[HCV infection and mixed cryoglubulinemia].

The authors present literature data and the results of their own studies of mixed cryoglobulinemia (MC) caused by chronic HCV infection, discuss issues concerning pathogenesis of MC as well as MC-associated cryoglobulinemic vasculitis and malignant lymphoproliferation, consider questions of MC influence on the course and prognosis of chronic HCV infection and anti-viral therapy effectiveness. MC was found in 43% of 207 patients with chronic hepatitis type C (CH-C), examined by the researchers. 30% of patients with CH-C and MC displayed clinical signs of vasculitis. The study established the direct correlation between MC severity and the frequency and degree of main clinical manifestations. The results show that more severe clinical variants of cryoglobulinemic glomerulonephritis are associated with MC type II. B-cell lymphoma, monoclonal immunoglobulinopathy and a range of autoimmune syndromes were observed in MC patients. The liver involvement in patients with MC was characterized by a significantly higher sclerosis index compared to the group of patients not having MC while medium liver process activity index was equal in both groups, which suggests possible existence of special mechanisms and faster progress of phibrosis in patients with MC.

[Chronic viral hepatitis--one of the most important problems of current medicine]. / Khronicheskii virusnyi gepatit--odna iz naibolee vazhnykh problem sovremennoi meditsiny.

Main aspects of the study of chronic virus infection now cover clinico-morphological characteristics, prognosis of chronic liver diseases (CLD) by HBV and HCV; characteristics of extrahepatic lesions produced by HBV and HCV; features of CLD of mixed etiology (viral and alcoholic); treatment of CLD of viral etiology. The hypothesis is suggested on the generalized character of HBV and HCV infection. Approach to the treatment of chronic viral hepatitis including extrahepatic manifestation is proposed.

A multicentre, randomized study to evaluate the safety and efficacy of histamine dihydrochloride and interferon-alpha-2b for the treatment of chronic hepatitis C.

Interferon- (IFN-)alpha is currently the standard of care treatment for patients with chronic hepatitis C virus (HCV) infection. A significant part of the benefit of IFN-alpha in chronic hepatitis C is believed to be related to the activation of lymphocytes such as T cells and natural killer (NK) cells, which participate in the elimination of infected cells. Histamine dihydrochloride (HDC) has been shown to potentiate the IFN-alpha-induced activation of T cells and NK cells by a mechanism that involves the protection of these lymphocytes against oxygen radical-induced functional inhibition and apoptosis. This study was designed to examine the efficacy and safety of HDC in combination with IFN-alpha-2b in treatment-naïve patients with chronic HCV infection. All patients received IFN-alpha-2b, 3 MIU, three times weekly via subcutaneous injection, and were randomized to one of four HDC regimens (1 mg of either: once a day, three times a week; once a day, five times a week; twice a day, three times a week or; twice a day, five times a week). The doses of HDC in combination with IFN-alpha-2b resulted in sustained viral response rates ranging from 31% to 38%. Sustained biochemical response rates ranged from 28% to 41% across the four treatment groups. Patients infected with HCV genotype 1, and those with high baseline viral levels, which are characteristics associated with poor prognosis, had sustained virologic response rates ranging from 18% to 42% and 15% to 39%, respectively. Combination treatment was generally well tolerated. We propose that the potential benefit of HDC + IFN therapy for chronic HCV infection should be the focus of further investigation.

[Pathogenesis of chronic hepatitis B]. / Patogenez khronicheskogo gepatita B.

The following problems are considered in chronic HBV infection: viral replication within and outside the liver, heterogenicity of genotypes and mutations of viral genome, immunogenetic basis of the host, direct cytopathic effect of the virus and immunological reactions induced by the virus.

[Extrahepatic manifestations of chronic viral liver diseases]. / Vnepechenochnye proiavleniia khronicheskikh virusnykh zabolevanii pecheni.

