Hepatitis: Baltimore

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

This publication has no abstract.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Groopman JD, Kensler TW, Wild CP. · Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA. · Annu Rev Public Health. · Pubmed #17914931 No free full text.

Abstract: The public health impact of aflatoxin exposure is pervasive in economically developing countries; consequently, we need to design intervention strategies for prevention that are practicable for these high-risk populations. The adverse health consequences of aflatoxins in populations are quite varied, eliciting acute effects, such as rapid death, and chronic outcomes, such as hepatocellular carcinoma. Furthermore, a number of epidemiological studies describe a variety of general adverse health effects associated with aflatoxin, such as impaired growth in children. Thus, the magnitude of the problem is disseminated across the entire spectrum of age, gender, and health status in the population. The aflatoxins multiplicatively increase the risk of liver cancer in people chronically infected with hepatitis B virus (HBV), which illustrates the deleterious impact that even low toxin levels in the diet can pose for human health. Thus other aflatoxin interactions, which likely contribute to the disease burden, still remain to be identified. Therefore, many diverse and appropriate strategies for disease prevention are needed to decrease the incidence of aflatoxin carcinogenesis in developing countries.

Baral S, Sherman SG, Millson P, Beyrer C. · Center for Public Health and Human Rights, Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA. · Lancet Infect Dis. · Pubmed #17897609 No free full text.

Abstract: Injection drug use is a prevalent global phenomenon; one not bound by a country's level of development or geographical location. Injection drug users (IDUs) are at high risk for a variety of parenterally acquired and transmitted infections. Licensed vaccines are available for some of these infectious diseases, such as tetanus, influenza, and hepatitis A and B viruses; however, there have been conflicting reports as to their immunogenicity in IDUs. We summarise the lessons learned from studies evaluating the immunogenicity of vaccination strategies in IDUs. A common theme across these diseases is that although there is a tendency towards decreased antibody responses after immunisation, there is no conclusive evidence linking these observations to a decrease in clinical protection from infection. There is a clear need for definitive studies of vaccination strategies in IDUs; however, a synthesis of the available published evidence suggests that immunisation does result in effective clinical protection from disease in this population. The inclusion of IDUs as a high-risk study population in future trials evaluating HIV and hepatitis C virus vaccines will help to assess the immunogenicity of candidate vaccines against parenteral exposure, and also to evaluate the efficacy of candidates as promising antigens become available.

Yates MS, Kensler TW. · Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA. · Acta Pharmacol Sin. · Pubmed #17723167 links to  free full text

Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, causing nearly 600,000 deaths each year. Increased risk of HCC due to chronic infection with hepatitis B virus (HBV) and exposure to dietary aflatoxins is responsible for many of these deaths. Prevention strategies targeting HBV infection and aflatoxin exposure could dramatically impact the rates of HCC. Universal HBV vaccination programs have begun in some high-risk areas. Strategies to reduce aflatoxin contamination in food stores have also been implemented. However, complete elimination of aflatoxin contamination might not be possible. For this reason, chemoprevention strategies which alter aflatoxin disposition are a practical strategy to reduce the incidence of HCC in populations with high dietary aflatoxin exposure. The mechanisms of aflatoxin-induced hepatocarcinogenesis are well known. This knowledge provides the basis for evaluation of both exposures to aflatoxin, as well as modulation of aflatoxin disposition by chemopreventive agents. Products of aflatoxin DNA damage and toxicity as well as other metabolites can be used as biomarkers to evaluate modulation of aflatoxin disposition. Modulation of aflatoxin disposition can be achieved through induction of conjugating and cytoprotective enzymes. Many of these enzymes are regulated through Kelch ECH-associating protein 1 (Keap1)-NF-E2-related factor 2(Nrf2)-antioxidant response element (ARE) signaling, making this pathway an important molecular target for chemoprevention. Rodent studies have identified several classes of chemopreventive agents which induce cytoprotective genes. These inducers include phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids. Furthermore, clinical interventions have shown that inducers of Keap1-Nrf2- ARE signaling increase cytoprotective enzyme expression, resulting in modulation of aflatoxin disposition. Much work remains to be done in order to take promising chemopreventive agents from preclinical evaluation to application in at-risk populations. However, appropriately designed clinical trials will aid in this process, which can have profound impact on the incidence of HCC.

