infection by Staphylococcus epidermidis, using the molecular epidemiology, in high-risk neonates. METHODS: We conducted a prospective study of a cohort of neonates with bloodstream infection using central venous catheters for more than 24 h. "National Healthcare Safety Network" surveillance was conducted. Genotyping was performed by DNA fingerprinting and mecA genes and icaAD were detected by multiplex-PCR. RESULTS: From April 2006 to April 2008, the incidence of bloodstream infection and central venous catheter-associated bloodstream infection was 15.1 and 13.0/1000 catheter days, respectively, with S. epidermidis accounting for 42.9% of episodes. Molecular analysis was used to document the similarity among six isolates of bloodstream infection by S. epidermidis from cases with positive blood and central venous catheter tip cultures. Fifty percent of neonates had bloodstream infection not identified as definite or probable central venous catheter-related bloodstream infection. Only one case was considered as definite central venous catheter-related bloodstream infection and was extraluminally acquired; the remaining were considered probable central venous catheter-related bloodstream infections, with one probable extraluminally and another probable intraluminally acquired bloodstream infection. Additionally, among mecA+ and icaAD+ samples, one clone (A) was predominant (80%). A polyclonal profile was found among sensitive samples that were not carriers of the icaAD gene. CONCLUSIONS: The majority of infections caused by S. epidermidis in neonates had an unknown origin, although 33.3% appeared to have been acquired intraluminally and extraluminally. We observed a polyclonal profile between sensitive samples and a prevalent clone (A) between resistant samples.

PURPOSE: To investigate the effects of the maternal caffeine consumption during pregnancy to adult male testis mice offspring.METHODS: Twenty pregnant mice were divided into control group (c) and caffeine group (cf). dams received daily saline or 20 mg/kg of caffeine subcutaneously. Male offspring were monitored daily until 13th week. The testis were used to evaluate both the proliferation (pcna) and apoptosis (bax); leptin receptor (ob-r); aromatase; follicle stimulating hormone (fshr), luteinizing hormone (lhr) and androgen receptors (ar); steroidogenic acute regulatory protein (star); vascular endothelial growth factor (vegf) and estrogen receptors (erα and erβ) by western blotting. Serum concentrations of testosterone, estradiol and leptin were measured.RESULTS: There was a significant reduction in food intake and the body mass gain (p<0.05) in the cf ; pcna (p=0.01), fshr (p=0.02), star (p=0.0007), vegf (p=0.009), ar (p=0.03) in the cf. while an increase were note in bax (p=0.01), ob-r (p=0.02), lhr (p=0.04) and in the aromatase (p=0.03) in the cf. only erα and erβ were not changed by maternal caffeine. The serum testosterone levels in the cf offspring were 90% lower than in the c offspring (p=0.04).CONCLUSION: Maternal caffeine consumption has a role and alters the testis of the offspring in adulthood.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) can be difficult to detect at the clinical practice. METHODS: We analyzed 140 MRSA isolates from inpatients to correlate the antimicrobial susceptibility with the SCCmec types. RESULTS: Type III (n = 63) isolates were more resistant to ciprofloxacin, clindamycin, cloramphenicol, erythromycin, gentamicin, and rifampin than type IV (n = 65) ones (p < 0.05). Moreover, type IV isolates were susceptible to tetracycline (100%) and trimethoprim/sulfamethoxazole (98%), while type III isolates presented resistance to them. CONCLUSIONS: In regions where these SCCmec types are prevalent, the detection of specific resistant phenotypes could help to predict them, mainly when there are no technical conditions to SCCmec typing.

The leptin hormone is important to satiety and an important link between the nutritional status and reproductive processes. Owing to the contradictory effects of leptin on the ovary and the failure to clarify the precise mechanism by which leptin affects the ovary, our aim was to contribute to evaluation if leptin can directly regulate the gene expression of leptin itself and its receptors, and the expression of several genes related to the ovary function by a model of tissue culture. Ovaries from Wistar dams were used at 90 days of age and were submitted to medium with presence and absence of leptin. The results can demonstrate that leptin regulates gonadotropins and steroid receptors, which could suggest that the ovarian leptin role could be secondary to the changes in these receptorse expression in rats.

