HIV, HEV and cirrhosis: evidence of a possible link from eastern Spain.

OBJECTIVES: The aim of the study was to assess the seroprevalence of hepatitis E virus (HEV) infection in an HIV-infected population, as determined by HEV immunoglobulin G (IgG) antibodies (anti-HEV). METHODS: The design of the study was cross-sectional. Serum anti-HEV IgG was determined by enzyme immunoassay in 238 HIV-infected patients consecutively attending our out-patient clinic between April and May 2011. In HEV-seropositive patients, HEV RNA was analysed by nested reverse transcriptase-polymerase chain reaction (RT-PCR). Associations between anti-HEV and liver cirrhosis, route of HIV infection, hepatitis B virus (HBV) and hepatitis C virus (HCV) serological markers, age, sex and alanine aminotransferase (ALT) levels were examined by univariate and multivariate analysis. RESULTS: One hundred and forty patients (59%) had chronic liver disease (99% were HBV- and/or HCV-coinfected). Liver cirrhosis was detected in 44 individuals (19%). Two hundred and twelve patients (89%) were on antiretroviral treatment; the median CD4 T-cell count was 483 cells/µL [interquartile range (IQR) 313-662 cells/µL] and the HIV viral load was <25 HIV-1 RNA copies/mL. Overall, 22 patients (9%) were anti-HEV positive. Liver cirrhosis was the only factor independently associated with the presence of anti-HEV, which was documented in 23% of patients with cirrhosis and 6% of patients without cirrhosis (P=0.002; odds ratio 5.77). HEV RNA was detected in three seropositive patients (14%), two of whom had liver cirrhosis. CONCLUSIONS: Our findings show a high prevalence of anti-HEV in HIV-infected patients, strongly associated with liver cirrhosis. Chronic HEV infection was detected in a significant number of HEV-seropositive patients. Further research is needed to ascertain whether cirrhosis is a predisposing factor for HEV infection and to assess the role of chronic HEV infection in the pathogeneses of cirrhosis in this population.

Clinical outcome of acute and chronic hepatitis delta over time: a long-term follow-up study.

Long-term changes in the frequency and outcome of hepatitis delta virus (HDV) infection have seldom been analysed. This retrospective, longitudinal study includes 398 consecutive hepatitis B surface antigen (HBsAg)-positive patients with anti-HDV antibodies who attended our institution between 1983 and 2008. At enrolment, 182 patients had acute and 216 chronic hepatitis. Patients were grouped into two periods. Those who attended between 1983 and 1995 and those between 1996 and 2008. The former group was significantly younger, mainly intravenous drugs users, and had a greater incidence of acute HDV and HIV and HCV coinfection. Patients with acute HBV/HDV coinfection cleared both infections in 90% of cases, while all patients with HDV superinfection evolved to chronic disease. One hundred and fifty-eight patients with chronic HDV were followed for a median period of 158months. Seventy-two per cent of the patients remained stable, 18% had hepatic decompensation, 3% developed hepatocellular carcinoma, and 8% cleared HBsAg. Liver-related death was observed in 13% of patients and mainly occurred in patients from the first period (P=0.012). These results indicate an outbreak of HDV at the end of the 1980s and the beginning of the 1990s, with a large number of acute HDV cases affecting predominately young, male intravenous drug users. Currently, patients with chronic HDV disease are older, and factors associated with worse prognosis include the presence of cirrhosis and age at the time of diagnosis.