Sulkowski MS. · Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. · J Acquir Immune Defic Syndr. · Pubmed #17704690 No free full text.

This publication has no abstract.

Valsamakis A. · Department of Pathology, The Johns Hopkins Hospital, 600 North Wolfe St., Meyer B1-193, Baltimore, MD 21287, USA. · Clin Microbiol Rev. · Pubmed #17630333 links to  free full text

Abstract: Hepatitis B virus (HBV) is an enveloped virus with a small (3.2-kb) partially double-stranded DNA genome that causes acute and chronic infections. The impact of these infections on public health worldwide is enormous, with an estimated prevalence of 2 billion acute infections and 360 million chronic infections globally. This review focuses on chronic hepatitis B and the molecular assays used in its diagnosis and management. Background information, including that about features of the hepatitis B virion, viral replication, and epidemiology of infection, that is important for understanding chronic hepatitis B and molecular diagnostic tests for HBV is provided. To facilitate an understanding of the utility of molecular testing for chronic hepatitis B, the four stages of chronic hepatitis B infection that are currently recognized, as well as an additional entity, occult hepatitis B, that can be diagnosed only by sensitive nucleic acid amplification methods, are reviewed in detail, including available therapeutic agents. The molecular diagnostic content focuses on tests for HBV DNA quantification, genotyping, and mutation detection (including precore/core promoter and antiviral resistance mutations). The discussion of these tests encompasses their current utility and performance characteristics, drawing from current clinical guidelines and other studies from the literature. In recognition of the continual evolution of this field, the final section describes emerging molecular markers with future diagnostic potential.

Thornton K. · Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. · Tech Vasc Interv Radiol. · Pubmed #17561213 No free full text.

Abstract: Interventional procedures for oncology patients are being used more frequently in the front line and palliative setting. It is important that interventional radiologists familiarize themselves with some of the frequently encountered symptoms and potential complications and develop guidelines to help manage and sometimes prevent these complications from occurring. Unfortunately, there is not much data to support various supportive measures specifically for the post-procedural patient. However, by extrapolating the information available for the management of systemic chemotherapy patients, as well as discussing the steps that can be taken to avoid certain complications like acute renal failure, we as oncologists and interventional radiologists can better care for this unique and often complicated patient population.

Gallant JE. · Division of Infectious Diseases, Johns Hopkins University School of Medicine, 1830 East Monument Street, Room 443, Baltimore, MD 21205, USA. · Curr HIV/AIDS Rep. · Pubmed #17547825 No free full text.

Abstract: Current treatment guidelines recommend that antiretroviral therapy be deferred until the CD4 count has fallen into the 200 to 350 cells/mm(3) range. However, treatment has become simpler, less toxic, and more forgiving of missed doses. Longer-term follow-up data from clinical cohorts are now showing better outcomes when therapy is started at higher CD4 cell counts. Therapy initiated early has better virologic and immunologic responses, is better tolerated, and is cost-effective. Recent developments and clinical data support a return to earlier initiation of therapy.

Hoffmann CJ, Thio CL. · Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. · Lancet Infect Dis. · Pubmed #17521593 No free full text.

Abstract: Hepatitis B virus (HBV) is the leading cause of chronic liver disease and liver-related death worldwide, with the majority of these cases occurring in areas of Africa and Asia where HBV prevalence is high. Many of the countries that are affected by hepatitis B are also affected by a high HIV burden, leading to frequent HIV/HBV co-infection. The consequences of co-infection, including increased liver-related morbidity and mortality, increased hepatitis B viral replication, immune reconstitution to HBV in the setting of antiretroviral therapy, and hepatotoxicity from antiretroviral drugs, are especially important in regions with expanding antiretroviral programmes. Little data, however, are available on HIV/HBV co-infection from regions with high chronic hepatitis B prevalence. This Review discusses the epidemiology, natural history, pathogenesis, and management of HIV/HBV co-infection from these areas. Topics for future research relevant to HIV/HBV co-infection in Africa and Asia are also highlighted.

