Hepatitis C viral infection and the risk of dementia.

BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) infection may cause cognitive impairment, but no studies have focused specifically on cognitive impairment stemming from HCV. The purpose of this study was to investigate the potential increased risk for dementia in HCV-infected patients. METHODS: A population-based cohort study based on the Taiwan National Health Insurance Research Database was conducted. From all potential participants aged 50 years or more, a total of 58,570 matched (1:1) pairs of HCV-infected patients and non-HCV-infected patients were included. Each subject was individually tracked from 1997 to 2009 to identify incident cases of dementia (onset in 1999 or later). Cox proportional hazards regressions were employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HCV infection and dementia. RESULTS: There were 2989 dementia cases from the HCV-infected cohort during the follow-up period of 533,861.1 person-years; the overall incidence rates of dementia differed from the non-HCV cohort (56.0 vs. 47.7 cases per 10,000 person-years, P < 0.05). The adjusted HR for dementia was 1.36 (95% CI 1.27-1.42) for HCV-infected patients after adjusting for alcohol-related disease, liver cirrhosis, hepatic encephalopathy and hepatocellular carcinoma. CONCLUSIONS: HCV infection may increase the risk for dementia. Further mechanistic research is needed.

Inchworm bipedal nanowalker.

Nanowalkers take either inchworm (IW) or hand-over-hand (HOH) gait. The IW nanowalkers are advantageous over HOH ones in force generation, processivity and high-density integration, though both gaits occur in intracellular nanowalkers from biology. Artificial IW nanowalkers have been realized or proposed, but all rely on different 'head' and 'tail' to gain an adventitious direction. Here we report an inherently unidirectional IW nanowalker that is a biped with two identical legs (i.e., indistinguishable 'head' and 'tail'). This walker is made of DNA, and driven by a light-powered G-quadruplex engine. The directional inchworm motion is confirmed by operating the walker on a DNA duplex track that is designed to show a distinctive fluorescence pattern for IW walkers as compared to HOH ones. Interestingly, this walker exhibits stride-controlled IW-to-HOH gait switch and direction reversal when the track's periodic binding sites have wider and wider separation. The results altogether present an integrated mechanism for implementing nanowalkers of different gaits and directions on molecular tracks, optical potentials or even solid-state surfaces.

Purification and characterization of a naturally processed hepatitis B virus peptide recognized by CD8+ cytotoxic T lymphocytes.

In vitro studies in patients with hepatitis B virus (HBV) infection have suggested that hepatocytolysis induced by CD8+ cytotoxic T lymphocytes (CTLs) is the most important effector pathway in eliminating infected cells. The recognition is implicated in the endogenously processed HBV antigens in the context of HLA class I molecules presented on the liver cell membrane. However, the naturally occurring HBV peptide antigens have not yet been demonstrated. We report here that a naturally processed peptide antigen P2 was isolated from HLA class I molecules of HBV-infected liver cell membrane. The P2 peptide exhibited the activity of sensitizing target cells for lysis by CD8+ CTLs. The P2 sequence (YVNVNMGLK) purified from liver tissue was in concordance with that encoded by the viral genome for the HBV nucleocapsid antigen or HBcAg 88-96. P2 peptide could also be isolated from the EBV-transformed B cells that were transfected by HBcAg-expressing vector. The P2 epitope, sharing the HLA-A11 binding motifs, was recognized by HLA-A11-restricted CD8+ CTLs. The data provided direct evidence that, in hepatitis B patients, antigenic peptides of HBV were processed by hepatocytes, presented with the class I MHC molecules, and recognized by CD8+ CTLs.

Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion.

T cell proliferative responses to hepatitis B virus-encoded envelope antigen (S + preS2 + preS1), recombinant core antigen (HBcAg), and natural hepatitis B e antigen (HBeAg) were examined in 22 HBeAg-positive patients with chronic type B hepatitis and 17 healthy hepatitis B surface antigen (HBsAg) carriers. The results showed that HBeAg-positive patients had (a) higher levels of T cell responses to HBcAg/HBeAg than those of healthy HBsAg carriers (P less than 0.001 and P less than 0.01, respectively); (b) a further increase in these T cell responses during acute exacerbations (P less than 0.05 and P less than 0.05, respectively); (c) subsidence in the T cell responses to HBcAg/HBeAg after recovery from acute exacerbations and HBeAg seroconversion, whereas the responses would persist at high levels if the patients did not enter a clinical remission; and (d) low levels of T cell responses to S + preS2 + preS1 either before or after HBeAg seroconversion. The appearance of increasing T cell responses to HBcAg/HBeAg usually occurred in the early phase of acute exacerbations. These findings imply that HBcAg/HBeAg-specific T cells play an important role in the exacerbations of chronic hepatitis B and in HBeAg seroconversion. HBcAg/HBeAg-specific precursor T cell frequencies were serially studied in selected cases by limiting dilution assay. Elevation (two- to fourfold) of HBcAg/HBeAg-specific precursor T cell frequencies contributed to the increase of HBcAg/HBeAg-specific T cell proliferation during acute exacerbations.