Laboratory testing of individuals with severe alpha1-antitrypsin deficiency in three European centres.

alpha(1)-Antitrypsin (AT) deficiency is a hereditary disorder that may lead to early-onset emphysema, and chronic liver disease later in life. Although there are validated methods for testing, the vast majority of alpha(1)-AT-deficient individuals remain undiagnosed. Recommendations have been published for the testing and diagnosis of alpha( 1)-AT deficiency; however, guidelines on best practice are not well established. In our article, we review the developments in diagnostic techniques that have taken place in recent years, and describe the practices used in our three European centres. The determination of the level of alpha(1)-AT and genotyping are reported as the main diagnostic steps, whereas isoelectric focusing (also referred to as phenotyping) is reserved for confirmatory analysis. The following recommendations for best practice are put forward: detection of all PiZZ and other severe deficiency individuals; automated genotyping; preparation of reference standards; quality control programmes; development of standard operating procedure documents; and standardised methods for the collection of dried blood samples. Closer cooperation between laboratories and the sharing of knowledge are recommended, with the objectives of improving the efficiency of the diagnosis of severe alpha(1)-AT deficiency, increasing the numbers of individuals who are detected with the disorder, and assisting the establishment of new patient identification programmes.

Changes in different regions of hepatitis B virus gene in hepatitis B 'e' antigen-negative patients with chronic hepatitis B: the effect of long-term lamivudine therapy.

BACKGROUND: Lamivudine therapy for chronic hepatitis B has been associated with changes in different regions of the hepatitis B virus nucleotide sequence. AIM: To study changes in the sequences of polymerase and precore/core promoter regions of hepatitis B virus, before and during 5 years of therapy with lamivudine. METHODS: Eighty consecutive samples were taken from 10 chronic hepatitis B 'e' antigen-negative patients. RESULTS: Nine patients carried hepatitis B virus precore mutations during the study. Before therapy, wild type was replaced by A1896 in two (20%) cases. During treatment, A1896 reverted transitory to wild type in five cases (50%) and in one case wild type was replaced by A1896. The continuous detection of precore mutations during therapy was associated with a lower response rate. YMDD mutations were observed in nine cases and both, L180M and M204V/I mutations were simultaneously detected in six cases. About 75% of the patients with M204V mutations were responders and none with M204I or mixed pattern sustained response. CONCLUSION: Hepatitis B 'e' antigen-negative patients exhibit changes in the precore regions both spontaneously and under lamivudine therapy, the transitory reversion to wild type being most frequently witnessed. Patients carrying M204V mutations are more likely to respond to therapy. If, in further studies, these results are confirmed some patients with YMDD mutations could benefit from prolonging the duration of lamivudine therapy.

High prevalence of hepatitis C virus infection in diabetic patients.

OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) infection in diabetic patients and to investigate the influence of several epidemiological and clinical factors on HCV infection. RESEARCH DESIGN AND METHODS: A total of 176 consecutive diabetic patients were compared with 6,172 blood donors, matched by recognized risk factors to acquire HCV infection. Serologic testing for anti-HCV was done using a second-generation commercial enzyme-linked immunosorbent assay (ELISA) and an immunoblot assay was performed in anti-HCV positive samples to confirm HCV specificity. Diabetic patients were divided in two groups according to their HCV antibody status and analyzed for the following variables: age, sex, type of diabetes, duration of disease, mode of therapy, late diabetic complications, previous blood transfusions, intravenous drug addiction, hospital admissions, major surgical procedures, and liver function tests (LFTs). RESULTS: A higher prevalence of HCV infection was observed in diabetic patients in comparison with blood donors (11.5 vs. 2.5%; P < 0.001; odds ratio 4.39; 95% Cl2.61-7.24). We did not detect any particular epidemiological factor for HCV infection in anti-HCV positive diabetic patients. In these patients, abnormal LFTs were observed in 72.3%, compared with only 24.7% of anti-HCV negative diabetic patients (P < 0.001). CONCLUSIONS: A high prevalence of HCV infection was detected in diabetic patients, and most of anti-HCV positive patients presented with abnormal LFTs. Therefore, testing for HCV infection of diabetic patients with an abnormal LFT is mandatory. The lack of any particular epidemiological factor for HCV infection in our diabetic population suggests that HCV may have a direct role in the development of diabetes.

Comparative analysis of serological markers of chronic delta infection: HDV-RNA, serum HDAg and anti-HD IgM.

