丙型肝炎病毒颗粒特性的研究现状

本文重点介绍有关丙型肝炎病毒颗粒在感染者血清和体外细胞培养系统中存在的状态和研究病毒颗粒特性的意义。

Nucleoporin 88 expression in hepatitis B and C virus-related liver diseases

AIM: To investigate the expression of nucleoporin 88 (Nup88) in hepatitis B virus (HBV) and C virus (HCV)-related liver diseases. METHODS: We generated a new monoclonal Nup88 antibody to investigate the Nup88 protein expression by immunohistochemistry (IHC) in 294 paraffin-embedded liver specimens comprising all stages of hepatocellular carcinogenesis. In addition, in cell culture experiments HBV-positive (HepG2.2.15 and HB611) and HBV-negative (HepG2) hepatoma cell lines were tested for the Nup88 expression by Western-immunoblotting to test data obtained by IHC.RESULTS: Specific Nup88 expression was found in chronic HCV hepatitis and unspecific chronic hepatitis, whereas no or very weak Nup88 expression was detected in normal liver. The Nup88 expression was markedly reduced or missing in mild chronic HBV infection and inversely correlated with HBcAg expression. Irrespective of the HBV- or HCV-status, increasing Nup88 expression was observed in cirrhosis and dysplastic nodules, and Nup88 was highly expressed in hepatocellular carcinomas. The intensity of Nup88 expression significantly increased during carcinogenesis (P < 0.0001) and correlated with dedifferentiation (P < 0.0001). Interestingly, Nup88 protein expression was significantly downregulated in HBV-positive HepG2.2.15 (P < 0.002) and HB611 (P < 0.001) cell lines as compared to HBV-negative HepG2 cells. CONCLUSION: Based on our immunohistochemical data, HBV and HCV are unlikely to influence the expression of Nup88 in cirrhotic and neoplastic liver tissue, but point to an interaction of HBV with the nuclear pore in chronic hepatitis. The expression of Nup88 in nonneoplastic liver tissue might reflect enhanced metabolic activity of the liver tissue. Our data strongly indicate a dichotomous role for Nup88 in non-neoplastic and neoplastic conditions of the liver.

Prevalence of hepatitis B and C markers among refugees in Athens

AIM: To assess the prevalence of hepatitis B and C serological markers in a population of refugees living in Athens.METHODS: One hundred and thirty refugees (81 males and 49 females, mean age ±SD: 31.7±8 years) were included in the study. The hepatitis B virus surface antigen (HBsAg),the hepatitis B virus core antibody (anti-HBc) and the hepatitis C virus antibody (anti-HCV) were detected using a third-generation immunoassay.RESULTS: Twenty individuals (15.4%) were HBsAg positive and 69 (53.1%) were anti-HBc positive. The prevalence of HBsAg and anti-HBc was higher among refugees from Albania and Asia (statistical significant difference, P＜0.008 and P＜0.001 respectively). The prevalence of these markers was found irrelevant to age or sex. Anti-HCV was detected in the serum of 3 individuals (2.3 %). No differences among age, sex or ethnicity regarding anti-HCV prevalence were found.CONCLUSION: It can be concluded that refugees living in Athens are an immigrant population characterized by a high incidence of HBV infection. The prevalence of HBV markers is higher among refugees from Albania and Asia. It is therefore believed that the adherence to general precautions and the initiation of HBV vaccination programs will be necessary in the future, especially in these communities.Although the prevalence of HCV infection seems to be relatively low, extended epidemiological surveys are needed to provide valid results.

