RESUMO
INTRODUCTION AND AIMS: International guidelines and routine clinical practice express concerns about antiviral treatment in intravenous drug users (IDUs). We analysed the effect of IDU and/or substitution therapy on chronic hepatitis C (CHC) treatment adherence and response. PATIENTS AND METHODS: Intravenous drug users with CHC were divided into three groups: (A) patients on a substitution programme; (B) active users; and (C) past IDUs. Patients were treated according to the standard of care and followed by a specialist team. RESULTS: A total of 175 patients (mean age 39.4±8.8) were included. One hundred and forty-four (65%) were adherent to therapy (completing treatment and 6 months of follow-up). Twenty-two patients (36%) discontinued because of side effects, 28 (46%) discontinued on their own and 11 (18%) completed treatment but did not present at follow-up. Of 142 patients with available treatment outcome, 99 (69.7%) achieved a sustained virological response (SVR), with no differences among the study groups. Patients with genotypes 2-3 and those who completed the treatment schedule had 2.78-fold (95% CI: 1.3-5.8) and 6.4-fold (95% CI: 2.6-15.6) higher probability of achieving SVR. CONCLUSION: Active use of illicit drugs and/or drug substitution do not affect the treatment outcome in patients with CHC as long as they are closely followed and remain adherent to the treatment.
Assuntos
Antivirais/uso terapêutico , Usuários de Drogas , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Ribavirina/uso terapêutico , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/reabilitação , Adolescente , Adulto , Distribuição de Qui-Quadrado , Contraindicações , Quimioterapia Combinada , Feminino , Genótipo , Grécia , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Humanos , Modelos Logísticos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Razão de Chances , RNA Viral/sangue , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Apoptotic caspases are substantially activated in liver and serum caspase activity has been suggested as a marker of early liver injury. AIM: To investigate whether serum levels of caspase-generated fragments of cytokeratin-18 are associated with the severity of histologic lesions in chronic hepatitis C virus (HCV) infection and nonalcoholic fatty liver disease (NAFLD). METHODS: We included 134 patients with chronic HCV infection and 58 patients with NAFLD, who consecutively underwent liver biopsy, and 40 healthy controls. Caspase-generated cytokeratin-18 fragment levels were blindly measured in stored serum samples. RESULTS: Median cytokeratin-18 fragment levels were lower in HCV-positive patients with minimal/mild than patients with moderate/severe histologic lesions (174 U/L vs. 223 U/L, P<0.001) offering moderate accuracy for differentiation between the 2 groups (c-statistic: 0.74). Cytokeratin-18 fragments levels were lower in healthy subjects (148 U/L) than patients with simple fatty liver (174 U/L, P=0.013) than patients with nonalcoholic steatohepatitis (355 U/L, P<0.001) offering excellent diagnostic accuracy for differentiation between the 2 latter groups (c-statistic: 0.87). CONCLUSIONS: Serum apoptotic caspase activity is associated with the severity of liver histologic lesions in both chronic HCV infection and NAFLD, but it has excellent diagnostic accuracy in NAFLD and moderate accuracy in chronic HCV patients.
Assuntos
Apoptose , Caspases/metabolismo , Fígado Gorduroso/sangue , Hepatite C Crônica/sangue , Queratina-18/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Diagnóstico Diferencial , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/fisiopatologia , Feminino , Hepacivirus , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/fisiopatologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Pylephlebitis is a condition with significant morbidity and mortality. We review herein 100 relevant case reports published since 1971. Eighty-one patients were reported with acute pylephlebitis, while the remaining patients had chronic pylephlebitis. The most common predisposing infections leading to pylephlebitis were diverticulitis and appendicitis. Cultures from blood or other tissues were positive in 77%. The infection was polymicrobial in half of the patients and the most common isolates were Bacteroides spp, Escherichia coli and Streptococcus spp. Thrombosis was extended to the superior mesenteric vein (SMV), splenic vein, and intrahepatic branches of the portal vein (PV) in 42%, 12%, and 39%, respectively. Antibiotics were administered in all and anticoagulation in 35 cases. Patients who received anticoagulation had a favourable outcome compared to those who received antibiotics alone (complete recanalization 25.7% vs 14.8% (p > 0.05), no recanalization 5.7% vs 22.2% (p < 0.05), and death 5.7% vs 22.2% (p < 0.01)). Cases with complete recanalization had prompt diagnosis and management and two-thirds were recently published. Nineteen patients died; the majority of these (73.7%) died over the period 1971-1990. In conclusion, pylephlebitis remains an entity with high morbidity and mortality, but modern imaging modalities have facilitated an earlier diagnosis and have improved the prognosis. Anticoagulation has a rather beneficial effect on patients with pylephlebitis.
