Hepatitis: Philadelphia

Mehta G, Rothstein KD. · Division of Gastroenterology and Hepatology, Department of Medicine, Drexel University College of Medicine, Mail Stop 913, 5th Floor, 219 N. Broad Street, Philadelphia, PA 19107, USA. · Med Clin North Am. · Pubmed #19577121 No free full text.

Abstract: Caring for patients with cirrhosis requires special consideration. The role of the hepatologist is to assist the primary care physician in caring for such patients. This involves an active role in immunizations, lifestyle modifications, and providing instructions on when to go to the emergency room (ER). There are also specific recommendations geared toward the patient with cirrhosis relating to slowing down the disease process, maintaining quality of life, and improving survival.

Mackelaite L, Alsauskas ZC, Ranganna K. · Division of Nephrology, Department of Medicine, Drexel University College of Medicine, 245 North 15th Street, Room 6144, Philadelphia, PA 19102, USA. · Med Clin North Am. · Pubmed #19577118 No free full text.

Abstract: Renal failure in cirrhosis poses unique diagnostic and therapeutic challenges. Laboratory values and predictive equations grossly overestimate renal function in patients with cirrhosis. Development of renal failure connotes a worse prognosis; mortality is especially high with hepatorenal syndrome. Classification of the causes of renal failure in patients with cirrhosis is provided with more extensive discussion of selected causes. Finally, a suggested diagnostic approach to renal failure in cirrhosis is given.

Lefton HB, Rosa A, Cohen M. · Department of Medicine, Drexel University College of Medicine, 216 Broad Street, Mail 1001, Philadelphia, PA 19102, USA. · Med Clin North Am. · Pubmed #19577114 No free full text.

Abstract: Cirrhosis is defined histologically as an advanced form of progressive hepatic fibrosis with distortion of the hepatic architecture and regenerative nodule formation. It may be due to a variety of causes. It can be diagnosed incidentally on liver biopsy or hepatic imaging studies, or patients may present clinically with one or more features of hepatic failure. This article gives the reader a broad overview of the epidemiology, diagnosis, and natural history of cirrhosis; laying the foundation for subsequent articles, which will discuss the diagnosis and management of each of the specific cirrhosis-related complications.

Cines DB, Liebman H, Stasi R. · University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, Philadelphia, PA 19104, USA. · Semin Hematol. · Pubmed #19245930 No free full text.

Abstract: Primary immune thrombocytopenic purpura (ITP) remains a diagnosis of exclusion both from nonimmune causes of thrombocytopenia and immune thrombocytopenia that develops in the context of other disorders (secondary immune thrombocytopenia). The pathobiology, natural history, and response to therapy of the diverse causes of secondary ITP differ from each other and from primary ITP, so accurate diagnosis is essential. Immune thrombocytopenia can be secondary to medications or to a concurrent disease, such as an autoimmune condition (eg, systemic lupus erythematosus [SLE], antiphospholipid antibody syndrome [APS], immune thyroid disease, or Evans syndrome), a lymphoproliferative disease (eg, chronic lymphocytic leukemia or large granular T-lymphocyte lymphocytic leukemia), or chronic infection, eg, with Helicobacter pylori, human immunodeficiency virus (HIV), or hepatitis C virus (HCV). Response to infection may generate antibodies that cross-react with platelet antigens (HIV, H pylori) or immune complexes that bind to platelet Fcgamma receptors (HCV), and platelet production may be impaired by infection of megakaryocyte (MK) bone marrow-dependent progenitor cells (HCV and HIV), decreased production of thrombopoietin (TPO), and splenic sequestration of platelets secondary to portal hypertension (HCV). Sudden and severe onset of thrombocytopenia has been observed in children after vaccination for measles, mumps, and rubella or natural viral infections, including Epstein-Barr virus, cytomegalovirus, and varicella zoster virus. This thrombocytopenia may be caused by cross-reacting antibodies and closely mimics acute ITP of childhood. Proper diagnosis and treatment of the underlying disorder, where necessary, play an important role in patient management.

