Chronic hepatitis

mediated lipid transfer. Of note, MAb C167 also potently blocked Huh-7.5 infection by an HCV strain recovered from HCVcc-infected chimpanzees. These results demonstrate that SR-B1 is essential for infection with HCV produced in vitro and in vivo and suggest the possible use of anti-SR-B1 antibodies as therapeutic agents.

We quantified hepatitis C virus (HCV) RNA at different times in plasma and peripheral blood mononuclear cells (PBMC) in 51 patients with chronic hepatitis C undergoing inter-feron-α2a (IFN-α2a) therapy. HCV RNA loads in plasma correlated with those in PBMC before and ...

Staging fibrosis accurately has always been a challenge in viral hepatitis and other liver diseases. Liver biopsy is an imperfect gold standard due to its intra and interobserver agreement limitations and additional characteristics such as its safety and cost. Hence, non-invasive tests have been developed to stage liver fibrosis. In addition to serological biomarkers, physical tests with reasonable accuracy are available and adopted in the daily clinic regarding viral hepatitis fibrosis staging. In this review, we discuss the published data regarding the staging of liver fibrosis in chronic hepatitis B and C, emphasizing non-invasive markers of fibrosis, both serological and physical. Moreover, we also discuss a persistent central gap, the evaluation of liver fibrosis after HCV cure.

A six-year-old boy presented with cough, cyanosis and clubbing. Investigations revealed hypoxia (PaO2 53 mm Hg on room air) which was only partially correctable (PaO2 73 mm Hg) with 100% oxygen administered through a non re breathing face mask. Liver function tests showed elevated total bilirubin, and transaminases, liver biopsy confirmed chronic hepatitis and endoscopy showed grade three varices. A contrast enhanced echocardiography (bubble study) revealed pulmonary arterio-venous communication. A diagnosis of hepatopulmonary syndrome was made based on the triad of hypoxemia, liver disease and intra pulmonary vascular communications.

plus ribavirin therapy. Conclusion: Our findings suggest that the combined treatment with pegylated IFN-␣ and ribavirin downmodulates the secretion of key cytokine IFN-␥ as early as 12 weeks after treatment in infected patients. These findings could encourage new exciting possibilities for immunebased interventions with the aim of restoring functional antiviral T cell responses combined with improved viral clearance.

Mutations that prevent the expression of the hepatitis B e antigen frequently emerge in the immunoreactive phase of infection. The predominant mutation, the precore G→A-1896 mutation, is restricted by the variability at position 1858 and is rare in strains with cytosine at nucleotide 1858. The C-1858 variant is characteristic of genotype A. It also occurs in genotypes C and F, but not in B, D, or E, explaining the geographical variation in the prevalence of precore mutants. C-1858 strains have been frequently observed in southeast Asia, but have not been phylogenetically characterized. By sequencing eight complete hepatitis B virus genomes, C-1858 variants of east Asian origin were found to constitute a phylogenetic entity within genotype C that probably diverged several hundred years ago. Further study of the distribution of this variant is warranted.

Altered cell cycle regulatory genes expression contributes to HCV-associated liver disease. We sought to assess the role of cyclins and cyclin dependent kinases (CDKs) in HCV-associated CH and HCC.Aberrant expression of cyclins A, E, D1, CDK2 and CDK4 was assessed by immunohistochemistry and differential PCR in HCV-associated CH and HCC with pericarcinomatous foci (PCF). S phase fraction (SPF) was determined

Although the pathogenetic significance of hepatitis B virus x protein (HBxAg) in chronic hepatitis, liver cirrhosis, and primary hepatocellular carcinoma has already been studied, the comparative analyses of both the actual serum HBxAg levels and antibody production against various HBx epitopes have been examined to lesser extent. We have simultaneously investigated the relationship between antibody production (IgG and IgM) against the HBxAg fragments and HBxAg level in the sera of patients with acute (14) or chronic hepatitis (80) and symptomless carriers (12). A recently developed sandwich-type ELISA was used for the quantitative measurements of HBxAg. Overlapping recombinant and synthetic antigens were used to map the fine epitope specificities of circulating anti-HBx antibodies. In acute hepatitis, we have found high and homogenous correlation in the IgM type immune responses against all the examined HBxAg regions. Moreover, strong correlation has been observed between IgG type immune responses to a characteristic C-terminal region (C1: 79-117) and the longest fragment (X: 10-143). Moderate correlation has been found between HBxAg concentration and the IgG type anti-HBx antibody levels against C-terminus of HBxAg in patients with chronic hepatitis. In the case of symptomless carriers, there were also demonstrable associations in the immune responses against the C-terminal sequences; however, significant correlations were found for antibody production against the N-terminal region as well. The examinations show that the C-terminal sequence, responsible for transactivation, promotes an efficient IgG antibody response in all three groups of patients, whereas the negative regulator N-terminal part of the HBxAg molecule for the most part does not trigger antibody production. This suggests that the immune responses against various-biologically active-epitopes of the HBxAg may have a different role in the pathogenesis of hepatitis and may be used as prognostic markers in human HBV infections.

