High prevalence of antibodies against hepatitis E virus in HIV-infected patients with unexplained liver disease / Prevalencia elevada de anticuerpos frente al virus de la hepatitis E en pacientes infectados por el VIH con enfermedad hepática de origen incierto

OBJECTIVE: To look for evidence of hepatitis E virus (HEV) exposure in HIV-infected patients with unexplained elevations of liver stiffness (LS). METHODS: Case-control study conducted in 31 HIV-infected patients with unexplained elevations of LS and in 31 HIV-controls with normal LS, matched by age, sex and CD4 cell-counts. Serum HEV antibodies were tested by two ELISA procedures and by Immunoblot. We defined exposure to HEV as the detection of serum HEV antibodies by at least one of the two ELISA assays, provided that it was confirmed by Immunoblot. A real-time PCR RNA assay was conducted in all plasma samples to identify subjects with active HEV infection. RESULTS: Exposure to HEV was demonstrated, according to the criteria used in this study, in 9 (29%) of the cases, whereas it was shown in 5 (16%) of the controls (p = .3). Serum HEV RNA was detected in none of the controls and in only in one case. This patient had a documented chronic hepatitis E with progression to cirrhosis. CONCLUSIONS: HEV antibodies are frequently found in HIV-infected patients with unexplained liver disease

OBJETIVO: Evaluar la existencia de exposición previa al virus de la hepatitis E (VHE) en pacientes infectados por el VIH con elevaciones inexplicadas de rigidez hepatica (RH). MÉTODOS: Estudio caso-control realizado en 31 pacientes con infección por el VIH y elevaciones inexplicadas de RH y 31 controles infectados por el VIH con RH normal, apareados por edad, sexo y recuento de células CD4. Se investigó la presencia de anticuerpos en suero frente al VHE mediante dos técnicas de ELISA y por Inmunoblot. La exposición previa al VHE se definió como la detección de anticuerpos séricos mediante al menos una de las dos técnicas de ELISA que se confirmó posteriormente mediante Inmunoblot. En todos los pacientes se realizó una PCR en tiempo real para identificar a aquellos pacientes con infección activa por el VHE. RESULTADOS: Se demostró la presencia de exposición previa al VHE, de acuerdo a los criterios usados en el estudio, en 9 (29%) de los casos y en 5 (16%) de los controles (p = 0.3). La PCR en tiempo real confirmó la presencia de RNA del VHE en el suero de uno de los casos y en ninguno de los controles. Este paciente presentó una hepatitis crónica por VHE documentada con progresión a cirrosis. CONCLUSIONES: Los pacientes infectados por VIH con enfermedad hepática de origen inexplicado presentan una frecuencia elevada de anticuerpos frente al VHE

Cambios en la prevalencia y distribución genotípica de la coinfección por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana / Prevalence and genotype distribution changes in hepatitis C virus co-infection among human immunodeficiency virus-infected patients

INTRODUCCIÓN: La prevalencia de hepatitis C es menor en los nuevos casos de pacientes infectados por VIH en España. El uso creciente del tratamiento frente al VHC podría haber cambiado la distribución genotípica del VHC. El objetivo de este estudio fue analizar los cambios en la prevalencia de la coinfección por VHC y en la distribución genotípica del VHC en pacientes infectados por VIH. Métodos Estudio de prevalencia seriada. Se incluyeron todos los pacientes infectados por VIH que acudieron a las consultas de un hospital de Andalucía entre septiembre de 2008 y febrero de 2009 (primer periodo) y entre enero y junio de 2013 (segundo periodo).Resultados Se incluyeron 520 y 651 pacientes en el primer y segundo periodos, respectivamente. El factor de riesgo de infección por VHC en el primer y segundo periodo fue: UDVP 319 (61%) vs. 348 (53%); contacto heterosexual, 111 (21%) vs. 135 (21%); homosexual, 76 (15%) vs. 114 (22%) (p = 0,006). La prevalencia de anti-VHC por periodos fue del 69% vs. el 58% (p=<0,001), y la de ARN-VHC detectable fue 49% vs. 37% (p=<0,001). En ambos periodos, la distribución genotípica fue: 1, 137 (60%) vs. 138 (59%); 3, 45 (20%) vs. 42 (18%); 4, 42 (18%) vs. 47 (20%) (p = 0,881). CONCLUSIONES: La prevalencia de infección por el VHC ha disminuido en los pacientes infectados por VIH en nuestro medio, incluyendo tanto la exposición al virus como la infección activa, en los últimos 5 años. Sin embargo, la distribución de los genotipos del VHC no ha cambiado

