Peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18 percent in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72 percent were genotype 1 and 34 percent were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78 percent EoT response and 51 percent SVR. Nonresponders showed 57 percent EoT response and 26 percent SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45 percent had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.

Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87 percent accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100 percent), but with reduction in diagnostic sensitivity (64 percent). When compared with the criteria of Ratziu et al. [Gastroenterology (2000) 118: 1117-1123] for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70 percent). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

Laminin concentration in ascites of patients with hepatic cirrhosis and peritoneal carcinomatosis

Laminin levels in ascitic fluid have been proposed as a marker for neoplastic ascites. We compared the concentration of laminin in serum and in ascitic fluid from patients with hepatic cirrhosis and peritoneal carcinomatosis and assessed the diagnostic value of serum laminin levels in differentiating neoplastic from benign ascites. Laminin concentrations were determined by ELISA with antibodies against laminin extracted from the human placenta, in patients with ascites due to peritoneal carcinomatosis (N = 20) and hepatic cirrhosis (N = 33). Patients with infected or hemorrhagic ascites were excluded. The receiver operating characteristic curve was used to determine the sensitivity and specificity of serum laminin for the diagnosis of neoplastic ascites. When compared to the group with cirrhosis, the carcinomatosis group presented significantly higher mean laminin levels in serum (3.3 ± 0.5 vs 2.1 ± 0.4 æg/ml, mean ± SD, P < 0.05) and ascites (2.8 ± 0.5 vs 1.6 ± 0.4 æg/ml, P < 0.05). Although laminin concentration was higher in serum than in ascites, the laminin serum/ascites ratio and serum-ascites gradient did not differ between the studied groups. A significant correlation (r = 0.93, P < 0.0001) was observed between the serum and ascites laminin values. Serum laminin levels >2.25 æg/ml showed 100 percent sensitivity and 73 percent specificity for the diagnosis of neoplastic ascites. Serum concentration seems to be the main determinant of laminin levels in ascitic fluid and its values can be used as a diagnostic parameter in the study of neoplastic ascites.

A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid

In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease, 30 patients with body mass indices higher than 25, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyltransferase (gamma-GT) at least more than 1.5 times the upper limit of normality, and hepatic steatosis demonstrated by ultrasonography were randomized into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1 ursodeoxycholic acid for three months. Abdominal computed tomography was performed to quantify hepatic fat content, which was significantly correlated with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass index remained stable for both groups throughout the study, but a significant reduction in mean (+ or - SEM) serum levels of ALT, AST and gamma-GT was observed only in the treated group (ALT = 81.2 + or - 9.7, 44.8 + or - 7,7, 48.1 + or - 7.7 and 52.2 + or - 6.3 IU/l at the beginning and after the first, second and third months, respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 + or - 9.8, 54.5 + or - 7, 60 + or - 7.6 and 43.7 + or - 5 IU/l, respectively. No alterations in hepatic lipid content were observed in these patients by computed tomography examination (50.2 + or - 4.2 Hounsfield units (HU) at the beginning versus 51.1 + or - 4.1 HU at the third month). These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content

Fibronectin in the ascitic fluid of cirrhotic patients: correlation with biochemical risk factors for the development of spontaneous bacterial peritonitis

Cirrhotic patients (23 with alcoholic cirrhosis, 5 with posthepatitic cirrhosis and 2 with cryptogenic cirrhosis) with ascites and portal hypertension were studied and divided into two groups corresponding to high or low risk to develop spontaneous bacterial peritonitis (SBP) related to the concentration of total protein in the ascite fluid (A-TP): group I (high risk): A-TP=1.5 g/dl and group II (low risk): A-TP>1.5 g/dl. Fibronectin (FN), C3 and C4 concentrations were measured by radial immunodiffusion while total protein was measured by the biuret method. The mean values (group I vs group II) of C3 (12.59+ 4.72 vs 24.53 + 15.58 mg/dl), C4 (4.26 + 3.87 vs 7.26 + 4.14 mg/dl) and FN (50.47 + 12.49 vs 75.89 + 24.70 mg/dl) in the ascitic fluid were significantly lower (P<0.05) in the group considered to be at high risk for SBP. No significant difference was observed in the plasma/ascites fibronectin ratio (3.91 + 1.21 vs 3.80 + 1.26) or gradient (131.46 + 64.01 vs 196.96 + 57.38) between groups. Fibronectin in ascites was significantly correlated to C3 (r = 0.76), C4 (r = 0.58), total protein (r = 0.73) and plasma FN (r = 0.58) (P<0.05). The data suggest that the FN concentration in ascites is related to the opsonic capacity of this fluid, and that its concentration in the ascitic fluid may be a biochemical risk factor indicator for the development of spontaneous bacterial peritonitis.

