Hepatitis: New York City

Stanca CM, Babar J, Singal V, Ozdenerol E, Odin JA. · Department of Medicine, The Mount Sinai School of Medicine, New York, New York 10029, USA. · J Immunotoxicol. · Pubmed #18382859 No free full text.

Abstract: Immune-mediated liver diseases contribute significantly to morbidity and mortality due to liver failure and the need for liver transplantation. The pathogenesis of the immune-mediated chronic liver diseases, primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cirrhosis, is poorly understood. Genetic susceptibility factors may play a role, but increasing attention is being given to the association between environmental factors and these diseases. The existence of such a relationship is supported by epidemiologic surveys, animal models, and geographic clustering analyses. Unearthing the cause of this association may provide insight into the pathogenesis of immune-mediated chronic liver diseases and autoimmunity.

Newell P, Villanueva A, Friedman SL, Koike K, Llovet JM. · Division of Liver Diseases, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA. · J Hepatol. · Pubmed #18314222 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is a common and deadly cancer whose pathogenesis is incompletely understood. Comparative genomic studies from human HCC samples have classified HCCs into different molecular subgroups; yet, the unifying feature of this tumor is its propensity to arise upon a background of inflammation and fibrosis. This review seeks to analyze the available experimental models in HCC research and to correlate data from human populations with them in order to consolidate our efforts to date, as it is increasingly clear that different models will be required to mimic different subclasses of the neoplasm. These models will be instrumental in the evaluation of compounds targeting specific molecular pathways in future preclinical studies.

Dieterich DT. · Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA. · Antivir Ther. · Pubmed #18284182 No free full text.

Abstract: Coinfection with HIV and hepatitis B virus (HBV) substantially alters the natural course of HBV infection as well as its management. Therapy for HBV infection in HIV-coinfected patients requires several factors to be taken into consideration, such as whether the antiviral activity of a particular agent is specific for HBV (that is, adefovir, entecavir, telbivudine and pegylated interferon) or for both viruses (that is, lamivudine, emtricitabine and tenofovir), whether the chosen drug has the potential for inducing drug resistance and cross-resistance, and whether use of the agent is associated with hepatotoxicity. For coinfected patients who do not require therapy for their HIV infection, clinicians should avoid prescribing monotherapy with agents that have activity against HIV (that is, tenofovir, entecavir, emtricitabine or lamivudine) so as not to compromise future HIV care. This review discusses the current status of treatment of hepatitis B in the setting of HIV infection. It describes emerging therapeutic strategies and addresses challenges in the treatment of coinfection.

Ferrando SJ, Freyberg Z. · Department of Psychiatry, The New York-Presbyterian Hospital, Weill Medical College of Cornell University, New York, USA. · Int Rev Psychiatry. · Pubmed #18240063 No free full text.

Abstract: The primary goal of this paper is to provide a critical review of the literature on treatment of depression in HIV/AIDS. There is a substantial research literature documenting the efficacy of conventional antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), novel agents such as dehydroepiandrosterone, psychostimulants and some psychotherapies, particularly interpersonal and group psychotherapy for the treatment of depression in HIV. However, lack of comparative studies makes it difficult to draw a firm consensus regarding the best course of treatment. In devising a treatment plan, clinicians should take into account stage of HIV illness, co-morbid illnesses such as Hepatitis B and C, the potential for drug interactions with antiretroviral and other medications used to treat HIV and patient preference.