Assuntos
Apendicite/complicações , Infecções Bacterianas/patologia , Diverticulite/complicações , Veia Porta/patologia , Trombose Venosa/patologia , Antibacterianos/uso terapêutico , Bactérias/classificação , Bactérias/isolamento & purificação , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Humanos , Veia Porta/microbiologia , Resultado do Tratamento , Trombose Venosa/tratamento farmacológico , Trombose Venosa/microbiologia , Trombose Venosa/mortalidadeRESUMO
The case of a 37-year-old man with chronic hepatitis C virus (HCV) infection is presented. The patient had received a 6-month course of antiviral therapy with peg interferon alpha-2a and ribavirin, with concomitant clearance of hepatitis C virus ribonucleic acid (HCV-RNA) from serum at the end of treatment. Three months after the treatment course he developed clinical and laboratory features of hypothyroidism along with high titers of thyroid peroxidase antibodies. Later on, while on treatment with levothyroxine, he developed all the clinical features of Graves disease along with increased levels of thyroid stimulating hormone (TSH)-receptor antibodies.This patient exhibited a rare sequence of immune-mediated thyroid disorders as a result of interferon alpha treatment. At the end of treatment, the patient developed Hashimoto thyroiditis, a typically Th1-response-mediated disease, followed sequentially after 6 months by Graves disease, a typically Th2-response-mediated disorder. Although both clinical entities have been described in patients receiving interferon-based regimens, to our knowledge, the changing pattern of immune-mediated thyroid disease in the same individual has not been reported in the literature.
Assuntos
Antivirais/efeitos adversos , Doença de Graves/induzido quimicamente , Doença de Hashimoto/induzido quimicamente , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Adulto , Antivirais/uso terapêutico , Autoanticorpos/sangue , Autoantígenos/imunologia , Progressão da Doença , Quimioterapia Combinada , Seguimentos , Doença de Graves/diagnóstico , Doença de Hashimoto/diagnóstico , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/diagnóstico , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Masculino , Polietilenoglicóis/uso terapêutico , Receptores da Tireotropina/imunologia , Proteínas Recombinantes , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologiaRESUMO
BACKGROUND/AIMS: The pathogenetic mechanisms of development of non-alcoholic steatohepatitis (NASH) and fibrosis are not clear, although thrombosis of small intrahepatic veins has been suggested to trigger liver tissue remodelling and thrombotic risk factors have been associated with more advanced fibrosis in chronic viral hepatitis (CVH). We evaluated the prevalence of thrombotic risk factors (RFs) in non-alcoholic fatty liver disease (NAFLD) and their possible association with fatty liver or NASH. METHODS: We included 60 patients with histologically documented NAFLD and a historical cohort of 90 patients with chronic hepatitis B (n=39) or C (n=51). Thrombophilic factors were evaluated on the day of the liver biopsy. RESULTS: One or more thrombotic RFs were detected in 37% of NAFLD patients, and >or= 2 RFs were detected in 12% of NAFLD patients, being less frequently present than in CVH patients (37% and 68%, respectively; P Assuntos
Fígado Gorduroso/complicações
, Fígado Gorduroso/patologia
, Trombose/complicações
, Adulto
, Anticorpos Anticardiolipina/sangue
, Estudos de Coortes
, Fator V/genética
, Fígado Gorduroso/sangue
, Fígado Gorduroso/etiologia
, Feminino
, Hepatite B Crônica/sangue
, Hepatite B Crônica/complicações
, Hepatite B Crônica/patologia
, Hepatite C Crônica/sangue
, Hepatite C Crônica/complicações