BACKGROUND: The prevalence of hepatitisC is decreasing among new diagnoses of HIV/HCV coinfection in Spain. The increasing use of the HCV treatment could have changed the HCV genotype distribution. The aim of this study is to analyze changes in the prevalence of HCV coinfection and in HCV genotype distribution among HIV-infected patients. METHODS: A serial cross-sectional study was conducted that included all HIV-infected patients who attended the Outpatient Clinic of a hospital in Andalusia, between September 2008 and February 2009 (first period), and between January 2013 and June 2013 (second period). RESULTS: A total of 520 and 651 patients were included in the first and second period, respectively. The risk factors of HCV infection in the first vs. second period were: IDU, 319 (61%) vs. 348 (53%); heterosexual contact, 111 (21%) vs. 135 (21%); homosexual men, 76 (15%) vs. 114 (22%) (P=.006). The prevalence of HCV antibody per period was: 358 (69%) vs. 380 (58%) (P=<.001), and for the HCV-RNA was 255 (49%) vs. 240 (37%) (P=<.001). In both periods, the HCV genotype distribution was: 1, 137 (60%) vs. 138 (59%); 3, 45 (20%) vs. 42 (18%); 4, 42 (18%) vs. 47 (20%) (P=.881). CONCLUSIONS: The prevalence of HCV infection in HIV-infected patients has decreased in our area, including overall exposure to HCV virus and active infection during the last 5 years. However, the HCV genotype distribution has not changed

High hepatitis E virus seroprevalence with absence of chronic infection in HIV-infected patients.

BACKGROUND & AIMS: The seroprevalence of the hepatitis E virus (HEV) and its chronicity rate in the HIV-infected population has not been well established. As a result, the magnitude of this emerging disease in this population cannot be established. METHODS: Prospective study that included HIV-infected patients followed up between September 2012 and May 2013. All included patients were tested for anti-HEV IgG/IgM. In patients with confirmed anti-HEV IgG/IgM positivity, RT-PCR was performed. In patients where HEV RNA was amplified, a second RT-PCR assay was performed 6 months later to identify transient or chronic HEV infections. RESULTS: Eight hundred and ninety-four HIV-infected patients were enrolled in the study. Of these patients, 399 (44.6%) were monoinfected with HIV; 462 (51.6%) were co-infected with HIV/HCV; 12 (1.3%) were co-infected with HIV/HBV; and 21 (2.3%) were co-infected with HIV/HCV/HBV. In 88 patients, anti-HEV IgG/IgM was detected (seroprevalence: 9.8% [95% CI: 8.02%-11.9%]). In five patients (0.5%; 95% CI: 0.2%-1.2%), HEV RNA was detected; 5.7% (95% CI: 2.1%-12.1%) of the patients were anti-HEV IgG/IgM positive. None of these patients showed detectable HEV RNA six months later. CONCLUSION: HEV infection is frequent in HIV-infected patients but developing a chronic HEV infection may be considered an uncommon liver disease in this population.

High prevalence of antibodies against hepatitis E virus in HIV-infected patients with unexplained liver disease.

OBJECTIVE: To look for evidence of hepatitis E virus (HEV) exposure in HIV-infected patients with unexplained elevations of liver stiffness (LS). METHODS: Case-control study conducted in 31 HIV-infected patients with unexplained elevations of LS and in 31 HIV-controls with normal LS, matched by age, sex and CD4 cell-counts. Serum HEV antibodies were tested by two ELISA procedures and by Immunoblot. We defined exposure to HEV as the detection of serum HEV antibodies by at least one of the two ELISA assays, provided that it was confirmed by Immunoblot. A real-time PCR RNA assay was conducted in all plasma samples to identify subjects with active HEV infection. RESULTS: Exposure to HEV was demonstrated, according to the criteria used in this study, in 9 (29%) of the cases, whereas it was shown in 5 (16%) of the controls (p=.3). Serum HEV RNA was detected in none of the controls and in only in one case. This patient had a documented chronic hepatitis E with progression to cirrhosis. CONCLUSIONS: HEV antibodies are frequently found in HIV-infected patients with unexplained liver disease.

[Prevalence and genotype distribution changes in hepatitis C virus co-infection among human immunodeficiency virus-infected patients]. / Cambios en la prevalencia y distribución genotípica de la coinfección por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana.