Reddy KR, Nelson DR, Zeuzem S. · GI Division, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, USA. · J Hepatol. · Pubmed #19091439 No free full text.

Abstract: Ribavirin in combination with peginterferon alfa shows strong clinical efficacy against chronic hepatitis C, and is now established as the standard of care. However, the precise role of ribavirin is still being defined, suggesting that optimal ribavirin dose should be maintained over the whole treatment period. Ribavirin dosage varies by bodyweight for genotype 1 disease (1000mg/day in patients <or =75kg and 1200mg/day in patients >75kg), whereas 800mg/day is sufficient to ensure optimal response in all genotype 2/3 patients. Similarly, genotype 1 patients benefit from 48 weeks of therapy, while 24 weeks is sufficient for genotype 2/3 disease. Recent data suggest treatment success is dependent on cumulative ribavirin exposure, as patients who receive <60% of the planned dose have lower response rates, regardless of whether reductions are from temporary interruptions or premature cessation of therapy. All patients should be monitored for hemolytic anemia, as early diagnosis allows management through small dose reductions and stepwise return to the target dose, maximizing cumulative exposure. Despite these recent advances in our knowledge, many questions remain, such as whether the role of ribavirin will change or even be eliminated as new therapies are developed.

Hashemi N, Rossi S, Navarro VJ, Herrine SK. · Thomas Jefferson University, Division of Gastroenterology and Hepatology, Philadelphia, PA, USA. · Expert Opin Drug Saf. · Pubmed #18983223 No free full text.

Abstract: BACKGROUND: Combination of 'pegylated' interferons (IFNs) plus ribavirin, the standard treatment of chronic hepatitis C (CHC), is frequently associated with side effects. Anticipation, recognition and proper management of these side effects are important to ensure compliance with therapy and achievement of sustained virologic response. OBJECTIVE: To illustrate the side effect profile of pegIFN-alpha in the treatment of CHC. METHODS: Studies and abstracts were identified through a computerized, English language literature search. Key search terms included peginterferon and CHC. Information available only in abstract form was retrieved from national and international hepatology associations. RESULTS: Most adverse events occurring with combination therapy can be anticipated and managed appropriately; therefore, premature discontinuation of therapy owing to side effects is not required in most patients.

Lang K, Weiner DB. · Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-6100, USA. · Expert Rev Vaccines. · Pubmed #18767942 No free full text.

Abstract: With more than 170 million individuals currently infected, HCV is a global pandemic, effecting approximately 3% of the entire world's population. HCV infection is a growing infectious disease pandemic with approximately 3-4 million new cases reported each year. Due to the persistent nature of the virus, 70-90% of infected individuals will develop chronic infection, which can lead to progressive liver disease including cirrhosis and hepatocellular carcinoma. Current standard treatment with a combination of IFN-alpha and ribavirin has improved the prognosis for many HCV sufferers; however, infection is very difficult to treat successfully and the protocol for treatment is neither simple, well tolerated nor economically favorable. Standard treatment can cost an average of US$22,000, and depending on genotype, as few as 42% of treated individuals will clear the infection. This collection of treatment issues combined with new concepts in immune therapy serve to underscore an urgent need for the development of improved immunotherapies, such as novel interferons, and support the possible development of therapeutic vaccines for the treatment of chronic HCV infection.

Tebas P. · AIDS Clinical Trials Unit, University of Pennsylvania, Philadelphia, PA 19104-4283, USA. · J Acquir Immune Defic Syndr. · Pubmed #18725817 No free full text.

