[Hepatitis virus genotype structure in patients with chronic hepatitis C].

AIM: Studies of hepatitis C virus (HCV) genotype and subtype structure in patients with chronic hepatitis C in 3 regions of the Central federal district of Russia. MATERIALS AND METHODS: Hepatitis C virus genotype and subtype structure was determined in patients with chronic HCV infection in Moscow (1993 - 1995 and 2005), Moscow region (2008) and Vladimir region (1993 -1995, 2005-2007). HCV genotype was determined by using A. Widell et al. (1994) technique, PCR (AmpliSens diagnostic kits), Genotype C test system. RESULTS: In all studied regions and during all the time periods the first position in rating belonged to HCV 1b subtype. In 1993 - 1995 and 2005 - 2007 period changes in HCV genotype and subtype structure were registered that consisted of relative weight of 1b subtype decrease and 3a subtype increase. Subtype 1b in females with chronic hepatitis C was registered more often than in males. In Vladimir region 3a subtype in males was detected more often than in females. In males older than 30 years the first rating position belongs to 1b subtype and in males younger than 30 years--subtype 3a. In females older than 30 years in Moscow region and Vladimir region, as well as in females younger than 30 years in Vladimir region subtype 1b was detected more often, while in Moscow region HCV subtypes 1b and 3a were detected with the same rate of 47.6%. CONCLUSION: Currently there is an urgent need to include mandatory monitoring of hepatitis C virus genetic variants into the system of hepatitis C epidemiologic control in Russia. This approach will allow for a significant increase in quality of hepatitis C serological diagnostics, and can be used in the prognosis of evolution of the epidemic process of this disease.

[Prognosis for patients with chronic diseases of the liver in formulating indications to orthotopic liver transplantation].

AIM: To analyse a clinical course of hepatic cirrhosis of various etiology in potential recipients of donor liver; to formulate symptom complex which determines life span prognosis in patients with chronic diffuse diseases of the liver (CDDL). MATERIAL AND METHODS: We studied 74 recipients of the liver (73 adults aged 15-58 years and 1 boy aged 13 years, mean age at liver transplantation 27.04 +/- 1.5 years, 41% males, 59% females). Orthotopic transplantation of the liver (OTL) was made from a live relative donor. All the patients have undergone clinical, biochemical, immunological, virological, ultrasonic, x-ray and other examinations. Severity of the patients' condition was assessed according to the Child-Pugh classification. Indications to transplantation of the liver were formulated basing on the syndromal approach. RESULTS: Asthenic syndrome was diagnosed in 34, pruritus--in 25, articular syndrome--in 11, jaundice--in 43, hepatomegaly--in 40, splenomegaly--in 65, ascitis--in 26, peripheral edema-- in 8, esophageal varicose veins--in 66, encephalopathy--in 5 patients. Main syndrome manifestations of CDDL involved in formulating indications for liver transplantation consisted in the syndrome of liver cell insufficiency (diagnosed in 77% cases), syndrome of portal hypertension (detected in 100% cases), edemo-ascitic syndrome (41% cases), cholestasis syndrome (95% cases), autoimmune cytopenia syndrome (77% cases), hepatorenal syndrome (5.4%). Most of potential recipients who had liver transplantation were classified as having class B and C by Child-Pugh (66.3%), but often indications for OTL were considered in terms of a combination of various syndromes significant for life prognosis in each patient and in terms of urgency of OTL performance. CONCLUSION: In determination of indications for OTL syndromal approach seems most adequate. Main syndromes influencing primarily on OTL decision making are portal hypertension with consideration of esophageal varicose veins, syndrome of hepatic cell deficiency, edemoascytic syndrome, hepatorenal syndrome, syndrome of autoimmune cytopenia and cholestasis.

[The extrahepatic site of hepatitis C virus: clinical manifestations and prognostic value].

The high incidence of recurrent chronic hepatitis C after a course of antiviral therapy determines the urgency of determining the extrahepatic reservoirs of hepatitis C virus (HCV). The most extrahepatic site for the virus is peripheral mononuclear cells (PMC). Assuming that there may be HCV replication in the PMC), these cells can be considered as a potential reservoir of HCV infection. The most common extrahepatic manifestation of HCV is cryoglobulinemia, the genesis of which may be active viral replication in the cells of the immune system. There is evidence that HCV is detectable just in the tissues of the involved organs. Thus, most systemic manifestations may be directly associated with extrahepatic HCV replication.

[Indications and optimal terms of liver transplantation in chronic diffuse hepatic disease].