BACKGROUND: The prevalence of hepatitisC is decreasing among new diagnoses of HIV/HCV coinfection in Spain. The increasing use of the HCV treatment could have changed the HCV genotype distribution. The aim of this study is to analyze changes in the prevalence of HCV coinfection and in HCV genotype distribution among HIV-infected patients. METHODS: A serial cross-sectional study was conducted that included all HIV-infected patients who attended the Outpatient Clinic of a hospital in Andalusia, between September 2008 and February 2009 (first period), and between January 2013 and June 2013 (second period). RESULTS: A total of 520 and 651 patients were included in the first and second period, respectively. The risk factors of HCV infection in the first vs. second period were: IDU, 319 (61%) vs. 348 (53%); heterosexual contact, 111 (21%) vs. 135 (21%); homosexual men, 76 (15%) vs. 114 (22%) (P=.006). The prevalence of HCV antibody per period was: 358 (69%) vs. 380 (58%) (P=<.001), and for the HCV-RNA was 255 (49%) vs. 240 (37%) (P=<.001). In both periods, the HCV genotype distribution was: 1, 137 (60%) vs. 138 (59%); 3, 45 (20%) vs. 42 (18%); 4, 42 (18%) vs. 47 (20%) (P=.881). CONCLUSIONS: The prevalence of HCV infection in HIV-infected patients has decreased in our area, including overall exposure to HCV virus and active infection during the last 5 years. However, the HCV genotype distribution has not changed.

Incidence and natural history of hepatitis E virus coinfection among HIV-infected patients.

OBJECTIVES: To know the prevalence, incidence and factors associated with hepatitis E virus (HEV) infection in HIV-infected individuals in Spain, as well as to provide information on the natural history of HIV/HEV coinfection. DESIGN: Prospective cohort study. METHODS: Serum HEV IgG antibodies were tested in 613 HIV-infected patients at baseline and 2 years thereafter. Positive samples were tested for HEV-RNA. In patients with seroconversion, changes in liver function tests, serum HEV IgM antibodies and HEV RNA in samples collected between the baseline and the final time points were analyzed. RESULTS: One hundred and sixty-one (26%) patients tested positive for serum HEV IgG antibodies at baseline. HEV exposure was more common in men than in women (28 vs. 18%; P = 0.022) and increased linearly with age: 16, 26 and 44% in younger than 40, from 40 to 49 and older than 50 years, respectively (P = 0.000002). One patient bore the serum HEV-RNA at baseline. Eighteen (4%) HEV-seronegative patients seroconverted during the follow-up. None of the factors predicted seroconversion. One patient with seroconversion developed acute hepatitis and four mild hypertransaminasemia without another apparent cause. No case of seroconversion evolved to chronic HEV infection. Seroreversion was detected in 19% of the HEV-seropositive patients at baseline. Patients with seroreversion showed more commonly CD4 cell counts below 500 cells/µl than those who remained seropositive (77 vs. 46%; P = 0.004). CONCLUSIONS: Exposure to HEV among HIV-infected patients in Spain is very common, and this increases with age. Evolution to chronic infection is extremely unusual. Most cases of acute HEV infection seem to be clinically and biochemically unexpressive, therefore going unnoticed.

Prevalence and factors associated with liver steatosis as measured by transient elastography with controlled attenuation parameter in HIV-infected patients.

OBJECTIVE: To assess the prevalence and factors associated with significant hepatic steatosis (SHS, steatosis involving ≥10% hepatocytes) in HIV-infected patients. DESIGN: A prospective, cross-sectional study. METHODS: Five hundred and five HIV-infected patients were included in this study. All patients underwent a transient elastography examination with the controlled attenuation parameter (CAP). SHS was defined using the previously identified CAP cut-off of 238 dB/m. We analysed the associations between SHS and demographics, metabolic data, coinfections and drug therapy. RESULTS: SHS was detected in 201 (40%) patients. Individuals with and without plasma HIV RNA of 50 copies/ml or less presented SHS in 168 (42%) and 33 (31%) cases, respectively (P = 0.030). Patients with SHS compared with those without SHS presented higher median (IQR) BMI [BMI, 25.6 (22.5-28) vs. 22.3 (20.3-24.2) kg/m; P < 10], DBP [79 (72-85) vs. 74 (68-81) mmHg; P = 0.0001], fasting plasma glucose [95 (87-106) vs. 91 (84-97) mg/dl; P = 0.002] and triglycerides [128 (92-189) vs. 109 (80-167) mg/dl; P = 0.002], and lower HDL cholesterol [44 (37-54) vs. 48 (40-59), mg/dl; P = 0.004]. In multivariate analysis, the only factor associated with SHS was BMI [per unit increase, adjusted odds ratio (95% confidence interval) 1.34 (1.22-1-47); P < 10]. CONCLUSION: SHS measured by CAP is highly prevalent among HIV-infected patients. High BMI is the main predictor of SHS in this setting.

