[Drugs treatment of hepatitis B]. / Tratamiento farmacológico de la hepatitis B.

OBJECTIVE: To define the role of those drugs available for hepatitis B treatment and analyse current treatment guides prepared by the leading scientific societies in the field. METHODS: Bibliographic searches were carried out in the databases PubMed and EMBASE, using the search word <>, limited by <> plus <>, <> or <>, within the period 1991-2007. RESULTS: Six drugs are currently available: interferon alpha (conventional or pegylated), lamivudine, adefovir, entecavir and telbivudine. In normal practice, pegylated interferon has almost completely displaced the conventional variety. HBeAg+ patients with high ALT levels, low HBV DNA counts and genotypes A and B show the best response to interferon. Lamivudine achieves faster and more potent viral suppression than adefovir; its principal drawback is the resistance that some patients develop. Its role will probably decrease as entecavir and telbivudine become more widespread, as they are associated with less resistance. Adefovir is useful in decompensated patients and/or those resistant to lamivudine. Because of the response rates it obtains, entecavir could be the drug of choice for HBeAG+ patients, particularly those with higher viral loads. For HBeAg- cases, any drug can be used as a first-choice drug. The main difference between the treatment guides lies in the way they define the illness and the serum markers that indicate active replication: viral loads and HBeAG positivity. CONCLUSIONS: All of the drugs are capable of accomplishing short-term biochemical, viral and histological objectives. There is no unanimous opinion on which patients should be treated with which drugs, during what length of time, and what objectives are to be reached.

Selective and energy efficient extraction of functional proteins from microalgae for food applications.

The use of a single controlled bead milling step of the microalga Tetraselmis suecica resulted in a soluble fraction, rich in functional proteins. This was achieved by fine-tuning the processing time, thereby exploiting the difference in rates of protein and carbohydrate release during milling. Soluble proteins were extracted under mild conditions -room temperature, no addition of chemicals, pH 6.5-, with a yield of 22.5% and a specific energy consumption of 0.6 kWh kgDW-1, which is within the recommended minimum energy for an extraction step in a biorefinery process. The resulting protein extract contained 50.4% (DW) of proteins and 26.4% carbohydrates, showed light green color and displayed superior surface activity and gelation behavior compared to whey protein isolate. The proposed process is simple (only one bead milling step), scalable, and allows the mild extraction of functional proteins, making it interesting for industrial applications in the food industry.

Energy efficient bead milling of microalgae: Effect of bead size on disintegration and release of proteins and carbohydrates.

The disintegration of three industry relevant algae (Chlorella vulgaris, Neochloris oleoabundans and Tetraselmis suecica) was studied in a lab scale bead mill at different bead sizes (0.3-1mm). Cell disintegration, proteins and carbohydrates released into the water phase followed a first order kinetics. The process is selective towards proteins over carbohydrates during early stages of milling. In general, smaller beads led to higher kinetic rates, with a minimum specific energy consumption of ⩽0.47kWhkgDW-1 for 0.3mm beads. After analysis of the stress parameters (stress number and stress intensity), it appears that optimal disintegration and energy usage for all strains occurs in the 0.3-0.4mm range. During the course of bead milling, the native structure of the marker protein Rubisco was retained, confirming the mildness of the disruption process.

[Sarcoidosis following combined ribavirin and interferon therapy: a case report and review of the literature]. / Sarcoidosis tras tratamiento con interferón y ribavirina. Presentación de un caso y revisión de la bibliografía.

Treatment of active chronic viral hepatitis type C with interferon alpha has proved effective and therefore its use is being extended to a large number of patients. Common side effects include respiratory manifestations. One side effect attributable to the immunomodulatory effect of interferon is the possible triggering or exacerbation of systemic or cutaneous sarcoidosis. We report a new case and offer an exhaustive review of the literature. A 49-year-old man with type C chronic, active hepatitis developed new respiratory symptoms and pulmonary infiltrates with hilar and mediastinal adenopathy after 4 months of treatment with pegylated interferon and ribavirin. The transbronchial biopsy showed multiple sarcoid granulomas. When the patient was diagnosed, he had already taken the total dose of interferon and no specific treatment was started. His hepatitis did not respond to therapy and his viral load and transaminase levels remained high.

[Prevalence and clinical significance of antiphospholipid antibodies in chronic hepatitis C]. / Prevalencia y significado clínico de los anticuerpos antifosfolipídicos en la hepatitis crónica por virus C.