, Hepatite C Crônica/patologia
, Humanos
, Fígado/patologia
, Cirrose Hepática/complicações
, Cirrose Hepática/patologia
, Masculino
, Pessoa de Meia-Idade
, Protrombina/genética
, Fatores de Risco
, Trombose/sangue
, Trombose/genética
RESUMO
Acute exacerbations in HBeAg negative patients with chronic hepatitis B virus (HBV) infection are invariably associated with concurrent increases in the index of IgM class antibodies against the core protein (anti-HBc) of the virus. This study aimed to investigate whether this was related to the clearance of variants from the quasispecies pool and the appearance of new ones, with aminoacid substitutions in well recognized B-cell epitopes. In this study, 5 HBeAg negative patients (A to E) with 13 sequential serum samples (A1-A2, B1-B2-B3, C1-C2, D1-D2-D3, E1-E2-E3) were investigated after amplification of the entire core encoding region followed by cloning/sequencing studies. The sequences at different time points were compared with those from a single HBeAg positive patient with no apparent acute exacerbations. The results from sequence comparison showed that virus variants emerged in all (A2, B3, C2, D3, E2, and E3) but two (B2 and D2) subsequent sera with amino-acid substitutions affecting B-cell epitopes. It is concluded that the rise in the values of IgM anti-HBc may be attributed to the alteration of the antigenic epitopes leading to new antibody production in the majority of the cases. However, it appears that increases in IgM anti-HBc indexes in a few cases may relate to other possible mechanisms which are discussed.
Assuntos
Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Imunoglobulina M/sangue , Mutação de Sentido Incorreto/imunologia , Adulto , DNA Viral/química , DNA Viral/genética , Epitopos/genética , Epitopos/imunologia , Feminino , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNARESUMO
UNLABELLED: The diagnosis of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNA >or=2,000 IU/mL. We evaluated the severity of liver histology and the presence of histological indication for treatment in patients with HBeAg-negative chronic HBV infection focusing on those with low viremia and/or normal alanine aminotransferase (ALT). In total, 399 patients with increased ALT and detectable serum HBV DNA (chronic hepatitis B patients) and 35 cases with persistently normal ALT and HBV DNA >2,000 IU/mL (inactive carriers) were included. Histological indication for treatment (grading score >or=7 and/or stage >or=2 in Ishak's classification) was found in 91% (185/203), 82% (75/91), 75% (47/63), and 62% (26/42) of chronic hepatitis B patients with HBV DNA >or=200,000, 20,000-199,999, 2,000-19,999, and <2,000 IU/mL, respectively (P < 0.001). Histological indication for treatment was more frequent in chronic hepatitis B patients with persistently elevated ALT (86% or 275/321), but it was also found in 74% (58/78) of those with transiently normal ALT (P = 0.025). All inactive carriers had HBV DNA <20,000 IU/mL. Histological indication for treatment was present in 17% (6/35) of inactive carriers always due to moderate (stage 2) fibrosis without active necroinflammation. CONCLUSION: HBeAg-negative chronic HBV patients with persistently or transiently increased ALT and HBV DNA >or=20,000 IU/mL almost always require therapeutic intervention, but histological indications for treatment are also present in the majority of such cases with HBV DNA <20,000 and even <2,000 IU/mL. In contrast, minimal histological lesions are observed in the majority of HBeAg-negative patients with persistently normal ALT and HBV DNA >2,000 IU/mL, who may not require immediate liver biopsy and treatment but only close follow-up.