A polymorphism linked to RRAS, SCAF1, IRF3 and BCL2L12 genes is associated with cirrhosis in hepatitis C virus carriers.

BACKGROUND & AIMS: Host genetic factors could play a primary role in determining risk for cirrhosis development in HCV-infected patients. The aims of this study were to discover new genetic variants associated with this trait and to replicate some associations formerly reported. METHODS: Three hundred and thirty-seven HCV carriers with available data about liver fibrosis status, who initiated treatment with pegylated interferon plus ribavirin, were included. Of them, 77 (22.85%) were cirrhotic. One hundred and forty-four SNPs from 40 genes related to cholesterol metabolism/transport, sustained viral response to HCV therapy, liver fibrosis, or immune response, were genotyped in all samples. Plink software was used to perform univariate association analyses. The results obtained were adjusted by other parameters related to cirrhosis using multivariate logistic regression models. RESULTS: Only the SNP rs12104272, linked to RRAS, SCAF1, IRF3 and BCL2L12 genes, was associated with cirrhosis. It was observed a higher proportion of rs12104272 A allele carriers in the non-cirrhotic group (60.63%) than in the cirrhotic group (38.15%) (adjusted OR = 0.36, 95% CI = 0.180-0.746, P = 0.006). This effect was stronger in the background of rs12979860 CC genotype of IL28B (adjusted OR = 0.069, 95% CI = 0.014-0.349, P = 0.001). CONCLUSION: The rs12104272 SNP could have clinical value to select those individuals at lower risk for cirrhosis development.

Sustained virological response to pegylated interferon plus ribavirin leads to normalization of liver stiffness in hepatitis C virus-infected patients / Respuesta viral sostenida con interferón pegilado y ribavirina conduce a la normalización de la rigidez hepática en pacientes infectados por el virus de la hepatitis C

INTRODUCTION: Pegylated interferon plus ribavirin (Peg-IFN/RBV) therapy leads to improvements in liver stiffness measurements (LSM) in hepatitis C virus (HCV)-infected patients. However, the rate of LSM return to normal values in response to Peg-IFN/RBV is unclear. Thus, our aim was to assess the probability and factors associated with LSM normalization in HCV-infected patients receiving Peg-IFN/RBV. METHODS: This prospective observational longitudinal study included 160 HCV-infected patients, 111 (69%) with human immunodeficiency virus and receiving Peg-IFN/RBV, with baseline LSM ≥ 7kPa. The outcome variable was LSM normalization, i.e. a stable decrease in LSM below 7kPa after starting Peg-IFN/RBV. RESULTS: After starting Peg-IFN/RBV, 56 [35%, 95% confidence interval (95% CI): 28-42%] patients showed LSM normalization. The probability of LSM normalization was 21% (95% CI: 13.2-32.4%) at 12 months, and 51.3% (95% CI: 39.9-63.9%) at 24 months after Peg-INF/RBV initiation for individuals with sustained virological response (SVR), and 8.3% (95% CI: 4-16.6%) at 12 months and 11.3% (95% CI: 6-20.7%) at 24 months for those without SVR (p < 0.001). For individuals with LSM ≥7kPa 24 weeks after the pre-planned end of treatment, LSM normalizations were only observed among those with SVR. Achievement of SVR [Hazard ratio (HR, 95% CI): 6.84 (3.39-13.81)] and lack of baseline cirrhosis [HR (95% CI): 4.17 (1.69-10)] were independently associated with LSM normalization after starting Peg-IFN/RBV. CONCLUSIONS: LSM normalizations during Peg-IFN/RBV treatment are more likely, and occur earlier among patients with SVR. In addition, LSM normalizations continue 24 weeks after the scheduled end of therapy, but only among individuals who reach SVR

