Course Of Chronic Viral Hepatitis Research Articles

Intestinal microbiota in children with chronic viral hepatitis

The article is devoted to a review of the literature on the study of intestinal microbiota in chronic viral hepatitis in children. The results of recent studies of microbial diversity of colon contents using 16S ribosomal RNA sequencing are presented. Scientific research in recent years has proven the influence of changes in the microbiota and its individual representatives on the formation of complications in patients with chronic viral hepatitis, the development of fibrosis/cirrhosis. Changed quantitative and species ratios of microorganisms can lead to the launch of pathological reactions in the intestinal-liver axis system. A significant reduction in the number of bacteria such as Clostridia and Bacteroidia (Faecalibacterium, Roseburia inilinivorans, Roseburia intestinalis, Coprococcus comes) causes low production of short-chain fatty acid butyrate, which can interfere with the functioning of tight junction proteins. Leaks and increased intestinal permeability create conditions for the formation of inflammation due to the activity of pro-inflammatory cytokines. Violation of the intestinal barrier function creates the opportunity for the penetration of bacteria, lipopolysaccharide complexes, bacterial ligands and metabolites, leading to the development of immunopathological reactions. These changes in the pediatric population are less noticeable than in the adult cohort of patients, since the clinical course of chronic viral hepatitis in children has a smoother course. However, periods of exacerbation, which are characterized by clinical and laboratory changes, may maintain the risk of developing fibrogenesis activity in older age groups. Data on intestinal microbial diversity in adult patients with chronic viral hepatitis B and C are presented separately. The possibilities of using pre- and probiotic therapy in the complex treatment of chronic liver diseases in adults and children are considered.

The value of osteopontin in predicting fibrosis in patients with chronic viral hepatitis C

Background. Diagnosis of an asymptomatic course of chronic viral hepatitis C (HCV) and the existing development of the fibrotic process by determining the marker capabilities of biochemical blood parameters (primarily osteopontin — OP) is an urgent issue in modern medicine. Purpose: to evaluate the prognostic value of biochemical blood markers for diagnosing an asymptoma­tic course of HCV and the existing fibrotic process. Materials and me­thods. Seventy-eight people were examined: 47 from the main group — 19 (40.4 %) women and 28 (59.6 %) men with chronic HCV, and 31 controls — 17 (54.8 %) women and 14 (45.2 %) men without chronic HCV. The median, as well as 25.0% and 75.0% quartiles and relative values were calculated for quantitative and qualitative measures, respectively. Predictors were determined using logistic regression analysis. Results. The data obtained by a univariate analysis indicate a significantly increased risk of develo­ping liver fibrosis on the background of chronic HCV, with alanine aminotransferase (ALT) levels increased by 1.037 times, aspartate aminotransferase (AST) by 1.051 times, gamma-glutamyl transferase (GGT) by 1.017 times; thymol turbidity test by 1.424 times; total protein by 1.162 times and OP by 3.002 times. With increased levels of triglycerides and very low-density lipoproteins, a significant decrease in these risks was found, by 74.7 and 94.7 %, respectively. A multivariate analysis found significantly increased risks of deve­loping liver fibrosis on the background of chronic HCV, with higher levels of AST, total protein, and OP (by 1.028, 1.195 and 2.510 times, respectively). Conclusions. With a significant liver damage by a fibrotic process (stage 3–4), as compared to stage 0–2, there is a probable predominance of biochemical liver markers in the blood of patients with HCV: ALT, AST, GGT, total protein and OP. AST, total protein, and OP were identified as reliable predictors of liver fibrosis. The developed mathematical model has high sensitivity and specificity: 87.5 and 83.9 %, respectively.

