Occult hepatitis B virus infection and surgical outcomes in non-B, non-C patients with curative resection for hepatocellular carcinoma

AIM To investigate the prevalence, clinicopathological characteristics and surgical outcomes of occult hepatitis B virus(HBV) infection(OBI) in patients with non-B, non-C(NBNC) hepatocellular carcinoma(HCC).METHODS This study retrospectively examined the cases of 78 NBNC patients with curative resection for HCC for whom DNA could be extracted from formalin-fixed paraffin-embedded tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqM an realtime polymerase chain reaction. Possibly carcinogenetic factors such as alcohol abuse, diabetes mellitus, obesity and non-alcoholic steatohepatitis(NASH) were examined. Surgical outcomes were evaluated according to diseasefree survival(DFS), overall survival(OS) and diseasespecific survival(DSS).RESULTS OBI was found in 27/78 patients(34.6%) with NBNC HCC. The OBI patients were significantly younger than the non-OBI cases at the time of surgery(average age 63.0 vs 68.1, P = 0.0334) and the OBI cases overlapped with other etiologies significantly more frequently compared to the non-OBI cases(P = 0.0057). OBI had no impact on the DFS, OS or DSS. Only tumorrelated factors affected these surgical outcomes.CONCLUSION Our findings indicate that OBI had no impact on surgical outcomes. The surgical outcomes of NBNC HCC depend on early tumor detection; this reconfirms the importance of a periodic medical examination for individuals who have NBNC HCC risk factors.

Prevalence of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is characterized by the persistence of HBV DNA in the liver tissue in individuals negative for the HBV surface antigen.The prevalence of OBI is quite variable depending on the level of endemic disease in different parts of the world,the different assays utilized in the studies,and the different populations studied.Many studies have been carried out on OBI prevalence in different areas of the world and categories of individuals.The studies show that OBI prevalence seems to be higher among subjects at high risk for HBV infection and with liver disease than among individuals at low risk of infection and without liver disease.

Occult hepatitis B virus infection in Egypt

The emerging evidence of the potentially clinical importance of occult hepatitis B virus(HBV) infection(OBI) increases the interest in this topic. OBI may impact in several clinical contexts, which include the possible transmission of the infection, the contribution to liver disease progression, the development of hepatocellular carcinoma, and the risk of reactivation. There are several articles that have published on OBI in Egyptian populations. A review of MEDLINE database was undertaken for relevant articles to clarify the epidemiology of OBI in Egypt. HBV genotype D is the only detectable genotype among Egyptian OBI patients. Higher rates of OBI reported among Egyptian chronic HCV, hemodialysis, children with malignant disorders, and cryptogenic liver disease patients. There is an evidence of OBI reactivation after treatment with chemotherapy. The available data suggested that screening for OBI must be a routine practice in these groups of patients. Further studies needed for better understand of the epidemiology of OBI among Egyptian young generations after the era of hepatitis B vaccination.

Clinical impact of occult hepatitis B virus infection in immunosuppressed patients

Occult hepatitis B infection(OBI), is characterized by low level hepatitis B virus(HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen(HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI.

Hepatitis B virus and hepatitis C virus infection inhealthcare workers

Approximately 3 million healthcare workers per year receive an injury with an occupational instrument, with around 2000000 exposures to hepatitis B virus(HBV) and 1000000 to hepatitis C virus(HCV). Although an effective HBV vaccine has been available since the early eighties, and despite the worldwide application of universal vaccination programs started in the early nineties, HBV still remains a prominent agent of morbidity and mortality. There is no vaccine to limit the diffusion of HCV infection, which progresses to chronicity in the majority of cases and is a major cause of morbidity and mortality worldwide due to a chronic liver disease. Healthcare workers are frequently exposed by a mucosal-cutaneous or percutaneous route to accidental contact with human blood and other potentially infectious biological materials while carrying out their occupational duties. Mucosal-cutaneous exposure occurs when the biological material of a potentially infected patient accidentally comes in contact with the mucous membranes of the eyes or mouth or with the skin of a healthcare worker. Percutaneous exposure occurs when an operator accidentally injures himself with a sharp contaminated object, like a needle, blade or other sharp medical instrument. About 75% of the total occupational exposure is percutaneous and 25% mucosal-cutaneous, the risk of infecting a healthcare worker being higher in percutaneous than in mucosal-cutaneous exposure. All healthcare workers should be considered for HBV vaccination and should meticulously apply the universal prophylactic measures to prevent exposure to HBV and HCV.

