Analysis of the evolution in the circulation of HAV and HEV in eastern Spain by testing urban sewage samples.

The aim of the study was to analyse the evolution of the prevalence of HAV and HEV in the population of eastern Spain by analysing the viruses excreted in urban sewage. Raw urban sewage samples were collected and analysed during several years using RT-PCR techniques and sequencing analysis. Two limiting regions were analysed, one of them having implemented HAV vaccination programs. Acute symptomatic HEV cases were also examined. Results were compared with those from previous studies in the area using identical methodology. The percentage of positive HAV samples in urban sewage fell from 57.4% to 3.1% in 5-10 years in the two studied areas in Spain. Around 30% of the urban sewage samples were positive for HEV in the absence of agricultural sources of contamination. HEV RNA was also detected in four clinical cases of acute hepatitis. The dramatic reduction in the presence of HAV in raw urban sewage observed in eastern Spain could be most likely related to the general improvement in sanitation. However, these improvements would not have an equivalent effect on the circulation of HEV and this observation could be explained by the presence of animal reservoirs for HEV, which act as external sources of infections.

Response-guided therapy for chronic hepatitis C virus infection in patients coinfected with HIV: a pilot trial.

BACKGROUND: To study the feasibility of a response-guided therapy for chronic hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus (HIV) in a tertiary care hospital. METHODS: Treatment duration was individualized on the basis of week 4 and week 12 virologic response. Sixty patients were enrolled and received pegylated interferon alfa-2b (1.5 microg/kg per week) plus weight-based ribavirin (800-1400 mg/day). Patients who achieved a rapid virologic response, defined as viral load <50 IU/mL at treatment week 4, completed 24 weeks of therapy. Patients who did not achieve a rapid virologic response were reassessed at treatment week 12. Patients with a complete early virologic response, defined as an HCV RNA level <600 IU/mL, were treated for 48 weeks. Patients with a partial response, defined as a decrease in the viral load > or = 2 log10 and an HCV RNA level > or = 600 IU/mL, who attained an undetectable viral load at week 24 were treated for 60 weeks. The primary efficacy end point was sustained virologic response, defined as HCV RNA <50 IU/mL, 24 weeks after the end of treatment. RESULTS: Overall, 33 (55%) of 60 patients achieved a sustained virologic response: 11 (44%) of 25 patients with HCV genotype 1, 3 (27%) of 11 patients with genotype 4, and 19 (79%) of 24 patients with genotype 3. One-third of patients showed a rapid virologic response. Of patients with genotype 1, there was a rapid virologic response in 4 (16%) of 25; with genotype 4, in 1 (9%) of 11; and with genotype 3, in 14 (58%) of 24. Of the 19 patients with a rapid virologic response, 17 (89.5%) eradicated the virus after 24 weeks of therapy. The rate of sustained virologic response was significantly higher among patients with genotype 3 and low pretreatment HCV RNA levels. A high relapse rate (46%) after 48 weeks of therapy occurred among patients infected with genotypes 1 or 4 who first achieved undetectable viral load at treatment week 12. CONCLUSION: A response-guide therapy is feasible and may be useful to optimize the individual outcome of HCV treatment in patients coinfected with HIV.

Diabetes is the main factor accounting for the high ferritin levels detected in chronic hepatitis C virus infection.

OBJECTIVE: A high prevalence of diabetes has been reported in patients with hepatitis C virus (HCV) infection. Both diabetes and HCV infection are associated with high serum ferritin levels. Although HCV infection could be the main factor responsible for the high ferritin levels, it is also possible that diabetes rather than HCV infection might be a major contributor to the high ferritin levels observed in patients with HCV infection. The aim of this study was to investigate the contribution of diabetes to the high ferritin levels observed in HCV-infected patients with chronic hepatitis. RESEARCH DESIGN AND METHODS: A total of 634 noncirrhotic individuals were prospectively recruited at a university hospital. According to the HCV antibody status and the presence of diabetes, the subjects were divided into four groups: group A (anti-HCV-positive diabetic patients, n = 53), group B (anti-HCV-negative diabetic patients, n = 242), group C (anti-HCV-positive nondiabetic patients, n = 191), and group D (anti-HCV-negative nondiabetic control subjects, n = 148). Multiple regression analyses were used to explore the variables independently related to ferritin levels. RESULTS: Serum ferritin levels in group A were significantly higher than in the other groups (A > B, P < 0.01; A > C, P < 0.001; A > D, P < 0.001). Ferritin levels were higher in group B than in group D (P = 0.001). However, group C has ferritin values similar to those of group D. In multivariate analyses, diabetes but not HCV infection was independently related to serum ferritin concentrations. CONCLUSIONS: Diabetes rather than HCV infection itself is the main factor associated with the increased ferritin levels detected in patients with HCV infection. Therefore, the presence of diabetes should be taken into account when iron metabolism is evaluated in HCV-infected patients.

