Hepatitis: García-Samaniego J

García-Samaniego J, Forns X. · No affiliation provided · Hepatology. · Pubmed #17879358 No free full text.

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Soriano V, Martín-Carbonero L, García-Samaniego J. · No affiliation provided · AIDS. · Pubmed #12646800 No free full text.

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Soriano V, García-Samaniego J. · No affiliation provided · HIV Clin Trials. · Pubmed #12407483 links to  free full text

Abstract: Liver biopsy was a common procedure in patients with chronic hepatitis C who planned to begin treatment with interferon. The greater response rates seen with the use of dual combination therapy with interferon plus ribavirin and the almost universal recognition of fibrosis and faster progression to cirrhosis seen in HIV-HCV coinfected patients does not justify the request of a liver biopsy before prescribing anti-HCV therapy in this population, outside clinical trials.

Soriano V, Rodríguez-Rosado R, García-Samaniego J. · No affiliation provided · AIDS. · Pubmed #10203378 No free full text.

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Pérez-Olmeda M, Rodríguez-Rosado R, García-Samaniego J, Soriano V. · No affiliation provided · Rev Clin Esp. · Pubmed #10089769 No free full text.

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Moreno S, García-Samaniego J, Moreno A, Ortega E, Pineda JA, del Romero J, Tural C, von Wichmann MA, Berenguer J, Castro A, Espacio R. · Department of Infectious Diseases, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain. · J Viral Hepat. · Pubmed #19215579 No free full text.

Abstract: The measurement of fibrosis stage critically affects the identification of the progression of liver disease, the establishment of a prognosis and therapeutic decision making. Liver biopsy has been the single, most useful method to determine the degree of liver fibrosis (LF), but with recognized limitations, mainly associated with its invasiveness. In recent years, alternative noninvasive methods have been developed, including imaging methods, such as transient elastometry, and assays based on serum biomarkers. This article reviews the available studies evaluating the value of various noninvasive methods for the assessment of LF in patients with HIV-infection and HBV/HCV co-infection, and makes recommendations on how to best use and combine them in clinical practice.

Barreiro P, Martín-Carbonero L, García-Samaniego J. · Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, España. · Enferm Infecc Microbiol Clin. · Pubmed #19100234 links to  free full text

Abstract: Chronic hepatitis B virus infection affects approximately 10% of HIV-infected patients. There are an estimated 4 million patients with HIV/HBV coinfection. HIV infection has a deleterious effect on the natural history of chronic hepatitis B and increases the risk of progression to cirrhosis and terminal liver disease. Since the widespread use of highly active antiviral therapy (HAART), liver disease has emerged as one of the main causes of morbidity and mortality in HIV-positive patients. Therefore, all patients with HIV/HBV coinfection should be evaluated for treatment of hepatitis B, independently of the CD4 lymphocyte count. Six drugs are currently authorized for the treatment of chronic hepatitis B: standard interferon-alpha (2a and 2b), pegylated interferon alpha-2a, lamivudine, adefovir, entecavir and telbivudine. Other drugs with activity against HBV, such as tenofovir and emtricitabine, are used for the treatment of HIV infection. In patients not requiring HAART, treatment of hepatitis B should preferably consist of drugs without activity against HIV, such as pegylated interferon or adefovir. In contrast, in patients requiring HAART, a combination of drugs with activity against both viruses should be used, such as lamivudine, emtricitabine and tenofovir, with the aim of achieving maximal viral suppression and avoiding the development of resistance. Patients with HIV/HBV coinfection require periodic clinical and virological monitoring. Patients with cirrhosis should undergo ultrasonography and alphafetoprotein determination every 6 months for the early detection of hepatocellular carcinoma.

