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Curr Hepat Rep. Author manuscript; available in PMC 2011 January 19.
Published in final edited form as: Curr Hepat Rep. 2010 ; 9(4): 260–269. doi:10.1007/s11901-010-0060-4.
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Current Concepts of HBV/HCV Coinfection: Coexistence, but Not Necessarily in Harmony
Shailaja Jamma, MD, Ghazi Hussain, MD, and Daryl T.-Y. Lau, MD, MSc, MPH Liver Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Hepatitis B and hepatitis C are important causes of chronic liver disease globally. Although HBV/ HCV coinfection is not uncommon, its epidemiology is poorly defined. Numerous studies provided evidence that coinfection accelerates liver disease progression and increases the risk of hepatocellular carcinoma. By applying new cell culture models to examine the interaction of both viruses, investigators concluded that HBV and HCV replicate in the same hepatocyte without interference. The roles of innate and adaptive immunity in determining the viral replication and disease outcomes still need rigorous investigation. To date, no standard-of-care recommendation exists for HBV/HCV coinfection. Pegylated interferon and ribavirin combination therapy demonstrated similar efficacy in suppressing HCV RNA in coinfection and HCV monoinfection. However, HBV reactivation during therapy can be a challenge. Future clinical trials evaluating the addition of a nucleoside/nucleotide analog for selective patients with HBV/HCV coinfection are essential for successful management of HBV/HCV coinfection.
Keywords Hepatitis B virus; Hepatitis C virus; Epidemiology; Natural history; Pathogenesis; Pegylated interferon
Hepatitis B and hepatitis C are both significant public health issues globally. It is estimated that about 350 and 170 million people worldwide are infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively [1]. HBV and HCV are distinct viruses with completely different life cycles. HBV belongs to a family of hepatotropic DNA viruses (Hepadnaviridae), whereas HCV is classified in the Hepacivirus genus within the Flaviviridae family [2]. Coinfection with HBV and HCV is common because of their common route of transmission, especially in regions of the world where both viruses are endemic. The interactions between HCV and HBV in the cellular levels and their resulting pathogenesis are not well understood, but important progress has been made with the availability of the novel cell culture model. Our knowledge of the epidemiology, disease progression, and clinical outcomes from HBV/HCV coinfection is still limited, because most of the reported literature is based on cross-sectional studies with heterogeneous populations
Corresponding author: Daryl Lau, MD, MSc, MPH, Liver Center, Division of Gastroenterology, Department of Medicine, 110 Francis Street, Suite 4A, Boston, MA 02215, USA. email@example.com, Tel: (617) 632-1098, Fax: (617) 632-1093; Associate Professor of Medicine, Harvard Medical School (HMS); Director of Translational Liver Research, Beth Israel Deaconess Medical Center, HMS. Disclosure: The author has served on advisory boards for, and received research grants, honoraria, and travel reimbursements from, Bristol-Myers Squibb and Gilead.
available in PMC 2011 January 19. namely. Most importantly. about 25% patients with hepatitis C in the United States had positive HBV serological markers. HBV and HCV share common modes of transmission and as a result. pathogenesis. This review summarizes our current understanding and limitation of knowledge in the epidemiology. Hence. and yielded conflicting results. Multiple studies evaluated the rates of HCV coinfection among hepatitis B surface antigen (HBsAg) carriers.9% to 44. or viral interference [3. [9••] shed new insights into this subject. and therapy of HBV/HCV coinfection and future research needs and directions. some studies demonstrated that HCV core and NS5A inhibit HBV replication. The prevalence of occult HBV infection in HCV-positive patients increased to 40% to 50% when the liver tissue was Curr Hepat Rep. the definition and terminology of HBV and HCV coinfection are not standardized. Page 2 and small sample sizes. we performed a detailed Medline search on the subject of HBV and HCV dual infection published between the years 1990 and 2010. This rate is nearly six times higher than populations without hepatitis C [13].4% in HCV-infected patients. Furthermore. The prevalence of occult HBV infection. the inhibition of one virus did not affect the replication or gene expression of the other. the statistics range from 3% and 18%. The virological and molecular aspects of HBV and HCV coinfection were not well understood in the past because of the lack of appropriate model systems [2]. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Pathogenesis of HBV/HCV Coinfection Both HBV and HCV are hepatotropic viruses whose primary site of replication is in the liver. but other studies could not confirm that [5–7]. To prepare for this review. Two recent publications by Eyre et al. depending on the geographic centers and selective patients [10–12]. natural history. these authors independently concluded that HBV and HCV could replicate in the same hepatocyte without evidence of interference. combined HBV and HCV infection is frequent.4]. although their prevalence of infection varies in different parts of the world. . Furthermore. For example. The exact prevalence of dual HBV and HCV infection is not known because most of the published statistics focused on highly selective and limited populations. the viral entry. At the same time. studies addressing the mechanisms of HBV and HCV coinfection were based on heterologous overexpression of viral proteins. defined by the presence of HBV DNA in the absence of HBsAg. cannot explain the possible roles of the host factors such as the innate and adaptive responses in determining the viral replication and ultimate disease outcomes in HCV and HBV coinfection. the Huh-7 cell line can be applied to study the entire HCV life cycle. Epidemiology of HBV/HCV Coinfection HBV and HCV are among the most common causes of liver disease globally. It is critically important to resolve the question whether direct interference occurs between HBV and HCV in order to understand the disease process and outcomes. Until recently.Jamma et al. The cells supporting HBV could be infected with cell culturederived HCV and the efficient production of infectious HCV. According to the third National Health and Nutrition Survey (NHNS III). [8••] and Bellecave et al. however. RNA replication. especially in HBV-endemic areas and among injection drug users. ranged from 11. By applying this cell culture system to conduct experiments of different designs. study results cannot be universally compared or compiled. Clinical observations on disease outcomes and progression among patients with both HBV and HCV are variable and contradictory. The Huh-7 human hepatocellular (HCC) can support HBV replication and HBV virion formation. Reports suggest reciprocal replicative suppression of the two viruses. and included the 58 most relevant articles in the References. and release of infectious particles. Author manuscript. These in vitro observations. their findings argued against the long-held concept of superinfection exclusion.