Colchicina na doença hepática crônica de etiologia alcoólica. Estudo duplo-cego, randomizado, de seus efeitos sobre os níveis séricos das proteínas plasmáticas e evoluçäo clínica dos pacientes / Colchicine in chronic liver disease of alcoholic etiology. Double-blind, randomized study of its effects on the serum levels of plasma proteins and clinical evolution of the patients

Pacientes portadores de hepatopatia crônica de etiologia alcoólica, quando tratados com colchicina durante período de 12 meses, apresentaram índices de recuperaçäo dos níveis plasmáticos de albumina e protrombina significantemente superiores aos de pacientes fazendo uso de placebo. Entretanto, nenhuma diferença estatística pôde ser observada entre os dois grupos quanto à taxa de mortalidade e de admissäo hospitalar dos pacientes, no período estudado. OBJETIVO. Analisar a evoluçäo clínica e os níveis plasmáticos de albumina, pré-albumina, transferrina e protrombina em portadores de hepatopatia crônica alcoólicaem uso de colchicina ou placebo, durante período de 12 meses. MÉTODOS. em um estudo duplo-cego, 41 pacientes portadores de hepatopatia crônica de etiologia alcoólica foram randomizados para receber placebo (20 pacientes) ou colchicina (21 pacientes), avaliando sua evoluçäo clínica e dos níveis das proteínas plasmáticasalbumina, pré-albumina e transferrina por imunodifusäo radial e do tempo e atividade de protrombina pelo método de Quick modificado. RESULTADOS. Apenas 7,3 por cento dos pacientes näo completaram os 12 meses de seguimento do estudo. Näo se observaram diferenças significantes entre os grupos, no que se refere à taxa de mortalidade ou ao número de internaçöes hospitalares. Quanto aos níveis séricos protéicos, observaram-se valores significantemente superiores no grupo da colchicina do que no grupo placebo, para as médias das variaçöes percentuais dos níveis de albumina (17,9 por cento colchicina x 3,6 por cento placebo, p<0,05) e da atividade de protrombina (19,2 por cento colchicina x 2,1 por cento placebo, p<0,05). As variaçöes dos valores da pré-albumina, apesar de apresentarem o mesmo comportamento observado para os níveis de albumina e protrombina, näo atingiram significância estatística. Já os níveis de transferrina sérica näo diferiram entreos dois grupos. CONCLUSÄO. Estes resultados sugerem que a administraçäo de colchicina tenha um efeito benéfico sobre os níveis de proteínas plasmáticas nos pacientes com hepatopatia crônica de etiologia alcoólica.

Alfafetoproteína nos tumores de fígado e hepatopatias benignas / Alphafetoprotein in hepatic tumours and benign liver diseases

A alfafetoproteína (AFP) é uma proteína oncofetal que se eleva nä só no carcinoma hepatocelualr, mas também em metástases hepáticas e hepatopatias benignas. Objetivo. O conhecimento das alteraçöes de AFP, nestas doenças, facilitará a interpretaçäo dos resultados frente à suspeita de carcinoma hepatocelular. Casuística e Métodos. Os autores estudaram AFP sérica por enzima imunoensaio (Abbott, normal até 15ng/mL) em 4 grupos: 1) hepatite aguda (HA), n=24;2) hepatopatia crônio (HC), viral ou alcoólica, n = 81; 3) metástase hepática (MH), n = 29: e 4) carcinoma hepatocelular (CHC), n = 15. Resultados Observaram os seguintes resultados em percentuais de AFP menor que 15ng/mL nos 4 grupos: 75 por cento HA; 86,4 por cento HC; 79,3 por cento MH; 6,6 por cento CHC. Entre 15 e 100: HA 25 por cento; HC 8,6; MH 20,6 por cento e CHC 20 por cento. Acima de 100ng/mL: 73,3 por cento CHC e 4,9 por cento HC. Discussäo. A medida que aumentaram o limite de corte, diminuiu a sensibilidade e aumentaram a especificidade diagnóstica para hepatocarcinoma. Os resultados mostraram que a AFP se eleva em hepatopatias benignas (HA e HC) e em MH, porém, níveis acima de 100ng/mL ocorrem com muito maior freqüência no CHC apresentaram AFP elevada, possivelmente porque a doença apresentava-se em estádios avançados