Núñez M, García-Samaniego J, Soriano V. · Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #15511395 links to  free full text

Abstract: Infection by the hepatitis B virus (HBV) is a significant cause of morbidity and mortality, mainly due to evolvement to cirrhosis and hepatocellular carcinoma. The prevalence and genotypic distribution of HBV infection has marked geographic differences. HBV infection is a very dynamic process, with a phase of immune tolerance and high viral replication, followed by HBeAg clearance, not always accompanied by complete suppression of HBV replication. The latter situation corresponds to negative HBeAg hepatitis, which represents a group relatively resistant to therapy. The three approved drugs for the treatment of HBV infection (interferon alpha, lamivudine and adefovir) have limited efficacy. Relapses are more common with lamivudine and adefovir, requiring often long-term treatment. While the selection of lamivudine resistance mutations is frequent, adefovir has a high genetic barrier. HIV infection negatively impacts on HBV disease, requiring these coinfected patients strategies aimed to manage both viruses.

Soriano V, Miró JM, García-Samaniego J, Torre-Cisneros J, Núñez M, del Romero J, Martín-Carbonero L, Castilla J, Iribarren JA, Quereda C, Santín M, González J, Arribas JR, Santos I, Hernández-Quero J, Ortega E, Asensi V, del Pozo MA, Berenguer J, Tural C, Clotet B, Leal M, Mallolas J, Sánchez-Tapias JM, Moreno S, Gatell JM, Téllez MJ, Rubio R, Ledesma E, Domingo P, Barreiro P, Pedreira J, Romero M, González-Lahoz J, Lissen E. · Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain. · J Viral Hepat. · Pubmed #14738553 No free full text.

Abstract: Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

Romero M, Pérez-Olmeda M, García-Samaniego J, Soriano V. · Gastroenterology and Hepatology Department, Hospital Carlos III, Instituto de Salud Carlos III, Madrid, Spain. · Drug Saf. · Pubmed #14720084 No free full text.

Abstract: Hepatitis C virus (HCV) infection is a significant public health problem and one of the most important causes of chronic liver disease worldwide. Co-infection with HCV and HIV occurs frequently, mainly because both viruses share the same transmission routes. In recent years, the life expectancy of patients with HIV disease has been increased due to the introduction of highly active antiretroviral therapy (HAART). Furthermore, several studies have established that HIV infection is associated with a major progression of the HCV-related liver disease. Thus, end-stage liver disease has become a leading cause of morbidity and mortality in this population, emphasising the importance of treatment of chronic hepatitis C in HIV-infected persons.The biological and histological benefit of interferon-alpha (IFNalpha) therapy in patients co-infected with HCV/HIV is not significantly different from that noted in similar patients without HIV when the HIV infection is adequately controlled. However, patients with low CD4+ cell counts tend to respond poorly to anti-HCV therapy.Given the relatively low sustained virological response rate to IFN alone, the use of IFNalpha monotherapy has been largely abandoned in favour of combination therapy with ribavirin. In the last 2 years, IFN plus ribavirin combination therapy has been the standard care for the treatment of chronic hepatitis C. Although information on the safety and efficacy of this dual therapy in HCV/HIV co-infected patients is scarce, recent trials have reported that the combination of IFN plus ribavirin is well tolerated and feasible in patients co-infected with HCV/HIV. However, the rates of sustained virological response seem to be worse than those observed in patients without HIV infection. New IFN formulations (e.g. pegylated interferon) plus ribavirin appear to be way of the future for the treatment of chronic hepatitis C in patients both with and without HIV co-infection.

García-Samaniego J, Soriano V, Miró JM, Romero JD, Bruguera M, Castilla J, Esteban JI, Gonźlez J, Lissen E, Moreno A, Moreno S, Moreno-Otero R, Ortega E, Quereda C, Rodríguez M, Sánchez-Tapias JM, Anonymous00176. · Hepatology, Hospital Carlos III, Instituto de Salud Carlos III, Madrid, Spain. · HIV Clin Trials. · Pubmed #11976988 links to  free full text

Abstract: Co-infection by human immunodeficiency virus and hepatitis B and C viruses is quite common because they share similar routes of transmission. The introduction of highly active antiretroviral therapy has significantly improved the life expectancy of HIV-infected patients in the last few years. However, chronic viral hepatitis represents an emerging cause of morbidity and mortality in this population, either as a result of end-stage liver disease or as a consequence of hepatotoxicity induced by antiretroviral drugs. The main goal of the Consensus Conference was to establish specific recommendations for the management of chronic viral hepatitis B and C in HIV-infected patients. The role of orthotopic liver transplantation for co-infected individuals with end-stage liver disease was also assessed.