Assuntos
Antivirais/uso terapêutico , DNA Viral/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Adulto , Idoso , Aspartato Aminotransferases/sangue , Biópsia , DNA Viral/genética , Técnicas de Apoio para a Decisão , Feminino , Hepatite B Crônica/patologia , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Análise de Regressão , Viremia/sangue , Viremia/fisiopatologiaRESUMO
The progress in treatment against hepatitis B virus (HBV) has substantially improved the outcome of all HBV-infected patients. We systematically reviewed the existing data in the management of HBV transplant patients in order to assess the optimal regimen in the pretransplant setting, for post-transplant prophylaxis and for therapy of HBV recurrent infection. All data suggest that an effective pretransplant anti-HBV therapy prevents post-transplant HBV recurrence. Pretransplant therapy has been based on lamivudine with addition of adefovir upon lamivudine resistance, but the use of newer, potent high-genetic barrier agents is expected to improve long-term efficacy. Moreover, it may lead to improvement of liver function, which sometimes removes the need for transplantation, although more objective criteria for removal from waiting lists are required. After liver transplantation, the combination of HBV immunoglobulin and one nucleos(t)ide analogue, mostly lamivudine, is currently the best approach, almost eliminating the probability of HBV recurrence. Treatment of post-transplant HBV recurrence has been mainly studied with lamivudine, but it will be most effective with entecavir and tenofovir, which have a low risk of resistance. In conclusion, the newer anti-HBV agents improve the treatment of HBV both pretransplant and post-transplant. HBV immunoglobulin is still used in combination with an anti-HBV agent for post-transplant prophylaxis. Monoprophylaxis with one of the new anti-HBV agents might be possible, particularly in patients preselected as having a low risk of HBV recurrence, but further data are needed and strategies to ensure compliance must be used.
Assuntos
Hepatite B/tratamento farmacológico , Transplante de Fígado , Antivirais/uso terapêutico , DNA Viral/análise , Hepatite B/prevenção & controle , Humanos , Imunoglobulinas/uso terapêutico , Cirrose Hepática/cirurgia , Complicações Pós-Operatórias/prevenção & controle , RecidivaRESUMO
Insulin resistance (IR) and metabolic syndrome have recently been implicated in the pathogenesis and progression of chronic liver diseases, especially chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). In this review, we provide current information on their deleterious effect on the liver, with particular interest in those two entities. In NAFLD, IR causes both the accumulation of fat in hepatocytes and the progression to non-alcoholic steatohepatitis (NASH). Moreover, the presence of metabolic syndrome seems to be associated with severe fibrosis in NASH patients. In CHC, IR develops early in the course of the disease and precedes steatosis. It is also independently associated with histological severity and negatively affects treatment response, irrespective of genotype. Consequently, therapies targeting IR and metabolic syndrome could indirectly ameliorate the prognosis of both NAFLD and CHC. As specific therapies do not exist, patients with metabolic syndrome and CHC and NAFLD should be counseled to lose weight and ameliorate their glycemic control and lipid profile.
Assuntos
Resistência à Insulina , Hepatopatias/complicações , Hepatopatias/metabolismo , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Glicemia/metabolismo , Doença Crônica , Fígado Gorduroso/complicações , Fígado Gorduroso/metabolismo , Hepatite C Crônica/complicações , Hepatite C Crônica/metabolismo , Humanos , Estilo de Vida , Cirrose Hepática/complicações , Cirrose Hepática/metabolismo , Prognóstico , Fatores de Risco , Comportamento de Redução do RiscoRESUMO
OBJECTIVE: The results of retrospective studies suggest an association between smoking, insulin resistance, steatosis and fibrosis in patients with chronic hepatitis C (CHC); no data are available for chronic hepatitis B (CHB). The purpose of this study was to evaluate the relationship, if any, of such factors on liver fibrosis in a cohort of patients with CHB and CHC. MATERIAL AND METHODS: The study prospectively included 271 consecutive patients with CHB (n=95) or CHC (n=176) who had undergone liver biopsies. Each patient completed a questionnaire on smoking habits; anthropometric measurements and laboratory examinations were carried out and histological lesions were recorded. RESULTS: In CHC patients, severe fibrosis was independently associated with a higher body mass index (BMI) (OR: 1.180, 95% CI: 1.028-1.354; p=0.019), heavy smoking (OR: 3.923, 95% CI: 1.356-11.348; p=0.012), higher alanine aminotransferase (ALAT) levels (OR: 1.010, 95% CI: 1.003-1.017; p=0.005) and alkaline phosphatase (ALP) levels (OR: 1.016, 95% CI: 1.001-1.030; p=0.03) and presence of necroinflammation (OR: 11.165, 95% CI: 1.286-96.970; p=0.029). Moreover, steatosis was independently associated with high gamma-glutamyl transpeptidase (GGT) values, heavy smoking and presence of necroinflammation. In CHB patients, no association between smoking habits and fibrosis or steatosis was noted. CONCLUSIONS: Heavy smoking is associated with severe fibrosis in CHC but not CHB. Heavy smoking is also significantly associated with steatosis in CHC and this could be the link between smoking and fibrosis progression.