Andemariam B, Psaila B, Bussel JB. · New York Presbyterian Hosp., Weill Cornell Medical Center, 525 E. 68th St., Payson 695, New York, NY 10021-4870, USA. · Hematology Am Soc Hematol Educ Program. · Pubmed #18024617 links to  free full text

Abstract: Thrombocytopenia is a primary manifestation of immune thrombocytopenic purpura (ITP) and may occur as a result of hepatitis C, malignancy, and treatment with chemotherapy. There is a need for additional means to treat thrombocytopenia in these settings. Recombinant thrombopoietin-like agents became available after the cloning of thrombopoietin in 1994. In clinical trials, these agents showed some efficacy in chemotherapy-induced thrombocytopenia, but their use was ultimately discontinued due to the development of neutralizing antibodies that cross-reacted with endogenous thrombopoietin and caused thrombocytopenia in healthy blood donors and other recipients. Subsequently, "second-generation" thrombopoietic agents without homology to thrombopoietin were developed. In the past 5 years, these second-generation thrombopoeitic growth factors have undergone substantial clinical development and have demonstrated safety, tolerability and efficacy in subjects with ITP and hepatitis C-related thrombocytopenia. These completed studies, many of which are available only in abstract form, and other ongoing studies suggest that thrombopoietic agents will enhance the hematologist's ability to manage these and other causes of thrombocytopenia.

Bhandari MS, Mazumder A, Vesole DH. · St. Vincent's Comprehensive Cancer Center, New York, NY 10011, USA. · Clin Lymphoma Myeloma. · Pubmed #18021472 No free full text.

Abstract: Clinical manifestations of liver involvement in multiple myeloma (MM) are uncommon. Rare cases of MM present as acute liver disease. We report a case of a 55-year-old woman with MM who presented with painless jaundice, mild pruritus, and abnormal liver function tests resembling acute cholestatic hepatitis without the stigmata of chronic liver disease. Initial laboratories included elevated liver function tests (aspartate aminotransferase 74 U/L and alanine aminotransferase 45 U/L) and an elevated white blood cell count of 19,600 cells/microL with 33% circulating plasma cells. Myeloma parameters demonstrated an immunoglobulin G lambda monoclonal protein with lambda light-chain Bence-Jones proteinuria. Bone marrow was hypercellular with 70% plasmacytosis. A liver biopsy revealed a diffuse portal and sinusoidal infiltration of plasma cells with lambda light-chain restriction. In this report, we review the literature of liver involvement in MM.

Gambarin-Gelwan M. · Division of Gastroenterology and Hepatology, Weill Cornell Medical College of Cornell University, 1305 York Avenue, 4th floor, New York, NY 10021, USA. · Clin Liver Dis. · Pubmed #17981236 No free full text.

Abstract: In countries with a high prevalence of chronic hepatitis B, perinatal transmission from mother to infant accounts for the majority of cases of chronic hepatitis B. Passive-active immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine at birth is 95% efficacious in reducing the risk of HBV transmission but is less effective in HBeAg-positive mothers with very high serum HBV DNA levels. In the last 4 weeks of pregnancy lamivudine may provide additional protection in pregnant women who have high-level viremia. Further studies are needed to evaluate the use of nucleos(t)ide analogues to treat chronic hepatitis B during pregnancy.

Cheruvu S, Marks K, Talal AH. · Division of Gastroenterology and Hepatology, Weill Medical College of Cornell University, 525 E. 68th Street, Box 319, New York, NY 10065, USA. · Clin Liver Dis. · Pubmed #17981235 No free full text.

Abstract: The approach to the hepatitis B virus (HBV)-infected patient who is also infected with HIV or hepatitis C virus (HCV) is very different from the approach to the patient with only one virus infection. HBV/HIV coinfection is common. Agents that have dual activity against HBV and HIV should be considered as treatment of choice in combination regimens in HBV/HIV-coinfected patients beginning antiretroviral therapy. In HBV/HCV coinfection HCV usually tends to predominate over HBV. More investigation is needed into the mechanisms by which viral pathogenesis is altered and the optimal treatment modalities for coinfected patients.

Weisberg IS, Brown RS, Sigal SH. · Division of Gastroenterology and Hepatology, New York Weill Cornell Medical Center, 525 E. 68th Street, New York, NY 10021, USA. · Clin Liver Dis. · Pubmed #17981234 No free full text.

