Hepatitis: Washington area

Thio CL. · Department of Medicine, Division of Infectious Diseases, Johns Hopkins University, Baltimore, MD 21205, USA. <> · Clin Liver Dis. · Pubmed #18625436 links to  free full text

Abstract: Human genome variations explain some of the heterogeneity in the immune response to antigenic stimuli. Such differences in response to hepatitis C virus (HCV) antigens can account for the ability of the immune response to clear HCV after an acute infection or to develop more rapidly progressive liver disease. Several studies have examined polymorphisms in several candidate immune-response genes for their relation to these HCV outcomes. Results of some of these studies complement knowledge gained from immunology studies, and others offer new insights into HCV biology. This review summarizes published studies on variation in immune-response genes and HCV outcomes.

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.

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.

Fine DM, Perazella MA, Lucas GM, Atta MG. · Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Drugs. · Pubmed #18457462 No free full text.

Abstract: With the introduction of highly active antiretroviral therapy, we have witnessed prolonged survival with the potential for normal life expectancy in HIV-infected individuals. With improved survival and increasing age, HIV-infected patients are increasingly likely to experience co-morbidities that affect the general population, including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C, cigarette smoking and injection drug use. Furthermore, they have exposures unique to this population, including antiretrovirals and other medications. Therefore, the differential diagnosis is vast.Early identification (through efficient screening) and definitive diagnosis (by kidney biopsy when indicated) of kidney disease in HIV-infected individuals are critical to optimal management. Earlier interventions with disease-specific therapy, often with the help of a nephrologist, are likely to lead to better outcomes. In those with chronic kidney disease, interventions, such as aggressive blood pressure control with the use of ACE inhibitors or angiotensin receptor antagonists where tolerated, tight blood glucose control in those with diabetes, and avoidance of potentially nephrotoxic medications, can slow progression and prevent end-stage renal disease. Only with greater awareness of kidney-disease manifestations and their implications in this particularly vulnerable population will we be able to achieve success in confronting this growing problem.

Sulkowski MS. · Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA. · J Infect Dis. · Pubmed #18447614 No free full text.

Abstract: In the era of effective antiretroviral therapy (ART), liver disease is the second most common cause of death among persons with human immunodeficiency virus (HIV) infection. Liver disease-related deaths mostly result from chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). In addition, recent reports suggest that HCV infection may be transmitted sexually between HIV-infected men who have sex with men. Management of these conditions in HIV-infected persons requires careful consideration, balancing the potential benefits of therapy with the potential for significant treatment-related adverse effects (HCV infection) and viral resistance and/or hepatitis flares (HBV infection). Furthermore, several antiretroviral agents are active against HBV infection, including lamivudine, emtricitabine, tenofovir, and, more recently, entecavir. Despite the complexity and potential for antiretroviral-associated hepatotoxicity, ART usually is safe for patients with viral hepatitis coinfection, and, in some cases, treatment for HIV infection may be beneficial for the liver.

Norris W, Paredes AH, Lewis JH. · Hepatology Section, Division of Gastroenterology, Georgetown University Hospital, Georgetown University Medical Center, Washington, DC 20007, USA. · Curr Opin Gastroenterol. · Pubmed #18408456 No free full text.

Abstract: PURPOSE OF REVIEW: To summarize the pertinent literature on the causes, epidemiology, prevalence, clinical features, evaluation and mechanisms of drug-induced liver injury reported during 2007. RECENT FINDINGS: Although the frequency of drug-induced liver injury remains low, new data from the Centers for Disease Control and Prevention confirm that of the approximately 1600 new acute liver failure cases annually, acetaminophen hepatotoxicity accounts for 41%; among children with acute liver failure, acetaminophen was the second most common cause. Antimicrobials lead the list of non-acetaminophen causes of drug-induced liver injury. In Asia, herbal compounds are the most common causes of the condition. Pravastatin was shown to be safe in patients with nonalcoholic fatty liver disease or chronic hepatitis C. The US Food and Drug Administration issued a draft guidance document on the premarketing clinical evaluation and stopping rules of drug-induced liver injury signals, including Hy's Law cases in clinical trials. SUMMARY: The year 2007 brought with it several reminders of the importance of drug-induced liver injury in the clinical trial as well as the clinical practice setting. There is additional evidence that statin drugs may be used safely in patients with chronic liver disease. Comments received by the US Food and Drug Administration to finalize their guidance document are eagerly awaited.

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.

Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F, Csako G. · National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland 20892, USA. · Ann Intern Med. · Pubmed #18378948 links to  free full text

Abstract: BACKGROUND: Lamivudine is increasingly being used to prevent hepatitis B reactivation in patients with cancer who test positive for hepatitis B surface antigen (HBsAg) and are undergoing chemotherapy. PURPOSE: To determine whether preventive lamivudine reduces chemotherapy-induced hepatitis B virus (HBV)-related morbidity and mortality in patients with cancer who test positive for HBsAg. DATA SOURCES: MEDLINE, Ovid MEDLINE, TOXNET, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched in all languages until June 2007. STUDY SELECTION: Clinical trials and cohort studies that reported the efficacy of preventive lamivudine versus control on HBV reactivation in patients who tested positive for HBsAg and were receiving chemotherapy were included. Additional requirements included minimum sample size (>5 participants per treatment group) and reported HBV-related morbidity and mortality data. DATA EXTRACTION: Two investigators independently did literature searches and data extraction, and 2 other investigators independently confirmed study eligibility and data retrieval. DATA SYNTHESIS: Fourteen studies (2 randomized, controlled trials; 8 prospective cohort studies; and 4 retrospective cohort studies) met the predefined criteria for analysis. There were 275 patients in the preventive lamivudine group and 475 control participants for the primary end point of HBV reactivation. With preventive lamivudine, the relative risk for both HBV reactivation and HBV-related hepatitis ranged from 0.00 to 0.21. None of the patients in the preventive lamivudine group developed HBV-related hepatic failure (0 of 108 patients vs. 21 of 162 patients), and only 4 deaths were attributable to HBV (4 of 208 patients vs. 27 of 394 patients) in the preventive lamivudine group. Lamivudine was well tolerated, and no adverse effects were noted. LIMITATIONS: The studies included in the meta-analysis did not consistently report all of the outcomes of interest. Sample sizes were small and only 2 studies had a randomized, controlled design. CONCLUSION: Preventive therapy with lamivudine for patients who test positive for HBsAg and are undergoing chemotherapy may reduce the risk for HBV reactivation and HBV-associated morbidity and mortality.

Stephen S, Borum M. · Department of Medicine, George Washington University, 900 23rd Street NW, #51074 South, Washington, DC 200037, USA. · Dig Dis Sci. · Pubmed #18357532 No free full text.

This publication has no abstract.

Li TK. · National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland 20892-9304, USA. · J Gastroenterol Hepatol. · Pubmed #18336658 No free full text.

Abstract: The aim of the present review was to: (i) highlight epidemiological and other studies that have generated important data on the harmful patterns of drinking that increase the risk for chronic diseases, including alcohol dependence, and on the mechanisms by which alcohol produces and, in some instances, may protect against damage; and (ii) discuss a conceptual basis for quantifying risk criteria for alcohol-induced chronic disease based on the quantity, frequency, and pattern of drinking. The relationship between heavy drinking and risk for adverse health conditions such as alcoholic liver disease (ALD), dementia, and alcohol dependence is well known. However, not everyone who drinks chronically develops ALD or dementia, and the major risk factors for disease development and the mechanisms by which this occurs have remained unclear. Large-scale, general population-based studies have provided the evidence by which quantifying the frequency of a pattern of high-risk drinking can be related directly to risk and the severity of alcohol dependence. Cellular and molecular biology studies have identified the major pathways of alcohol metabolism and how genetics and the environment can interact in some individuals to further increase the risk of organ damage. Extant databases should allow scientists and clinicians jointly to develop the framework for quantifying the drinking patterns that increase the risk of alcohol-induced organ pathologies, to develop clinical practice guidelines, such as those used to diagnose other common complex diseases (e.g. diabetes and hypertension), and to propose future studies for refining such guidelines. Attention must be paid to comorbid conditions such as hepatitis B and C infections, HIV, obesity, and environmental exposures other than alcohol. Developing trait and state biomarkers is critical to the process of discovery and to fulfilling the promise of personalized medicine.

Jagannath S, Puri K, Kantsevoy S, Thuluvath PJ. · Department of Medicine, The Johns Hopkins Hospital, 1830 Monument Street, Baltimore, MD 21287, USA. · Minerva Gastroenterol Dietol. · Pubmed #18319685 No free full text.