To study the concordance, sensitivity and specificity of HDV-RNA determination by molecular hybridization, serum HDAg by immunoblot and anti-HD IgM by commercial enzyme immunoassay as compared to intrahepatic HDAg detection by an immunoperoxidase method, a statistical analysis was applied to the results of serum sample and liver biopsy determinations in 50 patients with chronic delta hepatitis (38 positive to tissue HDAg and 12 negative). Of the 38 patients with hepatic HDAg, HDV-RNA was found in 31 (82%), serum HDAg by immunoblot in 27 (71%) and anti-HD IgM in 33 (87%). Among the 12 patients without hepatic HDAg, one was found with serum HDAg using the immunoblot technique, two (17%) had HDV-RNA, and 7 (58%) had anti-HD IgM. Serum HDAg determination by immunoblot was the most specific test, followed by HDV-RNA analysis. The least specific was the anti-HD IgM technique. The anti-HD IgM test was the most sensitive, followed by HDV-RNA and serum HDAg. The concordance with intrahepatic HDAg detection was highest for HDV-RNA determination, followed by HDAg in serum. The least degree of concordance was found with anti-HD IgM determination. These results suggest that the determination of HDV-RNA by the hybridization method can be of great value for the diagnosis and monitoring of chronic delta hepatitis.

Rapid detection of lamivudine-resistant hepatitis B virus polymerase gene variants.

The amino acid substitution from methionine to valine or isoleucine at the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the HBV polymerase gene is the main mutation responsible for resistance to lamivudine treatment. Detection of emerging HBV variants by direct sequencing of the HBV genome is excessively time-consuming for studying large numbers of clinical samples. The aim of the study was to analyse the emergence of lamivudine-resistant HBV genotypes by means of restriction fragment length polymorphism (RFLP) of the PCR product generated from a fragment of domain C of the polymerase gene, in clinical samples from patients receiving treatment. The results with this method were compared with those obtained with a direct sequencing technique. In total, 139 serum samples were studied from 37 patients with chronic hepatitis B, obtained at pre-treatment and at 9, 12, 18 and 24 months of treatment. Variants were detected by cleavage of the products of the three PCRs with the following enzymes: FokI (identifies the normal variant, YMDD, and the mutant variant YVDD), SspI (identifies the mutant variant, YIDD) and Alw44I (identifies the variant, YVDD). The digested fragments were separated by electrophoresis in 3% agarose gel. Of the 139 serum samples analysed, the wild-type YMDD sequence was detected in 106 (76%), the YVDD variant in 20 (15%) and the YIDD variant in 13 (9%) cases. The non-mutated variant, YMDD, was detected in all the pre-treatment samples. After 9 months of treatment the mutant variant was detected in four of 37 serum samples analysed (11%) (two YVDD and two YIDD). At 12 months, 12 of the 37 serum samples (32%) showed mutations in the YMDD sequence (seven YVDD and five YIDD). Among the 16 serum samples obtained at 18 months, nine had the YMDD variant (56%) (seven YVDD and two YIDD). At 24 months, variants in the YMDD sequence were detected in eight of the 12 patients treated (66%) (four YVDD and four YIDD). HBV genotypes were confirmed by direct sequencing, with consistent results. In 45% of cases, the emergence of HBV variants was not associated with ALT breakthrough. The PCR-RFLP assay used in this study, in perfect concordance with direct sequencing, is an accurate method for genotyping lamivudine-resistant HBV variants. Since it is a rapid low-cost technique, PCR- RFLP is suitable for large-scale screening of these polymorphisms in clinical samples.

Hepatitis E virus infection in acute hepatitis in Spain.