Mi R-122 in hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus(HBV) and hepatitis C virus(HCV) infections are the most common causes of chronic liver diseases and hepatocelluar carcinomas. Over the past few years, the liver-enriched micro RNA-122(mi R-122) has been shown to differentially regulate viral replication of HBV and HCV. It is notable that thelevel of mi R-122 is positively and negatively regulated by HCV and HBV, respectively. Consistent with the welldocumented phenomenon that mi R-122 promotes HCV accumulation, inhibition of mi R-122 has been shown as an effective therapy for the treatment of HCV infection in both chimpanzees and humans. On the other hand, mi R-122 is also known to block HBV replication, and HBV has recently been shown to inhibit mi R-122 expression; such a reciprocal inhibition between mi R-122 and HBV suggests an intriguing possibility that mi R-122 replacement may represent a potential therapy for treatment of HBV infection. As HBV and HCV have shared transmission routes, dual infection is not an uncommon scenario, which is associated with more advanced liver disease than either HBV or HCV mono-infection. Thus, there is a clear need to further understand the interaction between HBV and HCV and to delineate the role of mi R-122 in HBV/HCV dual infection in order to devise effective therapy. This review summarizes the current understanding of HBV/HCV dual infection, focusing on the pathobiological role and therapeutic potential of mi R-122.

Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection

Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.

Hepatitis B and C virus co-infections in human immunodeficiency virus positive North Indian patients

AIM: To determine the prevalence of hepatitis B and C virus infections in human immunodeficiency virus (HIV) -positive patients at a tertiary care hospital in New Delhi, India. METHODS: Serum samples from 451 HIV positive patients were analyzed for HBsAg and HCV antibodies during three years (Jan 2003-Dec 2005). The control group comprised of apparently healthy bone-marrow and renal donors. RESULTS: The study population comprised essentially of heterosexually transmitted HIV infection. The prevalence rate of HBsAg in this population was 5.3% as compared to 1.4% in apparently healthy donors (P < 0.001). Though prevalence of HCV co-infection (2.43%) was lower than HBV in this group of HIV positive patients, the prevalence was significantly higher (P < 0.05) than controls (0.7%). Triple infection of HIV, HBV and HCV was not detected in any patient. CONCLUSION: Our study shows a significantly high prevalence of hepatitis virus infections in HIV infected patients. Hepatitis viruses in HIV may lead to faster progression to liver cirrhosis and a higher risk of antiretroviral therapy induced hepatotoxicity. Therefore, it would be advisable to detect hepatitis virus co- infections in these patients at the earliest.

Hepatitis B virus infection and coronary atherosclerosis: Results from a population with relatively high prevalence of hepatitis B virus

AIM: To investigate the possible association between hepatitis B virus (HBV) infection and angiographically proven coronary artery disease (CAD) in a population with relatively high prevalence of HBV.METHODS: Sera from 434 patients who underwent coronary angiography were tested for HBV antigens (HBsAg, HBeAg) and antibodies (Anti-HBs, Anti-HBc and Anti-HBe) by ELISA.RESULTS: Seventy-seven percent (224/291) of the patients with CAD and 73.4% (105/143) of the patients without angiographic evidence of atherosclerosis were seropositive for HBV (P＞0.05). However, C-reactive protein (CRP) levels were significantly higher in patients with CAD (P = 0.008), while lower in HBV seropositive population (P= 0.043 and P = 0.021 after adjustment for conventional risk factors).CONCLUSION: Our results suggested HBV infection negatively correlates with CRP levels, but seems not to be associated with coronary atherosclerosis.

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

The systemic therapies available for the management of Psoriasis(PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs(c DMARDs) or biological ones(b DMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus(HBV) and hepatitis C virus(HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen(anti-HBs Ag), HBs Ag, and antibody to HCV(anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a(Cy A) or b DMARDs(etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBs Ag and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV.In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-α inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.

