Role Of Hepatitis Research Articles

Role of Hepatitis B Virus Infection in the Prognosis After Hepatectomy for Hepatocellular Carcinoma in Patients With Cirrhosis

The role of hepatitis B virus (HBV) infection in determining the prognosis after hepatectomy for hepatocellular carcinoma (HCC) in patients with cirrhosis is controversial. Retrospective study based on multicenter prospectively updated databases. Two tertiary referral centers specializing in hepatobiliary surgery. Two hundred four consecutive patients with cirrhosis undergoing hepatectomy for single nodules of HCC of 5 cm or smaller from January 1, 1997, through September 30, 2006. Patients were divided into the following groups according to their preoperative viral status: HBV positive and hepatitis C virus (HCV) negative (group 1); HBV negative and HCV positive (group 2); HBV negative and HCV negative (group 3); and HBV positive and HCV positive (group 4). A multivariate analysis was performed to determine factors associated with recurrence-free survival (RFS) among demographic, clinical, pathological, and surgical variables. The 2 centers had comparable RFS and early and late recurrence rates. Five-year RFS was significantly higher in groups 2 and 3 compared with group 1 (38%, 34%, and 9%, respectively; P = .007 and P = .05). Factors independently associated with RFS were HBV infection (P = .009; odds ratio, 1.79; 95% confidence interval, 1.15-2.78) and poor tumor differentiation (P < .001; odds ratio, 2.01; 95% confidence interval, 1.36-2.96). The concomitance of 0, 1, or 2 risk factors led to 5-year RFS rates of 49%, 20%, and 8%, respectively (P < .001). Infection with HBV is a strong predictive factor for lower RFS after hepatectomy for a single nodule of HCC of 5 cm or smaller in patients with cirrhosis, providing a further basis for adjuvant antiviral treatment. Patients who are seropositive for HBV with poorly differentiated HCC should also be considered to be at a high risk of recurrence and possibly included in a policy of salvage liver transplantation.

C-4 The role of hepatitis B virus surface proteins in immune protection and escape – Occult hepatitis B virus infections in vaccinated and non-vaccinated blood donors

C-4 The role of hepatitis B virus surface proteins in immune protection and escape – Occult hepatitis B virus infections in vaccinated and non-vaccinated blood donors

PP-097 Role of hepatitis B virus genotypes, BCP, precore/core and X gene mutations and the risk of hepatocellular carcinoma

PP-097 Role of hepatitis B virus genotypes, BCP, precore/core and X gene mutations and the risk of hepatocellular carcinoma

The role of hepatitis B virus X protein in liver metastasis

Hepatitis B virus X (HBx) is an important factor of the hepatitis B virus infection-associated liver disease, closely related to the occmrrence and development of HCC. Some studies show that HBx may be involved in angiogenesis, HGF/c-met pathway, matrix metalloproteinase and other related factors to promote liver cancer metastasis. Strengthening research of molecular mechanism that HBx involved in liver cancer metastasis can help to perfect the mechanism of invasion and metastasis of HCC to further improve the efficacy of liver cancer. Key words: Hepatitis B virus X protein ; Carcinoma,hepotocellular ; Neoplasm metastasis ;

Response to Therapy With Pegylated Interferon and Ribavirin for Chronic Hepatitis C in Hispanics Compared to Non-Hispanic Whites

