PROČ JE ODPOVĚĎ NA KOMBINOVANOU LÉČBUINTERFERONEM ALFA2b A RIBAVIRINEM U PACIENTŮS CHRONICKOU HEPATITIDOU C TAK SLABÁ?

Why is the Response to Combination Therapy with InterferonAlpha 2b and Ribavirin in Chronic Hepatitic so Poor?

Background.
Patients with chronic hepatitis C are now treated with a combination of interferon alpha (IFN) andribavirin. Therapy was used in initial treatment, for those who were resistant to interferon and in relapsed patients.The aim of the study was to evaluate our results and to compare them with the already published data.Methods and Results. 27 adult patients of the average age 46 years were cured from 1997 through 1999 for thehistologically verified chronic hepatitis C with IFN-alpha 2 and ribavirin. 16 patients suffered from the chronichepatitis with low, medium or high activity, 11 of them had cirrhosis. Serological testing was done using ELISA-3test HCV RNA in serum was estimated by the polymerase chain reaction and serotype HCV was identified by theMurex kit. Treatment lasted 6 to 12 months. Incidences of side effects to both remedies, complications in therapy,therapeutical responses and possible failures of the combination therapy were analysed. In 20/27 patients the HCVserotype could be identified and always serotype 1 was found. Average score of histological activity was in patientswith serious chronic active hepatitis and cirrhosis 10.1, in other patients 5.6. Sustained biochemical and virologicalresponse was found in 5 out of 27 patients (18.5 %). Their average age was 39 years. 9 patients (33 %) of averageage 49 years had no biochemical and virological response. Sustained biochemical response without the accompanyingvirological response was found at the end of therapy in 10 patients (37 %). After the end of therapy, 33 % of patientshad a relapse. The most frequently seen accompanying sign was the flu-like syndrome, in two female patients wefound impairment of thyroid gland function, and in another two the breakthrough phenomenon. Treatment withribavirin was in seven cases (26 %) complicated with rather serious haemolytic anaemia and the dose had to bereduced. Toxic-allergic exanthema in 5 patients (18.5 %) represented the second serious complication causing thetermination of therapy.Conclusions. Sustained biochemical and virological response to the combination therapy was found only in patientswith mild form of chronic hepatitis C. No such response was found in 8 patients with cirrhosis and in one femalepatients with medium activity of the chronic hepatitis. The age of patients with sustained response was significantlylower than in patients without the response (39 years versus 49 years). The most frequent serotype was HCV 1. Thecombination therapy was more frequently accompanied with clinically serious complications. To the adverse effectsto the combination therapy belonged in our population the liver cirrhosis, age about 50 or more years, and the genotypeHCV 1. It is also the answer to the question why the combination therapy of patients with chronic HCV infectionhas so poor results.

Key words:
chronic HCV infection, cirrhosis, combination therapy with interferon and ribavirin, HCV serotype.