Changes in the response to treatment against chronic hepatitis C between 1999 and 2015: data from a prospective cohort.

BACKGROUND: The drug options and strategies for treatment against hepatitis C virus (HCV) infection have changed considerably in the last few years. The aim of this study was to compare the changes in the proportion of nonresponders and patients who achieved a sustained virologic response (SVR) from 1999 to 2015 in one single cohort. PATIENTS AND METHODS: A total of 522 patients treated against chronic hepatitis C were included prospectively. The time periods were 1999-2002 [interferon (IFN)/ribavirin (RBV)], 2002-2009 (pegylated-IFN/RBV), 2010-2011 (use of IL28B genotype), 2012-2014 (pegylated-IFN/RBV/direct-acting antivirals) and 2015 (IFN-free direct-acting antiviral-based therapy). RESULTS: The numbers of nonresponders in the study periods in chronological order were as follows: 14 (40%), 76 (21.3%), 7 (8%), 10 (13%), and 0; P=1.1×10 and r=0.837. The corresponding numbers of patients who achieved SVR were 9 (25.7%), 14 (40.9%), 44 (50.6%), 51 (66.2%), and 64 (90.1%), P=3.3×10 and r=0.997. Characteristics that may impair SVR, such as advanced fibrosis, genotype 1 infection, HIV coinfection, or treatment experience, did not decrease in the last time periods. CONCLUSION: The proportion of nonresponders was significantly reduced using the IL28B genotype as a predictive tool and direct-acting antivirals further improved treatment outcome. Concomitantly, the rates of SVR showed a linear increase.

Liver Toxicity of Current Antiretroviral Regimens in HIV-Infected Patients with Chronic Viral Hepatitis in a Real-Life Setting: The HEPAVIR SEG-HEP Cohort.

OBJECTIVE: To assess the current frequency of ART-associated grade 3-4 transaminase elevations (TE) and grade 4 total bilirubin elevations (TBE) in HIV-infected patients with chronic hepatitis B and/or C, who start a new regimen of ART. PATIENTS AND METHODS: A total of 192 pre-treated or treatment-naive HIV infected patients with HBV and/or HCV-coinfection who started ART in eight Southern Spanish centers from July/2011-December/2013, were followed for 12 months in this prospective study. RESULTS: Forty-one (21.4%) subjects had been naïve to ART, median (IQR) follow-up was 11.6 (5.6-12.9) months. The most frequently initiated NRTI were tenofovir/emtricitabine [49 patients (25.5%)]. Eighty-nine (46.4%) patients started a ritonavir-boosted protease inhibitor and 77 (40.1%) individuals a NNRTI. Raltegravir and maraviroc were initiated in 24 (12.5%) and 9 (4.7%) individuals. Ten [5.21%; 95% confidence interval (CI): 2.53%-9.37%] patients presented grade 3 TE, while 8 (4.17%; 95%CI: 1.82%-8.04%) subjects showed grade 4 TBE. No episodes of grade 4 TE or ART discontinuation due to hepatotoxic events were observed. The use of ritonavir-boosted atazanavir was the only independent predictor for grade 4 TBE [adjusted odds ratio: 7.327 (95%CI: 1.417-37.89); p = 0.018] in an analysis adjusted for age, sex and baseline HIV-RNA levels, while no factor could be independently associated with grade 3-4 TE. CONCLUSIONS: Currently, the frequency of severe ART-associated TE and TBE under real-life conditions in patients with chronic viral hepatitis is similar to what has been reported previously. However, episodes of grade 4 TE are less frequent and severe TE appears to be of lesser concern.

Impact of IL28B genotype on first-week response to telaprevir-based therapy in HIV-HCV coinfection.

BACKGROUND: IL28B genotype predicts response to treatment against HCV with pegylated interferon/ribavirin (PR) and impacts on the outcome of therapy including telaprevir (TVR). This study aimed to determine the influence of the favourable IL28B genotype on early viral kinetics during therapy with TVR/PR in HIV-HCV-coinfected patients. METHODS: All HIV-HCV genotype 1 coinfected subjects who received TVR/PR for at least 4 weeks were included from populations prospectively followed in 22 centres throughout Germany, Switzerland and Spain. RESULTS: Of the 129 subjects included, 38 (29.5%) presented with IL28B genotype CC and 94 (72.9%) were treatment-experienced. A total of 96 (73.8%) patients showed undetectable plasma HCV RNA at treatment week (W)4: 30 (78.9%) of the IL28B-CC carriers and 65 (71.4%) of the non-CC carriers (P=0.377). Among treatment-naive patients, proportions of undetectable HCV RNA among IL28B-CC versus non-CC carriers were 8/9 (88.9%) versus 3/9 (33.3%; P=0.016) and 14/17 (82.4%) versus 11/18 (61.1%; P=0.164) at W2 and W4. The decrease of HCV RNA at W2 and W4 was similar among the IL28B carriers. CONCLUSIONS: IL28B genotype does not predict W4 response to TVR/PR in HIV-HCV-coinfected patients, regardless of their treatment history. However, there is evidence of an impact on response during the first weeks in treatment-naive patients.