Ethnicity has been shown to play an important role in hepatitis C virus (HCV) treatment response. However, few studies have examined the treatment response of Hispanics to combination therapy with pegylated interferon and ribavirin. The aim of this study was to compare the treatment responses of Hispanics and non-Hispanic whites (NHW) treated with pegylated interferon and ribavirin for chronic HCV. A retrospective review was conducted of all treatment-naive Hispanics and NHW with HCV who were treated at the University of New Mexico Hospital or Albuquerque VA Medical Center between October 2001 and January 2007. Genotype 1 patients received 48 weeks of therapy with pegylated interferon and ribavirin; genotype 2 and 3 patients received 24 weeks of treatment. A total of 396 patients were included in the analysis, consisting of 179 Hispanics and 217 NHW. Overall, fewer Hispanics completed therapy compared with NHW (64.8% vs. 80.2%, P<0.001). In genotype 1 patients, early virologic response (EVR), end-of-treatment response (ETR), and sustained virologic response (SVR) did not differ significantly between the two ethnic groups. In genotype 2 and 3 patients, Hispanics had similar EVR compared with NHW (81.3% vs. 88.2%, P=0.25), but lower ETR (64.1% vs. 83.1%, P=0.01) and SVR (45.3% vs. 75.3%, P<0.001). After correcting for patients who prematurely discontinued therapy, genotype 2 and 3 Hispanics continued to have a reduced SVR compared with NHW (65.9% vs. 87.3%, P=0.014). The attenuated SVR in Hispanics was because of a higher relapse rate after achieving ETR compared with NHW (25% vs. 7.5%, P=0.02). Hispanics with genotype 2 and 3 HCV infection treated with pegylated interferon and ribavirin are less likely to achieve SVR compared with NHW. The lower rate of SVR in Hispanic patients is, in part, because of an increased rate of relapse after ETR.

Role of hepatitis B surface antigen in the development of hepatocellular carcinoma: regulation of lymphoid enhancer-binding factor 1

BackgroundThere are around 350 million of hepatitis B surface antigen (HBsAg) carriers worldwide, and among them, high risk of developing hepatocellular carcinoma (HCC) has been identified by epidemiological studies. To date, the molecular role of HBsAg in HCC development has not been fully studied. We have previously reported that in cell cultures, HBsAg up-regulated the expression of lymphoid enhancer-binding factor 1 (LEF-1), a key component of the Wnt pathway. In this study we aimed to study this effect of HBsAg on LEF-1 in the development of HCC.MethodsExpression of HBsAg, LEF-1 and its downstream effector genes were compared among 30 HCCs, their peritumor tissue counterparts and 9 normal control liver tissues by quantitative real-time PCR. In addition, immunohistochemical staining studies on HBsAg and LEF-1 expression were conducted among these samples.ResultsThe expression of LEF-1 was compared between 13 HBsAg positive HCC tissues and 17 HBsAg negative HCC tissues. Simultaneous detection of LEF-1 and HBsAg was observed in HBsAg positive HCC tissues and, additionally, the simultaneous detection of HBsAg and LEF-1 was more pronounced in peritumor tissues, compared to that in the tumor tissues. The distribution of cellular LEF-1 in peritumor tissues was predominantly in the cytoplasm; while LEF-1 in the tumor tissues was located either exclusively in the nucleus or both in the nucleus and cytoplasm. By real-time PCR, the expression levels of LEF-1 downstream effector genes cyclin D1 and c-myc were higher in peritumor cells compared to that of the tumor cells. However, a 38 kDa truncated isoform of LEF-1, rather than the 55 kDa wild-type LEF-1, was significantly elevated in the HBsAg positive tumor cells.ConclusionData indicate that deregulation of the Wnt pathway by HBsAg occurred in HBV-associated HCCs, but was more pronounced in the peritumor cells. It is speculated that HBsAg could stimulate proliferation and functional modification of hepatocytes via LEF-1 through the Wnt pathway at the pre-malignant stage.