CLINICAL AND LABORATORY FEATURES OF THE COURSE OF CHRONIC VIRAL HEPATITIS B AND C IN CHILDREN OF PODILSKY REGION: POSSIBILITY FOR MODERN MONITORING

Introduction. In modern hepatology, a special place is occupied by chronic viral hepatitis, including B and C, because today they occupy the leading positions due to their high prevalence, the possibility of severe complications, and also they could lead to death in both adults and children. Specialists should have a comprehensive understanding of the clinical course and laboratory diagnosis of viral hepatitis to facilitate timely diagnosis and effective management of this condition.
 The aim: to evaluate the clinical and laboratory features of the course of chronic viral hepatitis B and C in children by determining patterns between parametric indexes characterizing the processes of liver fibrosis.
 Materials and methods. In the process of scientific research, 49 children were examined, including 29 children with diagnosed chronic viral hepatitis B and C (group I) and 20 almost healthy children (group II). The diagnoses of CHB and CHC were confirmed by the PCR method and specific markers detected by ELISA. All examined patients underwent anamnesis collection, general clinical examination, laboratory examination, calculation of CDS, Lok, GUCI, APRI, FIB-4 and "Fibrotest" diagnostic indexes. Statistical data analysis was carried out with "R-Studio" and "Statistica 10.0" software, using the methods of descriptive statistics, correlation analysis. Significance was considered significant at p<0.05. The study was conducted in compliance with the principles of the Declaration of Helsinki.
 Results. It was established that the levels of ALT, AST, GGT, ALP, indirect bilirubin, international normalized ratio (INR) were significantly higher in the examined patients of the I group. The level of the CDS index was significantly higher in the examined patients of the I group (5,97±0,30), compared with the patients of the II group (4,35±0,28) (p<0,001). A similar trend was noted with the Lok index and FIB-4 (p<0,001). The GUCI and APRI indices were significantly higher in patients of the I group (1,02±0,22; 0,73±0,04), compared to the examined patients of the II group (0,27±0,02; 0,23±0,02) (p<0,01).
 Conclusions. Implementation of non-invasive indices into clinical practice for the management of children with chronic hepatitis B and C will allow for dynamic monitoring of liver fibrogenesis processes.

A Current Management Strategy for Children with Chronic Viral Hepatitis B, Based on International and National Guidelines.

Peculiarities of the course of chronic viral hepatitis B in children cause an important medical and social problem of health care, despite the implementation of modern treatment and prevention protocols. Pathogenetic mechanisms of the development and progression of viral hepatitis B infection, the presence of occult poorly diagnosed form, the impossibility of completely eliminating the virus and the specificity of the immune response in children are still not fully solved scientific problems. The aim of this review is to examine current strategies for the diagnosis and treatment of chronic hepatitis B in children, based on international and national guidelines. A detailed analysis of modern guidelines on the course and pathogenesis of viral hepatitis B infection confirms the fact that chronic hepatitis B is characterised by a complex interaction between the immune system of the virus and the patient, whose dynamic balance is not only responsible for the various phases of chronic viral hepatitis B infection but also leads to the result of antiviral treatment. Despite the introduction of vaccination of children against hepatitis B, the level of viral hepatitis B vaccination of children in Ukraine remains insufficient, which leads to the further spread of the infection. Currently available antiviral drugs can provide functional treatment of viral hepatitis B infection in a limited number of patients, but today's Ukrainian realities have caused a change in approach to the treatment and monitoring of patients, which may negatively affect the implementation of the key goals of the World Health Organization Global Strategy on the prevention, diagnosis and treatment of viral hepatitis.

ВОЗМОЖНОСТИ КОНТРАСТ-УСИЛЕННОГО УЛЬТРАЗВУКОВОГО ИССЛЕДОВАНИЯ ПРИ ДИФФУЗНЫХ ЗАБОЛЕВАНИЯХ ПЕЧЕНИ (НА ПРИМЕРЕ ХРОНИЧЕСКИХ ВИРУСНЫХ ГЕПАТИТОВ)