Reassessment of genotype 1 hepatitis C virus subtype misclassification by LiPA 2.0: implications for direct-acting antiviral treatment.

The accuracy of LiPA 2.0 for hepatitis C virus 1 (HCV-1) subtype classification was analyzed. LiPA 2.0 genotype results from 101 HCV-1-infected patients were compared to genotype findings determined by direct core sequencing. Eleven (11%) samples were misclassified. Given the influence of the HCV-1-subtype in the anti-HCV therapy response, an alternative classification method is warranted.

A 24-week treatment strategy with pegylated interferon/ribavirin in HIV/hepatitis C virus genotype 3-coinfected patients who achieved a rapid virologic response results in a high sustained virologic response rate.

We designed a study to evaluate the efficacy of a 24-week treatment strategy in HIV/hepatitis C virus (HCV) genotype 3-coinfected patients achieving rapid virologic response for a first HCV treatment with pegylated interferon plus ribavirin (peg-IFN/RBV). Our results suggest that a shorter course of peg-IFN/RBV therapy may be sufficient in this population.

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

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.

Pegylated interferon plus ribavirin is suboptimal in IL28B CC carriers without rapid response.

OBJECTIVE: Some experts consider that hepatitis C virus (HCV) genotype 1-infected patients harboring IL28B genotype CC should be treated with interferon (Peg-IFN) plus ribavirin (RBV). This study aimed to assess the rate of sustained virological response (SVR) in these subjects, according to whether they achieve rapid virological response (RVR) or not. METHODS: Prospective cohort study conducted at the Infectious Diseases Units of three Spanish hospitals. 220 treatment-naive, HCV genotype 1-infected patients, 160 of them HIV/HCV-coinfected, who initiated dual therapy with peg-IFN plus RBV were analyzed in an on-treatment approach. RESULTS: 29 (18%) HIV/HCV-coinfected and 14 (23%) HCV-monoinfected (p = 0.44) individuals developed RVR. In the overall population, 32 (39%) patients with IL28B genotype CC versus 11 (8%) bearing genotype non-CC achieved RVR (p < 0.0001). In HCV-monoinfected patients with IL28B genotype CC, SVR was observed in 12 (92%) of those who achieved RVR and in 3 (30%) of those who did not (p = 0.0018). The corresponding figures for HIV/HCV-coinfected individuals were 19 (100%) and 14 (35%), respectively (p < 0.0001). CONCLUSION: Treatment-naïve HCV-genotype 1-infected patients bearing favorable IL28B genotype should not be treated with dual therapy including Peg-IFN plus RBV if they do not achieve RVR. These subjects clearly represent candidates for more effective therapy with direct-acting antivirals. SUMMARY: Some experts consider that hepatitis C virus (HCV) genotype 1-infected patients harboring the favorable IL28B genotype CC should be treated with interferon plus ribavirin. However, patients harboring favorable IL28B genotype should not be considered likely responders to the same extent. This prospective cohort study conducted in 220 treatment-naive HCV-infected patients with or without HIV coinfection patients shows that among the IL28B CC carriers, while the subset of those patients who achieve negative plasma HCV-RNA after 4 weeks (rapid virological response, RVR) of dual therapy have a rate of sustained virological response near to 100%, those who do not present RVR show a response rate lower than 40%. Therefore, treatment-naïve HCV-genotype 1-infected patients bearing favorable IL28B genotype who do not achieve RVR should be considered candidates for more effective therapy with direct-acting antivirals like boceprevir or telaprevir.

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.

Benefits from sustained virologic response to pegylated interferon plus ribavirin in HIV/hepatitis C virus-coinfected patients with compensated cirrhosis.

BACKGROUND: The objective of this study was to determine the impact of sustained virologic response (SVR) to pegylated interferon (peg-IFN) plus ribavirin (RBV) on the incidence of liver-related complications and overall mortality in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS: We included in this prospective cohort study 166 coinfected patients with compensated cirrhosis, who received peg-IFN plus RBV, to assess the time from the starting date of HCV therapy to the first hepatic decompensation and death due to any cause. RESULTS: SVR was observed in 43 (25%) individuals. Two (4.6%) patients with SVR developed liver decompensation vs 33 (26.8%) individuals without SVR (P = .002). The incidence of liver-related complications was 0.89 cases per 100 person-years (95% confidence interval [CI], .11-3.1) in SVR patients and 6.4 cases per 100 person-years (95% CI, 4.5-8.9) in non-SVR patients. Factors independently associated with liver decompensation were non-SVR (hazard ratio [HR], 8.1; 95% CI, 1.08-61.5; P = .042) and MELD score ≥9 at baseline (HR, 2.9; 95% CI, 1.2-7.2; P = .016). Two (4.6%) patients with SVR died due to any cause compared with 22 (17.9%) individuals without SVR (P = .02). MELD score ≥9 (HR, 3.1; 95% CI, 1.3-7.7; P = .011) and non-SVR (HR, 8.0; 95% CI, 1.07-61; P = .043) were independently associated with overall mortality. CONCLUSIONS: The achievement of SVR following peg-IFN plus RBV markedly reduces the incidence of liver-related decompensation and the overall mortality in HIV/HCV-coinfected patients with compensated cirrhosis.