Abstract: Hepatitis B virus (HBV) is the most common cause of chronic hepatitis and end-stage liver disease worldwide. Untreated, chronic hepatitis B acquired early in life results in cirrhosis, liver failure, or hepatocellular carcinoma in up to 40% of individuals. Until recently, the options for a patient who had end-stage hepatitis B cirrhosis were severely limited, but during the past 15 years great strides have been made in prevention and treatment of hepatitis B cirrhosis. This article reviews recent advances in the understanding of the natural history, prevention, and medical management of HBV-related end-stage liver disease.

Min AD, Dienstag JL. · Division of Digestive Diseases, Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003, USA. · Clin Liver Dis. · Pubmed #17981232 No free full text.

Abstract: Four oral antiviral agents have been approved by the United States Food and Drug Administration (FDA) for the treatment of chronic hepatitis B: lamivudine, adefovir, entecavir, and telbivudine. This article reviews the durability of response, dose regimen, predictors of response, safety, and problems with resistance of these four agents and of promising agents currently in phase III clinical trials for the treatment of patients who have hepatitis B e antigen-positive and -negative chronic hepatitis B.

Kulkarni K, Jacobson IM, Tennant BC. · Division of Gastroenterology and Hepatology, Department of Medicine, Weill Medical College of Cornell University, 1305 York Avenue, 4th floor, New York, NY 10021, USA. · Clin Liver Dis. · Pubmed #17981226 No free full text.

Abstract: Experimental studies of animals with chronic hepadnavirus infection could provide valuable insight into optimal therapeutic strategies for individuals with chronic HBV infection. In this review, we focus on the contributions of the woodchuck model to our understanding of HBV biology and on its role in the development of antiviral drug. Furthermore, we consider the implications of studies focusing on the natural history of WHV infection for the management of HBV and the capacity of treatment to prevent complications of chronic hepatitis B infection.

Brown RS. · Department of Medicine, Center for Liver Disease & Transplantation, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA. · Aliment Pharmacol Ther. · Pubmed #17958518 No free full text.

Abstract: BACKGROUND: Patients with chronic liver disease commonly experience thrombocytopenia resulting from disease or treatment. Such patients often require multiple platelet transfusions, and consequently can experience associated complications including systemic infection, iron overload, and platelet refractoriness. AIM: To discuss the limited data available on the impact of thrombocytopenia on the medical procedures and their associated costs. RESULTS: Thrombocytopenia and its treatment can have a negative impact on outcomes and cost of therapy; costs associated with platelet transfusion can constitute a significant portion of the hospital budget. Inability to initiate or complete antiviral therapy for chronic hepatitis C infection due to low platelet counts can lead to dose reduction or discontinuation, lower efficacy, increased risks, and increased overall costs. Routine medical procedures can be complicated, prolonged, or precluded as a result of severe thrombocytopenia. CONCLUSION: Novel therapies can safely and effectively prevent or treat thrombocytopenia in this patient population with chronic liver disease resulting in improved quality of care and significant cost savings in addition to improving treatment outcomes and quality of life (QOL) measures.

Weksler BB. · Division of Hematology and Medical Oncology, Weill Medical College of Cornell University, New York, NY 10021, USA. · Aliment Pharmacol Ther. · Pubmed #17958515 No free full text.

Abstract: BACKGROUND: The pathophystology of thrombocytopenia in patients with chronic liver disease resulting from hepatitis C virus (HCV) infection is complex and involves several complementary mechanisms that likely act in concert. AIM: To summarize the available data on the etiology of thrombocytopenia in patients with chronic liver disease. RESULTS: In patients with untreated hepatitis C, both prevalence and severity of thrombocytopenia increase in parallel with the extent of disease, usually becoming clinically relevant when patients develop extensive fibrosis and/or cirrhosis. Pathogenetic mechanisms include hypersptenism secondary to portal hypertension, bone marrow suppression resulting from either HCV itself or interferon treatment, aberrations of the immune system resulting in the formation of anti-platelet antibodies and/or immune-complexes that bind to platelets and facilitate their premature clearance, development of immunologically-mediated extrahepatic manifestations including mixed cryoglobulinemia with or without associated joint, renal, or cutaneous involvement, and thrombopoietin (TPO) deficiency secondary to liver dysfunction. In chronic liver disease, the natural inverse relationship between TPO and platelet levels is not maintained; therefore, blood TPO levels fail to have clinical relevance or predictive value in assessing the thrombocytopenic status of a given patient. CONCLUSIONS: The development of thrombocytopenisa in patients with chronic liver disease is complex and multifactorial.