Treatment of hepatitis C virus genotype 4 with peginterferon alfa-2a: Impact of bilharziasis and fibrosis stage

AIM： To evaluate pegylated interferon alpha2a （PegIFN-α2a） in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response rate. METHODS： A total of 73 nafve patients （61 with history of bilharziasis） with compensated chronic HCV genotype 4 were enrolled into： group A （38 patients） who received 180 mg PegIFN-alpha2a subcutaneously once weekly for a year and group B （35 patients） received IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at a dose of 1200 mg. Patients were followed for 72 wk and sustained response was assessed. RESULTS： Significant improvement in both end of treatment response （ETR） （P 〈 0.002） and sustained response （SR） （P 〈 0.05） was noted with pegylated interferon, where ETR was achieved in 29 （76.3%） and 14 patients （40%） in both groups respectively, and 25 patients in group A （65.8%） and 9 （25.7%） in group B could retain negative viraemia by the end of follow up period. Sustained virological response （SVR） showed a significant negative correlation with age and positive correlation with pretreatment inflammation in patients receiving PegIFN. Viral clearance after 3 mo of therapy was associated with high incidence of ETR and SR （P 〈 0.001）, but without significant difference between both forms of interferon. Significant improvement in response was achieved in patients with high grade fibrosis （grade 3 and 4） with PegIFN-α2a, where SR was seen in 5 out of 13 patients in group A, but none in group B. There was no significant difference in response between bilharzial and non-bilharzial patients in both groups. In terms of safety and tolerability, neutropenia was the predominant side effect, both drugs were comparable. CONCLUSION： PegIFN-~2a combined with ribavirin results in improvement in sustained response in HCV genotype 4, irrespective of history of bilharzial infestation.

Distinct expression patterns in hepatitis B virus-and hepatitis C virus-infected hepatocellular carcinoma

AIM： To identify biomarkers indicating virus-specific hepatocarcinogenic process, differential mRNA expression in 32 patients with hepatitis B virus （HBV）-/hepatitis C virus （HCV）-associated hepatocellular carcinoma （HCC） were investigated by means of cDNA microarrays comprising of 886 genes. METHODS： Thirty two HCC patients were divided into two groups based on viral markers： hepatitis B virus positive and HCV positive. The expression profiles of 32 pairs of specimens （tumorous and surrounding nontumorous liver tissues）, consisting of 886 genes were analyzed. RESULTS： Seven up-regulated genes in HBV-associated HCC comprised genes involved in protein synthesis （RPSS）, cytoskeletal organization （KRTS）, apoptosis related genes （CFLAR）, transport （ATPSF1）, cell membrane receptor related genes （IGFBP2）, signal transduction or transcription related genes （MAP3KS）, and metastasis-related genes （MMP9）. The up-regulated genes in HCV-infected group included 4 genes： V/M （cell structure）, ACTB （cell structure）, GAPD （glycolysis） and CD58 （cell adhesion）. The expression patterns of the 11 genes, identified by cDNA microarray, were confirmed by quantitative RT-PCR in 32 specimens.CONCLUSION： The patterns of all identified genes were classified based on the viral factor involved in HBV- and HCV-associated HCC. Our results strongly suggest that the pattern of gene expression in HCC is closely associated with the etiologic factor. The present study indicates that HBV and HCV cause hepatocarcinogenesis by different mechanisms, and provide novel tools for the diagnosis and treatment of HBV- and HCV-associated HCC.

Occult persistence and lymphotropism of hepatitis C virus infection

Recent discovery of occult hepatitis C virus (HCV) infection persisting after spontaneous or antiviral therapy-induced resolution of hepatitis C was made possible by the introduction of nucleic acid amplification assays capable of detecting HCV RNA at sensitivities superseding those offered by clinical tests. Although individuals with this seemingly silent HCV infection are usually anti-HCV antibody reactive and have normal liver function tests, occult HCV infection has also been reported in anti-HCV-negative individuals with persistently elevated liver enzymes of unknown etiology. Studies have shown that HCV RNA can persist for years in serum, lymphomononuclear cells and liver in the absence of clinical symptoms, although histological evidence of a mild inflammatory liver injury can be occasionally encountered. Furthermore, while HCV RNA can be detected in circulating lymphoid cells in approximately 30% of cases, a short-term culture under stimulatory conditions augments HCV replication in these cells allowing detection of virus in otherwise HCV-negative cases. HCV infects different immune cell subsets, including CD4+ and CD8+ T lymphocytes, B cells and monocytes. Studies employing clonal sequencing and single-stranded conformational polymorphism analyses have revealed unique HCV variants residing in immune cells, further strengthening the notion of HCV lymphotropism. Overall, the data accumulated suggest that occult HCV infection is a common consequence of resolution of symptomatic hepatitis C and that examination of the cells of the immune system is an effective approach to diagnosis of HCV infection and its long-term persistence. Further work is required to fully realize pathogenic and epidemiological consequences of occult HCV persistence.