Poor response to 18-month lamivudine monotherapy in chronic hepatitis B patients with IgM anti-HBc and acute exacerbation.

BACKGROUND: Appearance of immunoglobulin class M antibody against hepatitis B core antigen is a predictor of beneficial response to interferon-alpha therapy in chronic hepatitis B patients, but its relationship with the efficacy of lamivudine therapy remains unclear. AIM: To investigate the outcome of lamivudine therapy in chronic hepatitis B patients with immunoglobulin class M antibody against hepatitis B core antigen and acute exacerbation. METHODS: Chronic hepatitis B patients with acute exacerbation receiving a national-wide therapeutic trial of 18-month lamivudine monotherapy were enrolled for the analysis. Four consecutive seronegative patients were recruited as individual matching controls of one positive subject. Immunoglobulin class M antibody against hepatitis B core antigen in serum was assayed monthly by an automated microparticle enzyme immunoassay. RESULTS: Fifteen (8.9%) of 167 chronic hepatitis B patients with acute exacerbation were seropositive for IgM anti-HBc. Thus 60 seronegative patients were consecutively recruited as control group. At the end of therapy, two (13.3%) of the 15 seropositive patients achieved a sustained response, significantly lower than 26 (43.3%) of the control group. CONCLUSIONS: Appearance of immunoglobulin class M antibody against hepatitis B core antigen in chronic hepatitis B patients with acute exacerbation is a predictor of poor response to lamivudine monotherapy. This is clinically relevant to the decision-making in treating chronic hepatitis B patients with acute exacerbation.

YM155 down-regulates survivin and XIAP, modulates autophagy and induces autophagy-dependent DNA damage in breast cancer cells.

BACKGROUND AND PURPOSE: The aim of this study was to determine the potency and molecular mechanism of action of YM155, a first-in-class survivin inhibitor that is currently under phase I/II clinical investigations, in various drug-resistant breast cancers including the oestrogen receptor positive (ER(+) ) tamoxifen-resistant breast cancer and the caspase-3-deficient breast cancer. EXPERIMENTAL APPROACH: The potency of YM155 in SK-BR-3, MDA-MB-231, MCF7 and its tamoxifen-resistant sublines, TamR6, TamR7, TamR8, TamC3 and TamC6, were determined by MTT assay. Western blot analysis, flow cytometric analysis, reverse transcription-PCR, fluorescent microscopy and comet assay were used to determine the molecular mechanism of action of YM155 in different breast cancer cell lines. KEY RESULTS: YM155 was equally potent towards the parental ER(+) /caspase-3-deficient MCF7 breast cancer cells and its tamoxifen-resistant sublines in vitro. The ER(-) /HER2(+) SK-BR-3 breast cancer cells and the triple-negative/caspase-3-expressing metastatic aggressive MDA-MB-231 breast cancer cells were also sensitive to YM155 with IC50 values in the low nanomolar range. Targeting survivin by YM155 modulated autophagy, induced autophagy-dependent caspase-7 activation and autophagy-dependent DNA damage in breast cancer cells. Interestingly, YM155 also induced XIAP degradation and the degradation of XIAP might play an important role in YM155-induced autophagy in breast cancer cells. CONCLUSIONS AND IMPLICATIONS: YM155 is a potent survivin inhibitor that has potential for the management of various breast cancer subtypes regardless of the expression of ER, HER2 and caspase-3. Importantly, this study provides new insights into YM155's molecular mechanism of action and therapeutic potential in the treatment of tamoxifen-resistant breast cancer.

Response of patients with dual hepatitis B virus and C virus infection to interferon therapy.