BACKGROUND: To know the prevalence of antiphospholipid antibodies in chronic hepatitis C and their relationship with disease progression. METHODS: One hundred and twenty-eight patients with chronic hepatitis C and 93 healthy controls were enrolled up. We determined platelets, ALT, gamma GT, RNAHCV in serum and liver and non-organ specific antibodies, grade and stage in liver biopsy, risk factors, duration of disease and alcohol intake were also included. Portal hypertension and liver function parameters were studied. Antiphospholipid antibodies (APA): lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) (IgG and IgM) were measured by EIA. Anti-beta 2 glycoprotein I antibodies were also detected by EIA in ACA positive patients. RESULTS: Thirty one out of 128 (25%; 95% CI: 17.8%-33.4%) showed positive antiphospholipid antibodies. Positive ACA-IgG was higher in patients than controls (22% vs 3.2%; p < 0.05), whereas, ACA-IgM was similar (5% vs 3.2%; p = NS), and LA was absent in both groups. ALT levels, viraemia, viral load in liver, platelets, or ANA titre were similar in patients with and without positive ACA-IgG. Risk factors, duration of disease or alcohol intake were not related yet. Patients with staging F1 showed positive ACA-IgG 4 of 44 (9%; 95% CI: 2.5%-21.7%), in staging F2 7 of 39 (18%; 95% CI: 7.5%-33.5%) and in staging F4 17 of 45 (38%; 95% CI: 23.8%-53.5%; p < 0.005). ACA-IgG was significantly related to portal hypertension, Child-Pugh stage and presence of cirrhosis complications. Anti-beta 2 glycoprotein I antibodies were detected in ten (43.5%; CI 95%: 23.2%-65.5%) out of 23 ACA positive patients. CONCLUSIONS: ACA-IgG seems to be associated with chronic hepatitis C, and could play a potential role in fibrosis progression and liver disease in these patients.

[Influence of pregnancy in chronic hepatitis C virus infection]. / Influencia del embarazo en la infección crónica por el virus C de la hepatitis.

BACKGROUND: There is scarce information about the influence of pregnancy in patients with chronic hepatitis C virus infection is little know. PATIENTS AND METHODS: 6,556 pregnant women were screened for anti-HCV (ELISA II). We determine ALT, HCV-RNA by PCR (Amplicor Roche) and HCV viraemia (Amplicor-HCV-Monitor Roche) in the third trimester of pregnancy and after 6 months of delivery. HBsAg, anti-HIV and HCV serotype (Murex 1-3) were also determined. STATISTICAL ANALYSIS: Fisher test, paired-t and U Mann Whitney. RESULTS: Anti-HCV was positive in 59 out of 6,556 (0.9%). Mean (SD) age: 27 (9) years (range, 18-40). Drug users: 34 (57%), post-transfusion: 10 (18%) and unknown: 15 (25%). HIV positive 11 (19%). Serotype 1, 30 (51%), setotype 3, 7 (20%), and nontypeable, 22 (37%). We studied HCV-RNA before and after delivery in 35 women, 8 out of 35 (23%) had HCV-RNA negative in both analysis. ALT was normal in 88% of women during pregnancy and in 42% after delivery. ALT levels in pregnancy were 32.6 (39.5) and in postpartum 64.5 (53.4) U/l (p < 0.005). 6 women were RNA-VHC negative during pregnancy and positive in postpartum. HCV viraemia during pregnancy and postpartum was 503 (1,203) and 1,014 (1,907) thousand copies/ml (p < 0.05). No relation was found among ALT or HCV viraemia with risk factors, serotype or coinfection with HIV. CONCLUSIONS: The prevalence of anti-HCV in pregnant women is 0.9%. ALT is usually normal in pregnancy. A quarter of women were HCV-RNA negative in pregnancy and positive after delivery. The viraemia was lower in pregnancy than after delivery, which is consistent with the fact of the low mother-to-infant HCV transmission rate.

[Anti-Sp100 and anti-Gp210 in the diagnosis of primary biliary cirrhosis in patients with autoimmune cholangitis]. / Anti-Sp100 y anti-Gp210 en el diagnóstico de cirrosis biliar primaria en pacientes con colangitis autoinmune.

We describe 2 women with features of autoimmune cholangitis. Serum biochemical studies showed cholestasis and increased immunoglobulin M with negative antimitochondrial antibodies. Markers of hepatitis B and C viruses were absent. Both had positive antinuclear antibodies. One had a speckled pattern (multiple nuclear dots) and the other a perinuclear pattern (pore nuclear). In the first case anti-Sp100 was positive by EIA and in the second anti-Gp210 was detected by immunoblot. Diagnosis of primary biliary cirrhosis was made and the patients were treated with UDCA. Current knowledge indicates that determination of anti-Sp100 and anti-Gp210 substantially improves diagnosis of primary biliary cirrhosis as these ANA are highly specific for this disease. These autoantibodies may lead to the classification of different groups of patient included in autoimmune cholangitis. All patients with autoimmune cholangitis should be tested for anti-Sp100 and anti-Gp210.