The study of large groups of patients with chronic liver diseases of viral etiology (including those induced by HBV and HCV) has revealed extrahepatic manifestations which by their mechanisms formed 2 groups. The first group represents disorders related to delayed hypersensitivity in combination with immunocomplex reactions (lesions of the joints, skeletal muscles, lungs, myocardium, etc). The second group includes disorders of primarily immunocomplex genesis (vasculitis): skin vasculitis, Raynaud's syndrome, nodular periiarteritis, mixed cryoglobulinemia, etc.). Special group represents diseases of blood: immune cytopenias, monoclonal immunoglobulinopathy, malignant lymphoproliferative diseases. These findings and literature data on extrahepatic replication of HBV and HCV validate the diagnosis of "chronic generalized HBV or HCV infection" with listing of all manifestations of these infections.

[Autoimmune hepatitis (history of the research, current aspects)]. / Autoimmunnyi gepatitis (istoriia izucheniia, sovremennye aspekty).

Important achievement in the study of autoimmune hepatitis are shown, particularly in establishing the role of hepatitis viruses, other hepatotropic viruses and some medicines. The last classification of chronic hepatitis based on the etiology, autoimmune hepatitis considers autoimmune hepatitis as a disease of unknown etiology. It is thought valid that investigation of autoimmune reactions produced by hepatitis viruses and other agents will enable a revision of classification of chronic hepatitis.

[Extrahepatic manifestations of chronic hepatitis C]. / Vnepechenochnye proiavleniia khronicheskogo gepatita C.

AIM: To study incidence, special features and mechanisms underlying onset of extrahepatic lesions in HCV-infection. MATERIALS AND METHODS: Extrahepatic symptoms of chronic hepatitis C and its outcome--hepatic cirrhosis were studied in 157 patients. HCV-infection was confirmed by ELISA II and polymerase chain reaction (detection in the serum of anti-HCV and HCVRNA, respectively). Morphological studies of the liver were made in 134 patients, of other organs and tissues--in 20 patients. Immunological tests were made in 124 patients. Thyroid hormones, antibodies to thyroglobuline were measured with radioimmunoassay in 74 patients. RESULTS: Extrahepatic manifestations were found in 70(44.6%) patients with chronic hepatitis C (more frequently in hepatic cirrhosis), for the most part in women and in long-lasting disease. 54(43.5%) women had cryoglobulinemia, 27 of them showed it clinically. Patients with cryoglobulinemia and free of it exhibited varying frequency cutaneous vasculitis, Raynaud's syndrome, affection of the muscles and joints, nodular periartheritis, lesions of the lungs, myocarditis, autoimmune thyroiditis, Sjogren's syndrome, lichen ruber planus, porphyria cutanea tarda, immune cytopenia, autoimmune hemolytic anemia, hypoplastic anemia, monoclonal immunoglobulinopathy, B-cell lymphoma. Of high frequency were activity of rheumatic factor (66.9%), hypocomplementemia (31.8%), antinuclear antibodies (9.8%) and other immunological disorders. CONCLUSION: Some extrahepatic lesions in HCV-infection are detailed: frequent mixed cryoglobulinemia and associated vasculitides of different sites, malignant lymphoproliferative diseases, more frequent than in HBV-infection involvement of the thyroid and salivary glands, some skin lesions.

[The unique course of a chronic generalized infection with the hepatitis B virus (a clinico-morphological observation)]. / Svoeobraznoe techenie khronicheskoi generalizovannoi infektsii virusa gepatita B (kliniko-morfologicheskoe obsledovanie).

In a young male chronic generalized HBV infection (acute viral hepatitis in childhood, HBsAg, HBeAb, HBcAb in the blood serum) ran with a long-term fever and involvement of many organs and systems (the liver, lungs, CNS) complicating the diagnosis. The patient died in the presence of CNS affection and hepatorenal insufficiency. At biopsy and autopsy it was established that the patient had active hepatic cirrhosis, fibrosing alveolitis, pulmonary vasculitides, chronic pneumonia, cerebral vasculitis, myocarditis and postmyocarditis cardiosclerosis, necrotizing myositis, Sjogren's syndrome, mesangioproliferative glomerulonephritis.