In this study, we examined the expression of hepatitis C virus (HCV) components in hepatocytes and peripheral blood mononuclear cells (PBMC) from patients positive for anti-HCV antibodies and negative for serum HCV-RNA. The samples obtained from 25 randomly selected patients (13 of 25 patients showed no histological evidences of chronic hepatitis and had normal serum ALAT and GGTP levels) were studied by in situ Hybridization and Immunofluorescence assays. The findings show that HCV-RNA of both positive and negative polarity was carried in the hepatocytes of more than 80% of cases. The proportion of cells expressing the negative strand (mean ± SD, 10.25% ± 5.56%) was lower than those expressing positive strand (mean ± SD, 19.88% ± 9.19%) (p=0.0076; Student's t test). In addition, reaction products suggestive of HCV core, E1 and E2 antigens within hepatocytes were also observed. Both hybridization and immunofluorescence signals were localized in the cytoplasm suggesting that this is the place of active HCV replication. On the other hand, the HCV-RNA of positive polarity was detected in PBMC from 16 out of 17 samples analyzed (94%) while the HCV-RNA of negative polarity was detected in 82% of samples investigated. Positive hybridization signals were localized in the cytoplasm of PBMC. Interestingly, 12 out of 13 patients with clinical and histological resolution of hepatitis, contain HCV-RNA in either liver or PBMC. These results provide further evidences that the intermediate replicative form of the HCV genome can persist in hepatocytes and PBMC after apparently complete resolution of chronic hepatitis C.

The performance of a fully automated, random access, enhanced chemiluminescence immunoassay (Ortho/ ECi) for the detection of antibody to hepatitis C virus (HCV) (anti-HCV), HBsAg, and antibody to HBsAg (anti-HBsAg), in human serum was compared to a Abbott second-generation enzyme immunoassay (EIA 2.0). The Ortho/ECi assays employ an immunometric technique with enhanced chemiluminescence for optimal assay performance. With regard to the study of clinical laboratory performance, six groups of sera prescreened with Abbott EIAs were assayed: anti-HCV-negative samples (n ‫؍‬ 318), anti-HCV-positive samples (n ‫؍‬ 177), anti-HBsAg-negative samples (n ‫؍‬ 241), anti-HBsAg-positive samples (n ‫؍‬ 239), HBsAg-positive samples (n ‫؍‬ 158), and HBsAg-negative samples (n ‫؍‬ 312). Sera with discrepant results in the two serological assays were resolved by confirmatory tests. Sera with indeterminate results by one or more confirmatory tests were evaluated by reviewing medical records. The overall concordance between the Ortho/ECi assay and the Abbott EIA were 97.78, 93.54, and 97.66% for anti-HCV antibodies, anti-HBsAg antibodies, and HBsAg, respectively. After resolving the discrepancies, the specificities of the new assay for anti-HCV and anti-HBsAg antibodies and HBsAg were 98.1, 92.8, and 100%, respectively. The sensitivities of the new assay for anti-HCV, anti-HBsAg, and HBsAg were 100, 98.8, and 97.4%, respectively. In conclusion, The Ortho/ECi assays for diagnosis of HCV and hepatitis B virus (HBV) infections are highly specific and sensitive assays. The rapid turnaround time, random access, full automation, and high throughput make it an effective assay system for clinical laboratory diagnosis of HCV and HBV infections.

Liver chronic diseases constitute an important public health issue. When diagnosing diffuse hepatopathies, ultrasonography is a simple method bringing useful information but not safe enough when determining the difference between certain diseases (steatosis, chronic hepatitis or early cirrhosis) or quantifying their severity. Present study is focused on examining pure fibrosis tissues in order to get a clear overview on how the presence of the fibrosis affects the ultrasonographic aspect of liver. We tried to assess the usefulness of the computerized texture image analysis in noninvasive fibrosis grade quantification. From over 350 with biopsies we’ve selected 58 chronic hepatitis C patients, which have pure fibrosis without any steatosis. On each image we established a Region of Interest and we extracted 166 features using 4

An increasing frequency of hepatic granulomas, up to 10%, in chronic hepatitis C patients is reported, and their presence is considered to be a predictor of treatment success. However, there is only one prevalence study on granuloma in chronic hepatitis B, and its significance for ...