coinfected patients can have acute hepatitis.21–23]. Five of 40 patients (12. so unravelling the natural history and progression of this disease is challenging. The different patterns of viral clearance or persistence can also be related to the variable incubation periods. delayed HBsAg appearance. [19] reported 40 patients with fulminant and subfulminant hepatitis. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Natural History of HBV/HCV Coinfection The presentation of HBV and HCV coinfection can be variable. Most of the reports on acute coinfection occur in the settings of intravenous drug use. Coppola et al. 4) chronic HCV with occult HBV: HBsAg negative. Acute coinfection Simultaneous acquisition of both HBV and HCV is uncommon. Page 3 examined for the presence of HBV DNA [14]. the different study conclusions could be a result of the heterogeneous study populations.15]. among patients with chronic hepatitis C [14–16].Jamma et al. resulting in anti-HBs seroconversion. accidental needle stick. the rate of coinfection (9. however.5%) had HCV superinfection [19]. Hence. but superinfection was described also. different patient characteristics have been reported under the broad topic of HBV and HCV coinfection. Acute coinfection can result in clearance of one or both viruses as described below. spontaneous clearance of either or both viruses has been documented in the literature [17. Similar to patients with chronic hepatitis from a single infectious agent.5%) were identified to have acute coinfection with HBV and HCV. the exact immunological mechanisms have not been studied. Antibody to hepatitis B core antigen (antiHBc) is the long-lasting serological marker of past HBV infection. For clarification. [20] evaluated 25 patients with subfulminant and fulminant hepatitis.5% of HCV patients with isolated anti-HBc [14. Although the seroprevalence of isolated anti-HBc in blood donors is 2% to 5%. and 3 of 40 (7. Among the published literature. as determined by the detection of plasma HCV RNA. or can result in fulminant hepatitis or chronic coinfection. Two separate studies done in Saudi Arabia detected HBV DNA in 15. concentration of viral inoculums. Feray et al. 3) HBV superinfection: acute HBV in chronic hepatitis C. Another study by Wu et al. the rates are significantly higher. 2) HCV superinfection: acute HCV in chronic hepatitis B. suggesting HCV suppression of HBV. HBV DNA positive. HCV infection became evident only 30 days after the onset of symptoms.4%) was higher than HCV superinfection of chronic hepatitis B (3. Reciprocal inhibition of HBV and HCV genome leading to clearance of one virus and persistence of the other was postulated. anti-HBs negative. Curr Hepat Rep. In the setting of acute coinfection. available in PMC 2011 January 19. we systematically summarize the natural history of HBV and HCV dual infection based on the following five categories of clinical features and immune profiles: 1) acute coinfection: acute hepatitis with concurrent HBV and HCV infection. and 5) chronic coinfection: chronic hepatitis with HBV DNA positive and HCV RNA positive.6% to 71%. Again. whereas anti-HCV seroconversion became evident only on day 45 [22]. [21] observed that patients with coinfection had lower alanine transaminase (ALT) levels. Mimms et al. The HBV infection presented first and quickly resolved. chronic hepatitis with potential progression to cirrhosis and hepatocellular carcinoma (HCC). and blood transfusion [17–19]. . ranging from 18.1%) [20]. or genotypes.8% and 22. [22] monitored three patients with acute coinfection. HCV RNA positive. Author manuscript. and decreased HBs antigenemia. Patients who presented with fulminant and subfulminant hepatitis were often found to have acute HBV and HCV coinfection.
and the results were conflicting.28•]. controlled study from Italy. During follow-up. small sample size. and different methods of HBV DNA measurements. Kao et al. more than 90% of patients cleared HBsAg. All patients had undetectable HCV RNA during acute hepatitis B.34]. Author manuscript. Several case reports suggest the dominant role of HBV leading to HCV clearance after HBV superinfection [27.25.Jamma et al. the NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Curr Hepat Rep. future studies would need to take these factors into consideration to understand the outcome of HCV after HBV superinfection. host immune response. The difference in rates of fulminant hepatitis is likely secondary to various viral factors. Severe hepatitis with hepatic dysfunction and presence of ascites or encephalopathy occurred in 34.9% of those with acute HBV alone. [34] suggested in their study that occult HBV infection does not have clinical significance in chronic HCV patients residing in HBVendemic areas. [28•] conducted a long-term follow-up study in Italy on 29 anti-HCV carriers with acute HBV superinfection and an equal number of anti-HCV negative patients with acute HBV infection for a median of 5 years. Because the levels of serum HCV RNA and HCV genotypes were not well documented prior to HBV infection. 6 had persistent undetectable HCV RNA and 18 had chronic hepatitis C with detectable HCV RNA. Fulminant hepatitis was reported to be associated with HCV superinfection at rates from 3. serious complications. Similar to monoinfection with either virus. Superinfection with HBV HBV superinfection was less frequently reported than HCV superinfection. In a detailed. They observed that patients with HCV superinfection were 10 times more likely to have had a fulminant hepatitis compared to those without preexisting chronic hepatitis B [23]. and relatively small study sample size. . Those with HCV clearance had more severe hepatitis during the acute presentation. According to the available literature.1% to as high as 23% [23. Several reports have documented that de novo HCV superinfection in the setting of chronic hepatitis B can result in HBeAg seroconversion and in some cases. Occult HBV infection Numerous studies evaluated the clinical manifestations of occult or serologically silent HBV infection in the setting of chronic HCV. Most studies reported the association of occult HBV with more severe hepatic inflammation and outcomes such as cirrhosis and HCC [29–31]. More than 90% of this cohort had HBV genotype D. The discrepancies noted in these observations may be secondary to the absence of appreciate controls. including fulminant hepatitis. several studies observed no significant difference regarding inflammatory disease activity or hepatic fibrosis in HBV/ HCV-coinfected patients [16. Those patients had persistence of chronic hepatitis C after successful clearance of HBV. [32] found that 33% of patients with chronic HCV and occult HBV had evidence of cirrhosis compared to only 19% of those with chronic HCV without occult HBV. Sagnelli et al.26]. the clearance of HBsAg [3. were more common in acute HBV superinfection compared to acute HBV infection alone.5% of patients with HBV superinfection and in only 6. Mortality associated with HCV superinfection has been reported as high as 10% [25]. the difference is statistically significant. At the end of follow-up of 24 patients. Chronic HBV/HCV coinfection resulting in cirrhosis and HCC Chronic coinfection with HBV and HCV can result after acute coinfection or superinfection with HBV or HCV as described above. Page 4 Superinfection with HCV HCV superinfection is commonly seen in Asian countries where HBV is prevalent. in addition to host and viral factors from different geographical regions. In contrast.24].33. available in PMC 2011 January 19. [23] conducted a prospective study in Taiwan that included 11 patients with acute hepatitis C. Cacciola et al. Chu et al.
we found only 11 published clinical trials on populations with both HBV and HCV serological markers and five on patients with chronic hepatitis C and occult HBV. Standard Interferon Monotherapy Limited conclusions can be drawn from studies evaluating standard interferon for HBV and HCV coinfection because of the heterogeneous patient populations and methods of viral load measurements. In a study by Tanaka et al. The key findings and limitations of the published treatment trials of HBV and HCV coinfection are summarized in Tables 1. Several studies cautioned that hepatitis flare may be more frequent and can be severe during interferon therapy for patients with dual infection. Factors such as HCV RNA levels and liver histology were not evaluated or controlled for.3).57•] with ribavirin. Chiaramonte et al. In our literature search. decompensated liver disease. and one on interferon plus lamivudine [58]. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Most studies. [44] reported that the coinfected patients had lower HBV response to therapy. mutations. genotypes. Interferon-based therapy accounted for all the therapeutic studies because of its effectiveness against both viruses. and 3. Among these articles.Jamma et al. In a meta-analysis study by Donato et al. direct comparisons between studies were not possible. Zignego et al. Two studies examined the effects of occult hepatitis B in HCV response to interferon [43. In contrast. most of the studies did not examine the contribution of viral genotypes. Page 5 clinical spectrum of chronic coinfection include variable degrees of hepatic inflammation. Liaw et al. 28% for HCV. six were published between 1995 and 2005 and reported on standard interferon monotherapy [42–47]. [41] further calculated that the cumulative HCC risk at 10 years was 45% for coinfected patients.36]. 3% of patients with HCC were positive for HCV alone. Hasegawa et al. the mechanisms behind the observations are not clear. 2. Furthermore. However. viral replicative status. and HCC. . Their observations suggested that interferon is safe and can lead to both HBV and HCV viral clearance in a proportion of patients. 2% were positive for HBsAg.55•. hence. [37] in Japan. Therapy of HBV/HCV Coinfection National and international treatment guidelines are well-established for HBV and HCV monoinfected patients. Furthermore. no standard-of-care recommendation exists for patients with HBV and HCV coinfection. that was a retrospective analysis on a small number of subjects. and duration of therapy were not standardized.5) or HCV alone (OR 17. [43] Curr Hepat Rep. Although the association of coinfection with progressive liver disease and HCC is known.35. Guptan et al. available in PMC 2011 January 19. and host factors such as metabolic syndrome or genetic predispositions in the pathogenesis. and a significantly higher 12% were positive for both. [42] and Villa et al. Benvegnu et al. hepatitis flare can result in HBsAg clearance in some. Author manuscript. to date.56. [45] included patients with chronic coinfection with replicative HBV and HCV in their trials. [40]. 10 were published between 2003 and 2009 and focused on the findings of combination therapy with either standard interferon (N = 6) [48–53] or pegylated interferon (N = 4) [54••. progressive hepatic fibrosis to cirrhosis. However. and 18% for HBV patients. A South African study observed that HBV and HCV had synergistic risk of HCC [38]. [47] concluded that hepatitis C patients with occult hepatitis B had significantly lower biochemical and virological response to interferon compared to those who were HBV DNA negative. suggest that HBV/HCV coinfection has worse disease progression and outcome when compared to HBV or HCV alone [4. However. [39] conducted a prospective study on 290 cirrhotic patients and confirmed that coinfection was an independent predictor for development of HCC by both univariate and multivariate analyses. the early treatment trials on HBV and HCV dual infection included small numbers of patients and the serological markers.47]. the relative risk of developing HCC was found to be significantly higher in coinfected patients (OR 165) than in HBV (OR 22.
