AIM: Hepatitis G virus (HGV) is a newly identified RNA virus belonging to the Flaviviridae genus. HGV infection has been reported in 1-2% of blood donors and 5-20% of adult patients with various liver diseases. There are no published reports addressing the role of HGV infection in children. We have assessed the prevalence and impact of HGV infection in children with liver disease. METHOD: 107 children with liver disease were studied (12 chronic Hepatitis C virus (HCV) infection, 27 chronic Hepatitis B virus (HBV) infection, 12 fulminant hepatic failure (FHF, n = 12: 10 idiopathic; 2 due to HBV infection), 7 graft dysfunction following liver transplantation (GDF), 20 cryptogenic liver disease (CRY) and 29 autoimmune liver disease). Each patient was examined for HGV RNA by RT-PCR using primers specific for the 5′ non-coding region followed by ELISA (Boehringer Mannheim). Further samples were analysed from those who were found to be positive. RESULTS: HGV RNA was detected in 4/107 (one each with HBV, FHF, GDF and CRY). Risk factors were identified from 3 patients, including blood transfusion and/or medical treatment in Eastern Europe. In the case with HBV infection, HGV RNA was detected before interferon (IFN) therapy, but became negative after IFN. In the case of GDF, HGV RNA was positive before and after transplantation. No clear relationship between liver dysfunction and HGV RNA was found. CONCLUSIONS: The prevalence of HGV infection in children with liver disease is higher than that in blood donors but lower than that in adult patients with liver disease. However, HGV is not associated with any specific disease group and does not seem to be a major aetiological factor of liver disease in childhood in the UK.
Interferon alfa (IFN-α) is the primary treatment for chronic hepatitis B. The standard duration of IFN-α therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-α treatment in patients with chronic hepatitis B. To investigate whether treatment prolongation could enhance the rate of hepatitis B e antigen (HBeAg) seroconversion, we conducted a prospective, controlled, multicenter trial in which all patients were treated with a standard regimen of 10 million units IFN-α 3 times per week over 16 weeks. Patients who were still HBeAg-positive after 16 weeks of therapy were randomized to prolongation of the identical regimen up to 32 weeks (prolonged therapy) or discontinuation of treatment (standard therapy). Among the 162 patients who entered the study, 27 (17%) were HBeAg-negative after the first 16 weeks of treatment, and 118 were randomized to standard or prolonged therapy. After randomization, a response (HBeAg seroconversion and sustained hepatitis B virus [HBV]-DNA negativity) was observed in 7 of the 57 (12%) patients assigned to standard therapy versus 17 of the 61 (28%) patients assigned to prolonged therapy ( P = .04). A low level of viral replication after 16 weeks of treatment, as indicated by serum HBV-DNA values under 10 pg/mL, was found to be the only independent predictor of response (52% vs. 0%; P < .001) during prolonged therapy. The prolonged IFN-α schedule was well tolerated in the large majority of patients. In chronic hepatitis B, prolongation of IFN-α therapy up to 32 weeks is superior to a standard course of 16 weeks. Those patients who exhibit a low level of viral replication at the end of the standard regimen benefit most from prolonged treatment.
Weak T-cell reactivity to hepatitis B virus (HBV) is thought to be the dominant cause for chronic HBV infection. Treatment with adefovir dipivoxil (ADV) increases the rate of HBV e antigen (HBeAg) loss; however, the immune mechanisms associated with this treatment response are not understood. Serial analysis of HBV-specific CD4+ T-cell reactivity was performed during 48 weeks of therapy with ADV and correlated with treatment outcome for 19 HBeAg-positive patients receiving ADV (n = 13) or the placebo (n = 6). We tested T-cell reactivity to HBV at seven protocol time points by proliferation, cytokine production, and enzyme-linked immunospot assays. A panel of serum cytokines was quantitated by cytokine bead array. ADV-treated patients showed increased CD4+ T-cell responses to HBV and lower serum levels of cytokines compared to those of placebo-treated patients. Enhanced CD4+ T-cell reactivity to HBV, which peaked at treatment week 16, was confined to a subgroup of ADV-treated patients who achieved greater viral suppression (5.3 +/- 0.3 log(10) copies/ml [mean +/- standard error of the mean {SEM}] serum HBV DNA reduction from baseline) and HBeAg loss, but not to ADV-treated patients with moderate (3.4 +/- 0.2 log(10) copies/ml [mean +/- SEM]) viremia reduction who remained HBeAg positive or to patients receiving the placebo. In conclusion, T-cell reactivity to HBV increases in a proportion of ADV-treated patients and is associated with greater suppression of HBV replication and HBeAg loss.
Objective. Hepatitis C virus infection (HCV) has a high rate of chronic evolution; however, the underlying mechanisms remain to be elucidated. We investigated natural clinical, virological, and immunological course of acute HCV infection in order to identify possible prognostic factors of spontaneous resolution and to gain more understanding of early characteristics responsible for viral clearance or persistence. Materials and methods. Eight patients with acute symptomatic hepatitis C were prospectively followed up for more than 6 months (range, 8–14 months). None of the individuals received antiviral therapy during the study period. We analyzed biochemical, virological, and immunological parameters of these patients detected at different time-points of the follow-up. Plasma HCV RNA was quantitated using TaqManâ real-time polymerase chain reaction. Virusspecific CD4+ T cells were enumerated by interferon-gamma (IFN-g) ELISpot assay. Results. Two of eight individuals resolved HCV spontaneously, while the remaining patients developed chronic HCV infection. HCV RNA became undetectable within 14 days of the study, followed by a rapid alanine aminotransferase normalization in patients with resolved infection. On the contrary, chronically infected subjects demonstrated persistent viremia or intermittently undetectable HCV-RNA, accompanied by polyphasic alanine aminotransferase profile throughout the study. Patients with self-limited hepatitis C displayed the strongest virus-specific CD4+ T (IFN-g) cell reactivity within the first weeks of the follow-up, while persistently infected subjects initially showed a weak antiviral CD4+ T (IFN-g) cell response. Conclusions. In most cases, acute hepatitis C progresses to chronic disease. Viral clearance within the first month after clinical presentation accompanied by monophasic alanine aminotransferase profile could predict recovery. Early and strong CD4+/Th1 immune response against HCV might play an important role in the disease resolution.
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