Sulkowski MS, Benhamou Y. · Department of Medicine, Division of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0003, USA. · J Viral Hepat. · Pubmed #17501757 links to  free full text

Abstract: The importance of treating hepatitis C virus (HCV)-associated morbidities in a growing population of patients coinfected with human immunodeficiency virus (HIV) has increased since the introduction of highly active antiretroviral therapy. As a result, investigative attention is turning to HCV-related liver disease and treatment-associated issues in coinfection. HIV/HCV-coinfected patients have higher HCV RNA loads and show more rapid progression of fibrosis than do monoinfected patients. Combination therapy with pegylated interferon plus ribavirin (RBV) is the standard of care for HCV in coinfected patients. Therapy slows fibrosis progression, but toxicity prevents identification of the most effective RBV dose. Coinfected patients have about a threefold greater risk of antiretroviral therapy-associated hepatotoxicity than patients with HIV only. Other challenges include anaemia, mitochondrial toxicity, drug-drug interactions and leucopenia. Thus, chronic hepatitis C should be treated in HIV/HCV-coinfected patients, but steps must be taken to prevent and treat potential toxicities. The first European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected Patients was held March 2005 in Paris to address these issues. This article reviews the peer-reviewed literature and expert opinion published from 1990 to 2005, and compares results with presentations and recommendations from the Consensus Conference to best present current issues in coinfection.

Thio CL, Locarnini S. · Department of Medicine, Johns Hopkins University, 424 North Bond St, Baltimore, MD 21231, USA. · AIDS Rev. · Pubmed #17474312 No free full text.

Abstract: Chronic hepatitis B affects nearly 10% of HIV-infected patients. Thus, approximately four million people worldwide are HBV/HIV coinfected. Hepatitis B virus (HBV) infection is a dynamic disease and coinfection with HIV impacts directly on the outcome of HBV infection, considerably complicating its natural history, diagnosis, and management. Hepatic necroinflammation is lower in HBV/HIV coinfection, yet liver damage, especially fibrosis, progresses at a faster rate than in HBV monoinfection. With improved control of HIV disease with HAART, liver disease has emerged as one of the leading causes of death in patients with HIV Anti-HBV therapy should be considered for all HIV/HBV-coinfected patients with evidence of liver disease, irrespective of the CD4 cell count. In coinfected patients not requiring HAART, HBV therapy should be based on agents with no HIV activity such as adefovir. In contrast, in patients with CD4 counts less than 350 cells/microl, the use of agents with dual anti-HIV and anti-HBV activity should be considered. Combination therapy should ideally be used to avoid or delay the development of antiviral resistance. Regular monitoring of patients is imperative to recognize reactivation and subsequent need for treatment, and to identify drug resistance and viral breakthrough early. Similar close monitoring is required for patients presenting with advanced HIV infection and reduced functional hepatic reserve due to HBV-related cirrhosis. Effective antiviral treatment can precipitate immune reconstitution disease resulting in serious hepatic flare and precipitating liver decompensation. Clearly, more data are needed to more effectively treat HIV/HBV coinfection.

Sulkowski MS. · Johns Hopkins University School of Medicine, 600 North Wolfe Street, 1830 Building, Room 448, Baltimore, MD 21287, USA. · Curr Gastroenterol Rep. · Pubmed #17335672 No free full text.

Abstract: Since the discovery of the hepatitis C virus (HCV) as the major cause of non-A, non-B hepatitis in 1989, the search for specific targeted antiviral therapy for HCV (STAT-C) has been underway. Recently, major advances in the understanding of HCV biology and the development of an in vitro system of HCV replication have contributed to the selection of multiple candidate drugs for the treatment of hepatitis C. In 2006, five such candidate drugs have entered phase II clinical trials in patients chronically infected with hepatitis C, including small molecule inhibitors of the HCV NS3 serine protease and NS5B RNA-dependent RNA polymerase. This review focuses on hepatitis C protease and polymerase inhibitors that have progressed to phase II clinical development, foreshadowing the era of STAT-Cs.