Assuntos
Fígado Gorduroso/etiologia , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/etiologia , Fumar/efeitos adversos , Adulto , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and can vary from benign steatosis to end-stage liver disease. The pathogenesis of non-alcoholic steatohepatitis (NASH) is currently thought to involve a multiple-hit process with the first hit being the accumulation of liver fat which is followed by the development of necroinflammation and fibrosis. There is mounting evidence that cytokines secreted from adipose tissue, namely, adipokines, are implicated in the pathogenesis and progression of NAFLD. In the current review, we explore the role of these adipokines, particularly leptin, adiponectin, resistin, tumor necrosis factor-a, and interleukin-6 in NASH, as elucidated in experimental models and clinical practice. We also comment on their potential use as noninvasive markers for differentiating simple fatty liver from NASH as well as on their potential future therapeutic role in patients with NASH.
Assuntos
Adipocinas/fisiologia , Fígado Gorduroso/etiologia , Adiponectina/fisiologia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/tratamento farmacológico , Humanos , Interleucina-6/fisiologia , Leptina/fisiologia , Resistina/fisiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
Currently available options for the treatment of chronic hepatitis B virus (HBV) infection include standard and pegylated interferon alfa and four oral antiviral agents (lamivudine, adefovir, entecavir, and telbivudine). These treatment strategies are either therapies of finite duration that aim to achieve sustained off-therapy responses, or long-term treatments that aim to maintain on-therapy remission. Pegylated interferon alfa may offer higher sustained off-therapy responses after 1 year, but most patients do not respond. Oral antivirals are the only candidates for long-term treatment of patients with chronic HBV infection. Viral suppression has favourable effects on patients' outcome and modifies the natural history of the disease. Viral resistance is the main drawback of long-term antiviral therapy. Lamivudine monotherapy is associated with higher resistance (year 1, 10-27%; year 2, 37-48%; year 4, 60-65%) than adefovir (year 1, 0%; year 2, 3%; year 5, 29%) or telbivudine (year 1, 3-4%; year 2, 9-22%). Entecavir resistance is rare in naive individuals (year 4, <1%), but increases over time in lamivudine-resistant patients (year 4, 43%). The best strategy for long-term therapy in chronic HBV infection has yet to be established.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Administração Oral , Algoritmos , Antivirais/administração & dosagem , Esquema de Medicação , Humanos , Interferon-alfa/administração & dosagem , Resultado do TratamentoRESUMO
Extranodal NK/T cell lymphoma, 'nasal type,' is a rare clinicopathological entity in Europe. The main clinical features are nasal congestion, sore throat, dysphagia and epistaxis, due to a destructive mass involving the midline facial tissues. Pathologically, lymphoma cells exhibit angioinvasion, angiodestruction and coagulative necrosis. We report the case of a patient who presented with fever, dyspnea, nasal congestion, headache, distention of right nasal turbinates and exophytic lower leg ulcerating lesions. A CT scan of visceral scull demonstrated a filling mass of right frontal, ethmoidal and maxillary sinuses with erosion of the wall of right maxillary sinus and ventral portion of the diaphragm. A biopsy was performed in the skin lesion and showed an angioinvasive NK/T cell lymphoma CD56 negative with clonal rearrangement of the T-cell-receptor gamma gene. Up to our knowledge, this is a rare immunophenotype for NK/T-cell, 'nasal type,' lymphomas. However, the lymphoma may be classified as extranodal NK/T cell lymphoma, 'nasal type,' due to typical clinical presentation, radiologic findings and pathological characteristics of polymorphism, angioinvasion, angiodestruction and coagulative necrosis.