Lactulose is currently the drug of choice for the treatment of hepatic encephalopathy. It is, however, only available as a syrup which is contaminated with other sugars. Consequently patients may express aversion to its excessively sweet taste and many experience nausea because of its hyperosmolarity. Lactitol is a disaccharide analogue of lactulose which can be produced as a pure crystalline powder with a low relative sweetness. Theoretically it should have the same therapeutic effects as lactulose but fewer side effects. Five patients with chronic hepatic encephalopathy on maintenance lactulose were monitored clinically, psychometrically, and by measurement of venous blood ammonia, electroencephalogram mean cycle frequency, and cerebral blood flow during three months treatment with lactulose and a similar period on lactitol. Lactitol was at least as efficacious as lactulose but was more acceptable because its cathartic effect was more predictable, its formulation was more convenient and its less sweet taste preferred. Lactitol is the ideal successor to lactulose for treatment of this condition. Lactulose (P-galactosido-fructose) has been used since 1966 to treat hepatic encephalopathyl and is now accepted as the drug of choice for this condition. This compound is, however, only available as a syrup in which the parent compound is contaminated by other sugars, principally galactose and fructose. Its excessively sweet taste is unacceptable to a number of patients and many experience nausea because of its hyperosmolarity. Despite these disadvantages no analogues with more favourable physicochemical properties have been developed for use in this condition. Recently lactitol (13-galactosido-sorbital), a disaccharide analogue of lactulose has been described.3 This compound is easily produced from lactose in a chemically pure form and can be dispensed as a powder which has a relative sweetness, depending on its concentration, of only 35% compared with sucrose. Otherwise it is similar to lactulose in that it is neither broken down nor absorbed in the small intestine, but is extensively metabolised by colonic bacteria. It would seem the ideal successor to lactulose for treatment of hepatic

Objective: There are no data on the relationship between serum paraoxonase-3 (PON3) concentration and atherosclerosis in humans. Our aim was to investigate possible associations, using recently developed methods, in patients with peripheral artery disease (PAD) or coronary artery disease (CAD). Methods: We studied 118 PAD and 72 CAD patients and 175 healthy volunteers. Serum PON3 was determined by in-house ELISA using polyclonal antibodies generated against a synthetic peptide with a sequence specific to PON3. Polymorphisms of the PON3 promoter were analysed by the Iplex Gold MassArray TM method. Results: There was a significant increase in serum PON3 concentration in both groups of patients with respect to the control group. In PAD patients, we observed significant positive correlations between PON3, insulin levels and HOMA index. These associations were not observed in CAD. There were significant positive associations between serum PON3 and ␤-2-microglobulin, CCL2 and high-sensitivity C-reactive protein in CAD patients, but not in PAD. We did not find any significant differences in PON3 gene promoter polymorphisms and their haplotypes between patients and controls, indicating that associations were not genetically determined. Conclusion: In both atherosclerotic phenotypes, serum PON3 concentration was increased, but this was associated with decreased insulin sensitivity in PAD and with inflammation in CAD.

Hepatitis C virus (HCV) infection is a global health problem, being the second most common chronic viral infection in the world with a global prevalence of about 3% (about 180 million people). HCV is both an hepatotropic and a lymphotropic virus; and chronic infection could cause, on one hand, chronic hepatitis, cirrhosis and hepatocellular carcinoma and on the other hand several extrahepatic diseases including, first, mixed cryoglobulinemia and lymphoma. The association between hepatic (hepatocellular carcinoma) and extrahepatic (lymphoma, thyroid cancer) malignancies has justified the inclusion of HCV among human cancer viruses. The pathogenesis of HCV-related sequelae (hepatic or extrahepatic) is not fully understood representing a challenge of prime importance in light of the optimization of clinico-therapeutic management of these patients. Combined treatment with pegylated interferon plus ribavirin is presently the first-line, gold standard treatment of most HCV-related diseases. However, mainly in the case of extrahepatic manifestations, a cautious approach to the patient, with a case to case accurate tailoring of therapy is frequently requested. The present review will outline the principal aspects of such HCV-induced systemic disease focusing on extrahepatic manifestations.