Background. Contrast-enhanced ultrasound is a modern imaging modality providing with the possibility of real-time liver state assessment that is important in determining the degree of parenchymal damage in order to predict the course of the disease and to change the treatment strategy accordingly. Objective. To determine the diagnostic and prognostic value of contrast-enhanced ultrasound (CEUS) of the liver in patients with chronic viral hepatitis (CVH) B and C. Material and methods. 284 individuals were examined from 2018 to 2021. All the patients were divided into 3 groups. The experimental group included CVH patients who underwent CEUS examination; there were 2 control groups: № 1 – patients with CVH who did not undergo CEUS examination; the aim was to determine the predictive effectiveness of the method, № 2 - patients with CVH and without CEUS examination - to determine the diagnostic effectiveness of the method. Results. During the study, it was found out that the greatest changes in CEUS parameters were observed in patients with F4 fibrosis stage according to the METAVIR score. It was the assessment of qualitative parameters according to the proposed standardized program that had the highest prognostic and diagnostic potential. As far as the quantitative parameters of CEUS are concerned the values of the difference of quantitative parameters in the proximal and distal zones (ΔTOA, ΔTTP, ΔPI, ΔHTWo) were of considerable importance. Conclusions. Contrast-enhanced ultrasound makes it possible to detect signs of an unfavorable course of chronic viral hepatitis already at an early clinical stage, thus enabling to adjust the treatment strategy and improve long-term prognosis.

Comparison of clinical and laboratory characteristics and frequency of liver fibrosis in patients with chronic viral hepatitis C of the first and third genotypes

Introduction. There is a discussion about which genotype of viral hepatitis C (HCV) is the most aggressive. Some authors consider that the 1st genotype is the most aggressive, others define the 3rd HCV genotype as a factor that determines the high activity of the pathological process. The solution of this issue is important for optimizing the tactics of patient management.Aim. To compare the clinical and laboratory characteristics and the incidence of liver fibrosis in patients with chronic viral hepatitis C of the first and third genotypes.Materials and methods. 297 patients with genotype 1 of HCV and 231 patients with genotype 3 of HCV were examined. The diagnosis of chronic viral hepatitis C was established according to the recommendations of the European Association for the Study of the Liver (2016, 2018). Liver fibrosis was studied by shear wave transient elastometry with METAVIR score.Results and discussion. The frequency of elevated ALT in the blood prevailed in patients with HCV genotype 3 compared with persons with HCV genotype 1 (90.5% vs. 82.8%, p = 0.02). ALT levels above 3 norms were registered in 29.0% of patients with genotype 3 and in 16.8% patients with HCV genotype 1 (p = 0.001). The frequency of liver fibrosis F2 according to METAVIR was 11.8% in patients with genotype 1 and 21.2% in patients with genotype 3 of HCV (p = 0.005); the frequency of liver fibrosis F3–F4 according to METAVIR was 20.5% in patients with genotype 1 and 32.5% in patients with genotype 3 of HCV (p = 0.003). The combination of high viral load and high inflammatory activity, which was associated with liver fibrosis F3–F4 according to METAVIR in both compared groups, was determined in 16.9% of patients with genotype 3 and only in 10.4% of patients with genotype 1 of HCV (p = 0.04).Conclusion. The obtained data allow us to consider that in the surveyed population the course of chronic viral hepatitis C with genotype 3 is clearly more aggressive than in persons with genotype 1 of HCV.

Peculiarities of the Clinical Course of Chronic Viral Hepatitis C in the Background of End-Stage Chronic Renal Insufficiency

We investigated the clinical, epidemiologic, and pathogenetic features of viral hepatitis C in hemodialysis departments. This multicenter study included patients who were seen at the hemodialysis department in Tashkent, Uzbekistan and at regional departments located in the Republic of Uzbekistan. We examined 395 patients who were on hemodialysis from 3 to 15 years. A diagnosis of chronic viral hepatitis C was made on the basis of anamnesis, clinical laboratory data, and detection of immunoglobulin G antibodies for hepatitis C virus. From clinical and laboratory results analyzed in 395 patients, markers of infection with parenteral viral infections were shown in 181 patients (45.8%). Chronic viral hepatitis C had the highest incidence among infections, which was detected in 125 patients (31.6%). With regard to chronic renal failure, 11 patients (34%) with chronic viral hepatitis C had a transient form of chronic renal hepatic failure with development of adverse outcomes. Of patients with chronic viral hepatis C infection, 13 patients (40%) with hemorrhagic syndrome developed progressive anemia and 8 patients (25%) developed persistent polyserositis in the form of hydrothorax, ascites, and pericarditis. These developments reflect the aggravating effects of chronic viral hepatitis C on the course of chronic renal failure. In our study that included patients seen at hemodialysis departments in Uzbekistan, chronic viral hepatitis C was greatly prevalent, although occurring mainly in a minimal form of the pathologic process. Chronic viral hepatitis C has an aggravating effect on the course of underlying diseases with development of adverse outcomes.

