Model and neural control of the depth of anesthesia during surgery

At present, the experimentation of anesthetic drugs on patients requires a regulation protocol, and the response of each patient to several doses of entry drug must be well known. Therefore, the development of pharmacological dose control systems is a promising field of research in anesthesiology. In this paper it has been developed a non-linear compartmental pharmacokinetic-pharmacodynamical model which describes the anesthesia depth effect on a sufficiently reliable way over a set of patients with the depth effect quantified by the Bi-Spectral Index. Afterwards, an Artificial Neural Network (ANN) predictive controller has been designed based on the depth of anesthesia model so as to keep the patient on the optimum condition while he undergoes surgical treatment. For the purpose of quantifying the efficiency of the neural predictive controller, a classical proportional-integral-derivative controller has also been developed to compare both strategies. Results show the superior performance of predictive neural controller during Bi- Spectral Index reference tracking.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A metabolomic approach to study the rhizodeposition in the tritrophic interaction: tomato, Pochonia chlamydosporia and Meloidogyne javanica

A combined chemometrics-metabolomics approach [excitation–emission matrix (EEM) fluorescence spectroscopy, nuclear magnetic resonance (NMR) and high performance liquid chromatography–mass spectrometry (HPLC–MS)] was used to analyse the rhizodeposition of the tritrophic system: tomato, the plant-parasitic nematode Meloidogyne javanica and the nematode-egg parasitic fungus Pochonia chlamydosporia. Exudates from M. javanica roots were sampled at root penetration (early) and gall development (late). EMM indicated that late root exudates from M. javanica treatments contained more aromatic amino acid compounds than the rest (control, P. chlamydosporia or P. chlamydosporia and M. javanica). 1H NMR showed that organic acids (acetate, lactate, malate, succinate and formic acid) and one unassigned aromatic compound (peak no. 22) were the most relevant metabolites in root exudates. Robust principal component analysis (PCA) grouped early exudates for nematode (PC1) or fungus presence (PC3). PCA found (PC1, 73.31 %) increased acetate and reduced lactate and an unassigned peak no. 22 characteristic of M. javanica root exudates resulting from nematode invasion and feeding. An increase of peak no. 22 (PC3, 4.82 %) characteristic of P. chlamydosporia exudates could be a plant “primer” defence. In late ones in PC3 (8.73 %) the presence of the nematode grouped the samples. HPLC–MS determined rhizosphere fingerprints of 16 (early) and 25 (late exudates) m/z signals, respectively. Late signals were exclusive from M. javanica exudates confirming EEM and 1H NMR results. A 235 m/z signal reduced in M. javanica root exudates (early and late) could be a repressed plant defense. This metabolomic approach and other rhizosphere -omics studies could help to improve plant growth and reduce nematode damage sustainably.This research was funded by the Spanish Ministry of Science and Innovation Grants AGL 2008-00716/AGR, AGL 2011-29297 and with a grant from the University of Alicante to N. Escudero (UAFPU2011)

Evolución clínica y pronóstico de la ascitis neutrocítica con cultivo negativo (ANCN) y la peritonitis bacteriana espontánea (PBE)

263 pacients cirròtics que van presentar la primera descompensació ascítica es van seguir de forma prospectiva. A tots els pacients se'ls va realitzar anàlisi del líquid ascític. 58 pacients van desenvolupar 83 episodis d'infecció del líquid ascític. En 44 episodis el cultiu va ser negatiu i en 37 va ser positiu. A l'ingrès, els pacients amb ANCN van presentar una funció hepàtica i renal millor que aquells amb ANCN. La infecció del líquid ascític es va resoldre més precoçment als pacients amb ANCN, amb una menor incidència d'insuficiència renal. Es va observar una tendència a presentar una menor mortalitat acumulada a l'any al grup de pacients amb ANCN. La ANCN apareix sobretoto en cirròtics amb una malaltia hepàtica menys evolucionada.263 pacientes cirróticos que presentaron la primera descompensación ascítica fueron seguidos de forma prospectiva. En todos los pacientes se realizó análisis del líquido ascítico. 58 pacientes desarrollaron 83 episodios de infección del líquido ascítico. En 44 episodios el cultivo fue negativo y en 37 fue positivo. Al ingreso, los pacientes con ANCN presentaban una función hepática y renal mejor que aquéllos con PBE. La infección del líquido ascítico se resolvió de forma más precoz en los pacientes con ANCN, con una menor incidencia de insuficiencia renal. Se observó una tendencia a presentar una menor mortalidad acumulada al año en el grupo de pacientes con ANCN. La ANCN acontece principalmente en cirróticos con una enfermedad hepática menos evolucionada