Sporadic cases of acute autochthonous hepatitis E in Spain.

BACKGROUND/AIMS: In industrialized countries hepatitis E virus (HEV) infection is rare and its diagnosis is difficult because the utility of available tests is not well established. METHODS: We studied the presence of acute HEV infection markers in a cluster of 11 cases of acute hepatitis with IgG anti-HEV antibodies. RESULTS: Three cases were confirmed as acute hepatitis E and 8 as presumptive hepatitis E, two as a past HEV infection and one could not be determined. Three different HEV strains were identified in serum from 3 patients. Two strains belonged to genotype 3, the predominant genotype found in local urban sewage and the other strain belonged to genotype 1 and was considered an imported strain. CONCLUSIONS: Our findings demonstrate the presence of some autochthonous, sporadic acute hepatitis E cases as well as an imported case in our area and the transitory nature of virological and serological markers for HEV.

High prevalence of glucose abnormalities in patients with hepatitis C virus infection: a multivariate analysis considering the liver injury.

OBJECTIVE: The aim of this study was to compare the prevalence of both impaired fasting glucose (IFG) and diabetes between hepatitis C virus (HCV)-infected patients and patients with other liver diseases but anti-HCV-, taking into account the degree of liver damage. RESEARCH DESIGN AND METHODS: A total of 642 consecutive patients attending the outpatient liver unit of a university hospital (498 anti-HCV+ and 144 anti-HCV-) were prospectively recruited. Patients were classified as having chronic hepatitis (n = 472) or cirrhosis (n = 170) by means of the result of either a liver biopsy or by typical clinical features. A logistic regression model was used to determine independent associations of covariates (age, sex, BMI, HCV antibody status, and triglycerides) with the presence of glucose abnormalities. RESULTS: A threefold increase in the prevalence of glucose abnormalities was observed in HCV+ patients with chronic hepatitis in comparison with HCV- subjects (32 vs. 12%; P = 0.0003). In contrast, among patients with cirrhosis, although both diabetes and IFG were more prevalent in anti-HCV+ patients (40%) than in anti-HCV- patients (36%), the differences were not statistically significant. Finally, the logistic regression analysis showed that HCV infection was independently related to glucose abnormalities in those patients with chronic hepatitis (odds ratio 4.26 [95% CI 2.03-8.93]). In contrast, HCV was not an independent predictor of glucose abnormalities in cirrhotic patients. CONCLUSIONS: The high prevalence of IFG and diabetes found in HCV-infected patients observed in our study suggests that screening for glucose abnormalities should be indicated in these patients. In addition, we provide evidence that the genuine connection between HCV infection and diabetes is initiated at early stages of hepatic disease.

Hepatitis E virus epidemiology in industrialized countries.

To determine the prevalence of Hepatitis E virus (HEV) in industrialized nations, we analyzed the excretion of HEV strains by the populations of Spain, France, Greece, Sweden, and the United States. Twenty of 46 (43.5%) urban sewage samples collected in Barcelona from 1994 to 2002 tested positive for HEV. We identified 15 HEV strains, which were similar to two HEV isolates previously described in Barcelona in clinical samples and to strains from diverse geographic HEV-nonendemic areas. We also identified two HEV strains in sewage samples from Washington, D.C., and Nancy, France; these samples were also positive for Hepatitis A virus. In addition, we studied the role of pigs as a reservoir for HEV and identified one new swine HEV strain. Our results suggest that HEV may be more prevalent than previously considered in industrialized countries and that variants of the virus circulate simultaneously in one region.

[Prevalence of hepatitis B and hepatitis C viruses in different counties of Catalonia, Spain: cross-sectional study]. / Prevalencia de las hepatitis B y C en diversas comarcas de Cataluña: estudio transversal.