von Hahn T, Rice CM. · Center for the Study of Hepatitis C, The Rockefeller University, New York, New York 10065, USA. · J Biol Chem. · Pubmed #17881349 links to  free full text

This publication has no abstract.

Zeremski M, Petrovic LM, Talal AH. · Division of Gastroenterology and Hepatology, Department of Medicine, and The Center for the Study of Hepatitis C, Weill Medical College of Cornell University, New York 10021, USA. · J Viral Hepat. · Pubmed #17875002 No free full text.

Abstract: Hepatitis C virus (HCV) is a leading cause of chronic liver disease that can progress to cirrhosis and/or hepatocellular carcinoma. Intrahepatic inflammation and liver cell injury are defining features of chronic HCV infection. Chemokines, chemotactic cytokines that attract leucocytes to inflammatory sites, may be important in the development of intrahepatic inflammation. As T-helper (Th)1 inflammatory cells, characterized by interferon (IFN)-gamma and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, chemokines that attract these cells might be particularly important in disease progression. In this review, we focus on the role of Th1 chemokines, which are all members of the CXC or CC subfamilies. Among the CXC chemokines, the non-ELR group comprised of IFN-gamma-inducible protein 10 (IP-10), monokine induced by IFN-gamma (Mig) and IFN-inducible T-cell-alpha chemoattractant (I-TAC), attract Th1 cells through the interaction with their receptor, CXCR3. Among the CC subfamily, Th1-associated chemokines include regulated upon activation, normal T-cell expressed and secreted (RANTES) and macrophage inflammatory proteins (MIP)1alpha and beta. These chemokines attract cells through an interaction with their receptor, CCR5. While peripheral blood and intrahepatic levels of all of these chemokines are elevated in chronic hepatitis C patients, only select chemokines have been found to be correlated with hepatic inflammation. Among the six chemokines, IP-10 has uniquely been shown to have prognostic utility as a marker of treatment outcome. In the future, chemokines might be used to monitor the natural course and progression of HCV-associated liver disease, to identify patients with a high likelihood of achieving a therapeutic response, and they may even have potential as therapeutic targets.

Hagan H, Des Jarlais DC, Stern R, Lelutiu-Weinberger C, Scheinmann R, Strauss S, Flom PL. · Center for Drug Use and HIV Research, National Development and Research Institutes (NDRI), New York, NY 10010, United States. <> · Int J Drug Policy. · Pubmed #17854721 No free full text.

Abstract: Early acquisition of hepatitis C virus (HCV) infection appears to affect a substantial proportion of injection drug users (IDUs)--between 20 percent and 90 percent. Analysing the range of HCV prevalence estimates in new injectors may help identify factors that can be modified to reduce HCV transmission. The HCV Synthesis Project is a meta-analysis of studies of HCV epidemiology and prevention in drug users worldwide. In this preliminary analysis, we examined data from 127 studies of IDUs that reported HCV prevalence in relation to age or year since onset of drug injection, analysing heterogeneity and calculating summary statistics where appropriate. Six studies reported gender-specific HCV prevalence rates among young or new injectors; the group mean prevalence was 47 percent for men and 44 percent for women (NS). Group mean age for HCV-negatives was 24.7 years (range 24-28) and 26.1 years (range 21-31) for HCV-positives (n=8 studies). Data were examined from 13 studies that compared HCV prevalence among young injectors to older injectors using 5-year age categories; substantial variation was present within these categories such that measures of central tendency were not calculated. Similarly, among studies reporting HCV prevalence among IDUs in relation to 1-year intervals of duration of injection (<1 year, <2 years, and <3 years), considerable variability was observed. Notably, there were studies in each category that reported prevalence of 70 percent or higher among recent-onset drug injectors. Our findings confirm previous studies reporting high risk of acquiring HCV shortly after onset of injection; thus, HCV prevention programmes must emphasize methods to reach new injectors. Future research should (1) report data on time to infection in depth, (2) provide detailed information on study methodology, and (3) characterize the research setting with respect to underlying factors that affect injection practices and networks. This will permit synthesis of a greater number of studies and may lead to the identification of factors that impede HCV transmission.