Herbal drugs have become increasingly popular and their use is widespread. Licensing regulations and pharmacovigilance regarding herbal products are still incomplete and clearcut proof of their efficacy in liver diseases is sparse. Nevertheless, a number of herbals show promising activity including silymarin for antifibrotic treatment, phyllantus amarus in chronic hepatitis B, glycyrrhizin to treat chronic viral hepatitis, and a number of herbal combinations from China and Japan that deserve testing in appropriate studies. Apart from therapeutic properties, reports are accumulating about liver injury after the intake of herbals, including those advertised for liver diseases. Acute and/or chronic liver damage occurred after ingestion of some Chinese herbs, herbals that contain pyrrolizidine alkaloids, germander, greater celandine, kava, atractylis gummifera, callilepsis laureola, senna alkaloids, chaparral and many others. Since the evidence supporting the use of botanicals to treat chronic liver diseases is insufficient and only few of them are well standardised and free of potential serious side effects, most of these medications are not recommended outside clinical trials. Particularly with regard to the latter, adequately powered randomised-controlled clinical trials with well-selected end points are needed to assess the role of herbal therapy for liver diseases.

A 37-year-old splenectomized man affected by -thalassemia and chronic hepatitis, recently treated with pegylated interferon- (Peg-IFN), was admitted because of elevated fever lasting 3 months and unresponsiveness to broad-spectrum antibiotics. Laboratory studies showed white blood cell and platelet counts within the normal range but lower than observed before Peg-IFN treatment and an elevated erythrocyte sedimentation rate. The blood transfusion rate

To describe the incidence and nature of neurologic complications following liver transplantation. Methods: Adult patients who received liver transplants at St. James's University Hospital between September 1, 1990, and August 31, 2000, were identified. Case notes were reviewed and demographic data, details of the liver disease, neurologic complications, and discharge information were recorded. Results: The authors identified 657 patients and traced the case notes of 627 (95.4%). These patients had a total of 711 transplants. Neurologic complications occurred following 185 transplants (26%) affecting 170 patients (27%). The most common complications were diffuse encephalopathies, which affected 66 patients (11%), and seizures, which affected 37 patients (6%). Forty-three percent of patients with alcoholic liver disease and 41% of patients with primary biliary cirrhosis experienced a neurologic complication. These proportions were higher than for other transplant indications (p Ͻ 0.001). Patients who experienced a neurologic problem spent longer in hospital (p Ͻ 0.01) and had a poorer outcome (p Ͻ 0.001). Conclusions: Neurologic complications occur following 26% of liver transplants. A higher proportion of patients who received transplants for alcoholic liver disease and primary biliary cirrhosis experienced neurologic complications than those receiving transplants for other reasons. Patients who experience a neurologic problem spend longer in hospital and have a poorer outcome.

Background/Aims: Interferon treatment causes a sustained loss of virus replication only in a proportion of patients with chronic hepatitis B. This study investigated whether genomic variations in the precore/core gene of hepatitis B virus affect the response to interferon alfa. Methods: The precore/core region was sequenced in 46 serum samples obtained before, during, and after interferon treatment of 12 patients. Results: In 23 samples from 7 responders (group A), there were 24 missense mutations, whereas in 23 samples from 5 patients who did not respond or relapsed after treatment (group B), there were 141 missense mutations (P <: 0.001). All group B patients had cirrhosis, but only 2 of 7 patients in group A had cirrhosis (P = 0.026). Substitutions in amino acids 21-27 of the core protein, known to diminish HLA-A2-restricted cytotoxic T-cell function, were found in all nonresponders but in none of the responders. No significant changes occurred in the precore/core region in responders after seroconversion to antibody to hepatitis B e antigen, but multiple variations persisted in group B during treatment and new mutations appeared with the relapse of hepatitis. Conclusions: Specific mutations in the core protein that can interfere with T-cell function occur frequently in patients with advanced chronic hepatitis B and may affect the response to interferon.

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Hepatitis G virus (HGV) has been recently identified as a new transfusion-transmissible agent. This study was performed to evaluate the role of HGV infection in patients with acute posttransfusion hepatitis in Taiwan. Sera from 63 patients with acute posttransfusion hepatitis and 61 patients with normal serum aminotransferase levels after transfusion were tested for HGV RNA by reverse-transcription polymerase chain reaction. Six of the 63 patients (9.5%) with acute posttransfusion hepatitis were positive for HGV RNA in pretransfusion sera; 4 were superinfected with hepatitis C virus (HCV) after transfusion and 3 developed chronic hepatitis. Seven (12.3%) of the remaining 57 patients had acute posttransfusion HGV infection; 5 were coinfected with HCV and 2 infected with HGV alone. None with acute HGV infection alone developed chronic hepatitis, whereas 4 of 5 patients (80%) with acute HGV and HCV coinfection developed chronic hepatitis. The clinical course of acute HGV and HCV coinfection was similar to that of acute HCV infection alone. Four of 61 subjects (6.6%) with normal serum aminotransferase levels after transfusion were subclinically infected with HGV. HGV infection accounted for 12.3% of acute posttransfusion hepatitis in Taiwan before anti-HCV screening of blood donors. The clinical course of acute posttransfusion HGV infection alone was relatively benign.

