RESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common lethal cancer, and there is a need for effective therapies. Selective internal radiation therapy (SIRT) has been increasingly used, but is not supported by guidelines due to a lack of solid evidence. AIMS: Determine the efficacy and safety of SIRT in HCC across the Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C. METHODS: Consecutive patients that received SIRT between 2006 and 2016 at two centers in Canada were evaluated. RESULTS: We analyzed 132 patients, 12 (9%), 62 (47%), and 58 (44%) belonged to BCLC stages A, B, and C; mean age was 61.2 (SD ± 9.2), and 89% were male. Median survival was 12.4 months (95% CI 9.6-16.6), and it was different across the stages: 59.7 (95% CI NA), 12.8 (95% CI 10.2-17.5), and 9.3 months (95% CI 5.9-11.8) in BCLC A, B, and C, respectively (p = 0.009). Independent factors associated with survival were previous HCC treatment (HR 2.01, 95% CI 1.23-3.27, p = 0.005), bi-lobar disease (HR 2.25, 95% CI 1.30-3.89, p = 0.003), ascites (HR 1.77, 95% CI 0.99-3.13, p = 0.05), neutrophil-to-lymphocyte ratio (HR 1.11, 95% CI 1.02-1.20, p = 0.01), Albumin-Bilirubin (ALBI) grade-3 (HR 2.69, 95% CI 1.22-5.92, p = 0.01), tumor thrombus (HR 2.95, 95% CI 1.65-5.24, p < 0.001), and disease control rate (HR 0.62, 95% CI 0.39-0.96, p = 0.03). Forty-four (33%) patients developed severe adverse events, and ALBI-3 was associated with higher risk of these events. CONCLUSIONS: SIRT has the potential to be used across the BCLC stages in cases with preserved liver function. When using it as a rescue treatment, one should consider variables reflecting liver function, HCC extension, and systemic inflammation, which are associated with mortality.
Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radioterapia Assistida por Computador/mortalidade , Canadá , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION AND AIM: Sarcopenia is an independent predictor of mortality in cirrhosis. Hypogonadism is common in cirrhosis and has been associated with sarcopenia in non-cirrhotic chronic liver disease populations. The aim of this study is to investigate if sarcopenia is associated with low testosterone levels in patients with cirrhosis. MATERIAL AND METHODS: This is a retrospective analysis of prospectively collected data of 211 cirrhotic patients undergoing evaluation for liver transplantation. Sarcopenia was defined by computed tomography (CT) scan using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L3 SMI). Morning testosterone levels were obtained in all patients. RESULTS: Of the 211 patients, sarcopenia was noted in 94 (45%). Testosterone levels were lower in sarcopenic patients (10.7 ± 1.1 vs. 13.7 ± 1.4 nmol/L, p = 0.03) and hypotestosteronemia was more frequent in them too (34 vs. 16%, p = 0.004). In males, those with sarcopenia had lower testosterone levels (14.6 ± 1.4 vs. 21.9 ± 1.8, p = 0.002), and the corresponding frequency of hypotestosteronemia (42 vs. 19%, p = 0.006) was also higher. There were no significant differences in female patients. There was a weak correlation between L3 SMI and testosterone levels (r 0.37, p < 0.001). On multivariable regression analysis including sex, body mass index (BMI), hypotestosteronemia, MELD and etiology of cirrhosis, only hypotestosteronemia (RR 2.76, p = 0.005) and BMI (RR 0.88, p < 0.001) were independently associated with sarcopenia. CONCLUSION: Low testosterone levels are associated with sarcopenia in male cirrhotic patients. The potential therapeutic effect of testosterone to reverse sarcopenia in these patients warrants evaluation in future trials.
Assuntos
Composição Corporal , Hipogonadismo/sangue , Cirrose Hepática/complicações , Músculo Esquelético/fisiopatologia , Sarcopenia/fisiopatologia , Testosterona/deficiência , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/etiologia , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Testosterona/sangue , Tomografia Computadorizada por Raios XRESUMO
The revised score of the International Autoimmune Hepatitis Group (R-IAIHG) and the simplified criteria (SC) are used for diagnosis of autoimmune hepatitis (AIH). Our aim is to evaluate the performance of these classifications to differentiate AIH from other autoimmune liver diseases. The frequency of diagnosis of definite AIH was similar both by the R-IAIHG and the SC systems (41% versus 40%), whereas diagnosis of probable AIH was made more commonly by the R-IAIHG than the SC (59% versus 29%), and 23 patients that have been graded as definite (n = 7) or probable (n = 16) AIH by the R-IAIHG had non-diagnostic scores by the SC system. The scoring systems rendered concordant diagnosis of definite (n = 15) and probable (n = 13) AIH in 28/73 patients (38%). Discordant diagnoses of AIH were rendered in 45/73 patients (62%). The R-IAIHG exhibited a sensitivity of 95%, specificity of 90%, and positive predictive value (PPV) and negative predictive value (NPV) of 93% for both. On the other hand, the SC had a lower sensitivity (65%) but a higher specificity (100%), PPV of 100%, and NPV of 68%. In conclusion, both international scoring systems diagnosed the same number of cases as definite AIH. The R-IAIHG showed a higher sensitivity in diagnosing AIH, whereas the SC showed a higher specificity. SC are easier to apply at the bedside and exclude more patients that could have a different etiology.