INTRODUCCIÓN: El retorno de la rigidez hepática (RH) a valores normales en respuesta al tratamiento de la infección por hepatitis C (VHC) con Peg-IFN/RBV no está claro. Por ello, evaluamos la probabilidad y los factores asociados con la normalización de la RH en pacientes tratados con Peg-IFN/RBV. MÉTODOS: Se incluyeron 160 pacientes infectados por VHC en este estudio longitudinal prospectivo, 111 (69%) de ellos por el virus de la inmunodeficiencia humana, con RH basal ≥ 7kPa y que recibieron Peg-IFN/RBV. La variable principal fue la disminución estable de la RH < 7kPa. RESULTADOS: Después de iniciar Peg-IFN/RBV, 56 (35%; intervalo de confianza del 95% [IC 95%]: 28-42%) pacientes normalizaron la RH. La probabilidad de la normalización de la RH fue del 21% (IC 95%: 13,2-32,4%) 12 meses y del 51,3% (IC 95%: 39,9-63,9%) 24 meses después de iniciar Peg-IFN/RBV en los pacientes con respuesta viral sostenida (RVS), y del 8,3% (IC 95%: 4-16,6%) 12 meses y del 11,3% (IC 95%: 6-20,7%) 24 meses en los sin RVS (p < 0,001). La normalización de la RH en los pacientes con ≥ 7kPa 24 semanas después de finalizar el tratamiento se observó solo en aquellos con RVS. La RVS (hazard ratio [HR]: 6,84; IC 95%: 3,39-13,81) y la ausencia de cirrosis [HR (95%IC): 4.17 (1.69-10)] se asociaron independientemente con la normalización de la RH después de iniciar Peg-IFN/RBV. CONCLUSIONES: La normalización de la RH durante la terapia con Peg-IFN/RBV es más probable y ocurre más temprano en los pacientes con RVS; además, continúa 24 semanas después del fin de tratamiento, pero solo en aquellos con RVS

Incidence of liver damage of uncertain origin in HIV patients not co-infected with HCV/HBV.

BACKGROUND AND AIMS: Several studies have reported that a significant number of HIV patients not co-infected with HCV/HBV develop liver damage of uncertain origin (LDUO). The objective of our study was to evaluate the incidence of and risk factors for the development of LDUO in HIV infected patients not co-infected with HCV/HBV. METHODS: Prospective longitudinal study that included HIV-infected patients free of previous liver damage and viral hepatitis B or C co-infections. Patients were followed up at 6-monthly intervals. Liver stiffness was measured at each visit. Abnormal liver stiffness (ALS) was defined as a liver stiffness value greater than 7.2 kPa at two consecutive measurements. For patients who developed ALS, a protocol was followed to diagnose the cause of liver damage. Those patients who could not be diagnosed with any specific cause of liver disease were diagnosed as LDUO and liver biopsy was proposed. RESULTS: 210 patients matched the inclusion criteria and were included. 198 patients completed the study. After a median (Q1-Q3) follow-up of 18 (IQR 12-26) months, 21 patients (10.6%) developed ALS. Of these, fifteen patients were diagnosed as LDUO. The incidence of LDUO was 7.64 cases/100 patient-years. Histological studies were performed on ten (66.6%) patients and all showed liver steatosis. A higher HOMA-IR value and body mass index were independently associated with the development of LDUO. CONCLUSION: We found a high incidence of LDUO in HIV-infected patients associated with metabolic risk factors. The leading cause of LDUO in our study was non-alcoholic fatty liver disease.

Hepatitis C virus genotype 4 in Southern and Central Spain does not originate from recent foreign migration waves.

Hepatitis C virus genotype 4 (HCV-4) is highly prevalent in Spain, but the information on the molecular characterization of HCV-4 in this region is scarce. Due to this, the molecular characteristics and the evolution of HCV-4 infection in Seville were analyzed (Southern Spain) and compared them with samples from Madrid. HCV genotype was determined by LIPA 2.0 assay and confirmed by sequence analysis of NS5B. Phylogenetic tree was estimated by MEGA 5.10. Bayesian coalescent-based methods were used to estimate the substitution rate and the age of the most recent common ancestor (MRCA). In the phylogenetic analysis of 50 NS5B HCV-4 from Seville and 11 from Madrid, 2 clusters were distinguished: The first cluster (HCV-4a) included 48% of the sequences from Seville and 9% of sequences from Madrid. The second cluster included the remaining sequences belonging to HCV-4d. The mean estimated substitution rate was 2.39 × 10(-3) for HCV-4a and 1.81 × 10(-3) for HCV-4d for Seville and 2.32 × 10(-3) for HCV-4d from Madrid. The date for MRCA was estimated to be around 1981-1984 for HCV-4 from Seville. The dates for MRCA were dated before the recent flow of immigration in Spain. Therefore, the results presented in this study argues against the possibility of a foreign introduction of the HCV-4 from other regions with high prevalence, at least during the last two, decades in which there was a great flow of immigrants. Additionally, an unusual high prevalence of subtype 4a was observed in Seville.

