Peripheral Th17 cells expressing ß7 intestinal homing receptor in recent and chronic HIV infections.

The objective of this study was to conduct an analysis of peripheral blood Th17 cells with the ability to home to gut mucosa (CD4+ Th17+ ß7+ ) during recent or chronic human immunodeficiency virus (HIV) infections. The relationship between HIV load and systemic inflammation markers was studied. Twenty-five patients with recent (n = 10) or chronic (n = 15) untreated HIV infections; 30 treated HIV-infected patients with undetectable HIV load at the time of inclusion and 30 healthy controls were included. Bacterial translocation markers (16S rDNA), soluble CD14 (sCD14) and interleukin (IL)-6 monocyte activation parameters, CD4/CD8 ratio and T helper type 17 (Th17) subpopulations [CD4+ Th17+ expressing the IL-23 receptor (IL-23R) or ß7] were analysed at baseline and after 6 and 12 months of anti-retroviral therapy (ART). 16S rDNA was detected in all patients. Significantly increased serum levels of sCD14 and IL-6 and a decreased CD4/CD8 ratio were observed in patients. Similar percentages of CD4+ IL-23R+ and CD4+ Th17+ ß7+ cells were observed in healthy controls and patients at baseline. After 12 months of therapy, patients with a recent HIV infection showed significant increases of CD4+ IL-23R+ and CD4+ Th17+ ß7+ cell percentages and a decrease in IL-6 levels, although 16S rDNA continued to be detectable in all patients. No significant differences were observed in Th17 subpopulations in patients with chronic HIV infection after therapy. Early initiation of ART helps to increase the number of Th17 cells with the ability to home to the intestinal mucosa and to partially restore gut mucosal homeostasis. These results provide a rationale for initiating ART during the acute phase of HIV infection.

[Diagnosis and empirical treatment for community-acquired pneumonia in special situations: immunocompromised HIV negative and elderly patients]. / Diagnóstico y tratamiento empírico de la neumonía adquirida en la comunidad en situaciones especiales: pacientes inmunocomprometidos sin infección por el VIH y ancianos.

In the elderly, pneumonia often has a less florid clinical presentation and is frequently complicated by decompensation of concomitant diseases. Elderly patients have special characteristics in terms of the pathogens involved in pneumonia; they are at greater risk of multiresistant bacterial infections because of their frequent contact with the health services. Lung infections in immunosuppressed individuals have different causes depending on the immune deficiency in question. Admission to hospital or ambulatory treatment will be decided after stratifying the risk; this treatment will be determined by the characteristics at the time of onset of the pneumonia, the local epidemiological situation in terms of the percentage of antibiotic resistance in the area, and the clinical particularities.

Impact of universal access to hepatitis C therapy on HIV-infected patients: implementation of the Spanish national hepatitis C strategy.

In April 2015, the Spanish National Health System (SNHS) developed a national strategic plan for the diagnosis, treatment, and management of hepatitis C virus (HCV). Our aim was to analyze the impact of this on human immunodeficiency virus (HIV)-infected patients included in the HERACLES cohort during the first 6 months of its implementation. The HERACLES cohort (NCT02511496) was set up in March 2015 to evaluate the status and follow-up of chronic HCV infection in patients co-infected with HIV in the south of Spain. In September 2015, the data were analyzed to identify clinical events (death, liver decompensation, and liver fibrosis progression) and rate of treatment implementation in this population. The study population comprised a total of 3474 HIV/HCV co-infected patients. The distribution according to liver fibrosis stage was: 1152 F0-F1 (33.2 %); 513 F2 (14.4 %); 641 F3 (18.2 %); 761 F4 (21.9 %); and 407 whose liver fibrosis was not measured (12.3 %). During follow-up, 248 patients progressed by at least one fibrosis stage [7.1 %; 95 % confidence interval (CI): 6.3-8 %]. Among cirrhotic patients, 52 (6.8 %; 95 % CI: 5.2-8.9 %) developed hepatic decompensation. In the overall population, 50 patients died (1.4 %; 95 % CI: 1.1-1.9 %). Eight hundred and nineteen patients (23.56 %) initiated interferon (IFN)-free treatment during follow-up, of which 47.8 % were cirrhotic. In our study, during 6 months of follow-up, 23.56 % of HIV/HCV co-infected patients included in our cohort received HCV treatment. However, we observed a high incidence of negative short-term outcomes in our population.

