Hepatitis: Washington area

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.

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.

DeCastro MG, Denys GA, Fauerbach LL, Ferranti JK, Hawkins K, Masters LC, Rimland D, Sharbaugh RJ, Zeller J. · APIC, Washington, DC 20036, USA. · Am J Infect Control. · Pubmed #9949378 No free full text.

Abstract: The Association for Professionals in Infection Control and Epidemiology, Inc (APIC), is a multidisciplinary, voluntary, international organization of professionals who practice infection control and the application of epidemiology in all health settings. APIC is an international leader in prevention and control of infection transmission.

Treisman GJ. · Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · AIDS Read. · Pubmed #18770901 No free full text.

This publication has no abstract.

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.

Urban S. · Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. · Nat Rev Microbiol. · Pubmed #19421188 No free full text.

Abstract: Proteolysis in cellular membranes to liberate effector domains from their transmembrane anchors is a well-studied regulatory mechanism in animal biology and disease. By contrast, the function of intramembrane proteases in unicellular organisms has received little attention. Recent progress has now established that intramembrane proteases execute pivotal roles in a range of pathogens, from regulating Mycobacterium tuberculosis envelope composition, cholera toxin production, bacterial adherence and conjugation, to malaria parasite invasion, fungal virulence, immune evasion by parasitic amoebae and hepatitis C virus assembly. These advances raise the exciting possibility that intramembrane proteases may serve as targets for combating a wide range of infectious diseases. This Review focuses on summarizing the advances, evaluating the limitations and highlighting the promise of this newly emerging field.

Williamson CD, Colberg-Poley AM. · Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, 111 Michigan Ave, NW, Washington, DC 20010, USA. · Rev Med Virol. · Pubmed #19367604 No free full text.

Abstract: By exploiting host cell machineries, viruses provide powerful tools for gaining insight into cellular pathways. Proteins from two unrelated viruses, human CMV (HCMV) and HCV, are documented to traffic sequentially from the ER into mitochondria, probably through the mitochondria-associated membrane (MAM) compartment. The MAM are sites of ER-mitochondrial contact enabling the direct transfer of membrane bound lipids and the generation of high calcium (Ca2+) microdomains for mitochondria signalling and responses to cellular stress. Both HCV core protein and HCMV UL37 proteins are associated with Ca2+ regulation and apoptotic signals. Trafficking of viral proteins to the MAM may allow viruses to manipulate a variety of fundamental cellular processes, which converge at the MAM, including Ca2+ signalling, lipid synthesis and transfer, bioenergetics, metabolic flow, and apoptosis. Because of their distinct topologies and targeted MAM sub-domains, mitochondrial trafficking (albeit it through the MAM) of the HCMV and HCV proteins predictably involves alternative pathways and, hence, distinct targeting signals. Indeed, we found that multiple cellular and viral proteins, which target the MAM, showed no apparent consensus primary targeting sequences. Nonetheless, these viral proteins provide us with valuable tools to access the poorly characterised MAM compartment, to define its cellular constituents and describe how virus infection alters these to its own end. Furthermore, because proper trafficking of viral proteins is necessary for their function, discovering the requirements for MAM to mitochondrial trafficking of essential viral proteins may provide novel targets for the rational design of anti-viral drugs.

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.

Younossi ZM, McCullough AJ. · Inova Fairfax Hospital, Falls Church, VA, USA. · Liver Int. · Pubmed #19187068 No free full text.

Abstract: Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disease ranging from simple steatosis to non-alcoholic steatohepatitis, is increasingly recognized as the hepatic manifestation of metabolic syndrome and is an important cause of liver-related morbidity and mortality. It is among the most common forms of liver disease. NAFLD reflects abnormal partitioning of fat, such that fat deposition is increased in the liver, and provides a link between NAFLD and the metabolic syndrome, a constellation of metabolic disorders that can also be associated with visceral fat or central adiposity. Together, the features of the metabolic syndrome presage overt diabetes and increase cardiovascular risk. Hepatitis C virus (HCV) appears to exacerbate the metabolic syndrome by eliciting increased insulin resistance (IR) and promoting truncal obesity. Moreover, the concomitant presence of HCV and NAFLD is associated with an increased likelihood of diabetes, hypertension and/or hypertriglyceridaemia. Metabolic abnormalities have been shown to influence response to treatment such that the presence of IR or obesity reduces the likelihood of a sustained virological response (SVR); conversely, SVR has been demonstrated to ameliorate IR and improve beta-cell function. Clinically, these data suggest that attention must be paid not only to optimizing antiviral response but also to screening for and treatment of the various components of the metabolic syndrome.

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.

Mindikoglu AL, Miller RR. · Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, Maryland 21201-1595, USA. · Clin Gastroenterol Hepatol. · Pubmed #19084480 No free full text.