Chronic hepatitis E in HIV patients: rapid progression to cirrhosis and response to oral ribavirin.

Chronic hepatitis E virus infection with rapid progression to cirrhosis is reported in 2 human immunodeficiency virus (HIV)-infected patients with severe immunosuppression. Monotherapy with ribavirin led to temporary viral response and marked improvement of liver damage. Chronic hepatitis E should be regarded as another opportunistic event within HIV infection.

Interobserver concordance in controlled attenuation parameter measurement, a novel tool for the assessment of hepatic steatosis on the basis of transient elastography.

BACKGROUND: The combination of transient elastometry with a controlled attenuation parameter (CAP) is available to evaluate hepatic steatosis (HS) along with liver stiffness. AIMS: To assess the concordance of CAP measurements between two independent observers in patients infected by HIV and/or hepatitis virus, as well as to determine the concordance of classification of the grade of HS using two cut-off values. MATERIALS AND METHODS: In a cross-sectional prospective study, CAP-enabled transient elastometry acquisitions were performed by two independent observers in patients with HIV or hepatitis virus infection. The interobserver concordance between the CAP examinations was assessed using the intraclass correlation coefficient and the concordance in the classification of patients in the grades of HS was characterized using the κ index. RESULTS: A total of 118 patients were included. Twenty (17%) patients were HIV monoinfected, 44 (37.3%) were hepatitis C virus monoinfected, and 52 (44%) had HIV/hepatitis C virus coinfection. The median (Q1-Q3) of the absolute difference of CAP values between the two observers was 20 (10-41) dB/m. The overall intraclass correlation coefficient was 0.84 (95% confidence interval: 0.77-0.88). The corresponding figures for liver stiffness measurements were 0.9 (0.4-2.6) kPa and 0.96 (95% confidence interval: 0.94-0.97). The κ indexes for the concordance of classification for the presence of HS, cut-off of 215 dB/m, and significant HS, cut-off of 252 dB/m, were 0.53 and 0.62, respectively. CONCLUSION: The determination of HS by means of CAP in HIV and/or hepatitis virus infection represents an observer-independent and easily performable method. However, the use of cut-off values for the classification of patients is suboptimal.

Sustained virological response to pegylated interferon plus ribavirin leads to normalization of liver stiffness in hepatitis C virus-infected patients.

INTRODUCTION: Pegylated interferon plus ribavirin (Peg-IFN/RBV) therapy leads to improvements in liver stiffness measurements (LSM) in hepatitis C virus (HCV)-infected patients. However, the rate of LSM return to normal values in response to Peg-IFN/RBV is unclear. Thus, our aim was to assess the probability and factors associated with LSM normalization in HCV-infected patients receiving Peg-IFN/RBV. METHODS: This prospective observational longitudinal study included 160 HCV-infected patients, 111 (69%) with human immunodeficiency virus and receiving Peg-IFN/RBV, with baseline LSM ≥ 7kPa. The outcome variable was LSM normalization, i.e. a stable decrease in LSM below 7kPa after starting Peg-IFN/RBV. RESULTS: After starting Peg-IFN/RBV, 56 [35%, 95% confidence interval (95% CI): 28-42%] patients showed LSM normalization. The probability of LSM normalization was 21% (95% CI: 13.2-32.4%) at 12 months, and 51.3% (95% CI: 39.9-63.9%) at 24 months after Peg-INF/RBV initiation for individuals with sustained virological response (SVR), and 8.3% (95% CI: 4-16.6%) at 12 months and 11.3% (95% CI: 6-20.7%) at 24 months for those without SVR (p<0.001). For individuals with LSM ≥ 7kPa 24 weeks after the pre-planned end of treatment, LSM normalizations were only observed among those with SVR. Achievement of SVR [Hazard ratio (HR, 95% CI): 6.84 (3.39-13.81)] and lack of baseline cirrhosis [HR (95% CI): 4.17 (1.69-10)] were independently associated with LSM normalization after starting Peg-IFN/RBV. CONCLUSIONS: LSM normalizations during Peg-IFN/RBV treatment are more likely, and occur earlier among patients with SVR. In addition, LSM normalizations continue 24 weeks after the scheduled end of therapy, but only among individuals who reach SVR.