462 - Lipid Peroxidation Activity in Women with Chronic Viral Hepatitis

Background Chronic viral hepatitis B and C represent a serious medical and social problem, due to their widespread, severe course and significant rejuvenation of the main groups of patients. Currently, sharp increase of chronic forms of hepatitis incidence recorded mainly due to active involvement of reproductive age women in epidemic process. Lipid peroxidation and antioxidant defense system (POL-AOD) playing important place in adaptive reactions, reduction of inflammatory processes and pathology activity and homeostasis maintaining. Because of that, the aim of this study was to analyze peculiarities of POL-AOD parameters changes in women of reproductive age with chronic viral hepatitis B and C. Methods The study included 44 patients (mean age 28,8±7,5 years) with chronic viral hepatitis B (20 patients-45%) and C (24 patients -55%). The control group (mean age 30,8±2,9 years) consisted of 28 healthy women. Spectrophotometric and fluorimetric methods were carried out on Shimadzu RF-1501 spectrofluorophotometer (Japan) and Shimadzu RF-1650 spectrophotometer (Japan) used to investigate lipid peroxidation products and antioxidant defense components in serum and hemolysate. Results The results showed that women with chronic viral hepatitis have statistically significant 1.9 times (p=0,006) increase of POL end-of TBA-active products compared to control values. No statistically significant differences of lipid peroxidation primary products - diene conjugates revealed (p>0,05). The AOD system in women with chronic viral hepatitis in comparison with the control showed 39% decrease (p Conclusion In the course of chronic viral hepatitis the inflammatory process in the liver leads to the generation of reactive oxygen species, initiating lipid peroxidation processes, significant intensification of oxidative stress reactions accompanied by simultaneous inhibition of the antioxidant defense system functions. Data obtained prove the necessity of more thorough approach in diagnostic and therapeutic activities in such patients.

Variations of serum levels of adiponectin and resistin in chronic viral hepatitis.

Several studies investigated the possible role of adipokines during chronic viral hepatitis, not producing defined results neither clearly establishing their behavior in course of anti-viral treatment. Our study evaluated blood concentrations of adiponectin and resistin in patients with chronic hepatitis C (CHC), B (CHB), and D (CHD) receiving anti-viral treatment, at baseline and after therapy. We examined 122 subjects, divided into two groups: 64 patients with chronic hepatitis C virus (HCV) infection (38 males and 26 females, mean age 47.25 yr) and 58 patients including 39 ones with chronic hepatitis B virus (HBV) infection (26 males and 13 females, mean age 48.46 yr) and 19 ones with chronic HBV-hepatitis D virus (HDV) infection (15 males and 4 females, mean age 45.79 yr). Serum levels of adiponectin and resistin were assayed by enzyme-linked immunosorbent assay. In the group of CHC patients we observed a significant decrease in resistin after therapy (p=0.006), while not a significant increase in adiponectin after treatment (p=0.32). Evaluation of changes in adiponectin and resistin levels after anti-viral treatment, both in responders and non-responders, revealed no significant variations. In the group of HBV+ and HBV-HDV+ patients, we found a decrease in resistin after therapy (p=0.0016) and a not significant reduction in adiponectin after treatment (p=0.13). Furthermore, we noticed a significant reduction of resistin (p=0.006) in the sub-group of responders. Our data suggested the possible marker role of adiponectin and resistin in the inflammatory process in course of chronic viral hepatitis.