Rodríguez-Rosado R, Pérez-Olmeda M, García-Samaniego J, Soriano V. · Service of Infectious Diseases, Hospital Carlos III, Instituto de Salud Carlos III, C/Nueva Zelanda 54, 4th B, 28035 Madrid, Spain. · Antiviral Res. · Pubmed #11672829 No free full text.

Abstract: The life expectancy of HIV-infected persons has extended significantly since the introduction of highly active antiretroviral therapies. Although classical opportunistic infections are now rarely seen, the toxicity of antiretroviral drugs as well as liver disease caused by hepatitis viruses represent an increasing cause of morbidity and mortality among HIV-positive persons. Since the rate of hepatitis C virus (HCV) infection is high among HIV carriers (up to 75% among intravenous drug users), HCV/HIV coinfection is widely prevalent. Predisposing liver damage favors a higher rate of hepatotoxicity of antiretroviral drugs, which can limit the benefit of HIV treatment in some individuals. Overall, severe hepatotoxicity appears in around 10% of subjects who began triple combinations including either protease inhibitors or non-nucleosides. The progression to cirrhosis seems to occur faster in the setting of HIV infection, and conversely recent data demonstrate that HCV infection can accelerate the progression to AIDS in HIV-positive persons. Although clinicians have been reluctant to treat hepatitis C in HIV-infected people, this therapeutic nihilism is unwarranted. The availability of new more successful regimens to treat hepatitis C, in particular using the new pegylated forms of interferon in combination with ribavirin, open new hopes for the care of HIV-HCV-coinfected persons.

Martín-Carbonero L, Puoti M, García-Samaniego J, De Luca A, Losada E, Quinzan G, Bruno R, Mariño A, González M, Núñez M, Soriano V. · Department of InfectiousDiseases, Hospital Carlos III, Madrid, Spain. · J Viral Hepat. · Pubmed #18637070 No free full text.

Abstract: SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.

Núñez M, Miralles C, Berdún MA, Losada E, Aguirrebengoa K, Ocampo A, Arazo P, Cervantes M, de Los Santos I, San Joaquín I, Echeverría S, Galindo MJ, Asensi V, Barreiro P, Sola J, Hernandez-Burruezo JJ, Guardiola JM, Romero M, García-Samaniego J, Soriano V, Anonymous00252. · Department of Infectious Diseases, Hospital Carlos III, Calle Sinesio Delgado 10, Madrid 28029, Spain. · AIDS Res Hum Retroviruses. · Pubmed #17725413 No free full text.

Abstract: The response to pegylated interferon (pegIFN) plus ribavirin (RBV) as treatment of chronic hepatitis C virus (HCV) infection is lower in HIV-coinfected than in HCV-monoinfected patients and could be due to suboptimal RBV dosing and/or insufficient duration of therapy in prior trials. In a prospective, multicenter, open, comparative trial, HCV/HIV-coinfected patients received pegIFN plus weight-based RBV for 48 or 72 weeks (HCV genotypes 1 and 4) and 24 or 48 weeks (HCV genotypes 2 and 3). Use of didanosine was not allowed. Out of 389 patients included in the trial, 61% were infected by HCV-1/4 and 67% had serum HCV-RNA >500,000 IU/ml. Sustained virological response (SVR) was achieved by 49.6%, significantly higher in HCV-2/3 than HCV-1/4 (72.4% vs. 35%; p < 0.0001). A high drop-out rate in the longer treatment arms precluded obtaining definitive conclusions about the efficacy of prolonging therapy. Premature treatment discontinuations due to serious adverse events occurred in 8.2%. Infection with HCV-2/3, lower baseline HCV-RNA, and negative HCV-RNA at week 12 were all independent predictors of SVR in the multivariate analysis. The use of RBV 1000-1200 mg/day plus pegIFN is relatively safe and provides SVR in nearly half of coinfected patients, twice as high in HCV-2/3 than HCV-1/4.