Critical points in ethylcellulose matrices: influence of the polymer, drug and filler properties.

Percolation theory has been applied to study the drug release behaviour in multicomponent inert matrices containing ethylcellulose as a matrix forming polymer. Global influence of major formulation factors such as polymer viscosity, polymer particle size, drug and filler solubility and porosity of the tablets in drug release kinetics has been studied for the first time. Batches containing three viscosity grades of Ethocel™, microcrystalline cellulose (MCC) and lactose as fillers, a lubricant and flow aid mixture and three drugs with different solubility have been manufactured. For some batches, compression pressure was varied in order to obtain matrices with five levels of initial porosity. The behaviour of inert matrices was explained based on the percolation ranges of the main components of the formulation. The effect of the porosity percolation threshold was observed and the existence of a tricoherent drug-polymer-filler system is hypothesized.

Prevalencia de los marcadores de infección de los virus de las hepatitis en pacientes portadores del VIH en el sur de España / Prevalence of hepatitis virus infection markers in HIV-infected patients in Southern Spain

Objetivos Determinar en pacientes infectados por VIH: a) La prevalencia de infección activa por el virus de la hepatitis C (VHC) y el virus de la hepatitis B (VHB), así como de la exposición previa al virus de la hepatitis A (VHA), VHB y VHC. b) La proporción que han sido vacunados frente al VHA y/o VHB. c) La distribución genotípica del VHC y el porcentaje de pacientes que han iniciado tratamiento frente al VHC. Métodos Estudio prospectivo de corte transversal. Se incluyeron los pacientes infectados por VIH que acudieron a las consultas de enfermedades infecciosas de un hospital de Andalucía entre septiembre 2008 y febrero 2009.Resultados Se incluyeron 520 pacientes. Trescientos cincuenta y ocho (69%) enfermos presentaban anticuerpos del VHC positivo, mientras el 71% de ellos tenían ARN-VHC detectable. La distribución genotípica del VHC fue: 153 (62%) genotipo 1, 49 (20%) genotipo 3, y 45 (18%) genotipo 4. Ciento trece (36,5%) sujetos habían recibido tratamiento anti-VHC. La prevalencia de infección activa por VHB fue del 4,4%, mientras que la de exposición previa fue del 54,8%. Cuatrocientos treinta y siete (84%) enfermos presentaron anti-VHA positivo. El 25,6 y el 22,3% de los pacientes susceptibles habían sido vacunados frente al VHA y al VHB, respectivamente. Conclusiones La prevalencia actual de infección activa por VHC en los pacientes infectados por VIH sigue siendo elevada en nuestra área. La distribución genotípica del VHC no parece haber sufrido modificaciones notables. El número de pacientes susceptibles de ser vacunados frente al VHA y al VHB que reciben esta terapia preventiva es bajo (AU)

Objectives: To determine: (a) The prevalence of active infection by the hepatitis C virus (HCV) and hepatitis B virus (HBV) in HIV-infected patients, as well as previous exposure to hepatitis A virus (HAV), HBV and HCV. (b) The proportion of patients who have been vaccinated against HAV and/or HBV. (c) The HCV genotype distribution and the percentage of patients who have started treatment against HCV infection. Methods: All HIV-infected patients who attended the Infectious Diseases Unit of a tertiary care hospital in Southern Spain between September 2008 and February 2009 were included in a prospective crosssectional study Results: A total of 520 patients were included. Three hundred and flfty-eight (69%) patients had positive HCV antibody, while 71% of them showed detectable HCV-RNA. The HCV genotype distribution was: 153(62%) genotype 1, 49 (20%) genotype 3, and 45 (18%) genotype 4. One hundred and thirteen (36.5%) subjects had received treatment against HCV. The prevalence of active HBV infection was 4.4%, while the exposure to HBV was 54.8%. Four hundred and thirty-seven (84%) patients had positive markers of infection of HAV. Of the patients eligible to be vaccinated, 25.6% and 22.3% patients were vaccinated against HAV and HBV, respectively. Conclusions: The current prevalence of active HCV infection remains high in our area. There were no changes in the HCV genotype distribution. The number of patients with indication for HBV and HAV vaccination and receive these vaccines is low (AU)

HIV-coinfection leads to a modest increase in plasma HCV-RNA load in patients with chronic HCV infection.

