Personalized therapy in chronic viral hepatitis

Chronic carriers of major hepatitis viruses (i.e., hepatitis B and C viruses, HBV and HCV) account for at least 600 millions people worldwide. About 50% of them are at risk for chronic hepatitis and 20-30% of patients with chronic hepatitis develop progressive liver disease and symptomatic life-threatening liver lesions. Therefore, the identification of the carrier at risk is mandatory to prevent progressive liver disease, avoiding non-appropriate treatments. The decision making has three major steps. The 1st is the identification of the patient who needs to be treated; the 2nd is the choice of the best therapeutic strategy and the most appropriate drugs and timing during the phase of infection and disease; the 3rd is the treatment optimization to reduce non effective therapy and avoid drug resistance virus mutants. This careful evaluation takes into account the individual variability, the host/virus interplays and the drug impact on viral replication with the risk of selection of resistant mutants. The complexity of the virus/host interactions, however, cannot be managed by simple mean of probabilistic statistics and/or step-wise algorithms based on population statistics. A better answer for personalized antiviral therapy may come from the combined use of molecular biology and bio-mathematical modeling that can help the medical doctor to follow the dynamic of viral infection during therapy, like the flight simulator helps the pilot. We provide a concise review of the potentials of this approach in clinical practice.     

Glycosylation in viral hepatitis

BackgroundThe interaction between hepatitis viruses and host cells is regulated by glycans exposed on the surfaces of human and viruses cells. As the biosynthesis and degradation of human glycoproteins take place at the highest level in the liver, the changes in glycosylation of serum proteins may potentially be useful in the diagnosis of liver pathology. On the other hand, specific alterations in viruses envelope glycans could cause large changes in the entry process of hepatitis viruses into a host cells.Scope of reviewUnique alterations in glycosylation of specific proteins can be detected in HBV and HCV infected patients especially with confirmed fibrosis/cirrhosis. On the other hand, viral envelope proteins that bind to host cells are glycosylated. These glycosylated proteins play a key role in recognition, binding and penetration of the host cells. In this review we summarized the knowledge about significance of glycosylation for viral and host factors.Major conclusionsGlycosylation changes in single serum glycoproteins are noticed in the sera of patients with viral hepatitis. However, a more specific biomarker for the diagnosis of chronic hepatitis than that of a single glycosylated molecule is systemic investigation of complete set of glycan structures (N-glycome). Glycans play important roles in the viral biology cycle especially as a connecting element with host receptors.General significanceThe interaction between virus glycoproteins and cellular receptors, which are also glycoproteins, determines the possibility of virus penetration into host cells. Therefore these glycans can be the targets for the developing of novel treatment strategies of viral hepatitis.     

Pathogenesis of viral hepatitis

The aim of our research is to use animal models to elucidate the molecular basis for viral clearance and liver disease in the pathogenesis of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. The results herein discussed provide insight into immunological and virological processes that may lead to the development of new therapeutic strategies to terminate chronic HBV and HCV infections.     

Trace elements in viral hepatitis

In this study, serum trace elements, including selenium (Se), zinc (Zn), copper (Cu), were determined by using Atomic Absorption Spectrophotometer (SpectrAA 250 Plus Zeeman, Varian, Australia) in sera of patients with viral hepatitis (A, B, C, D, E) cases (n = 102), and statistically compared with the controls (n = 52). In viral hepatitis, Cu levels were found as 3.23 ± 1.02 mg/L, and this value was significantly higher than the control group (1.13 ± 0.21) (p < 0.01). Both, Se and Zn levels found to be significantly low in viral hepatitis cases (p < 0.01). While Se level was 81.4 ± 26.01 μg/L in viral hepatitis (n = 101), it was found to be 166.15 ± 4.58 μg/L in healthy individuals. Meanwhile, Zn levels were 0.230 ± 0.081 mg/L and 0.748 ± 0.392 mg/L in hepatitis cases (n = 101) and the control group, respectively. There was no difference amongst viral hepatitis groups classified in regard with agents and clinical manifestation, such as A, acute hepatitis B, chronic hepatitis B, C, D and E. Previously, it was indicated that absorption disorders in gastrointestinal system, especially in chronic cases, were not main causes of decrease of trace elements by iron and several other parameters in sera of the cases. Therefore, we suggest that decrease in Zn and Se levels and elevation in Cu levels are probably resulted from defence strategies of organism and induced by the hormone-like substances.     

Serologic studies in viral hepatitis]

Comparative studies of sera from 710 patients with viral hepatitis and contacts were made during the 1958-1973 period for hepatitis antigens (Au antigen and the Botevgrad antigen). The percentage of virus hepatitis in patients positive for the Au and the Botevgrad antigens varied in different years. The percentage of those positive for the Au antigen ranged from 50 in 1958 to 8.8 in 1970-1971, while for the Botevgrad antigen--it ranged from 32.6 in 1962-1963 to 6.1 in 1966. In case of contacts, mostly in the 7-14 age group the sera positive for the Au antigen were found in a low percentage (2.09 percent) of cases; as to the Botevgrad antigen, 20 persons were found positive during various epidemics (55 percent). Simultaneous presence of both antigens was found in 4 of the 710 patients with virus hepatitis (0.56 percent), and in 2 of 431 contacts (0.46 percent).