Assuntos
Classificação/métodos , Hepatite Autoimune/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hepatite Autoimune/classificação , Hepatite Autoimune/imunologia , Hispânico ou Latino , Humanos , Masculino , México , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
Autoimmune liver diseases are sometimes difficult to differentiate from hepatic overlap syndromes (OS). The objective of this study was to use polymorphic genetic markers to better distinguish clinical heterogeneity in autoimmune liver disease. Since autoimmunity is the result of autoantibody production we studied HLA-DR alleles in 20 patients with autoimmune hepatitis (AIH), 16 with primary biliary cirrhosis (PBC), 10 with OS, and in 99 ethnically matched healthy individuals. Patients with OS had significantly higher alkaline phosphatase and total bilirubin levels than patients with AIH. OS patients had a higher prevalence of positive antinuclear antibodies and a higher AIH score than patients with PBC. Patients with OS also had higher total immunoglobulin levels (IgG isotype) as compared to patients with PBC. We found in PBC patients a higher gene frequency of HLA-DR4 and DR1 as compared to healthy controls (p = 0.03, OR = 2.2 and p = 0.004, OR = 4.3, respectively) and to OS patients (p = 0.01, OR = 6.8, and p = 0.004, OR = 10.0, respectively). On the other hand, the gene frequency of HLADR5 was significantly decreased in the total group of patients as compared to healthy controls suggesting a protective role of this allele for developing autoimmune liver disease.
Assuntos
Doenças Autoimunes/genética , Biomarcadores/análise , Predisposição Genética para Doença , Antígenos HLA-DR/genética , Hepatopatias/genética , Anticorpos Antinucleares/sangue , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Frequência do Gene , Humanos , Imunoglobulina G/sangue , Hepatopatias/sangue , Hepatopatias/imunologia , Testes de Função Hepática , México , SíndromeRESUMO
OBJECTIVES: To study the prevalence, risk factors, outcome, and molecular epidemiology in patients with bacteremia caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (Kp) (cases), in comparison with patients with bacteremia caused by a susceptible Kp (controls). METHODS: This was a retrospective case-control study including all episodes of Kp bacteremia for the period 1993 to 2002 at a referral hospital for adults in Mexico. ESBL production was tested for by E-test. All isolates were typed by pulsed field gel electrophoresis (PFGE). A subset of isolates underwent plasmid analysis, conjugal transfer of cefotaxime resistance to Escherichia coli J53-2, isoelectric focusing bioassay, colony-blot hybridization, PCR, and sequencing. RESULTS: Of the 121 patients with bacteremia due to Kp included in the study, 17 (14.0%) had an ESBL-Kp isolate (cases). Multivariate analysis identified prior use of cephalosporins (OR 7.6, 95% CI 1.1-53.5; p=0.039) and stay in the intensive care unit (ICU; OR 5.6, 95% CI 1.1-27.9; p=0.033) as significant risk factors. No differences were observed in hospital stay or mortality after the event. Multi-drug resistance was more frequent in ESBL-Kp. There was no clonal predominance. A distinct beta-lactamase profile was identified, which included a combination of TEM-1 (pI 5.4) and SHV-5 (pI 8.2) in 13/17 ESBL-Kp isolates. Cefotaxime resistance was transferred by conjugation in 14/17 isolates with a >120-kb plasmid encoding ESBL. CONCLUSIONS: The prevalence of ESBL-Kp was found to be lower than that previously reported in Latin America. ESBL-Kp bacteremia was not associated with a worse clinical outcome. We were able to identify a plasmid-mediated horizontal dissemination over the 10-year period.