The putative core protein of hepatitis C virus (HCV) regulates cellular growth and a number of cellular promoters. To further understand its effect, we investigated the role of the core protein in the endogenous regulation of two distinct transcription factors, nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1), and the related mitogen-activated protein kinase kinase (MAPKK) and c-Jun N-terminal kinase (JNK). Stable cell transfectants expressing the HCV core protein suppressed tumor necrosis factor (TNF)-induced NF-kappaB activation. Supershift analysis revealed that NF-kappaB consists of p50 and p65 subunits. This correlated with inhibition of the degradation of IkappaBalpha, the inhibitory subunit of NF-kappaB. The effect was not specific to TNF, as suppression in core protein-expressing cells was also observed in response to a number of other inflammatory agents known to activate NF-kappaB. In contrast to the effect on NF-kappaB, the HCV core protein constitutively...

Between 07•92 and 12/99 192 patients received 213 liver transplants (OLT) We retrospectively reviewed the outcome of patients in different disease categories. Methods: Patient demographics, pretransplant and operative details were retrieved from the database. Hospital files were reviewed for post-operative details. Results: Between 07/92 and [2/99 192 patients received 213 OLT. The disease groups were: Group 1 alcohol 40(2 I%): Group 2 PBC, PSC, AI 35(18%1; Group 3 HCV, HBV 78(41%); Group 4 FHF 12(6%): Group 5 eryptogonie, miscellaneous 27(14%). Age, sex, race, blood group, UNOS status were similar in all groups. There was no difference between the groups in operating time, blood transfused, ICU stay, total LOS and re-operations (analysis of variance) Post-OLT complications both early and late occurred in GI 35 (87.5%), G2 28 (80%), G3 65(83%), G4 9(75%) and G5 21(78%). Septic complications occurred in 13(33%1 of patients in GI, 12(34%) G2, 44(56%1 G3, 2(16%1 G4, and 12(44%1 G5 The incidence of" CMV infection was: G 1 5(13%), G2 4(I 1%), G3 16(2 I%), G4 2(17%) and G5 6(22%). Recurrent disease was only significant in G3. There were 32(47%) incidences of recurrence of HCV: 53% < 180 days, 22% 181-365 days and 23% 366-1320 days. 11/32(34%) grafts were retransplanted and 4/29(14%) patients are relisted.. There was no difference between the groups in the incidence of rejection or administration of OKT3. The rates of steroid withdrawal are: GI 11(28%), G2 $(26%1, G3 19(29%), G4 2(22%1 and G5 6(27%). The mean time to withdrawal was signiflcandy longer in G4 1260±1053days (p< 0.05). lyr and 3yr patient survival are: GI 90% and 90%; G2 88% and 84%; G3 81% and 67%; G4 75% and 75%: G5 80% and 72% (log rank test p=0.52) OF the total population 19% developed long term complications related to immunosuppressive drugs. The incidence did not differ between groups. Conclusion: Post OLT complications occurred in all groups with a trend towards a higher incidence of septic complications in G3. Recurrent disease was only significant in G3 and a major source of morbidity. The mean time to steroid withdrawal was significantly longer in the FHF group.