Efficacy of and risk of bleeding during pegylated interferon plus ribavirin treatment in HIV/HCV-coinfected patients with pretreatment thrombocytopenia.

The aim of this study was to assess the efficacy of and the risk of major bleeding during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients according to the pretreatment platelet count. Two hundred and seventy-four HCV/HIV-coinfected, previously naïve individuals with compensated cirrhosis enrolled in one Spanish prospective cohort who received peg-IFN/RBV were included in this study. The frequency of severe bleeding and sustained virological response (SVR) rate were compared between patients with a pretreatment platelet count ≤70,000/mm(3) and >70,000/mm(3), respectively. Sixty-one (22 %) patients had a baseline platelet count ≤70,000/mm(3). The median (Q1-Q3) pretreatment platelet count was 58,000 (49,000-65,000) cells/mm(3) in the platelet ≤70,000 group and 129,000 (102,500-166,000) cells/mm(3) in the platelet >70,000 group (p < 0.0001). Seventeen (28 %) subjects of the platelet ≤70,000 group and 71 (33 %) patients of the platelet >70,000 group achieved SVR (p = 0.4). Only 2 (3.2 %) patients in the platelet ≤70,000 group developed a severe hemorrhagic event, specifically esophageal variceal bleeding. The efficacy of therapy with peg-IFN/RBV in HIV/HCV-coinfected patients with low pretreatment platelet counts is comparable to that found in the overall subset of subjects with compensated cirrhosis. The frequency of severe hemorrhagic events related with this therapy is low in this population.

Acute Q fever and the risk of developing endocarditis. / Fiebre Q aguda: riesgo de desarrollo de endocarditis.

OBJECTIVES: Assess clinical and serological data as parameters indicative of a possible evolution to endocarditis after an episode of acute Q fever. PATIENTS AND METHODS: Retrospective cohort study of evolution to endocarditis after an acute Q fever episode, analyzing the clinical and serological evolution and the antibiotic treatment administered. RESULTS: Eighty patients were recruited, 20% of whom had phase i IgG antibody levels ≥ 1:1024 in the first 3 months. Only 44% of the patients underwent antibiotherapy in the acute phase; only 2 patients underwent extended antibiotherapy. Fifteen percent of the patients underwent an echocardiogram. None of the patients had symptoms suggestive of chronic infection or progressed to endocarditis after a median follow-up of 100 months, regardless of the early increase in phase i IgG antibodies. CONCLUSIONS: The early increase in phase i IgG antibodies in asymptomatic patients is not associated with progression to endocarditis despite not undergoing prolonged antibiotic treatment.

Hepatocyte growth factor and chronic hepatitis C.

OBJECTIVE: The hepatocyte growth factor (HGF) is a pleiotropic cytokine produced by hepatic stellate cells and implicated in liver regeneration and fibrosis. Serum levels of HGF vary in liver diseases, reflecting hepatic damage and hepatocellular dysfunction. In this study, serum levels of HGF and the relationship between HGF and biochemical, histological and virological data, have been analysed in patients suffering from chronic hepatitis C (CHC). PATIENTS AND METHODS: Serum HGF concentration was measured by ELISA in sandwich in 45 patients with CHC. Correlation between HGF levels and histological (necroinflammatory activity and fibrosis score) and biochemical (transaminases, prothrombin activity, albumin, bilirubin), or virological (hepatitis C virus load) parameters was analyzed. Serum HGF concentration was also studied in a subgroup of the original sample treated with interferon and ribavirin. RESULTS: Sserum HGF concentrations of patients with CHC were significantly higher than those detected in healthy controls. Patients with significant fibrosis (F > or = 2) had a significantly older age, lower count of platelets and higher values of AST, GGT and HGF, than those patients with a fibrosis score F < 2. HGF concentration was identified by multivariate analysis as the only independent factor associated with significant fibrosis. Moreover, area under receiver operating curve, using HCG levels, showed similar values to those of previously validated non-invasive indexes of fibrosis. However, levels of HGF did not show a significant decrease in patients with a sustained response to anti-virus C therapy. CONCLUSION: Serum HGF concentration correlates with fibrosis score in patients with CHC, but is insensitive to monitor changes induced by anti-virus C therapy.

