Hepatitis: US Non-Military

Ghany MG, Strader DB, Thomas DL, Seeff LB, Anonymous00017. · Department of Health and Human Services, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. · Hepatology. · Pubmed #19330875 No free full text.

This publication has no abstract.

Anonymous00392, Yee HS, Currie SL, Darling JM, Wright TL. · Department of Veterans Affairs Hepatitis C Resource Center Program, San Francisco, California, USA. · Am J Gastroenterol. · Pubmed #17032203 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the general U.S. population and 5-10% of veterans who use Department of Veterans Affairs medical services. Chronic HCV is clearly linked to the development of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring liver transplantation. The consequences of HCV infection constitute a significant disease burden and demonstrate the need for effective medical care. Treatment of chronic HCV is aimed at slowing disease progression, preventing complications of cirrhosis, reducing the risk of HCC, and treating extrahepatic complications of the virus. As part of a comprehensive approach to HCV management, antiviral therapy with peginterferon alfa combined with ribavirin is the current standard of care. Antiviral therapy should be provided to those individuals who meet criteria for treatment and who are at greatest risk for progressive liver disease. Many of these patients may have comorbid medical and psychiatric conditions, which may worsen while on antiviral therapy. Current antiviral regimens are associated with significant adverse effects that can lead to noncompliance, dose reduction, and treatment discontinuation. To overcome these barriers and to address these issues, it has become crucial to facilitate a multidisciplinary team who can respond to and provide HCV-specific care and treatment. Screening for HCV, preventing transmission, delaying disease progression, ensuring appropriate antiviral therapy, and managing treatment-related adverse effects can improve patient quality of life, treatment adherence, and ultimately, improve patient outcomes.

Tien PC, Anonymous00369, Anonymous00370. · VAMC Infectious Disease Section, San Francisco, CA 94121, USA. · Am J Gastroenterol. · Pubmed #16181388 No free full text.

Abstract: Nearly 40% of human immunodeficiency virus- (HIV-) infected veterans on highly active antiretroviral therapy (HAART) in the United States are coinfected with hepatitis C virus (HCV). With the increased survival due to declining opportunistic infections as a result of HAART, HCV-associated liver disease has become a leading cause of death in HIV-infected individuals. HCV infection has been shown to lead to rapid progression of HCV-related liver disease in HIV infection. Results from recent clinical trials in HIV/HCV-coinfected patients show improved response rates using pegylated formulations of interferon plus ribavirin when compared to standard interferon plus ribavirin. However, the treatment of HCV in HIV/HCV-coinfected patients can be complicated by the hepatotoxic and myelosuppressive effects of HIV therapy and HIV infection itself. Prior to initiating HCV therapy, HIV therapy should be optimized by improving immune suppression and avoiding specific antiretroviral drugs that may cause hepatotoxicity and myelosuppression. In the event of treatment-related neutropenia or anemia during HCV therapy, the use of growth factors should be considered to maximize sustained virologic response to HCV therapy. In HIV/HCV-coinfected patients with end-stage liver disease, liver transplantation is being investigated and shows promise as a potential therapeutic option. With the recent advances in the treatment of HCV in HIV/HCV-coinfected individuals, all HIV/HCV-coinfected patients eligible for HCV treatment should be evaluated for HCV combination therapy with careful consideration of their HIV disease.

Mofenson LM, Oleske J, Serchuck L, Van Dyke R, Wilfert C, Anonymous00013, Anonymous00014, Anonymous00015. · Pediatric, Adolescent and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20852, USA. · MMWR Recomm Rep. · Pubmed #15577752 links to  free full text

Abstract: In 2001, CDC, the National Institutes of Health, and the Infectious Diseases Society of America convened a working group to develop guidelines for therapy of human immunodeficiency virus (HIV)-associated opportunistic infections to serve as a companion to the Guidelines for Prevention of Opportunistic Infections Among HIV-Infected Persons. In recognition of unique considerations related to HIV infection among infants, children, and adolescents, a separate pediatric working group was established. Because HIV-infected women coinfected with opportunistic pathogens might be more likely to transmit these infections to their infants than women without HIV infection, guidelines for treating opportunistic pathogens among children should consider treatment of congentially acquired infections among both HIV-exposed but uninfected children and those with HIV infection. In addition, the natural history of opportunistic infections among HIV-infected children might differ from that among adults. Compared with opportunistic infections among HIV-infected adults, which are often caused by reactivation of pathogens acquired before HIV infection when host immunity was intact, opportunistic infections among children often reflect primary acquisition of the pathogen and, among children with perinatal HIV infection, infection acquired after HIV infection has been established and begun to compromise an already immature immune system. Laboratory diagnosis of opportunistic infections can be more difficult with children. Finally, treatment recommendations should consider differences between adults and children in terms of drug pharmacokinetics, dosing, formulations, administration, and toxicities. This report focuses on treatment of opportunistic infections that are common in HIV-exposed and infected infants, children, and adolescents in the United States.

