[Efficacy and safety of boceprevir based triple therapy in Hungarian patients with hepatitis C genotype 1 infection, advanced stage fibrosis and prior treatment failure]. / Bocepreviralapú hármas kezelés hatékonyságának és biztonságosságának retrospektív elemzése elorehaladott fibrosisstádiumú, hepatitis C-vírus 1-es genotípussal fertozött, korábban sikertelenül kezelt magyar betegeknél.

INTRODUCTION: During 2011 and 2013, 155 Hungarian hepatitis C genotype 1 infected patients, mostly with advanced liver fibrosis, who did not respond to prior peginterferon + ribavirin dual therapy, started boceprevir based triple therapy in an early access program. AIM AND METHOD: Efficacy and safety of the therapy was retrospectively assessed based on sustained virologic responses, as well as on frequency and type of serious adverse events and of those leading to therapy discontinuation. RESULTS: In an intent-to-treat analysis 39.4% patients (61/155) reached sustained virologic response. Amongst pervious relapsers, partial responders and null-responders 59.5%, 41.4 % and 22.9% (p<0.05 compared to the other two categories) reached sustained virologic response, respectively, while amongst non-cirrhotics and cirrhotics 52.5% and 31.3% (p<0.05 compared to the non-cirrhotics) achieved sutained virologic response, respectively. Six out of the 33 most difficult to cure patients (previous null responder and cirrhotic) have reached sustained virologic response (18.2%). Frequency of early discontinuations due to insufficient virologic response was 31.1%, while due to adverse event 10.3%. Reported frequency of serious adverse event was 9.8%. These events represented anemia, diarrhoea, depression, agranulocytosis, elevated aminotransferases, generalized dermatitis and severe gingivitis with loss of teeth, prolonged QT interval on ECG, generalized oedema and severe dyspnoea, uroinfection, exacerbation of Crohn's disease, Campylobacter pylori infection and unacceptable weakness and fatigue. Eight patients received transfusion, 4 patients erythropoietin and 1 granulocyte colony stimulating factor during therapy. No death has been reported. CONCLUSIONS: With boceprevir based triple therapy, one of the bests available in 2011-2013 in Hungary, a relevant proportion of hepatitis C infected patients with advanced liver fibrosis achieved sustained viral response. In this cohort, side-effects resembled those reported in registration studies, and resulted in therapy discontinuation with consequent treatment failure in a relevant number of patients. Efficacy and tolerability of boceprevir-based triple therapy are suboptimal, particularly in the most difficult to cure patient population. Orv. Hetil., 2016, 157(34), 1366-1374.

[Determination of the lamivudine-resistant mutants of hepatitis B virus]. / A hepatitis B-vírus lamivudinrezisztens mutánsainak meghatározása.

INTRODUCTION: In addition to interferon, lamivudine is the other widely used antiviral agent in the therapy of chronic hepatitis B. This nucleoside analogue inhibits the RNA-dependent DNA polimerase and the reverse transcription by integrating in the viral DNA, which results in the secondary suppression of viral protein synthesis and replication of HBV. It has numerous advantages such as effective viral inhibition, mild side effects and the possibility of oral administration; on the other hand it poses the problem of time-correlated appearance of lamivudine resistant mutants during therapy. AIMS: In the Virusserology Laboratory of the Department I. Internal Medicine, Szent György Hospital, Székesfehérvár, detection and type determination of the therapy resistant mutants in the C and B domains of HBV DNA polimerase gene has been carried out the for one year. In this paper, the authors review the molecular biological background of lamivudine resistance and summarise the applied test methodologies and the early results. PATIENTS: Six-month and/or 12-, 18-month samples of 18 chronic hepatitis B patients (4 women/14 men) treated in seven Hepatology Centres in Hungary were analysed. METHODOLOGY: Mutants of codons 528, 552, and 555 in the HBV polimerase gene were determined by nested polimerase chain reaction and reverse hybridisation. RESULTS: M528, V552, I552 and I555 mutants in different variations could be detected in ten out of 18 patients. CONCLUSIONS: Nowadays, drug therapy is the only treatment option used for the therapy of early and progressed chronic hepatitis B in Hungary. This new diagnostic technique was introduced to clarify the background of ineffective lamivudine therapy. Therapy resistance can occur due to the lack of reaction or the appearance of the special, therapy resistant mutants of the virus. Detection of these YMDD mutants together with the clinical picture and the biochemical and virological parameters can help in forming a decision about cessation of lamivudine therapy or application of a new drug.