Abstract: The contribution of current antiretroviral treatment regimens to the long-term survival of HIV-infected individuals is accompanied by increased risk of glucose metabolism abnormalities in this patient population. The risk of insulin resistance and diabetes in HIV-infected patients receiving antiretroviral treatment stems from 2 sources: exposure to the same environmental factors that have led to an increased incidence of these conditions in the general population and the negative effects on glucose metabolism inherent to components of antiretroviral treatment regimens. This article reviews the pathogenesis and diagnosis of insulin resistance and diabetes and the contribution of components of antiretroviral therapy regimens to increased risk for these conditions. Optimization of antiretroviral treatment regimens for HIV-infected patients with or at increased risk for development of abnormalities in glucose metabolism is discussed.

Feitelson MA, Clayton MM, Reis HM, Wu G, Lu EP. · Temple University, Department of Biology, College of Science and Technology, Suite 409, BioLife Science Building, 1900 North 12th Street, Philadelphia, PA 19122, USA. · Expert Opin Pharmacother. · Pubmed #18710349 No free full text.

Abstract: BACKGROUND: Hepatitis B virus (HBV) is a major etiologic agent of chronic liver disease (CLD) and hepatocellular carcinoma. Drugs have been developed and shown to be effective against HBV replication. These treatments are often associated with the resolution of CLD. However, they are too expensive, not well tolerated, and result in the development of resistance when given as mono or salvage therapies. In addition, most of these drugs target only the virus polymerase. OBJECTIVE: To revitalize the field, drugs with other targets and combination therapies need to be developed. METHODS: Major advances in HBV and liver cancer drug development over the past decade, focusing on Phase III trials and FDA-approved compounds, are presented. RESULTS/DISCUSSION: A number of potent nucleoside/nucleotide analogs are now available for treatment, but for the long-term management of CLD, the development of combination therapies will probably be required. Development of compounds with new virus targets will enhance the utility of combination therapies. Development of compounds to host targets altered prior to or after the development of liver cancer, as demonstrated by sorafenib, need to be developed. The goal is to devise drug cocktails that will yield sustained virus responses and halt disease progression and tumor development.

Tedaldi EM. · Temple Comprehensive HIV Program, Temple University Hospital, 1316 West Ontario Street, Philadelphia, PA 19140, USA. · J Addict Dis. · Pubmed #18681195 No free full text.

Abstract: New drug therapies to treat hepatitis C (HCV) and HIV infection are being developed with improved understanding of the molecular structures of the viruses themselves, the pathogenesis of infection and the specific immune responses needed to eradicate or control these infections. Interferon and ribavirin based therapies will continue to be a component of HCV therapy for the near future combined with other novel compounds directed at targets of viral replication, immunomodulation or cell entry. The goals of anti-HCV therapy are viral eradication for differing genotypes and prevention of hepatic morbidity such as hepatocellular carcinoma and cirrhosis. Future antiretroviral therapies for HIV will include agents that focus on new classes of inhibitors of viral replication and cell binding. The new treatment choices in HIV will need to ensure effective and durable viral suppression especially against highly resistant virus strains, regimen tolerability and improved toxicity.

Blonski W, Reddy KR. · Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. · Clin Liver Dis. · Pubmed #18625433 No free full text.

Abstract: Primary liver cancer is the sixth most common cancer in the world and the third most common cause of death attributable to cancer. Most primary liver cancers are hepatocellular carcinoma (HCC), accounting for 85% to 90% of cases. There is a trend of growing incidence of HCC in the United States. One of the most important risk factors for developing HCC is chronic hepatitis C virus (HCV) infection. Although several studies suggested the preventive effect of interferon from developing HCC in HCV-infected individuals, these findings need to be validated in large prospective and randomized trials.