Masur H, Kaplan JE, Holmes KK, Anonymous00122, Anonymous00123. · National Institutes of Health, Bethesda, Maryland, USA. · Ann Intern Med. · Pubmed #12617574 No free full text.

Abstract: In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) among persons infected with human immunodeficiency virus (HIV); these guidelines were updated in 1997 and 1999. This fourth edition of the guidelines, made available on the Internet in 2001, is intended for clinicians and other health-care providers who care for HIV-infected persons. The goal of these guidelines is to provide evidence-based guidelines for preventing OIs among HIV-infected adults and adolescents, including pregnant women, and HIV-exposed or infected children. Nineteen OIs, or groups of OIs, are addressed, and recommendations are included for preventing exposure to opportunistic pathogens, preventing first episodes of disease by chemoprophylaxis or vaccination (primary prophylaxis), and preventing disease recurrence (secondary prophylaxis). Major changes since the last edition of the guidelines include 1) updated recommendations for discontinuing primary and secondary OI prophylaxis among persons whose CD4+ T lymphocyte counts have increased in response to antiretroviral therapy; 2) emphasis on screening all HIV-infected persons for infection with hepatitis C virus; 3) new information regarding transmission of human herpesvirus 8 infection; 4) new information regarding drug interactions, chiefly related to rifamycins and antiretroviral drugs; and 5) revised recommendations for immunizing HIV-infected adults and adolescents and HIV-exposed or infected children.

Lin K, Vickery J. · Center for Primary Care, Prevention and Clinical Partnerships, Agency for Healthcare Research and Quality, Rockville, Maryland 20850, USA. · Ann Intern Med. · Pubmed #19528566 No free full text.

Abstract: BACKGROUND: Screening for hepatitis B virus (HBV) infection in pregnant women to identify newborns who will require prophylaxis against perinatal infection is a well-established, evidence-based standard of current medical practice. In 2004, the U.S. Preventive Services Task Force (USPSTF) recommended universal screening of pregnant women for HBV infection at the first prenatal visit. PURPOSE: To search for large, high-quality studies related to hepatitis B screening in pregnancy that have been published since the 2004 USPSTF recommendation. DATA SOURCES: English-language studies indexed in PubMed and the Cochrane Database of Systematic Reviews and published between 1 January 2001 and 5 March 2008. STUDY SELECTION: For benefits of screening and newborn prophylaxis, we included systematic reviews; meta-analyses; and randomized, controlled trials. For harms of screening, we included systematic reviews; meta-analyses; randomized, controlled trials; cohort studies; case-control studies; and case series of large, multisite databases. Abstracts and full articles were independently reviewed for inclusion by both reviewers. DATA EXTRACTION: Data on the benefits of screening, including benefits of hepatitis B immune globulin and hepatitis B vaccine prophylaxis of newborns of hepatitis B surface antigen-positive mothers, were extracted by 1 reviewer. DATA SYNTHESIS: No new studies met inclusion criteria. A 2006 systematic review of randomized, controlled trials found that newborn prophylaxis reduced perinatal transmission of HBV infection; all relevant trials were published in 1996 or earlier. LIMITATION: The focused search strategy, which was restricted to English-language articles, may have missed some smaller studies or new research published in languages other than English. CONCLUSION: No new evidence was found on the benefits or harms of screening for HBV infection in pregnant women. Previously published randomized trials support the 2004 USPSTF recommendation for screening.

Osna NA. · Department of Internal Medicine, University of Nebraska Medical Center, Liver Study Unit R151, VA Medical Center, 4101 Woolworth Ave, Omaha, NE 68105, United States. · World J Gastroenterol. · Pubmed #19291820 links to  free full text

Abstract: Alcoholic patients have a high incidence of hepatitis C virus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV-induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) class I- and class II-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class II in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFbeta) predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class II-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I-restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.