La hormona leptina es importante en la sensación de la saciedad y un vínculo importante entre el estado nutricional y los procesos reproductivos. Debido a los efectos contradictorios de la leptina en el ovario y la falta de esclarecimiento del mecanismo exacto por el cual la leptina afecta el ovario, nuestro objetivo es contribuir a la evaluación si la leptina puede regular directamente la expresión del gen de la leptina sí mismo y sus receptores, y la expresión de varios genes relacionados con la función del ovario por un modelo de cultivo de tejidos. Los ovarios de las presas Wistar fueron usadas en los 90 días de edad y se sometieron a medio con presencia y ausencia de leptina. Los resultados pueden mostrar que la leptina regula las gonadotropinas y los receptores de esteroides, lo que podría sugerir que la función ovárica de la leptina podría ser secundario a los cambios en la expresión de sus receptores en ratas.

JUSTIFICATIVA E OBJETIVOS: Uma compreensão melhor das alterações fisiopatológicas associadas ao trauma e ao choque hemorrágico pode ajudar no desenvolvimento de terapêuticas capazes de reduzir a mortalidade relacionada ao trauma. O objetivo deste estudo é descrever um modelo de choque hemorrágico não controlado em porcos. MÉTODOS: Como medicação pré-anestésica, os animais receberam cetamina e midazolan. A anestesia foi induzida com propofol e a intubação traqueal foi realizada na vigência de respiração espontânea. Após a intubação, realizou-se bloqueio neuromuscular. Os animais foram mantidos em respiração mecânica controlada e normocapnia. A anestesia foi mantida com propofol e fentanil, de acordo com a necessidade. Solução de soro fisiológico 0,9% foi infundida em todo o período de preparação. MONITORAÇÃO: Foram utilizados cardioscópio, oxímetro de pulso, medida de pressão arterial invasiva, cateter volumétrico de artéria pulmonar e medida de débito urinário por cistostomia. Modelo experimental: após registro inicial de variáveis hemodinâmicas, metabólicas e de coagulação, realizaram-se incisão subcostal direita e biópsia hepática do lobo esquerdo. A infusão de anestésicos foi reduzida, enquanto a de solução de salina isotônica interrompida. Uma incisão de 12 cm de extensão por 2 cm de profundidade foi feita no lobo hepático direito, seguida de divulsão digital do ferimento. Durante a fase de hemorragia, uma sonda de aspiração foi posicionada junto ao ferimento e o volume de sangue aspirado foi registrado. Quando a pressão arterial média chegou a 40 mmHg e o sangramento foi superior a 700 mL, pôde ser iniciada a fase de intervenção de acordo com o tipo de estudo. CONCLUSÃO: É importante continuar o desenvolvimento de modelos experimentais com o objetivo final de reduzir a alta mortalidade e os custos associados ao trauma.

BACKGROUND AND OBJECTIVES: A better understanding of pathophysiologic changes associated to trauma and hemorrhagic shock can help the development of therapies capable of reducing trauma-related mortality. The objective of this study was to describe a model of non-controlled hemorrhagic shock in pigs. METHODS: Animals received ketamine and midazolam as pre-anesthetic medications. Anesthesia was induced with propofol, and tracheal intubation was performed with the animals on spontaneous ventilation. After intubation neuromuscular blockade was performed. Animals were maintained in controlled mechanical ventilation and normocapnia. Anesthesia was maintained with propofol and fentanyl as needed. Saline was infused during the entire preparation period. MONITORING: Cardioscope, pulse oximeter, invasive blood pressure, volumetric catheter in the pulmonary artery, and urine output by cystostomy were used. Experimental model: after the initial recording of hemodynamic, metabolic, and coagulation variables, right subcostal incision and left lobe liver biopsy were performed. Anesthetic infusion was reduced while the infusion of saline was interrupted. An incision 12 cm long 2 cm deep was performed in the right liver lobe followed by digital divulsion of the wound. During the hemorrhagic phase, an aspiration probe was placed close to the wound and the volume of aspirated blood was recorded. When mean arterial pressure reached 40 mmHg and bleeding was above 700 mL the intervention phase was initiated according to the type of study. CONCLUSION: The development of experimental models to reduce high mortality and costs related to trauma is important.