Cytokine-induced stimulation of p38 mitogen activated protein kinase (MAPK) has been shown to influence behaviorally-relevant pathophysiologic pathways including monoamine neurotransmission and neuroendocrine function and thus may contribute to behavioral changes that occur during chronic administration of the innate immune cytokine, interferon (IFN)-alpha. Accordingly, in the current study, phosphorylation (activation) of intracellular p38 MAPK in peripheral blood lymphocytes was analyzed by flow cytometry every 2 hours for 12 hours following the initial injection of IFN-alpha in eleven patients with chronic hepatitis C. Hourly assessments of plasma concentrations of adrenocorticotropic hormone, cortisol and interleukin-6 were also obtained. Symptoms of depression and fatigue were measured at baseline and after 4 and 12 weeks of IFN-alpha treatment. Acute administration of IFN-alpha significantly increased the percentage of lymphocytes staining positive for intracellular phosphorylated p38 (p-p38). IFNalpha-induced increases in p-p38 were significantly greater in patients that developed clinically significant depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS) score ≥15] during the first 12 weeks of IFN-alpha treatment. Increases in the percentage of p-p38positive lymphocytes following the first IFN-alpha injection also highly correlated with depression severity at weeks 4 (r=0.85, p=0.001) and 12 (r=0.70, p=0.018). Similar relationships were observed for fatigue. Examination of relationships between p-p38 induction and factors previously reported to predict IFN-alpha-induced depressive symptoms revealed strong associations of p-p38 with baseline MADRS (r=0.82, p=0.002) and cortisol responses to the initial injection of IFNalpha (r=0.91, p=0.000). Taken together, these findings indicate that sensitivity of p38 MAPK signaling pathways to immune stimulation is associated with depressive symptoms during chronic IFN-alpha treatment.

Although in vitro replication of the hepatitis C virus (HCV) JFH1 clone of genotype 2a (HCVcc) has been developed, a robust cell culture system for the 1a and 1b genotypes, which are the most prevalent viruses in the world and resistant to interferon therapy, has not yet been established. As a surrogate virus system, pseudotype viruses transiently bearing HCV envelope proteins based on the vesicular stomatitis virus (VSV) and retrovirus have been developed. Here, we have developed a replication-competent recombinant VSV with a genome encoding unmodified HCV E1 and E2 proteins in place of the VSV envelope protein (HCVrv) in human cell lines. HCVrv and a pseudotype VSV bearing the unmodified HCV envelope proteins (HCVpv) generated in 293T or Huh7 cells exhibited high infectivity in Huh7 cells. Generation of infectious HCVrv was limited in some cell lines examined. Furthermore, HCVrv but not HCVpv was able to propagate and form foci in Huh7 cells. The infection of Huh7 cells with HCVpv...

Although in vitro replication of the hepatitis C virus (HCV) JFH1 clone of genotype 2a (HCVcc) has been developed, a robust cell culture system for the 1a and 1b genotypes, which are the most prevalent viruses in the world and resistant to interferon therapy, has not yet ...

The diagnostic and prognostic significance of the different types of serum smooth muscle antibodies (SMA) were investigated in sera of 24 patients with chronic active hepatitis (CAH) and 15 patients with primary biliary cirrhosis (PBC). SMA of IgG class were found in 92 % of sera from patients with CAH but in only 20 % of sera from PBC patients, whereas the incidence of IgM-SMA was higher in PBC (67 %) than in CAH (38 %). All six patients with the atypical cholestatic form of CAH had SMA of IgM class, whereas other CAH patients had SMA of mainly IgG class. SMA reacting with rabbit liver (bile canaliculus antibodies, BCA) and with rat glomeruli (glomerulus antibodies) were of anti-actin specificity and were more common in CAH than in PBC. Organ specific BCA or glomerulus antibodies were not found. Anti-actin antibodies were detected in the majority of the investigated sera by an immunoenzymatic anti-actin assay. The results suggest that the determination of SMA titres with heavy chain specific antisera may help in the assessment of diagnosis and prognosis of chronic hepatitis.

Autoimmune hepatitis (AIH) has been reported to show considerable geographical variation in frequency and clinical manifestations. It is considered a rare cause of liver disease in India. The present study was undertaken to determine the incidence, clinical, biochemical and histological profile of AIH in this part of the world. Patients presenting with acute or chronic liver disease between January 1999 and June 2002 were evaluated prospectively. AIH was diagnosed using the international autoimmune hepatitis group criteria. Workup included clinical, biochemical, USG, viral markers, UGI endoscopy, AI markers (ANA, SMA, Anti-LKM, AMA, RF, p-ANCA) using indirect immunofluorescence and liver biopsy if possible. Forty-one of 2401 (1.70%) patients were diagnosed to have autoimmune liver disease. Out of these, 38 had autoimmune hepatitis and the rest 3 had primary biliary cirrhosis. The mean age of the patients of autoimmune hepatitis was 36.2 (15.9) years, 34 (89.4%) were females, and the...

