Hepatitis: Vispo E

Tuma P, Vispo E, Barreiro P, Soriano V. · Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, España. · Enferm Infecc Microbiol Clin. · Pubmed #19195436 links to  free full text

Abstract: Chronic hepatitis C virus (HCV) infection is common in HIV-infected individuals, especially if the route of infection is intravenous (e.g. intravenous drug use or blood transfusion). Prognosis is poorer in patients with HCV and HIV coinfection than in those with HCV monoinfection, mainly due to the immunodepression caused by HIV infection and probably also to a direct effect of HIV on the liver. Moreover, although antiretroviral therapy can cause liver damage, there is little doubt about the net benefits obtained with triple therapy in coinfected individuals, since suppression of HIV replication and immune recovery help to halt liver damage. However, not all antiretroviral agents are equal and those with the lowest hepatotoxicity and best metabolic profile should be used in coinfected patients, since hepatic steatosis accelerates progression of hepatic fibrosis and insulin resistance hampers the success of treatment with interferon and ribavirin. Tenofovir is currently one of the safest nucleos(t)ide analogues, due to its low hepatotoxicity and its lack of negative interference on treatment of HCV infection.

Soriano V, Vispo E, Bottecchia M, Sheldon J, Tuma P, Garcia-Samaniego J, Barreiro P. · Department of Infectious Diseases, Hospital Carlos III, Calle Sinesio Delgado 10, Madrid 28029, Spain. · Curr HIV/AIDS Rep. · Pubmed #18510894 No free full text.

Abstract: Chronic hepatitis B virus (HBV) infection is recognized in 5% to 10% of persons with HIV. Co-infected individuals show an accelerated course of HBV-associated liver disease with faster progression to cirrhosis. The number of anti-HBV drugs has increased in the past few years, and some agents (eg, lamivudine, emtricitabine, tenofovir) also exert activity against HIV-1. Emergence of drug resistance challenges the long-term benefit of anti-HBV monotherapy. Data derived from studies using new more potent anti-HBV drugs are very promising, and strategies to use these antiretrovirals sequentially or in combination are being developed. Appropriate diagnosis and monitoring of chronic hepatitis B, including the use of noninvasive tools for assessing liver fibrosis, measurement of serum HBV-DNA, and drug-resistance testing, along with wise use of antivirals may convert HBV/HIV co-infection in to a manageable disease. Hopefully, this success will translate into a halt of liver-related complications and death in the co-infected population.

Soriano V, Madejon A, Vispo E, Labarga P, Garcia-Samaniego J, Martin-Carbonero L, Sheldon J, Bottecchia M, Tuma P, Barreiro P. · Hospital Carlos III, Department of Infectious Diseases, Calle Sinesio Delgado 10, Madrid 28029, Spain. · Expert Opin Emerg Drugs. · Pubmed #18321145 No free full text.

Abstract: BACKGROUND: Chronic hepatitis C virus (HCV) infection remains a global health threat with approximately 200 million carriers worldwide. Current treatment consists of the use of peginterferon (pegIFN)/ribavirin (RBV) for 24 or 48 weeks depending on HCV genotype. Serious side effects and the fact that less than half of patients infected with HCV genotypes 1 and 4 (which are the most common) accomplish sustained virological response with this medication warrant the need for novel anti-HCV therapies. OBJECTIVE: Description of specifically targeted antiviral therapies for hepatitis C (STAT-C) designed to inhibit the serine protease and the RNA-dependent HCV-RNA polymerase. METHODS: Review of available data reported in peer-reviewed journals and medical conferences. RESULTS/CONCLUSIONS: Early preclinical studies using these compounds produced encouraging results, but the initial enthusiasm has been hampered by toxicity issues and rapid selection of resistance. Therefore, combination therapy with a backbone of pegIFN/RBV, or perhaps in the future using several of these small molecules, preferably having distinct modes of action and resistance profiles, will be required.

Soriano V, Barreiro P, Martin-Carbonero L, Vispo E, Garcia-Samaniego J, Labarga P, Gonzalez-Lahoz J. · Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. · AIDS Rev. · Pubmed #17694677 No free full text.