In order to study the prevalence of hepatitis E virus (HEV) infection in developed countries, IgG and IgM anti-HEV were determined in serum samples from 382 patients with acute viral hepatitis (244 hepatitis A, 48 hepatitis B and/or D, and 90 non-A, non-B, non-C hepatitis), 76 healthy subjects, 55 hemophiliacs and 50 patients on hemodialysis. IgG anti-HEV antibodies were detected and confirmed by a synthetic peptide-based EIA in 5 (5.6%) non-A, non-B, non-C acute hepatitis, in 3 (6.5%) B and D acute hepatitis, in 10 (4%) acute A hepatitis, in 3 (5.5%) of 54 healthy adults in none of the hemophiliacs and in 3 (6%) patients on hemodialysis. IgM anti-HEV antibodies were only detected in two cases of acute hepatitis B and/or D. Analysis of serial serum samples demonstrated IgG anti-HEV seroconversion in 3 of the 18 confirmed cases; one of them was also positive for IgM anti-HEV. All 3 acute anti-HEV-positive hepatitis cases occurred in adults, were community-acquired (two of them were intravenous drug addicts) and had a self-limited course. These results demonstrate that HEV is a minor cause of acute hepatitis in Spain. A similar low rate of IgG anti-HEV antibodies was detected in patients with different diseases, suggesting that HEV has a very low epidemiological impact. An apparent association of HEV infection with hepatitis B and D suggests a possible parenteral transmission of a mainly enteral pathogen.

Usefulness of a national registry of alpha-1-antitrypsin deficiency. The Spanish experience.

Severe alpha-1-antitrypsin (AAT) deficiency, phenotype Pi ZZ, is a rare condition with an estimated prevalence of 1/4500 individuals in Spain. Given this low prevalence, it seems useful to accumulate all the information derived from the care of these patients. In this context, the Spanish Registry of patients with AAT deficiency was founded in 1993; its main objectives were to establish guidelines adapted to our country for the treatment and management of AAT-deficient patients, offer expert support to physicians all over the country treating these patients, and provide technical support on the determination of Pi phenotyping and genotyping of individuals suspected of being AAT-deficient. From 1993 to January 1998 the number of enrollees increased from 48 to 223, of which 216 were Pi ZZ. Seventy-three per cent were male and only 31.5% were never smokers, mean age was 46 years (SD = 13 years) and mean FEV1 53% predicted (SD = 31%). 83% were index cases who, compared with non-index cases, were older (49 +/- 11 vs. 35 +/- 13 years, P < 0.001), more likely to have a smoking history (85% vs. 47%, P < 0.01) and displayed more severe impairment in pulmonary function (FEV1% = 40% +/- 19% vs. 96% +/- 23%, P < 0.001). Augmentation therapy was administered to 129 patients (58%). Treated patients had more severe impairment in pulmonary function than the untreated (FEV1% = 40% +/- 21% vs. 72% +/- 32%, P < 0.001) and were more likely to be index cases (81% vs. 43%, P < 0.001). Characteristics of the patients included are similar to those described for other Registries. The Registry has extended knowledge of the disease throughout the country and has established local guidelines for treatment and follow-up. It may be a valid database for future co-operation in international initiatives.

Influence of deficient alpha1-anti-trypsin phenotypes on clinical characteristics and severity of asthma in adults.

Severe alpha1-anti-trypsin (AAT) deficiency implies a high risk of pulmonary emphysema development. The possible relationship between partial deficiencies of this enzyme and bronchial asthma remains controversial. The objective of this study was to ascertain the distribution of AAT phenotypes in a non-selected asthmatic patient population. Across-sectional study on a sample of 111 patients with asthma was carried out. Demographic and clinical variables were collected with serum IgE concentrations, plasma eosinophil number and serum AAT concentrations determined, together with the Pi phenotype. Asthma was mild in 36 (32.4%) patients, moderate in 45 (40.5%) and severe in 30 (27%). No differences were observed in eosinophil count or serum IgE or AAT concentrations among patients with different degrees of severity. Twenty-two (19.8%) asthmatics with deficient phenotypes for AAT were identified, distributed equally in all severity stages of the disease. No significant differences were found in clinical and functional characteristics, or in asthma morbidity between PiMM and PiMS patients or the heterozygote group (PiMS and PiMZ). Eosinophil count and IgE concentrations did not differ significantly between asthmatics with normal phenotype and heterozygotes. In conclusion, the distribution of AAT phenotypes in asthmatic patients did not differ from that found in the general population. Heterozygote phenotypes for the deficiency do not appear to confer greater severity or different clinical expression of asthma in adults.

