Impact of Pegylated Interferon-alfa-2a on Perforin Level in Patients With Chronic Hepatitis B; Preliminary Study

Background: Chronic hepatitis B is one of the most common causes of cirrhosis and hepatocellular toxicity in many countries, including Iran. Cytotoxic T lymphocyte (CTL) and Natural killer (NK) cells are the two of main cell populations considered as cytotoxic cells. One of the distinct pathways CTL and NK cells exert cytotoxicity is perforin/granzyme. After the cytotoxic cell/target cell junction, perforin is released from granules by exocytosis. Once it is anchored, perforin forms cylindrical pores through which granzymes and granulysin enter and induce apoptosis. Objectives: Large controlled trials have demonstrated the efficacy of PEG-IFN-alpha-2a in treatment of chronic hepatitis B. This study was aimed to examine whether the enhancement of cytotoxicity by PEG-IFN-alpha-2a is mainly due to the perforin pathway. Patients and Methods: This research work was performed on 50 patients and five healthy people. Patients with chronic hepatitis B were further subdivided into two groups: patients with inactive chronic hepatitis B (carriers, n = 30), and those with active chronic hepatitis B who were under treatment with PEG-IFN-alfa-2a (n = 20) for minimum six and maximum 12 months. Serum perforin level was measured using ELISA method (CUSABIO Company), HBV viral load was assessed using COBAS Taq-man, and we used Elecsys hepatitis B surface antigen (HBs Ag) II quantitative assay method for HBs Ag determination. HBeAg was evaluated by ELISA method, and AST and ALT were measured by routine laboratorymethods. Results: Based on the results obtained serum perforin level in healthy group was 0.64 ng/mL, the mean of serum perforin level in inactive HBs Ag carriers was 2.63ng/mL, and 4.63 ng/mL in patients with active chronic hepatitis B under treatment with PEG-IFN-alpha-2a. The mean of serum perforin level in patients with and without virologic response to treatment were 5.45 ng/mL, and 3.4 ng/mL respectively. Finally in patients with virologic response and seroconverted serum perforin level was 7.23 ng/mL. Conclusions: Based on our results higher perforin level in patients under treatment with PEG-IFN-alpha-2a, could be an indication of elevated cytotoxicity via perforin/granzyme pathway.