Association of IL-18 promoter polymorphism with liver disease severity in HCV-infected patients

Interleukin (IL)-18 plays an important dual role in Th1 polarization and viral clearance, as well as in the development of liver fibrosis. Single-nucleotide promoter polymorphisms influence the transcription of IL-18 mRNA. Promoter polymorphisms are linked to delayed virus clearance and disease susceptibility in many diseases. However, there is no information about their role in hepatitis C virus (HCV) infection. To investigate the association between -607 or -137 polymorphism with susceptibility and severity of HCV infection. Two hundred and four serologically proven patients with chronic HCV infection and 350 matched healthy controls were included in this study. Patients were segregated in 2 groups: group A with mild liver disease and group B with severe liver disease on the basis of histological activity index (HAI </=5 or >5) and hepatic fibrosis score (</=2 or >2). IL-18 promoter genotyping was performed with sequence-specific primers. There was no significant difference in the frequencies of -607 and -137 allelic distribution in patients and controls. The -607 A/A allele was more common in group A patients with mild liver disease than in patients with severe liver disease on the basis of HAI (38.6% vs. 21%, P = 0.05; odds ratio [OR] = 0.424, confidence interval [CI] = 0.233-0.773; R (2) = 0.631) and stage of fibrosis (38.7% vs. 16.7%, P = 0.008; OR = 0282, CI = 0.134-0.596; R (2) = 0.434). IL-18 promoter polymorphism at -607 position with A/A allele is a potential protective marker, as it is associated with milder liver disease in patients with chronic HCV infection.

Epidemiological and genetic analyses of Hepatitis C virus transmission among young/short- and long-term injecting drug users from Rio de Janeiro, Brazil

Background Injecting drug users (IDU) have a key role in Hepatitis C Virus (HCV) epidemiology. Young/short-term IDUs constitute a target group for preventive/harm reduction interventions. Objectives To investigate HCV transmission among young/short-term (ST) and long-term (LT) IDUs, from the perspective of epidemiology and molecular biology. Study design Cross-sectional study assessing the prevalence of HCV infection/genotypes, as well as risk behaviours/practices among IDUs from Rio de Janeiro. Phylogenetic analyses were performed and the extent of segregation between sequences was quantified by the Association Index. Results ST were more likely to engage into needle-sharing ( p = .021) and LT to attend Needle Exchange Programs ( p = .006). HCV prevalence was 10.1% vs. 23.4% among initiates and LT, respectively ( p < .001). Older age vs. imprisonment and longer duration of IDU career were independent predictors for HCV infection among ST and LT, respectively. Among the latter, NEP attendance was inversely associated with viral infection. HCV3a infections were the most prevalent. A moderate extent of phylogenetic segregation between sequences was found, suggestive of transmission between IDU subgroups. Conclusions The lower HCV prevalence among young/short-term IDUs cannot be viewed with complacency, due to their frequent engagement into direct/indirect sharing practices and the ongoing transmission between IDU subsets. To avert new infections, preventive/harm reduction policies must be tailored to empirical findings.

Role of hepatitis B virus X repression of C/EBPβ activity in the down-regulation of glutathione S-transferase A2 gene: implications in other phase II detoxifying enzyme expression

A genome-wide in silico screening rendered the genes of phase II enzymes in the rat genome whose promoters contain the putative DNA elements interacting with CCAAT/enhancer binding protein (C/EBP) and NF-E2-related factor (Nrf2). The hepatitis B virus X (HBx) protein strongly modulates the transactivation and/or the repression of genes regulated by some bZIP transcription factors.This study investigated the effects of HBx on the induction of phase II enzymes with the aim of elucidating the role of HBx interaction with C/EBPβ or Nrf2 bZIP transcription factors in hepatocyte-derived cells.Immunoblot and reporter gene analyses revealed that transfection of HBx interfered with the constitutive and inducible GSTA2 transactivation promoted by oltipraz (C/EBPβ activator), but not that by tert-butylhydroquinone (t-BHQ, Nrf2 activator). Moreover, HBx transfection completely inhibited GSTA2 reporter gene activity induced by C/EBPβ, but failed to inhibit that by Nrf2.Gel shift assays identified that HBx inhibited the increase in C/EBPβ−DNA complex formation by oltipraz, but not the increase in Nrf2−DNA complex by t-BHQ. Immunoprecipitation and immunoblot assays verified the direct interaction between HBx and C/EBPβ. Moreover, chromatin immunoprecipitation assays confirmed HBx inhibition of C/EBPβ binding to its binding site in the GSTA2 gene promoter. HBx repressed the induction of other phase II enzymes including GSTP, UDP-glucuronyltransferase 1A, microsomal epoxide hydrolase, GSTM1, GSTM2, and γ-glutamylcysteine synthase.These results demonstrate that HBx inhibits the induction of phase II detoxifying enzymes, which is mediated by its interaction with C/EBPβ, but not Nrf2, substantiating the specific role of HBx in phase II detoxifying capacity.

