Interferon and other therapies for hepatitis B and hepatitis C infections

Interferon is currently the only approved medication in the United States for treatment of chronic hepatitis B and C infections. The mechanism of action of interferon and guidelines for its administration are reviewed. Important clinical studies involving its use in hepatitis B and C infections are discussed, and investigational therapies for chronic viral hepatitis are highlighted.     

Early therapy with interferon for acute hepatitis C acquired through a needlestick

Chinese hamster lung fibroblast V79 cells have been widely used in studies of DNA damage and DNA repair. Since the p53 gene is involved in normal responses to DNA damage, we have analyzed the molecular genetics and functional status of p53 in V79 cells and primary Chinese hamster embryonic fibroblast (CHEF) cells. The coding product of the p53 gene in CHEF cells was 76 and 75% homologous to human and mouse p53 respectively, and was 95% homologous to the Syrian hamster cells. The V79 p53 sequence contained two point mutations located within a presumed DNA binding domain, as compared with the CHEF cells. Additional immunocytochemical and molecular studies confirmed that the p53 protein in V79 cells was mutated and nonfunctional. Our results indicate that caution should be used in interpreting studies of DNA damage, DNA repair and apoptosis in V79 cells.     

Interferon treatment of children with chronic hepatitis C

Hepatitis C virus (HCV) is the major cause of acquired non-A, non-B hepatitis. Interferon is becoming the standard treatment in adults for chronic hepatitis C, however, the experience with interferon treatment in children is very limited. The review article describes the current approach in the management of children with chronic hepatitis C infection and the review of the literatures.     

Interferon treatment for hepatitis C virus infection in patients on haemodialysis

BACKGROUND: This study examined the efficacy and tolerability of interferon alpha-2b (IFN) in the treatment of chronic hepatitis C virus (HCV) infection in patients on maintenance haemodialysis. METHODS: A 24-month prospective cohort study was performed in 11 HCV RNA-positive haemodialysis patients, who were treated with IFN at 3 MU thrice weekly for 6 months. Serial biochemical and virological monitors included serum alanine aminotransferase levels, and HCV RNA by both qualitative PCR assay and quantitative bDNA assay. HCV genotypes were determined by PCR and nucleotide sequencing. Ten patients had baseline liver biopsy. RESULTS: HCV genotypes 1b and 2b were identified in 10 and one patients respectively. Six (55%) patients had biochemical and/or histological features of chronic active hepatitis before treatment. All 11 patients became HCV RNA-negative by PCR, with normalization of deranged aminotransferase levels, within 2-8 weeks of IFN therapy. HCV RNA reappeared in eight (73%) patients 2-8 weeks after the cessation of IFN, while biochemical relapse occurred in six (55%) patients. Sustained eradication of HCV was achieved in three (27%) patients. Sustained responders were characterized by pretreatment HCV RNA level < 3.5 x 10(5) Eq/ml as determined by the bDNA assay, and less severe histological abnormalities ('Total score' 1.7 +/- 1.2 compared to 5.4 +/- 2.2 in relapsers, P < 0.05). HCV RNA levels were similar before and after IFN treatment in non-responders and relapsers. Persistent malaise and poor appetite were noted in eight (73%) patients during IFN therapy. Other side-effects of IFN included the exacerbation of anaemia, induction of resistance to erythropoietin, weight loss, and reduced serum albumin level. CONCLUSIONS: Eradication of chronic HCV infection with IFN can be achieved in 27% of haemodialysis patients. Predictors of sustained response include low baseline HCV RNA level and mild liver pathology. Virological relapse can occur despite normal liver biochemistry. Exacerbation of anaemia, erythropoietin resistance, and malnutrition constitute the side-effects of IFN that deserve special attention in uraemic subjects.     

Interferon and thymosin combination therapy in naive patients with chronic hepatitis C: preliminary results

The prevalence of Helicobacter pylori (HP) IgG antibodies was analysed in a group of 142 asymptomatic children (group A) and in 31 pediatric patients (group B) with recurrent abdominal pain. HP IgG antibodies were measured by a commercially available fluorescence-enzyme immuno-assay test (Heloritest IgG, Fa Eurospital). In asymptomatic children the prevalence of HP IgG antibodies increased significantly with age from 17% with 6 years to more then 40% with 14 years. A higher prevalence of HP IgG antibodies was found in children living in more crowded housing conditions. Comparing the number of HP IgG positive children in group B (58%) to a matched population from group A (35%) no statistically different prevalence rates were found. Thus HP IgG antibodies are found in similar frequencies, in both, symptomatic and asymptomatic children. Therefore the presence of HP-IgG antibodies does not necessarily indicate that the HP infection is the cause for the recurrent abdominal pain in these children.     

Current therapeutic trends in therapy for chronic viral hepatitis

Hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis delta virus (HDV) are associated with clinically significant chronic infection that may lead to the development of cirrhosis or even hepatocellular carcinoma (HCC). Intervention at the earliest possible stage is needed to prevent such untoward sequelae. Currently, interferon (IFN) is the only approved and widely used agent for the treatment of these infections, including in HBV patients with precore mutant hepatitis or decompensated cirrhosis, but its efficacy is far from satisfactory. Corticosteroid priming has been shown to increase the efficacy of IFN therapy in HBV patients with low abnormal serum transaminase levels, but only a few responders will clear serum hepatitis Bs antigen (HBsAg). Ongoing randomized controlled trials of thymosin alpha 1, lamivudine and famcyclovir have demonstrated encouraging preliminary results. Therapeutic vaccines, such as polypeptides with human leucocyte antigen (HLA)-specific hepatitis B core antigen (HBcAg) epitopes, are under phase II/III clinical trial. For HDV infection, the use of IFN in the early phase of acute superinfection tends to prevent chronic progression. For HCV infection, IFN used at higher doses for a longer period of time is associated with a higher sustained response, but overall it is still not satisfactory. The combined use of ribavirin or corticosteroid priming may improve the effect of IFN therapy by enhancing the durability of the response. Interferon in the acute phase of HCV infection may also prevent chronic progression. There is evidence to suggest that IFN therapy, when associated with response, tends to reduce the risk of cirrhosis or HCC and prolongs survival. There is no doubt that satisfactory treatment of chronic viral infection will require more effective agents and demand optimal treatment strategies, many of which are yet to be found.     

Uridine diphosphate glucose in acute viral hepatitis

200 mg UDPG or placebo respectively were administered after an observation period of 1 week to two randomly constructed groups of patients aged 15-35 yr with acute viral hepatitis but no prior history of disease. In the treated patients, mean decreases were most marked and most rapid in the case of SGOT, SGPT, alkaline phosphatase and total bilirubinaemia. These results offer good reason for supposing that UDPG can be usefully employed in the management of acute viral hepatitis.     

Interferon increases serum thrombopoietin in patients with chronic hepatitis C

We measured serum thrombopoietin (TPO) in chronic hepatitis C treated with interferon (IFN). The platelet count before the therapy was 161.9 x 10(9) +/- 64.1 x 10(9)/l, which decreased to 116.3 x 10(9) +/- 48.4 x 10(9)/l 1 week after IFN therapy (P < 0.01). On the other hand, serum TPO increased from 1.96 +/- 0.60 fmol/ml to 2.68 +/- 0.69 fmol/ml (P < 0.02). Contrary to a recent report that serum TPO was not altered in liver cirrhosis, these data indicate that serum TPO was increased in chronic hepatitis C in response to thrombocytopenia by IFN therapy.