Patients with dual infection with hepatitis B virus (HBV) and delta virus (HDV) responded poorly to interferon (IFN) therapy. Little is known about the effect of IFN therapy in patients with HBV and hepatitis C virus (HCV) dual infection. The patients in two randomized controlled trials with chronic HBV infection were retrospectively assayed for HCV markers. The HBV responses to IFN therapy in patients with and without HCV markers were compared. An open trial was conducted in 4 patients who had lost their serum HBV surface antigen (HBsAg) but had continuing HCV viremia and hepatitis. Of the 15 patients seropositive for HCV marker(s), only 1 (6.7%) responded with seroclearance of HBV DNA and HBV e antigen, as compared with 46 (28%) of 164 HCV-negative patients (p = 0.058). Icteric hepatitis developed in 1 patient on emergence of serum HCV RNA in association with seroclearance of HBV DNA. In contrast, good response was demonstrated in 3 of the 4 patients who had lost serum HBsAg before therapy. The results suggest that IFN therapy is not only of limited value in patients with dual infection with HBV and HCV but also has a potential risk of severe hepatitis if the clearance of one virus removes its suppressive effect on and facilitates the emergence of the other. However, patients with continuing HCV hepatitis after termination of the chronic HBsAg carrier state responded well to IFN therapy.

Characterization of T Cell Clones Specific to a Determinant of Hepatitis B Virus Core and e Antigens in Chronic Type B Hepatitis: Implication for a T Cell Mechanism of HBV Immunopathogenesis.

T cell clones specific for hepatitis B core (HBcAg) and e (HBeAg) antigens of hepatitis B virus (HBV) were generated from liver infiltrates of HBeAg-positive patients. Analyzed with a panel of overlapping synthetic peptides spanning the complete sequences of HBcAg and HBeAg, eight clones responded specifically to the e2 peptide (PAYRPPNAPIL; amino acid residues 130-140 of HBcAg and HBeAg), which was doubly restricted by class I and II molecules. A preferential usage of the T cell receptor (TCR) alpha chain variable (V(alpha)) gene was found: V(alpha)12.1 for five HLA-Cw9(3)-restricted cytotoxic T lymphocyte (CTL) clones, and V(alpha)7.1 for three other HLA-DRw52-restricted type 1 helper T cell (Th1) clones. Although heterogeneous in the usage of TCR alpha chain joining region (J(alpha)) segments, their junctional-region sequences revealed conserved hydrophilic serine residues in seven of the eight e2-specific T cell clones. Single alanine substitution of the centrally located and the only hydrophilic asparagine residue of e2 peptide abrogated T cell responsiveness. The nonstimulatory e2 analogue could competitively inhibit e2-specific responses. These results demonstrate that both CTL and Th1 clones recognizing a determinant of HBcAg and HBeAg are present in the liver of chronic hepatitis B patients. The preferential V(alpha) gene usage and the expression of conserved residues in junctional-region sequences of TCRalpha chains by viral-peptide-specific, intrahepatic T cells may provide a T cell mechanism of HBV immunopathogenesis. Copyright 1994 S. Karger AG, Basel

Genetic alternations of p73 are infrequent but may occur in early stage hepatocellular carcinoma.

p73, a structural homologue of the tumor suppressor gene, p53, has recently been identified and mapped to chromosome 1p36, where genomic loss of heterozygosity (LOH) often occurs in human hepatocellular carcinoma (HCC). To determine whether p73 is involved in the development of HCC and whether there is an inverse correlation between the mutations of p73 and p53, we examined 22 paired tumors/noncancerous liver tissues for allelic expression, LOH and mutation of p73 and for mutation of p53. p73 was biallelically expressed in noncancerous liver tissues and in 7 out of the 8 informative tumors. One tumor tissue expressed only a single allele. LOH of p73 was found in 2 out of the 11 (18%) informative cases. A tumor-specific five-nucleotide deletion mutation causing a reading frameshift/early truncation of p73 DNA-binding domain was found, in which case no concomitant mutation in the DNA-binding domain of p53 was identified. Nine out of the 22 cases (41%) contained tumor-specific mutations in the DNA-binding domain of p53. Two of the three cases with p73 genetic alternations had a tumor size of less than 2 centimeters. These results suggest that p73 is a biallelically expressed gene in the liver and that allelic loss and mutation of p73 is infrequent and may occur early in HCC. p73 is unlikely to be the putative tumor suppressor gene located at chromosome 1p36 in HCC.

Assessment of intragastric pH value changes after early nasogastric feeding.