Abstract: Liver disease is currently the second leading cause of death in HIV-infected persons in Western countries. Hepatitis C virus infection accounts for the majority of cases of hepatic illness in this population. Although great progress has been made in the treatment of chronic hepatitis C in HIV-positive patients, many challenges still remain unsolved. The combination of pegylated interferon plus ribavirin is the current treatment of choice in hepatitis C virus/HIV-coinfected patients, regardless of hepatitis C virus genotype. However, the limited efficacy of this therapy in the HIV setting makes necessary the development of new strategies and/or drugs for the treatment of hepatitis C infection. Several anti-hepatitis C virus compounds are currently under investigation, although most are still in the early stages of clinical development. There is a relatively large group of patients who will be unable to be treated with the current hepatitis C virus medication based on interferon, mainly due to contraindications such as serious neuropsychiatric or cardiovascular history. However, for those without contraindications, treatment should be provided with no restrictions at the start (e.g. asking unnecessarily for a liver biopsy), and reassessed at weeks 4 and 12, considering virologic responses. Treatment should only be continued in early virologic responders. The use of standard doses of ribavirin (1000-1200 mg/day) and for at least 12 months seems crucial to maximize the effect of current hepatitis C treatment in the HIV setting, while no further benefit seems to derive from using higher than recommended pegylated interferon dosages. In patients with rapid virologic response (undetectable viremia at week 4) to anti-hepatitis C therapy, shorter periods of therapy (24 weeks) may be advisable in hepatitis C genotypes 2 and 3. Finally, adequate selection of candidates and careful selection of concomitant antiretroviral medications must be encouraged. Patients with low CD4 percentages (< 15%) should be deferred for treatment and HAART prioritized in order to improve CD4 counts. When possible, nucleoside analogs such as zidovudine, stavudine, and abacavir should be replaced by others having no deleterious interactions with ribavirin (e.g. tenofovir, lamivudine, or emtricitabine). Didanosine should never be coadministered with ribavirin due to potential life-threatening complications.

Macías J, Recio E, Vispo E, Rivero A, López-Cortés LF, Ríos MJ, Merino D, González M, Barreiro P, de Lédinghen V, Quereda C, Pineda JA. · Clinical Unit of Infectious Diseases, Department of Internal Medicine, Seville, Spain. · J Hepatol. · Pubmed #18929426 No free full text.

Abstract: BACKGROUND/AIMS: Transient elastometry (TE) is accurate for detecting cirrhosis (F=4) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients. However, this procedure is less precise to differentiate mild (F < or = 1) from moderate to severe (F > or = 2) fibrosis using the cut-off value of 7.2kPa, a level previously proposed by some authors. Because of this, we elaborated and validated cut-off values of liver stiffness (LS) to better discriminate F < or = 1 from F > or = 2 in HIV/HCV co-infected subjects to aid therapy decisions. METHODS: One hundred and ninety-seven co-infected patients with liver biopsy and TE measurement, without prior therapy against HCV infection, were included. RESULTS: To diagnose F < or = 2, a cut-off of 9.0kPa showed a positive predictive value of 87%. To discard F > or = 2, a cut-off of 6.0kPa showed a negative predictive value of 90%. Considering all the patients, 61 (31%) patients yielded LS values < or = 6.0kPa and 81 (41%) patients showed LS values > or = 9.0kPa. There were no severe classification errors as the NPV of L < or = S6.0kPa for F > or = 3 was 100% and the NPV LS > or = 9.0kPa for F=0 was also 100%. CONCLUSIONS: The usefulness of TE can be enhanced using two different cut-off values to identify patients with F < or = 1 and F > or = 2.

Vispo E, Barreiro P, Rodriguez-Nóvoa S, Morello J, Labarga P, Martín-Carbonero L, Maida I, García-Gascó P, Soriano V. · Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. · Antivir Ther. · Pubmed #18672529 No free full text.