[Usefulness of the quantification of the alpha-1 serous protein band in the screening of alpha-1-antitrypsin deficiency]. / Utilidad de la cuantificación de la banda alfa-1 del proteinograma sérico en el cribado del déficit de alfa-1-antitripsina.

BACKGROUND: Population studies indicate that alpha-1-antitrypsin (AAT) deficiency is an under diagnosed disease. Although alpha-1 serum protein is widely known to accompany AAT deficiency, the diagnostic utility of measuring the alpha-1 band to screen for this condition has not been assessed in the literature. SUBJECTS AND METHOD: Electropherograms with alpha-1 band widths under the reference values were collected over a period of 3 months. The Pi phenotype of AAT was identified for these sera by isoelectric point determination. The phenotypes were compared to those obtained for the population of the same geographic area (n = 440). The alpha-1 band reference values were obtained from 73 healthy individuals with no Pi phenotype deficiency. Moreover, the alpha-1 band was also measured for a group of 17 PiZZ deficient patients. RESULTS: We analyzed 7,305 electropherograms. One hundred four individuals (1.4%) without hypoproteinemia had alpha-1 readings below reference (set at 2.3%). The phenotypes in this group were 25 PiMM (24%), 52 PiMS (54%), 13 PiMZ (12.5%) and 5 PiSS 5 (5%). The odds ratios (CI 95%) in comparison with the normal population were, respectively, 0.10 (0.16-0.06); 4.58 (2.97-7.04); 4.35 (2.09-9.04) and 5.51 (1.66-18.16) (p < 10-5 in all cases except PiSS, which was p < 0.05). The levels for PiZZ patients were 1.4% +/- 0.3% (range 1.0%-2.1%). CONCLUSIONS: Three times fewer subjects with a normal PiMM phenotypes are found among individuals with low alpha-1 band serum protein levels, and many more of such individuals are carriers of Z allele heterozygotes. Alpha-1 band readings in patients with AAT deficiency (PiZZ phenotype) have alpha-1 values below reference. Measuring alpha-1 protein is an easy technique, within the expertise of any laboratory, and may be very useful for screening for AAT deficiency in patients with chronic respiratory diseases.

[Screening program for alpha-1 antitrypsin deficiency in patients with chronic obstructive pulmonary disease, using dried blood spots on filter paper]. / Programa de cribado para el déficit de alpha 1-antitripsina en pacientes con EPOC mediante el uso de gota de sangre en papel secante.

Alpha-1 antitrypsin (AAT) deficiency is an under-diagnosed disease and screening programs have therefore been recommended for patients with chronic obstructive pulmonary disease (COPD). We present the results of the pilot phase of a screening program for AAT deficiency in order to evaluate the technique used, the procedures for transporting samples and the results obtained. Over a period of one month, five centers collected samples from all COPD patients for whom plasma concentrations of AAT or Pi phenotype had not yet been determined. Capillary blood spots were dried on filter paper and then sent by surface mail to a central laboratory for study. An immunonephelometric assay was used to determine AAT and DNA phenotyping was done by use of a Light Cycler. Samples were analyzed from 86 COPD patients (76 men, 10 women) with a mean age of 68.2 years. AAT deficiency was ruled out for 74 patients (86%) who had concentrations above the cutoff established, although one of them was MZ heterozygote by genotype. Among the 12 remaining patients (13.9%), only two also had a Z allele. The rest were individuals with concentrations below the established threshold and no evidence of a Z allele (10 patients, 11.6%). The Z allele frequency observed (3/172; 1.74%) was very similar to that found in the general population. The results of this pilot study allowed us to confirm that the method used to collect samples worked well. The sampling method is applicable, easy and well-accepted by participating physicians. It allowed AAT concentrations and Z allele deficiency to be determined. The method correlates well with standard techniques used for samples in whole blood.