Seeff LB. · National Institute of Diabetes and Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. · Liver Int. · Pubmed #19207971 No free full text.

Abstract: In the late 1960's, only types A and B hepatitis were believed to exist, distinguished by circumstances of exposure and incubation periods. In the early 1970's, studies of transfusion recipients were begun with the belief that hepatitis B would be responsible should transfusion-associated hepatitis develop. After discovery of the viruses of hepatitis A and B, neither agent was found responsible, hence non-A, non-B (NANB) hepatitis. Initial follow-up of these cases showed that approximately 50% developed chronic hepatitis based on persistence of serum enzymes for at least 6 months. Approximately 15 years later, after the hepatitis C virus had been identified as the cause for NANB hepatitis, chronic hepatitis was found to develop more frequently as indicated by persistent viral infection in over 80% of infected adults but in only about 50% of infected children or young women. Follow-up over 2 to 4 decades indicated that many infected persons developed progressive hepatic fibrosis, sometimes culminating in cirrhosis and/or liver cancer. Long-term natural history studies have proved to be challenging because disease onset is often silent and progression extremely slow. Differing strategies have been used to determine the natural history, the descriptions and results of which are presented in this review.

Kane RC, Farrell AT, Madabushi R, Booth B, Chattopadhyay S, Sridhara R, Justice R, Pazdur R. · Office of Oncology Drug Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993-0004, USA. · Oncologist. · Pubmed #19144678 links to  free full text

Abstract: PURPOSE: To describe the U.S. Food and Drug Administration (FDA) review and approval of sorafenib (Nexavar; Bayer Pharmaceuticals Corp., Montville, NJ, and Onyx Pharmaceuticals Corp., Emeryville, CA), an oral kinase inhibitor, for the treatment of patients with unresectable hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: The FDA independently analyzed an international, double-blind, placebo-controlled trial comparing the effect of best supportive care plus sorafenib or matching placebo on overall survival. Eligible patients had unresectable, biopsy-proven HCC and had not received prior systemic therapy. RESULTS: Among the 602 randomized patients (placebo, 303; sorafenib, 299), baseline characteristics were well balanced, and 97% were Child-Pugh score A. HCC was "advanced" in 70% overall, as defined by extrahepatic metastases or by tumor radiographically visible in venous structures outside the liver. Underlying liver diseases included hepatitis B (18%), hepatitis C (28%), and alcohol-related (26%). The trial was stopped following a prespecified second interim analysis showing a statistically significant survival advantage for sorafenib [median, 10.7 vs 7.9 months; hazard ratio, 0.69 (95% confidence interval, (0.55, 0.87)), p = 0.00058]. Adverse events in sorafenib-treated patients included diarrhea in 55% (grade 3, 10%), hand-foot syndrome in 21% (grade 3, 8%), rash in 19% (grade 3, 1%), and cardiac ischemia or infarction in 2.7% (versus 1.3% for placebo). On sorafenib, treatment-emergent hypertension occurred in 9% of patients (placebo, 4%) and was grade 3 in 4% (placebo, 1%); elevated serum lipase occurred in 40% (placebo, 37%); hypophosphatemia occurred in 35% (placebo, 11%). CONCLUSIONS: Sorafenib is the first systemic therapy to demonstrate a survival benefit in a randomized trial for unresectable HCC and has received FDA approval for this indication.

Gao B, Radaeva S, Jeong WI. · Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2S-33, Bethesda, MD 20892-8115, USA. · Expert Rev Gastroenterol Hepatol. · Pubmed #19072444 No free full text.

Abstract: Liver lymphocytes are enriched in natural killer (NK) cells, which are involved in innate immune defenses against viral infection and tumor transformation in the liver. Recent evidence indicates that NK cell activation by IFN-alpha, IFN-gamma or dsRNA attenuates liver fibrosis through the direct killing of activated hepatic stellate cells (HSCs). Interestingly, NK cells do not kill quiescent or fully activated HSCs, but only early-activated HSCs, as only these cells express elevated levels of the NK cell-activating ligand retinoic acid-induced early transcript (RAE)-1 and TNF-related apoptosis-inducing ligand receptors, in addition to downregulated levels of the NK-cell inhibitory ligand, MHC-I. Inhibition of liver fibrosis by NK cells can also be achieved through production of IFN-gamma, which induces HSC cell cycle arrest and apoptosis in a STAT1-dependent manner. Clinically, it has also been observed that NK cell activity is negatively correlated with liver fibrosis in patients with chronic hepatitis C infection. Therefore, since NK cells inhibit liver fibrosis, stimulating NK activity could potentially be a novel strategy to treat liver fibrosis. Clinical studies will be required to confirm whether stimulating NK cell activity is effective and safe in treating human liver fibrosis.

