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.

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 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.

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.

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.

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.

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.

[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.

Twelve week post-treatment follow-up predicts sustained virological response to pegylated interferon and ribavirin therapy in HIV/hepatitis C virus co-infected patients.

OBJECTIVES: The aim of this study was to evaluate whether the assessment of hepatitis C virus (HCV) RNA serum at 12 weeks after the end of treatment (W12) was as informative as after 24 weeks (W24) for determining sustained virological response (SVR) in HIV/HCV co-infected patients who received a combination of pegylated interferon (PEG-INF) plus ribavirin (PEG-INF/RBV) and had a virological response at the end of treatment. METHODS: Treatment-naive HIV/HCV patients were included in this prospective study if they had completed a full course of therapy with PEG-INF/RBV, had an undetectable serum HCV RNA at the end of treatment and complied with the W12 and W24 schedule for determining HCV RNA. HCV RNA levels were measured using a quantitative PCR assay (detection limit = 15 IU/mL). Positive predictive value (PPV) was defined as the probability of an undetectable serum HCV RNA at W12 and W24 after the end of treatment. RESULTS: Of 186 patients treated during the study period, 104 (55.9%) were included in the study. At W24, 83 (79.8%) patients had an SVR and 21 (20.2%) had a virological relapse. At W12, HCV RNA was undetectable in 83 (79.8%) patients and all of these had SVR. Undetectable HCV RNA at W12 had a 100% PPV [95% confidence interval (CI) 96.5%-100%] for SVR. CONCLUSIONS: Our results show that undetectable HCV RNA at W12 post-treatment has a high PPV for SVR. Testing for HCV RNA at this moment may therefore be considered an appropriate point in time for identifying SVR and relapse in HIV/HCV co-infected patients receiving treatment with PEG-INF/RBV.

Liver toxicity associated with antiretroviral therapy including efavirenz or ritonavir-boosted protease inhibitors in a cohort of HIV/hepatitis C virus co-infected patients.

OBJECTIVES: To compare the frequency of grade 3 or 4 transaminase elevations (TEs) in HIV/hepatitis C virus (HCV) co-infected patients who started a three-antiretroviral drug regimen including efavirenz or a ritonavir-boosted protease inhibitor (PI/r) and the influence of pre-existing significant hepatic fibrosis or cirrhosis. PATIENTS AND METHODS: All pre-treated or treatment-naive HIV/HCV co-infected patients who started an antiretroviral regimen including two nucleos(t)ide reverse transcriptase inhibitors along with efavirenz or a PI/r in seven Spanish centres from January 2007 to December 2009 were included in this prospective study. RESULTS: Of 262 patients included in this study, 76 (29%) individuals began antiretroviral therapy (ART) including efavirenz and 186 (71%) a PI/r-based combination. The median (interquartile) follow-up was 14.0 (6.2-23.7) months. A total of 20 (7.6%) patients presented grade 3-4 TEs. Four (1.5%) subjects discontinued ART due to this adverse event. Grade 3-4 TEs were observed in 5 (6.6%) subjects receiving efavirenz and 15 (8.1%) treated with PI/r (P = 0.681). Three (6.5%) patients in the efavirenz group with significant fibrosis developed grade 3-4 TEs versus 2 (8.7%) without pre-existing significant fibrosis (P = 0.743). In the PI/r group, the corresponding figures were 10 (8.8%) and 5 (9.3%), respectively (P = 0.931). CONCLUSIONS: The frequency of grade 3-4 TEs associated with efavirenz-based ART combinations under clinical practice conditions is low and similar to that found in patients receiving PI/r currently used in HIV/HCV co-infected patients. The baseline fibrosis stage does not have an impact on the development of TEs caused by these antiretroviral drugs in this population.

Prediction of response to pegylated interferon plus ribavirin by IL28B gene variation in patients coinfected with HIV and hepatitis C virus.