[Tubulointerstitial nephritis in chronic viral diseases of the liver]. / Tubulointerstitsial'nyi nefrit pru khronicheskikh virusnykh zabolevaniiakh pecheni.

The paper reports 4 cases of tubulointerstitial nephritis (TIN) in chronic diffuse diseases of the liver (CDDL). The latter comprised such conditions of virus etiology as chronic active hepatitis, chronic lobular hepatitis. TIN presented with pronounced renal tubular affections: defects of concentration capacity, distal renal tubular acidosis, renal diabetes insipidus. In 3 cases renal lesions occurred 1 and 6 years prior to CDDL detection. TIN pathogenesis in CDDL of viral etiology is discussed.

[Viral hepatitis C]. / Virusnyi gepatit C.

This review is indicative of a considerable progress in the study of viral hepatitis C: HCV biology (its structural and antigenic analysis, genotype heterogenicity and genome mutation, mechanisms of replication), serological diagnosis, epidemiology, pathogenesis and clinico-morphological characteristics of liver involvement, systemic manifestations as well as carcinogenesis in HCV contamination. There exist data in favour of HCV role in a wide spectrum of pathology in parallel to what was earlier established in relation to HCV.

[The incidence of detecting HB viral infection in the families of patients with kidney diseases]. / Chastota vyiavleniia HB-virusnoi infektsii v sem'iakh bol'nykh s zabolevaniiami pochek.

A total of 33 families were surveyed with a view to determine the presence of viral hepatitis B markers in persons with diagnosed renal diseases. In all patients markers of hepatitis B virus infection (HBsAg, anti-HBs antibodies, anti-HBc total and IgM antibodies) were determined in the enzyme immunoassay. Those families in which examinees with renal pathology were found to have markers of hepatitis B virus infection exhibited a high level of contamination with hepatitis B virus. A high proportion of examinees with viral hepatitis B was established in the families where mothers were found to have markers of hepatitis B virus infection. These facts indicate that everyday contacts play an important role in the transmission of the virus. The study points out that in the family foci of hepatitis B virus infection non-manifest or slightly manifest forms of this infection are mainly registered.

[Chronic viral diseases of the liver and pregnancy]. / Virusnye khronicheskie zabolevaniia pecheni i beremennost'.

Sixty patients with chronic active hepatitis and liver cirrhosis of viral etiology had in the course of the disease a total of 130 pregnancies, that eventuated in labor in 62 (48%), in spontaneous abortions in 13 (10%), and in artificial abortions in 55 (42%) cases. The incidence of preterm labor was 18%, of late gestosis 46%; early detachment of a normally positioned placenta occurred in 2 women, and 3 women suffered an abnormal blood loss. Cesarean sections were carried out in 9% of cases. Perinatal mortality has made up 64.5%. Two babies died within the first months of life of congenital cerebral paralysis. The pregnancy and its outcome did not result in 78% of cases in deterioration of the patients' health status and did not influence the disease development. The authors discuss the policy of management of patients with chronic active hepatitis and liver cirrhosis of a viral origin in pregnancy and labor.

[Detection of hepatitis B virus DNA using local nucleic acid amplification (polymerase chain reaction) in fixed tissues in chronic viral liver diseases]. / Vyiavlenie DNK virusa gepatita v metodom lokal'noi amplifikatsii nukleinovykh kislot (polimeraznaia tsepnaia reaktsiia) v fiksirovannykh tkaniiakh pri khronicheskikh virusnykh zabolevaniiakh pecheni.

PCR is a highly sensitive, convenient and rapid method for detection of viral DNA in fixed tissue samples which allows one to analyse the material from the pathology files, mainly biopsies. PCR in a fixed material requires larger amounts of DNA-polymerase and longer duration of every stage of thermo-cycles compared to PCR in the purified DNA samples.