and decreased treatment response compared to HCV monoinfected patients. [53] concluded that the presence of anti-HBc did not affect the virological response of chronic hepatitis C. Combination Therapy With Pegylated Interferon and Ribavirin More recently. They observed that four patients with undetectable serum HBV DNA at baseline had reactivation of HBV after HCV RNA clearance. The response for hepatitis B is more difficult to compare between studies. available in PMC 2011 January 19. several clinical trials evaluated the efficacy of this combination regimen for patients with HBV/HCV coinfection. Although all patients must be HBsAg positive to be enrolled in all studies. all three studies reported that a proportion of patients with undetectable HBV DNA at baseline experienced HBV DNA resurgence after therapy. Author manuscript.50. They found that the HCV genotype 1 patients had SVR of 70% and non-genotype 1 patients had SVR of 78%. [55•] prospectively treated 19 Caucasian patients with chronic hepatitis C and HBsAg-positive status. [56] compared the efficacy of standard interferon/ribavirin (N = 19) and pegylated interferon/ ribavirin (N = 17) combination therapy in HBV/HCV coinfection. [52] reported that HCV patients with HBsAg-negative. Three articles examined the effects of standard interferon and ribavirin combination therapy on patients with chronic hepatitis C and evidence of past hepatitis B exposure or occult hepatitis B [49. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Combination Therapy With Standard Interferon and Ribavirin With the proven synergistic beneficial effects between interferon and ribavirin for the treatment of chronic hepatitis C. they did not evaluate serum HBV DNA prior to or during the course of therapy. the impact of occult HBV on HCV treatment response remains debatable. Potthoff et al. In contrast. Despite these limitations. Page 6 observed that neither the presence of anti-HBc nor HBV DNA influenced the virological response of hepatitis C. They concluded that the presence of HBV DNA in liver did not influence the liver histology or treatment response of hepatitis C. Furthermore. Most importantly. The study was inconclusive because of the small number of patients in each group and the high dropout rate. Myers et al. controlled studies published between 2003 and 2005 compared the results of a 6-month course of standard interferon (3–6 million IU three times weekly) and ribavirin for HBV/HCV dual infection and HCV monoinfection [48.52. The limitations of both studies are the relatively small number of patients with occult hepatitis B. Only one patient had detectable HBV DNA in serum. However. four publications evaluated the efficacy of pegylated interferon and weight-based ribavirin on HBV/HCV coinfection.53]. [49] identified HBV DNA in liver tissues in 15 of 51 HCV patients without HBsAg. the proportions with HBeAg and undetectable serum HBV DNA were variable. only 38 of 47 patients with occult HBV infection had quantifiable HBV DNA in serum by reverse transcriptase–polymerase chain reaction (RT-PCR). This significant difference between studies could be related to the different HCV genotype distributions in the study populations.Jamma et al. The exact rate is unclear because of the relative small patient sample size. On closer examination. Fabris et al. Because of the generally low level of HBV DNA among patients with occult HBV and the variable detection limits of virological assays. None of the HBsAg carriers had detectable HBV DNA in serum prior to therapy and serum HBV DNA and HBsAg were not monitored during therapy. The actual SVR varied between 43% and 69%. . because all subjects received 6 months of combination therapy regardless of viral genotypes. serum HBV DNApositive status experienced more severe hepatic inflammation and fibrosis.51]. Mrani et al. All three trials reported similar sustained virological response (SVR) rates for hepatitis C in both dual and monoinfection. Curr Hepat Rep. Senturk et al. A prospective. the general trend is that a proportion of patients can achieve HBV DNA suppression and clearance of HBsAg and HBeAg on this combination regimen. the levels of HBV DNA or HCV genotypes were not taken into account in the analyses or conclusions. in 2008 and 2009. Three randomized.
In agreement with the two studies mentioned previously.7%). . HCV-monoinfected patients. Curr Hepat Rep. nucleoside/nucleotide analog should be considered for those with resurgence of HBV DNA while on interferon-based therapy. and whenever possible. All patients were HBeAg-positive and had replicative HBV DNA and HCV RNA in serum. Encouragingly. especially if patients have significant hepatic fibrosis. Liu et al. HCV RNA and HBV DNA should be monitored every 4 weeks during therapy. biochemical. histological baseline. and 160 matched. Patients with signs of hepatic decompensation should be referred for liver transplantation evaluation. The decision to continue or discontinue HCV therapy is based on established national guidelines. [54••] compared the treatment outcome of 161 patients with chronic hepatitis C and HBsAg positive. serological. All five patients were treated with lamivudine and had normalization of serum aminotransferases and undetectable HBV DNA within 1 month. The general treatment recommendations based on the authors' experience are summarized below. They reported similar HCV SVR rates between HBV/HCV dually infected and HCV monoinfected patients. the authors also observed a relatively high rate (36%) of HBV reactivation among the 77 patients with undetectable HBV DNA at baseline. General Treatment Recommendations Although no standard-of-care guideline exists for the treatment of HBV/HCV coinfection. Three patients achieved HBeAg loss and four had HCV SVR. [58] reported their observation using a combination of lamivudine and standard interferon for 12 months followed by lamivudine for an additional 6 months on eight patients with HBV/HCV coinfection. For those patients with replicative HBV DNA and less than 1 log reduction of HBV DNA by 12 weeks. they did not observe a preferentially higher incidence of HBV reactivation among those with HCV SVR. It is the strategy of the authors to initiate pegylated interferon and weight-based ribavirin combination therapy for those with active chronic hepatitis C regardless of their HBV status. To date. This pilot study suggests that an oral nucleoside/nucleotide in combination with interferon may be an attractive strategy in treating patients with chronic hepatitis C and active HBV replication. the largest prospective. knowledge of the genotyping information is important for the selection of antiviral agents. detectable HBV DNA at baseline) had undetectable HBV DNA after therapy.Jamma et al. it is reasonable to add a nucleoside/nucleotide analog and continue to monitor viral load monthly for the duration of the triple therapy. they reported 11% of patients achieved HBsAg loss and 10 patients with occult HBV (HBsAg negative. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Combination Therapy With Standard Interferon and Lamivudine What is the role of oral nucleoside/nucleotide analogs in the setting of HBV/HCV dual infection? Marrone et al. available in PMC 2011 January 19. the principles of patient evaluation and management remain the same as for patients with HBV or HCV monoinfection. controlled trial using pegylated interferon and ribavirin therapy on HBV and HCV coinfection was conducted in Taiwan. Depending on the individual treatment response. Author manuscript. randomized. Serum ALT became elevated in 5 of 11 patients with HBV reactivation. nucleoside/nucleotide may be necessary for prolonged suppression of HBV DNA after completion of the HCV therapy. All patients with cirrhosis or persistent HBsAg should undergo regular HCC surveillance with abdominal ultrasound every 6 months. Page 7 controlled study conducted by Yu et al. HBeAg negative serology. Similarly. It is important to establish a complete virological. Because patients with HBV genotype A respond better to interferon therapy. However. [57•] in Taiwan concurred that the HBV reactivation rate was significantly higher among those who achieved HCV SVR (9/27 or 33%) compared to those without SVR (2/23 or 8.