Hepatitis C virus genotypes in Serbia and Montenegro: The prevalence and clinical signifi cance

AIM： To investigate the prevalence of hepatitis C virus （HCV） genotypes in Serbia and Montenegro and their influence on some clinical characteristics in patients with chronic HCV infection. METHODS： A total of 164 patients was investigated. Complete history, route of infection, assessment of alcohol consumption, an abdominal ultrasound, standard biochemical tests and liver biopsy were done. Gene sequencing of 5＇ NTR type-specific PCR or commercial kits was performed for HCV genotyping and subtyping. The SPSS for Windows （version 10.0） was used for univariate regression analysis with further multivariate analysis. RESULTS： The genotypes 1, 2, 3, 4, 1b3a and 1b4 were present in 57.9%, 3.7%, 23.2%, 6.7%, 6.7% and 1.8% of the patients, respectively. The genotype 1 （mainly the subtype 1b） was found to be independent of age in subjects older than 40 years, high viral load, more severe necro-inflammatory activity, advanced stage of fibrosis, and absence of intravenous drug abuse. The genotype 3a was associated with intravenous drug abuse and the age below 40. Multivariate analysis demonstrated age over 40 and intravenous drug abuse as the positive predictive factors for the genotypes lb and 3a, respectively.CONCLUSION： In Serbia and Montenegro, the genotypes 1b and 3a predominate in patients with chronic HCV infection. The subtype lb is characteristic of older patients, while the genotype 3a is common in drug abusers. Association of the subtype lb with advanced liver disease, higher viral load and histological activity suggests earlier infection with this genotype and eventually its increased pathogenicity.

Chronic liver disease in Aboriginal North Americans

A structured literature review was performed to detail the frequency and etiology of chronic liver disease (CLD) in Aboriginal North Americans. CLD affects Aboriginal North Americans disproportionately and is now one of the most common causes of death. Alcoholic liver disease is the leading etiology of CLD, but viral hepatitis, particularly hepatitis C, is an important and growing cause of CLD. High rates of autoimmune hepatitis and primary biliary cirrhosis (PBC) are reported in regions of coastal British Columbia and southeastern Alaska. Non-alcoholic liver disease is a common, but understudied, cause of CLD. Future research should monitor the incidence and etiology of CLD and should be geographically inclusive. In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholic fatty liver disease (NAFLD) in this population.

Generation of the regulatory protein rtTA transgenic mice

AIM: To translate Tet-on system into a conditional mouse model, in which hepatitis B or C virus (HBV or HCV) gene could be spatiotemporally expressed to overcome 'immune tolerance' formed during the embryonic development and 'immune escape' against hepatitis virus antigen(s), an effector mouse, carrying the reverse tetracycline-responsive transcriptional activator (rtTA) gene under the tight control of liver-specific human apoE promoter, is required to be generated. METHODS: To address this end, rtTA fragment amplified by PCR was effectively inserted into the vector of pLiv.7 containing apoE promoter to create the rtTA expressing vector, I.e., pApoE-rtTA. ApoE-rtTA transgenic fragment (-6.9 kb) released from pApoE-rtTA was transferred into mice by pronucleus injection, followed by obtaining one transgene (+) founder animal from microinjection through PCR and Southern blot analysis.RESULTS: rtTA transgene which could be transmitted to subsequent generation (F1) derived from founder was expressed in a liver-specific fashion. CONCLUSION: Taken together, these findings demonstrate that rtTA transgenic mice, in which rtTA expression is appropriately targeted to the murine liver, are successfully produced, which lays a solid foundation to 'off-on-off' regulate expression of target gene (s) (e.g., HBV and/or HCV) in transgenic mice mediated by Tet-on system.

