Non-invasive models for predicting histology in patients with chronic hepatitis B

10.1111/j.1478-3231.2006.01287.xLiver International266666-67

Telomerase reverse transcriptase mRNA expression in peripheral lymphocytes of patients with chronic HBV and HCV infections

Telomerase activity is present at low levels in peripheral lymphocytes (PL) and is upregulated upon activation, possibly protecting PL from telomere shortening. As decreased telomere length is considered a sign of cellular senescence, telomerase may, therefore, play an important role on immune function, organ regeneration and carcinogenesis. So far, quantification of human telomerase reverse transcriptase levels (hTERT) in PL, has not been reported. We determined hTERT mRNA levels in PL of hepatitis B virus (HBV) and hepatitis C virus (HCV) patients, in an attempt to address whether hTERT transcripts in PL are altered in these viral diseases, which are characterized by immune dysfunction and increased incidence of hepatocarcinogenesis. hTERT mRNA levels in PL of HBV (n = 17), HCV (n = 24) patients and healthy controls (n = 22) were quantified by real-time polymerase chain reaction. We observed significantly lower hTERT mRNA levels in HBV and HCV patients compared with healthy individuals (P < 0.05). hTERT mRNA levels were not associated with the patients' clinical status (inactive, hepatitis and cirrhosis). Also no correlation was observed between hTERT mRNA expression, and HBV and HCV replicative activity. In the inactive group (n = 18) we observed a negative correlation between hTERT mRNA expression and disease duration (r(s) = -0.52, P < 0.03). We performed for the first time an accurate quantification of hTERT mRNA expression in PL of HBV and HCV patients. The observed low levels of hTERT mRNA expression in the above patients may suggest its involvement in the immunopathogenesis of chronic viral hepatitis

Peginterferon-alpha 2a for the Treatment of Hepatitis B Infection

Chronic hepatitis B is one of the world's most common serious diseases with > 300 million patients worldwide. Currently recommended treatments include conventional interferon (IFN), lamivudine and adefovir. Recently, peginterferon-α (PEG-IFN-α, Pegasys®; Hoffmann-La Roche & Co.) has been approved for use in patients with chronic hepatitis B in the US, the EU, Switzerland, Turkey and in several countries in the Asia-Pacific region. Several trials have been carried out using PEG-IFN-α (40 kDa) compared with conventional IFN, lamivudine monotherapy and a combination of PEG-IFN-α and lamivudine in patients with hepatitis Be antigen- (HBeAg)positive chronic hepatitis B, and patients with HBeAg-negative chronic hepatitis B. PEG-IFN-α was shown to be superior to conventional IFN in HBeAg-positive disease and to lamivudine in both HBeAg-positive and HBeAg-negative chronic hepatitis B. Although there was greater suppression of virus while on therapy, the combination of lamivudine and PEG-IFN-α did not enhance sustained response at the end of the 24-week follow-up period, compared with PEG-IFN monotherapy. In addition, ∼ 3% of patients underwent hepatitis B surface antigen (HBsAg) seroconversion - the ultimate marker of therapeutic response, which is rarely seen following treatment with antiviral agents. The side effect profile was reasonable. PEG-IFN-α could become the treatment of choice in many patients with both HBeAg-positive and HBeAg-negative disease and, in those who fail to respond, consideration could then be given to the use of antiviral agents