Abstract: Liver cancer is one of the most frequent solid cancers. The major risk factor associated with the development of hepatocellular carcinoma (HCC) is cirrhosis caused by hepatitis B, hepatitis C virus or chronic alcohol consumption. The overall prognosis of patients with HCC is very poor and this is mainly due to the advanced stages of cancer at presentation and also because of underlying cirrhosis. When HCC is diagnosed at early stages, prognosis is better with five-year disease free survival of around 50% with resection, or local ablative treatments such as radio-frequency ablation or percutaneous ethanol injection, and 70-80% with liver transplantation. Therefore, systematic screening of all the high-risk patients is the key to an early diagnosis of small HCC and the use of an appropriate treatment modality. The currently available tools for the screening, surveillance and diagnosis of HCC in the presence of cirrhosis remain sub-optimal. The advancements made in the past 10 years, however, have made HCC a potentially curable disease in a highly selected group of patients. This review will briefly discuss the current guidelines for surveillance and diagnosis of HCC in high-risk subjects and then review the potential role of endoscopic ultrasound and fine needle aspiration for the diagnosis of small HCC.

Loomba R, Liang TJ. · Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MA, USA. · Antivir Ther. · Pubmed #18284181 No free full text.

Abstract: Hepatitis B virus (HBV) infection is the leading cause of chronic liver disease and hepatocellular carcinoma worldwide. Approximately 350 million individuals are infected with HBV and >500,000 deaths per year can be attributed to HBV. Although universal vaccination has reduced HBV incidence in many countries, it still remains a major public health problem, especially in parts of Asia and Africa. Improved understanding of HBV virology and virus-host interactions has revolutionized chronic hepatitis B therapy in the past two decades. Development of oral nucleoside/nucleotide analogues heralds a new era of safe and effective treatment of this disease. On the basis of these advances, new guidelines for the treatment of chronic hepatitis B have been issued. Successful long-term treatment of chronic hepatitis B may rest on combination therapy that is based on molecular approaches targeting various stages of the HBV life-cycle. In this review, we summarize the current modalities and highlight important issues in the treatment of chronic hepatitis B monoinfection.

Thio CL. · Johns Hopkins University, Baltimore, MD, USA. · Antivir Ther. · Pubmed #18284180 No free full text.

Abstract: With the recent approval of several drugs for the management of chronic hepatitis B, the proper diagnosis and classification of this disease is necessary to determine if therapy is needed and what the best treatment options are. The diagnosis of chronic hepatitis B relies on serological testing, and disease stage is further characterized with HBV DNA levels and an assessment of liver disease through biopsy or non-invasive methods. A regular screening protocol is necessary for patients with chronic hepatitis B to monitor the development of cirrhosis and hepatocellular carcinoma. Patients receiving treatment also need regular monitoring for response to determine if a different therapeutic regimen is needed or if drug-resistant variants are being selected. This review discusses the various tests for hepatitis B diagnosis and for monitoring disease progression and treatment response. In addition, noninvasive methods for classifying liver disease stage are discussed, as are special considerations that are needed for individuals coinfected with HIV.

Nath A, Schiess N, Venkatesan A, Rumbaugh J, Sacktor N, McArthur J. · Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA. · Int Rev Psychiatry. · Pubmed #18240060 No free full text.

Abstract: Dementia remains one of the most fearsome complications of HIV infection. It also poses a significant challenge for the clinician both in terms of diagnosis and treatment. The use of antiretroviral agents has led to a decrease in the incidence of HIV dementia but the prevalence of milder forms of neurocognitive impairment has increased. Occasionally, the immune reconstitution caused by these agents may target the brain leading to a syndrome characterized by a severe, progressive and often fatal dementia. The progression of HIV dementia may also be determined by host and viral genetic factors, and the existence of co-morbid factors such as drug abuse, hepatitis C infection and aging. Oxidative stress markers appear to be predictive of active dementia. However, currently there is no specific treatment available for HIV dementia.

Pacher P, Gao B. · Laboratory of Physiological Studies, National Institutes of Health/NIAAA, 5625 Fishers Lane, MSC-9413, Bethesda, Maryland 20892-9413, USA. · Am J Physiol Gastrointest Liver Physiol. · Pubmed #18239059 links to  free full text

Abstract: Recent studies have implicated dysregulation of the endocannabinoid system in various liver diseases and their complications (e.g., hepatitis, fibrosis, cirrhosis, cirrhotic cardiomyopathy, and ischemia-reperfusion), and demonstrated that its modulation by either cannabinoid 2 (CB(2)) receptor agonists or CB(1) antagonists may be of significant therapeutic benefits. This review is aimed to focus on the triggers and sources of endocannabinoids during liver inflammation and on the novel role of CB(2) receptors in the interplay between the activated endothelium and various inflammatory cells (leukocytes, lymphocytes, etc.), which play pivotal role in the early development and progression of inflammatory and other liver diseases.

Xiao X, Dimitrov DS. · CCRNP, CCR, NCI-Frederick, NIH, Frederick, Maryland 21702-1201, USA. · Recent Pat Antiinfect Drug Discov. · Pubmed #18221173 No free full text.

