Assessment of therapeutic benefit of antiviral therapy in chronic hepatitis C: is hepatic venous pressure gradient a better end point?

Chronic hepatitis C is a major healthcare problem. The response to antiviral therapy for patients with chronic hepatitis C has previously been defined biochemically and by PCR. However, changes in the hepatic venous pressure gradient (HVPG) may be considered as an adjunctive end point for the therapeutic evaluation of antiviral therapy in chronic hepatitis C. It is a validated technique which is safe, well tolerated, well established, and reproducible. Serial HVPG measurements may be the best way to evaluate response to therapy in chronic hepatitis C.

Hepatitis G virus infection in primary Sj��gren's syndrome: analysis in a series of 100 patients.

OBJECTIVE To determine the prevalence and clinical significance of hepatitis G virus (HGV) infection in a large cohort of patients with primary Sj��gren��s syndrome (SS). PATIENTS AND METHODS The study included 100 consecutive patients (92 female and eight male), with a mean age of 62 years (range 31��80) that were prospectively visited in our unit. All patients fulfilled the European Community criteria for SS and underwent a complete history, physical examination, as well as biochemical and immunological evaluation for liver disease. Two hundred volunteer blood donors were also studied. The presence of HGV-RNA was investigated in the serum of all patients and donors. Aditionally, HBsAg and antibodies to hepatitis C virus were determined. RESULTS Four patients (4%) and six volunteer blood donors (3%) presented HGV-RNA sequences in serum. HGV infection was associated with biochemical signs of liver involvement in two (50%) patients. When compared with primary SS patients without HGV infection, no significant differences were found in terms of clinical or immunological features. HCV coinfection occurs in one (25%) of the four patients with HGV infection. CONCLUSION The prevalence of HGV infection in patients with primary SS is low in the geographical area of the study and HCV coinfection is very uncommon. HGV infection alone does not seen to be an important cause of chronic liver injury in the patients with primary SS in this area.

Hepatitis G virus infection in primary Sj��gren's syndrome: analysis in a series of 100 patients.

OBJECTIVE To determine the prevalence and clinical significance of hepatitis G virus (HGV) infection in a large cohort of patients with primary Sj��gren��s syndrome (SS). PATIENTS AND METHODS The study included 100 consecutive patients (92 female and eight male), with a mean age of 62 years (range 31��80) that were prospectively visited in our unit. All patients fulfilled the European Community criteria for SS and underwent a complete history, physical examination, as well as biochemical and immunological evaluation for liver disease. Two hundred volunteer blood donors were also studied. The presence of HGV-RNA was investigated in the serum of all patients and donors. Aditionally, HBsAg and antibodies to hepatitis C virus were determined. RESULTS Four patients (4%) and six volunteer blood donors (3%) presented HGV-RNA sequences in serum. HGV infection was associated with biochemical signs of liver involvement in two (50%) patients. When compared with primary SS patients without HGV infection, no significant differences were found in terms of clinical or immunological features. HCV coinfection occurs in one (25%) of the four patients with HGV infection. CONCLUSION The prevalence of HGV infection in patients with primary SS is low in the geographical area of the study and HCV coinfection is very uncommon. HGV infection alone does not seen to be an important cause of chronic liver injury in the patients with primary SS in this area.

Selecci��n de p��ptidos sint��ticos del Virus de la Hepatitis G (GBV-C/HGV) inhibidores del P��ptido de Fusi��n HIV-I