AT-61, a member of a novel class of phenylpropenamide derivatives, was found to be a highly selective and potent inhibitor of human hepatitis B virus (HBV) replication in four different human hepatoblastoma cell lines which support the replication of HBV (i.e., HepAD38, HepAD79, 2.2.15, and transiently transfected HepG2 cells). This compound was equally effective at inhibiting both the formation of intracellular immature core particles and the release of extracellular virions, with 50% effective concentrations ranging from 0.6 to 5.7 microM. AT-61 (27 microM) was able to reduce the amount of HBV covalently closed circular DNA found in the nuclei of HepAD38 cells by &gt;99%. AT-61 at concentrations of &gt;27 microM had little effect on the amount of viral RNA found within the cytoplasms of induced HepAD38 cells but reduced the number of immature virions which contained pregenomic RNA by &gt;99%. The potency of AT-61 was not affected by one of the mutations responsible for (-)-beta-L-...

Hepatitis C virus (HCV) causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. In this review, we summarize molecular virology, replication and immune responses against HCV and discussed how HCV escape from adaptive and humoral immune responses. This advance knowledge will be helpful for development of vaccine against HCV and discovery of new medicines both from synthetic chemistry and natural sources.

Of 153 patients with chronic liver disease in Jakarta, Indonesia, who were positive for antibody to hepatitis C virus (HCV), 129 (84%) had HCV RNA in serum. HCV genotypes were II/lb in 55 (43%), 111/2a in 33 (26%) and lc in 15 (12%) patients; genotypes were not classifiable into the common five (I/la, II/lb, 111/2a, IVj2b and V/3a) or lc in the remaining 25 (19%) patients. RNA of a putative non-A-E hepatitis virus, designated GB virus C (GBV-C), was tested for by reverse-transcription polymerase chain reaction with nested primers deduced from the 5'-noncoding region, and detected in 18 (12%) patients of whom 14 (78%) possessed serum HCV RNA. These results indicate that lc and the other indigenous genotypes of HCV, as well as the co-infection with GBV-C, would be common among Indonesian patients with HCV-associated chronic liver disease.

Understanding the mechanism of Hepatitis C Virus (HCV) pathogenesis is an important part of HCV research. In this study, the presence of apoptosis in HCV-infected liver and Peripheral Blood Mononuclear Cells (PBMC) from patients positive for anti-HCV antibodies and negative for serum HCV-RNA was investigated. The samples obtained from 21 patients were studied by in situ Hybridization (ISH), Immunofluorescence, TUNEL reaction and caspase 3 activation assays. The findings show that both DNA fragmentation by TUNEL assay and activation of caspase 3 were detected in hepatocytes from patients histologically confirmed as bearing chronic hepatitis or with abnormal ALAT or GGTP as well as in patients with no histological evidences of chronic hepatitis and normalization of transaminases. Apoptotic cells were also detected in PBMC samples by the TUNEL assay. ISH analysis of liver biopsies and PBMC samples showed both positive and negative strands of the HCV genome localized in some cells showing nuclear characteristics of apoptosis such as chromatin margination, condensation and fragmentation. These typical morphological changes of apoptotic cell death were also observed in some hepatocytes showing reaction products suggestive of HCcAg. Data suggest that under certain conditions HCV induces apoptosis in the absence of liver injury. Induction of apoptosis in HCV-infected cells may interfere with viral replication, which may lead to undetectable levels of HCV-RNA in serum.

Paraoxonase 1 (PON1) is an ester hydrolase present in serum and in the liver. The aims of the present study were to investigate the following: (a) the relationship between serum PON1 activity alterations and the degree of liver damage in patients with chronic liver disease; (b) the influence of genetic variability on serum PON1 activity; and (c) the efficacy of serum PON1 activity measurement, alone and in combination with standard liver function tests, in the assessment of liver damage. We studied 68 patients with liver cirrhosis, 107 patients with chronic hepatitis, and 368 apparently healthy volunteers. Baseline and salt-stimulated PON1 activities were measured by the hydrolysis of paraoxon. PON1 genotyping at positions 55 and 192 was analyzed by PCR and restriction isotyping. Baseline and stimulated PON1 activities were decreased (P &lt;0.001) in chronic hepatitis and in liver cirrhosis. PON1 activity was significantly correlated with serum total proteins, albumin, and bilirubin...

Liver is the main organ that plays an important role in the biotransformation of medicine in human body. Therefore, drug-induced liver injuries are much more common than official medical statistics show in different countries and on different continents. This circumstance is associated with many factors: the latent course of drug-induced liver injuries, inadequate interpretation of clinical symptoms and clinical laboratory parameters, insufficiently careful investigation of anamnesis, different frequency of use of various medicine in different countries.