Schinazi RF, Coats SJ, Bassit LC, Lennerstrand J, Nettles JH, Hurwitz SJ. · Laboratory of Biochemical Pharmacology, VA Medical Center, Emory University School of Medicine, 1670 Clairmont Road, Decatur, GA 30033, USA. · Handb Exp Pharmacol. · Pubmed #19048196 No free full text.

Abstract: Traditional methods for general drug discovery typically include evaluating random compound libraries for activity in relevant cell-free or cell-based assays. Success in antiviral development has emerged from the discovery of more focused libraries that provide clues about structure activity relationships. Combining these with more recent approaches including structural biology and computational modeling can work efficiently to hasten discovery of active molecules, but that is not enough. There are issues related to biology, toxicology, pharmacology, and metabolism that have to be addressed before a hit compound becomes nominated for clinical development. The objective of gaining early preclinical knowledge is to reduce the risk of failure in Phases 1, 2, and 3, leading to the goal of approved drugs that benefit the infected individual. This review uses hepatitis C virus (HCV), for which we still do not have an ideal therapeutic modality, as an example of the multidisciplinary efforts needed to discover new antiviral drugs for the benefit of humanity.

Khalsa JH, Treisman G, McCance-Katz E, Tedaldi E. · National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, USA. · Subst Abus. · Pubmed #19042203 links to  free full text

Abstract: Substance abuse still remains one of the major problems in the world today, with millions of people abusing legal and illegal drugs. In addition, a billion people may also be infected with one or more infections. Both drugs of abuse and infections are associated with enormous burden of social, economic, and health consequences. This article briefly discusses a few medical consequences of drugs of abuse and infections such as human immunodeficiency virus, hepatitis C virus, psychiatric complications in hepatitis C infection, pharmacokinetic drug-drug interactions among medications used in the treatment of addiction and infections, and new drugs in development for the treatment of infections. Research is encouraged to study interactions between infections, drugs of abuse, and underlying pathophysiologic and molecular/genetic mechanisms of these interactions.

Waldman M, Marshall V, Whitby D, Kopp JB. · Kidney Disease Section, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-1268, USA. · Semin Nephrol. · Pubmed #19013331 No free full text.

Abstract: SUMMARY: Human immunodeficiency virus (HIV)-infected patients may acquire new viral co-infections; they also may experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections owing to immunodeficiency or risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and treatment of hepatitis C virus, BK virus, adenovirus, cytomegalovirus, and parvovirus B19 in patients with HIV disease. We also discuss an approach to the identification of new viral renal pathogens, using a viral gene chip to identify viral DNA or RNA.

Alter HJ, Klein HG. · Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, USA. · Blood. · Pubmed #18809775 No free full text.

Abstract: The beginning of the modern era of blood transfusion coincided with World War II and the resultant need for massive blood replacement. Soon thereafter, the hazards of transfusion, particularly hepatitis and hemolytic transfusion reactions, became increasingly evident. The past half century has seen the near eradication of transfusion-associated hepatitis as well as the emergence of multiple new pathogens, most notably HIV. Specific donor screening assays and other interventions have minimized, but not eliminated, infectious disease transmission. Other transfusion hazards persist, including human error resulting in the inadvertent transfusion of incompatible blood, acute and delayed transfusion reactions, transfusion-related acute lung injury (TRALI), transfusion-associated graft-versus-host disease (TA-GVHD), and transfusion-induced immunomodulation. These infectious and noninfectious hazards are reviewed briefly in the context of their historical evolution.

Smith JP. · Department of Gastroenterology and Hepatology, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA. · Pharmacotherapy. · Pubmed #18752386 No free full text.

