Implicancia del polimorfismo de IL28B en la infección por el virus de la Hepatitis C / Role of IL28B ppolymorphism in Hepatitis C infection

La evolución de la infección por HCV está influenciada por factores del virus y del hospedador. Entre los que atañen al virus, el genotipo es el principal factor predictivo basal de la respuesta virológica sostenida. En cuanto al hospedador, recientemente tres grupos independientes identificaron, mediante estudios de asociación genómica amplia (GWAS), una correlación entre el polimorfismo rs12979860 cercano al locus de la interleuquina 28B y la respuesta virológica sostenida. Esta contribución es sustancial en pacientes infectados por HCV-1/4; mientras que en infecciones con HCV-2/3, que usualmente son las más exitosas per se, la ventaja conferida por el polimorfismo es exigua. Por otra parte, en pacientes HIV/HCV co-infectados la contribución del polimorfismo es similar a la observada en pacientes HCV mono-infectados. La determinación del polimorfismo de IL28B conjuntamente con el genotipo de HCV podría ser de utilización del tratamiento anti-HCV

The likelihood of attaining a sustained virological response in patients with chronic HCV infection depends on viral and host related factores. Among those related to the virus, the genotype is the strongest basal predictor of sustained virological response. As regards host factores three independent studies recently identified, through genome-wide association study (GWAS), a relationship between the rs12979860 single nucleotide polymorphisms near the interleukin 28B locus and the sustained virological reponse. This contribution had been proven in HCV-1/4 infected patients; whereas, in HCV-2/3 infections, usually the most successful treated, the advantage conferred by the polymorphism was limited. In addition, in HIV/HCV co-infections the contribution fof IL28B polymorphism is similar to that observed in HCV mono-infected patients. used in conjunction with HCV genotype, IL28B rs12979860 polymorphism may provide addional discriminatory power to identify kikely responders to treatment. These findings sugest the possibility of personalized medicine for the treatmet of this desease

How to distinguish normal liver from chronic hepatitis in anti-HCV positive individuals with normal alanine aminotranferase levels

The aim of this study was to characterize the biochemical, virological and histological profile of patients with HCV infection and persistently normal alanine aminotransferase levels (PNALT) in order to discriminate between normal liver and chronic hepatitis. Twenty eight anti-HCV positive patients with PNALT were studied. Twelve (42.9) patients showed normal liver while 16 (57.1) had chronic hepatitis. In patients with normal liver, the mean of ALT level differed from patients with chronic hepatitis (16.3 IU/L versus 25.6 IU/L, p 0.000089). By considering different ALT values as upper normal limit, sensitivity, specificity, positive and negative predictive values were calculated and the value of 18 IU/l showed 88, 90, 94 and 82, respectively, in predicting chronic hepatitis. In conclusion, patients with normal liver had lower ALT levels than those with chronic hepatitis and by establishing 18 IU/L as a new upper limit of normal ALT value, it was possible to differentiate normal liver from chronic hepatitis in HCV patients with PNALT (AU)#S

Relationship between diversity of hepatitis C quasispecies and histological severity of liver disease

The aim of this work to assess in the diversity of hepatitis C virus (HCV) quasispecies is related to histological severity and duration of infection in a cohort of untreated patients with an estimated onset of the disease. A total of 27 patients with diagnosis of chronic liver disease and history of blood transfusion (n = 16) or intravenous drug use (IDU) (n = 11) were included. All were anti-HCV positive and had detectable serum drug injection. Patients who consumed drugs for more than 2 years, or were coinfected with HBV or HIV were excluded. History of alcohol intake (> 80 g/day), ALT level and age at infection were recorded. Histological assessment of grading and staging was performed according to knodell score. The quasispecies diversity was investigated by single strand conformation polymorphism (SSCP) target to HVR-E2 region and SSCP pattern was evaluated as a single or multiple bands. The number of quasispecies did not correlate with estimated duration of the disease. Patients who acquired hepatitis C by blood transfusion did not differ in number of bands from patients who were IDU. There was no correlation between the heterogeneity of HCV quasispecies and age, serum ALT, Knodell score, HAI and fibrosis. In clonclusion the quasiespecies diversity of E2 had no correlation with grade and stage of chronic HCV infection and the presence of quasispecies was independent of the duration of the disease.

In vivo down regulation of HIV replication after hepatitis C superinfection

There are increasing molecular and clinical evidences that the effects of human immunodeficiency virus (HIV) infection can be modified by coinfection with other viruses. The objective was to investigate the viral interaction between HIV and hepatitis C virus (HCV) after HCV superinfection. A 16 year-old pregnant woman was evaluated because of icteric acute hepatitis. Admission laboratory tests showed the following results: ALT 877 IU/L; AST 1822 1822 IU/L; bilirubin 6.79 mg/dl. Diagnosis of acute HCV was based on detection of serum HCV RNA by PCR and anti-HCV seroconversion. ELISA for anti HIV testing was positive and confirmed by western blot. Serum markers for other viruses were negative. The patient was followed during 19 months; serum samples were taken monthly during this period for detection of plasma HIV and HCV RNA. Levels of plasma HIV-RNA were positive in all samples ttested before and after the onset of acute hepatitis C. Six months later and a for two month period, and 13 months later for a period of one month HIV viremia was undetectable; then HIV-RNA in plasma was detectable again. In conclusion, HCV superinfection may have temporarily interfered with HIV replication in our patient. The following observations support our hypothesis: it has been demonstrated that HIV-1 replication is suppressed by HCV core protein which has transcriptional regulation properties of several viral and cellular promoters. Clinical implications of this event are not generally known and the interaction between these two viruses in dual infections is worth considering.