J Hepatol 1998. Brass V. J Hepatol 2009. Liaw YF.28:27–33. Eyre NS. Displacement of hepatitis B virus by hepatitis C virus as the cause of continuing chronic hepatitis. Hepatology 1997. Fiedler N. Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. Liaw YF. et al. Suppression of hepatitis B virus enhancer 1 and 2 by hepatitis C virus core protein. Chang JJ. Mechanisms for inhibition of hepatitis B virus gene expression and replication by hepatitis C virus core protein. as well as host factors such as metabolic syndrome. available in PMC 2011 January 19. et al. et al. The roles of HCV and HBV genotypes.25:719–727. Bellecave P. Schmidt K.Jamma et al. [PubMed: 12401801] 7. and HBV mutants such as pre-core and core promoter mutations. Zarski JP. Tsai SL. ribavirin. and unpredictable treatment response. Koff RS.22(4 Pt 1):1101–1108. New insights into hepatitis B and C virus co-infection. J Hepatol 2003. Characteristics of patients with dual infection by hepatitis B and C viruses. [PubMed: 9049225] 6. Bastie A.278:591–607.106:1048–1053. [PubMed: 7557857] Curr Hepat Rep.50:46–55. Hepatitis B virus and hepatitis C virus interaction in Huh-7 cells. the immune response and other host factors contributing to viral replication. J Hepatol 2002. Risks associated with hepatitis A and hepatitis B in patients with hepatitis C. et al. Hepatology 1995. et al. Pasquinelli C. and therapeutic trials. Precone DF. Chung J. Chen CM. Role of hepatitis C virus in dual and triple hepatitis virus infection. [PubMed: 11418785] 2. [PubMed: 19333911] This study independently concluded that cells with replicating HBV could be infected by HCV without superinfection exclusion. Hepatitis C virus core and E2 protein expression in transgenic mice. The terminology of HBV/HCV coinfection based on serological and virological profiles needs to be uniformly defined to allow comparison of future studies on epidemiology.39:1036– 1041. [PubMed: 19596477] This study demonstrated absence of direct interference between HBV and HCV in a highly reproducible cell culture system.33:20–26. Chen SY. level of viremia. Therapeutic trials evaluating combinations of pegylated interferon. J Clin Gastroenterol 2001. A multicenter Italian study. 10. Page 8 Conclusions HBV/HCV coinfection is a challenging and important medical condition because of its variable clinical manifestations. [PubMed: 19596479] 3. and development of HCC remain poorly understood. Gastroenterology 1994. have been highlighted as: • Of importance •• Of major importance 1. and nucleoside/nucleotide analog are necessary prior to establishing standard-of-care treatment recommendations for this important disease. Hepatology 2009. Recent advances have occurred in the understanding of HBV and HCV interactions in vitro. Phillips RJ. Schuttler CG. [PubMed: 9537860] 5. increased risk of cirrhosis and HCC. published recently. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript References and Recommended Reading Papers of particular interest. J Hepatol 2009.51:423–425. [PubMed: 8143971] 4. Stornaiuolo G. . J Biol Chem 2003. [PubMed: 14642623] 11.51:446–457. et al. 9••. et al. should be considered in evaluating natural history and treatment response. Gaeta GB. natural history. et al. Gajer M. disease progression. Shoenberger JM. Gouttenoire J. Kao CF. Bowden S. The presence or absence of HBV DNA and HCV RNA should be determined by standardized RT-PCR methods. Bohn B.37:855–862. Hepatitis B and C virus coinfection: a novel model system reveals the absence of direct viral interference. however. Moradpour D. [PubMed: 12445429] 8••. Author manuscript.