Abstract: Hepatitis C continues to be a major public health problem affecting approximately 3% of the global population. According to the World Health Organization, an estimated 170 million people have chronic hepatitis C. Ten percent to 20% of those who are chronically infected with hepatitis C will progress to cirrhosis and 5% will develop hepatocellular carcinoma. Although the safety and efficacy of hepatitis C therapies have been studied extensively in patients between the ages of 18 and 65, patients who are older than 65 still remain an understudied and difficult-to-treat population. This review discusses the epidemiology, natural history, and treatment of chronic hepatitis C in older adults.

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.

Rafiq N, Younossi ZM. · Center for Liver Diseases at Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA. · Expert Rev Gastroenterol Hepatol. · Pubmed #19072356 No free full text.

Abstract: Nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent liver diseases in the Western world. NAFLD represents a wide spectrum of histologic subgroups, with nonalcoholic steatohepatitis as the most aggressive form. The risk of developing NAFLD is strongly associated with metabolic syndrome and insulin resistance. The pathogenesis of NAFLD is a multiple-hit process resulting from hepatic fat deposition that is related to several conditions, including insulin resistance and central obesity. Additional hits, such as oxidative stress or adipocytokines produced by white adipose tissue, can further enhance liver damage leading to nonalcoholic steatohepatitis or fibrosis. Although NAFLD is often the primary liver disease of metabolic conditions, it can also exacerbate other liver diseases such as hepatitis C (HCV); indeed, more than 50% of patients with HCV have hepatic steatosis. Hepatic steatosis can be related to host factors (e.g., obesity, metabolic syndrome or insulin resistance) or to the genotype of virus (e.g., HCV genotype 3). Increasing evidence suggests that hepatic steatosis, insulin resistance and obesity in the setting of HCV have a negative impact on the efficacy of treatment and hepatic progression of fibrosis.

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.

Fine DM, Fogo AB, Alpers CE. · Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Semin Nephrol. · Pubmed #19013325 No free full text.

Abstract: SUMMARY: Various forms of kidney disease have been related directly to human immunodeficiency virus (HIV) viral infection, including HIV-associated nephropathy (HIVAN), immune complex diseases, and thrombotic microangiopathy (TMA). HIVAN and HIV immune complex glomerulonephritides are the most common HIV-specific nephropathies. HIV-associated TMA, although far less common, remains an important consideration. The diagnosis of TMA in HIV, which has a poorly understood pathogenesis, can be suggested by thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure, but only definitively diagnosed by kidney biopsy. Not surprisingly, the incidence and prevalence of the HIV-specific entities have declined with the advent of highly active antiretroviral therapy. With this decline, however, other glomerular diseases are of increasing importance in this high-risk population. The differential diagnosis of glomerular disease in an HIV-positive patient is therefore broad. Glomerular diseases seen in this population include classic focal segmental glomerulosclerosis, IgA nephropathy, postinfectious glomerulonephritis, hepatitis B- and C-related glomerulonephritides, and membranous nephropathy. In addition, as the HIV-infected population ages, diabetic and hypertensive nephropathies are likely to become more prevalent. With overlapping presentations of these entities, definitive diagnosis often is difficult, necessitating kidney biopsy. As a consequence of establishing an accurate diagnosis, improved patient outcome can best be accomplished through disease-specific intervention.

Cohen SD, Kimmel PL. · Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington, DC 20037, USA. · Semin Nephrol. · Pubmed #19013324 No free full text.

Abstract: Immune complex glomerulonephritis is a common diagnosis in renal biopsy series of human immunodeficiency virus (HIV)-infected patients. There are a variety of glomerulonephritides associated with HIV infection, including IgA nephropathy, membranoproliferative glomerulonephritis, membranous nephropathy, lupus-like glomerulonephritis, immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, HIV-related proteins may be implicated in circulating immune complexes directly related to a response to the infection. In some cases, the relationship of the HIV infection to the glomerulonephritis is unclear. HIV infection is associated with the development of polyclonal hypergammaglobulinemia, which can promote the development of circulating immune complexes. It is not clear if HIV-associated glomerulonephritis is caused by the passive trapping of these circulating immune complexes or the in situ deposition of antibodies binding to HIV viral antigens. Some renal lesions that are seen in the setting of HIV infection more likely may be related to the presence of a co-infection such as hepatitis C virus infection. The optimal therapy for immune complex glomerulonephritis in the setting of HIV infection is unknown. Because of the underlying immunosuppressed state of many HIV-infected patients, caution with traditional cytotoxic therapies is advised. The role of antiretroviral therapy in modifying the course of these renal lesions is unclear.