BACKGROUND: Variation in the IL28B gene is associated with sustained virologic response (SVR) to pegylated interferon plus ribavirin in hepatitis C virus (HCV)-monoinfected patients with genotype 1. Data on other genotypes and on patients coinfected with human immunodeficiency virus (HIV) and HCV are more limited. We aimed to assess the predictive ability of variations in the single-nucleotide polymorphism rs12979860 for SVR in HIV/HCV-coinfected patients, regardless of HCV genotype. METHODS: The rs12979860 genotype was determined by polymerase chain reaction in 154 patients who had received therapy against HCV with pegylated interferon plus ribavirin. RESULTS: rs12979860 genotype was TT in 20 patients (13%), TC in 66 patients (43%), and CC in 68 patients (44%). Rates of SVR in patients with genotype CC and in those with genotype TC or TT, according to HCV genotype, were, respectively, 50% and 17% (P < .001) in patients with genotype 1, 80% and 25% (P = .027) in patients with genotype 4, and 93% and 77% (P = .115) in patients with genotype 3. The median (interquartile range) low-density lipoprotein cholesterol level in patients with rs12979860 CC was 89 mg/dL (73-120 mg/dL) versus 75 mg/dL (55-91 mg/dL) (P = .001) in those with TC or TT. Independent predictors of SVR were HCV genotype 2-3 (odds ratio [OR], 13.98; 95% confidence interval [CI], 4.87-40.1; P < .001), rs12979860 CC (OR, 5.05; 95% CI, 2.04-12.5; P < .001), baseline plasma HCV RNA load of < or =600,000 IU/mL (OR, 1.99; 95% CI, 1.18- 3.34; P = .009), and female sex (OR, 4.28; 95% CI, 1.08-16.96; P = .039). CONCLUSIONS: IL28B gene variations independently predict SVR in HIV/HCV-coinfected patients with HCV genotype 1 and non-genotype 1 HCV infection. The association between rs12979860 and plasma low-density lipoprotein cholesterol suggests that the system low-density lipoprotein ligand/receptor might be involved in the effect of this genotype.

Changes in liver stiffness in patients with chronic hepatitis C with and without HIV co-infection treated with pegylated interferon plus ribavirin.

OBJECTIVES: To evaluate the changes in liver stiffness measurement (LSM) in patients infected by hepatitis C virus (HCV) under pegylated interferon (Peg-IFN) plus ribavirin therapy. METHODS: One hundred and forty-three HCV-infected patients, of whom 97 (68%) were also carrying HIV, who started treatment with Peg-IFN/ribavirin were included in this prospective cohort study. The outcome variable of the study was the change in LSM between baseline and the scheduled date for evaluating sustained virological response (SVR). RESULTS: The median (Q1-Q3) LSM values at baseline and at the SVR assessment date were 8.1 (6.2-11.6) kPa and 6.8 (5.2-9.8) kPa (P<0.001), respectively. The median (Q1-Q3) decrease between both timepoints was -1 (-2.75, 0.3) kPa. The baseline LSM decreased ≥20% in 37 (46%) patients with SVR and in 19 (30%) without SVR (P=0.05). In the linear regression analysis, baseline LSM {beta [standard error (SE)] -0.712 (0.044), P=0.004}, alcohol intake ≥50 g/day [beta (SE) 0.202 (0.030), P=0.014] and achievement of SVR [beta (SE) -0.238 (0.026), P=0.029] were independently associated with changes in LSM. CONCLUSIONS: LSM decreases significantly among patients with chronic HCV infection who achieve SVR with Peg-IFN/ribavirin. These patients show a higher frequency of LSM reduction ≥20% at the date of SVR evaluation.

Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus.

