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.

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

In vitro-induced antibody production in chronic hepatitis C virus infection

The objectives of the present study were to assess the in vitro-induced anti-hepatitis C virus (HCV) antibody production (IVIAP) in relation to the clinical, biochemical, virologic and histologic variables of patients with HCV infection. The study included 57 patients (60 percent males) with HCV infection (anti-HCV and HCV-RNA positive). Alanine aminotransferase (ALT) was elevated in 89 percent of the patients. Mean viral load was 542,241 copies/ml and histology of the liver showed chronic hepatitis in 27/52 (52 percent) and cirrhosis in 11/52 (21 percent) patients. IVIAP levels were determined by immunoenzymatic assay at median absorbance of 0.781 at 450 nm. IVIAP was negative in 14 percent of the patients. When groups with IVIAP levels above and below the median were compared, high IVIAP levels were associated with the male sex, elevated ALT levels and more advanced disease stage. After logistic regression analysis, advanced histologic damage to the liver remained as the only independent variable associated with elevated IVIAP levels. Using a receiver operator characteristic curve, the best cut-off level for IVIAP was established (= 1.540), with 71 percent sensitivity and 94 percent specificity for the detection of more advanced disease stages (grades 3 and 4). These findings are consistent with the participation of immunological mechanisms in the genesis of the hepatic lesions induced by HCV and indicate that the IVIAP test may be useful as a noninvasive marker of liver damage either alone or in combination with other markers

Evaluation of an enzyme immunoassay for hepatitis C virus antibody detection using a recombinant protein derived from the core region of hepatitis C virus genome

This study was undertaken to evaluate an enzyme immunoassay (EIA) for hepatitis C virus antibody detection (anti-HCV), using just one antigen. Anti-HCV EIA was designed to detect anti-HCV IgG using on the solid-phase a recombinant C22 antigen localized at the N-terminal end of the core region of HCV genome, produced by BioMérieux. The serum samples diluted in phosphate buffer saline were added to wells coated with the C22, and incubated. After washings, the wells were loaded with conjugated anti-IgG, and read in a microtiter plate reader (492 nm). Serum samples of 145 patients were divided in two groups: a control group of 39 patients with non-C hepatitis (10 acute hepatitis A, 10 acute hepatitis B, 9 chronic hepatitis B, and 10 autoimmune hepatitis) and a study group consisting of 106 patients with chronic HCV hepatitis. In the study group all patients had anti-HCV detected by a commercially available EIA (Abbott(r)), specific for HCV structural and nonstructural polypeptides, alanine aminotransferase elevation or positive serum HCV-RNA detected by nested-PCR. They also had a liver biopsy compatible with chronic hepatitis. The test was positive in 101 of the 106 (95 percent) sera from patients in the study group and negative in 38 of the 39 (97 percent) sera from those in the control group, showing an accuracy of 96 percent. According to these results, our EIA could be used to detect anti-HCV in the serum of patients infected with hepatitis C virus.

Hipoinsulinemia em alcoolistas com hepatopatia mínima / Hypoinsulinemia in alcoholics with minimal liver disease

OBJETIVO: Em alcoolistas portadores de lesões hepáticas mínimas avaliar os níveis de glicose e insulina séricas após estímulo com glicose intravenosa. MÉTODOS: Em oito etilistas, portadores de alterações hepáticas mínimas, caracteriza por biópsia hepática, e em 26 controles sadios não-alcoólicos, foram estudados os níveis glicêmicos e insulinêmicos (RIE) nos tempos 1, 3, 5, e 10 minutos após estímulo com glicose intravenosa (0.5g/Kg de peso). RESULTADOS: As médias da insulina sérica dos tempos 1, 3 minutos e resposta integrada total (RIT-10min) após estímulo foram menores no grupo alcoolista em relação ao controle (p < 0,05) apesar de curvas glicêmicas normais. CONCLUSÃO: Etilistas crônicos com lesões hepáticas mínimas, à semelhança do observado anteriormente em etilistas assintomáticos, apresentam níveis diminuídos de insulina sérica, mas com curvas glicêmicas normais, após estímulo com glicose intravenosa, indicando hipofunção de células beta do pâncreas.

Significance of the presence of antibodies against hepatitis C virus in asymptomatic blood donors