Studies have suggested that early feeding after injury decreases morbidity and mortality. Few reports, however, have focused on the change in pH inside the stomach after early tube feeding. The aim of the present study was the assessment of 1) the change in intragastric pH after surgery, and 2) the effect of early nasogastric tube feeding on intragastric pH value. From April 1997 to February 1998, 80 patients who underwent colon resection for colorectal cancer by a single surgeon entered the study and were randomized into four groups. Twenty patients (group I) were kept on NPO for 1 wk, and 20 patients per group (groups II, III, and IV) were fed through a nasogastric tube from the second to the seventh postoperative day with low-residual (Osmolite HN), high-fat (Pulmocare), and glutamine-containing (AlitraQ) enteral formulas. Feeding started at 500 kcal/500 cc/d. If the patient tolerated the formula well, feeding increased to 1500 kcal/1500 cc(-1)/d(-1) the following day. Intragastric pH was measured preoperatively and then twice daily until the sixth postoperative day. The pH value of intragastric juice increased significantly once feeding started (3. 67 +/- 1.33 on the third postoperative day; 4.28 +/- 1.26 on the six postoperative day). The pH value seemed only mildly affected by the patient's tolerance for tube feeding (poorly tolerated group, pH 3. 52 +/- 1.75 versus 3.75 +/- 1.21 in the well-tolerated group on the third postoperative day; poorly tolerated group, pH 3.67 +/- 1.02 versus 4.45 +/- 1.27 in the well-tolerated group on the sixth postoperative day). The pH value of intragastric juice was higher in group II than in groups III and IV (4.51 +/- 1.57, 3.90 +/- 1.20, 4. 42 +/- 0.89 respectively, on the sixth postoperative day). This series suggests that early nasogastric feeding can significantly elevate the intragastric pH value in patients after resection of colorectal cancer. Nasogastric feeding may decrease the incidence of stress ulceration by elevating the pH value of intragastric juice.

Ticlopidine-induced cholestatic hepatitis with anti-nuclear antibody in serum.

We describe a case of severe cholestatic hepatitis following administration of ticlopidine. A 57-year-old man without known liver disease developed jaundice approximately 3 weeks after initiation of ticlopidine for secondary prevention of stroke. Hyperbilirubinemia and abnormal liver function test values resolved 5 months after withdrawal of ticlopidine. The diagnosis of ticlopidine-induced cholestasis was made after thorough investigations had excluded other causes of jaundice. He was not retreated with ticlopidine. This case may serve to illustrate the possibility of ticlopidine hepatotoxicity, which has rarely been reported. Furthermore, to the best of our knowledge, ticlopidine-induced cholestatic hepatitis accompanied by autoantibody has not been previously reported. This case suggests that regular assessment of liver function should be performed in the initial 3 months of ticlopidine treatment due to the potential risk of adverse effects. In patients with abnormal biochemical test results, autoantibodies should be assessed.

Nurses' participation and utilization of research in the Republic of China.

A survey was done to improve understanding of nurses' participation in research activities and their utilization of research for practice in one developing country, the Republic of China. The sample for this 1996-1997 study was 382 staff nurses and nurse managers. Using two instruments designed for the project it was found that although research participation was low overall, 64% participated in some research activities with data collection and presentation at national conferences the most frequent activities. Nearly half the nurses had utilized research to change practice in the previous three years. The main barriers to utilization were lack of time and lack of staff. Role models, consultation and guidance to locate useful research were the main types of needed assistance. The findings provide direction for future training, education and managerial policy, especially for nurses in developing countries, which account for 84% of the world's population and 93% of the worldwide burden of disease.

High frequency of functional anti-YMDD and -mutant cytotoxic T lymphocytes after in vitro expansion correlates with successful response to lamivudine therapy for chronic hepatitis B.

BACKGROUND: Many determinants for a sustained response to lamivudine therapy have been reported but the role of T cell responsiveness remains unclear. The finding that tyrosine-methionine-aspartate-aspartate (YMDD) motif of the reverse transcriptase domain of hepatitis B virus (HBV) DNA polymerase carries a HLA-A2 restricted cytotoxic T lymphocyte (CTL) epitope makes quantitative measurement of the numbers of peptide specific CTLs feasible using MHC tetramer-peptide complex staining. AIM: To investigate the correlation between anti-YMDD motif CTL activity and the efficacy of lamivudine therapy in HLA-A2 positive patients with chronic hepatitis B (CH-B). METHODS: The function and phenotype of peptide and interleukin 2 expanded peripheral blood mononuclear cells were quantified by cell lytic assay and immunocytochemical analysis by staining with HLA-A2-peptide tetramer complexes. RESULTS: After in vitro expansion, sustained responders had more potent CTL responses against YMDD, YVDD, and YIDD, as well as other epitopes on HBV antigens than non-responders. The frequency of YMDD/YVDD/YIDD motif specific CTLs increased significantly with an effective cell lytic function during and after therapy in sustained responders but not in non-responders. YMDD specific CTLs cross reacted with YIDD and YVDD mutant epitopes, and shared T cell receptor gene usages with YIDD and YVDD specific CTLs. CONCLUSIONS: Sustained responders, at least HLA-A2 patients, elicited a more potent CTL immunity against YMDD and its mutants. YMDD specific CTLs are cross reactive with YVDD and YIDD mutant epitopes, which may further contribute to immune clearance of the mutant viruses and a successful response to lamivudine therapy in CH-B patients.