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19 : a multicentre, randomised, double-blind, non-inferiority phase IIb trial

A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with , . From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4 + and CD8 + T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. HIPRA SCIENTIFIC, S.L.U

Preemptive-TIPS improves outcome in high-risk variceal bleeding : An observational study

Objective Patients admitted with acute variceal bleeding (AVB) and Child Pugh C score (CP\u2010C) or Child Pugh B plus active bleeding at endoscopy (CP\u2010B+AB) are at high risk for treatment failure, rebleeding and mortality. Preemptive TIPS (p\u2010TIPS) has been shown to improve survival in these patients but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high\u2010risk patients. Design Multicenter, international, observational study including 671 patients from 34 centers admitted for AVB and high\u2010risk of treatment failure. Patients were managed according to current guidelines and use of drugs and endoscopic therapy (D+E) or preemptive TIPS (p\u2010TIPS) was based on individual center policy. Results p\u2010TIPS in the setting of AVB is associated with a lower mortality in Child C patients compared to D+E (1 year mortality 22% vs 47% in D+E group; P=0.002). Mortality rate in CP\u2010B+AB patients was low and p\u2010TIPS did not improve it. In CP\u2010C and CP\u2010B +AB patients, p\u2010TIPS reduces treatment failure and rebleeding (1 year CIF\u2010probability of remaining free of the composite endpoint: 92% vs 74% in the D+E group; P=0.017), development of \u201cde novo\u201d or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion p\u2010TIPS must be the treatment of choice in CP\u2010C patients with AVB. Due to the strong benefit in preventing further bleeding and ascites, p\u2010TIPS could be a good treatment strategy for CP\u2010B+AB patients

Cancer data quality and harmonization in Europe: the experience of the BENCHISTA Project – international benchmarking of childhood cancer survival by stage

IntroductionVariation in stage at diagnosis of childhood cancers (CC) may explain differences in survival rates observed across geographical regions. The BENCHISTA project aims to understand these differences and to encourage the application of the Toronto Staging Guidelines (TG) by Population-Based Cancer Registries (PBCRs) to the most common solid paediatric cancers.MethodsPBCRs within and outside Europe were invited to participate and identify all cases of Neuroblastoma, Wilms Tumour, Medulloblastoma, Ewing Sarcoma, Rhabdomyosarcoma and Osteosarcoma diagnosed in a consecutive three-year period (2014-2017) and apply TG at diagnosis. Other non-stage prognostic factors, treatment, progression/recurrence, and cause of death information were collected as optional variables. A minimum of three-year follow-up was required. To standardise TG application by PBCRs, on-line workshops led by six tumour-specific clinical experts were held. To understand the role of data availability and quality, a survey focused on data collection/sharing processes and a quality assurance exercise were generated. To support data harmonization and query resolution a dedicated email and a question-and-answers bank were created.Results67 PBCRs from 28 countries participated and provided a maximally de-personalized, patient-level dataset. For 26 PBCRs, data format and ethical approval obtained by the two sponsoring institutions (UCL and INT) was sufficient for data sharing. 41 participating PBCRs required a Data Transfer Agreement (DTA) to comply with data protection regulations. Due to heterogeneity found in legal aspects, 18 months were spent on finalizing the DTA. The data collection survey was answered by 68 respondents from 63 PBCRs; 44% of them confirmed the ability to re-consult a clinician in cases where stage ascertainment was difficult/uncertain. Of the total participating PBCRs, 75% completed the staging quality assurance exercise, with a median correct answer proportion of 92% [range: 70% (rhabdomyosarcoma) to 100% (Wilms tumour)].ConclusionDifferences in interpretation and processes required to harmonize general data protection regulations across countries were encountered causing delays in data transfer. Despite challenges, the BENCHISTA Project has established a large collaboration between PBCRs and clinicians to collect detailed and standardised TG at a population-level enhancing the understanding of the reasons for variation in overall survival rates for CC, stimulate research and improve national/regional child health plans