Diagnostic usefulness of anti-HBc-IgM and anti-HD antibodies in acute viral hepatitis.

To evaluate diagnostic improvement achieved with the determination of antibody to hepatitis core antigen of IgM type (anti-HBc-IgM) and antibody to delta antigen (anti-HD) in acute type B hepatitis, 155 patients (of whom 100 were drug addicts) were studied, using these markers in association with the classical markers of viral hepatitis (anti-HBc, anti-HBs, anti-HAV-IgM and anti-cytomegalovirus antibodies). With classical diagnostic criteria, 121 patients would have been diagnosed as having B hepatitis (HBs Ag and/or anti-HBc antibody positive without anti-HBs antibody), 33 non A non-B hepatitis (all markers negative or anti-HBc and anti-HBs positive) and 3 A hepatitis (anti-HAV-IgM antibody positive). With the current markers, 89 were B hepatitis (anti-HBc-IgM antibody positive), 18 were simultaneous B and D infections (anti-HBc-IgM and anti-HD antibodies positive), 6 were D hepatitis (anti-HBc-IgM antibody negative and anti-HD antibody positive), 39 non-A non-B hepatitis (anti-HBc-IgM, anti-HD, HAV-IgM and anti-cytomegalovirus antibodies negative) and 3 hepatitis A. Of the 121 cases initially diagnosed as B hepatitis, only 79 were actually B hepatitis, 16 were simultaneous B and D infections, 6 D hepatitis, 18 non-A non-B hepatitis and 2 A hepatitis. Of the 33 cases considered to be non A non-B hepatitis, only 21 were really non-A non-B hepatitis; 10 were B hepatitis and 2 B and D hepatitis. When anti-HBc-IgM and anti-HD antibodies were determined, the initial diagnosis was modified in 54 of 155 cases (35 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS)

[Molecular characterization of two variants of alpha-1-antitrypsin deficiency: PI Mpalermo and PI Plovel]. / Caracterización molecular de dos variantes deficitarias de la alfa-1-antitripsina: PL Mpalermo y PL Plovel.

BACKGROUND: Alpha 1 antitrypsin (AAT) is a highly polymorphic protein, having more than 75 different variants. In this work two rare AAT deficient variants were characterized by DNA study. PATIENTS AND METHODS: Members of three generations of two separate families were studied. In family 1, the index case was affected with pulmonary emphysema and presented AAT deficiency (23 mg/dl). In family 2, the index case had a normal pulmonary function, an AAT serum level of 72 mg/dl and a phenotype heterozygous for an AAT variant migrating in the P variant region. The AAT variants were characterized by polymerase chain reaction amplification of the coding exons and direct sequencing of the amplification products. RESULTS: Direct DNA sequencing from a member of family 1 demonstrates that in the exon II of the normal M1 (Val213) allele there was a 3-bp deletion (TTC), corresponding to Phe51 or Phe52. This mutation is characteristic of the Pl Mpalermo variant. In our study, Pl Mpalermo was detected in six members of three generations of this same family. Sequencing of exon III in a member of family 2, identified in the common M1 (Val213) allele a single base substitution of GAT-GTT, with the resulting amino acid change Asp256 for Val256. This mutation characterizes the Pl Plovel allele. The Pl Plovel was also detected in nine members of five others independent families. All of them have AAT serum levels between 80 and 102 mg/dl. None of the studied subjects had clinical evidence of lung disease. CONCLUSIONS: The results of our study show the presence of the two AAT deficient variants in Spain and suggest that the Pl Plovel variant might be more common than expected.

[Study of the frequency of different phenotypes of alpha-1-antitrypsin in a population of Barcelona]. / Estudio de la frecuencia de los diferentes fenotipos de la alfa-1-antitripsina en una población de Barcelona.

