Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e Antigen–negative patients receiving lamivudine therapy

Lamivudine has been shown to be effective in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, but its long-term efficacy and the rate of resistant mutations in patients with HBeAg-negative chronic hepatitis B is less clear. Twenty-nine patients with HBeAg-negative chronic hepatitis B, who have received lamivudine for at least 1 year were studied to determine the antiviral response, the rate and pattern of lamivudine-resistant mutations, and the effect of lamivudine-resistant mutations on HBeAg status. The mean duration of treatment was 21 ± 7 months. Before treatment, core promoter variant was detected in 16 (55%) patients and precore stop codon variant in 18 (62%) patients. Serum hepatitis B virus (HBV) DNA was detected by solution hybridization assay in 62%, 4%, and 24% and by polymerase chain reaction (PCR) assay in 100%, 31%, and 40% at months 0, 6, and 24, respectively. The cumulative rates of detection of lamivudine-resistant mutations after 1 and 2 years of treatment were 10% and 56%, respectively. In addition to the duration of treatment, core promoter mutation was associated with the selection of lamivudine-resistant mutants. Three patients with lamivudine-resistant mutations had reversion of the precore stop codon mutation; in 2 patients this was accompanied by the reappearance of HBeAg. We found that lamivudine-resistant mutants were detected at similar rates in patients with HBeAg-negative as in patients with HBeAg-positive chronic hepatitis B. Additional changes in other parts of the HBV genome may restore the replication fitness of lamivudine-resistant mutants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34780/1/510320535_ftp.pd

Calcineurin inhibitors levels reduction during treatment with Sofosbuvir in liver transplanted patients

In liver transplant, during anti-viral therapy for hepatitis C virus (HCV) recurrence, the immunosuppressant levels should be monitored to prevent both toxicity and rejection. Sofosbuvir (SOF) has been used within compassionate programs for HCV recurrence and, according to pharmacokinetic analyses, is not supposed to have significant pharmacological interactions with tacrolimus (Tac) or ciclosporin.1 This was reported in the review article by Koff recently published.2 We treated eight transplant recipients with SOF/ribavirin (RBV) for a severe HCV recurrence, and observed unexpected Tac/ciclosporin reduction during SOF

Genetic heterogeneity of hepatitis C virus in HBV/HCV co-infection

none8noneM.S. De Mitri; G. Morsica; R. Cassini; S. Bagaglio; P. Andreone; G. Bianchi; M. Margotti; M. BernardiM.S. De Mitri; G. Morsica; R. Cassini; S. Bagaglio; P. Andreone; G. Bianchi; M. Margotti; M. Bernard

In vitro effect of indomethacin and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C

Current evidences suggest that non-steroidal anti-inflammatory drugs could enhance the antiviral activity of interferon-\u3b1 in chronic HCV infection. In this study, we investigated the effect of indomethacin, a non-steroidal anti-inflammatory drug, and interferon-\u3b1 on cytokine production by peripheral blood mononuclear cells from 12 untreated patients with chronic hepatitis C. We evaluated the effect of incubation with indomethacin, interferon-\u3b1 or both on synthesis of Th1- (interleukin-2, interferon-\u3b3) and Th2-associated cytokines (interleukin-4, interleukin-10), and of the antiviral protein 2\u2032,5\u2032-oligoadenylate synthetase. Interferon-\u3b1 induced a significant increase in production of interleukin-2. Smaller increases were also seen in the presence of indomethacin, while incubation with both indomethacin and interferon-\u3b1 leads to a synergistic effect. Incubation with indomethacin decreased both interleukin-4 and interleukin-10, whereas interferon-\u3b1 increased these cytokines. The addition of indomethacin to interferon-\u3b1 significantly reversed this interferon-induced increase. Finally, both indomethacin and the association interferon-\u3b1 plus indomethacin determined a significant increase in 2\u2032,5\u2032-oligoadenylate synthetase production compared to both baseline and interferon-\u3b1 alone. In conclusion, indomethacin was able to enhance the antiviral activity of interferon-\u3b1 and to modulate the interferon-induced Th1 and Th2 cytokine response by increasing the Th1-response, fundamental for sustained clearance of HCV, and by decreasing the Th-2 type response, associated with HCV persistenc

In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with eAg-negative chronic hepatitis B

none11mixedLoggi E; Gramenzi A; Margotti M; Cursaro C; Galli S; Vitale G; Grandini E; Scuteri A; Vukotic R; Andreone P; Bernardi M.Loggi E; Gramenzi A; Margotti M; Cursaro C; Galli S; Vitale G; Grandini E; Scuteri A; Vukotic R; Andreone P; Bernardi M