El GB virus C (GBV-C) o virus de l'hepatitis G (HGV) es un virus format per una ��nica cadena de RNA que pertany a la familia Flaviviridae. En els ��ltims anys, s'han publicat nombrosos treballs en els quals s'associa la coinfecci�� del GBV-C i del virus de la immunodefici��ncia humana (VIH) amb una menor progressi�� de l'esmentada malaltia aix�� com amb una major superviv��ncia dels pacients una vegada que la SIDA s'ha desenvolupat. El mecanisme pel qual el virus GBV-C/HGV exerceix un ���efecte protector��� en els pacients amb VIH encara no est�� descrit. L���estudi de la interacci�� entre els virus GBVC/HGV i VIH podria donar lloc al desenvolupament de nous agents terap��utics per al tractament de la SIDA.Treballs recents mostren com la capacitat inhibit��ria del virus del GBV-C/HGV ��s deguda a la seva glicoproteina estructural E2. S���ha vist que aquesta proteina seria capa�� d���inhibir la primera fase de replicaci�� de VIH, aix�� com la uni�� i la fusi�� amb les membranes cel���lulars. Sobre la base d���aquests estudis, l���objectiu d���aquest treball ha estat seleccionar inhibidors del p��ptid de fusi�� del VIH utilitzant p��ptids sint��tics de la proteina E2 del GBV-C/HGV. El treball realitzat ha consistit en estudiar, utilitzant assajos biof��sics de leakage i de lipid mixing, la capacitat dels p��ptids de la proteina estructural del virus del GBV-C/HGV per inhibir la interacci�� i el proc��s de desestabilitzaci�� de membranes indu��des pel p��ptid de fusi�� de la glicoproteina de l���embolcall, GP41, del VIH. Aquests assajos, com es descriu en treballs anteriors, han resultat ��tils per a la selecci�� i la identificaci�� de compostos amb activitat espec��fica anti-GP41. Es pot afirmar que efectivament els p��ptids seleccionats de la proteina E2 del virus del GBV-C/HGV inhibeixen l���activitat del p��ptid de fusi�� del VIH probablement com a consequ��ncia d���un canvi conformacional en aquest darrer.

An��lisis de supervivencia post-trasplante hep��tico por Cirrosis post-hepatitis C en pacientes coinfectados VIH/VHC, en comparaci��n con monoinfectados por VHC.

La TARGA (terapia antirretroviral de gran activitat) ha camviat el pron��stic dels pacients infectats pel VIH. Actualment la cirrosi per VHC y el hepatocarcinoma son les principales causes de mort. El trasplantament hep��tic (TH) es una indicaci�� recent en aquests pacients. Objectius: Comparar la superviv��ncia post-TH en pacients coinfectats VHC/VIH front a monoinfectats VHC. Conclusions: Els resultats preliminars en el nostre centre son inferiors en pacients coinfectats en comparaci�� amb els controls, que podr��a ser degut a contraindicacions para el tractament antiviral i a una menor eficacia del mateix.

Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid

Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.

Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid

Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.

Ultra-Deep Pyrosequencing Detects Conserved Genomic Sites and Quantifies Linkage of Drug-Resistant Amino Acid Changes in the Hepatitis B Virus Genome

Selection of amino acid substitutions associated with resistance to nucleos(t)ide-analog (NA) therapy in the hepatitis B virus (HBV) reverse transcriptase (RT) and their combination in a single viral genome complicates treatment of chronic HBV infection and may affect the overlapping surface coding region. In this study, the variability of an overlapping polymerase-surface region, critical for NA resistance, is investigated before treatment and under antiviral therapy, with assessment of NA-resistant amino acid changes simultaneously occurring in the same genome (linkage analysis) and their influence on the surface coding region.

Seguimiento a 5 a��os de pacientes con hepatits cr��nica C y respuesta viral sostenida

L'objectiu va ser avaluar la persist��ncia de resposta viral sostinguda als 5 anys de seguiment en pacients amb hepatitis cr��nica per virus C tractats amb interfer�� pegilat i ribavirina. Des d'agost de 2001 fins a maig de 2004, es van incloure tots els pacients del nostre centre tractats amb interfer�� pegilat i ribavirina que van assolir resposta viral sostinguda. Es van recollir dades demogr��fiques, histol��giques, bioqu��mics i virol��giques durant el tractament i als 5 anys d'haver obtingut la resposta viral sostinguda. Nom��s un dels pacients va presentar recurr��ncia virol��gica (taxa de recurr��ncia viral a llarg termini molt baixa).

Cost del tractament del SIDA i d'Hepatitis C per a l'Estat : Comparaci�� de la despesa d'una persona en llibertat vs. un pres