Evolución a largo plazo de pacientes con hepatitis C y fibrosis leve-moderada después del tratamiento antivírico. Importancia de su evaluación mediante biopsia hepática o elastografía

La infección por virus C afecta entre 130-150 millones de personas, siendo una de las infecciones víricas más prevalentes y la principal causa de enfermedad hepática en los países desarrollados. La mayoría de casos detectados son en la fase crónica que ocasiona un grado variable de inflamación y fibrosis, que puede evolucionar a cirrosis hepática y/o carcinoma hepatocelular, y puede ser modificado por el tratamiento antivírico. Los objetivos de la presente Tesis son analizar la progresión de la fibrosis en pacientes con fibrosis leve-moderada mediante BH previa y BH o ET posterior, además valorar la influencia del tratamiento antivírico en esta progresión así como en la evolución de la hepatopatía. Se incluyeron un total de 291 pacientes que habían realizado tratamiento. En el grupo 1 se incluyeron 107 pacientes con BH pareada y en el grupo 2, 184 pacientes con ET. Se evaluó en el período de seguimiento la progresión de la fibrosis que se definió como el incremento en el estadío de fibrosis, así como, la evolución a una hepatopatía y sus posibles complicaciones. La fibrosis en la BH inicial fue grado 0 en 87 pacientes (29,9%), grado 1 en 134 pacientes (46%) y grado 2 en 70 pacientes (24,1%), sin diferencias entre ambos grupos de estudio. Se objetivaron diferencias significativas entre los 3 estadíos de fibrosis en el valor de plaquetas, protrombina, colesterol, GOT, GPT y GGT, lo que puede traducir un grado mayor de afectación hepática. Todos los pacientes iniciaron tratamiento antivírico tras la BH. Al final de seguimiento, la fibrosis había progresado en 79 pacientes (27,1%), en 120 pacientes (41,2%) se mantenía igual y en 92 pacientes (31,6%) hubo mejoría. La tasa de progresión cuantificada por la variación de la puntuación METAVIR por año fue del 0,091+-0,11 en NR y de -0,083+-0,08 en RVS (P<0,0001). Los pacientes con F0 presentaron menor progresión de la fibrosis respecto a F1 y F2 (P<0,0001). La probabilidad actuarial global de tener una fibrosis avanzada (F3/4) fue del 1,9% a los 10 años y del 27,6% a los 20 años. En los pacientes con y sin RVS a alguno de los tratamientos fue respectivamente del 0 y 10,2% (RVS) y del 7,2 y 55,7% (NR) (P<0,0001). La probabilidad de presentar cirrosis fue del 1,5% y del 22,6% a los 10 y 20 años, observándose también unas marcadas diferencias entre pacientes que consiguieron la RVS (0 y 5,8% a 10 y 20 años) y los NR (9,8 y 50,5% en dichos períodos (P<0,0001). La probabilidad actuarial de presentar CHC durante el seguimiento global fue del 1 y del 9,8% a los 10 y 20 años. La probabilidad actuarial de supervivencia fue del 1 y el 13,8% a los 10 y 20 años respectivamente. En esta Tesis se ha observado que los pacientes sin fibrosis en la BH inicial tienen una menor progresión de la fibrosis, y es casi nula en los que alcanzan RVS. La ET permite una evaluación de la progresión de la fibrosis con una eficacia similar a la PBH. Se ha observado que el retratamiento de los pacientes NR evita la progresión en los que alcanzan RVS. En cambio, la probabilidad de cirrosis hepática en pacientes NR al tratamiento y retratamiento es del 50% a los 20 años. La actual Tesis pone de manifiesto la importancia de realizar tratamiento antiviral lo antes posible y de alcanzar la RVS.Hepatitis C infection affects between 130-150 million people, being one of most prevalent viral infections and leading cause of liver disease in developed countries. Majority of detected cases are in chronic phase that causes a variable degree of inflammation and fibrosis, which can evolve to hepatic cirrhosis and / or hepatocellular carcinoma, and may be modified by antiviral treatment. Objectives of this Thesis are to analyze progression of fibrosis in patients with mild-moderate fibrosis by previous LB and subsequent LB or ET, in addition to assessing the influence of antiviral treatment in this progression as well as in the evolution of liver disease. A total of 291 patients who had been treated were included. Group 1 included 107 patients with paired LB and in group 2, 184 patients with TE. Progression of fibrosis was defined as increase in the stage of fibrosis, as well as the progression to liver disease and its possibles complications. Fibrosis in initial LB was grade 0 in 87 patients (29.9%), grade 1 in 134 patients (46%) and grade 2 in 70 patients (24.1%), with no difference between two study groups. Significant differences were observed between 3 stages of fibrosis in the value of platelets, prothrombin, cholesterol, GOT, GPT and GGT, which may translate into a higher degree of hepatic involvement. All patients started antiviral treatment after LB. At the end of follow-up, fibrosis progressed in 79 patients (27.1%), 120 patients (41.2%) remained the same and in 92 patients (31.6%) there was improvement. Rate of progression quantified by variation of METAVIR score per year was 0.091 + -0.11 in NR and -0.083 + -0.08 in RVS (P <0.0001). Patients with F0 presented lower fibrosis progression than F1 and F2 (P <0.0001). Overall probability of advanced fibrosis (F3 / 4) was 1.9% at 10 years and 27.6% at 20 years. In patients with and without SVR, was 0 and 10.2% (SVR) and 7.2 and 55.7% (NR), respectively (P <0.0001). Probability of cirrhosis was 1.5% and 22.6% at 10 and 20 years. There were also marked differences between patients who achieved SVR (0 and 5.8% at 10 and 20 years) and who not (9,8 y 50,5% in same periods) (P<0,0001). Probability of CHC during the global follow up was 1 and 9.8% at 10 and 20 years. Survival probability was 1 and 13.8% at 10 and 20 years, respectively. This Thesis has shown that patients without fibrosis in the initial BH have a smaller progression of fibrosis, and is almost null in those that reach RVS. TE allows an evaluation of the progression of fibrosis with an efficacy similar to LB. It has been observed that the retreatment of NR patients avoids the progression in those who reach SVR, whereas the probability of cirrhosis in patients NR to treatment and retreatment is 50% at 20 years. Current Thesis shows value of antiviral treatment and importance to achieve SVR