Chinese nurse stress in Taiwan, Republic of China.

An exploratory study was conducted to understand the Chinese nurses' perceptions of their work stress in Taiwan, Republic of China (ROC). Data were based on the written answers to two open-ended questions from the randomly selected Chinese nurses working at 3 of the 10 first-ranked teaching hospitals that had 900-2,000 hospital beds. The findings showed that stressors in work situations for Chinese nurses were similar to those of their Western colleagues in four categories: nursing care related to patient condition, interpersonal relationships, workload, and opportunity for promotion. In addition, the Chinese respondents especially identified pressure in the role of a unit educator as stressful. Any troubled interpersonal relationship of the Chinese nurse may have been experienced as a greater source of pressure than nurses in other cultures. It is suggested that there might be some similar stressors in the nurse work situation when comparing the Chinese nurse working in the modern hospital in Taiwan to the nurses in large hospitals in the Western culture. Yet the difference between these nurses was the greater emphasis the Chinese nurses placed on the value of advanced study and interpersonal harmony.

The development of a nurse stress checklist from English to Chinese version.

Work stress has been identified as a relevant problem in the field of professional nursing. Many instruments measuring nurse work stress have already been developed in the United States. The Nurse Stress Checklist (NSC), a Likert-type questionnaire with 47 items, was selected for adaptation into the Chinese language from among these instruments, following a literature review and a comparison with the author's personal nursing experiences. The processes of developing the validity of an NSC Chinese version--content validity, concurrent validity, and construct validity--were conducted. In this pilot study, 13 Chinese nurses who had previously worked in the United States and who were fluent in both Chinese and English filled out the NSC in both the Chinese and English versions. Pearson's correlation was performed to build up concurrent validity. Next, 138 Chinese nurses were randomly selected from three medical centers in Taiwan to be participants in the major study. They filled out the NSC in the Chinese version, and a factor analysis was used to build up construct validity. Four factors were extracted: nonproductive reactions, satisfactory responses, professional concerns, and falling behind. A comparison was made of these four factors with the five factors of the NSC in the English version.

Immunopathogenesis of viral hepatitis B and C.

Considerable evidence suggests that immune mechanisms are involved in the pathogenesis of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Both class I-restricted CD8+ T cell and class II-restricted CD4+ T cell responses to viral antigens are important mechanisms that may be responsible for the hepatocyte damage in hepatitis B and C. CD4+ T cell proliferative responses to hepatitis B core antigen (HBcAg) in terms of stimulation index are correlated with hepatitis activity. These responses can be demonstrated in both adult and pediatric patients, and are more vigorous in patients with acute self-limited hepatitis B than in patients with chronic hepatitis B. Patients with hepatitis C also have a significant CD4+ T cell response to HCV antigens. These responses are also more vigorous in acute hepatitis C patients who recover than in patients who evolve to chronic hepatitis. In terms of major histocompatibility complexes (MHC) class I-restricted, CD8+ cytotoxic T lymphocyte (CTL) response, antigenic peptides derived from HBcAg, hepatitis B surface antigen (HBsAg), and polymerase have been demonstrated to be the targets for CTL recognition in hepatitis B patients. Multiple CTL epitopes within HBsAg, HBcAg and polymerase can be detected by sensitizing target cells with synthetic peptides. Likewise, multispecific, HCV-specific CTL responses can coexist with an extensive quasispecies of viral variants. The mechanisms of viral persistence in both hepatitis B and C remain to be clarified.

Effects of relaxation training, combining imagery, and meditation on the stress level of Chinese nurses working in modern hospitals in Taiwan.