UNLABELLED: A few studies have assessed the observed fibrosis progression between serial liver biopsies (LB) in human immunodeficiency virus (HIV) / hepatitis C virus (HCV)-coinfected patients. Approximately half of the patients progressed at least one fibrosis stage over a short period of time. The risk factors for this fast progression need clarification. Because of this, we evaluated the observed fibrosis progression rates of HIV/HCV-coinfected patients and the risk factors for accelerated progression. Overall, 135 HIV-infected patients with positive serum HCV RNA, without other possible causes of liver disease, who underwent two LB, separated at least by 1 year, were included in this retrospective cohort study. The median (Q1-Q3) time between both LBs was 3.3 (2.0-5.2) years. Patients showed the following changes in fibrosis stage: regression >or =1 stage: 23 (17%), no change: 52 (39%), progression 1 stage: 38 (28%), and progression > or =2 stages: 22 (16%). Seventeen (13%) patients had cirrhosis in the second biopsy. Factors independently associated with progression > or =1 stage were undetectable plasma HIV RNA during the follow-up (relative risk [RR] [95% confidence interval, 95% CI] 0.61 [0.39-0.93], P = 0.03), moderate-to-severe lobular necroinflammation (1.77 [1.16-2.7], P = 0.009), time between biopsies (1.11 [1.08-1.2], P = 0.01), and end of treatment response to anti-HCV therapy (0.41 [0.19-0.88], P = 0.02). CONCLUSION: Fibrosis progresses with high frequency in HIV/HCV-coinfected patients over a period of time of 3 years. Absent-to-mild lobular necroinflammation at baseline, achievement of response with anti-HCV treatment, and effective antiretroviral therapy are associated with slower fibrosis progression.

Efficacy and safety of pegylated interferon plus ribavirin in HIV and hepatitis C virus-coinfected patients with advanced immunosuppression.

BACKGROUND: The aim of this study was to assess the efficacy and safety of pegylated interferon (IFN) plus ribavirin (RBV) in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected patients with severe immunodeficiency in a clinical cohort. BACKGROUND. A total of 542 HIV-infected patients receiving treatment with pegylated IFN plus RBV from June 2001 through April 2007 were included in this study. The outcome variables were sustained virologic response (SVR) rate and the emergence of AIDS-defining events during HCV infection therapy. SVR rates among patients with a CD4 cell count 250 cells/mm(3). The association between SVR and potential predictors was analyzed. RESULTS: Ten (26%) of 39 individuals with a baseline CD4 cell count 250 cells/mm(3) and 198 (39%) of 503 with baseline CD4 cell counts >or=250 CD4 cells/mm(3) achieved SVR (P = .09). In a nested case-control study with populations matched at a 1:2 ratio, the SVR rate was 26% in the CD4 cell count 250 cells/mm(3) group and 32% in the CD4 cell count >250 cells/mm(3) group (P = .5). Baseline CD4 cell count (250 cells/mm(3) vs >250 cells/mm(3)) was not associated with SVR in the multivariate analysis. Two (5%) individuals in the CD4 cell count 250 cells/mm(3) group experienced opportunistic events during follow-up. In the CD4 cell count 250 cells/mm(3) group, severe hematological toxicity and pegylated IFN or RBV dosage reductions occurred in 16 (41%) and 12 (31%) patients, respectively. In the CD4 cell count >250 cells/mm(3) group, severe hematological toxicity and pegylated IFN or RBV dosage reductions occurred in 29% (P = .1) and 20% (P = .1) of patients, respectively. CONCLUSIONS: The efficacy of pegylated IFN plus RBV in HIV-HCV-coinfected patients with advanced immunosuppression is substantial and not significantly different to that observed in the overall coinfected population. HCV therapy is generally safe in the population of coinfected patients with advanced immunosuppression.

Insulin resistance is not a relevant predictor of sustained virological response to pegylated interferon plus ribavirin in HIV/HCV co-infected patients.

BACKGROUND/AIMS: To evaluate the possible influence of baseline insulin resistance in sustained virological response. METHODS: One hundred and fifty-five consecutive individuals from a multicentric cohort of HIV/HCV co-infected patients who underwent therapy with pegylated interferon plus ribavirin were included. The main outcome variable was sustained virological response, defined as undetectable plasma HCV RNA at week 24 after the end of the therapy. Insulin resistance was determined using the HOMA method. RESULTS: Sustained virological response was achieved in 55 (36%) patients. Forty-two (38%) patients with a HOMA lower than 4 developed sustained virological response vs 13 (29%) of those with a HOMA above 4 (p=0.27). Analyses restricted to patients harbouring genotype 1 or 4 showed similar rates of sustained virological response among patients with a HOMA below and above 4 [19 (27%) vs 7 (24%); p=0.8]. In the multivariate analysis, genotype 3 [AOR 9.26; 95% CI 3.03-28.30; p<0.0001], a baseline HCV viral load below 600.000IU/mL [AOR 2.97; 95% CI 1.03-8.57; p=0.04] and baseline LDL cholesterol above 100mg/dL [AOR 6.62; 95% CI 1.97-22.19; p=0.002] were independently associated with sustained virological response. CONCLUSIONS: Insulin resistance is not a relevant predictor of sustained virological response to pegylated interferon plus ribavirin in HIV/HCV co-infected patients.