BACKGROUND: Severe alpha-1-antitrypsin (AAT) deficiency is caused by homozygous inheritance of gene Z, and is associated with a high risk of developing pulmonary emphysema. Determination of frequencies of different genes associated with the deficiency (especially S and Z) gives a clue to estimate the number of individuals homozygous PiZZ, carrying a high risk for pulmonary disease, in any given population. PATIENTS AND METHODS: Pi phenotypes of 440 healthy individuals were determined by means of isoelectrofocusing in polyacrylamide gel. Seric values of AAT were determined by immunonephelometry. Mean age of participants was 30 years (range 18-49 yrs.). Results are compared with other published series. RESULTS: Distribution of phenotypes was: PiMM 333 individuals (75%), PiMS 84 (19%), PiMZ 14 (3%), PiSS 4 (0.9%), PiM 3 (0.6%), PiMF 1 (0.2%), PiMP 1 (0.2%). The corresponding gene frequencies were Pi*M 87%, Pi*S 10.4%, and Pi*Z 1.5%. Normal values of AAT (phenotype PiMM) established in our laboratory were 116-232 mg/dl (21-41 micromol/I) (mean +/- 2 SD). According to Hardy-Weinberger equation, expected frequency of PiZZ individuals in our area would be 225 per million. CONCLUSIONS: The frequency of Z gen individuals observed in our study is one of the highest in the Iberian Peninsula, but lower than the frequency in northern Europe. According to these results, AAT deficiency (PiZZ) is not a rare condition in contrast with the small number of patients diagnosed. The gen frequency of the S variant is higher than that of the rest of Europe, and similar to others found in some Spanish populations.

[A study of 158 cases of acute delta hepatitis]. / Estudio de 158 casos de hepatitis aguda delta.

We have prospectively studied 158 cases of acute hepatitis delta observed during the last 7 years in a general hospital. Among them 136 were male and 22 female. The mean age was 22.7 years with a range between 16 and 61 years. The epidemiologic factors were drug addiction by parenteral route in 145 cases (92%), sexual transmission in 5 (3%), post transfusional in 2 (1%) and unknown in 6 (4%). With respect to the delta type infection, 105 cases (66%) were coinfections with type B and delta, and 53 patients had a type delta superinfection (34%). The clinical course was a fulminant hepatitis in three cases (two cases of coinfection B and delta an one case of delta superinfection), and an acute benign hepatitis in 155 patients. The follow-up of 118 patients revealed that 96% of coinfections by type B and delta evolved to the chronicity showing findings of active chronic hepatitis or hepatic cirrhosis. It should be noted that in 4 cases of superinfection delta type (11%) the HBsAg was negative after several months of positivity. In these patients the level of transaminases normalized and the hepatic histology evidenced alterations of chronic active hepatitis (2 cases) and hepatic cirrhosis (2 cases) without identification of tissular delta antigen.

Rapid method for the detection of anti-HCV antibodies in patients with chronic hepatitis C.

OBJECTIVE: to evaluate the usefulness of a simple, rapid, qualitative technique (MedMira Rapid Test) to detect antibodies against hepatitis C virus (HCV) and compare this approach with an immunometric technique in patients with chronic hepatitis C infected with different genotypes. METHODS: anti-HCV antibodies were determined with the MedMira rapid technique and an immunometric method in samples from 138 patients with chronic hepatitis C infected with different HCV genotypes, and in 50 samples from healthy individuals. RESULTS: the MedMira rapid technique detected anti-HCV antibodies in 135 (98%) of 138 serum samples from patients with chronic hepatitis C, whereas the immunometric method gave positive results in all 138 samples. Three of the 138 anti-HCV-positive samples identified with the immunometric method and confirmed by inmunoblotting were repeatedly negative with the MedMira rapid technique. Two of these samples were genotype 1 and the third was not genotyped. All samples from the control group were negative for anti-HCV antibodies by both methods. The sensitivity and specificity of the MedMira rapid technique relative to the immunometric technique were 98% and 100% respectively. CONCLUSION: the MedMira rapid technique is a quick, specific and sensitive method that is easy to use by nonspecialized personnel, and is a good alternative to other, slower methods for the diagnosis of chronic hepatitis C.