Abstract: Antibodies have a long, successful and yet bumpy history of effectiveness against viruses and bacteria. Polyclonal antibodies have a century-old history of being effective against some viruses and bacteria; recently, monoclonal antibodies (mAbs) have also shown success. The humanized mAb Synagis (palivizumab), which is still the only mAb against a viral disease approved by the U.S. Food and Drug Administration (FDA), has been widely used as a prophylactic measure against respiratory syncytial virus (RSV) infections in neonates and immune-compromised individuals. Patents and patent applications in anti-infective monoclonal antibodies reflect to certain degree the advancement of the relevant technologies, the room for improvement, and the potential for commercialization. This article reviews representative monoclonal antibody patents and patent applications that reflect the current state of monoclonal antibody development and its future prospects.

Purcell RH, Emerson SU. · Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-8009, USA. · J Hepatol. · Pubmed #18192058 No free full text.

Abstract: Although hepatitis E was recognized as a new disease in 1980, the virus was first visualized in 1983 and its genome was cloned and characterized in 1991, the disease is probably ancient but not recognized until modern times. Hepatitis E is the most important or the second most important cause of acute clinical hepatitis in adults throughout Asia, the Middle East and Africa. In contrast, hepatitis E is rare in industrialized countries, but antibody (anti-HEV) is found worldwide. HEV is a small round RNA-containing virus that is the only member of the genus Hepevirus in the family Hepeviridae. Although similar to hepatitis A virus in appearance, there are significant differences between the two viruses. Hepatitis E is principally the result of a water-borne infection in developing countries and is thought to be spread zoonotically (principally from swine) in industrialized countries. Because diagnostic tests vary greatly in specificity, sensitivity and availability, hepatitis E is probably underdiagnosed. At present, control depends upon improved hygiene; a highly efficacious vaccine has been developed and tested, but it is not presently available.

Thomas DL. · Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA. · Annu Rev Med. · Pubmed #18186707 No free full text.

Abstract: Hepatitis C virus (HCV) coinfection occurs in an estimated one quarter of HIV-infected persons in Europe, Australia, and the United States. As use of highly active antiretroviral drugs has markedly reduced opportunistic infections, HCV-related liver disease has emerged as a leading cause of death. HIV infection adversely affects both the natural history and the treatment of hepatitis C. Because there are no experimental models of coinfection and because the pathogenesis of each infection is incompletely understood, how HIV infection alters hepatitis C is not clear. This review considers the epidemiology, natural history, treatment, and pathogenesis of hepatitis C in HIV-infected persons.

Modi AA, Liang TJ. · The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. · Oral Dis. · Pubmed #18173443 No free full text.

Abstract: Hepatitis C is a major cause of chronic liver disease. It has been recognized as a global health problem because of the progression to cirrhosis and hepatocellular cancer. Chronic hepatitis C is usually asymptomatic but can cause considerable liver damage before its recognition. This review discusses the natural history, clinical features, diagnosis, therapy, treatment responses and the side effects associated with the treatment of hepatitis C.

Sulkowski MS. · Johns Hopkins University School of Medicine, 600 North Wolfe Street, 1830 Building, Room 448, Baltimore, MD 21287, USA. · J Hepatol. · Pubmed #18155314 No free full text.

Abstract: Persons at high risk for human immunodeficiency virus (HIV) infection are also likely to be at risk for other infectious pathogens, including hepatitis B virus (HBV) or hepatitis C virus (HCV). These are bloodborne pathogens transmitted through similar routes; for example, via injection drug use (IDU), sexual contact, or from mother to child during pregnancy or birth. In some settings, the prevalence of coinfection with HBV and/or HCV is high. In the context of effective antiretroviral therapy (ART), liver disease has emerged as a major cause of morbidity and mortality in HIV-infected persons. Further, coinfection with viral hepatitis may complicate the delivery of ART by increasing the risk of drug-related hepatoxicity and impacting the selection of specific agents (e.g., those dually active against HIV and HBV). Expert guidelines developed in the United States and Europe recommend screening of all HIV-infected persons for infection with HCV and HBV and appropriate management of those found to be chronically infected. Treatment strategies for HBV infection include the use of nucleos(t)ide analogues with or without anti-HIV activity and/or peginterferon alfa (PegIFN) whereas HCV treatment is limited to the combination of PegIFN and ribavirin (RBV). Current approaches to management of HIV-infected persons coinfected with HBV or HCV are discussed in this review.