Soriano V, Miralles C, Berdún MA, Losada E, Aguirrebengoa K, Ocampo A, Arazo P, Cervantes M, de los Santos I, San Joaquín I, Echeverria S, Galindo MJ, Asensi V, Barreiro P, Sola J, Hernandez-Burruezo JJ, Guardiola J, Blanco F, Martin-Carbonero L, García-Samaniego J, Nuñez M, Anonymous00056. · Hospital Carlos III, Madrid, Spain. · Antivir Ther. · Pubmed #17668555 No free full text.

Abstract: BACKGROUND: Chronic hepatitis C therapy in HIV patients is often penalized by more frequent premature treatment discontinuations. It is unclear what the relative contribution of more adverse events and/or early virological failures are. METHODS: PRESCO was a prospective, multicentre, comparative trial, in which 389 HIV/HCV-coinfected patients with CD4+ T-cell counts >300 cells/ml and elevated aminotransferases received pegylated interferon-alpha2a (peg IFN-alpha2a) 180 mg per week plus ribavirin (RBV) 1,000-1,200 mg daily. Patients with HCV genotypes 1 or 4 were treated for 48 or 72 weeks while HCV genotypes 2 or 3 carriers were treated for 24 or 48 weeks. Use of didanosine was not allowed. RESULTS: Sustained virological response (SVR) was achieved by 193 (49.6%), and was significantly greater in HCV-2/3 than in HCV-1/4 patients (72.4% versus 35%; P<0.0001). Premature treatment discontinuations occurred in 174 patients (44.7%). This was due to early virological failure in 66 (17%), serious adverse events in 32 (8.2%), loss-to-follow-up in 12 (3.1%) and voluntary withdrawal in 64 (16.4%). Only 10 patients (2.6%) stopped HCV therapy due to severe anaemia. Two patients stopped HCV medication due to symptomatic mitochondrial toxicity. There were no episodes of hepatic decompensation. CONCLUSIONS: Treatment with RBV 1,000-1,200 mg/day plus peg IFN-alpha2a is relatively safe and provided SVR in nearly half of the HIV/HCV-coinfected patients, twice as many amongst the HCV-2/3 than HCV-1/4 carriers. Avoidance of didanosine, limited use of zidovudine and therapy restricted to patients with CD4+ T-cell counts >300 cells/ml most probably explains the lower and different spectrum of serious adverse events in PRESCO compared with prior trials conducted in coinfected patients.

Núnez M, Camino N, Ramos B, Berdún MA, Barreiro P, Losada E, Santos I, Echevarría S, Ocampo A, Miralles C, Arazo P, Martín-Carbonero L, Romero M, García-Samaniego J, Soriano V. · Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. · Antivir Ther. · Pubmed #16152759 No free full text.

Abstract: BACKGROUND: The use of pegylated interferon (PEG-IFN) plus ribavirin (RBV) is currently the recommended treatment for chronic hepatitis C virus (HCV) infection. Coinfection with HIV is a negative predictor of response, for reasons not well understood. METHODS: We examined the virological response at weeks 4 and 12 in 198 HCV/HIV-coinfected patients enrolled in a prospective trial in which PEG-IFN alpha 2a (180 microg per week) and RBV (1000-1200 mg daily) were provided. RESULTS: In an on-treatment analysis, 52.8% of patients achieved undetectable HCV-RNA (<600 IU/ml) at week 4, while 63% and 77.2% of patients had a decline of at least 2 and 1 log10, respectively. At week 12, 73.1% of patients reached undetectable HCV-RNA, and 83.5% and 89% achieved at least a 2- and 1-log10 drop, respectively. More than 85% of HCV genotypes 2/3 cleared HCV-RNA at week 4, a proportion significantly higher when compared with genotypes 1 (33.8%) and 4 (28.6%). Multivariate logistic regression analysis identified genotype 3 and RBV exposure (mg/kg of body weight) as independent predictors of virological response at week 12 of therapy. CONCLUSION: Early virological response rates to PEG-IFN plus RBV in HCV/HIV-coinfected patients seem to be similar to those reported for HCV-monoinfected subjects. The use of suboptimal doses of RBV in most earlier trials might account for the low response rates seen in coinfected patients. To our knowledge, this is the first report demonstrating that RBV exerts a significant independent effect on early virological response. Therefore, strategies aimed at optimizing doses and adherence to RBV might help to improve responses to HCV therapy in coinfected patients.