P019 Regional prevalence of IL28B SNPS rs8099917& rs12979860 in general population and in a cohort of chronic liver diseases patients

Introduction The minor IL28b SNPs rs8099917& rs12979860 have been associated with progression to chronic infection and failure of antiviral therapy in HCV patients. Considerable variation in carriage frequencies have been reported in different ethnicities. Our AIM was to study their allele frequency and genotype distribution in our ethnic specific general population and in a cohort of chronic liver diseases patients. Methods Rs8099917 genotyping was performed by PCR/SSCP analysis; rs12979860 by PCR/RFLP. A total of 255 subjects were studied. The control Group A consisted of 79 randomized and anonymized ethnic DNA bank samples; Group B – 50 chronic HBV patients; Group C – 83 HCV patients; Group D – 43 patients, advanced liver disease and transplanted livers (Ci/Ltx). HCV RNA, HBV DNA and genotyping was done by Roche TaqMan IVD FDA approved RT-PCR. Results The allele frequency of rs8099917 in the control group reached Hardy Weinberg equilibrium (HWE); the study population did not. The frequencies of GG,GT and TT genotypes were as follows. In Group A: 0.05, 0.33, 0.62; in Group B: 0.07, 0.4, 0.54; in Group C: 0.07, 043, 0.33 Group D: 0.05, 0.25, 0.13 respectively. The difference of the allele frequencies was statistically significant for Group A vs. combined (B + C+D), p = 0.0071 and for Group A vs. Group D, p = 0.0062, two-tailed Fisher’s exact test. Peg-interferon/ribavirin therapy received 28 HCV (genotype G1 = 25). Of those who completed 48 week therapy, 6 had SVR and 8 were non-responders or relapsers. In the SVR group, G containing genotypes were significantly lower compared to the NR/R group Chi sq. = 5.091, P = 0.012. For rs12979860 the control group is not yet studied, but the patients group (No = 80) was in HWE, with genotype frequency of CC 0.325, CT 0.475, TT 0.2. Conclusion The frequency of rs8099917 in healthy individuals in our region is similar to that of Italians from Toscana. The prevalence of the minor/heterozygous genotype in HCV patients was higher as compared to the reported for Spanish, Australian and Swiss populations. Minor allele frequency was greater in the HCV therapy non-responder patients. The rs12979860 genotype frequency in patients with advanced chronic liver disease and liver transplant recipients was similar to the recently reported for Ci/Ltx by Fabris in J.Hepatol. References Fabris C. IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: role in the course of chronic viral hepatitis and the development of HCC. J Hepatol 2011;54(4):716–22.

Modern aspects of the natural course of chronic viral hepatitis B

Currently there are about 400 million people infected with the hepatitis B virus, including five million people - in Russia. A serious problem is the development of complications of chronic viral hepatitis’ - liver cirrhosis and hepatocellular carcinoma, from which eventually 20-35% of patients die. Undoubtedly, the outstanding science achievement of the XX century was the creation of a genetically engineered vaccine against hepatitis B. The pursued immunizations on a global scale has led to significant results - reduction of the number of cases of acute forms of viral hepatitis B, the frequency of formation of the chronic variant of the disease. Despite these successes, there remains the problem of prevention of the perinatal transmission path. Identified were the risk factors for neonatal infection, amongst which the most significant are the presence of the antigen of the hepatitis B virus, which is not a part of the Dane particles (HBEAg), and the level of viremia prior to delivery. The basis of prevention is an active-passive immunization, which helps prevent infection in infants in 90-95% of cases. Encouraging results (reduction in the risk of infant infection) were obtained in studies of antiviral therapy in the III trimester of pregnancy. The introduction of new molecular biological diagnostic methods (polymerase chain reaction) made it possible to determine the genetic material of the virus in serum and tissues, the presence of mutations and genetic variability of the virus. At present, identified are the factors that determine the progression of the disease, the efficacy of antiviral therapy. Identified are the new variants of the clinical course of viral hepatitis B, depending on the profile of the serological (antigen-antibody) markers. The latent course of viral hepatitis B deserves special attention. The serological feature of this variant is the presence of «isolated» antibodies and/or deoxyribonucleic acid of the virus, or the absence of all markers of hepatitis B. It is obvious that patients with a latent course of infection pose a real threat in spreading viral hepatitis B.

Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel

AbstractChelation therapy with new drugs prevents cardiac damage and improves the survival of thalassemia patients. Liver diseases have emerged as a critical clinical issue. Chronic liver diseases play an important role in the prognosis of thalassemia patients because of the high frequency of viral infections and important role of the liver in regulating iron metabolism. Accurate assessment of liver iron overload is required to tailor iron chelation therapy. The diagnosis of hepatitis B virus– or hepatitis C virus–related chronic hepatitis is required to detect patients who have a high risk of developing liver complications and who may benefit by antiviral therapy. Moreover, clinical management of chronic liver disease in thalassemia patients is a team management issue requiring a multidisciplinary approach. The purposes of this paper are to summarize the knowledge on the epidemiology and the risks of transmission of viral infections, to analyze invasive and noninvasive methods for the diagnosis of chronic liver disease, to report the knowledge on clinical course of chronic viral hepatitis, and to suggest the management of antiviral therapy in thalassemia patients with chronic hepatitis B or C virus or cirrhosis.

IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: Role in the course of chronic viral hepatitis and the development of HCC

A single nucleotide polymorphism (rs12979860 C/T) 3kb upstream of the interleukin 28B (IL-28B) gene was shown to be associated with hepatitis C clearance. We verified whether this association also translates into a different genotype distribution at the end of the disease trajectory. A RFLP-PCR technique was used to genotype 412 patients with cirrhosis due to hepatitis C (n=199), hepatitis B (n=75), alcohol (n=110), and other causes (n=28), of whom 256 underwent liver transplantation (OLT). Hepatocellular carcinoma (HCC) was demonstrated in the native liver of 85 OLT patients, 52 with viral cirrhosis, and 33 with non-viral cirrhosis respectively. A group of 292 patients (235 HCV and 57 HBV positive) with mild chronic hepatitis and 344 healthy subjects served as controls. A significant difference (p=0.0005) was observed in IL-28B rs12979860 genotype frequencies between patients with viral cirrhosis (C/C=99, C/T=137, T/T=38) and those with non-viral cirrhosis (C/C=72, C/T=58, T/T=8). Patients with HCV related cirrhosis carried more frequently the T/T genotype in comparison to mild hepatitis C or HBV-related cirrhosis. IL-28B rs12979860 genotype frequencies were C/C=23, C/T=50, T/T=12 among OLT patients with cirrhosis complicated by HCC, and C/C=79, C/T=78, T/T=14 among patients with cirrhosis not complicated by HCC (p<0.005). IL-28B rs12979860 C/T polymorphism T allele is more prevalent in patients with viral cirrhosis due to HCV in comparison to other aetiologies and to patients with mild chronic hepatitis C. Among OLT patients, carriage of this allele seems to augment the risk of developing HCC.

Liver Fibrosis Is Associated with Decreased Peripheral Platelet Count in Patients with Chronic Hepatitis B and C

Thrombocytopenia is a common complication of chronic liver diseases, but its pathogenesis is not clear. Although generally attributed to hypersplenism, other factors should also be considered. We investigated the relationship between the peripheral platelet count and the degree of fibrosis in patients with chronic viral hepatitis. In an effort to avoid the effects of hypersplenism, we excluded patients with splenomegaly and/or bi- or pan-cytopenia. Seven hundred eighty-four patients (265 chronic viral hepatitis C and 519 chronic viral hepatitis B) were included in the study. Univariate analysis showed that the peripheral platelet count had a negative correlation with fibrosis score, necroinflammatory activity, and age in both groups. In multivariate analysis, the peripheral platelet count had a similar correlation with the fibrosis score and age, but not with necroinflammatory activity, in both groups. The peripheral platelet count decreased more significantly in females with chronic hepatitis C but not in the chronic hepatitis B group. In conclusion, a decrease in peripheral platelet count may be a sign of an increase in the degree of fibrosis during the course of chronic viral hepatitis B and C and factors other than hypersplenism may play a role in this decrease in the peripheral platelet count.

Significance of Alterations in PBMC Immunophenotype of Children with Chronic Viral Hepatitis C – the Role of Dendritic Cells