INFLUENCE OF HEPATITIS B AND HEPATITIS C VIRUS INFECTION ON THE OUTCOME OF KIDNEY TRANSPLANTATION

Objective To investigate the impact of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the long-term survival of renal transplantation recipients. Methods A total of 443 patients who received renal allografts from 1992 to 2002 were analyzed. Outcome and survival were compared among four groups retrospectively. Results Twelve patients were positive for both hepatitis B surface antigen (HBsAg) and HCV antibody (anti-HCV) (group 1), 18 were HBsAg-positive and anti-HCV-negative (group 2), 26 were HBsAg-negative and anti-HCV-positive (group 3) and 387 were negative for both markers (group 4). The mean follow-up period was 6.1 ± 2.8 years (range, 0.5-10 years) for all patients. Group 2 had significantly higher liver-related complications (38.9%) and liver-related death (16.7%) than did group 4 (0%, P < 0.01). Among all patients, 4 HBsAg-positive patients had fulminant hepatitis and died within two years of transplantation. Three patients (group 2) who died were seropositive for HBeAg and/or HBV DNA and none had a history of or positive serologic marker to indicate hepatitis of other etiologies. One (group 1), two (group 2), and one patient (group 3) developed liver cirrhosis respectively, and hepatocellular carcinoma occurred in two patients (group 2) and one patient (group 3). Despite high liver-related mortality in HBV-infected patients, no significant differences among the four groups in the long-term graft and patient survivals were demonstrated. The presence of HBsAg or anti-HCV was not associated with poor prognosis as determined by Cox regression analysis. Conclusion HBV or HCV infection is not a contraindiction to kidney transplantation in Chinese patients. However, it should be noted that serious liver-related complications may occur and limit survival in patients infected with HBV and/or HCV after kidney transplantation.

Impact of comorbidities on the severity of chronic hepatitis B at presentation

AIM:To evaluate the clinical relevance of each cofactor on clinical presentation of chronic hepatitis B.METHODS:Out of 1366 hepatitis B surface antigen(HBsAg) positive subjects consecutively observed in 79 Italian hospitals,53(4.3%) showed as the only cofactor hepatitis D virus(HDV) infection [hepatitis B virus(HBV)/HDV group],130(9.5%) hepatitis C virus(HCV)(group HBV/HCV),6(0.4%) human immunodeficiencyvirus(HIV)(group HBV/HIV),138(10.2%) alcohol abuse(group HBV/alcohol);109(8.0%) subjects had at least two cofactors and 924 were in the cofactor-free(CF) group.RESULTS:Compared with patients in group CF those in group HBV/alcohol were older and more frequently had cirrhosis(P < 0.001),those in group HBV/HDV were younger(P < 0.001),more frequently resided in the south of the country and had cirrhosis(P <0.001),those in group HBV/HCV were older(P < 0.001) and more frequently had cirrhosis(P < 0.001).These cofactors were all independent predictors of liver cirrhosis in HBsAg positive patients.Multivariate analysis showed that an older age [odds ratio(OR) 1.06,95% CI:1.05-1.08],alcohol abuse with more than 8 drinks daily(OR 2.89,95% CI:1.81-4.62) and anti-HDV positivity(OR 3.48,95% CI:2.16-5.58) are all independently associated with liver cirrhosis.This association was found also for anti-HCV positivity in univariate analysis,but it was no longer associated(OR 1.23,95% CI:0.84-1.80) at multivariate analysis.CONCLUSION:Older age,HDV infection and alcohol abuse are the major determinants of severe liver disease in chronic HBV infection,while HCV replication plays a lesser role in the severity of hepatic damage.