Abstract: Chronic hepatitis C is associated with substantial morbidity and mortality and poses a considerable socioeconomic burden. Improved treatment regimens, including the standard of care pegylated interferon alfa and ribavirin, have increased sustained virologic response rates; however, treatment has a long duration and is often associated with adverse events that may affect adherence. The goal of therapy is viral eradication and reduced disease-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma. The clinical outcome of hepatitis C virus infection is altered with antiviral treatment, which can be influenced by host (e.g., weight, ethnicity, health) and viral (e.g., genotype, baseline viremia) factors. Overall, sustained virologic response was attained by 54-63% of patients in clinical trials treated with pegylated interferon alfa-2a or -2b and ribavirin. However, this benefit is not without risk. Interferon-induced adverse events include flu-like symptoms, bone marrow suppression, and emotional or cognitive effects, whereas hemolytic anemia accounts for most ribavirin dosage reductions. These adverse events may be ameliorated with dosage adjustments, symptom therapy, and judicious use of preventive strategies (e.g., antidepressants, hematopoietic growth factors). Appropriate management of adverse events can increase treatment adherence, thereby enhancing outcomes and improving quality of life. Pharmacists are in an ideal position to improve the treatment of patients with chronic hepatitis C by providing education about the disease and its treatments and associated adverse events and by emphasizing the importance of treatment adherence for successful outcomes.

Monto A, Currie S, Wright TL. · San Francisco Veterans Affairs Medical Center, CA, USA. · J Addict Dis. · Pubmed #18681191 No free full text.

Abstract: Liver disease is a major health problem for individuals with a history of injection drug use. This is mainly from the hepatitis C virus (HCV), with or without co-infection with HIV. HCV-associated liver disease takes decades to develop into cirrhosis, from which it can adversely affect health. HIV coinfection is among the factors that are often associated with liver disease progression, and efforts to understand liver disease progression in HIV-HCV coinfected patients remain important. Maintaining high CD4 counts and avoiding alcohol intake are associated with slower liver disease progression. Pegylated interferon and ribavirin combination therapy has the potential to clear HCV, which provides the strongest health benefit to patients affected by the virus, although this can be difficult to accomplish for many reasons. Steatosis, fat within the liver, may also have important pathological implications for liver disease related to HCV. Limiting liver disease progression in IDUs with hepatitis C may well be best accomplished through promoting their full utilization of health care.

Khalsa JH, Vocci F. · Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on Drug Abuse, NIH, 6001 Executive Boulevard, Bethesda, MD 20892, USA. · J Addict Dis. · Pubmed #18681186 No free full text.

Abstract: Substance abuse and infections remain two of the major problems in the world today. Both are associated with serious morbidity and mortality, including immunological impairment leading to opportunistic infections, mental and neuropsychiatric complications of HIV and HCV infections, and liver damage of chronic HCV infection. Clinical management of substance abusers with infections is possible, available, and effective if individuals in drug treatment programs are closely monitored for adherence and compliance to HIV/HCV treatment regimens.

Mannon RB. · Transplantation Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, MD 20892, USA. · Transplant Rev (Orlando). · Pubmed #18631864 No free full text.

Abstract: Diabetes mellitus continues to be a common metabolic complication after solid organ transplantation. The etiology is multifactorial and includes both modifiable and nonmodifiable factors. Immunosuppression may play a critical role in its development. Targets of treatment include oral hypoglycemics as well as insulin. More recently, several novel agents have been approved by the Food and Drug Administration for treatment of type 2 diabetes. There is limited experience with these agents in transplant recipients. Use of oral and subcutaneous therapies as well as insulin will be reviewed. As diabetes has a negative impact on patient and graft outcome, the transplant practitioner must be vigilant in screening and managing diabetes after transplantation.

Verma V, Shen D, Sieving PC, Chan CC. · Immunopathology Section, Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892-1857, USA. · Surv Ophthalmol. · Pubmed #18572051 links to  free full text

Abstract: Given the fact that infectious agents contribute to around 18% of human cancers worldwide, it would seem prudent to explore their role in neoplasms of the ocular adnexa: primary malignancies of the conjunctiva, lacrimal glands, eyelids, and orbit. By elucidating the mechanisms by which infectious agents contribute to oncogenesis, the management, treatment, and prevention of these neoplasms may one day parallel what is already in place for cancers such as cervical cancer, hepatocellular carcinoma, gastric mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma. Antibiotic treatment and vaccines against infectious agents may herald a future with a curtailed role for traditional therapies of surgery, radiation, and chemotherapy. Unlike other malignancies for which large epidemiological studies are available, analyzing ocular adnexal neoplasms is challenging as they are relatively rare. Additionally, putative infectious agents seemingly display an immense geographic variation that has led to much debate regarding the relative importance of one organism versus another. This review discusses the pathogenetic role of several microorganisms in different ocular adnexal malignancies, including human papilloma virus in conjunctival papilloma and squamous cell carcinoma, human immunodeficiency virus in conjunctival squamous carcinoma, Kaposi sarcoma-associated herpes virus or human herpes simplex virus-8 (KSHV/HHV-8) in conjunctival Kaposi sarcoma, Helicobacter pylori (H. pylori,), Chlamydia, and hepatitis C virus in ocular adnexal mucosa-associated lymphoid tissue lymphomas. Unlike cervical cancer where a single infectious agent, human papilloma virus, is found in greater than 99% of lesions, multiple organisms may play a role in the etiology of certain ocular adnexal neoplasms by acting through similar mechanisms of oncogenesis, including chronic antigenic stimulation and the action of infectious oncogenes. However, similar to other human malignancies, ultimately the role of infectious agents in ocular adnexal neoplasms is most likely as a cofactor to genetic and environmental risk factors.