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Response of patients with dual hepatitis B virus and C virus infection to interferon therapy. Crewe EB. Liver Int 2005. et al. Tositti G. [PubMed: 15751770] 49.112:184–187. available in PMC 2011 January 19. Combination therapy with interferon-alpha and ribavirin in patients with dual hepatitis B and hepatitis C virus infection. Cancer 1999. et al. Lin SM. Coinfection with hepatitis B and C or B. Hepatogastroenterology 1997. [PubMed: 9282824] 45. et al. alanine aminotransferase level at donation and interaction with hepatitis B virus.29:160–166. Hepatology 2003. [PubMed: 8978357] 39. et al. et al. Page 10 33. Impact of occult hepatitis B virus infection on efficacy and prognosis of interferon-alpha therapy for patients with chronic hepatitis C. [PubMed: 7922998] 40. Hung CH. et al. [PubMed: 15386355] 38. Brotodihardjo A. Piazzola E. Tanaka H.2:39–45. Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis. Chen PJ.51:313– 318.75:347–354. [PubMed: 9093946] 48.25:247– 253. Am J Gastroenterol 2001. Ribavirin and interferon is effective for hepatitis C virus clearance in hepatitis B and C dually infected patients. Int J Cancer 2004. J Viral Hepat 1995. Boffetta P.96:2973–2977. A prospective study.20:727–732. [PubMed: 1648540] 36. Orito E.37:568–576. Liaw YF. Antivir Ther 2005. High doses of alpha-interferon are required in chronic hepatitis due to coinfection with hepatitis B virus and hepatitis C virus: long term results of a prospective randomized trial. Cancer 1994. [PubMed: 12409376] 35. Occult hepatitis B virus infection does not affect liver histology or response to therapy with interferon alpha and ribavirin in intravenous drug users with chronic hepatitis C. Prospective study on the risk of hepatocellular carcinoma among hepatitis C virus-positive blood donors focusing on demographic factors. Dai CY. Noventa F. Fabris P. Di Bisceglie AM. Weltman MD. Yamano H.Jamma et al. et al. [PubMed: 11693335] 46. A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. et al. Hepatology 1991.10:125–133. et al. et al. Relevance of inapparent coinfection by hepatitis B virus in alpha interferon-treated patients with hepatitis C virus chronic hepatitis. Alpha-interferon therapy in chronic hepatitis due to active dual infection with hepatitis B and C viruses. Author manuscript. Donato F. Thakur V. Tanaka Y. Hasegawa I. J Med Virol 1997. Buttafoco P. Brown D.74:2442–2448. Lee CM. [PubMed: 10535471] 43. Kew MC. Tsukuma H. J Gastroenterol Hepatol 1999. Lu SN. Fontana R. Fong TL.17:449–452. Kao JH. [PubMed: 14962784] 50. al Karawi MA. Gastroenterology 1997. Lai MY. Viral interaction and responses in chronic hepatitis C and B coinfected patients with interferon-alpha plus ribavirin combination therapy. . Chen DS. Benvegnu L. Chien RN.112:1075–1080.40:4068–4071. Dhillon AP. Int J Cancer 1998. The relative roles of hepatitis B and C viruses in the etiology of hepatocellular carcinoma in southern African blacks. Raina V. Waggoner JG. Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis.85:2132–2137. [PubMed: 9356863] 37.22:319–325. J Interferon Cytokine Res 1997. Mohamed Ael S. [PubMed: 15853986] 51. Vian A.14:64–67. Chang WY. Puoti M. Histopathology 1993. [PubMed: 8514275] 34. Stroffolini T. Colombari R. C and delta viruses results in severe chronic liver disease and responds poorly to interferon-alpha treatment. The significance of antibody to hepatitis C virus in patients with chronic hepatitis B. et al. Chronic hepatitis in multiple virus infection: histopathological evaluation.44:1404–1406. Zignego AL. [PubMed: 7493293] 47. et al. et al. Fattovich G. Sarin SK. [PubMed: 15780046] 44. J Clin Virol 2004. Grottola A. Chiaramonte M. [PubMed: 9455792] 41. Dual infection with hepatitis C and B viruses: clinical and histological study in Saudi patients.14:893–898. Chen PJ. Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C. [PubMed: 10326690] 42. Villa E. et al. [PubMed: 12601355] NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Curr Hepat Rep. Yu MC. Lai MY. J Clin Microbiol 2002. J Gastroenterol Hepatol 2005. Guptan RC. Chuang WL. Kedda MA. et al. Mesa GA. Liu CJ. Puliti S.
controlled trial using pegylated interferon and ribavirin therapy on HBV and HCV coinfection. et al.66:191–195. et al. randomized.29:1485–1493. et al. Peginterferon alfa-2a plus ribavirin for the treatment of dual chronic infection with hepatitis B and C viruses. Author manuscript.10:103–110. 55•. 58. [PubMed: 17596829] 53.79:1075–1081. Menouar K. Sun LJ. Liver Int 2009. Thibault V. Analysis of the efficacy of treatment with peginterferon alpha-2a and ribavirin in patients coinfected with hepatitis B virus and hepatitis C virus. et al. [PubMed: 18490796] 57•. They observed four patients with undetectable serum HBV DNA at baseline had reactivation of HBV after HCV RNA clearance. Senturk H. Boecher WO. Liu CJ. [PubMed: 19084016] This article describes the largest prospective. Wedemeyer H. Potthoff A. [PubMed: 12614466] 54••. Chronic hepatitis C responds poorly to combination therapy in chronic hepatis B carriers. available in PMC 2011 January 19. Tahan V. J Viral Hepat 2003. [PubMed: 15582146] NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Curr Hepat Rep. et al. Marrone A. 56. The HEP-NET B/C co-infection trial: A prospective multicenter study to investigate the efficacy of pegylated interferon-alpha2b and ribavirin in patients with HBV/HCV co-infection. Canbakan B. Zampino R. This Taiwanese study confirmed high HCV SVR but also high rate of HBV reactivation during combination therapy. Poynard T.49:688–694. Chemin I.136:496–504 e3. Lee CM.Jamma et al. Occult HBV infection may represent a major risk factor of non-response to antiviral therapy of chronic hepatitis C. [PubMed: 18490077] This study reported that HCV genotype 1 and non-1 patients both had excellent SVR in the setting of co-infection. Zhao YH. Yu JW. D'Onofrio M. Chuang WL.41:1064–1065. Mrani S. et al. . Neth J Med 2008. Gastroenterology 2009. J Hepatol 2008. Page 11 52. J Hepatol 2004. Myers RP. The impact of prior hepatitis B virus infection on liver histology and the response to interferon therapy in chronic hepatitis C. Combined interferon plus lamivudine treatment in young patients with dual HBV (HBeAg positive) and HCV chronic infection. J Med Virol 2007. [PubMed: 19602134] This study showed that HBV reactivation rate was significantly higher among those who achieved HCV SVR compared to those without SVR.
Lower HBV response in coinfection. N 8 15 Anti-HCV+ HBsAg+ Anti-HCV+ HBsAg+ Anti-HCV+ HBsAg+ Anti-HCV+ HBsAgAnti-HCV+ HBsAg+ (100%)/+ (N = 11. 7. NA—not available.by hybridization. available in PMC 2011 January 19. [46] (1995) Liaw et al. [43] (2005) Curr Hepat Rep. Author manuscript. SVR—sustained virologic response. HCV— hepatitis C virus.(N = 1) Anti-HCV+ HBsAg+ NA/NA N/A HBsAg loss (N = 1) Serology HCV RNA/HBV DNA HCV SVR HBV response Comments/limitations Coinfected patients had more severe liver histology. HBV—hepatitis B virus. [44] (1997) Guptan et al. HBsAg—hepatitis B surface antigen. [42] (1999) 30 7 Villa et al. IFN therapy is safe and effective.7%) HBV DNA.Table 1 Standard interferon for HBV/HCV coinfection Jamma et al. Higher dose of IFN is more effective. Retrospective evaluation of anti-HCV in 2 HBV clinical trials.(N = 6) +/+ N=2 HBsAg loss (N = 2) HBV DNA. All patients were tested HBV DNA.6 mo post but + during follow-up +/+ 0% HBV DNA. HBeAg—hepatitis B e antigen. no HCV genotype information. 6 positive by PCR at baseline. 20%) N = 10 (31%) 9 IU IFN HBsAg loss (N = 1) HBV DNA. but can be associated with hepatitis flare. Anti-HBc or HBV DNA+ did not affect HCV virologic response. [47] (1997) 140 14 Hasegawa et al. [45] (2001) Zignego et al. Severe flare from HCV with HBV DNA clearance in 1 case.9%) N = 43 (30. PCR—polymerase chain reaction. NIH-PA Author Manuscript Page 12 NIH-PA Author Manuscript NIH-PA Author Manuscript .(N = 6) ?/+ N/A HBeAg loss (N = 1) HBV DNA. HBc—hepatitis B core. IFN—interferon. Study (year) Weltman et al.(0%) + (100%)/+ (N = 6. Lower HCV response in patients with occult HBV.