There are differences in the clinical course of chronic viral hepatitis C between adults and children, but it is generally accepted that the disease has cell-mediated immune background. The aim of this study was to evaluate PBMC subsets in children with chronic hepatitis C before treatment in order to find some predictive factors, useful for patients management. Several PBMC subsets, in particular lymphoid and dendritic cell (DC) ones, were tested by flow cytometry in HCV(+) paediatric patients (n = 46) and in control children matched in terms of age and sex (n = 20). Data were subjected to extensive statistics. It was found that cells with cytotoxic potential such as CD8(+)CD28(-) T cells, NK and NKT cells as well as lineage(-)HLA-DR(+) DC were increased in per cent values, while CD4(+) T cells and CD4:CD8 ratio were decreased in hepatitis C group. In HCV(+) patients, CD4(+) T cells were inversely correlated with alanine aminotransferase (ALT) levels and with viraemia. DC subset of myeloid origin (CD11c(+)) assessed both in per cent values and as mean fluorescence intensity (MFI) of HLA-DR expression was shown to be downregulated in hepatitis patients, in spite of increased numbers. To conclude, PBMC subsets, and in particular DC, are affected by HCV chronic infection in children, reflected by the correlation with clinical parameters, such as ALT and viraemia.

Conserved balance of hepatocyte nuclear DNA content in mononuclear and binuclear hepatocyte populations during the course of chronic viral hepatitis

To analyze the percentages of hepatocytes with increased nuclear DNA content, i.e., tetraploid (4n) and octoploid (8n) nuclei, and then compared mononuclear and binuclear hepatocyte populations. The percentages of mononuclear diploid (2n), 4n, and 8n hepatocytes and those of binuclear 2 x 2n, 2 x 4n, and 2 x 8n hepatocytes were determined with a method that can simultaneously measure hepatocyte nuclear DNA content and binuclearity in 62 patients with chronic hepatitis B or C. The percentage of 4n and 8n hepatocytes in the mononuclear hepatocyte population was compared with the percentage of 2 x 4n and 2 x 8n hepatocytes in the binuclear hepatocyte population. The percentages of 4n and 8n hepatocytes in mononuclear hepatocytes and 2 x 4n and 2 x 8n hepatocytes in binuclear hepatocytes were similar, regardless of the activity or fibrosis grade of chronic hepatitis and regardless of the infecting virus. The distribution of nuclear DNA content within mononuclear and binuclear hepatocyte populations was conserved during the course of chronic viral hepatitis.

Inducible nitric oxide synthase expression in chronic viral hepatitis. Evidence for a virus-induced gene upregulation.

Increased nitric oxide (NO) production may contribute to the pathological changes featuring in some inflammatory diseases, but the role of NO in chronic viral hepatitis is still unknown. We compared the inducible NO synthase (NOS2) expression in the liver of patients with chronic viral hepatitis with that of both nonviral liver disease and histologically normal liver. NOS2 expression was assessed by immunohistochemical and in situ hybridization studies of liver biopsy sections. An intense hepatocellular NOS2 reactivity was detected in chronic viral hepatitis, whereas it was weakly or not observed in nonviral liver disease or normal liver, respectively. In addition, we determined whether the hepatitis B virus (HBV) might regulate the synthesis of this enzyme. NOS2 mRNA and protein levels as well as enzyme activity were assessed in cytokine-stimulated HBV-transfected and untransfected hepatoma cells. Transfection with either HBV genome or HBV X gene resulted in induction of NOS2 mRNA expression, and the maximal induction of this transcript and NO production was observed in cytokine-stimulated HBV-transfected cells. These results indicate that hepatotropic viral infections are able to upregulate the NOS2 gene expression in human hepatocytes, suggesting that NO may mediate important pathogenic events in the course of chronic viral hepatitis.

Recent developments in autoimmune liver diseases.

Several diseases are regarded as autoimmune liver diseases. Apart from the cholestatic liver diseases, primary biliary cirrhosis, primary sclerosing cholangitis, these include autoimmune hepatitis, hepatitis as part of the autoimmune polyendocrine syndrome type 1 (APS-1) and particular overlap syndromes such as autoimmune cholangitis (also called antimitochondrial antibody negative primary biliary cirrhosis [PBC]), overlap syndrome chronic active hepatitis (CAH)/PBC and the overlap syndrome primary sclerosing hepatitis (PSC)/CAH. In addition, auto-antibodies may be observed during the course of chronic viral hepatitis, in particular chronic hepatitis C and D. Finally, a small number of drug-induced liver diseases is immune mediated. The following article will review our recent progress in the field of autoimmune hepatitis including APS-1 and autoimmunity in viral hepatitis and immune-mediated drug-induced liver disease.