Subramanian GM, Fiscella M, Lamousé-Smith A, Zeuzem S, McHutchison JG. · Human Genome Sciences, Inc., 14200 Shady Grove Road, Rockville, Maryland 21042, USA. · Nat Biotechnol. · Pubmed #18066038 No free full text.

Abstract: Treatment regimens based on the use of interferon-alpha (IFN-alpha) remain the cornerstone of therapy for chronic hepatitis C virus infection, which affects nearly 170 million people worldwide. Treatment options include unmodified IFN-alpha given three times weekly or pegylated IFNs given once weekly. The albumin-fusion platform takes advantage of the long half-life of human albumin to provide a new treatment approach that allows the dosing frequency of IFN-alpha to be reduced in individuals with chronic hepatitis C. Albinterferon alpha-2b (alb-IFN), a recombinant polypeptide composed of IFN-alpha2b genetically fused to human albumin, has an extended half-life and early evidence indicates that it is efficacious and well tolerated. Pharmacodynamic modeling supports treatment with alb-IFN at 2- or 4-week intervals. Phase 3 registration trials are in progress. The albumin-fusion platform is currently being applied to other important bioactive peptides with short half-lives. These fusion proteins, which are at present in different phases of clinical development, might lead to improved therapies across a broad range of diseases.

Zakhari S, Li TK. · National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9304, USA. · Hepatology. · Pubmed #18046720 No free full text.

Abstract: More than 70% of alcohol is consumed by 10% of the population in the United States. Implicit in this statistic is that tremendous variation in the pattern of drinking (quantity, frequency, and duration) exists among alcohol consumers. Individuals who are binge or chronic drinkers will have different health outcomes than social drinkers. Therefore, knowing the pattern of drinking will shed light on how severely individuals are alcohol-dependent and on the extent of liver damage. Thus, these parameters assume particular relevance for the treatment-providing physician. Genetic factors contribute substantially to differences in alcohol metabolism. Variations in the activities of the alcohol-metabolizing enzymes, cytosolic alcohol dehydrogenase and mitochondrial aldehyde dehydrogenase, in part determine blood alcohol concentration, thereby contributing to the predisposition to becoming alcohol-dependent and to susceptibility to alcohol-induced liver damage. Chronic alcohol consumption induces cytochrome P450 2E1, a microsomal enzyme that metabolizes alcohol at high concentrations and also metabolizes medications such as acetaminophen and protease inhibitors. Alcohol metabolism changes the redox state of the liver, which leads to alterations in hepatic lipid, carbohydrate, protein, lactate, and uric acid metabolism. The quantity and frequency of alcohol consumption severely impact the liver in the presence of comorbid conditions such as infection with hepatitis B or C and/or human immunodeficiency virus, type 2 diabetes, hemochromatosis, or obesity and thus have implications with respect to the extent of injury and response to medications. Conclusion: Knowledge of the relationships between the quantity, frequency, and patterns of drinking and alcoholic liver disease is limited. A better understanding of these relationships will guide hepatologists in managing alcoholic liver disease.

Emerson SU, Purcell RH. · Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. · Pediatr Infect Dis J. · Pubmed #18043454 No free full text.

This publication has no abstract.

Gonzalez FJ, Shah YM. · National Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA. · Toxicology. · Pubmed #18006136 No free full text.

Abstract: Peroxisome proliferator chemicals are classic non-genotoxic carcinogens. These agents cause liver cancers when chronically administered to rats and mice. Peroxisome proliferators include the widely prescribed lipid and cholesterol lowering fibrate drugs. In contrast to the results in rodents, there is no evidence that fibrates are associated with elevated risk of liver cancer or any other neoplasms in humans thus indicating a species difference in the hepatocarcinogenic response. The biological effects of peroxisome proliferators are mediated by the peroxisome proliferator-activated receptor (PPAR)alpha. Pparalpha-null mice are resistant to all of the pleiotropic effects of peroxisome proliferators, including cell proliferation and hepatocarcinogenesis. The mechanism of hepatocellular proliferation involves downregulation of the microRNA let-7c gene by PPARalpha. Let-7c controls levels of proliferative c-myc by destabilizing its mRNA. Thus, upon suppression of let-7c, c-myc mRNA and protein are elevated resulting in enhanced hepatocellular proliferation. In contrast, PPARalpha-humanized mice, that respond to Wy-14,643 by lower serum triglycerides and induction of genes encoding fatty acid metabolizing enzymes, are resistant to peroxisome proliferator-induced cell proliferation and cancer. These mice do not exhibit downregulation of let-7c gene expression thus forming the basis for the resistance to hepatocellular carcinogenesis.