Lo Re V, Kostman JR, Amorosa VK. · Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6073, USA. <> · Clin Liver Dis. · Pubmed #18625430 links to  free full text

Abstract: Because of shared routes of transmission, hepatitis C virus (HCV) coinfection is common among HIV-infected persons. Because of the effectiveness of antiretroviral therapy, chronic HCV has now emerged as a major cause of morbidity and mortality in this population. Because chronic HCV is highly prevalent among HIV-infected patients and has a rapid disease progression, antiviral therapy with pegylated interferon plus ribavirin is critical for the long-term survival of HIV/HCV-coinfected patients. In this article, the authors review the (1) epidemiology of HCV among HIV-infected individuals, (2) effect of HIV on the natural history of chronic HCV, (3) impact of antiretroviral therapy on HCV coinfection, and (4) management of chronic HCV in the HIV-infected person.

Kotlyar DS, Blonski W, Rustgi VK. · University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · Clin Liver Dis. · Pubmed #18625428 No free full text.

Abstract: Noninvasive approaches in the diagnosis and monitoring of fibrosis are still evolving. Transient elastography is an inexpensive, rapid, and relatively accurate form of noninvasive monitoring, especially in severe fibrosis It is a nascent technology, however, and there is no clear indication that elastography is better than biopsy for less severe fibrosis. With improved resolution and longer term data, it may become a vital supplement. The combined use of transient elastography and biochemical markers seems to be the most promising noninvasive technique.

Freudenberg JA, Bembas K, Greene MI, Zhang H. · Department of Pathology & Laboratory Medicine, University of Pennsylvania, 252 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6082, USA. · Methods. · Pubmed #18573345 No free full text.

Abstract: Many diseases are easier to treat and control when detected at an early stage of disease progression. Often, disease-related antigens or biomarkers are shed from the primary site and present in the blood. Unfortunately, there are very few tests capable of detecting these rare biomarkers in the blood. A blood test would be very useful to diagnose the disease earlier, monitor effectiveness of treatments, predict recurrence, and monitor recurrence. There is certainly a need to develop assays that are ultra-sensitive, non-invasive, and high-throughput. Here we describe several highly sensitive immunological assays we have developed to detect rare serum antigens. Initially we created an assay named immuno-detection amplified by T7 RNA polymerase (IDAT). To enhance the effectiveness and streamline the procedure, this assay was amended to the facile amplification system termed fluorescent amplification catalyzed by T7 polymerase technique (FACTT). These assays have been used to analyze the tumor antigen HER2 and the prion protein PrPSc. They can also be applied to other tumor markers or antigens from a variety of diseases such as cardiovascular disease, rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, and hepatitis. These tests are not limited to testing only serum, but may also be applicable to detecting biomarkers in tissue, saliva, urine, cerebrospinal fluid, etc. Clearly, the FACTT-based technology represents an important step in the detection of rare molecules in fluids or tissues for a variety of diseases.

Hsu EK, Murray KF. · Pediatric Gastroenterology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #18414457 No free full text.

Abstract: Chronic infection with hepatitis B affects nearly 350 million individuals worldwide and is the leading cause of hepatocellular carcinoma and liver cirrhosis. Universal infant immunization has decreased rates of HBV infection, although transmission continues to occur via vertical (mother-to-child) and horizontal (sexual, parenteral and household) routes. Treatments are now available for children with chronic HBV infection, but appropriate selection of those most likely to respond to treatment is important. Interferon alpha and lamivudine are currently approved in the US for the treatment of children older than 2 years of age who have chronic HBV infection. Hepatitis C infection affects almost 170 million individuals worldwide. Of individuals exposed to HCV, 60-80% develop chronic hepatitis, and 10-15% of those chronically infected develop cirrhosis within several decades. No vaccine exists for HCV; therefore, prevention of parenteral transmission is important. A high index of suspicion is essential for the diagnosis of HCV infection given its silent clinical presentation. Appropriate evaluation of infected individuals is warranted when considering their suitability for therapy. Interferon alpha and ribavirin, used in combination, are currently approved in the US for the treatment of children older than 3 years of age with chronic HCV infection.

Hann HW. · Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, PA, USA. · Minerva Gastroenterol Dietol. · Pubmed #18299665 No free full text.