Su IJ, Wang HC, Wu HC, Huang WY. · Division of Clinical Research, National Health Research Institutes, Tainan, Taiwan. · J Gastroenterol Hepatol. · Pubmed #18505413 No free full text.

Abstract: The discovery of "ground glass" hepatocytes (GGH) that contain hepatitis B virus (HBV) surface antigens by Hadziyannis and Popper in 1973 represents a historical landmark in the pathology of chronic HBV infection. Different types of GGH have been correlated to the expression patterns of surface/core antigens and the stages of virus replication. The original two types (designated types I & II) of GGH were found to contain specific pre-S mutants with deletions over either pre-S1 or pre-S2 regions, respectively. Type II GGH consistently harbor pre-S2 deletion mutants, which can escape from immune attack and grow preferentially to form clusters. Both types of pre-S mutants can induce endoplasmic reticulum (ER) stress and oxidative DNA damage. The pre-S2 mutants, albeit inducing a weaker level of ER stress signals, could additionally initiate ER stress-independent retinoblastoma/adenovirus E2 promoter binding factor/cyclin A signaling through their interaction with c-Jun activation domain binding protein 1 to degrade p27, illustrating the growth advantage of type II GGH. The combined effects of genomic instability and the proliferation of hepatocytes harboring pre-S mutants could potentially lead to hepatocarcinogenesis over the decades of chronic HBV infection. The presence of pre-S mutants in sera was reported to carry a high risk of developing hepatocellular carcinoma (HCC). Furthermore, transgenic mice harboring pre-S2 mutant plasmids have been shown to develop a dysplastic change of hepatocytes and HCC. Therefore, in addition to being a histological marker of chronic HBV infection, GGH, particularly type II GGH, may represent the preneoplastic lesions of HBV-related HCC.

McGee S, Hirschmann J. · Department of Medicine, University of Washington, Seattle-Puget Sound Veterans Affairs Health Care System, Seattle, WA 98108, USA. · Arch Intern Med. · Pubmed #18504331 links to  free full text

Abstract: Clinicians have generally avoided prescribing corticosteroids for active infection because of their known immunosuppressive effects and concern about long-term complications. We conducted a review of the published randomized, double-blind trials comparing corticosteroids and placebo in infections. Except in some trials of viral infections, sore throat, and cerebral cysticercosis, all patients also received active antimicrobial agents in addition to placebo or corticosteroids. For patients with bacterial meningitis, tuberculous meningitis, tuberculous pericarditis, severe typhoid fever, tetanus, or pneumocystis pneumonia with moderate to severe hypoxemia, treatment with corticosteroids improved patient survival (group 1 infections). For patients with bacterial arthritis, corticosteroids were also beneficial and reduced long-term disability (group 2 infections). For about a dozen other infections, corticosteroids significantly relieved symptoms (group 3 infections), and clinicians should consider using them if symptoms are substantial. Corticosteroids were harmful in 2 infections, viral hepatitis and cerebral malaria (group 5 infections). We conclude that corticosteroids are beneficial and safe for a wide variety of infections, although courses longer than 3 weeks should be withheld from patients with concomitant human immunodeficiency virus infection and low CD4 counts.