Coinfection of TT virus and response to interferon therapy in patients with chronic hepatitis B or C

AIM: To investigate the serum positive percentage of TT virus (TTV) in patients with chronic hepatitis B or C and the response of the coinfected TTV to interferon (IFN) during IFN therapy for chronic hepatitis B and C. METHODS: We retrospectively studied the serum samples of 70 patients with chronic hepatitis who had received IFN-alpha therapy from January 1997 to June 2000, which included 40 cases of hepatitis B and 30 hepatitis C. All the patients had been followed up for at least 6 months after the end of IFN therapy. The serum TTV DNA was detected using the polymerase chain reaction (PCR) before and every month during the course of IFN treatment. RESULTS: TTV infection was detected in 15% (6/40) of the chronic hepatitis B group and 30% (9/30) of the chronic hepatitis C group. Loss of serum TTV DNA during IFN therapy occurred in 3 of 6 patients (50%) and 6 of 9 (67%) of hepatitis B and C groups, respectively. Seronegativity of TTV was found all during the first month of IFN therapy in the 9 patients. There was no correlation between the seroconversion of TTV and the biochemical changes of the patients. CONCLUSION: TTV is not infrequently coinfected in patients with chronic hepatitis B and C in Taiwan, and more than half of the TTV infections are IFN-sensitive. However, the loss of serum TTV DNA does not affect the clinical course of the patients with chronic hepatitis B or C.

Relationship between hepatitis C virus infection and type 2 diabetes mellitus:Meta-analysis

AIM:To investigate the association between hepatitis C infection and type 2 diabetes mellitus.METHODS:Observational studies assessing the relationship between hepatitis C infection and type 2 diabetes mellitus were identified via electronic and hand searches.Studies published between 1988 to March 2011 were screened,according to the inclusion criteria set for the present analysis.Authors performed separate analyses for the comparisons between hepatitis C virus(HCV) infected and not infected,and HCV infected and hepatitis B virus infected.The included studies were further subgrouped according to the study design.Heterogenity was assessed using I2 statistics.The summary odds ratios with their corresponding 95% CIs were calculated based on a random-effects model.The included studies were subgrouped according to the study design.To assess any factor that could potentially affect the outcome,results were further stratified by age group(proportion of ≥ 40 years),gender(proportion of male gender),body mass index(BMI)(pro-portion of BMI ≥ 27),and family history of diabetes(i.e.,self reported).For stability of results,a sensitivity analysis was conducted including only prospective studies.RESULTS:Combining the electronic database and hand searches,a total of 35 observational studies(in 31 articles) were identified for the final analysis.Based on random-effects model,17 studies(n = 286 084) compared hepatitis C-infected patients with those who were uninfected [summary odds ratio(OR):1.68,95% CI:1.15-2.45].Of these 17 studies,7 were both a cross-sectional design(41.2%) and cohort design(41.2%),while 3 were case-control studies(17.6%).Nineteen studies(n = 51 156) compared hepatitis C-infected participants with hepatitis B-infected(summary OR:1.92,95% CI:1.41-2.62).Of these 19 studies,4(21.1%),6(31.6%) and 9(47.4%) were cross-sectional,cohort and case-control studies,respectively.A sensitivity analysis with 3 prospective studies indicated that hepatitis C-infected patients had a higher risk of developing type 2 diabetes compared with uninfected controls(summary odds ratio:1.41,95% CI:1.17-1.7;I2 = 0%).Among hepatitis C-infected patients,male patients(OR:1.26,95% CI:1.03-1.54) with age over 40 years(summary OR:7.39,95% CI:3.82-9.38) had an increased frequency of type 2 diabetes.Some caution must be taken in the interpretation of these results because there may be unmeasured confounding factors which may introduce bias.CONCLUSION:The findings support the association between hepatitis C infection and type 2 diabetes mellitus.The direction of association remains to be determined,however.Prospective studies with adequate sample sizes are recommended.

Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA- dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear. METHODS: HCV quasispecies were studied by clon- ing and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or com- bined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their re- sponse to the treatments: 7 with sustained virological re- sponse (SVR) (quasispecies = 150) and 3 non-respond- ers (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispe- cies during therapy. Analysis of amino acids substitu- tions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate thetwo groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed mo- lecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection.