JUSTIFICATIVA Y OBJETIVOS: Una comprensión mejor de las alteraciones fisiopatológicas asociadas al trauma y al choque hemorrágico, puede ayudar en el desarrollo de las terapéuticas capaces de reducir la mortalidad relacionada con el trauma. El objetivo de este estudio es describir un modelo de choque hemorrágico no controlado en cerdos. MÉTODOS: Como medicación preanestésica, los animales recibieron cetamina y midazolan. La anestesia fue inducida con propofol, y la intubación traqueal fue realizada con la respiración espontánea. Después de la intubación, se realizó el bloqueo neuromuscular. Los animales se mantuvieron bajo respiración mecánica controlada y normocapnia. La anestesia se mantuvo con propofol y fentanil, a tono con la necesidad. Una solución de suero fisiológico al 0,9% fue infundida durante todo el período de la preparación. MONITOREO: Se usaron el cardioscopio, oxímetro de pulso, medida de presión arterial invasiva, catéter volumétrico de arteria pulmonar y medida de débito urinario por cistostomía. Modelo experimental: después del registro inicial de las variables hemodinámicas, metabólicas y de coagulación, se realizaron la incisión subcostal derecha y la biopsia hepática del lóbulo izquierdo. La infusión de anestésicos fue reducida, mientras que la solución de salina isotónica se interrumpió. Una incisión de 12 cm de extensión por 2 cm de profundidad se hizo en el lóbulo hepático derecho, seguida de una divulsión digital de la herida. Durante la fase de hemorragia, una sonda de aspiración fue posicionada junto a la herida, y el volumen de sangre aspirado fue registrado. Cuando la presión arterial promedio llegó a 40 mmHg y el sangramiento fue superior a 700 mL, pudo iniciarse la fase de intervención de acuerdo con el tipo de estudio. CONCLUSIÓN: Es importante continuar desarrollando modelos experimentales con el objetivo final de reducir la alta mortalidad y los costes asociados al trauma.

Os vírus do herpes simplex tipos 1 e 2 são os principais agentes infecciosos associados às ulcerações orais e vaginais. Estas infecções são amplamente reconhecidas como doenças sexualmente transmissíveis. Entre as opções de tratamento, o laser de baixa intensidade (LBI) mostrou resultados promissores como terapia de supressão de longa duração. Descrevemos dois casos clínicos com herpes labial recorrentes nos quais o LBI foi utilizado que permaneceram assintomáticos durante 17 meses de controle clínico.

Herpes simplex virus types 1 and 2 are the main infectious agents associated with oral and genital ulcerations. These infections are now widely recognized as sexually transmitted diseases. Among treatment options, low-level laser therapy (LLLT) has shown promising clinical results as a longer-lasting suppression therapy. Two clinical cases are described with recurrent labial herpes for which LLLT was used. Following treatment, both patients remained symptom free during the 17-month clinical follow-up period.

A total of 138 isolates, 118 methicillin-resistant Staphylococcus aureus (MRSA) isolates (staphylococcal cassette chromosome type II, 20 isolates, type III, 39 isolates and type IV, 59 isolates) and 20 methicillin-sensitive S. aureus isolates were evaluated by phenotypic methods: cefoxitin and oxacillin disk diffusion (DD), agar dilution (AD), latex agglutination (LA), oxacillin agar screening (OAS) and chromogenic agar detection. All methods showed 100% specificity, but only the DD tests presented 100% sensitivity. The sensitivity of the other tests ranged from 82.2% (OAS)-98.3% (AD). The LA test showed the second lowest sensitivity (86.4%). The DD test showed high accuracy in the detection of MRSA isolates, but there was low precision in the detection of type IV isolates by the other tests, indicating that the genotypic characteristics of the isolates should be considered.