Barth H, Robinet E, Liang TJ, Baumert TF. · Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. · J Hepatol. · Pubmed #18457898 links to  free full text

Abstract: Hepatitis C virus (HCV) is a major cause of chronic liver disease including steatosis, cirrhosis and hepatocellular carcinoma. The development of transgenic mice expressing HCV proteins and the successful repopulation of SCID/Alb-uPA mice with human hepatocytes provides an important tool for unraveling virus-host interactions in vivo. Several of these mouse models exhibit aspects of HCV-related liver disease. Thus, these in vivo models play an important role to further understand the pathogenesis of HCV infection and to evaluate the pre-clinical safety and efficacy of new antiviral compounds against HCV. This review summarizes the most important mouse models currently used to study HCV pathogenesis and infection. Finally, the perspective of these models for future HCV research as well as the design of novel small animal models is discussed.

Nelligan JA, Loftis JM, Matthews AM, Zucker BL, Linke AM, Hauser P. · Northwest Hepatitis C Resource Center, Behavioral Health & Clinical Neurosciences Division, Portland Department of Veterans Affairs (VA) Medical Center, Oregon Health and Science University, Portland, Oregon 97207, USA. · J Clin Psychiatry. · Pubmed #18426262 No free full text.

Abstract: BACKGROUND: The 2002 National Institutes of Health Consensus Conference Statement recommended that both clinical and research efforts be made to increase the availability of hepatitis C virus (HCV) treatment to patients who were previously ineligible because of comorbid psychiatric illness and substance use disorders. However, little research on patients with HCV and comorbid depression has been conducted that can serve to inform and guide treatment of HCV. In this study we characterize the prevalence and severity of co-morbid depression, as well as antidepressant and other psychotropic prescribing patterns, in a sample of U.S. veterans with HCV. METHOD: Participants were recruited between November 2002 and July 2005 from the liver specialty clinic and from a 1-time HCV patient education class conducted through the Portland Department of Veterans Affairs Northwest Hepatitis C Resource Center. Patients who signed informed consent were asked to complete the Beck Depression Inventory, Second Edition (BDI-II), and their medical records were reviewed for information regarding active prescriptions for psychotropic medications and prior psychiatric diagnoses. RESULTS: Of the 881 veterans enrolled in the study, 783 (89%) completed the BDI-II. Approximately one third (34%, 264/783) of the veterans endorsed moderate to severe symptoms of depression (BDI-II score >or= 20), and 37% (290/783) were prescribed an antidepressant; however, 48% (140/290) of veterans prescribed an antidepressant continued to endorse moderate to severe depressive symptoms. Furthermore, of all veterans endorsing moderate to severe symptoms of depression (N = 264), only about half (56%, 148/264) were prescribed an antidepressant. CONCLUSION: On the basis of BDI-II scores, a significant proportion of veterans with HCV experience moderate to severe depressive symptoms. Although antidepressants were the most commonly prescribed psychotropic medication, many who were prescribed an antidepressant continued to experience high levels of depressive symptoms, an important consideration when deciding whether to initiate antiviral therapy to treat HCV.

Ramanarayanan J, Krishnan GS. · Stratton VA Medical Center, Albany, NY 12208, USA. · Clin Adv Hematol Oncol. · Pubmed #18391919 No free full text.

This publication has no abstract.

Meyers D, Wolff T, Gregory K, Marion L, Moyer V, Nelson H, Petitti D, Sawaya GF, Anonymous00232. · U.S. Preventive Services Task Force, Agency for Healthcare Research and Quality Center for Primary Care, Prevention, and Clinical Partnerships, Rockville, Maryland 20850, USA. · Am Fam Physician. · Pubmed #18386598 links to  free full text

Abstract: Since 2000, the U.S. Preventive Services Task Force (USPSTF) has issued eight clinical recommendation statements on screening for sexually transmitted infections. This article, written on behalf of the USPSTF, is an overview of these recommendations. The USPSTF recommends that women at increased risk of infection be screened for chlamydia, gonorrhea, human immunodeficiency virus, and syphilis. Men at increased risk should be screened for human immunodeficiency virus and syphilis. All pregnant women should be screened for hepatitis B, human immunodeficiency virus, and syphilis; pregnant women at increased risk also should be screened for chlamydia and gonorrhea. Nonpregnant women and men not at increased risk do not require routine screening for sexually transmitted infections. Engaging in high-risk sexual behavior places persons at increased risk of sexually transmitted infections. The USPSTF recommends that all sexually active women younger than 25 years be considered at increased risk of chlamydia and gonorrhea. Because not all communities present equal risk of sexually transmitted infections, the USPSTF encourages physicians to consider expanding or limiting the routine sexually transmitted infection screening they provide based on the community and populations they serve.