Diago M, Castellano G, García-Samaniego J, Pérez C, Fernández I, Romero M, Iacono OL, García-Monzón C. · Section of Hepatology, University General Hospital, Valencia, Spain. · Gut. · Pubmed #16150856 links to  free full text

Abstract: BACKGROUND: Increased serum and intrahepatic interferon gamma inducible protein 10 (IP-10) levels in patients with chronic hepatitis C (CHC) have been described. AIM: To analyse the possible association of serum IP-10 levels with different outcomes to antiviral therapy. PATIENTS: A total of 137 CHC patients treated with peginterferon plus ribavirin. METHODS: Serum IP-10 levels were determined by enzyme linked immunosorbent assay before therapy, after 12 weeks of treatment, and 24 weeks after cessation of therapy. Variables significantly associated with a sustained virological response (SVR) on univariate analysis were included in a multivariate logistic regression model. RESULTS: Pretreatment serum IP-10 levels in patients with SVR were significantly lower than in non-responders (NR) (332.4 (222.1) v 476.8 (305.3) pg/ml, respectively; p=0.004). Serum IP-10 concentrations significantly decreased in patients with SVR (pretreatment: 332.4 (222.1) pg/ml; post-treatment: 170.2 (140.1) pg/ml; p<0.001) but not in NR (pretreatment: 476.8 (305.3) pg/ml; post treatment: 387.3 (268.1) pg/ml; p=0.06). By multivariate analysis, non-1 genotype (odds ratio (OR) 3.5 (95% confidence interval (CI) 1.1-10.4); p=0.003) and low viral load at baseline (OR 0.34 (95% CI 0.14-0.79); p=0.01) were independent predictors of SVR in all patients. When multivariate analysis was restricted to patients with genotype 1, only baseline viral load (OR 0.38 (95% CI 0.155-0.96); p=0.04) and pretreatment serum IP-10 levels (OR 0.99 (95% CI 0.996-0.999); p=0.03) were identified as predictive factors of SVR. CONCLUSION: Pretreatment serum IP-10 behaves as a predictive factor of SVR to peginterferon plus ribavirin therapy in genotype 1 infected patients.

Soriano V, Núñez M, Sánchez-Conde M, Barreiro P, García-Samaniego J, Martín-Carbonero L, Romero M, González-Lahoz J. · Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain. · Antivir Ther. · Pubmed #15751774 No free full text.

Abstract: BACKGROUND: The hepatitis C virus (HCV) genotype is the main predictor of response to interferon (IFN)-based therapies. HCV genotype 4 is spreading among European intravenous drug users, who are frequently coinfected with HIV. Information about treatment response in this subset of patients is scarce and conflicting results have been reported. METHODS: All HIV-infected patients treated for chronic hepatitis C at our institution with a minimum follow-up of 6 months after discontinuing therapy were retrospectively analysed. They had received one of three HCV treatment modalities: IFN monotherapy, IFN plus ribavirin (RBV) or pegylated interferon (PEG-IFN) plus RBV. Treatment responses were stratified according to HCV genotype. RESULTS: A total of 390 patients were analysed. Sustained virological response (SVR) to HCV therapy had been reached by 90 (23.1%): 22/119 (18.5%) with IFN monotherapy; 17/106 (16%) with IFN plus RBV; and 51/165 (30.9%) with PEG-IFN plus RBV. SVR was significantly higher among those with HCV genotypes 2 or 3 (40.4%; 61/151) than in patients with either HCV genotype 1 (11.2%; 22/197) or HCV genotype 4 (16.7%; 7/42) (P<0.0001). In contrast, there were no significant differences in the response rate comparing HCV genotypes 1 and 4 (P=0.53). CONCLUSIONS: Response to IFN-based therapies in HIV-positive patients with hepatitis C due to HCV genotype 4 is poor, similar to that obtained for HCV genotype 1 and much lower than for HCV genotypes 2 and 3. Therefore, HIV-infected patients with hepatitis C due to genotype 4 should be considered as a particular subset of difficult-to-treat patients. New treatment strategies and drugs for these patients are eagerly awaited.