Patients with chronic diffuse hepatic disease (CDHD) take a great part in structure of morbidity of adult population. Problem of treatment of patients with hepatic cirrhosis (HC) is still very important. Main contingent of these patients who need hepar transplantation consists from HC patients with various ethiology, cholestatic diseases, inborn metabolism disturbances and hepatic tumors. At present in the world there is a tendency to early performing of operation while decompensation of other organs and systems still do not exist. When there is diagnosis of inborn metabolism disturbance indication to ortotopic transplantation of hepar (OTH) are put at the same time with verification of diagnosis. In case of HC urgency of OTH depends on stage of disease (system assessment of severity of hepatic insufficiency by 'hild-Pugh, MELD), response of patients on therapy and frequency of hospitalizing. Performance of OTH makes possible to prolongate of patients' life and significantly improve its quality.

[Spectrum, incidence and prognostic value of systemic manifestations in chronic hepatitis C of low activity].

AIM: To study the incidence and prognostic significance of extrahepatic manifestations of chronic HCV-infection with low activity of hepatic process and to specify treatment policy. MATERIAL AND METHODS: Sixty-two patients with low-active chronic hepatitis C (CHC) entered the study. Blood samples from all the patients were studied clinically, biochemically, immunologically and virusologically. In 58 patients the diagnosis was confirmed morphologically (liver tissue). RESULTS: Systemic manifestations of CHC were observed in 23 (37.1%) patients, in 12 of them they were associated with cryoglobulinemia. Most frequent was cryoglobulinemic vasculitis with skin (12.9%) and joint (9.7%) involvement, cryoglobulinemic glomerulonephritis (11.3%), arthralgia without association with cryoglobulinemia (11.3%). Independent risk factors for development of systemic disorders in CHC of low activity comprised female gender, age over 45, the disease duration and presence of cryoglobulinemia. CONCLUSION: CHC of low activity is characterized by high occurrence of systemic manifestations primarily associated with cryoglobulinemia. Renal affection with development of cryoglobulinemic glomerulonephritis is most prognostically significant.

[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.

[Efficacy of lamivudine in HBeAg-negative chronic hepatitis B]. / Effektivnost' lamibudina pri HBeAg-hegativnom khronocheskom gepatite B.

The necessity of the search for new drugs to treat chronic hepatitis B (CHB) is explained by the necessity to prevent hepatic cirrhosis (HC) and hepatocellular carcinoma. Treatment of HBeAg-negative CHB rests on the same principles as of HBeAg-positive one. Efficacy of nucleoside analogue lamivudin is well studied in HBeAg-positive CHB. The aim of this study was to evaluate lamivudine efficacy in therapy of HBeAg-negative CHB. Lamivudine (epivir--150 mg/day or zeffix--100 mg/day) was given for 1 year to 10 patients (5 males, 5 females, mean age 49.5 +/- 13.5). Their blood serum contained no HBeAg but contained HBeAb and HBVDNA. Chronic hepatitis was verified morphologically in 9 patients of whom 2 had HC and 2 developing HC. Moderate activity of the disease was in 4 patients, low--in 5. All the patients had a high ALT level (150 +/- 140 U/l, 60-528 U/l, high normal value 40 U/l). ALT and HBV DNA in the serum were examined by polymerase chain reaction in the course of treatment and for 6 months after its end. To the end of the treatment a complete response (absence of HBVDNA and normalization of ALT) was achieved in 8 (80%) patients. 5 (63%) of them 2-4 months after the end of the treatment had the exacerbation with appearance of HBVDNA in the serum and elevation of ALT level. A persistent response (6 months after lamivudin treatment) was in 3 (30%) patients, in 2 of them HBsAg was not detected. Lamivudin therapy is effective in HBeAg-negative CHB. In this study a high baseline level of ALT was the factor predisposing to a lasting response to treatment.

[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.

[Expression of receptors for human alpha- and gamma-interferons on the surface of peripheral blood mononuclear cells in viral infections]. / Ekspressiia retseptorov dlia chelovecheskikh alpha- i gamma-interferonov na poverkhnosti mononuklearnykh kletok perifericheskoi krovi pri virusnykh infektsiiakh.

Expression of receptors on peripheral blood mononuclears of donors and patients with viral infections during therapy was studied using FITC-labeled monoclonal antiidiotypical antibodies with the "internal image" of human alpha- and gamma-interferons and monoclonal antibodies to these interferons. Activation of the immune system caused by infection modifies the expression of interferon receptors and leads to appearance of membrane-bound interferons, mainly gamma-interferon.

[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.