[Study of HLA-II antigens in chronic hepatitis C and B and in acute hepatitis B]. / Estudio de los antígenos HLA-II en las hepatitis crónicas C y B y en las hepatitis agudas B.

The aim of this study was to analyze the variability of the HLA-II system in a series of patients with chronic hepatitis B, chronic hepatitis C and acute hepatitis B to know whether there is any relationship between the polymorphism of the HLA system, the different types of hepatitis and the evolution of the infection. HLA-II antigens were determined by a PCR technique in serum samples of 24 controls, 22 cases of chronic hepatitis C, 38 cases of chronic hepatitis B and 11 with acute hepatitis B. The prevalence of the HLA-DR4 antigen was lower in the cases of chronic hepatitis B (10.5%) and C (13.6%) than in the controls (33.3%), particularly the DRB1*0401 allele (p = NS). The prevalence of HLA-DR6 was similar in chronic hepatitis B (42.1%) and acute hepatitis B (45.5%). Predominance of the DRB1*1301 and DRB1*1302 alleles were, however, observed in acute hepatitis B (36.4%) versus chronic hepatitis B (13%). These data suggest that immunologic factors such as HLA antigens may influence in the susceptibility to infection by HBV and HCV. The use of PCR techniques which discriminate between the different alleles of the HLA antigens may provide better knowledge of the immune response.

[Seroepidemiology of hepatitis A virus infection in medical and nursing students. The role of vaccination]. / Seroepidemiología de la infección por el virus de la hepatitis A en estudiantes de medicina y enfermería. Papel de la vacunación.

BACKGROUND: Recent seroepidemiologic studies have demonstrated a decrease in the prevalence of hepatitis A virus infection (HAV) in relation with an improvement in hygienic conditions. The prevalence of anti-HAV in a group of health care students was studied and a vaccination program initiated in this collective. METHODS: Serum anti-HAV determination was performed by an enzymoimmunoanalysis method. A inactivated hepatitis A vaccine was administered. RESULTS: Only 18.5% of the subjects between 17-23 years-old presented anti-HAV antibodies. The prevalence of anti-HAV was related with age and the number of partners. All of the 129 immunized individuals responded to the HAV vaccine with protector antibody titles. CONCLUSION: The present study demonstrates the decrease in HAV infection among youths as well as the immunogenicity of the anti-hepatitis A vaccine.

[One year treatment with lamivudine in different hepatitis B virus related hepatic diseases]. / Tratamiento con lamivudina durante un año en distintas formas de afectación hepática por el virus de la hepatitis B.

BACKGROUND: Three month administration of lamivudine in patients with chronic hepatitis B produces a transitory inhibition of the DNA of the hepatitis B virus (HBV). AIM: The aim of this study was to evaluate the efficacy and safety of one year treatment with lamivudine in patients with chronic hepatitis B and liver transplantation (LTx) with recurrence of HBV infection. PATIENTS AND METHODS: Sixteen patients with chronic hepatitis B, 4 patients with decompensated hepatic cirrhosis and 4 patients having undergone LTx with recurrence of HVB infection were treated with the oral administration of 100 mg/day of lamivudine for one year. RESULTS: At 3 months of treatment, the HBV-DNA became negative in 94% of the cases of chronic hepatitis B, in 10% of those with decompensated hepatic cirrhosis and in 100% of the cases of LTx. At one year of treatment, the HBV-DNA was negative in 81% of the chronic hepatitis B, in 100% of the decompensated cirrhotics and in 100% of the LTX cases which survived. The tolerance to treatment was excellent in all the cases. In 34% of the cases, mutations were observed in the gene of the polymerase DNA at one year of treatment. CONCLUSIONS: Lamivudine produces intense, rapid inhibition in viral replication not only in chronic hepatitis B but also in cases of decompensated cirrhosis or recurrence following liver transplantation. Around 30% of the patients undergoing one year of treatment with lamivudine developed gene mutations of the HBV polymerase.