Evolución clínica y pronóstico de la ascitis neutrocítica con cultivo negativo (ANCN) y la peritonitis bacteriana espontánea (PBE)

263 pacients cirròtics que van presentar la primera descompensació ascítica es van seguir de forma prospectiva. A tots els pacients se’ls va realitzar anàlisi del líquid ascític. 58 pacients van desenvolupar 83 episodis d’infecció del líquid ascític. En 44 episodis el cultiu va ser negatiu i en 37 va ser positiu. A l’ingrès, els pacients amb ANCN van presentar una funció hepàtica i renal millor que aquells amb ANCN. La infecció del líquid ascític es va resoldre més precoçment als pacients amb ANCN, amb una menor incidència d’insuficiència renal. Es va observar una tendència a presentar una menor mortalitat acumulada a l’any al grup de pacients amb ANCN. La ANCN apareix sobretoto en cirròtics amb una malaltia hepàtica menys evolucionada.263 pacientes cirróticos que presentaron la primera descompensación ascítica fueron seguidos de forma prospectiva. En todos los pacientes se realizó análisis del líquido ascítico. 58 pacientes desarrollaron 83 episodios de infección del líquido ascítico. En 44 episodios el cultivo fue negativo y en 37 fue positivo. Al ingreso, los pacientes con ANCN presentaban una función hepática y renal mejor que aquéllos con PBE. La infección del líquido ascítico se resolvió de forma más precoz en los pacientes con ANCN, con una menor incidencia de insuficiencia renal. Se observó una tendencia a presentar una menor mortalidad acumulada al año en el grupo de pacientes con ANCN. La ANCN acontece principalmente en cirróticos con una enfermedad hepática menos evolucionada