Drug-induced liver injuries are lesions that are associated with the use of medicine. Drug-induced liver injuries must be diagnosed as early as possible, as the continued administration of medicine can repeatedly exacerbate the severity of clinical manifestations and significantly affect the outcome of the disease as a whole. In addition, legal aspects are also important in this regard, since an unrecognized drug-induced liver injury with continued use of this medicine that allegedly caused this injury is a matter of a frequent professional investigations.

The reaction of the liver on medicine depends on many factors: the initial state of liver function (already existing liver disease), heredity, gender, age, alcohol intake and other medicine. Presence of these factors in patients significantly increases the risk of development of liver injuries associated with taking medications, and if the drug-induced liver injury develops, the prognosis of its course will be heavier. Statistically-valid are frequent drug-induced liver injuries in women. The same type of medicine can cause different types of liver injuries in terms of clinical and morphological manifestations. Diagnostics of drug-induced liver injury is often difficult and requires from a specialist certain skills not only the necessity to carefully collect an anamnesis of a patient with a developed disease, but also a good orientation in his clinical and morphological manifestations.

Chronic liver disease and hepatocellular carcinoma associated with chronic hepatitis B virus (HBV)-infection are among the most serious human health problems in highly endemic regions. Current therapeutic approaches to control chronic hepatitis such as interferon-alpha and lamivudine are unsatisfactory. Vaccination would be the therapeutic procedure with the lowest cost and the potentially greatest benefit. The immunogenicity of selected HBV envelope-or capsid-based vaccine formulations for the induction or the broadening of T and B cell responses, deficient in HBV chronic carriers, are currently under study in animal models and in clinical trials.

Background/Aims: Markers for hepatitis C virus are often detectable in patients suffering chronic hepatitis with liver-kidney microsomal type 1 antibodies. Several authors have suggested that two subsets of those patients can be defined: a) hepatitis C virus negative and b) hepatitis C virus positive. The aim of this work was to further analyze the possible genetic association, HLA class I and II, in these two groups of patients.

Background/Aim: Occult hepatitis B virus (HBV) infection is characterized by the presence of HBV DNA in the absence of hepatitis B surface antigen (HBsAg) in the patient serum. Although such infections have been identified in patients with chronic hepatitis C, the clinical significance of those co-infections is still not understood. Our aim was, therefore, to assess the prevalence and clinical consequences of occult HBV infection in chronic hepatitis C patients undergoing antiviral therapy. Methods: The study population consisted of 53 HBsAg-negative patients with chronic hepatitis C treated with IFN/ribavirin or IFN/ribavirin/amantadine. Nine patients experienced a viral breakthrough (BT), 30 were non-responders (NR) and 14 were responders (R). HBV-DNA detection by PCR was performed using primers specific for the S region of the HBV genome and HCV-RNA detection by PCR with primers localised in both the 5 NC and core region of HCV genome, before, during and after treatment. Viral genome sequences were also studied. Results: Occult HBV genomes were found in the serum of four of 53 (7.5%) patients, unrelated to anti-HBc status. No significant differences in biochemical, virological, or histological markers, age, duration of infection, were observed in patients with or without HBV DNA. There was an inverse correlation in the evolution of HBV DNA and HCV RNA levels. Direct sequencing showed that S gene of occult HBV presented mutations in the "a" determinant while no specific mutation in the core region of HCV was observed. None of the four patients co-infected with HBV and HCV were responders to anti-HCV therapy. Conclusion: In our clinical setting, the prevalence of occult HBV co-infection among patients with chronic hepatitis C was low and independent of the presence of markers of previous HBV infection. Further studies in larger cohort of patients are warranted to determine if occult HBV co-infection may be involved in HCV resistance to combination therapy.

Hepatitis C virus (HCV) is the leading cause of chronic hepatitis worldwide and its subtypes/genotypes are clinically important for clinical management and vaccine development. The present study describes frequency distribution of different HCV genotypes and their treatment status in HCV RNA positive patients from district Swat. A total of 185 HCV infected sera were analyzed by molecular genotyping assay. The most prevalent genotype was 3a (34.1%), followed by 2a (8.1%), 3b (7%) and 1a (5.4%). The samples found untypable by the present method of genotypes was 37.8% while, patients with mixed genotype infections were 7.6%. More than 80% of untypable cases were from those HCV patients who had received interferon plus ribavirin standard therapy in the past and either were non-responders and were relapsed thereafter or were under treatment. In conclusion, genotype 3a is the most prevalent HCV genotype in the region. A high prevalence rate of untypable genotypes is present in treated patients that need further investigation for the successful genotyping by developing new assays or using viral sequencing method.