Cohen SD, Chawla LS, Kimmel PL. · Division of Nephrology, Department of Medicine, College of Physicians and Surgeons, Columbia University, Washington, District of Columbia, USA. · Curr Opin Crit Care. · Pubmed #19005305 No free full text.

Abstract: PURPOSE OF REVIEW: To present an overview of the epidemiology and etiology of acute kidney injury (AKI) in patients infected with human immunodeficiency virus (HIV). RECENT FINDINGS: HIV-infected patients are at an increased risk of developing AKI. Potential risk factors for the development of AKI in this patient population include increased HIV viral loads, reduced CD4 cell counts, hepatitis C virus coinfection, a history of diabetes, black race, male gender, and baseline chronic kidney and hepatic disease. Observational studies have found an increased morbidity and mortality in HIV-infected patients who develop AKI. There are diverse etiologies of AKI in HIV-infected patients, with increasing reports of highly active antiretroviral therapy-related nephropathy secondary to tenofovir nephrotoxicity. There have also been recent case reports of HIV-infected patients who develop a unique form of acute interstitial nephritis secondary to diffuse infiltrative lymphocytosis syndrome. SUMMARY: There are a variety of etiologies of AKI in HIV-infected patients. Prompt diagnosis and treatment of AKI is critical to help prevent morbidity and mortality in this patient population.

Lazo M, Clark JM. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. · Semin Liver Dis. · Pubmed #18956290 No free full text.

Abstract: Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver disease in the United States and worldwide. With obesity being an important risk factor universally, NAFLD is now receiving greater attention and is regarded as a public health issue. In addition, as a result of an aging population and the improving control of other major causes of chronic liver disease, such as hepatitis C and hepatitis B, the burden of NAFLD is expected to increase in years to come. Prevalence estimates of this disease vary widely across populations because of differences in methods for diagnosis and/or definition. New strategies for the prevention, diagnosis, and management will be required to alter the course of this disease.

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.

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.

Gupta NK, Lewis JH. · Division of Gastroenterology, Georgetown University Medical Center, Washington, DC 20007, USA. · Aliment Pharmacol Ther. · Pubmed #18671777 No free full text.

Abstract: BACKGROUND: Misconceptions surround the use of hepatotoxic drugs in chronic liver disease. While many prescription and over-the-counter (OTC) agents can be used safely, this often runs counter to labelled warnings/contraindications, especially for the statins and other commonly used agents. AIM: To evaluate published data on the use of hepatotoxic drugs in chronic liver disease including pharmacokinetic changes in cirrhosis and drug interactions, where available, to formulate recommendations on their use. METHODS: Using a combination of PubMed searches, review texts, the Physicians' Desk Reference and expert opinion, drugs considered at higher risk of hepatotoxicity in chronic liver disease were evaluated. RESULTS: Most drugs and OTC products including herbals have not been formally studied in chronic liver disease, but available data suggest that several of the most commonly used agents, especially the statins, can be used safely. While there is an increased risk of drug-induced liver injury for drugs used in the treatment of tuberculosis and HIV patients with hepatitis B or C, recommendations for their safe use are emerging. CONCLUSIONS: Although many clinicians remain hesitant to use hepatotoxic drugs in chronic liver disease, the database supporting this view is limited to just a few agents. Most medications can be used safely in patients with chronic liver disease with appropriate monitoring.

Maheshwari A, Ray S, Thuluvath PJ. · Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Lancet. · Pubmed #18657711 No free full text.

Abstract: Symptomatic acute hepatitis C occurs in only about 15% of patients who are infected with hepatitis C virus (HCV). Acute hepatitis C is most often diagnosed in the setting of post-exposure surveillance, or seroconversion in high-risk individuals (eg, health-care professionals or injecting drug users) previously known to be seronegative. Although transmission via transfusion and injecting drug use has declined in developed countries, unsafe blood products and medical practices continue to increase transmission of HCV in many developing countries. Clinically, acute hepatitis C can increase concentrations of alanine aminotransferase to ten times the upper limit of normal but almost never causes fulminant hepatic failure. Diagnosis of HCV infection in the acute phase is difficult since production of antibodies against HCV can be delayed by up to 12 weeks, and about a third of infected individuals might not have detectable antibody at the onset of symptoms. Therefore, testing for HCV RNA by PCR is the only reliable test for the diagnosis of acute infection. Symptomatic patients with jaundice have a higher likelihood of spontaneous viral clearance than do asymptomatic patients, and thus should be monitored for at least 12 weeks before initiating antiviral therapy. By contrast, asymptomatic patients have a much lower chance of spontaneous clearance, and might benefit from early antiviral therapy. Antiviral therapy for 12 weeks is generally effective in treating patients who are HCV RNA negative after 4 weeks of treatment; lengthier courses could be needed for those who relapse or fail to show early virological clearance.

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.