Factor de crecimiento hepatocitario y hepatitis crónica C / No disponible

Objetivo: el factor de crecimiento hepatocitario (HGF) es una citocinapleiotrópica producida por las células estrelladas hepáticas,que está implicada en la regeneración y la fibrosis hepática. La concentraciónsérica del HGF en las enfermedades hepáticas es variable,reflejando daño hepático y disfunción hepatocelular. En este estudiose ha analizado la concentración sérica del HGF en pacientes conhepatitis crónica por virus de la hepatitis C (VHC) y su relación conlos datos bioquímicos, histológicos y virológicos.Pacientes y métodos: se determinó la concentración séricade HGF mediante ELISA en sándwich y se analizó la correlaciónentre los niveles del HGF y los datos histológicos (actividad necroinflamatoria,estadio de fibrosis), bioquímicos (transaminasas,actividad de protrombina, albúmina, bilirrubina) y virológicos (cargaviral VHC) en 45 pacientes con hepatitis crónica C (HCC).También fueron evaluadas las cifras del HGF en el suero de unsubgrupo de pacientes de la muestra original sometidos a tratamientoantiviral con interferón y ribavirina.Resultados: la concentración sérica del HGF en pacientescon HCC fue significativamente mayor que la medida en controlessanos. Los pacientes con fibrosis hepática significativa (F ≥ 2) teníanuna edad significativamente mayor, unas cifras plaquetariassignificativamente inferiores y concentraciones séricas significativamentesuperiores de AST, GGT y HGF, en comparación conaquellos pacientes con un índice de fibrosis F < 2. En el análisismultivariante la concentración de HGF fue la única variable independienteasociada a la fibrosis significativa. El área bajo la curvaROC (receiver operating curve), usando las concentraciones séricasde HGF, mostró valores similares a los obtenidos con otros índices,previamente validados, que estiman fibrosis significativa enpacientes con HCC...(AU)

Objective: the hepatocyte growth factor (HGF) is a pleiotropiccytokine produced by hepatic stellate cells and implicated in liverregeneration and fibrosis. Serum levels of HGF vary in liver diseases,reflecting hepatic damage and hepatocellular dysfunction.In this study, serum levels of HGF and the relationship betweenHGF and biochemical, histological and virological data, have beenanalysed in patients suffering from chronic hepatitis C (CHC).Patients and methods: serum HGF concentration was measuredby ELISA in sandwich in 45 patients with CHC. Correlationbetween HGF levels and histological (necroinflammatory activityand fibrosis score) and biochemical (transaminases, prothrombinactivity, albumin, bilirubin), or virological (hepatitis C virus load)parameters was analyzed. Serum HGF concentration was alsostudied in a subgroup of the original sample treated with interferonand ribavirin.Results: sserum HGF concentrations of patients with CHCwere significantly higher than those detected in healthy controls. Patientswith significant fibrosis (F ≥ 2) had a significantly older age,lower count of platelets and higher values of AST, GGT and HGF,than those patients with a fibrosis score F < 2. HGF concentrationwas identified by multivariate analysis as the only independent factorassociated with significant fibrosis. Moreover, area under receiveroperating curve, using HCG levels, showed similar values to thoseof previously validated non-invasive indexes of fibrosis. However,levels of HGF did not show a significant decrease in patients with asustained response to anti-virus C therapy.Conclusion: serum HGF concentration correlates with fibrosisscore in patients with CHC, but is insensitive to monitorchanges induced by anti-virus C therapy(AU)

Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis.