Effects of albumin on survival after a hepatic encephalopathy episode: randomized double-blind trial and meta-analysis

No therapies have been proven to increase survival after a hepatic encephalopathy (HE) episode. We hypothesize that two doses of albumin could improve 90-day survival rates after a HE episode. Methods: (1) a randomized double-blind, placebo-controlled trial (BETA) was conducted in 12 hospitals. The effect of albumin (1.5 g/kg at baseline and 1 g/kg on day 3) on 90-day survival rates after a HE episode grade II or higher was evaluated. (2) A meta-analysis of individual patient's data for survival including two clinical trials (BETA and ALFAE) was performed. Results: in total, 82 patients were included. Albumin failed to increase the 90-day transplant-free survival (91.9% vs. 80.5%, p = 0.3). A competing risk analysis was performed, observing a 90-day cumulative incidence of death of 9% in the albumin group vs. 20% in the placebo (p = 0.1). The meta-analysis showed a benefit in the albumin group, with a lower rate of clinical events (death or liver transplant) than patients in the placebo (HR, 0.44; 95% CI, 0.21-0.82), when analyzed by a competing risk analysis (90-days mortality rate of 11% in the albumin group vs. 30% in the placebo, p = 0.02). Conclusions: repeated doses of albumin might be beneficial for patient's survival as an add-on therapy after an HE episode, but an adequately powered trial is needed

Evolución a largo plazo de pacientes con hepatitis C y fibrosis leve-moderada (F0-2) después del tratamiento antivírico : importancia de su evaluación mediante biopsia hepática o elastografía /