35%) Serology HCV RNA/HBV DNA HCV SVR HBV response Comments/limitations Similar SVR rates between coinfected and HCV alone for both HCV genotype 1 and non-1. HBeAg—hepatitis B e antigen. [50] (2005) 36 Chuang et al. treatment response. NIH-PA Author Manuscript Page 13 NIH-PA Author Manuscript NIH-PA Author Manuscript . available in PMC 2011 January 19. [49] (2004) Mrani et al. Anti-HBc+ status did not affect the rate of SVR in HCV.(N = 5. Similar HCV SVR rates between coinfected and HCV alone patients. Study (year) Liu et al. and all treated for 6 mo. [51] (2003) Hung et al.100%) HBV DNA. 31%) +/+ N = 18 (50%) 25 (69%) HBsAg loss (0%) HBeAg loss (0%) HBV DNA. HCV genotype was not determined. N 21 Anti-HCV+ HBsAg+ Anti-HCV+ HBsAg+ Anti-HCV+ HBsAg+ Anti-HCV+ HBsAgAnti-HCV+ HBsAgAnti-HCV+ HBsAg+/+ N = 11 (28%) NA +/+ N = 15 (29%) liver tissue N = 20 (40%) NA +/NA N = 23(17%) NA +/+ N = 16 (38%) 69% HBsAg loss (N = 5. SVR—sustained virologic response.(N = 6. HBV DNA became positive in 8 of 18 patients. HBV DNA in serum was associated with more severe liver disease and decreased HCV treatment response. [53] (2003) Fabris et al. HBV DNA levels was not assessed before or after therapy. [48] (2005) 51 51 47 42 Myers et al. Serum HBV DNA became positive in all 4 with undetectable HBV at baseline. 11%) +/+ N = 17 (81%) N = 9 (43%) HBsAg loss (0%) HBeAg loss (N = 3. [52] (2007) Curr Hepat Rep. HBV DNA frequently identified in liver of HCV patients. HBV—hepatitis B virus. Its presence did not affect liver histology. HCV responders had significantly higher rates of HBV DNA resurgence than nonresponders during and after treatment. HCV— hepatitis C virus.(N = 2. HBc—hepatitis B core. NA—not available. 12%) HBeAg loss (50%) HBV DNA. Author manuscript. Similar HCV SVR rates between coinfected and HCV alone patients. HBsAg—hepatitis B surface antigen.Table 2 Combination therapy for HBV/HCV coinfection: standard interferon with ribavirin Jamma et al.
[57•] (2009) 50 Anti-HCV+ HBsAg+ + (100%)/+ (N = 4. HCV—hepatitis C virus. HBeAg—hepatitis B e antigen. 11%) HBV DNA. HBV reactivation after HCV RNA clearance in 4 (31%) patients with initial undetectable HBV DNA. 8. Prospective. 10 patients with occult HBV had undetectable HBV DNA after therapy. Suboptimal HBV response. 56%) +/1 (6%) N/A Serology HCV RNA/HBV DNA HCV SVR HBV response Comments/limitations All HCV genotype 1 patients treated for up to 48 wk but 5 (29%) discontinued therapy because of side effects. NIH-PA Author Manuscript Page 14 NIH-PA Author Manuscript NIH-PA Author Manuscript . HBV reactivation rate was high (N = 28/77. Good HBV response. HBsAg—hepatitis B surface antigen. [55•] (2008) Yu et al. 42%) Curr Hepat Rep. SVR—sustained virologic response. HCV response similar to HCV alone. N 17 Anti-HCV+ HBsAg+ Anti-HCV+ HBsAg+ + (100%)/+ (N = 6. Prospective.(N = 38. [56] (2008) 19 Potthoff et al. None had replicative HBV DNA at baseline. [54••] (2009) 161 Anti-HCV+ HBsAg+(excluded HBeAg+) + (100%)/+ (N = 68. controlled. available in PMC 2011 January 19.Table 3 Combination therapy for HBV/HCV coinfection: pegylated interferon with ribavirin Jamma et al. 36%) but no difference between those with or without HCV SVR.(N = 2. Prospective. 32%) G1 7/10 (70%) G2/3 7/9 (78%) HBsAg loss (0%) HBeAg loss (0%) HBV DNA.7%). 33%) HBsAg loss (0%) HBeAg loss (N = 2. HCV response similar to HCV alone. Study (year) Senturk et al. 8%) G1 12/30 (40%) G2/3 15/20 (75%) G1 70/97 (72%) G2/3 53/64 (83%) Liu et al. 33%) than those without SVR (2/23. Excellent HCV response. Author manuscript. 33%) HBsAg loss (N = 18. HBV—hepatitis B virus. NA—not available. HBV reactivation rate was significantly higher with HCV SVR (9/27. controlled.
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The Understand Stuff Around You Test
Their result for The Understand Stuff Around You Test ...
Pretty good
You are 76% smarty pants!
Good work! There's more for you to learn, but you have a very good foundation to build on. You should be proud of what you know.
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They scored 76% on Knowledge, higher than 54% of your peers.
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A long way to go
Oooh. Not good. You don't understand much of what's going around you in everyday life just yet. You have plenty left to learn, so seize the opportunity. Good luck! Also check out a hre... Read more
Need to learn more
Hmm. You definitely have an idea of what's going on around you, but there's a good amount of work left for you to do. Keep hitting those books and keep asking questions. Also check out a... Read more
Pretty good
Good work! There's more for you to learn, but you have a very good foundation to build on. You should be proud of what you know. Also check out a href="http://www.okcupid.com/tests/take?... Read more
Great job! You clearly know what's going on in the world around you. All those times you paid attention in class are showing dividends, or maybe you're just an inquisitive person. Either way, yo... Read more
PERFECT! Genius!
Woo-hoo! You got every question right! There's no doubt that you have a great understanding of how the world around you works. You can think clearly about what's going on in a given situation, a... Read more
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12/5/2014, 12/1/2016
Atlantic Records recording group Straight No Chaser has unwrapped details of their festive new holiday single. 'Text Me Merry Christmas (Feat. Kristen Bell)' is available now at all DSPs via a newly r...
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Today's Devotional
Red HousesWhat has God given you—time, finances, ability—that you can use to help someone in need today?
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I'm in love with Jesus, military brat


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...I have extensive knowledge of the curriculum. I was also a tutor for "No Child Left Behind" for 4 years. Many of my students in that program were also Pre-Algebra students.
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...This course takes the Calculus knowledge base a step further and creates new ways of problem solving and critical thinking. There are techniques to solve certain equations which allow students to understand other similar problems. My background in Greek comes mainly from my family.
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...My students regularly achieve higher grades and build increased confidence. I have more than 8 years of experience teaching in high schools and community colleges, as well as working with private students. My experience includes: - Teaching intensive semester-long courses covering the complete ...
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Today's Devotional
FulfilledWhy is it important to view Old Testament laws through the lens of Jesus' fulfillment of them?
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My name is Breanna I have a awesome relationship with Jesus! I go to Central Christian Church every so often, I attend Sky Valley Bible Church, I go to Selah A Free Methodist Church every Sunday and I am apart of their setup crew. I pray constantly for every one in the world, for my family, and for anything else God leads me to pray for. I read my Bible daily currently I am reading in Zechariah it is a great book of the Bible. I love to help others and take care of animals. I take art lessons from Chris Hopkins who is a world renown famous christian artist. I love to see smiles on peoples face that are brought by God it is so wonderful to see how God blesses people. I am going to be starting a womens Bible study in mid April and I will let all of you ladies know hope you will all come to it. it will be at my house.


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Kids Voting lets youngsters participate in election day
Jessica McClanahan, 10, and Sam Six, 10, cast their ballots Tuesday morning at Hillcrest School as a part of Kids Voting. International visitors, led by Diana Carlin, observed the process.