Coinfection of hepatitis B and hepatitis C virus in HIV-infectedpatients in south India

AIM: To screen for the co-infection of hepatitis B (HBV) and hepatitis C virus (HCV) in human immunodeficiency virus (HIV) infected patients in southern India. METHODS: Five hundred consecutive HIV infected patients were screened for Hepatitis B Virus (HBsAg and HBV-DNA) and Hepatitis C virus (anti-HCV and HCV-RNA) using commercially available ELISA kits; HBsAg, HBeAg/ anti-HBe (Biorad laboratories, USA) and anti-HCV (Murex Diagnostics, UK). The HBV-DNA PCR was performed to detect the surface antigen region (pre S-S). HCV-RNA was detected by RT-PCR for the detection of the constant 5' putative non-coding region of HCV. RESULTS: HBV co-infection was detected in 45/500 (9%) patients and HCV co-infection in 11/500 (2.2%) subjects. Among the 45 co-infected patients only 40 patients could be studied, where the detection rates of HBe was 55% (22/40), antiHBe was 45% (18/40) and HBV-DNA was 56% (23/40). Among 11 HCV co-infected subjects, 6 (54.5%) were anti-HCV and HCV RNA positive, while 3 (27.2%) were positive for anti-HCV alone and 2 (18%) were positive for HCV RNA alone. CONCLUSION: Since the principal routes for HIV transmission are similar to that followed by the hepatotropic viruses, as a consequence, infections with HBV and HCV are expected in HIV infected patients. Therefore, it would be advisable to screen for these viruses in all the HIV infected individuals and their sexual partners at the earliest.

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 TTvirus (TTV) in patients with chronic hepatitis B or C and theresponse of the coinfected TTV to interferon (IFN) duringIFN therapy for chronic hepatitis B and C.METHODS: We retrospectively studied the serum samples of70 patients with chronic hepatitis who had received IFN-alfatherapy from January 1997 to June 2000, which included 40cases of hepatitis B and 30 hepatitis C. All the patients hadbeen followed up for at least 6 months after the end of IFNtherapy. The serum TTV DNA was detected using thepolymerase chain reaction (PCR) before and every monthduring the course of IFN treatment.RESULTS: TTv infection was detected in 15 % (6/40) of thechronic hepatitis B group and 30 % (9/30) of the chronichepatitis C group. Loss of serum TTV DNA during IFNtherapy occurred in 3 of 6 patients (50 % ) and 6 of 9 (67 % )of hepatitis B and C groups, respectively. Seronegativity ofTTV was found all during the first month of IFN therapy inthe 9 patients. There was no correlation between theseroconversion of TTv and the biochemical changes of thepatients.CONCLUSION: TTV is not infrequently coinfectsd in patientswith chronic hepatitis B and C in Taiwan, and more thanhalf of the TTv infections are IFN-sensitive. However, theloss of serum TTV DNA does not affect the clinical course ofthe patients with chronic hepatitis B or C.

TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

AIM: To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea, to investigate the association of TTV and HGV infections with blood transfusion, and to assess the correlation between TTV and HGV viremia and hepatic damage.METHODS: A total of 391 serum samples were examined in this study. Samples were obtained from healthy blood donors (n= 110), hepatitis B surface antigen (HBsAg)-positive donors (n=112), anti-hepatitis C virus (anti-HCV)-positive donors (n=69), patients with type B chronic liver disease (n=81), and patients with type C chronic liver disease (n= 19).TTV DNA was detected using the hemi-nested PCR. HGV RNA was tested using RT-PCR. A history of blood transfusion and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also determined.RESULTS: TTV DNA was detected in 8.2 % of healthy blood donors, 16.1% of HBsAg-positive donors, 20.3 % of antiHCV-positive donors, 21.0 % of patients with type B chronic liver disease, and 21.1% of patients with type C chronic liver disease. HGV RNA was detected in 1.8 % of healthy blood donors, 1.8 % of HBsAg-positive donors, 17.4 % of anti-HCV-positive donors, 13.6% of patients with type B chronic liver disease, and 10.5% of patients with type C chronic liver disease. The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors (P＜0.05),except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors. There was a history of transfusion in 66.7% of TTV DNA-positive patients and 76.9% of HGV RNA-positive patients (P＜0.05). No significant increase in serum ALT and AST was detected in the TTV- or HGV-positive donors and patients.CONCLUSION: TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors. However, there is no significant association between TTV or HGV infections and liver injury.