The objectives of this work were the analysis of the functional characteristics of circulating monocytes and T lymphocytes in patients with liver cirrhosis, and evaluation of the relationship with an increased exposure to antigens due to bacterial translocation. Forty patients with liver cirrhosis (20 with compensated cirrhosis and 20 with ascitic decompensation) and 20 healthy control subjects were studied. Bacterial translocation was evaluated by serum levels of lipopolysaccharide binding protein (LBP). Macrophage activation was studied by CD40 antigen expression. T lymphocytes were analysed for activation (CD25(+), CD122(+)), effector function (CD8(+)CD45RO(+)CD57(+)), apoptosis (CD95(+)) and regulatory abilities, either by analysis of the membrane expression of co-stimulatory molecules CD80, CD86 and CD28, or by quantification of regulatory T cells CD4(+)CD25(high)forkhead box P3 (FoxP3). The percentage of activated monocytes and T lymphocytes in patients was increased significantly. The proportions of effector senescent cells and of those near to apoptosis were also significantly higher. With respect to these proportions, there were no significant differences between patients in function of the presence or absence of decompensation or in function of the increased or normal values of LBP. Conversely, those patients with elevated levels of LBP presented a significantly higher frequency of regulatory T cells than those with normal levels. In conclusion, patients with liver cirrhosis showed an intensive activation state with a higher percentage of cells committed to activation-induced death, even in non-advanced stages. It is possible that bacterial permeability and endotoxaemia contribute to the expansion of those lymphocyte populations implicated in the prevention of a more severe antigen-induced immunopathology.

Health-related quality of life in patients with primary Sjögren's syndrome: relationship with serum levels of proinflammatory cytokines.

OBJECTIVE: A cross-sectional study of 30 patients with primary Sjögren's syndrome (pSS) was performed to analyse the health-related quality of life and its relationship with serum levels of macrophage- and lymphocyte-derived cytokines. PATIENTS AND METHODS: Health-related quality of life was evaluated using the 36-item Short Form Health Survey (SF-36). Serum levels of interleukin (IL)-1beta, IL-6, IL-10, tumour necrosis factor (TNF)-alpha, and gamma-interferon (gamma-INF) were analysed by a sandwich immunoassay-based protein array system. RESULTS: Each of the eight scales of the SF-36 evaluating quality of life, as well as the physical composite score (PCS) and the mental composite score (MCS), showed a decrease in pSS patients. Similarly, patients with pSS showed significantly increased concentrations of each of the five cytokines analysed, when compared with the healthy control group (n = 20). In pSS patients, a significant negative correlation was detected between serum levels of IL-6 and the PCS of the SF-36. Those patients with concentrations of IL-6 higher than those of the healthy controls showed a significantly lower score in the dimensions of bodily pain and physical functioning, and in the PCS. CONCLUSIONS: Patients with pSS showed increased levels of several macrophage- and lymphocyte-derived cytokines, indicating the existence of an immune activation state. Serum levels of one of these cytokines, IL-6, were correlated with poor quality of life in these individuals.

Implications of immunomodulatory interleukins for the hyperimmunoglobulinemia of Sjögren's syndrome.

A prospective study of 37 patients with pSS and 20 healthy controls was performed to analyze the differences in circulating levels of macrophage-derived and Th1/Th2 cytokines which could explain the hyperimmunoglobulinemia, characteristic of primary Sjögren's syndrome (pSS). Serum levels of interleukin (IL)-6, IL-10, IL-12, gamma-interferon (gamma-INF) and IL-4 were analyzed by a sandwich immunoassay-based protein array system. When compared with the control group, higher levels of IL-6, IL-12 and IL-10 and a lower Th1/Th2 ratio, as demonstrated by the gamma-INF/IL-4 ratio, were detected in patients. The levels of IL-4 were notably higher in pSS patients with monoclonal gammopathy. Serum IL-4 and IL-10 levels and immunoglobulin G concentrations were significantly correlated. In conclusion, patients with pSS show a state of macrophage and T-lymphocyte activation with increased concentrations of cytokines implicated in the differentiation of B cells and secretion of immunoglobulins.

Venous thromboembolism in patients with advanced cancer under palliative care: additional risk factors, primary/secondary prophylaxis and complications observed under normal clinical practice.