[Peritoneal mesothelioma: the importance of ultrastructural study. A report of 2 cases and a review of the Spanish literature]. / Mesotelioma peritoneal: importancia del estudio ultraestructural. Aportación de dos casos y revisión de la literatura española.

Two cases of peritoneal mesothelioma (PM), with ultrastructural study, of females who lived in a rural area without asbestos exposition history are described and the Spanish literature reviewed. We highlight the association with severe autoimmune hemolytic anemia, due to the presence of cold agglutinins, in one patient without relationship to drugs or concomitant diseases. We focus on the need for thorough and multiple biopsies through laparoscopy to avoid false negative. We believe that there are no totally specific morphological data on mesothelioma, which means that the initial study is based on optical microscopy performed with hematoxylin-eosin and PAS-diastase stain using the electronic microscopy to confirm the diagnosis.

Antiphospholipid antibodies are related to portal vein thrombosis in patients with liver cirrhosis.

The pathogenesis of portal vein thrombosis (PVT) in cirrhotic liver patients is not known. PVT has been related to liver dysfunction, neoplasm, hemodynamic factors, and hypercoagulability states. PVT has been reported in patients with antiphospholipid syndrome without liver cirrhosis. Our aim was to find the role of antiphospholipid antibodies (APAs) and coagulation inhibitors in PVT in patients with liver cirrhosis. We present a case-controlled study, matched by age, liver function, and etiology, to discover the role of APAs and anticoagulant protein activity in PVT in cirrhotic patients. We studied 30 cirrhotic patients: 6 of 10 (60%) patients with PVT were APA-positive, whereas only 2 of 20 (10%) in the cirrhotic control group were APA-positive (p < 0.005). Low serum levels of protein C, protein S antithrombin III, and plasminogen were found in cirrhotic patients; and, no differences were found between patients with and without PVT. Significantly lower protein S and antithrombin III levels were found in patients with Child-Pugh class C. Therefore, APAs were related to PVT in cirrhotic patients; but, a lower concentration of coagulation inhibitors was associated with liver dysfunction alone.

Lens culinaris, Phaseolus vulgaris and vicia faba lectins specifically trigger IL-8 production by the human colon carcinoma cell line CACO-2.

Cultured Caco-2 cells were stimulated with Lens culinaris, Phaseolus vulgarisandVicia fabalectins. The production of IL-1, IL-6, IL-8 and MCP-1 was measured by ELISA and RT-PCR. IL-8 production appeared to be specifically triggered upon stimulation with all three lectins used, since none of the other cytokines tested were produced. The IL-8 secreted may induce the extravasation of activated neutrophils and generate tissue damage. A similar mechanism may be implicated in the lesions observed after infection by some enteric pathogens, with lectin-like domains on their membrane. Finally, this model may be suitable one to study the regulation of IL-8 production.

Sarcoidosis, sclerosing cholangitis, and chronic atrophic autoimmune gastritis: a case of infiltrative sclerosing cholangitis.

We report a patient in whom sarcoidosis coexisted with sclerosing cholangitis and chronic atrophic autoimmune gastritis. There are some autoimmune diseases associated with primary sclerosing cholangitis; the difference between sarcoidosis and all other autoimmune diseases associated with primary sclerosing cholangitis is the ability of the former to damage the biliary tree. Moreover, when sarcoidosis behaves like cholestasis it can damage the biliary tree, mimicking primary sclerosing cholangitis, with high immunoglobulin M but without inflammatory bowel disease and p-ANCAs negative. We believe that it should be regarded as a single disease "infiltrative sclerosing cholangitis" because this is not a primary disease and sarcoidosis would be responsible for a beaded biliary tree.

Posttransfusion non-A, non-B hepatitis. A prospective study.

We have prospectively studied the clinical data, prognostic factors and chronic liver sequelae in 68 patients who developed posttransfusion non-A, non-B hepatitis. The mean incubation period was 5.9 weeks with a range from 2.1 to 12 weeks; 63.5% of the patients were asymptomatic and 60.6% anicteric. The chronicity rate (elevated ALT values for a period of more than 6 months) was 67.6%. The chronicity rate of symptomatic hepatitis (95.5%) was significantly higher than that of asymptomatic hepatitis (54.5%) (P less than 0.01). Monophasic hepatitis, characterized by a rapid elevation in serum ALT followed by a rapid decline with no further fluctuations, had a chronicity rate (42.5%) significantly lower than polyphasic hepatitis (86.6%) (P less than 0.05) and plateau type hepatitis (94.4%) (P less than 0.01). Results of 35 liver biopsies carried out among 46 patients with elevated ALT after 6 months were as follows: chronic active hepatitis, 15 cases; prolonged acute hepatitis, 12 cases; chronic persistent hepatitis, 6 cases; posthepatitis liver changes, 1 case; and secondary hemosiderosis, 1 case.