Search

Background/aims: Viral serum concentrations are considered to have a clinical, prognostic and epidemiological impact on patients with hepatitis C infection. The purpose of this study was to test whether quantitation of HCV-RNA is possible by PCR in combination with DNA-ELISA., Methodology: PCR with 25 to 35 cycles was performed with variable concentrations of cloned HCV-cDNA or the serum of patients with chronic hepatitis C. The amplified PCR-products were detected by agarose gel or by DNA-ELISA., Results: The detection limit of PCR with DNA-ELISA or gel detection decreased with increasing numbers of PCR cycles. However, the correlation of the optical density of the DNA-ELISA with the HCV-cDNA concentration decreased with increasing numbers of PCR as well (r=0.8 vs. r=0.29; 25 vs. 35 PCR-cycles). HCV-RNA was found in the sera of 19 of 30 patients (63%) with chronic hepatitis C by gel detection and in 14 of 30 patients (47%) by DNA-ELISA subsequent to PCR with 35 cycles., Conclusions: The PCR/DNA-ELISA technique allows a semiquantitative determination of HCV-cDNA concentrations down to 103 genomes/ul. However, to obtain a reasonable sensitivity for HCV concentrations in the serum of patients with hepatitis C, the number of PCR cycles has to be increased to numbers too high to provide reliable quantification. Further studies should be done to evaluate whether the detection systems can be improved to obtain a sufficient sensitivity for quantitative HCV-PCR. A prerequisite for the use of PCR in combination with quantifiable detection systems is that a PCR-cycle number is chosen that keeps amplification within the logarithmic phase.

Background/aims: Polyunsaturated phospatidyl-choline (PPC) has been shown to reduce serum aminotransferases in experimental hepatitis. This multi-center, randomized, double-blind, placebo-controlled trial evaluated the effects of PPC in patients with chronic hepatitis B and C in combination with interferon alpha 2a or 2b. The diagnosis of chronic viral hepatitis was based on an abnormal serum alanine aminotransferase (ALT) value (more than twice the upper value of normal), viral replication and chronic hepatitis found on liver biopsy., Methodology: Patients received 5 million I.U. (Hepatitis B) and 3 million I.U. (hepatitis C) interferon s.c. thrice weekly for 24 weeks, respectively, and were randomly assigned to additional oral medication with either 6 capsules of PPC (total daily dose: 1.8 g) or 6 capsules of placebo per day for 24 weeks. Biochemical response to therapy was defined as a reduction of ALT by more than 50% of pre-treatment values. The responders were treated for further 24 weeks after cessation of interferon therapy with either PPC or placebo., Results: 176 patients completed the study protocol (per-protocol population: 92 in the PPC and 84 in the placebo group). A biochemical response (> 50% ALT reduction) was seen in 71% of patients who were treated with PPC, but only in 56% of patients who received placebo (p < 0.05). PPC increased the response rate in particular in patients with hepatitis C: 71% of those patients responded in the PPC group versus 51% in the placebo group (p < 0.05). Prolonged PPC therapy given to responders beyond the cessation of interferon therapy tended to increase the rate of sustained responders at week 48 in patients with hepatitis C (41% versus 15% in the control group; p = 0.064). In contrast, PPC did not alter the biochemical response to interferon in patients with hepatitis B. PPC did not accelerate elimination of HBV-DNA, HBeAg and HCV-RNA., Conclusions: In conclusion, PPC may be recommended in patients with chronic hepatitis C in combination with interferon and after termination of interferon in order to reduce the high relapse rate. PPC may not be recommended for patients with chronic hepatitis B. In contrast to IFN and other antiviral agents PPC does not carry major risks and is tolerated very well.

Background/aims: The present analysis evaluates whether the type, dose, and duration of interferon treatment affect its short- and long-term responses, and also analyzes whether the presence of liver cirrhosis predicts response rates., Material and Methods: The present review analyzes 52 randomized clinical trials of a-interferon in chronic NANB and C hepatitis. Normalization of serum ALT during and 3-6 months after interferon treatment served to assess short- and long-term response rates., Results: Interferon initially induced ALT normalization in 1499/2927 patients (51.2%); due to a high relapse rate (> 50%), only 482/2218 patients (21.7%) still had normal ALT values three months after interferon therapy had been stopped. Nevertheless, ALT normalization was increased more than 8-fold by a-interferon treatment (21.7%) when compared with the spontaneous normalization rate in untreated or placebo-treated controls (22/822 controls; 2.7%)(chi 2 = 156.1; p < or = 10(-15). The long-term response rate significantly increased with increasing weekly doses and with the duration of interferon therapy (r = 0.25 and 0.38 with p < 0.01, respectively). Correspondingly, the response rate was correlated most closely with the total dose of interferon given (r = 0.49, p < 0.001). Total interferon doses > 240 M.U. resulted in a threefold higher long-term response when compared with doses < 240 M.U. (X2 = 103.3; p < or = 10(-15). The presence of cirrhosis markedly reduced the response rate to almost 1/3 of noncirrhotic patients (chi 2 = 12.1; p = 0.00013). The response rate did not depend on the type of interferon used., Conclusions: The present data strongly suggest that future studies which evaluate effects of a-interferon in chronic hepatitis C should focus on higher doses and longer duration of therapy, preferably in noncirrhotic patients.

Background/aims: The incidence of hepatitis C infection is increased in subjects with human immunodeficiency virus infection, although the relative frequency of hepatitis b infection is higher than that hepatitis c. The present study assessed the effect of IFN-a on chronic hepatitis C in HIV infected patients., Material and Methods: Twenty patients with chronic hepatitis C, nine positive for antibodies to the human immunodeficiency virus and eleven HIV-seronegative, were treated with interferon a-2b., Results: Five HIV-positive patients responded to therapy with a complete (three) or partial (two) remission of hepatitis at the end of treatment. A sustained response was achieved in four patients. From the HIV-negative patients eight responded with a complete (six) or partial (two) remission. The response was sustained in six patients. Hepatitis C virus-RNA became at least temporarily undetectable in three HIV-positive and six HIV-negative patients. No severe toxicity of interferon treatment was seen in either the HIV-positive or the HIV-negative patients., Conclusion: The present results indicate that interferon treatment of chronic hepatitis C in HIV-positive patients is successful in a considerable number of individuals. However it might be inferior to the results in HIV-negative patients.