Abstract: BACKGROUND: Pegylated interferon (PEG-IFN) alpha2a and alpha2b differ in their pharmacokinetic properties, which might have an effect on their antiviral effects against hepatitis C virus (HCV). Differences between PEG-IFN-alpha molecules could be more pronounced in HIV-coinfected individuals, in whom response to HCV treatment is impaired. METHODS: All HCV-HIV-coinfected patients included in PRESCO and EXTENT trials recruited at one referral centre were retrospectively analysed. In both trials, ribavirin (RBV) 1,000-1,200 mg/day was prescribed together with standard doses of PEG-IFN-alpha2a or -alpha2b. The attainment of serum HCV RNA <10 IU/ml at weeks 4, 12 and 24 was assessed. On-treatment analyses were made to estimate the intrinsic potency of PEG-IFN-alpha2a versus -alpha2b. RESULTS: A total of 218 patients were examined, 138 on PEG-IFN-alpha2a and 80 on PEG-IFN-alpha2b. Baseline characteristics were comparable in both groups. Undetectable serum HCV RNA at weeks 4, 12 and 24 was more frequently attained using PEG-IFN-alpha2a than -alpha2b (45% versus 27% [P=0.02]; 65% versus 45%/ [P=0.01]; and 75% versus 55%/ [P=0.01], respectively), regardless of HCV genotype. Plasma RBV levels did not differ between groups. In multivariate analysis, HCV genotypes 2/3 (odds ratio [OR] 12.5; 95% confidence interval [95% CI] 3.45-33.33; P<0.001), use of zidovudine (OR 0.30; 95% CI 0.11-0.85; P=0.02) and treatment with PEG-IFN-alpha2a (OR 2.12; 95% CI 1.02-4.54; P=0.04) were independent predictors of undetectable HCV RNA at week 24. Conversely, the incidence of serious adverse events was more common with PEG-IFN-alpha2a than -alpha2b (13.2% versus 3.6%; P=0.018). CONCLUSIONS: The antiviral effect against HCV seems to be greater for PEG-IFN-alpha2a than -alpha2b in the HIV setting. A shorter half-life of PEG-IFN-alpha2b could explain this finding.

Vispo E, Barreiro P, Del Valle J, Maida I, de Ledinghen V, Quereda C, Moreno A, Macías J, Castera L, Pineda JA, Soriano V. · Infectious Diseases Department, Hospital Carlos III, Madrid, Spain. · Antivir Ther. · Pubmed #19430093 No free full text.

Abstract: BACKGROUND: Transient elastography (TE) is a non-invasive method that allows liver fibrosis staging on the basis of hepatic stiffness measurements. Little is known about the influence of chronic liver inflammation on the stiffness of hepatic tissue. METHODS: A total of 112 patients with chronic hepatitis C underwent a liver biopsy and TE. RESULTS: Mean values of liver stiffness (in kPa) by inflammation strata were 4.8, 6.4, 9.4 and 12.6 for A0, A1, A2 and A3, respectively, in hepatitis C virus (HCV)-monoinfected individuals (P=0.018). These figures were 8.0, 10.4, 12.9 and 12.6 for A0, A1, A2 and A3, respectively, in HIV-HCV-coinfected patients (P=0.35). In HCV-monoinfected patients with fibrosis staging F3-F4, mean liver stiffness was greater if inflammation was > or =A2 versus A0-A1 (14.6 versus 6.2 kPa; P=0.04). By contrast, no differences in liver stiffness according to inflammation were seen in HCV-monoinfected patients with <F3 or in HIV-HCV-coinfected patients regardless of liver fibrosis staging. Among HCV-monoinfected patients, mean liver stiffness was greater for alanine aminotransferase >100 versus <100 IU/l (10.5 versus 8.5 kPa; P=0.04). CONCLUSIONS: The extent of liver inflammation might affect the accuracy of TE for staging liver fibrosis, particularly in HCV-monoinfected patients with advanced fibrosis on liver biopsy and/or increased alanine aminotransferase levels.

Soriano V, Vispo E, Martin-Carbonero L, Labarga P, Garcia-Samaniego J, Barreiro P. · aDepartment of Infectious Diseases, Spain bHepatology Unit, CIBEREHD, Hospital Carlos III, Madrid, Spain. · Curr Opin HIV AIDS. · Pubmed #19372931 No free full text.

Abstract: PURPOSE OF REVIEW: Chronic hepatitis C is currently one of the leading causes of hospitalization and death in HIV+ persons. Treatment is particularly challenging in coinfected patients due to lower efficacy and more side effects. RECENT FINDINGS: The combination of pegylated interferon plus ribavirin is the current treatment of choice. In the absence of contraindications, treatment should be provided with no restrictions up front (e.g., asking unnecessarily for a liver biopsy) and revisited at weeks 4 and 12. Treatment should only be continued in early virological responders. The use of standard ribavirin doses (1000-1200 mg/day) and for at least 12 months is crucial to maximize the effect of therapy. In patients with rapid virological response (undetectable viraemia at week 4), shorter periods of therapy (24 weeks) may be advisable for hepatitis C virus genotypes 2 and 3. Patients with low CD4 percentages should defer treatment and prioritize highly active antiretroviral therapy. Didanosine should never be co-administered with ribavirin due to potential life-threatening complications. When possible, zidovudine, stavudine and abacavir should be replaced by other agents having no deleterious interactions with ribavirin. SUMMARY: The treatment of chronic hepatitis C has become a priority in hepatitis C virus/HIV-coinfected patients, and the best results are obtained by tailoring therapy to the individual patient's characteristics.