BACKGROUND: There are few data available in our community regarding the prevalence of hepatitis B (HBV) and hepatitis C (HCV) virus infection in the general population. MATERIAL AND METHOD: The aim of this study was to determine the prevalence and serologic characteristics of HBV and HCV in Catalonia. For this purpose, HBsAg and anti-HCV were assessed in serum aliquots obtained from a sample of 2194 individuals, who were chosen at random out from different Catalonian counties. In those cases in which any of the markers were positive, the following analyses were performed afterwards: serum transaminases, HBV-DNA detection by PCR (in HBsAg positives) and HCV-RNA detection by PCR and genotypes (in antiHCV positives). All subjects yielding positive results were interviewed in order to determine possible risk factors. RESULTS: HBV prevalence was 1.69% (95% CI, 1.62-1.76) and that of HCV was 2.64% (95% CI, 2.53-2.75). HCV prevalence increased with age (1.7% in younger than 50 years and 3.6% in older than 50 years, p < 0.01), but not that of HBV. Only a small proportion (12.1%) of HBV carriers had detectable HBV-DNA levels. On the contrary, quite an important proportion of HCV carriers (68.6%) had detectable HCV-RNA levels. Predominant HCV genotype was 1 (79.3%). Transaminases levels were within normal limits in many HBV and HCV carriers (70.9 and 60%, respectively). CONCLUSIONS: Prevalence of HBV and HCV in Catalonia was 1.69% and 2.64%, respectively. Most HCV carriers had positive serum HCV-RNA, whereas serum HBV-DNA was negative in most HBV carriers

Prevalencia de las hepatitis B y C en diversas comarcas de Cataluña: estudio transversal / Prevalence of hepatitis B and hepatitis C viruses in different counties of Catalonia, Spain: cross-sectional study

FUNDAMENTO: Existen pocos estudios sobre la prevalencia de las infecciones por los virus de la hepatitis B (VHB) y C (VHC) en nuestro medio. MATERIAL Y MÉTODO: Para conocer la prevalencia y las características serológicas del VHB y el VHC se han determinado HBsAg y anti-VHC en alícuotas de suero de una muestra aleatoria, estratificada a partir de las listas censales, de 2.194 individuos de diversas comarcas de Cataluña. En los casos en que resultó positivo alguno de los marcadores se determinaron transaminasas séricas, ADN-VHB (PCR) (en HBsAg+) y genotipos (DIA@) y ARN-VHC (PCR) (en anti-VHC+). Los sujetos positivos fueron entrevistados con el fin de conocer los factores de riesgo. RESULTADOS: La prevalencia del VHB fue del 1,69 per cent (IC del 95 per cent, 1,62-1,76), y del VHC del 2,64 per cent (IC del 95 per cent, 2,53-2,75). La prevalencia del VHC aumentó con la edad (1,7 per cent y 3,6 per cent en los menores y mayores de 50 años, respectivamente; p < 0,01), no así la prevalencia de VHB. Sólo una pequeña parte (12,1 per cent) de los individuos positivos para el VHB presentó valores detectables de ADN-VHB. Por el contrario, una parte importante de los positivos para el VHC (68,6 per cent) presentó cifras detectables de ARN-VHC. El genotipo del VHC más frecuente en la población estudiada fue el 1 (79,3 per cent). Las concentraciones de transaminasas fueron normales en la mayoría de los portadores del VHB y VHC (70,9 y 60 per cent, respectivamente). CONCLUSIONES: La prevalencia del VHC en las poblaciones estudiadas de Cataluña es del 2,64 per cent, y en la mayoría de los casos cursa con ARN-VHC sérico positivo. Por el contrario, en la mayoría de los portadores del VHB (1,69 per cent) el ADN-VHB sérico es negativo (AU)

Genetic analysis of hepatitis A virus strains recovered from the environment and from patients with acute hepatitis.

The molecular epidemiology of hepatitis A virus (HAV) was studied by analysing HAV strains recovered from environmental water samples over a 7 year period and strains recovered from patients with acute hepatitis over a 5 year period. A total of 54 samples of raw domestic sewage and 66 samples of river water were collected. HAV particles were concentrated and detected by nested RT-PCR. HAV infection in patients with acute hepatitis was serologically diagnosed in 26 of 74 serum samples, which were also analysed by nested RT-PCR. HAV RNA was detected in 57.4% of sewage samples, 39.2% of Llobregat river water samples, 20% of Ter river water samples and 61.6% of serum samples. The HAV genomes detected were characterized further by directly sequencing a region of the 5' non-translated region, the VP1/2A junction region and, in some samples, the 2B region. Results showed a 95% prevalence of genotype I, with nearly 50% being either subgenotype IA or subgenotype IB. Various strains were found simultaneously in both environmental and clinical samples. These strains were closely related to those described in distant geographical areas. Genotype IIIA was also found in 5% of sewage samples and in 12.5% of serum samples. Strains belonging to a common endemic genotype were not identified. The abundance of HAV in the environment produces a situation of sanitary risk, especially considering the low prevalence of antibodies in the young population.