Assuntos
Células Matadoras Naturais/patologia , Linfoma de Células T/genética , Linfoma de Células T/patologia , Neoplasias Nasais/genética , Neoplasias Nasais/patologia , Idoso de 80 Anos ou mais , Biópsia , Antígeno CD56/metabolismo , Evolução Fatal , Feminino , Rearranjo Gênico do Linfócito T , Humanos , Imunofenotipagem , Linfoma de Células T/diagnóstico por imagem , Neoplasias Nasais/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Leptin and adiponectin have been implicated in the pathogenesis and progression of non-alcoholic steatohepatitis (NASH) and chronic hepatitis C (CHC), but little is known about the role of resistin in chronic liver diseases. The objective of this study was to investigate serum levels of the above three adipokines in relation to the etiology of liver disease and to determine their associations with histological severity. MATERIAL AND METHODS: We prospectively evaluated 146 patients (HBeAg-negative chronic hepatitis B (CHB): 52, CHC: 70, NASH: 24) who consecutively underwent liver biopsy. Detailed epidemiological, anthropometric and laboratory data were recorded. Histological lesions were evaluated blindly according to the Ishak and the Brunt classifications for CHB/CHC and NASH, respectively. RESULTS: Serum adipokine levels were similar between CHB and CHC patients, while CHB/CHC patients had significantly lower leptin levels compared with NASH patients (8.3+/-7.3 versus 17.6+/-16.6 ng/ml, p=0.012) and higher adiponectin (10.2+/-5.1 versus 7.5+/-4 microg/ml, p=0.018) and resistin levels (7.1+/-2.5 versus 5.7+/-2.8 ng/ml, p=0.016). In CHB/CHC, there was no significant association between steatosis or necroinflammation and levels of adipokines, while the presence of moderate/severe fibrosis (stages 4-6) was associated with higher leptin and adiponectin levels in male but not in female patients and with lower resistin levels irrespective of gender or other factors (adjusted odds ratio=0.788, p=0.035). CONCLUSIONS: Serum adipokine levels depend on the etiology of liver disease differing between chronic viral hepatitis and NASH, but not between CHB and CHC. In CHB/CHC, resistin levels are independently associated with fibrosis severity, whereas in the association of leptin and adiponectin levels with fibrosis, it seems to be a gender effect.
Assuntos
Adipocinas/sangue , Hepatite B Crônica/sangue , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Resistina/sangue , Adulto , Análise de Variância , Biomarcadores/sangue , Biópsia por Agulha , Doença Crônica , Fígado Gorduroso/sangue , Fígado Gorduroso/patologia , Fígado Gorduroso/fisiopatologia , Feminino , Hepatite B Crônica/patologia , Hepatite B Crônica/fisiopatologia , Hepatite C Crônica/sangue , Hepatite C Crônica/patologia , Hepatite C Crônica/fisiopatologia , Humanos , Imuno-Histoquímica , Cirrose Hepática/fisiopatologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Probabilidade , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
The optimal approach to the management of several marginal cases with chronic hepatitis B virus (HBV) infection is controversial. Serum HBV DNA and aminotransferase levels, and the degree of necroinflammation and fibrosis determine the therapeutic decisions. All patients with elevated aminotransferase (>twice the upper limit of normal) and serum HBV DNA above 20000 IU/mL should be treated. Liver biopsy is important for therapeutic decisions in cases with mild aminotransferase elevations and serum HBV DNA below 20000 IU/mL. Chronic HBV patients who do not receive treatment should be followed for life. There are seven agents licensed for chronic hepatitis B: standard and pegylated interferon-alpha, lamivudine, adefovir, entecavir, telbivudine and tenofovir. One-year courses with pegylated interferon-alpha induce sustained off-therapy remission in 30%-32% of patients with HBeAg-positive chronic hepatitis B and in a smaller proportion of patients with HBeAg-negative chronic hepatitis B. Oral antivirals achieve initial on-therapy responses in the majority of patients, but are intended as long-term therapies. Viral suppression has favourable effects on patients' outcome and modifies the natural course of the disease. Viral resistance, however, is the major drawback of long-term oral antiviral therapy. Lamivudine monotherapy is associated with the highest and entecavir monotherapy with the lowest resistance rate so far. There has been no resistance to tenofovir, but after only 18 mo of treatment to date. The optimal first-line anti-HBV therapy with the best long-term cost/benefit ratio remains unclear. If oral antiviral agents are used, compliance should always be ascertained and HBV DNA levels should be regularly tested.