Hepatitis Status and Mortality in Hemodialysis Population

The role of hepatitis B (HBV) and C (HCV) virus infection in mortality among MHD patients is poorly understood. Recent studies have shown that HCV positivity is associated with significantly higher cardiovascular mortality, especially in dialysis patients younger than 65 years. However, little information is available in European renal registries about mortality among HBV and HCV positive MHD patients. We prospectively followed all patients (prevalents and incidents) attending the dialysis center in the Sicilian region since January 1, 1999, up to December 31, 2000. Those who died for any cause after the starting point were identified and included in the cases population. In all, 698 eligible cases were found. For each case, three controls extracted from the Registry were matched by age at death (within five years) and sex. We calculated the sample size of 698 cases and three controls for each case, assuming the power of the study to be 80%, with an estimated prevalence of exposure among controls of 3.0%. The χ2 and the t-test were used to evaluate possible differences among cases and controls for the different variables under investigation. The ORs of the association between hepatitis infection and mortality, adjusted for each of the possible confounding factors, was calculated using the Mantel-Haenszel test. The prevalence of Hepatitis C (HCV) was much higher among case compared with controls, both in males (23.4% vs. 17.7 %) and females (25.0% vs. 22.4%). In the multivariate model, the association between HCV and mortality maintained a significant association only among women aged <65 years with an OR of 1.77 (95% CI: 1.12–2.79). We also observed a correlation between increased risk of mortality in hemodialysis and HCV-positive patients with a longer time on dialysis. Our results suggest that HCV positivity among MHD patients is associated with significantly higher mortality in female aged <65 years. For this reason we should be more aggressive in identifying, preventing, and treating HCV infection among patients with end stage renal disease.

Biological role of hepatitis C virus proteins

Biological role of hepatitis C virus proteins

Structural and Functional Characterization of Nonstructural Protein 2 for Its Role in Hepatitis C Virus Assembly

The hepatitis C virus (HCV) is a flavivirus replicating in the cytoplasm of infected cells. The HCV genome is a single-stranded RNA encoding a polyprotein that is cleaved by cellular and viral proteases into 10 different products. While the structural proteins core protein, envelope protein 1 (E1) and E2 build up the virus particle, most nonstructural (NS) proteins are required for RNA replication. One of the least studied proteins is NS2, which is composed of a C-terminal cytosolic protease domain and a highly hydrophobic N-terminal domain. It is assumed that the latter is composed of three trans-membrane segments (TMS) that tightly attach NS2 to intracellular membranes. Taking advantage of a system to study HCV assembly in a hepatoma cell line, in this study we performed a detailed characterization of NS2 with respect to its role for virus particle assembly. In agreement with an earlier report ( Jones, C. T., Murray, C. L., Eastman, D. K., Tassello, J., and Rice, C. M. (2007) J. Virol. 81, 8374-8383 ), we demonstrate that the protease domain, but not its enzymatic activity, is required for infectious virus production. We also show that serine residue 168 in NS2, implicated in the phosphorylation and stability of this protein, is dispensable for virion formation. In addition, we determined the NMR structure of the first TMS of NS2 and show that the N-terminal segment (amino acids 3-11) forms a putative flexible helical element connected to a stable alpha-helix (amino acids 12-21) that includes an absolutely conserved helix side in genotype 1b. By using this structure as well as the amino acid conservation as a guide for a functional study, we determined the contribution of individual amino acid residues in TMS1 for HCV assembly. We identified several residues that are critical for virion formation, most notably a central glycine residue at position 10 of TMS1. Finally, we demonstrate that mutations in NS2 blocking HCV assembly can be rescued by trans-complementation.