We analyzed the principal risk factors of venous thromboembolism (VTE) (immobilization, recent surgery and previous VTE), prophylaxis with low-molecular weight heparin (LMWH) and complications (i.e. severe bleeding, recurrence and death). Patients with advanced cancer under palliative care (PC) and with VTE, were reviewed during the three years before the study. 71 Patients were diagnosed with VTE. 88.7% were outpatients. The risk factors present were: immobilizations in 28 patients (39.4%), recent surgery in 5 (7%) and previous VTE in 23 (32.5%). Prophylaxis was used in 4 (14.3%) patients with immobilization, no patient with recent surgery, and 10 (43.4%) patients with previous VTE. After diagnosis, all patients received treatment with LMWH in therapeutic dosage. The complications observed were: 6 recurrences (8.5%), 11 VTE-related deaths (15.5%), and bleeding events occured in 8 cases (11.3%), 4 (5.6%) of whom suffered severe bleeding; of these patients, 3 (4.2%) died as a result of the bleeding events. In PC patients with advanced cancer, VTE is a serious complication that conditions control of symptoms. The presence of other risk factors, immobilization and previous VTE, is common and LMWH prophylaxis is limited in clinical practice. The risks vs benefits of anticoagulation need to be counterbalanced.

[Progressive multifocal leukoencephalopathy in the province of Cadiz, Spain]. / Leucoencefalopatía multifocal progresiva en la provincia de Cádiz, España.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML), which is caused by the reactivation of an infection due to the JC human polyoma virus, affects immunocompromised patients and more especially those infected by the human immunodeficiency virus. It produces a multifocal neurological clinical picture due to the destruction of oligodendrocytes and the subsequent demyelination. AIMS: To analyse the epidemiological, semiological and radiological characteristics of a sample of patients diagnosed with PML in the province of Cadiz, and to study their rates of survival. PATIENTS AND METHODS: Our sample consisted of 23 patients with PML who presented an unfavourable immunological situation and deficient therapeutic compliance. Factors studied included time to progression of the symptoms, clinical features, neuroimaging and survival. RESULTS: The mean time elapsed between the appearance of symptoms and diagnosis was 30 days. There was a wide range of manifestations: motor symptoms were the most prevalent and cognitive compromise was far less common. All the patients submitted to magnetic resonance imaging of the head and only eight of those who underwent computerised axial tomography displayed multiple insults. The mean survival time was 60 days in the case of the seven deaths and over two years in those who survived. CONCLUSIONS: The symptoms of the patients were similar to those reported in the literature, except for the absence of dementia. Magnetic resonance imaging was better than tomography at detecting multiple, dispersed insults and is more cost-effective for diagnosing PML. The survival time of most of the patients was higher than that reported in previous studies.

[Renal failure and insulin resistance: effect of the dialysis dose]. / Insuficiencia renal y resistencia insulínica: efecto de la dosis de diálisis.

BACKGROUND: The main cause of death in patients undergoing hemodialysis are cardiovascular events. We have analyzed the association between intradialysis fractional clearance of urea or Kt/V index in patients with chronic renal failure in hemodialysis as an indicator of adequate dialysis and the classical factors of cardiovascular risk. PATIENTS AND METHODS: A total of 47 patients with chronic renal failure on hemodialysis were included. Diabetes mellitus was considered an exclusion criteria. Optimization of dialysis was analyzed by Kt/v index in accordance with the Daugirdas formula. The cardiovascular risk factors evaluated were: insulin resistance, calculated according to the HOMA method, total cholesterol, LDL-cholesterol, triglycerides, arterial hypertension, obesity and metabolic syndrome. The relationship between cardiovascular risk factors and Kt/V index was analyzed with the variant and multivariant analysis. RESULTS: The HOMA median (interquartile range) of the patients was 1.16 (0.53-5.77). HOMA was correlated with triglycerides and HDL-cholesterol levels. HOMA was significantly greater in those who had less adapted dialysis (Kt/V < 1.4) (1.9 +/- 1.3 vs 1.0 +/- 0.3, p = 0.02). Furthermore, a negative correlation was found between HOMA and Kt/V. The multivariant analysis of the factors associated to HOMA demonstrated that the only associated parameters were Kt/V greater than 1.4, body mass index and age. CONCLUSIONS: In patients with chronic renal failure, adapted dialysis, determined by the Kt/V index, correlated negatively with insulin resistance. Based on these data, we suggest the need for longitudinal studies that consider this index as a predictive variable of cardiovascular events in this type of patients.