Autoantibodies and hepatitis C virus genotypes in chronic hepatitis C patients in Estonia

AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes. METHODS: Sera from 90 consecutive patients with chronic hepatitis C were investigated on the presence of anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA), anti-liver-kidney microsomal type 1 (LKMA1), anti-parietal cell (PCA), anti-thyroid microsomal (TMA), and anti-reticulin (ARA) autoantibodies. The autoantibodies were identified by indirect immunofluorescence. HCV genotypes were determined by a restriction fragment length polymorphism analysis of the amplified 5' noncoding genome region. RESULTS: Forty-six (51.1%) patients were positive for at least one autoantibody. Various antibodies were presented as follows: ANA in 13 (14.4%) patients, SMA in 39 (43.3%), TMA in 2 (2.2%), and ARA in 1 (1.1%) patients. In 9 cases, sera were positive for two autoantibodies (ANA and SMA). AMA, PCA and LKMAI were not detected in the observed sera. HCV genotypes were distributed as follows: 1b in 66 (73.3%) patients, 3a in 18 (20.0%), and 2a in 6 (6.7%) patients. CONCLUSION: A high prevalence of ANA and SMA can be found in chronic hepatitis C patients. Autoantibodies are present at low titre (1:10) in most of the cases. Distribution of the autoantibodies show no differences in the sex groups and between patients infected with different HCV genotypes.

Composition of inflammatory infiltrate and its correlation with HBV/HCV antigen expression

AIM： To study the composition of liver inflammatory infiltrate in biopsy material from patients chronically infected with hepatotropic viruses and to evaluate the correlation of inflammatory infiltrate with hepatitis B virus （HBV） and hepatitis C virus （HCV） viral antigen expression in chronic B and C hepatitis. METHODS： The phenotype of inflammatory cells was evaluated by the EnVision system, using a panel of monoclonal antibodies. HBV and HCV antigens were detected with the use of monoclonal anti-HBs, polyclonal anti-HBc and anti-HCV antibodies, respectively. RESULTS： The cellular composition of liver inflammatory infiltrate was similar in the patients with B and C hepatitis： ～50%-60% of cells were T helper lymphocytes. Approximately 25% were T cytotoxic lymphocytes; B lymphocytes comprised 15% of inflammatory infiltrate; other cells, including NK, totalled 10%. Expression of HLA antigens paralleled inflammatory activity. Portal lymphadenoplasia was found more often in hepatitis C （54.5%） than in hepatitis B （30.6%）. Expression of HB-cAg was found more often in chronic B hepatitis of moderate or severe activity. Overall inflammatory activity in HBV-infected cases did not correlate with the intensity of HBsAg expression in hepatocytes. Inflammatory infiltrates accompanied the focal expression of HCV antigens. A direct correlation between antigen expression and inflammatory reaction in situ was noted more often in hepatitis C than B. CONCLUSION： Irrespective of the etiology and activity of hepatitis, components of the inflammatory infiltrate in liver were similar. Overall inflammatory activity did not correlate with the expression of HBsAg and HCVAg; HBcAg expression, however, accompanied chronic hepatitis 8 of moderate and severe activity.

Hepatitis C virus genotypes distribution and transmission risk factors in Luxembourg from 1991 to 2006