Clinicopathological features and natural history of acute sporadic non‐(A‐E) hepatitis

The aim of the present study was to describe the clinicopathological characteristics and the natural history of acute non-(A-E) hepatitis and to assess the possible role of hepatitis G virus (HGV), TT virus (TTV) and mainly SEN virus (SENV). A cohort of 55 patients with sporadic acute non-(A-E) hepatitis with a mean follow up of 31 (6-55) months was studied. The clinical presentation was fulminant in one (1.8%), protracted with impaired regeneration in seven (12.7%) and benign in the remaining 47 (85.5%) cases. Progression to chronic hepatitis was observed in 15 (27.3%) patients; it was more frequent in clinically severe than in non-severe cases (five of eight patients or 62.5% vs 10 of 47 patients or 21.3%, P = 0.028). Six of 10 biopsied chronic non-(A-E) cases developed cirrhosis within 10-33 months. Serum HGV-RNA was detected in 16 of 55 (29.1%) patients, TTV in 20 of 38 (52.6%) patients and SENV-D/H DNA in 20 of 55 (36.4%) cases. HGV-RNA was detected more frequently in clinically severe than in non-severe cases (five of eight or 62.5% vs 11 of 47 or 23.4%, P = 0.038). There was no other association between the presence of HGV, TTV, or SENV infection and patient characteristics or severity and outcome of disease. HGV, TTV, and SENV do not seem to be responsible for the majority of sporadic acute non-(A-E) hepatitis cases. Our cohort further supports the existence of new, unknown hepatitis agent(s) with uncertain mode of transmission. The non-(A-E) agent(s) can also cause chronic hepatitis, which often has an aggressive course with rapid development of cirrhosis.

Hepatitis B Virus Infection and Intrahepatic Cholangiocarcinoma in Korea: A Case-Control Study

There is a wide variation in risk factors for intrahepatic cholangiocarcinoma (ICC) among various populations. Several studies have suggested that hepatitis C virus (HCV) infection may play a role in the development of ICC, whereas the role of hepatitis B virus (HBV) infection is less clear. To determine whether HBV or HCV infection is a risk factor of ICC, we compared baseline demographic and clinical factors in 622 patients diagnosed between 2000 and 2004 with histologically confirmed ICC and 2,488 healthy controls, matched 4:1 with ICC patients for sex and year of birth. HBV infection (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.6-3.3), but not HCV infection, was significantly related to ICC. Other significant risk factors for ICC included liver cirrhosis (OR 13.6), heavy alcohol consumption (OR 6.6), diabetes (OR 3.2), Clonorchis sinensis infection (OR 13.6), hepatolithiasis (OR 50.0), and choledochal cysts (OR 10.7). Our results indicate that development of ICC seems to be more closely related to HBV infection than to HCV infection in Korea, where both HBV and ICC are endemic.

Hepatitis C virus, an important risk factor for tuberculosis in immunocompromised: experience with kidney transplantation

Little is known about the role of hepatitis C virus (HCV) infection in the development of tuberculosis (TB) in patients with immunosuppression. We performed a retrospective case-control study (1:4) to investigate by univariate and multivariate logistic regression analysis the importance of HCV infection in the development of TB in a cohort of kidney transplant recipients (KTR). TB was diagnosed in 16 out of 2012 (0.8%) KTR between 1976 and 2004. The percentage of HCV-positive patients was significantly higher in cases than in controls (56.3% vs. 18.8%; P=0.02). By multivariate analysis, the only two independent risk factors associated with the development of TB were the presence of HCV infection (P=0.003; OR=6.5; 95% CI 1.9-23) and serum creatinine over 1.5 mg/dl (P=0.03; OR=4.8; 95% CI 1.1-21). HCV infection and chronic graft dysfunction are important risks factors for TB in KTR.