Occult hepatitis B virus co-infection in human immunodeficiency virus-positive patients: A review of prevalence, diagnosis and clinical significance

The prevalence of human immunodeficiency virus(HIV) and hepatitis B virus(HBV) co-infection is high as they share similar mechanisms of transmission. The development and widespread use of highly sensitive tests for HBV diagnosis has demonstrated that a significant proportion of apparently healthy individuals with evidence of exposure to HBV continue to carry fully functional HBV DNA in their hepatocytes, a situation that predisposes them to the development of progressive liver disease and hepatocellular carcinoma. The presence of co-infections frequently influences the natural evolution of each of the participating infections present by either facilitating their virulence or competing for resources. Furthermore, the drugs used to treat these infections may also contribute to changes in the natural course of these infections, making the analysis of the impact of co-infection more difficult. The majority of studies has examined the impact of HIV on overt chronic hepatitis B, finding that co-infection carries an increased risk of progressive liver disease and the development of hepatocellular carcinoma. Although the effect of HIV on the natural history of occult hepatitis B infection(OBI) has not been fully assessed, all available data suggest a persisting risk of repeated flares of hepatitis and progressive liver disease. We describe studies regarding the diagnosis, prevalence and clinical significance of OBI in HIVpositive patients in this short review. Discrepancies in worldwide prevalence show the urgent need for the standardization of diagnostic criteria, as established by the Taormina statements. Ideally, standardized protocols for testing should be employed to enable the comparison of data from different groups. Additional studies are needed to define the differences in risk for OBI without HIV and in HIV-HBV co-infected patients with or without overt disease.

Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment

The relationships between lymphomas and their microenvironment appear to follow 3 major patterns:(1)an independent pattern;(2)a dependent pattern on deregulated interactions;and(3)a dependent pattern on regulated coexistence.Typical examples of the third pattern are hepatitis C virus(HCV)-associated marginal zone lymphomas(MZLs)and mucosa-associated lymphoid tissue lymphomas.In these lymphomas,a regulated coexistence of the malignant cells and the microenvironmental factors usually occurs.At least initially,however,tumor development and cell growth largely depend on external signals from the microenvironment,such as viral antigens,cytokines,and cell-cell interactions.The association between HCV infection and B-cell lymphomas is not completely defined,although this association has been demonstrated by epidemiological studies.MZL and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV infection.Many mechanisms have been proposed for explaining HCV-induced lymphomagenesis;antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell lymphomas.Recently,antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent lymphomas.Importantly,clinically responses were linked to the eradication of the HCV-RNA,providing a strong argument in favor of a causative link between HCV and lymphoproliferation.

Comparative Assay of Hepatitis B and C Virus Infection Markers by Different Assay Kits^1

In order to compare sensitivity of EIA and RIA assay kits for hepatitis B and C virus (HBV and HCV, respectively) infection markers, 100 serum samples in total were collected form 50 adult women each in urban and rural areas in northeast China. The number of positive cases to the three infection markers on HBV (i.e., HBsAg +, anti HBs +, and anti HBc +) and the one on HCV (anti HCV +) were examined in two laboratories, i.e., in Laboratory A with EIA kits produced in China and in Laboratory B with RIA kits. HCV infection positivity (anti HCV +) was examined by EIA kits in both laboratories, but from different sources in and outside of China, respectively. The assay in Laboratory A gave 2 HBsAg + cases out of the 100 cases examined, whereas there were 9 positive cases in Laboratory B. In contrast, 19 cases were positive to anti HCV when examined in Laboratory A, and there were 3 cases in Laboratory B. Thus, the kits used in Laboratory A gave fewer HBsAg + and more anti HCV + cases than the kits used in Laboratory B. The prevalence of anti HBs + or anti HBc + and cases did not differ when assayed in the two laboratories with EIA and RIA kits, respectively. The agreement of positive and negative findings between the two sets of testing were 93%, 93%, 93%, 86% and 82% for HBsAg, anti HBs, anti HBc, HBV (i.e., either positive to anyone of the three markers or negative to all three markers), and anti HCV, respectively. The implication of the observation on epidemiology on HBV and HCV infection prevalence was discussed.