Vispo E, Maida I, Barreiro P, Moreno V, Soriano V. · Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. · HIV Clin Trials. · Pubmed #19203910 No free full text.

Abstract: Three HIV individuals with chronic hepatitis C presented with esophageal variceal bleeding. They had mild liver fibrosis and normal liver function tests. All had received didanosine for long periods. Noncirrhotic portal hypertension associated with didanosine may appear in HIV patients without any liver disease or added to chronic hepatitis C.

Ryan P, Blanco F, García-Gascó P, García-Merchán J, Vispo E, Barreiro P, Labarga P, González-Lahoz J, Soriano V. · Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. · HIV Med. · Pubmed #19018879 No free full text.

Abstract: OBJECTIVE: Multiple factors may lead to hepatic steatosis (HS) in HIV-positive patients. HS may result in severe liver damage on its own and/or by accelerating the progression of chronic viral hepatitis B or C. METHODS: The sensitivity/specificity of liver ultrasound (US) to recognize severe HS is above 85%. A cross-sectional case-control study of all HIV out-patients who underwent liver US since 2004 was conducted at our institution. RESULTS: Eight hundred and thirty (36.1%) out of 2300 HIV-positive patients on regular follow-up underwent liver US during the study period. Severe HS was diagnosed in 108 (13%) patients. A total of 117 matched HIV controls lacking HS were selected randomly. In patients with severe HS, we found significantly higher values of body mass index (BMI), plasma viral load, serum glucose, alkaline phosphatase, triglycerides and low-density lipoprotein cholesterol, as well as significantly higher prevalence of diabetes, elevated alcohol consumption, lipohypertrophy and advanced liver fibrosis. Furthermore, a trend towards longer exposure to nucleoside analogues was noticed. In the multivariate analysis, only elevated alcohol consumption [odds ratio (OR) 7, P=0.013], lipohypertrophy (OR 5.3, P=0.008), plasma viral load (OR 2.1, P=0.02), BMI (OR 1.2, P=0.013) and serum glucose (OR 1.03, P=0.027) were significantly associated with severe HS. CONCLUSIONS: Severe HS in HIV-positive patients is associated with predisposing factors that are similar to those of HIV-negative individuals. However, its characteristic association with elevated plasma viral load might suggest a direct involvement of HIV in liver fat deposition. Therefore, the benefit of controlling HIV replication with antiretroviral therapy should be balanced against its effect of occasionally inducing metabolic abnormalities and lipodystrophy.

Rodríguez-Nóvoa S, Morello J, González M, Vispo E, Barreiro P, González-Pardo G, Jiménez-Nácher I, Gonzalez-Lahoz J, Soriano V. · Pharmacokinetic and Pharmacogenetic Unit, Hospital Carlos III, Madrid, Spain. · AIDS. · Pubmed #19005277 No free full text.

Abstract: Atazanavir use is associated with increases in serum bilirubin. Ribavirin, used to treat hepatitis-C infection, cause hemolysis and may worsen hyperbilirubinemia. We studied HIV/hepatitis-C virus-coinfected patients who initiated hepatitis-C therapy. Hyperbilirubinemia grade 3-4 increased from 9% to 45% after the start of hepatitis-C treatment in patients who used atazanavir concomitantly. Atazanavir use and hemoglobin (Hb) drops were predictors of increases in bilirubin. A substantial proportion of patients under atazanavir-therapy experienced significant hyperbilirubinemia and jaundice following initiation of hepatitis-C therapy.

Vispo E, Barreiro P, Pineda JA, Mira JA, Maida I, Martín-Carbonero L, Rodríguez-Nóvoa S, Santos I, López-Cortes LF, Merino D, Rivero A, Soriano V. · Hospital Carlos III, Madrid, Spain. · Antivir Ther. · Pubmed #18572756 No free full text.

Abstract: 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.

Vispo E, Maida I, Moreno A, Barreiro P, Soriano V. · No affiliation provided · J Antimicrob Chemother. · Pubmed #18835807 No free full text.

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Soriano V, Vispo E, Labarga P, Barreiro P. · No affiliation provided · AIDS. · Pubmed #18427216 No free full text.

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Vispo E, Martinez-Alarcon J, Poveda E, Toro C, Soriano V. · No affiliation provided · AIDS. · Pubmed #18097239 No free full text.

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Soriano V, Sheldon J, García-Gasco P, Vispo E. · No affiliation provided · AIDS. · Pubmed #18090058 No free full text.

This publication has no abstract.