[HBx Protein Potentiates Hepatitis B Virus Reactivation].

Hepatitis B virus (HBV) can cause chronic hepatitis B, one of the most prevalent infectious diseases in the world. Global estimates suggest that over 2 billion people are affected by HBV, with over 250 million people developing chronic infection. Upon treatment of comorbidities, patients with chronic infection may develop an abrupt increase of viral replication-HBV reactivation-leading to liver decompensation and, in some cases, death. HBV reactivation occurs mostly due to suppression of antiviral immune response and activation of intracellular pro-viral signaling. Defining the mechanisms of HBV reactivation is necessary for the rational use of drugs and reduction of mortality rates in patients with chronic infection. In this study, for the first time we analyzed the effects of HBx protein on HBV reactivation, described reactivation of HBV from the transcriptionally inactivated state at the methylated recombinant HBV genome model, and investigated HBV reactivation upon treatment with genotoxic agents (doxorubicin and hydrogen peroxide) and targeted drug therapies (sunitinib and bortezomib). We report that both wild-type HBx protein and, to a greater extent, the mutant form of HBx protein lacking the nuclear exportation signal, potentiate viral replication and promote HBV reactivation. For the first time, we demonstrate that HBV can reactivate from the transcriptionally inactive state. Doxorubicin and hydrogen peroxide induce HBV reactivation at models of both transcriptionally active and transcriptionally silenced viral genome. Sunitinib weakly reactivates HBV, while bortezomib does not affect HBV replication in vitro.

[The interferon therapy of patients with chronic viral hepatitis: the factors affecting the treatment results]. / Interferonoterapiia bol'nykh khronicheskim virusnym gepatitom: faktory, vliiaiushchee na rezul'taty lecheniia.

The paper presents clinicoimmunological characterization or therapeutic efficacy of alpha-interferons produced in Russia and criteria of their administration in patients with chronic viral hepatitis. A 6 to 12 months course (single dose 1 x 10(6)-3 x 10(6) IU improves the disease running, hepatic function and corrects immune status in 55.6% of patients with chronic active hepatitis eventuating in liver cirrhosis and in 57.9% of patients in chronic active hepatitis of moderate activity. Alpha-interferons are indicated in chronic active hepatitis and cirrhosis under high activity of cytolytic process, immunodeficiency, weak autoimmune process and protein shifts.

[The problem of the interferon therapy of patients with chronic viral hepatitis]. / Problema interferonoterapii bol'nykh khronicheskim virusnym gepatitom.

In this work the results of the clinico-immunological evaluation of the therapeutic effectiveness of alpha-interferon preparations are presented and criteria suitable for use in screening patients with chronic virus hepatitis, sensitive to interferon therapy, are discussed. The study revealed that the use of alpha-interferon preparations in single doses of 1-3 x 10(6) in a prolonged course of treatment (6-12 months) facilitated essential improvement in the clinical course of the disease and ensures correction of the immune status in 55.6% of patients with chronic active hepatitis (CAH) resulting in cirrhosis of the liver and 57.9% of patients with CAH moderate activity. Indications for the use of alpha-interferon preparations in patients with CAH-induced cirrhosis were high activity of the cytolytic process, the presence of immunodeficiency, faintly pronounced autoimmune process and the presence of protein shifts.

[The treatment of patients with chronic persistent hepatitis B with interferon preparations]. / O lechenii bol'nykh khronicheskim persistiruiushchim gepatitom B preparatami interferona.

Alpha-interferon preparations were injected intramuscularly in a single weekly dose 1.10(6) - 1.5.10(6) IU in courses lasting from 1 to 6 months to 37 patients with chronic persistent hepatitis B (CPHB) who entered a randomized clinicoimmunological trials. Except for moderate hyperfermentemia and HBs-antigenemia CPHB patients responsive to 3-4-month courses, alpha-interferon treatment of CPHB had no advantages over conventional therapy of the disease.

[The clinico-morphological characteristics and efficacy of interferon therapy in patients with chronic delta hepatitis]. / Kliniko-morfologicheskaia kharakteristika i éffektivnost' interferonoterapii u bol'nykh khronicheskim gepatitom del'ta.

The results of the examination of 20 patients having chronic hepatitis delta (CHD) with the disease lasting 1-2 years (8 patients) and 3-6 years (12 patients) are presented. In most of the patients of both groups, irrespective of the duration of the disease, the development of severe hepatic lesions has been established. The morphological study has revealed in 45% of the examined patients the presence of chronic active hepatitis leading to the cirrhosis if the liver. A prolonged course of treatment (8-12 months) with reaferon (recombinant interferon alpha 2, obtained by gene engineering technique), injected intramuscularly in a dose of 1 x 10(6) I.U. once or twice a week, has proved to be effective in 47% of CHD patients aged 15-30 years with a weak expression of autoimmune process. It is recommended that interferon therapy in patients with CHD requires individual indications.

[The use of reaferon in treating patients with protracted viral hepatitis]. / Primenenie reaferona v lechenii bol'nykh zatiazhnym virusnym gepatitom.

The paper reports the results of a randomized clinicoimmunological trial of domestic recombinant alpha 2-interferon (reaferon) in 30 patients with protracted viral hepatitis (27 subjects had viral hepatitis B and 3 patients HBV + HDV-coinfection). The reaferon treatment started on the disease week 7-8 and lasted for 2 months (1 x 10(6) IU, once a week, i.m.). VHB patients benefited from reaferon treatment as evident from improved clinical and laboratory indices, cases of complete cure and the agent elimination. In a protracted course of HBV + HDV coinfection reaferon in the above doses failed to produce any effect.

[The comparative characteristics of the indices of lymphocyte and neutrophil functional activity in patients with HIV infection and chronic viral hepatitis B]. / Sravnitel'naia kharakteristika nekotorykh pokazatelei funktsional'noi aktivnosti limfotsitov i neitrofilov u bol'nykh s infektsiei VICh i khronicheskim virusnym gepatitom B.

In 34 patients with human immunodeficiency virus (HIV) infection at the asymptomatic stage and 29 patients with chronic viral hepatitis B at the period of exacerbation (of these 14 patients had chronic persistent hepatitis and 15 patients had chronic active hepatitis) the complex study of the functional activity of lymphocytes and neutrophils was carried out by cytochemical methods with the simultaneous determination of the content of immunoregulating lymphocyte subpopulations. In patients with chronic active hepatitis a decrease in the percentage and the absolute number of helper T-lymphocytes and the ratio of CD4/8 in comparison with those in patients with HIV infection were revealed. At the same time patients with HIV infection exhibited more pronounced decrease in the activity of all lymphocytic enzymes under study (neutrophil esterase, acidic phosphatase and succinate dehydrogenase in lymphocytes), as well as in the activity of myeloperoxidase and the content of cation proteins and glycogen in neutrophils in comparison with patients having chronic active hepatitis.