Impact of observer experience on the reproducibility of transient elastometry in HIV/HCV co-infected patients.

BACKGROUND: Data on the influence of observer experience on transient elastometry (TE) in hepatitis C virus (HCV) infection are scarce, and there are no data on HCV/HIV co-infected patients. METHODS: TE determination was conducted by an experienced and an inexperienced observer in 93 patients who were divided into three groups according to the chronological order of their attendance. The interobserver variability of TE results was analyzed by the intraclass correlation index (ICC) and the interobserver agreement of the classification of significant fibrosis and cirrhosis by the kappa index. RESULTS: The overall ICC was 0.970 (95% confidence interval [CI] 0.954-0.980). For groups 1, 2, and 3, the ICCs were 0.952 (95% CI 0.901-0.977), 0.966 (95% CI 0.931-0.984), and 0.986 (95% CI 0.971-0.993), respectively. The kappa index for the classification of cirrhosis (cutoff value >or=14.6 kPa) for the three groups was 0.53, 1.00, and 0.91. The use of two cutoff points to exclude (<6 kPa) or diagnose significant fibrosis (>9 kPa) yielded a kappa index of 0.72, 1.00, and 1.00, respectively. CONCLUSIONS: In HIV/HCV co-infected patients, the concordance between an inexperienced and an experienced observer is acceptable after a short instruction period. To maximize this concordance, a training period of 60 measurements should be recommended.

[Non alcoholic steatosis in HIV infection]. / Esteatosis hepática no alcohólica en la infección por el virus de la inmunodeficiencia humana.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatosis (NASH) are common conditions in the setting of HIV infection, especially if HCV coinfection or metabolic syndrome's features are present. The factors that contribute to the progression of NAFLD to NASH and fibrosis are not completely known and the role of antiretroviral therapy is especially controversial. Although the natural history of NASH in the setting of HIV infection is unknown, it may emerge as one of the leading causes of liver disease over the long term in these patients. Liver biopsy is still the gold standard for the diagnosis of NASH. Indeed, although non-invasive techniques are promising tools for the diagnosis of NAFLD, they do not assess liver damage. There is no specific therapy for NASH in HIV infection, as the role of glitazones has not been evaluated in these patients.

Low response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C treated with abacavir.

BACKGROUND: There is little information about the influence of antiretroviral drugs on the antiviral activity of pegylated interferon (PEG-IFN) plus ribavirin (RBV) against hepatitis C virus (HCV). METHODS: All HIV-infected patients with chronic hepatitis C who received first-line PEG-IFN plus RBV were retrospectively analyzed. Only patients in whom virological stopping rules were applied and who did not change their antiretrovirals were chosen. Plasma RBV concentrations were measured at week 4. RESULTS: A total of 493 patients (78% males, mean age 41 years, 78% on antiretroviral therapy, mean CD4+ T-cell count 561 cells/microl) fit the study inclusion criteria. Mean baseline serum HCV RNA was 5.89 log10 IU/ml, 65% were infected by genotypes 1 or 4 and 40% had advanced liver fibrosis (Metavir F3F4). The overall rate of sustained virological response (SVR) was 38%. Factors associated with lack of SVR in the multivariate analyses (odds ratio [95% confidence interval], P-value) were higher baseline serum HCV RNA (2.42 per log10 IU/ml [1.31-4.46], 0.005), HCV genotypes 1 or 4 (5.95 [2.50-14.29], < 0.001) and lower RBV plasma trough concentrations (1.74 per microg/ml [1.15-2.63], 0.009). Interestingly, a trend was noticed for abacavir use (2.22 [0.91-5.40], 0.08), which become significant when only considering the subset of patients with RBV plasma levels < 2.3 microg/ml (7.63 [1.39-41.67], 0.02). CONCLUSIONS: The use of abacavir might interfere with the anti-HCV activity of PEG-IFN plus RBV. As both antivirals are guanosine analogues, an inhibitory competition between abacavir and RBV might explain this observation, which is more prominent in patients with lower RBV exposure.