Hepatocarcinoma: análise de 14 casos / Hepatocarcinoma: analysis of 14 cases

No Brasil, o hepatocarcinoma näo é frequente. Constituem grupos de risco os portadores de vírus B da hepatite e cirróticos. Os autores descrevem 14 casos de hepatocarcinoma atendidos em 33 meses. OBJETIVO. Analisar as alteraçöes clínicas e laboratoriais dos doentes com hepatocarcinoma atendidos em 33 meses. CASUISTICA. Relatamos 14 casos de hepatocarcinoma atendidos de agosto de 1990 a maio de 1993, sendo dez do sexo masculino, com idade média de 53 anos. RESULTADOS. Os principais sintomas e sinais foram dor, emagrecimento e icterícia. Marcadores virais: 6 HBsAg, 1 HBeAg, 1 anti-HCV. A AFP elevou-se em 92 por cento. Oito tinham cirrose, 11 tumores multicêntricos. O tratamento cirúrgico foi realizado em três doentes, sendo em um ressecçäo parcial de tumor. Quimioterapia sistêmica foi feita em cinco doentes, sem resposta. CONCLUSAO. O carcinoma hepatocelular é uma doença infrequente em nosso meio. A maioria (80 por cento) apresentava doença avançada e 42 por cento dos pacientes foram HBsAg positivos

Parasite and egg burden, hepatic collagen and histologic pattern of liver granulomas in selection III high and low antibody responder mice infected with Schistosoma mansoni

Selection III mice have particular immunological characteristics: they are high (H III) or low (L III) antibody producer animals, yet both lines display similar T cell responses and macrophage activities. We submittedthese mice to infection with Schistosoma mansoni to assess in vivo parasite and egg burden, hepatic collagen and cellular composition of granulomas in both lines. Titration of anti-Schistosoma IgG by ELISA showed remarkably higher values inH III line, at both studied periods (8th and 12th weeks post-infection). Nevertheless, the number of adult worms recovered from the portal system was similar inboth lines, being not associated with anti-Schistosoma antibody levels. There isan increase in hepatic collagen from the 8th to the 12th weeks post-infection, which is paralleled by an increase in the number of eggs in the liver. This association apparently occurs at the same radio in H III and L III animals. The most important difference found between the two lines was the outstanding contrast interms of volume and eosinophil counts in the granulomas, with lesions from H IIImice clearly being larger and containing more of these cells than LIII lesions

Serum laminin in hepatosplenic human schistosomiasis

Serum laminin level was measured in chronic schistosomiasis. A significant increase in the mean serum laminin levels was observed in patients with hepatosplenic (HS) schistosomiasis (2,57 ñ 0,83U/ml), as compared to those in patients with the hepatointestinal (HI) form of the disease (1,38 ñ 0,45-U/ml) and in the control group (1,15 ñ 0,31 U/ml). In the HS patients there was a significant direct relatiom between serum laminin and percutaneous splenic pulp pressure (r = 0,68). These findigs are compatible with an increased production of lamin in hepatosplenic schistosomiasis with may be related to the observed enlarged liver and spleen basement membranes in such disease

Dosagem plasmatica dos acidos biliares conjungados na hepatopatia cronica esquistossomotica. / Plasma levels of conjugated bile acids in chronic schistosomal liver diseases

A concentracao de 2 acidos biliares conjugados, a colilglicina(CG) e a sulfolitocolilglicina(SLCG), foi determinada atraves de RIE no sangue periferico de pacientes portadores de hepatopatia cronica esquistossomotica e cirrose hepatica.Nos pacientes esquistossomoticos, forma hepatointestinal (HI) observou-se uma tendencia a reducao nos niveis plasmaticos da SLCG.A media de valores obtida para a dosagem da CG com o paciente em jejum apresentou especial utilidade na distincao entre as fases compensada e descompensada da esquistossomose hepatesplenica (HE) e da cirrose hepatica. Ja a dosagem pos-prandial da CG, alem de ter sido a determinacao bioquimica que demonstrou maior percentagem de valorea anormais, foi a unica a apresentar media de valores significativamente diferentes entre as formas HI e HE compensada e descompensada, embora falhasse em diferenciar as fases compensada e descompensada da cirrose hepatica. Se os resultados obtidos para CG pos-prandial na hepatopatia esquistossomotica estao relacionados diretamente a uma disfuncao hepatocelular ou a fatores extra-hepaticos, ainda resta a ser estabelecido