Abstract: The ultimate goal of treatment for chronic hepatitis B (CHB) is to prevent hepatocellular carcinoma (HCC). During the last decade, great strides have been made in the treatment of hepatitis B virus (HBV) infections. Six highly effective anti-HBV agents are currently available and more agents are on the horizon. Prospective and retrospective studies of large numbers of CHB patients with advanced liver disease, including cirrhosis, have demonstrated that the treatment with lamivudine not only delays the disease progression but also reduces the incidence of HCC. In a large prospective study of 3,653 HBV carriers in Taiwan, 164 persons developed HCC in a 12-year follow-up period; an extensive analysis of their condition led to the conclusion that the most important risk factor for HCC is an increased serum level of HBV DNA >10,000 copies/mL regardless of the HBeAg status, alanine aminotransferase levels or presence of cirrhosis. The incidence of HCC correlated with serum HBV DNA level at entry in a dose-response relationship. These pivotal studies re-emphasize the need for an active anti-HBV therapy for CHB patients with viral replication as the ultimate prevention and/or delay for the development of HCC.

Halegoua-De Marzio D, Navarro VJ. · Department of Medicine, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA 19107, USA. · Curr Opin Drug Discov Devel. · Pubmed #18175267 No free full text.

Abstract: A contemporary understanding of the clinical aspects of drug-induced liver injury (DILI) is paramount for timely diagnosis and appropriate management. An accurate diagnosis of DILI is based upon a combination of appropriate history, clinical presentation, biochemical tests and the exclusion of other causes of liver injury. In clinical drug development, elevations in levels of alanine aminotransferase of up to five-fold the upper limit of normal are tolerated; however, the occurrence of hepatocellular jaundice may jeopardize a development program. At the very least, such an occurrence should trigger an extremely careful reassessment of the risk/benefit ratio of a drug. New methods to predict and detect DILI are currently being aggressively investigated.

Giarelli E. · University of Pennsylvania School of Nursing, Philadelphia, USA. · Oncology (Williston Park). · Pubmed #18154203 No free full text.

Abstract: Vaccines have been exceptionally effective against diseases such as smallpox, measles, chickenpox, and polio. They are among the safest and most cost-effective agents for disease prevention. In recent years, vaccination has been considered for other diseases, including AIDS and cancer. Cancer vaccines can be categorized as preventive or therapeutic. Preventive vaccines, which are commercially available for cervical cancer and liver cancer, block infection with the causative agents of human papillomavirus and hepatitis B virus, respectively. The benefit of cancer treatment vaccines lies in their ability to "boost" the immune system response to cancer cells, which is generally low. Using vaccines in the treatment of cancer is relatively new, however, and chiefly experimental. Therapeutic vaccines for breast, lung, colon, skin, renal, prostate, and other cancers are now being investigated in clinical trials. Oncology nurses may play a significant role in reducing barriers to uptake of preventive vaccines among the general public and in increasing patients' acceptance of therapeutic cancer vaccines.

Mason WS, Litwin S, Xu C, Jilbert AR. · Fox Chase Cancer Center, Philadelphia, PA 19111, USA. · J Viral Hepat. · Pubmed #17958639 No free full text.

Abstract: Hepatocyte turnover appears to be an important feature in the resolution of transient and progression of chronic hepadnavirus infections. Hepatocyte death, initiated through attack by antiviral cytotoxic T-lymphocytes (CTL), and compensatory hepatocyte proliferation, are both believed to be major contributing factors in the loss of virus DNA during immune resolution of transient infections. Noncytopathic curing of hepatocytes is also suggested to occur, though this mechanism does not prevent the death of large numbers of hepatocytes. Hepatocyte death, proliferation and curing are also important features of chronic infections, though the outcomes are different. In particular, immune selection due to persistent attack by antiviral CTL is thought to play a role in the emergence of hepatocytes infected with mutant strains of hepatitis B virus (HBV) (e.g. HBV e antigen-negative strains) and in the emergence of hepatocytes that appear refractory to HBV infection. In both instances, clonal expansion of subpopulations of hepatocytes may be inferred to have taken place. Interestingly, foci of altered hepatocytes and hepatocellular carcinomas (HCC) typically do no support virus replication. Thus, immune selection of hepatocytes by antiviral CTL, by inducing clonal expansion, may also play an important role in the progression to HCC. In this review, we discuss the evidence in support of roles for hepatocyte turnover in the resolution of transient and progression of chronic HBV infections.