The purpose of this study was to test the effectiveness of relaxation training, which was based on the cognitive-behavioral model and specifically focused on helping Chinese registered nurses employed in large teaching hospitals to reduce their work stress in Taiwan, Republic of China. The study design was a pretest-posttest control design with two posttest points. The 137 subjects were selected randomly from three first-ranked teaching hospitals. Twenty-three subjects in the experimental group and 23 in the control group from each hospital participated in the study. The treatment of the experimental group consisted of two sessions of relaxation training based on Smith's (1988) cognitive behavioral model of relaxation at weeks 1 and 2, with a follow-up session in the fifth week. The control group had the same sequence of sessions with a presentation by the researcher on theory analysis in nursing. The mean scores on the Nurse Stress Checklist (NSC) and the Chinese General Health Questionnaire (CGHQ) differed significantly between the experimental and control group in posttest 2 at week 5. These results supported the hypotheses that the relaxation training decreased the Chinese nurses' self-reported work stress as measured by NSC and increased the Chinese nurses' self-reported psychophysiologic health as measured by CGHQ. The significant difference on means of the CGHQ in posttest 1 at week 2 showed that the self-reported psychophysiologic health level responded to the relaxation training earlier than to the self-reported work stress level. In the relaxation treatment, duration of practice was an important factor of the effectiveness of the treatment on the dependent variable of NSC. It is suggested that even brief teaching of relaxation techniques may reduce work stress levels and promote a sense of psychophysiologic health in Chinese nurses who are employed in large teaching hospitals in Taiwan.

T cell mechanisms in the immunopathogenesis of viral hepatitis B and C.

Considerable evidence suggests that immune mechanisms are involved in the pathogenesis of both hepatitis B and C. Both CD4+ and CD8+ T cell responses to viral antigens are important mechanisms that may be responsible for the hepatocyte damage in hepatitis B and C. CD4+ T cell proliferative responses to hepatitis B core antigen (HBcAg) in terms of stimulation index are correlated with hepatitis activity. These responses can be demonstrated in both adult and paediatric patients, and are more vigorous in patients with acute self-limited hepatitis B than in patients with chronic hepatitis B. Patients with hepatitis C also had a significant CD4+ T cell response to hepatitis C virus (HCV) antigens. These responses are also vigorous in acute hepatitis C with recovery than in those cases that evolve to chronic hepatitis C. In terms of human leucocyte antigen (HLA) class I-restricted, CD8+ cytotoxic T lymphocyte (CTL) response, antigenic peptides derived from HBcAg, hepatitis B surface antigen (HBsAg), and polymerase have been demonstrated as the targets for CTL recognition in hepatitis B patients. Multiple CTL epitopes within both HBsAg and HBcAg can be detected by sensitizing target cells with synthetic peptides. Similar to hepatitis B virus (HBV) infection, multispecific, HCV-specific CTL responses can coexist with an extensive quasispecies of viral variants. The mechanisms of viral persistence in both hepatitis B and C are not yet clarified.

Apoptosis in viral hepatitis B and C.

Tumor necrosis factor (TNF) and TNF receptors (TNFR) are members of the growing TNF ligand and receptor families known to be involved in apoptosis, viral pathogenesis and immune regulation. The present report will focus on the role of apoptosis in the pathogenesis of viral hepatitis B and C. Although TNF was reported years ago to modulate viral infections, recent findings on the molecular pathways involved in TNFR signaling have allowed a better understanding of the molecular interactions between cellular and viral factors within the infected cell. The interactions of viral proteins with intracellular components downstream of the TNFR have highlighted at the molecular level that viruses can manipulate the cellular machinery to escape the immune surveillance and to favor spread infection. We will review here the mechanism of apoptosis and the role of viral proteins that regulate apoptosis in viral hepatitis B and C.

Impact of acute hepatitis B virus superinfection on chronic hepatitis C virus infection.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection is not uncommon, but the impact of acute HBV superinfection in patients with chronic HCV infection is still unknown. Two patients with well documented chronic HCV infection were hospitalized for acute hepatitis, which was serologically confirmed to be acute HBV superinfection. One patient who was seropositive for both HBV-DNA and HCV-RNA upon admission died of hepatic failure. The other became seronegative for HCV-RNA and recovered with alanine aminotransferase normalization, seroclearance of HBsAg, and antibodies to HCV. These findings confirm that acute superinfection in patients with chronic hepatitis may increase the risk for severe hepatitis, and suggest that HBV as the newcomer may suppress the pre-existing HCV. Together with the earlier observation that acute HCV superinfection suppresses pre-existing HBV, it seems that the timing or sequence of infection is a factor influencing the outcome of viral interactions.