The role of hepatitis C virus in the pathogenesis of hepatocellular carcinoma

Hepatitis C virus (HCV) is a worldwide pandemic, chronically affecting over 170 million people worldwide. It is a major risk factor for the development of hepatocellular carcinoma (HCC) and there is increasing experimental evidence to suggest that the virus plays a direct role in neoplastic transformation. The purpose of this letter is to review the literature regarding two individual proteins of HCV, namely NS5A and core, and their role in the pathogenesis of HCC through perturbations of cellular pathways, in addition to their immunopathological effects of chronic inflammation. A systematic search of MEDLINE in addition to manual searches of citations in key papers was employed to identify relevant studies. There is overwhelming evidence suggesting the direct and indirect roles HCV plays in the pathogenesis of HCC. Recent progress in our understanding of the pathophysiology of HCV coupled with advances in in vitro models will ensure that positive strides are made in the treatment and management of this potentially fatal virus.

Hepatitis C and Non-Hodgkin Lymphoma Among 4784 Cases and 6269 Controls From the International Lymphoma Epidemiology Consortium

Increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the risk of non-Hodgkin's lymphoma (NHL) subtypes after HCV infection. The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded. HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40-2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44-4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.68-2.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14-5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65-1.60). These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma).

Is there a direct role of hepatitis C virus in portosystemic encephalopathy?

Is there a direct role of hepatitis C virus in portosystemic encephalopathy?

HCV and HBV infections in Nigerian Patients with Liver Cirrhosis and Hepatocellular Carcinoma

Although efforts have been made to determine the significant of Hepatitis b virus (HBV) infection in Nigerians with chronic liver disease, the role of Hepatitis C virus (HCV) infection has not been fully elucidated. The present study is aimed at determining the incidence of HCV and HBV infections in Nigerian patients with Liver Cirrhosis (LC) and Hepatocellular Carcinoma (HCC). The incidence of HBV and antibodies to HVC was determined by Enzyme Linked Immunosorbent Assey (ELISA) in 24 Nigerians with histologically confirmed Liver Cirrhosis (n=10) and Hepatocullular carcinoma (n=14), as well as healthy adult Nigerians who served as controls (n=14) at the University College Hospital, Ibadan. Incidence rates of 50%, 71% and 40% of HBsAG were obtained in patients with LC, HCC and controls respectively while 20%, 14% and 20% were Anti HCV positive in the respective groups (P

Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinoma

Identification of risk factors for recurrence and metastasis of HCC is important for the prognosis of HCC surveillance in chronic HBV infection. In this article, 125 HCC patients recruited were followed up prospectively for tumor metastasis and recurrence for a median of 104 (10-130) weeks. HBV DNA level was detected by LightCycler-based real-time fluorescence quantitative polymerase chain reaction-restriction system. HBV genotypes were determined by using PCR restriction-fragment length polymorphism. BCP and PC mutations were performed by PCR and direct sequencing of amplified products. Among 125 HCC patients, 19 patients were excluded because of the lack of follow-up data and the remaining 106 patients were followed up of 2 years and entered into analysis. Sixty-nine patients had tumor metastasis or recurrence during the follow-up and the cumulative probability of HCC metastasis or recurrence was 65.1%. On multivariate analysis, genotype C and HBV DNA level were the risk factors for HCC recurrence or metastasis. The incidence of recurrence or metastasis increased with baseline HBV DNA level in a dose-response relationship ranging from 22% for HBV DNA level of less than 3 log10 copies/ml to 80% for HBV DNA level of 5 log10 copies/ml or greater (P = 0.012). Fifty-seven (74.0%) and 12 (41.4%) patients had metastasis or recurrence in patients with genotype C and B, respectively. The adjusted OR of recurrence or metastasis for genotype C compared with genotype B was 9.755 (P = 0.009). In conclusion, elevated HBV DNA level and genotype C are strong risk predictors of HCC metastasis or recurrence.