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by Rockstar Games
Rated 6.4
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by 2K Games
Rated 7.0
NEW!DLC is available for this game
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Online Only
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Rated 8.7
In a hurry?
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Rated 9.0


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The last big weekend of racing before the Breeders' Cup World Thoroughbred Championships could also be a big weekend of betting. A new Pick 3 wager--the NTRA Fall Pick 3--will be offered on Oct. 5 in conjunction with the telecast of three 2-year-old races that day. The wager is on the Lane's End Breeders' Futurity (gr. II) at Keeneland, the Champagne Stakes (gr. I) from Belmont Park, and the Norfolk Stakes (gr. II) from Santa Anita. All three races will be televised on CNBC as part of the Bessemer Trust Two-Year-Old Challenge from 5-6 p.m. ET.The minimum amount for the wager will be $1. Keeneland is the wagering hub for the bet. Fans should askf ro Keeneland race 9. The Bessemer Trust Two-Year-Old Challenge leads up to the Bessemer Trust Breeders' Cup Juvenile (gr. I) on Oct. 26 at Arlington Park.
New Pick 3 In Conjuction with Bessemer 2-Year-Old Challenge
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groovy jobs
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Java Web Application Developer
Virginia Tech - Blacksburg, VA
Broad experience with other programming languages, e.g. PHP , Groovy, Python, Perl, C, Ruby; CALS -IT is seeking a skilled Java web application developer to...
Java/Open Source Developer
Solution Design Group, Inc. - Minnetonka, MN
Full-time salaried position with sdg – voted #1 Best Places to Work! Challenging and rewarding consulting opportunities with well-established clients around
Java Developer (FT)
RTS Labs - Glen Allen, VA
Java, Groovy, Ruby. Interested in joining a solid, fast-growing software development company specializing in Web, Mobile, Data Analytics and Big Data?...
Java Developer
Object Partners Inc. - Minneapolis-Saint Paul, MN
JVM languages such as Java, Groovy, Scala or Clojure. Why consider OPI, and why do people dig working here?...
Deployment Engineer
Technology Ventures - Reston, VA
Jenkins, Artifactory, Ansible, SonarQube, Fortify, Ant, Maven, Groovy scripting, ETCD Key/Value store, Shell scripting, Groovy scripting....
Sr. Java Application Developer
Clear Capital - Roseville, CA
SCRUM, DevOps, JIRA, GIT, Continuous Integration, JUnit, Mockito, JMeter, Groovy - Our people:. You are a high-performing Java Developer implementing core...
Lead Java Developer
Lifetouch - Eden Prairie, MN
Lifetouch, the industry leader in capturing and preserving photographic memories with a rich 80 year history, is currently at the forefront of technology
Senior Grails Developer
TollFreeForwarding.com - Los Angeles, CA
Job Scope The ideal candidate is someone with deep experience in Java, Spring, Akka, Groovy/Grails, and MySQL. S/he participates as a high level technical
Java Developer
GetWellNetwork - Bethesda, MD
Scripting language skills (python, ruby, groovy) is a plus. GetWellNetwork, Inc.® is changing the world of millions of patients in hospitals, in clinics, at...
Restaurant Team Member (Crew)
SONIC® Drive-In - Joplin, MO
Sure, classic cars and vintage threads may be things of the past, but the SONIC Drive-In experience will always be groovy, right on, awesome, wicked, fab, the...


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To any A CHORUS LINE aficionado, the mere mention of Baayork Lee will conjure up vivid memories of the original Connie Wong - the youthful-looking, 4'10' Asian-American, perky dynamo who repeatedly evaded revealing her biological age to Zach, the interviewing choreographer. Now in 2016, Baayork will be choreographing and directing her most recent production of A CHORUS LINE at the Hollywood Bowl in Los Angeles. (more...)
The City of Fairfax Theatre Company's production of The Music Man by Meredith Willson runs at Sydney Lanier Middle School, July 22 - July 30, 2016. (more...)
Meredith Willson's six-time, Tony Award-winning musical The Music Man has arrived at the Cape Playhouse, a wonderful professional theater one can visit to see Broadway-quality productions right in the heart of Dennis, and has invited each and every one of us to join this miraculous parade that is considered "America's favorite family musical." (more...)
The Muny continues its spectacular 98th season this week with The Music Man, starring Hunter Foster (Harold Hill), Elena Shaddow (Marian Paroo), Mark Linn-Baker (Mayor Shinn), Liz McCartney (Mrs. Paroo), Todd Buonopane (Marcellus) and more. BroadwayWorld is excited to bring you highlights from the show, which runs through July 11, below! (more...)
Michael Lowe, born in Chepstow and a recent graduate of the Royal Welsh College of Music and Drama, is the 2016 Welsh Young Musical Theatre Singer Of The Year. Michael - the 2016 winner of the RWCD Stoutzker Prize for Outstanding Musicianship, and who recently performed as a soloist for HRH the Prince Of Wales at Buckingham Palace - was awarded the prestigious title after a closely fought contest with fellow finalists Dafydd Gape, Jonathan Radford and Rachel Lee Stephens at the Tailiesin Arts Centre in Swansea on Sunday 3 July. (more...)
Annette Warren, the "secret" singing voice of Ava Gardner and Lucille Ball in such films as the MGM classic "Show Boat," and a nightclub, TV and recording star who career spans the past 70 years, will celebrate her 94th birthday with a special performance of her new one-woman show, "I Ain't Done Yet" at the Catalina Jazz Club in Hollywood on Wed., July 13 at 8:30 PM. The show will trace her life with songs and stories from her beginning in Cleveland, through her successes in New York, London and Los Angeles. (more...)
Continuing its season "The Best of Times is Now," The Ziegfeld Theater presents family entertainment at its finest with The Music Man. (more...)
Happy Birthday, Robert Preston! best remembered for his performance as 'Professor' Harold Hill in Meredith Willson's musical The Music Man (1962). He had already won a Tony Award for his performance in the original Broadway production, in 1957. In 1965 he was the male part of a duo-lead musical, I Do! I Do! with Mary Martin, for which he won his second Tony Award. He played the title role in the musical Ben Franklin in Paris and originated the role of Henry II in the original production of The Lion in Winter. In 1974 he starred alongside Bernadette Peters in Jerry Herman's Broadway musical Mack & Mabel as Mack Sennett, the famous silent film director. That same year (1974) the film version of Mame, another famed Jerry Herman musical, was released with Preston starring, alongside Lucille Ball, in the role of Beauregard Burnside. (more...)
Hottest Articles on BroadwayWorld.com from this weekend Sunday, June 5, 2016 - Sunday, June 5, 2016.
Today in 1980, The Music Man opened at City Center, where it ran for 21 performances. The Music Man is a musical with book, music, and lyrics by Meredith Willson, based on a story by Willson and Franklin Lacey. The plot concerns con man Harold Hill, who poses as a boys' band organizer and leader and sells band instruments and uniforms to naive townsfolk before skipping town with the cash. In 1957, the show became a hit on Broadway, winning five Tony Awards, including Best Musical, and running for 1,375 performances. (more...)
A new Canadian musical, "Like a Fly in Amber", by Vancouver writer Karen Kelm, debuts at the 2016 Toronto Fringe Festival. Through breaking hearts and belly laughs, the show dares the audience to laugh in the face of the inevitability of deterioration and death, and cry for their own missteps on the relationship path. (more...)