Wedged beam are often used in clinical radiotherapy to compensate missing tissues and dose gradients. In this work, the Fricke Xylenol Gel (FXG) dosimeter was used for 6 MV photons radiation wedge field profiles measurements, allowing to infer the wedge filter physical attenuation coefficient. This dosimeter is a chemical system of a Fe3+-Xylenol complex concentration, that when measured spectrophotometrically, the absorbance is directly proportional to the absorbed dose. From theses results one can infer that the FXG can be used also as an alternative dosimetric system for measurements of wedge filters.

RACIONAL: OBJETIVO: Avaliar a evolução de 20 pacientes com insuficiência hepática aguda e indicação de transplante hepático. MÉTODOS: Foi realizado estudo retrospectivo de 20 pacientes com insuficiência hepática aguda e indicação de transplante hepático. Os pacientes foram divididos em dois grupos: grupo A com 12 pacientes que foram submetidos a transplante hepático e grupo B com oito pacientes não submetidos a transplante hepático. Ambos os grupos foram analisados de acordo com idade, sexo, tipagem sangüínea, etiologia da insuficiência hepática aguda, tempo em lista até o transplante ou até o óbito e sobrevida. Os pacientes do grupo A foram ainda analisados de acordo com o escore MELD (Model for End-stage Liver Disease), valores de pico pré-operatório de INR, AST e ALT, necessidade de transfusão de concentrado de hemácias e plasma fresco congelado durante o transplante, tempo de isquemia fria, tempo de permanência hospitalar e em unidade de terapia intensiva e necessidade de diálise no pós-transplante imediato. RESULTADOS: Grupo A: o tempo médio de espera em lista até o transplante foi de 3,4 dias e o MELD médio, de 36. Sete pacientes continuam vivos com boa função hepática em um tempo médio de seguimento de 26,2 meses. A sobrevida atuarial em 1 ano foi de 65,2%. Grupo B: foram estudados dois homens e seis mulheres com média de idade de 30,9 anos. O tempo médio de espera em lista até o óbito foi de 7,4 dias. Todos os pacientes foram a óbito esperando por um doador. CONCLUSÃO: Mesmo com todos os avanços nos cuidados de terapia intensiva, a maioria dos pacientes com insuficiência hepática aguda e indicação de transplante hepático não sobrevivem por muito tempo sem o transplante. O transplante hepático é potencialmente a única terapêutica curativa atualmente disponível e melhorou consideravelmente o prognóstico desses pacientes.

BACKGROUND: Fulminant hepatic failure carries a high morbidity and mortality. Liver transplantation has markedly improved the prognosis of patients with fulminant hepatic failure. AIM: To evaluate the outcome of 20 patients with acute liver failure and indication for liver transplantation. METHODS: A retrospective review of 20 patients with acute liver failure and indication for liver transplantation was performed. Patients were divided into two groups: group A with 12 patients who underwent liver transplantation and group B with 8 patients who did not receive liver transplantation. Both groups were analyzed according to age, sex, ABO blood type, etiology of acute liver failure, time on list until transplantation or death, and survival rates. Group A patients were additionally analyzed according to preoperative INR, AST, and ALT peak values and MELD (Model for End-stage Liver Disease) scores; intraoperative red blood cells and plasma transfusion and cold ischemia time; postoperative lenght of intensive care unit and hospital stay, and needed for dialysis. RESULTS: Group A: there were four men and eight women with an average age of 24.6 years. The average liver waiting time period was 3.4 days and MELD score 36. Seven patients are alive with good hepatic function at a medium follow-up of 26.2 months. The actuarial survival rate was 65.2% at 1 year. Group B: There were two men and six women with an average age of 30.9 years. The mean waiting time on list until death was 7.4 days. All patients died while waiting for a liver donor. CONCLUSION: Despite the improvements in intensive care management, most patients with acute liver failure and indication for liver transplantation ca not survive long without transplant. Liver transplantation is potentially the only curative modality and has markedly improved the prognosis of those patients.