Singal AK, Anand BS. · James J Peters Bronx Veterans Affairs Medical Center, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10468, USA. · J Clin Gastroenterol. · Pubmed #17700425 No free full text.

Abstract: BACKGROUND: Since the discovery of the hepatitis C virus (HCV), extensive literature has emerged on alcohol and HCV interaction. GOAL: To understand the impact of alcohol and HCV infection on the severity of liver disease and the mechanisms of interaction between the two. STUDY: Of 1269 articles (1991 to 2006) searched through MEDLINE and cited cross references, 133 were thoroughly reviewed to assess: (a) prevalence of combined alcohol use and HCV, (b) severity of liver disease (c) treatment response, and (d) mechanisms of interaction between HCV and alcohol. Data on study design, patient demographics, diagnostic tests used, and study outcomes were extracted for critical analysis. RESULTS: Prevalence of HCV is 3-fold to 30-fold higher in alcoholics compared with the general population. Patients with HCV infection and alcohol abuse develop more severe fibrosis with higher rate of cirrhosis and hepatocellular cancer compared with nondrinkers. Increased oxidative stress seems to be the dominant mechanism for this synergism between alcohol and the HCV. Abstinence is the key to the management of liver disease due to HCV and alcohol. Data have shown that lower response rates to interferon in alcoholics with HCV infection are likely due to noncompliance. CONCLUSIONS: Alcoholics with HCV infection have more severe liver disease compared with nondrinkers. Patients should be encouraged to enroll in rehabilitation programs so as to improve treatment adherence and response.

Dadachova E, Wang XG, Casadevall A. · Department of Nuclear Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA. · Cancer Biother Radiopharm. · Pubmed #17651036 No free full text.

Abstract: "Virus-associated cancer" (VAC) refers to a cancer where viral infection results in the malignant transformation of the host's infected cells. Examples of viruses linked to cancers are the Epstein-Barr virus (EBV), which is associated with lymphomas, as well as nasopharyngeal and breast cancer; hepatitis B virus (HBV) and hepatitis C virus (HCV), which are both associated with hepatocellular carcinoma; and human papilloma viruses (HPVs), which are associated with cancer of the cervix. We have recently demonstrated that HIV-1-infected cells can be eliminated in vitro and in vivo by targeting viral glycoproteins expressed on the surface of infected cells with radiolabeled viral protein-specific monoclonal antibodies and proposed that this approach can be applicable to the broad range of viral infectious diseases. In VAC, the tumor cells can exhibit viral antigens both internally or on their surfaces. As a result, viral antigens in tumors represent a potential antigenic target that is clearly different from normal tissues. In principle, these proteins could be targeted by radioimmunotherapy (RIT). In this paper, we describe the potential of this approach and review some of the issues involved in the development of this approach. RIT of VAC is fundamentally different from the previously described uses of RIT, which have targeted tumor-associated antigens that are "self" proteins.

Schwartz M, Roayaie S, Konstadoulakis M. · Mount Sinai School of Medicine, New York, NY 10029, USA. · Nat Clin Pract Oncol. · Pubmed #17597707 No free full text.