Role of genetic polymorphisms in hepatitis C virus chronic infection

AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C(CHC).METHODS: We conducted an electronic search on the Pub Med and MEDLINE(2000-2014) databases and Cochrane library(2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article.RESULTS: Several studies associated polymorphisms in the interleukin 28 B gene on chromosome 19(19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon(PegIFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation. CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.

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 expres-sion in 32 patients with hepatitis B virus (HBV)-/hepa-titis C virus (HCV)-associated hepatocellular carcinoma (HCC) were investigated by means of cDNA microar-rays 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 non-tumorous liver tissues),consisting of 886 genes were analyzed. RESULTS: Seven up-regulated genes in HBV-associat-ed HCC comprised genes involved in protein synthesis (RPS5 ),cytoskeletal organization (KRT8 ),apoptosis related genes (CFLAR),transport (ATP5F1),cell mem-brane receptor related genes (IGFBP2),signal trans-duction or transcription related genes (MAP3K5),and metastasis-related genes (MMP9). The up-regulated genes in HCV-infected group included 4 genes: VIM (cell structure),ACTB (cell structure),GAPD (glycolysis) and CD58 (cell adhesion). The expression patterns of the 11 genes,identified by cDNA microarray,were con-firmed 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 pres-ent study indicates that HBV and HCV cause hepato-carcinogenesis by different mechanisms,and provide novel tools for the diagnosis and treatment of HBV-and HCV-associated HCC.

Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Liver transplantation for human immunodeficiency virus(HIV)positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers.Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients coinfected with hepatitis B virus(HBV).However,liver transplantation in HIV positive patients with hepatitis C virus(HCV)has poorer outcomes overall,requiring careful selection of candidates.This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management.In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.

Single amino acid mutation of SR-BI decreases infectivity of hepatitis C virus derived from cell culture in a cell culture model

AIM To investigate the effect of a single amino acid mutation in human class B scavenger receptor I(SR-BI) on the infectivity of cell culture-derived hepatitis C virus(HCVcc) in SR-BI knock-down Huh7-si SR-BI cells.METHODS Site-directed mutagenesis was used to construct the SR-BI S112 F mutation,and the mutation was confirmed by nucleotide sequencing. SR-BI knock-down Huh7-si SR-BI cells were transfected with SR-BI S112 F,SR-BI wild type(WT) and control plasmids,and then infected with HCVpp(HCV pseudoparticles) and hepatitis C virus derived from cell culture(HCVcc). A fluorescence assay was performed to analyze the effect of the S112 F mutation on HCV entry; quantitative real-time PCR,immunofluorescence,and Western blot assays were used to analyze the effect of the S112 F mutation on HCV infectivity. CHO cells expressing WT and SRBI S112 F were incubated with the HCV E2 protein expressed in HEK 293 T cells,and flow cytometry was performed to examine the ability of SR-BI S112 F to bind to the HCV E2 protein. Huh7-si SR-BI cells were transfected with SR-BI WT and the S112 F mutant,andthen Di I-HDL was added and images captured under the microscope to assess the ability of SR-BI S112 F to take up HDL.RESULTS The SR-BI S112 F mutation was successfully constructed. The S112 F mutation decreased the expression of the SR-BI m RNA and protein. SR-BI S112 F decreased HCV entry and HCVcc infectivity in Huh7-si SR-BI cells. The S112 F mutation impaired the binding of SR-BI to HCV E2 protein and decreased the HDL uptake of SR-BI.CONCLUSION The S112 F single amino acid mutation in SR-BI decreased the levels of the SR-BI m RNA and protein,as well as the ability of SR-BI to bind to the HCV E2 protein. Amino acid 112 in SR-BI plays important roles in HCV entry and the infectivity of HCVcc in vitro.