Efikasnost i bezbednost pegilovanog interferona alfa-2a u terapiji hroničnog virusnog hepatitisa B u uslovima ograničenih resursa: iskustvo jednog centra u Srbiji
Sažetak
Uvod/Cilj. Pegilovani interferon (PEG-IFN) alfa-2a je registrovan u Srbiji od 2013. godine za lečenje bolesnika sa hroničnim hepatitisom B (HHB). S obzirom na njegove mnogobrojne prednosti u odnosu na dotadašnju terapiju, nova iskustva u periodu od proteklih pet godina i nedostatak publikovanih rezultata u našoj populaciji, cilj rada bio je da se prvi put među bolesnicima sa HHB u Srbiji ispita efikasnost i bezbednost primene PEG-IFN u tercijarnoj zdravstvenoj ustanovi. Metode. U prospektivnoj studiji u petogodišnjem periodu od 2012. do 2017. godine analizirano je ukupno 36 bolesnika sa HHB, lečenih standardnim protokolom PEG-IFN tokom 48 nedelja, u Hepatološkom odeljenju Klinike za infektivne i tropske bolesti Kliničkog centra Srbije u Beogradu. Svim bolesnicima su merene bazalne vrednosti transaminaza, serologije i viremije, uključujući praćenje tih parametara tokom terapije, na kraju terapije i u periodu praćenja. Za procenu uspeha terapije analiziran je serološki odgovor (gubitak HBeAg), biohemijski odgovor [normalizacija alanin aminotransferaze (ALT)] i virusološki odgovor na terapiju [supresija DNK hepatitis B virusa (HBV) < 2000 IU/mL. Rezultati. Virusološki uspeh terapije kod bolesnika sa HBeAg pozitivnim HHB postignut je kod 50% bolesnika, gubitak HBeAg kod 62,5%, a biohemijski odgovor kod 37,5% bolesnika. Kod HBeAg negativnog HHB, virusološki uspeh terapije postignut je kod 38% bolesnika, biohemijski odgovor kod 47,6%, a samo jedan (4,7%) bolesnik imao je i gubitak HBsAg. Zaključak. Primena PEG-IFN u lečenju HBV infekcije važna je u dobro selektovanoj grupi bolesnika, a u našoj populaciji lečenih bolesnika procenat uspešnosti terapije sličan je onom od drugih autora. Bezbednost i podnošljivost terapije je dobra, ali se mogu očekivati i ozbiljniji neželjeni događaji zbog čega je neophodno redovno praćenje bolesnika tokom lečenja.
Reference
European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012; 57(1): 167–85.
European Association for the Study of the Liver. EASL 2017 Clini-cal Practice Guidelines on the management of hepatitis B vi-rus infection. J Hepatol 2017; 67(2): 370–98.
Health Insurance Fund of the Republic of Serbia. List C. Drugs with a special regime of release. [Cited 2018 May 30] Available from: https://www.rfzo.rs/download/pravilnici/lekovi/Lista %20Cprimena%20od%2001.01.2018..pdf
Sonnevald MJ, Hansen BE, Piratvisuth T, Jia J, Zeuzem S, Gane E, et al. Response guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen level. Hepatology 2013; 58(3): 872–80.
Chon YE, Kim DJ, Kim SG, Kim HG, Bae SH, Hwang SG, et al. An observational, muticenter, cohort study evaluating the an-tiviral efficacy and safety in korean patients with chronic hep-atitis B receiving pegylated interferon-alfa 2a (Pegasys). Medi-cine 2016; 95(14): e3026.
Vlachogiannakos J, Papatheodoridis GV. Optimal therapy of chronic hepatitis B: how do I treat HBeAg-positive patients? Liver Int 2015; 35(Suppl 1): 100–6.
Lampertico P, Rothe V, Caputo A, Papatheodoridis GV. A base-line predictive tool for selecting HBeAg-negative chronic hep-atitis B patients who have a high probability of achieving sus-tained immune control with peginterferon alfa-2a. Hepatology 2014; 60: 1107A.
Goulis I, Karatapanis S, Akriviadis E, Deutsch M, Dalekos GN, Raptopoulou-Gigi M, et al. On-treatment prediction of sustained response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B patients. Liver Int 2015; 35(5): 1540–8.
Milosevic I, Delic D, Lazarevic I, Pavlovic IP, Korac M, Bojovic K, Jevtovic D. The significance of hepatitis B virus (HBV) geno-types for the disease and treatment outcome among patients with chronic hepatitis B in Serbia. J Clin Virol 2013; 58(1): 54–8.
Bojović K, Božić M, Stanojević B, Popović N. The first resultsof genotyping hepatitis B virus in Serbia and Montenegro, Falk symposium 157 Chronic Hepatitis: metabolic, Cholestatic, Vi-ral and Autoimmune. Freibug; 2006. Abstracts 21.
Lampertico P, Maini M, Papatheodoridis G. Optimal management of hepatitis B virus infection - EASL Special Conference. J Hepatol 2015; 63(5): 1238–53.
Marcellin P, Bonino F, Yurdaydin C, Hadziyannis S, Moucari R, Kapprell HP, et al. Hepatitis B surface antigen levels: associa-tion with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients. Hepatol Int 2013; 7(1): 88–97.
Buster EH, Flink HJ, Cakaloglu Y, Simon K, Trojan J, Tabak F, et al. Sustained HBeAg and HBsAg loss after long-term fol-low-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology 2008; 135(2): 459–67.
Piratvisuth T, Marcellin P, Brunetto M, Bonino F, Farci P, Yurday-din C, et al. Sustained immune control 1 year post-treatment with Peginterferon Alfa -2a [40KD] (PEGASYS) is durable up to 5 years post-teratment and is associated with a hihg rate of HBsAg clearance in HbeAg-negative chronic hepatitis B. 20th Conference of the Asian Pacific Asspciation for the Study of the Liver (APASL); Bejing, China 2010 March 25–28.
Vigano M, Invernizzi F, Lampertico P. Optimal therapy of chronic hepatitis B: how do I treat my HBeAg-negative pa-tients? Liver Int 2015; 35(Suppl 1): 107–13.
Yeh ML, Peng CY, Dai CY, Lai HC, Huang CF, Hsieh MY, et al. Pegylated-interferon alpha therapy for treatment-experienced chronic hepatitis B patients. PLoS One 2015; 10(4): e0122259.
Rijckborst V, Hansen BE, Ferenci P, Brunetto MR, Tabak F, Cakaloglu Y, et al. Validation of a stopping rule at week 12 us-ing HBsAg and HBV DNA for HBeAg-negative patients treat-ed with peginterferon alfa-2a. J Hepatol 2012; 56(5): 1006–11.
Lampertico P, Viganò M, Di Costanzo GG, Sagnelli E, Fasano M, Di Marco V, et al. Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B. Gut 2013; 62(2): 290–8.