Efficacy of pegylated interferon and ribavirin for retreatment of chronic HCV infection in HIV co-infected patients failing a previous standard interferon-based regimen.

BACKGROUND: Combination of pegylated interferon (Peg-IFN) and ribavirin is the standard treatment for HCV infection in HIV co-infected patients. However, data available on the efficacy of this therapy in co-infected patients who failed a former interferon-based regimen are limited. METHODS: We analysed the efficacy and safety of the Peg-IFN alfa-2a or alfa-2b plus ribavirin combination in a multicentre observational cohort study including 54 HCV/HIV co-infected patients who had failed to respond to or relapsed on interferon-based treatment. The primary efficacy endpoint was the proportion of patients who achieved a sustained virological response (SVR), defined as HCV RNA <50 IU/mL 24 weeks after completion of therapy. RESULTS: By intention-to-treat analysis, 30% of the patients achieved an SVR. Viral eradication by genotype was 18.9% (7/37) genotype 1; 57.1% (8/14) genotype 3 and 33.3% (1/3) genotype 4. The only independent predictor of SVR was genotype 3 (odds ratio: 5.3; 95% confidence interval: 1.4-19.8). Fourteen (38%) patients with genotype 1 had undetectable viral load at week 48 of treatment. Nevertheless, 50% of them relapsed during the follow-up period. Severe adverse events or progression of HIV infection did not occur during the study; however, 39% of the patients required Peg-IFN dose reduction because of intolerance or haematological toxicity. CONCLUSIONS: Combined Peg-IFN and ribavirin achieved a substantial rate of SVR in HCV/HIV co-infected patients who failed a prior standard interferon-based regimen. The decision to retreat any co-infected patient should be individual-based. More aggressive strategies may be necessary to avoid the high relapse rate observed among patients with genotype 1.

Efficacy of pegylated interferon plus ribavirin treatment in HIV/hepatitis C virus co-infected patients receiving abacavir plus lamivudine or tenofovir plus either lamivudine or emtricitabine as nucleoside analogue backbone.

OBJECTIVES: To compare the response to hepatitis C virus (HCV) therapy among human immunodeficiency virus (HIV)/HCV co-infected patients receiving a nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] backbone consisting of abacavir plus lamivudine with that observed in subjects who receive tenofovir plus lamivudine or emtricitabine. METHODS: A total of 256 subjects, enrolled in a cohort of 948 HIV-infected patients who received pegylated interferon and ribavirin from October 2001 to January 2006, were included in this study. All patients were taking one protease inhibitor or one non-nucleoside reverse transcriptase inhibitor and abacavir plus lamivudine or tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone during HCV therapy. Sustained virological response (SVR) rates in both backbone groups were compared. RESULTS: In an intention-to-treat analysis, 20 out of 70 (29%) individuals under abacavir and 83 out of 186 (45%) under tenofovir showed SVR (P = 0.02). N(t)RTI backbone containing tenofovir was an independent predictor of SVR in the multivariate analysis [adjusted odds ratio (95% CI), 2.6 (1.05-6.9); P = 0.03]. The association between abacavir use and lower SVR was chiefly seen in patients with plasma HCV-RNA load higher than 600 000 IU/mL and genotype 1 or 4. Among patients treated with ribavirin dose <13.2 mg/kg/day, 3 (20%) of those under abacavir versus 22 (52%) under tenofovir reached SVR (P = 0.03), whereas the rates were 31% and 38% (P = 0.4), respectively, in those receiving >/=13.2 mg/kg/day. CONCLUSIONS: HIV-infected patients who receive abacavir plus lamivudine respond worse to pegylated interferon plus ribavirin than those who are given tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone, especially in those receiving lower ribavirin doses.