Assuntos
Bacteriemia/epidemiologia , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae , Epidemiologia Molecular , beta-Lactamases/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Estudos de Casos e Controles , Feminino , Humanos , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Masculino , México/epidemiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem , Resistência beta-Lactâmica/genética , beta-Lactamases/genéticaRESUMO
BACKGROUND: Patients with inflammatory bowel disease have an increased risk of thrombosis. Hyperhomocysteinemia is one of the factors that have been related to thromboembolic complications. Patients with hyperhomocysteinemia and normal fasting homocysteine levels can be identified with an oral methionine load. We studied homocysteine levels in patients with IBD during fasting and after methionine load to determine the true prevalence of hyperhomocysteinemia and its relation with thrombotic events. METHODS: Prospective analysis of homocysteine levels in consecutive patients with IBD during fasting and 6-8 hours after an oral methionine load. Levels of folate and vitamin B12 were also determined. History of thrombotic events were recorded. RESULTS: Eighty-two patients with IBD, 56 with UC and 26 with CD were included. Eighteen patients (22%) had hyperhomocysteinemia during fasting. Mean levels of homocysteine after methionine load were 20.4 +/- 18.1 micromol/l (range, 1-79.7 micromol/l), and 43 patients (52%) had hyperhomocysteinemia (> or =20 micromol/l) after methionine load. Six patients (7.3%) had history of thrombosis. The homocysteine levels during fasting and after methionine load were significantly higher in patients with thrombotic events than in patients without thrombosis (15.5 +/- 3.7 micromol/l vs. 6.6 +/- 6.5 micromol/l; P = 0.002; 44.5 +/- 20.9 micromol/l vs. 18.4 +/- 16.5 micromol/l; P < 0.001, respectively). CONCLUSIONS: There is a higher prevalence of hyperhomocysteinemia in IBD patients than previously thought, this can be identified with an oral challenge of a methionine load. Hyperhomocysteinemia increases the risk of thromboembolic complications in patients with IBD.
Assuntos
Homocisteína/sangue , Hiper-Homocisteinemia/diagnóstico , Doenças Inflamatórias Intestinais/complicações , Metionina , Trombose/etiologia , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/epidemiologia , Incidência , Doenças Inflamatórias Intestinais/sangue , Masculino , Metionina/administração & dosagem , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Trombose/sangue , Trombose/epidemiologia , Vitamina B 12/sangueRESUMO
BACKGROUND/AIMS: Patients with primary Sjögren's syndrome may present liver involvement. Our goals were to establish the prevalence of abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome and correlate their presence with other clinical and laboratory features. METHODS: Ninety-five patients with diagnosis of primary Sjögren's syndrome were studied. Data on gender, age, clinical features, liver biochemistries, tests of inflammation and autoimmunity, and concomitant diseases were collected. RESULTS: Forty-two patients (44%) had abnormal hepatic biochemistries, and of these 19 patients (20%) had clinical liver disease. Patients with abnormal hepatic biochemistries had higher frequency of autoimmune hypotiroidism, arthritis, vasculitis, Raynaud's phenomenon, higher sedimentation rate,and higher frequency of antinuclear and antimitochondrial antibodies than patients with normal liver biochemistries (P < 0.05 for each). Patients with clinical liver disease had higher frequency of arthritis, vasculitis, and higher frequency of antimitochondrial antibodies than patients without clinical liver disease (P < 0.05 for each). Twenty-one patients had diagnosis of a specific liver disease, such as hepatitis C virus infection (n = 11), autoimmune hepatitis (n = 2), primary biliary cirrhosis (n =5),nonalcoholic fatty liver disease (n = 2), and hepatitis B virus infection (n = 1). In half of patients with liver involvement a definitive cause could not be identified. CONCLUSION: Liver involvement is frequently found in patients with primary Sjögren's syndrome, and its presence is associated with clinical features of systemic disease, and markers of autoimmunity and inflammation. There may be a subgroup of patients with liver involvement secondary to primary Sjögren's syndrome.
Assuntos
Hepatopatias/etiologia , Fígado/metabolismo , Síndrome de Sjogren/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Autoimunidade/fisiologia , Feminino , Humanos , Inflamação/fisiopatologia , Hepatopatias/metabolismo , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Síndrome de Sjogren/metabolismoRESUMO
Autoantibodies are a nonpathogenic manifestation of immune reactivity that may occur in acute and chronic liver diseases. Autoantibodies are the consequence rather than the cause of liver injury, and they can be used as diagnostic tools rather than etiologic markers. Conventional autoantibodies used in the categorization of liver disease are antinuclear antibodies, smooth muscle antibodies, antibodies to liver/kidney microsome type 1, antimitochondrial antibodies, and perinuclear antineutrophil cytoplasmic antibodies. However, the final diagnosis and the treatment strategies do not depend solely on the serological markers. Autoantibodies titles vary overtime and their behavior does not correlate with disease activity. Over-interpretation is the major pitfall in the clinical application of the serological results. Recognition and characterization of new autoantibodies is expected to improve the diagnostic precision, provide diagnostic parameters, and elucidate target autoantigens for the management of liver diseases.