[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.

[Clinical pathology due to hepatitis B virus]. / Klinicheskaia patologiia, obyslovlennaia virusom gepatita B.

All information accumulated during last 10 years allows the view on the alterations produced by hepatitis B virus as ubiquitous. Extrahepatic pathology in hepatitis B is associated with the immunocomplex and immunocellular mechanisms but more frequently with their combination. Wide spread of hepatitis B virus infection and high level of morbidity, persistence of the virus in the organism necessitate further study of clinical pathology associated with this virus.

[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.

[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.

[Clinico-morphological characteristics of extrahepatic pathology caused by the hepatitis B virus]. / Kliniko-morfologicheskaia kharakteristika vnepechenochnoi patologii, obuslovlennoi virusom gepatita B.

The current literature and the authors data on the clinics and morphology of the extrahepatic (visceral) pathology provoked by the hepatitis virus are analysed.

[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.

[Clinico-morphological characteristics of Sjögren's syndrome (biopsy and autopsy data)]. / Kliniko-morfologicheskaia kharakteristika bolezni Shegrena (po dannym biopsii i sektsii).

Sixty patients with Sjogren's disease (SD) were examined. In all the patients--women aged 23 to 70, apart from the generalized "dry syndrome", there were signs of involvement of other organs and systems. Biopsy and autopsy material was studied histologically and histochemically, in some cases immunofluorescent and electron-microscopical study was performed. The most pronounced morphological and clinical manifestations of SD were linked with the damage to exocrine glands. Their alterations were represented by delayed type hypersensitivity and were similar in all exocrine glands, hence the exocrine tissue might be regarded as a target tissue in SD. One of the mechanisms of the exocrine tissue damage is connected with a mutual duct antigen of exocrine glands represented by the serum component IgA. The involvement of certain organs and systems with the development of chronic persistent hepatitis, fibrosing alveolitis, mesangioproliferative and tubulointerstitial nephritis, pronounced hyperplasia of lymphoid tissue with its plasmatization and generalized affection of the microcirculatory system of the immunocomplex nature, is noted in SD with various frequency.

[Dynamics of chronic active hepatitis with varying degrees of severity]. / Dinamika khronicheskogo aktivnogo gepatita razlichnoi stepeni tiazhesti.

Clinico-morphological examinations (repeated laparoscopies, histological and electron microscopic examinations of liver biopsies) were performed in 30 patients with chronic active hepatitis (CAH), in 20 of them in the time course of the disease. In 25 patients the viral etiology of CAH was established, in 5 patients the etiology remained obscure. In most cases of CAH there was a correlation between the intensity of clinico-laboratory and morphological manifestations of the disease activity. The following morphological variants of the CAH course were distinguished: progression of CAH with transition into liver cirrhosis (LC); decreasing activity of CAH under the influence of treatment; transition of chronic persisting hepatitis into CAH. Prognostically the most unfavourable form is CAH with pontile necrosis which rapidly terminates with LC. In patients with CAH of high activity with septal necroses the prognosis is more favourable and positive time course of the disease is possible. Patients with CAH treated with immunosuppressive drugs exhibited a decrease in the size of hepatocytic necroses and cell infiltration with increased sclerosis of the portal and lobular stroma up to the development of LC in some of them. The electron microscopic examinations specified the mechanisms of interaction of lymphocytes with hepatic cells in relation to the severity of the pathological process.

[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.

[Biopsy of the mucosa of the lower lip for purposes of diagnosing Sjögren's syndrome]. / Biopsiia slizistoi obolochki nizhnei guby s tsel'iu diagnostiki sindroma S'egrena.

Thirty biopsies of the lower lip mucosa from patients with clinical and subclinical manifestations of Sjögren syndrome were studied. The results indicate characteristic morphological changes in small salivary glands. The dynamics of these changes consists in progressive lymphoid infiltration of the gland tissue and includes 4 stages: I--weak lymphoid infiltration, II--focal lymphoid infiltration, III--focal-extensive lymphoid infiltration, IV--diffuse lymphoid infiltration, that is, lymphomatosis. In parallel with the progressive lymphoid infiltration there occur sclerosis of the stroma, atrophy and loss of parenchyma of the salivary glands in which the chemical composition of the secrete is changes as confirmed by tests done for mucus. The results obtained and data from literature permit a conclusion that Sjögren syndrome is a generalized autoimmune disease underlain by the disturbance of immunological homeostasis.

[Nonspecific indices of cellular and humoral immunity in viral hepatitis A and B patients]. / Sostoianie nespetsificheskikh pokazatelei kletochnogo i gumoral'nogo immuniteta u bol'nykh virusnym gepatitom A i B.

The article deals with the comparative study of the state of phagocytosis, as manifested by the ingestion of bacterial cells and by the results of the specific lupus erythematosus test, in 65 patients with acute viral hepatitis A and 45 patients with acute viral hepatitis B; these patients were also compared with respect to the presence of the markers of antigenemia and the state of their nonspecific immunity, determined by the level of serum immunoglobulins.

[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.

[Chronic active hepatitis and generalized viral infection]. / Khronicheskii aktivnyi gepatit i generalizovannaia virusnaia infektsiia.

Virus infection of organs and tissues in chronic active hepatitis (CAH) is generalized, therefore CAH may be considered to be a generalized viral infection in which liver involvement is only one but most important manifestation thereof. The involvement of both liver and other internal organs in CAH is underlain by delayed type hypersensitivity reaction supported by immune complexes containing hepatitis B virus antigens. The intensity of hypersensitivity reaction (immune inflammation) and autoimmunization is mediated genetically.