AIM： To analyze the Hepatitis C virus （HCV） genotype distribution and transmission risk factors in a population of unselected patients in Luxembourg.METHODS： Epidemiological information （gender, age and transmission risks） were collected from 802 patients newly diagnosed for hepatitis C and living in Luxembourg, among whom 228 patients referred from prison. Genotyping using 5＇noncoding （5＇NC） sequencing was performed. We compared categorical data using the Fisher＇s exact F-test and odds ratios （OR） were calculated for evaluating association of HCV genotype and risk factors.RESULTS： The sex ratio was predominantly male （2.2） and individuals aged less than 40 years represented 49.6% of the population. Genotype 1 was predominant （53.4%） followed by genotype 3 （33%）. Among risk factors, intravenous drug usage （IVDU） was the most frequently reported （71.4%） followed by medical-related transmission （17.6%） including haemophilia, transfusion recipients and other nosocomial reasons. Genotype 3 was significantly associated to IVDU （OR = 4.84, P 〈 0.0001） whereas genotype 1 was significantly associated with a medical procedure （OR = 2.42, P 〈 0.001）. The HCV genotype distribution from inmate patients differed significantly from the rest of the population （Chi-square test with four degrees of freedom, P 〈 0.0001） with a higher frequency of genotype 3 （46.5% vs 27.5%） and a lower frequency of genotype 1 and 4 （44.7% vs 56.8% and 5.3% vs 9.6%, respectively）. IVDU was nearly exclusively reported as a risk factor in prison.CONCLUSION： We report the first description of the HCV genotype distribution in Luxembourg. The repartition is similar to other European counties, with one of the highest European prevalence rates of genotype 3 （33%）. Since serology screening became available in 2992, IVDU remains the most common way of HCV transmission in Luxembourg.

Clinical significance of"anti-HBc alone"in human immunodeficiency virus-positive patients

AIM： TO determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection （“anti-HBc alone”） among human immunodeficiency virus （HIV） type-1 infected patients. Occult hepatitis B infection frequency was also evaluated. METHODS： Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed. Patients with serological markers of hepatitis B virus （HBV） infection were classified into three groups： past hepatitis, ＂anti-HBc alone＂ and chronic hepatitis. Determination of DNA from HBV, and RNA and genotype from hepatitis C virus （HCV） were performed on ＂anti-HBc alone＂ patients. RESULTS： One hundred and eighty seven （53.7%） HIV-positive patients had markers of HBV infection： 118 past infection （63.1%）, 14 chronic hepatitis （7.5%） and 55 ＂anti-HBc alone＂ （29.4%）. Younger age [2.3-fold higher per every 10 years younger; 95% confidence intervals （Cl） 1.33-4.00] and antibodies to HCV infection [odds ratio （OR） 2.87; 95% CI 1.10-7.48] were factors independently associated with the ＂anti-HBc alone＂ pattern. No differences in liver disease frequency were detected between both groups. Serum levels of anti-HBs were not associated with HCV infection （nor viral replication or HCV genotype）, or with HIV replication or CD4 level. No ＂anti-HBc alone＂ patient tested positive for HBV DNA. CONCLUSION： ＂Anti-HBc alone＂ prevalence in HIM- positive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection. In clinical practice, HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury,

New animal models for hepatitis C viral infection and pathogenesis studies

Hepatitis C virus （HCV） is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma （HCC）. In man, the pathobiological changes associated with HCV infection have been attributed to both the immune system and direct viral cytopathic effects. Until now, the lack of simple culture systems to infect and propagate the virus has hampered progress in understanding the viral life cycle and pathogenesis of HCV infection, including the molecular mechanisms implicated in HCV-induced HCC. This clearly demonstrates the need to develop small animal models for the study of HCV-associated pathogenesis. This review describes and discusses the development of new HCV animal models to study viral infection and investigate the direct effects of viral protein expression on liver disease.

Fibrosing cholestatic hepatitis following cytotoxic chemotherapy for small-cell lung cancer

Fibrosing cholestatic hepatitis(FCH) is a variant of viral hepatitis reported in hepatitis B virus or hepatitis C virus infected liver,renal or bone transplantation recipients and in leukemia and lymphoma patients after conventional cytotoxic chemotherapy.FCH constitutes a well-described form of fulminant hepatitis having extensive fibrosis and severe cholestasis as its most characteristic pathological findings.Here,we report a case of a 49-year-old patient diagnosed with small-cell lung cancer who developed this condition following conventional chemotherapy-induced immunosuppression.This is the first reported case in the literature of FCH after conventional chemotherapy for a solid tumor.In addition to a detailed report of the case,a physiopathological examination of this potentially life-threatening condition and its treatment options are discussed.