Soriano V, Maida I, Núñez M, García-Samaniego J, Barreiro P, Martín-Carbonero L, González-Lahoz J. · Service of Infectious Diseases, Hospital Carlos II, Madrid, Spain. · Antivir Ther. · Pubmed #15651757 No free full text.

Abstract: BACKGROUND: Chronic hepatitis C virus (HCV) infection is frequent among HIV-infected patients. Clearance of serum HCV RNA 6 months after discontinuing HCV therapy is generally interpreted as a cure of HCV infection in HIV-negative subjects. However, the occurrence of liver complications (including hepatocellular carcinoma) and/or HCV relapses in coinfected patients when followed for long periods of time after HCV therapy is not well known. METHODS: All HIV-infected patients who had been treated for chronic hepatitis C at our institution and had a minimum follow-up of 6 months after discontinuing therapy were retrospectively analysed. They had received one of three HCV treatment modalities: IFN monotherapy, IFN plus ribavirin (RBV) or pegylated interferon (PEG-IFN) plus RBV. RESULTS: A total of 351 patients were retrospectively analysed. Sustained virological response (SVR) to HCV therapy had been reached by 77 (22%) of them: 22/119 (18.5%) with IFN monotherapy, 17/106 (16%) with IFN plus RBV and 38/126 (30.2%) with PEG-IFN plus RBV. Considering the HCV genotypes, SVR had been reached by 19/184 (10.3%) of patients with genotype 1, 54/138 (39.1%) with genotypes 2 or 3, and 4/29 (13.8%) of those with genotype 4. Within a total of 4466 patient-months follow-up (mean of 58 months), none of the 77 patients with SVR showed HCV-RNA rebounds, elevations in liver enzymes potentially linked to HCV, development of hepatocellular carcinoma or episodes of decompensated cirrhosis. In contrast, all 274 patients who did not reach SVR with HCV therapy showed evidence of persistent serum HCV RNA and 90% of them showed liver enzyme elevations during a total of 15344 patient-months follow-up (mean of 56 months). Moreover, 11 (4%) developed clinical complications of liver cirrhosis and two of them died of end-stage liver disease. CONCLUSIONS: HCV replication and HCV-related liver disease seem to be permanently halted in HIV/HCV-coinfected patients showing HCV-RNA clearance 6 months after completing any kind of IFN-based therapy. In contrast, complications of liver disease due to persistent HCV infection continue to occur in non-responders. The role of maintenance HCV therapy should be explored in HIV/HCV-coinfected patients.

Pérez-Olmeda M, Soriano V, Asensi V, Morales D, Romero M, Ochoa A, Sánchez-Montero F, Santin M, Guardiola J, Blanch J, Núñez M, Jiménez-Nácher I, García-Samaniego J, Anonymous00115. · Instituto de Salud Carlos III, Madrid 28029, Spain. · AIDS Res Hum Retroviruses. · Pubmed #14709244 No free full text.