[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.

[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 active hepatitis and pregnancy]. / Khronicheskii aktivnyi gepatit i beremennost'.

In the course of chronic active hepatitis (CAH) 61 patients (CAH of virus etiology in 75% and of obscure etiology in 25%) had 211 pregnancies which terminated in delivery in 80 (38%) cases, spontaneous abortions in 12 (6%) cases, and medical abortions in 119 (56%) cases. In most cases there was successful termination of pregnancies without deterioration resulting from liver disease including patients treated adequately with immunosuppressive drugs. CAH exacerbations associated with pregnancies and their outcomes were noted in 23 (38%) cases. They were more frequent and more severe in patients with liver cirrhosis (LC) unrecognized by the time of pregnancy. There were no mothers' deaths. CAH made a negative effect on the course and outcomes of pregnancies: the frequency of premature delivery was 9%, that of cesarean-5%, perinatal mortality-75%. Of 74 infants born alive 2 died within the first months after birth as a result of congenital liver cirrhosis, a double kidney was detected in one infant, the rest of the infants were healthy. Problems of therapeutic tactics in CAH patients after onset of pregnancy are discussed.

[The development of multiple myeloma in chronic diffuse liver diseases with a long course of monoclonal immunoglobulinopathy (a description of 2 cases)]. / Razvitie mielomnoi bolezni pri khronicheskikh diffuznykh zabolevaniiakh pecheni, dlitel'no protekavshikh s monoklonal'noi immunoglobulinopatiei (opisanie dvukh nabliudenii).

The authors describe 2 patients with chronic active hepatitis accompanied for many years by stable monoclonal immunoglobulinopathy. In addition to the formation of liver cirrhosis, these patients were diagnosed to have multiple myeloma. Analysis of the authors' and reported data (including those on transformation of liver cirrhosis associated with monoclonal immunoglobulinopathy to hepatocellular carcinoma) makes it possible to regard patients suffering from chronic diffuse liver diseases associated with monoclonal immunoglobulinopathy as a group at risk for paraproteinemic hemoblastosis and hepatocellular carcinoma. The pathogenesis of the development of paraproteinemic hemoblastoses and hepatocellular carcinoma in the indicated group of patients is under discussion.

[Hepatitis B virus infection and glomerulonephritis]. / Infitsirovanie virusom hepatita B i glomerulonefrit.

HBsAg was detected in the blood serum of patients with glomerulonephritis (GN) in 21.1% of cases. During examination of patients with other diseases of the kidneys HBsAg was detected in the blood serum much less frequently (8.3%). In patients with systemic autoimmune diseases it was found in 12.1%, in patients with pyelonephritis and amyloidosis in 7.4%. Anti-HBs and HBsAg in GN patients were defined with equal frequency (20.3%). Among patients with other renal diseases anti-HBs were found more frequently in systemic autoimmune diseases (36.7%). The presence of the other hepatitis B virus marker (HBeAg) was noted in 3 out of 15 patients with chronic GN with HBSAg in the blood serum and was undetectable in either of 3 patients with HBsAg in the group with some other renal diseases. Anti-HBe were detected in 6 patients with chronic GN. Of 16 GN patients HBsAg was detected in a kidney biopsy specimen of one patient.

[Characteristics of chronic liver diseases with the presence of serum markers of the hepatitis B virus]. / Kharakteristika khronicheskikh zabolevanii pecheni s nalichiem syvorotochnykh markerov virusa gepatita B.

Different patterns of serum HBV markers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) were identified in 82 patients (12 with chronic active hepatitis, 67 with hepato-cirrhosis developing in the outcome of chronic active hepatitis, and in 3 with primary biliary cirrhosis) of 105 (78%) patients with chronic liver diseases. Besides, IgM HBcAb were identified in 9 of 47 patients (19.1%), HBsAg IgM in 4 of 9 patients (44.4%), antibodies to the delta-agent in 8 of 23 (34.8%) suffering from chronic liver diseases with the presence of serum HBV markers. Chronic liver diseases with the presence of HBsAg and/or other serum HBV markers were characterized by a variety of clinico-laboratory manifestations determined by the involvement of some organs and systems in a process. A degree of activity of chronic liver diseases was not correlated with a replication phase, an integration phase, and an immunological resolution phase in 49 patients with identified phases of development of HBV-infection. More frequent identification of serum HBV markers including those of a replication phase was not noticed among patients on prolonged immunosuppressant therapy.

[Monoclonal immunoglobulinopathy in chronic active hepatitis and liver cirrhosis]. / Monoklonal'naia immunoglobulinopatiia pri khronicheskom aktivnom gepatite i tsirroze pecheni.

The clinico-laboratory and morphological studies were performed to examine and characterize 15 patients with chronic active hepatitis and liver cirrhosis mainly of viral etiology, going in association with monoclonal immunoglobulinopathy. The diagnostic difficulties determined by the syndrome of monoclonal immunoglobulinopathy are demonstrated. The results of a long follow-up (up to 17 years) of the indicated patients' group are provided. A possible role is discussed of hepatitis B virus as a source of long antigenic stimulation in the origin of monoclonal immunoglobulinopathy in chronic diffuse diseases of the liver.