Becker M, Axelrod DJ, Oyesanmi O, Markov DD, Kunkel EJ. · Department of Psychiatry, Thomas Jefferson University, Philadelphia, PA, USA. · Psychiatr Clin North Am. · Pubmed #17938043 No free full text.

Abstract: Vitamin B12 deficiency is associated with problems in cognition, mood, psychosis, and less commonly, anxiety. Folate deficiency primarily is associated with problems in mood. Patients who have sickle cell disease, a disease of chronic pain, experience difficulties with depression, anxiety, stigma, and are at risk for substance abuse and dependence. Patients with hemophilia have benefited from advances in treatment; however, their morbidity and mortality were compounded in those who received blood products contaminated with HIV, or hepatitis B and C. Psychiatrists who practice psychosomatic medicine should expect to encounter patients with the above problems, as they are frequently seen in medical settings. Finally, most of the commonly used psychotropic medications have uncommon but potentially important hematologic side effects or may interact with the anticoagulants used in medically ill patients.

Carrillo-Infante C, Abbadessa G, Bagella L, Giordano A. · Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA. · Int J Oncol. · Pubmed #17487374 No free full text.

Abstract: In order to promote carcinogenesis multiple factors must be orchestrated. The alteration of the cellular genome after a carcinogenic exposure may result in malignancy if apoptosis is prevented and the immune surveillance fails to eliminate the transformed cell. Infectious agents may exert these properties and transform a host cell. Viruses associated with human cancer are known as 'tumor viruses'. Most of them are capable of integrating into the host genome and have the ability to immortalize the target cell in order to allow their own replication. The infected cell expresses the viral genes, which are able to induce cell growth, proliferation and prevent apoptosis. This review focuses on Epstein-Barr virus, human papilloma virus, hepatitis C virus, hepatitis B virus, human herpes virus 8 and human T-cell leukemia virus, since they have been already established as causative agents of human cancer. An understanding of the viral replication mechanism may provide new targets for the development of specified viral therapy that may have an impact not only on viral infections but in human cancer as well.

Woo K, Spatz D. · Emergency Department, Children's Hospital of Philadelphia, PA, USA. · MCN Am J Matern Child Nurs. · Pubmed #17479050 No free full text.

Abstract: The American Academy of Pediatrics (AAP) strongly endorses that human milk is species specific and the optimal nutrition for infants, and that banked human milk is a suitable alternative. After the death of an infant, breast milk often is disposed of without consideration of donation because the public and healthcare providers are unaware of human milk banks. In the United States, 10 human milk banks operate under strict guidelines established by the Human Milk Banking Association of North America. Donors are screened, and milk is pasteurized while preserving many of the beneficial components of breast milk. It is imperative that healthcare providers become educated regarding human milk banking because of the increase in informal sharing of breast milk via the Internet. Breast milk that has not been screened and treated has the risk of transmitting infections such as hepatitis and HIV. Healthcare providers should be familiar with the selection criteria for suitable donors and how to approach families when the death of an infant is imminent. Human milk banks are able to provide human milk to adopted, preterm, or ill infants whose mothers are unable to provide their own milk.

Blackburn SD, Wherry EJ. · Immunology Program, The Wistar Institute, Philadelphia, PA 19104, USA. · Trends Microbiol. · Pubmed #17336072 No free full text.