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Antivirais/economia , Análise Custo-Benefício , DNA Viral/sangue , Farmacorresistência Viral/genética , Vírus da Hepatite B/genética , Humanos , Transaminases/sangue , Resultado do TratamentoRESUMO
AIM: To evaluate survival rate and clinical outcome of cholangiocarcinoma. METHODS: The medical records of 34 patients with cholangiocarcinoma, seen at a single hospital between the years 1999-2006, were retrospectively reviewed. RESULTS: Thirty-four patients with a median age of 75 years were included. Seventeen (50%) had painless jaundice at presentation. Sixteen (47.1%) were perihilar, 15 (44.1%) extrahepatic and three (8.8%) intrahepatic. Endoscopic retrograde cholangiography (ERCP) and/or magnetic resonance cholangiography (MRCP) were used for the diagnosis. Pathologic confirmation was obtained in seven and positive cytological examination in three. Thirteen patients had co-morbidities (38.2%). Four cases were managed with complete surgical resection. All the rest of the cases (30) were characterized as non-resectable due to advanced stage of the disease. Palliative biliary drainage was performed in 26/30 (86.6%). The mean follow-up was 32 mo (95% CI, 20-43 mo). Overall median survival was 8.7 mo (95% CI, 2-16 mo). The probability of 1-year, 2-year and 3-year survival was 46%, 20% and 7%, respectively. The survival was slightly longer in patients who underwent resection compared to those who did not, but this difference failed to reach statistical significance. Patients who underwent biliary drainage had an advantage in survival compared to those who did not (probability of survival 53% vs 0% at 1 year, respectively, P = 0.038). CONCLUSION: Patients with cholangiocarcinoma were usually elderly with co-morbidities and/or advanced disease at presentation. Even though a slight amelioration in survival with palliative biliary drainage was observed, patients had dismal outcome without resection of the tumor.
Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar , Colangiocarcinoma/mortalidade , Colangiocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Procedimentos Cirúrgicos do Sistema Biliar/instrumentação , Colangiocarcinoma/patologia , Colangiopancreatografia Retrógrada Endoscópica , Colangiopancreatografia por Ressonância Magnética , Feminino , Grécia/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Stents , Fatores de Tempo , Resultado do TratamentoRESUMO
Pseudohyperkalemia, a rise in serum potassium concentration with concurrently normal plasma potassium concentration, is an in vitro phenomenon that was first described 50 years ago. It was originally attributed to the release of potassium from platelets during platelet aggregation and degranulation, and a significant correlation between pseudohyperkalemia and platelet count was established. During the last decade, new data were added to this phenomenon. In particular, pseudohyperkalemia was defined when serum potassium concentration exceeded that of plasma by more than 0.4 mmol/L provided that samples are collected under strict techniques, remain at room temperature and are tested within 1 hour from blood specimen collection. Moreover, it is positively correlated to (1) thrombocytosis due to the release of potassium from platelet granules during coagulation, (2) erythrocytosis due to the dilution of the released potassium in smaller volumes of serum, and (3) the presence of activated platelets, which have the capability of aggregation at a higher speed and release more potassium during degranulation. However, pseudohyperkalemia may be "masked" when in a state of hypokalemia because potassium moves back into the intracellular space in vitro, and the phenomenon is ameliorated or even not detected.