Short communication: atazanavir-based therapy is associated with higher hepatitis C viral load in HIV type 1-infected subjects with untreated hepatitis C.

We assessed the relationship between atazanavir (ATV)-based antiretroviral treatment (ART) and plasma hepatitis C virus (HCV) viral load in a population of HIV/HCV-coinfected patients. HIV/HCV-coinfected patients who received ART based on a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) were included. Patients were stratified by ART drug [ATV/rtv, lopinavir (LPV/rtv), efavirenz (EFV), nevirapine (NVP), and other PIs], HCV genotype (1/4 and 2/3), and IL28B genotype (CC and non-CC). The Kruskal-Wallis test and chi-squared test were used to compare continuous and categorical variables, respectively. Multivariate analysis consisted of a stepwise linear regression analysis. Six hundred and forty-nine HIV/HCV-coinfected patients were included. HCV genotype 1/4 patients who received ATV had higher HCV RNA levels [6.57 (5.9-6.8) log IU/ml] than those who received LPV [6.1 (5.5-6.5) log IU/ml], EFV [6.1 (5.6-6.4) log IU/ml], NVP [5.8 (5.5-5.9) log IU/ml], or other PIs [6.1 (5.7-6.4) log IU/ml] (p=0.014). This association held for the IL28B genotype (CC versus non-CC). The association was not found in patients carrying HCV genotypes 2/3. The linear regression model identified the IL28B genotype and ATV use as independent factors associated with HCV RNA levels. ATV-based therapy may be associated with a higher HCV RNA viral load in HIV/HCV-coinfected patients.

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)

Response to pegylated interferon plus ribavirin among HIV/hepatitis C virus-coinfected patients with compensated liver cirrhosis.

BACKGROUND: The objective of this study was to determine the efficacy of pegylated interferon (peg-IFN) plus ribavirin (RBV) in human immunodeficiency virus (HIV)-infected patients with hepatitis C virus (HCV)-related compensated liver cirrhosis, as well as the predictors of response in these individuals. METHODS: All subjects enrolled in a prospective cohort of 841 HIV/HCV-coinfected patients who received peg-IFN and RBV and who had a liver biopsy or a liver stiffness measurement within the year before starting peg-IFN plus RBV were included in this study. The sustained virologic response (SVR) rate and predictors of SVR response were analyzed. RESULTS: A total of 629 patients were included in this study; 175 (28%) had cirrhosis. In an intention-to-treat analysis, 44 (25%) patients with cirrhosis and 177 (39%) without cirrhosis achieved SVR (P = .001). Among patients with cirrhosis, SVR was observed in 14%, 47%, and 30% of individuals with HCV genotypes 1, 2-3, and 4, respectively. Discontinuation of therapy owing to adverse events was observed in 30 (17%) individuals with cirrhosis and 37 (8%) subjects without cirrhosis (P = .001). CONCLUSIONS: The efficacy of peg-IFN plus RBV among HIV/HCV-coinfected patients with cirrhosis is lower than in those without cirrhosis, although this antiviral combination still leads to a substantial rate of SVR in those carrying HCV genotype 3. A higher rate of discontinuations of HCV therapy due to adverse events among cirrhotic patients could partially explain the differences in the SVR rate between both populations.

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.

Hepatitis C virus genotype 4 responds better to pegylated interferon with ribavirin than genotype 1 in HIV-infected patients.

We assess the efficacy of pegylated interferon (peg-IFN) with ribavirin (RBV) and the predictors of sustained virological response (SVR) among HIV/hepatitis C virus genotype 4 (HCV-4)-coinfected patients. Thirty-nine (31.5%) of 124 individuals with HCV-4 achieved SVR compared with 103 (22.7%) of 453 individuals with HCV genotype 1 (P=0.046). Only interleukin-28B (IL28B) genotype CC was independently associated with SVR in HIV/HCV-4-coinfected patients. The efficacy of peg-IFN with RBV in coinfected individuals with genotype 4 is significantly higher than in those with genotype 1. IL28B CC genotype is the main predictor of response in this population.

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

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 cross-sectional study. RESULTS: A total of 520 patients were included. Three hundred and fifty-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.