T cell receptor excision circles (TRECs), CD4+, CD8+, and their CD45RO+, and CD45RA+, subpopulations in hepatitis C virus (HCV)-HIV-co-infected patients during treatment with interferon alpha plus ribavirin: analysis in a population on effective antiretroviral therapy.

Interferon (IFN)-alpha induced CD4(+) T lymphopenia is a toxic effect of the treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-co-infected patients. To increase the knowledge about this secondary effect, we performed an analysis of the evolution of the T cell receptor excision circles (TRECs), CD4(+) and CD8(+) T cells and of their CD45RO(+) and CD45RA(+) subpopulations during the treatment of chronic hepatitis HCV with peginterferon alpha (pegIFN-alpha) + ribavirin. Twenty HCV/HIV-co-infected patients, with undetectable HIV load after highly active antiretroviral therapy (HAART), were treated with pegIFN-alpha + ribavirin. TRECs were determined using real-time polymerase chain reaction. CD4(+) and CD8(+) T cells and their CD45RO(+) and CD45RA(+) subpopulations were analysed by two-colour flow cytometry. Median baseline CD4(+) and CD8(+) T cells were 592 mm(3) and 874 mm(3), respectively. Median baseline CD45RO(+) subpopulation was 48% for CD4(+) T and 57% for CD8(+) T lymphocytes. A progressive decrease in both T cell populations, as well as of their CD45RO(+) and CD45RA(+) subpopulations, was detected, with a difference between the baseline and nadir levels approaching 50%. The evolution of T cell populations and TRECs was independent of the response to the treatment. T lymphocytes and their subpopulations returned to baseline levels at 24 weeks after the end of treatment, with the exception of the T CD4(+) CD45RA(+) subpopulation. The ratio of CD4(+) CD45RO(+)/CD4(+) CD45RA(+) increased from 0.89 (baseline) to 1.44 (24 weeks after the end of the therapy). TRECs/ml did not return to the basal values. In conclusion, a significant reduction of CD4(+) and CD8(+) T cells, and of their CD45RA(+) and CD45RO(+) subpopulations, in HIV/HCV co-infected patients treated with pegIFN-alpha was observed. Both subpopulations increased after the suppression of treatment, but the CD4(+) CD45RA subpopulation did not reach the basal levels as a consequence, at least in part, of a decrease in thymic production.

Modificaciones en los ingresos y mortalidad de los pacientes con infección por VIH durante el período 2001-2003 (réplica) / Modifications in admissions and mortality of patients with HIV infection during the period 2001-2003 (response)

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Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: effects on leptin and TNF-alpha.

The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

Modulation of the anti-inflammatory interleukin 10 and of proapoptotic IL-18 in patients with chronic hepatitis C treated with interferon alpha and ribavirin.

The aim of this work was to analyse apoptosis rate, measured by the serum levels of proapoptotic interleukin (IL)-18 and of soluble Fas (sFas), as well as of anti-inflammatory IL-10, in patients with chronic hepatitis C, at baseline and after treatment with interferon alpha and ribavirin. Twenty-seven patients with biopsy-proven chronic hepatitis C were studied, at baseline and after treatment with interferon alpha (21 cases) or pegylated interferon (6 cases) plus ribavirin. A group of 15 healthy sex- and age-matched individuals was selected as control. Serum concentrations of sFas, IL-10 and IL-18 were determined by ELISA in sandwich. The relationship of these molecules to necro-inflammatory and fibrotic activity was evaluated. Evolution of the serum concentrations of these molecules was analysed after treatment. Significantly increased serum concentrations of sFas were detected in patients with chronic hepatitis, compared with controls. Levels of this molecule were significantly correlated with necroinflammatory activity. Likewise, concentrations of IL-10 were significantly increased in the group of patients, compared with controls. Treatment with interferon and ribavirin induced a significant decrease of IL-18 concentration independently of the viral response. In contrast, levels of sFas decreased only in those patients with sustained response to therapy. Finally, baseline levels of IL-10 were significantly increased in patients without response to treatment, compared with those with sustained response, but the concentration did not change with the treatment. Increased serum levels of IL-10 are a negative prognostic marker of response to hepatitis C treatment. A significant decrease of apoptotic rate, as determined by sFas, can be expected in patients with a response to therapy.