Could the recently reworked version of Meredith Willson musical THE UNSINKABLE MOLLY BROWN soon land on Broadway? (more...)
The Las Vegas Philharmonic performs its final concert of the season, Dream of Now, Dream of Then: Lisa Vroman Brings Broadway to Las Vegas on Saturday, June 4, 2016 at 7:30 p.m. in Reynolds Hall at The Smith Center. The performance will feature sixteen Broadway selections with arrangements sung by esteemed vocalist, Lisa Vroman. (more...)
Today in 2000, the second Broadway revival of The Music Man openened at the Neil Simon Theatre, where it ran for 699 performances. The Music Man is a musical with book, music, and lyrics by Meredith Willson, based on a story by Willson and Franklin Lacey. The plot concerns con man Harold Hill, who poses as a boys' band organizer and leader and sells band instruments and uniforms to naive townsfolk before skipping town with the cash. In 1957, the show became a hit on Broadway, winning five Tony Awards, including Best Musical, and running for 1,375 performances. The cast album won the first Grammy Award for 'Best Original Cast Album'. The show's success led to revivals and a popular 1962 film adaptation and a 2003 television remake. (more...)
The University of Pennsylvania's century-old band in a march arrangement of HAMILTON's anthem of ambition. (more...)
American Conservatory Theater (A.C.T.) Artistic Director Carey Perloff is thrilled to announce the appointment of Andy Donald as the company's new Associate Artistic Director. Andy will take on producing and presenting duties within the artistic department, as well as taking the lead in the commissioning and development of new work. Andy will begin his role as Associate Artistic Director on July 5, 2016. (more...)
I am currently in the final stages of presenting a one weekend performance of Peter Shaffer's award winning play, "Amadeus". Researching the Sam French website, I notice yet again that few high schools attempt to take on this intricate and thought-provoking piece of art. And in this instance, although this is my second time directing this play for high school, this is now a new, revised script, due to the author's constant amendments. I've spent the last six months designing and the last three months directing this award winning classic for our school community here in North Adams. With three dress rehearsals next week, we open April 28th at Drury High School for a three-night run. (more...)
As previously announced, Barbara Cook's anticipated autobiography, BARBARA COOK: THEN AND NOW, will be released by HarperCollins Publishers on June 28, and you can check out the cover art on Amazon (and left) now! (more...)
On Tuesday April 12 I eagerly returned to Rockwell Table and Stage for the third time to see An Evening of Classic Broadway. The show comes to Rockwell for one evening every couple of months. Why do I keep coming back? Produced by Dianne Fraser and musically directed by extraordinarily talented Brad Ellis ... and with a bevy of great singers on board, it's guaranteed fun, extra high on entertainment, and it incorporates Broadway standards both classic and contemporary. If that isn't enough, the structure is laid back and spontaneous, allowing one to sit back, relax and just savor the sounds. (more...)
Germantown Community Theatre has announced the slate of productions for their 2016-2017 season. This marks the 45th season of shows the theatre has produced from their home in Germantown, TN. The season blends music, theatre for youth, classic literature and raucous fun. (more...)
1 2 3 4 … 71 next »
Interview: Tony Nominee Tammy Blanchard Takes Dramatic Turn in New Film TALLULAH
TV/MOVIES - VIDEO: Ewan McGregor & Original TRAINSPOTTING Cast Reunite for Sequel to Cult Classic
ART - The British Museum Launches Interactive Family Guide for Family Exploration
FITNESS - Fit Food Finds: PN WOOD FIRED PIZZA in NYC has Healthy and Delicious Crust Choices
MUSIC - VIDEO: Maren Morris Performs '80's Mercedes' on LATE NIGHT
CLASSICAL - Interview: Tenor Barry Banks Counts Himself Lucky
OPERA - Interview: Tenor Barry Banks Counts Himself Lucky
DANCE - Reviews: Doug Varone and Dancers Further the Art


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hospitality jobs near Harrisburg, PA
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The Gutter Guys - Harrisburg, PA
Waiters, waitress, chefs, or anyone in the hospitality industry can do this job as long as you follow our proven method. Required license or certification:....
Immediate Need for: Catering Coordinator
Panera Bread - Camp Hill, PA
Our bakery-cafes are focused on taking care of our guests. Must Have Own Vehicle. We are very proud of the variety of awards that recognize our great food and...
Catering Operations Manager
Sir D's Catering - New Cumberland, PA
Valid PA Driver's License. Required license or certification:. Completing pack lists for deliveries in accordance to event orders....
Hershey Entertainment & Resorts Company - Hershey, PA
Monitor guest communication and satisfaction levels and adjust and implement operating standards that support our vision of operating a premium hospitality...
Catering Operations Coordinator
Sir D's Catering - New Cumberland, PA
Valid PA Driver's License. Required license or certification:. Assist in completing pack lists for deliveries in accordance to event orders as appointed by the...
Caricature Artist
Kaman's Art Shoppes, Inc. (Hershey Park, PA) - Hershey, PA
Learn our quick Meet/Greet and "Demonstration Sketch" techniques to successfully approach potential customers!...
Administrative Assistant
Method 3 - Middletown, PA
Arrange travel plans for all manufacturing employees and visiting German guests. Process internal mail for Manufacturing....
Physical Therapist - Workers' Compensation Network Management
KeyScripts LLC - Mechanicsburg, PA
Assist in the development of marketing materials and communications, as they pertain to the physical medicine network....
Housekeeping / cleaning
La Quinta Inns & Suites - Harrisburg, PA
Maid, janitorial, house cleaning, commercial cleaning, hospital cleaning, part time cleaning, part-time cleaning, office cleaning, full-time cleaning, full time...
Sales Manager
Dynasty Hospitality, LLC - Harrisburg, PA
Ability to listen effectively and to speak English clearly to communicate with guests, clients and team members, and prepare written reports....


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Putin Isn't Responsible for How the Democrats Treated Sanders' Campaign
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text:
Music Lyrics
Bass and Guitar Tabs
and More...
I Fall Down
Julie says: "John I'm getting nowhere.
I wrote this letter, hoped to get to some place soon.
I wanna get up when I wake up,
but when I get up, I fall down."
Julie wake up, Julie tell the story.
You wrote the letter, said you were gonna get there some day.
Gonna walk in the sun and the wind and the rain.
Never walk back again, but now you fall down.
You're falling down, you fall down, you fall down.
Julie say something, Julie say you're sorry.
You're gonna get better, you better not leave me here anyway.
I wanna get up when you wake up,
but when I get up, I fall down.
I'm falling down, I fall down, I broke myself.
I fall, I fall down. I'm falling down.
I fall down when you fall down.
When I'm falling down is when you're falling down.
And when you fall down, I fall down, I fall down.
Return to my to my U2 tabs page
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Website © 2000-2014 mattsmusicpage.com. All rights reserved.
Legal & DMCA: Matt's Music Page has been providing lyrics and tabs in a legal way, paying royalties each year to a few organizations. Then, all lyrics and tabs were removed from the site. Now, there's a new owner to the site, which purchased it August 26, 2014, and he is in negotiation to obtain licensing from BMI at the moment. If you have a specific DMCA request -- please do not hesitate to contact me via the contact button on top. I will do my very best to keep this site fully legal.
Sega Model 3 Stereo Amplifier Board 838-12796/ SJ25-0303-01
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