Un dels principals motius que ens va impulsar en l���elecci�� del tema ��s que es tracta d���untema que pot despertar curiositat entre la poblaci��.Un altre motiu, es que varem trobar que est�� ��ntimament relacionat amb els estudis queestem cursant, donat que afecta als pressupostos de l���estat i a la seva restricci��pressupost��ria, i per tant, est�� directament relacionat amb la macroeconomia. En el nostrecas, reduirem l�����mbit d���estudi al territori catal��, de manera que estudiarem aquestes duesmalalties dins la despesa en sanitat p��blica catalana. A dem��s, estan finan��ades amb elsnostres impostos, i per tant la seva despesa afecta a la restricci�� pressupost��ria delsciutadans.L���elecci�� d���aquestes malalties no ha estat feta a l���atzar. Inicialment, varem pensar enestudiar els costos dels interns penitenciaris que patien aquestes malalties. Com que laSIDA i d���hepatitis C s��n les malalties m��s freq��ents dins la pres��, i les que tenen unscostos m��s caracter��stics donada la complexitat dels seus tractaments, varem pensar queserien prou representatives.No obstant, a mesura que ens an��vem endinsant en el tema, ens varem adonar que tamb��seria molt interessant comparar el cost de les malalties amb el de les persones no recluses, iesbrinar si hi havia algun tipus de cost diferencial. ��s per aix�� que varem decidir analitzaraquestes dues malalties tant dins com fora.Un altre factor que ens ha impulsat en l���elecci�� del tema ��s el fet que el nombre d���interns ales presons t�� un ritme de creixement constant que s���ha accelerat en els ��ltims anys,sobretot degut a l���augment de la immigraci��. Aix�� implica un augment progressiu de ladespesa, que es tradueix en una necessitat d���ingressos majors per tal de poder equilibrar larestricci�� de la qual parl��vem abans.Tamb�� varem voler anar una mica m��s lluny i analitzar el pes d���aquestes malalties dins dela despesa que la generalitat ha establert per a la sanitat p��blica. Com les dues son MDO (malalties de declaraci�� obligat��ria ) estan finan��ades completament pel sector p��blic.L���objectiu era veure si representaven un cost tant elevat com pens��vem.OBJECTIUS DEL TREBALL:�� Demostrar l���elevat cost que suposen certes malalties per l���estat.�� Manifestar els canvis en el cost de les malalties amb l���evoluci�� delstractaments.�� Analitzar els costos sanitaris extres que es produeixen a les presons.�� Destacar l���augment accelerat del nombre d���interns i l���augment del cost sanitarique aix�� suposa. METODOLOGIA: Per tal de poder realitzar l���estudi comparatiu, hem hagut de calcular manualment els costosde les malalties, tot informant-nos del preu dels medicament, les dosis, el cost de lesconsultes externes,etc. A m��s, per a calcular el cost del tractament dins la pres��, ens hemhagut d���informar dels aspectes m��s generals que envolten a un pres, per poder veure sirealment existeix un cost diferencial respecte la malaltia a l���exterior. Per obtenir aquestesdiverses informacions, ens hem hagut de posar en contacte amb el personal que treballa ala pres�� que hem pres com a model d���estudi.Aix��, podem dividir les nostres fonts d���informaci�� en 3 categories:��� Obtenci�� d���informaci�� directament amb el personal de la pres��:��� Entrevista amb la directora d���infermeria de la Secretaria de ServeisPenitenciaris, Rehabilitaci�� i Just��cia Juvenil��� Entrevista amb la Cap d���infermeria del Centre Quatre Camins.��� Informaci�� a partir de mostres facilitades pels propis funcionaris de la pres����� Informaci�� a partir d���estudis sobre el tema i de dades oficials, concretament lesdades oficials sobre els Pressupostos de la Generalitat.

Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis.

Background: There is little information about the effect of infliximab on the clinical course of liver disease in Crohn's disease patients with concomitant hepatitis B virus (HBV) infection. Theoretically, immunosuppression induced by infliximab will facilitate viral replication which could be followed by a flare or exacerbation of disease when therapy is discontinued. There are no specific recommendations on surveillance and treatment of HBV before infliximab infusion. Two cases of severe hepatic failure related to infliximab infusions have been described in patients with rheumatic diseases. Patients and methods: Hepatitis markers (C and B) and liver function tests were prospectively determined to 80 Crohn's disease patients requiring infliximab infusion in three hospitals in Spain. Results: Three Crohn��s disease patients with chronic HBV infection were identified. Two of the three patients with chronic HBV infection suffered severe reactivation of chronic hepatitis B after withdrawal of infliximab therapy and one died. A third patient, who was treated with lamivudine at the time of infliximab therapy, had no clinical or biochemical worsening of liver disease during or after therapy. From the remaining 80 patients, six received the hepatitis B vaccine. Three patients had antibodies to both hepatitis B surface antigen (anti-HBs) and hepatitis B core protein (anti-HBc) with normal aminotransferase levels, and one patient had positive anti-hepatitis C virus (HCV) antibodies, negative HCV RNA, and normal aminotransferase levels. Except for the patients with chronic HBV infection, no significant changes in hepatic function were detected. Conclusions: Patients with Crohn's disease who are candidates for infliximab therapy should be tested for hepatitis B serological markers before treatment and considered for prophylaxis of reactivation using antiviral therapy if positive.