Abstract: Viral infections can have one of two outcomes: control of viral replication and acute infection or viral persistence and chronic infection. It is clear that both pathogen and host characteristics influence the acute versus chronic outcome of viral infection. The early events in the host immune response that favor immunosuppression and viral persistence, however, have remained poorly understood. Using the well-characterized mouse model of acute versus chronic lymphocytic choriomeningitis virus (LCMV) infection, two groups have recently identified the interleukin-10 (IL-10)/IL-10R pathway as a key regulator of acute versus chronic infection. Blockade of IL-10R converted a chronic LCMV infection into a rapidly controlled acute viral infection and prevented the functional exhaustion of memory T cells. These insights into the role of IL-10 in the establishment of chronic infection could lead to new therapeutic opportunities during human infections with pathogens such as HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV).

Neofytos D, Ojha A, Mookerjee B, Wagner J, Filicko J, Ferber A, Dessain S, Grosso D, Brunner J, Flomenberg N, Flomenberg P. · Division of Infectious Diseases and Environment Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. · Biol Blood Marrow Transplant. · Pubmed #17222755 No free full text.

Abstract: Invasive adenovirus (AdV) disease is fatal in >50% of allogeneic hematopoietic stem cell transplant (SCT) recipients. Treatment with cidofovir may improve outcomes based on in vitro susceptibility data and case reports. Six consecutive cases of invasive AdV disease treated with cidofovir were reviewed among 84 allogeneic adult SCT recipients (incidence, 7.1%). Cidofovir was administered intravenously at 5 mg/kg per dose (1-7 doses). All patients received intravenous immune globulin. Blood AdV DNA levels (viral loads, VLs) were monitored with a real-time quantitative polymerase chain reaction assay. Published reports of cidofovir treatment of AdV disease in SCT recipients were critically reviewed. The primary manifestations of AdV disease were hepatitis (n = 3), colitis (n = 2), and nephritis (n = 1). All patients had detectable AdV VLs, with peak values from 5 x 10(5) to 2 x 10(8) copies/mL. All patients received CD34+ selected grafts (n = 3) and/or had graft-versus-host disease (n = 4) and had CD4 counts <100 cells/mm3. Only 1 of 5 patients (20%) who received >or=2 doses of cidofovir died with active AdV disease. Four patients exhibited improvement within days of treatment with cidofovir as documented by clinical criteria and declines in AdV VLs (without a change in immunosuppression). In contrast, 1 patient treated late after onset of AdV disease died after 1 dose of cidofovir. In our review of 70 published cases treated with >or=2 doses of cidofovir, 13 (19%) died from AdV disease. In conclusion, early treatment of AdV disease with cidofovir inhibits viral replication in vivo and reduces mortality in allogeneic SCT recipients compared with historical data.

Feitelson MA, Lee J. · Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. · Cancer Lett. · Pubmed #17188425 No free full text.

Abstract: Chronic liver disease associated with long term hepatitis B virus (HBV) infection contributes importantly to the development of hepatocellular carcinoma (HCC). A salient feature of these chronic infections is the integration of subgenomic HBV DNA fragments into many different locations within the host DNA, suggesting that integration is random. Although this may promote genetic instability during liver regeneration which accompanies a bout of chronic liver disease, the actual role of integrated HBV DNA in hepatocarcinogenesis is uncertain. Importantly, most integration events retain the HBV open reading frame encoding the HBx antigen (HBxAg), which is the virus contribution to HCC. In addition, many integration events reported in the literature occur near or within fragile sites or other cancer associated regions of the human genome that are prone to instability in tumor development and progression. Genetic instability associated with integration potentially alters the expression of oncogenes, tumor suppressor genes, and microRNAs (miRNAs) that may contribute importantly to tumorigenesis. If so, then selected integration events may alter pathways that are rate limiting in hepatocarcinogenesis, thereby providing targets with diagnostic/prognostic potential and for therapeutic intervention.