Abstract: One hundred six HIV-infected patients with chronic hepatitis C virus (HCV) infection were randomized to receive ribavirin (RBV) 400 mg bid plus interferon alpha-2b (IFN-alpha) at two different doses, 3 mU tiw (control arm) or 5 mU daily for the first 6 weeks, followed by 3 mU tiw until completing 6 months of therapy (induction arm). All patients had CD4 counts above 350 cells/microl and 89% were taking antiretroviral therapy. Adverse effects leading to treatment discontinuation occurred in 12.3% of patients, a rate quite similar to that seen in HCV-monoinfected patients. Negative serum HCV-RNA values (< 60 IU/ml) were recorded in 24.7% and 35.5% of patients at 3 and 6 months of therapy. However, in the intent-to-treat analysis, sustained response was reached by only 16% of patients (22.4% in the on-treatment analysis). No differences between treatment arms were noticed. Patients with HCV genotypes 2 or 3 had a 7-fold higher response rate than those with HCV genotypes 1 or 4. Therefore, early, end-of-treatment, and sustained response rates are lower in HIV/HCV-coinfected patients treated with RBV/IFN-alpha combination therapy. Since HCV-related liver disease is currently one of the leading causes of morbidity and mortality among HIV-infected patients, new treatment options are urgently needed for coinfected individuals.

Pérez-Olmeda M, Núñez M, Romero M, González J, Castro A, Arribas JR, Pedreira J, Barreiro P, García-Samaniego J, Martín-Carbonero L, Jiménez-Nácher I, Soriano V. · Service of Infectious Diseases and bHepatology Unit, Instituto de Salud Carlos III, Madrid, Spain. · AIDS. · Pubmed #12700452 No free full text.

Abstract: BACKGROUND: Treatment of hepatitis C virus (HCV) has become a major challenge in HIV-infected individuals. No data exist on the efficacy and tolerability of pegylated IFN (peg-IFN) plus ribavirin in HIV-co-infected patients. METHODS: Subcutaneous peg-IFN (150 microg weekly during the first 12 weeks and 100 microg weekly thereafter) plus ribavirin (400 mg twice a day) was given to 68 HIV-infected patients with chronic hepatitis C, having CD4 cell counts greater than 300 cells/microl, plasma HIV-RNA less than 5000 copies/ml, and elevated aminotransferase levels. All were naive for IFN, and 73% were receiving antiretroviral drugs. RESULTS: Plasma HCV-RNA levels greater than 800 000 IU/ml were seen in 50%, and 35% carried HCV genotype 3. Adverse events leading to treatment discontinuation occurred in 10 patients (15%). One patient taking didanosine developed pancreatitis. Severe weight loss occurred in 70% of patients. Clearance of HCV-RNA at the end of therapy (6 months for HCV-3 and 12 months for HCV-1/4) occurred in 50% of patients (81% with HCV-3 versus 30% with HCV-1/4). As 30% relapsed, the overall sustained response rate was 35% (28% in the intent-to-treat analysis). The main predictors of response were infection with HCV-3 and low HCV load. CONCLUSION: Treatment with peg-IFN and ribavirin is relatively well-tolerated in HIV/HCV-co-infected patients, although new side-effects, including pancreatitis and severe weight loss, may result from the interaction of ribavirin with antiretroviral drugs. Overall, therapy provides cure to one third of patients, a rate significantly lower than that seen in HCV-monoinfected individuals. Given that relapses are common, extended periods of therapy should be investigated.

Enríquez J, Gallego A, Torras X, Pérez-Olmeda T, Diago M, Soriano V, Luján MS, García-Samaniego J. · Department of Gastroenterology, Hospital de la Sta Creu i St Pau, Barcelona, Spain. · J Viral Hepat. · Pubmed #11115050 No free full text.

Abstract: We assessed the efficacy of interferon (IFN) plus ribavirin over 24 or 48 weeks for the retreatment of patients with chronic hepatitis C who had relapsed or did not respond to a previous course of IFN. One-hundred and twenty patients (69 non-responders and 51 relapsers) were randomly assigned to receive IFN-alpha2b (3 million units thrice weekly) plus ribavirin (1,000-1,200 mg per day) for 24 weeks (group A: 58 patients) or 48 weeks (group B: 62 patients). Treatment was discontinued at week 12 if the alanine aminotransferase (ALT) level remained elevated. The rate of sustained response was 15.5% in group A and 37.1% in group B (P = 0.013). Relapsers treated for 48 weeks had a sustained response rate of 66.6% compared with a sustained response rate of only 25% in those treated for 24 weeks (P = 0.004). Moreover, a sustained response was seen in 14.3% of non-responders treated for 48 weeks and in 8.8% of those treated for 24 weeks (P = 0.71). Fifty-three per cent of patients with a normal ALT level and undetectable hepatitis C virus (HCV) RNA at week 12 had a sustained response compared with 14% of those who were HCV RNA positive at week 12 (P < 0.001). Independent predictive factors of sustained response were: therapy for 48 weeks (P = 0.0026), relapse after IFN treatment (P = 0.0006), loss of HCV RNA at week 12 (P = 0.0008) and HCV genotype non-1 (P = 0.024). Hence, in patients with chronic hepatitis C who failed to respond to a previous course of IFN monotherapy, combination therapy with IFN plus ribavirin for 48 weeks seems to be more effective than IFN plus ribavirin for 24 weeks.

