ABSTRACT
Chronic hepatitis B is one of the world's most common infectious diseases. In the Czech Republic it has a prevalence of 0.56%. Antiviral therapy for chronic hepatitis B demonstrably increases quality of life and where indication criteria are met and standard therapeutic procedures are followed, it is clearly cheaper than treatment for the complications of advanced cirrhosis of the liver or hepatocellular carcinoma. At the time of issuing of this recommendation, 4 medicines were classified for the treatment of chronic hepatitis B in the Czech Republic--pegylated interferon (IFN) alpha-2a, conventional IFN alpha, lamivudine (LAM) and adefovir dipivoxil (ADV). In a number of other developed states, entecavir (ETV) and telbivudine (LdT) have also been approved for treatment. The most effective treatment available at present is pegylated IFN alpha-2a, which should be the medication of first choice for initial treatment of hepatitis B, HBeAg positive and negative forms, provided that there are no contraindications for IFN alpha treatment. Conventional (standard, classical) IFN alpha can also be used, though clinical studies have shown it to be less effective than pegylated IFN alpha-2a. The main advantage of interferon compared to other commercially available medications is its relatively shorter and more clearly defined treatment period, the high probability of permanent suppression of virus replication and seroconversion of HBeAg/anti-HBe (in HBeAg positive forms of the illness) and the non-creation of mutant strains of HBV resistant to IFN in the course of treatment. If there are contraindications for IFN alpha (pegylated or conventional) or it is ineffective or poorly tolerated, ADV, ETV, LAM or LdT can be used. LAM and LdT treatments are often accompanied by the appearance of mutant strains of HBV, that are resistant to lamivudine or LdT and therefore they are not preferred.
Subject(s)
Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , HumansABSTRACT
The currently used standard treatment for chronic hepatitis C using a dual combination of IFNalpha/RBV is only successful in 50% cases. With the exception of some clinical and biochemical factors, degree of inflammation (grading) and degree of fibrosis (staging), there are no other known markers which may serve as valid predictors of response to therapy. Interference of hepatitis C virus (HCV) with signaling pathways modulated by JAK-STAT, ERK 1/2, NFkappaB and MAP proteins is one mechanism which may influence the interaction between HCV and IFNalpha. These proteins regulate different cell processes such as activation of cytokines, activation of apoptosis, regulation of cell proliferation etc. Therefore, it is possible that impaired signaling or inhibition/dysregulation of some of these proteins by HCV infection may cause resistance to IFNalpha treatment. This review is completed by results of preliminary study the aim of which was immunohistochemical assessment and analysis of expression of STAT 2, 3 proteins, their inhibitors SOCS 2, 3 and PIAS 3 and proteins JAK 1 and ERK 1/2 in liver biopsies of 26 patients with chronic hepatitis C treated by dual combination IFNalpha/RBV and subsequent correlation of the results of immunohistochemical analysis (histoscore) with histological picture and clinical response to treatment. The results shows increased expression of STAT 3, STAT 2 and ERK 1 proteins and decreased expression of SOCS 3 and SOCS 2 in hepatocytes of patients with more marked inflammation and fibrosis. In patients with sustained virological response there was increased expression of SOCS 3 and JAK 1 and decreased expression of SOCS 2. Relapse was associated with increased expression of SOCS 3 and PIAS 3. However, owing to the small sample size, the results only approximated statistical significance, but we suggest that proteins of STAT family and their inhibitors SOCS and PIAS probably play an important regulatory role during response to treatment for chronic hepatitis C.