The influence of HIV coinfection on plasma hepatitis C virus (HCV) RNA load has not been reliably evaluated. We analyzed plasma HCV RNA load in 396 HCV-monoinfected and 467 HIV/HCV-coinfected patients. Median HCV RNA concentrations (interquartile range) in HCV-monoinfected patients were 5.88 (5.3-6.2) log(10)IU/mL versus 5.96 (5.6-6.5) log(10)IU/mL in HIV/HCV-coinfected individuals (p=0.033) as determined with the Cobas Amplicor Test and 6.06 (5.4-5.7) log(10)IU/mL versus 6.3 (5.5-6.9) log(10)IU/mL (p=0.026) using the Cobas TaqMan System. The plasma HCV RNA load in patients with HIV infection and undetectable plasmatic HIV RNA was similar to that observed in HCV-monoinfected individuals [6.02 (5.45-6.61) log(10)IU/mL versus 6.01 (5.36-6.59) log(10)IU/mL, respectively (p=1.0)]. In conclusion, HIV coinfection tends to be associated with higher plasma HCV RNA load, however, the magnitude of the differences is small and this effect can be counterbalanced with antiviral therapy.

Low prevalence of occult HBV infection among HIV-infected patients in southern Spain

Introduction: The aim of this study was to assess the prevalence of occult HBV infection in HIV-positive patients in a centre in Southern Spain. Methods: The HBV serological markers were investigated in all the patients and the presence of HBV-DNA was tested by PCR in patients with isolated anti-HBc. Results: An isolated anti-HBc pattern was detected in 144/520 (27.7%) patients. HBV-DNA was detected in one of these patients (0.7%).Conclusions: In Southern Spain, there is a low prevalence of occult HBV infection among HIV-infected patients, despite increasing immigration from endemic countries (AU)

Introducción: El objetivo de este estudio fue evaluar la prevalencia de infección oculta por VHB en pacientes infectados por VIH del sur de España. Métodos: Se investigaron los marcadores serológicos para VHB y se analizó la presencia de ADN-VHB en los anti-HBc "solo". Resultados: El patrón anti-HBc "solo" fue detectado en 144/520 (27,7%) pacientes. El ADN-VHB fue detectado en un paciente (0,7%).Conclusiones: La prevalencia de infección oculta por VHB es baja entre los pacientes infectados por VIH a pesar del aumento en la inmigración desde países endémicos (AU)

No influence of antiretroviral therapy on the mutation rate of the HCV NS5B polymerase in HIV/HCV-coinfected patients.

OBJECTIVES: To assess the impact of antiretroviral treatment (ART), including nucleoside analogues retrotranscriptase inhibitors (NRTIs), on the mutation rate of hepatitis C virus (HCV) NS5B polymerase and on the ratio of substitution at synonymous and nonsynonymous sites (dN/dS) this polymerase in HIV/HCV-coinfected patients. PATIENTS AND METHODS: Sixty-one patients on defined ART were included in this study. The NS5B polymerase of HCV was sequenced at baseline and after at least two years of ART. The mutation rate and the dN/dS were calculated at both times. RESULTS: The NS5B gene from forty-nine (80.3%) patients including; 19 HCV-1a (38.8%), 13 HCV-1b (26.5%), 8 HCV-3a (16.3%) and 9 HCV-4d (18.4%), could be sequenced. Thirty-two (65.3%) patients received non-nucleoside analogues and 41 (83.7%) received protease inhibitor. The mean estimated substitution rates at baseline and at the end of follow-up were from 1.38 to 3.5×10(-3)substitution/site/year (s/s/y) and from 1.39 to 3.18×10(-3)s/s/y, respectively, varying according to HCV genotype. All HCV genotypes at baseline and the end time point had values of dN/dS <1. At the end of follow-up, most of sites experienced negative selection and positive selection occurred only in a few sites. CONCLUSION: The mutation rate of NS5B in HIV/HCV-coinfected patients is within the range previously reported in studies in HCV-monoinfected patients. Additionally, the use of ART, including NRTIs, in these patients does not affect neither mutation rate nor the dN/dS of the HCV NS5B protein, suggesting that its use would not generate new resistance mutants to the polymerase inhibitors of HCV.