In order to determine the significance of anti-hepatitis C virus (anti-HCV) antibodies in blood donors, 46 consecutive asymptomatic individuals were recruited at the blood bank of Hospital Sao Paulo, Sao Paulo, Brazil. They were submitted to an interview to collect epidemiological data and to clinical examination and blood samples were obtained for biochemical, serological and virological analysis. All patients were followed for a minimum period of six months and those with abnormal mean alanine aminotransferase (ALT) levels were submited to a liver biopsy after giving informed consent. Hepatitis C virus RNA (HCVRNA) was detected by the polymerase chain reaction (PCR) in 22/46 (47.8 per cent) patients and this finding was associated with parenteral risk factors (P = 0.03) and ethanol abuse (P - 0.03). HCVRNA positivity was also associated with abnormal levels of ALT (P<0.001) and gamma-glutamyl transpeptidase (gamma-GT) (P=0.01). Abnormal ALT levels were a good marker of viremia, with 86.4 per cent sensitivity and 79.2 per cent specificity. Twenty-three patients with elevated mean ALT levels were submitted to a liver biopsy and histopathological changes were observed in 17 of them (73.9 per cent). HCVRNA positivity was associated with severe forms of hepatic disease (chronic hepatitis and cirrhosis). These results indicate the need for a judicious evaluation of all anti-HCV-positive blood donors, including clinical examination, biochemical tests and liver histology when ALT is persistently elevated.

Depuraçäo hepática da calicreína plasmática na cirrose experimental / Plasma kallikrein clearance by the liver in experimental cirrhosis

OBJETIVO. Estudar a depuraçao de glicoproteína, e calicreína plasmática, pelo fígado de ratos com cirrose descompensada. MATERIAL E MÉTODO. Produçao de cirrose pela administraçao de tetracloreto de carbono, 520 mg/kg de peso corporal, uma vez por semana, intragastricamente, durante 16 a 19 semanas. Após o período de tratamento cada fígado foi isolado, exsanguinado e perfundido a 37 graus Celsius com calicreína plasmática de rato (CPR) 10nM. A velocidade de depuraçao da CPR na cirrose foi comparada com a de grupos-controle. RESULTADOS. 58 por cento dos animais morreram durante o tratamento. Os sobreviventes desenvolveram prostraçao, ascite, icterícia e sangramentos; ao final do período de tratamento as aminotransferases séricas eram normais e a albumina sérica diminuída. A histologia hepática (hematoxilina-eosina e coloraçao para reticulina) mostrou cirrose no grupo tratado. A velocidade de depuraçao hepática da CPR no grupo cirrótico (5,4 + 0,9pmol/g fígado/10 min) foi significativamente menor (p < 0,05) do que no grupo controle (13,5 + 2,7pmol/g fígado/10min). CONCLUSAO. O desenvolvimento de cirrose descompensada acompanha-se de diminuiçao da capacidade hepática de depurar glicoproteína, que é internalizada por endocitose mediada por receptor.

Papiloma de células escamosas do esôfago: apresentaçäo de 3 casos; aspectos diagnósticos / Esophageal squamous cell papilloma: report of 3 cases; diagnostic aspects

Pacientes com papiloma escamoso de esôfago podem apresentar disfagia, porém há casos cujo diagnóstico é decorrente de mero achado de exame. OBJETIVO. Os autores apresentam três casos de papiloma de células escamosas de esôfago, discutindo seu diagnóstico e a associaçao ou nao com o papilomavírus humano. CASUISTICA. Trata-se de dois pacientes do sexo masculino e uma do feminino. Todos os pacientes foram submetidos a endoscopia digestiva alta: em um dos casos o tumor era maior do que normalmente relatado e, em todos, estava localizado no esôfago médio ou distal. Em um dos casos, utilizou-se cromoscopia e a lesao náo foi corada. Empregando testes de hibridizaçao de DNA, nao se conseguiu identificar papilomavírus humanos em nenhum dos casos. É feita revisao da literatura e os resultados dos autores sao semelhantes aos publicados. RESULTADO. De acordo com levantamento bibliográfico computadorizado, este é o primeiro relato de caso em nosso país, e o primeiro a utilizar cromoscopia para melhor identificaçao da lesao. CONCLUSAO. Nos casos deste trabalho, nao foi identificada correlaçao entre o papiloma vírus e papiloma escamoso de esôfago.

Use of ampicilin plus ranitidine for Helicobacter pylori gastritis

Helicobacter pylori (formerly Campylobacter pylori) is now recognized as an etiological factor in gastritis and duodenal ulcers and probably also gastric ulcers. Eradication of the bacteria is fundamental to avoid ulcer relapse. Although bismuth salts have been shown to be effective for treatment, they are not commercially available in Brazil. We report an attempt to treat patients with Helicobacter pylori-associated gastritis with ampicilin (1000 mg twice daily for one month) and compare the results with the conventional treatment used in Brazil (ranitidine, 300 mg daily for one month) and with a combination of the two drugs. We studied 44 patients with histologically confirmed gastritis and with Helicobacter pylori, who were examined at the beginning and after one month of treatment. Ampicilin associated with ranitidine was better than ampicilin or ranitidine alone for the treatment of gastritis. Although ampicilin may be more efficient in patients with lower acid output we did not find a statistically significant difference between these two groups (ampicilin vs drug combination), perhaps owing to the small number of patients studied. When ampicilin was with ranitidine there was 25% normalization of the histological picture of the gastric mucosa. We conclude that ampicilin in combination with ranitidine may be a useful treatment for Helicobacter pylori-associated gastritis