Pérez-Olmeda M, González J, García-Samaniego J, Arribas JR, Peña JM, Soriano V. · No affiliation provided · J Acquir Immune Defic Syndr. · Pubmed #10770353 No free full text.

This publication has no abstract.

Núñez-Fernández C, Martín-Carbonero L, Valencia ME, Aguilera J, García-Samaniego J, Gonzalez-Lahoz J, Soriano V. · Infectious Diseases Department, Hospital Carlos III , Madrid, Spain. · AIDS Res Hum Retroviruses. · Pubmed #19320566 No free full text.

Abstract: Hospital admissions and deaths due to liver-related complications as result of chronic viral hepatitis are globally on the rise in HIV patients. However, a steady decline in liver-related hospitalizations and deaths has occurred at our HIV clinic in Madrid since year 2003. Hepatic complications are currently still responsible for 8.7% of all hospital admissions and one-third of in-hospital deaths, with hepatitis C virus infection by far the leading etiologic agent.

Tural C, Tor J, Sanvisens A, Pérez-Alvarez N, Martínez E, Ojanguren I, García-Samaniego J, Rockstroh J, Barluenga E, Muga R, Planas R, Sirera G, Rey-Joly C, Clotet B. · HIV Clinical Unit, Fundació de la Lluita contra la SIDA, Barcelona, Spain. · Clin Gastroenterol Hepatol. · Pubmed #19171202 No free full text.

Abstract: BACKGROUND & AIMS: We assessed the ability of 3 simple biochemical tests to stage liver fibrosis in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). METHODS: We analyzed liver biopsy samples from 324 consecutive HIV/HCV-positive patients (72% men; mean age, 38 y; mean CD4+ T-cell counts, 548 cells/mm(3)). Scheuer fibrosis scores were as follows: 30% had F0, 22% had F1, 19% had F2, 23% had F3, and 6% had F4. Logistic regression analyses were used to predict the probability of significant (>or=F2) or advanced (>or=F3) fibrosis, based on numeric scores from the APRI, FORNS, or FIB-4 tests (alone and in combination). Area under the receiver operating characteristic curves were analyzed to assess diagnostic performance. RESULTS: Area under the receiver operating characteristic curves analyses indicated that the 3 tests had similar abilities to identify F2 and F3; the ability of APRI, FORNS, and FIB-4 were as follows: F2 or greater: 0.72, 0.67, and 0.72, respectively; F3 or greater: 0.75, 0.73, and 0.78, respectively. The accuracy of each test in predicting which samples were F3 or greater was significantly higher than for F2 or greater (APRI, FORNS, and FIB-4: >or=F3: 75%, 76%, and 76%, respectively; >or=F2: 66%, 62%, and 68%, respectively). By using the lowest cut-off values for all 3 tests, F3 or greater was ruled out with sensitivity and negative predictive values of 79% to 94% and 87% to 91%, respectively, and 47% to 70% accuracy. Advanced liver fibrosis (>or=F3) was identified using the highest cut-off value, with specificity and positive predictive values of 90% to 96% and 63% to 73%, respectively, and 75% to 77% accuracy. CONCLUSIONS: Simple biochemical tests accurately predicted liver fibrosis in more than half the HIV/HCV co-infected patients. The absence and presence of liver fibrosis are predicted fairly using the lowest and highest cut-off levels, respectively.