Assuntos
Plaquetas/metabolismo , Degranulação Celular , Hiperpotassemia/sangue , Agregação Plaquetária , Potássio/sangue , Vesículas Secretórias/metabolismo , Coagulação Sanguínea , Humanos , Hipopotassemia/sangue , Policitemia/sangue , Fatores de TempoRESUMO
BACKGROUND/AIMS: Treatment of chronic delta hepatitis is long and difficult and better monitoring is needed. METHODS: In this study, hepatitis delta virus (HDV) RNA, hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA were retrospectively quantified in 53 patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis delta. Twenty-one had received 28 courses of 3-5 MU interferon-alpha2b (IFN-alpha2b) thrice weekly for a median of 12.6 months (interquartile range [IQR]: 7.3-31.6), five had received eight courses of 100 mg lamivudine (LAM) daily for 23.6 months (IQR: 8.4-61.5) and 27 were untreated. The controls were 54 untreated, randomly selected, HBeAg-negative chronic hepatitis B patients without delta infection. Quantification of serum HDV RNA, HBsAg and HBV DNA were performed at baseline, during and at the end of treatment and end of follow up. RESULTS: Untreated patients had significantly higher median HBsAg levels than controls (5,872 vs 3,501 IU/ml; P = 0.046), but lower median HBV DNA levels (2.933 vs 6.459 log10 copies/ml; P < 0.001). Median baseline HDV RNA (6.374 log10 copies/ml) was similar in IFN-alpha2b-treated, LAM-treated and untreated patients. At the end of treatment, IFN-alpha2b significantly suppressed in paired measurements HDV RNA (P = 0.012) and HBsAg (P = 0.043), but LAM was inefficient. In IFN-alpha2b-treated patients, HDV RNA became undetectable in five patients within a median of 30 months (IQR: 8-90), followed by a slower decrease in HBsAg. CONCLUSIONS: In untreated chronic delta hepatitis, suppressed HBV replication is associated with significantly increased HBsAg serum levels. IFN-alpha2b significantly suppresses both HDV RNA and HBsAg, but LAM has no effect. Long-term IFN-alpha2b treatment (IQR: 1.5-5.0 years) appears necessary for undetectable serum HDV RNA and further treatment is required for HBsAg loss. Monitoring of HDV RNA and HBsAg serum levels in patients with chronic delta hepatitis provides insight during treatment.
Assuntos
Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Hepatite D Crônica/tratamento farmacológico , Vírus Delta da Hepatite/genética , Interferon-alfa/uso terapêutico , RNA Viral/sangue , Adolescente , Adulto , DNA Viral/sangue , Feminino , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite D Crônica/sangue , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Interferon alfa-2 , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
A 47-year-old woman presented with severe hemolytic uremic syndrome (HUS) followed by heart failure. An echocardiogram showed an ejection fraction of 20%, and a cardiac catheterization followed by a myocardial histologic evaluation demonstrated dilated cardiomyopathy. Plasma exchange and hemodialysis were performed regularly. The later outcomes of renal function and cardiomyopathy were favorable. A review of the literature confirmed the rare and severe nature of cardiac lesions occurring in the course of HUS. This case indicates the importance of cardiac monitoring in HUS and the need for prolonged support.
Assuntos
Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/patologia , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Hepatic granulomas have been reported in 2-15% of unselected liver biopsies, with a wide clinical profile responsible for their presence. To date, no series concerning the prevalence and the etiology of granulomas from Greece has been reported. OBJECTIVES: To evaluate the prevalence and the etiology of hepatic granulomas and to investigate whether there has been an alteration in distribution of diagnoses in our series compared with those published so far in the literature. STUDY: The results of liver biopsy specimens performed in a Department of Medicine, between 1999 and 2004, were retrospectively reviewed and the cases revealing hepatic granulomas had their medical notes and the liver biopsies recorded. RESULTS: Over the study period, 1768 liver biopsies were performed. Hepatic granulomas were identified in 66 (3.7%). Of those, 51 were female with a mean age of 57 years (range 34-74 years) and 15 were male with a mean age of 42 years (range 18-78 years). Autoimmune liver diseases including primary biliary cirrhosis, overlap syndrome and autoimmune hepatitis accounted for the majority of cases (68%), followed by sarcoidosis (7.5%), chronic hepatitis B virus and hepatitis C virus infection (7.5%), idiopathic (6%), drugs (3%) and other miscellaneous causes (7.5%). CONCLUSIONS: Our series showed that autoimmune liver diseases, mainly primary biliary cirrhosis was the most common cause of granuloma formation, a finding rather similar to that stated in the studies from Western countries. A rather small number of idiopathic cases were recorded. Chronic viral hepatitis and sarcoidosis rates were equal, a finding possibly reflecting a fairly high proportion of viral hepatitis in our sample.