La infección por virus C afecta entre 130-150 millones de personas, siendo una de las infecciones víricas más prevalentes y la principal causa de enfermedad hepática en los países desarrollados. La mayoría de casos detectados son en la fase crónica que ocasiona un grado variable de inflamación y fibrosis, que puede evolucionar a cirrosis hepática y/o carcinoma hepatocelular, y puede ser modificado por el tratamiento antivírico. Los objetivos de la presente Tesis son analizar la progresión de la fibrosis en pacientes con fibrosis leve-moderada mediante BH previa y BH o ET posterior, además valorar la influencia del tratamiento antivírico en esta progresión así como en la evolución de la hepatopatía. Se incluyeron un total de 291 pacientes que habían realizado tratamiento. En el grupo 1 se incluyeron 107 pacientes con BH pareada y en el grupo 2, 184 pacientes con ET. Se evaluó en el período de seguimiento la progresión de la fibrosis que se definió como el incremento en el estadío de fibrosis, así como, la evolución a una hepatopatía y sus posibles complicaciones. La fibrosis en la BH inicial fue grado 0 en 87 pacientes (29,9%), grado 1 en 134 pacientes (46%) y grado 2 en 70 pacientes (24,1%), sin diferencias entre ambos grupos de estudio. Se objetivaron diferencias significativas entre los 3 estadíos de fibrosis en el valor de plaquetas, protrombina, colesterol, GOT, GPT y GGT, lo que puede traducir un grado mayor de afectación hepática. Todos los pacientes iniciaron tratamiento antivírico tras la BH. Al final de seguimiento, la fibrosis había progresado en 79 pacientes (27,1%), en 120 pacientes (41,2%) se mantenía igual y en 92 pacientes (31,6%) hubo mejoría. La tasa de progresión cuantificada por la variación de la puntuación METAVIR por año fue del 0,091+-0,11 en NR y de -0,083+-0,08 en RVS (P 0,0001). Los pacientes con F0 presentaron menor progresión de la fibrosis respecto a F1 y F2 (P 0,0001). La probabilidad actuarial global de tener una fibrosis avanzada (F3/4) fue del 1,9% a los 10 años y del 27,6% a los 20 años. En los pacientes con y sin RVS a alguno de los tratamientos fue respectivamente del 0 y 10,2% (RVS) y del 7,2 y 55,7% (NR) (P 0,0001). La probabilidad de presentar cirrosis fue del 1,5% y del 22,6% a los 10 y 20 años, observándose también unas marcadas diferencias entre pacientes que consiguieron la RVS (0 y 5,8% a 10 y 20 años) y los NR (9,8 y 50,5% en dichos períodos (P 0,0001). La probabilidad actuarial de presentar CHC durante el seguimiento global fue del 1 y del 9,8% a los 10 y 20 años. La probabilidad actuarial de supervivencia fue del 1 y el 13,8% a los 10 y 20 años respectivamente. En esta Tesis se ha observado que los pacientes sin fibrosis en la BH inicial tienen una menor progresión de la fibrosis, y es casi nula en los que alcanzan RVS. La ET permite una evaluación de la progresión de la fibrosis con una eficacia similar a la PBH. Se ha observado que el retratamiento de los pacientes NR evita la progresión en los que alcanzan RVS. En cambio, la probabilidad de cirrosis hepática en pacientes NR al tratamiento y retratamiento es del 50% a los 20 años. La actual Tesis pone de manifiesto la importancia de realizar tratamiento antiviral lo antes posible y de alcanzar la RVS.Hepatitis C infection affects between 130-150 million people, being one of most prevalent viral infections and leading cause of liver disease in developed countries. Majority of detected cases are in chronic phase that causes a variable degree of inflammation and fibrosis, which can evolve to hepatic cirrhosis and / or hepatocellular carcinoma, and may be modified by antiviral treatment. Objectives of this Thesis are to analyze progression of fibrosis in patients with mild-moderate fibrosis by previous LB and subsequent LB or ET, in addition to assessing the influence of antiviral treatment in this progression as well as in the evolution of liver disease. A total of 291 patients who had been treated were included. Group 1 included 107 patients with paired LB and in group 2, 184 patients with TE. Progression of fibrosis was defined as increase in the stage of fibrosis, as well as the progression to liver disease and its possibles complications. Fibrosis in initial LB was grade 0 in 87 patients (29.9%), grade 1 in 134 patients (46%) and grade 2 in 70 patients (24.1%), with no difference between two study groups. Significant differences were observed between 3 stages of fibrosis in the value of platelets, prothrombin, cholesterol, GOT, GPT and GGT, which may translate into a higher degree of hepatic involvement. All patients started antiviral treatment after LB. At the end of follow-up, fibrosis progressed in 79 patients (27.1%), 120 patients (41.2%) remained the same and in 92 patients (31.6%) there was improvement. Rate of progression quantified by variation of METAVIR score per year was 0.091 + -0.11 in NR and -0.083 + -0.08 in RVS (P 0.0001). Patients with F0 presented lower fibrosis progression than F1 and F2 (P 0.0001). Overall probability of advanced fibrosis (F3 / 4) was 1.9% at 10 years and 27.6% at 20 years. In patients with and without SVR, was 0 and 10.2% (SVR) and 7.2 and 55.7% (NR), respectively (P 0.0001). Probability of cirrhosis was 1.5% and 22.6% at 10 and 20 years. There were also marked differences between patients who achieved SVR (0 and 5.8% at 10 and 20 years) and who not (9,8 y 50,5% in same periods) (P 0,0001). Probability of CHC during the global follow up was 1 and 9.8% at 10 and 20 years. Survival probability was 1 and 13.8% at 10 and 20 years, respectively. This Thesis has shown that patients without fibrosis in the initial BH have a smaller progression of fibrosis, and is almost null in those that reach RVS. TE allows an evaluation of the progression of fibrosis with an efficacy similar to LB. It has been observed that the retreatment of NR patients avoids the progression in those who reach SVR, whereas the probability of cirrhosis in patients NR to treatment and retreatment is 50% at 20 years. Current Thesis shows value of antiviral treatment and importance to achieve SVR