Abstract: Hepatocellular carcinoma (HCC) generally develops as a consequence of underlying liver disease, most commonly viral hepatitis. The development of HCC follows an orderly progression from cirrhosis to dysplastic nodules to early cancer development, which can be reliably cured if discovered before the development of vascular invasion (typically occurring at a tumor diameter of approximately 2 cm). The identifiable population at risk makes screening a realistic possibility, and liver imaging is recommended every 6 months for patients with cirrhosis. For patients with preserved liver function and no portal hypertension who develop HCC that is confined to one region of the liver, resection is the preferred treatment. If resection is not possible because of poor liver function, and the HCC is within the Milan criteria (1 nodule > or =5 cm, 2-3 nodules > or =3 cm), liver transplantation is the treatment of choice. To prevent tumor progression while waiting, nonsurgical treatments including percutaneous ethanol injection, radiofrequency ablation, and transarterial chemoembolization are employed, but drop-out from the waiting list remains a problem. Living donor transplantation is an alternative that can eliminate drop-out and enable liver transplantation for patients with HCC whose disease does not fall within the Milan criteria. There is a need for more effective adjuvant therapies after resection and liver transplantation; newer antiangiogenic agents offer hope for improved outcomes in the future.

Thanjan MT, Ramaswamy P, Lai WW, Lytrivi ID. · Department of Pediatric Cardiology, Mount Sinai Medical Center, New York, New York, USA. · Pediatrics. · Pubmed #17515437 links to  free full text

Abstract: We report a case of postvaccination acute myopericarditis in an adolescent. The patient presented with acute chest pain, diffuse ST-segment elevation, and elevated cardiac enzyme levels. Cardiac MRI was consistent with acute myocarditis. He recovered within a few days with nonsteroidal antiinflammatory treatment and remains clinically stable, with improvement of MRI findings at the 10-week follow-up. Postvaccination cases of myopericarditis reported in the pediatric literature are also reviewed.

Petrovic LM. · Department of Pathology, New York University School of Medicine, NY, USA. · Liver Int. · Pubmed #17498243 No free full text.

Abstract: Human immunodeficiency virus/hepatitis C virus (HIV/HCV) co-infection has emerged as a leading cause of liver morbidity in the last two decades. Liver failure is also frequently a cause of death in HIV/HCV co-infected patients. Highly active antiretroviral treatment (HAART) has revolutionized the HIV treatment, leading to a significantly decreased morbidity, prolonged survival, and an overall better outcome of HIV infection. Hepatotoxicity associated with antiretroviral treatment, however, has been recognized as one of the serious complications of the treatment. The effects of HIV infection on the natural history and progression of HCV-associated chronic liver disease that had been well documented in the pre-HAART treatment era have been changing, and there are now many indications that HIV/HCV co-infection should be recognized as an evolving and a challenging disease entity.

Theise ND. · Department of Pathology, Beth Israel Medical Center of Albert Einstein College of Medicine, New York, NY, USA. · Mod Pathol. · Pubmed #17486049 links to  free full text

Abstract: The terminology for assessment of chronic viral hepatitis in liver biopsy specimens has become confusing with the proliferation of grading and staging schemes that have paralleled the rise of the hepatitis C epidemic and the importance of mixed viral infections. This review represents a personal approach to the interpretation of these biopsy specimens, aiming at clarifying and simplifying the important points for the general pathologist confronted by these diagnostic dilemmas. The most commonly used schemes-Ishak modification of the Knodell 'hepatic activity index', Scheuer, Metavir, Batts-Ludwig classifications-are presented with evaluation of their pros and cons. Which scheme is selected is less important than the consistent use of a single scheme and the clear naming of that scheme in pathology reports. The importance and clinical implications of identifying severe necroinflammatory activity in the form of 'confluent necrosis' is discussed. Pathologists must also be clear about assessing concomitant diseases, in particular, alcoholic or non-alcoholic fatty liver disease, and be aware that grading/staging schemes for chronic hepatitis do not apply to mixed disease conditions. Other important features to be evaluated in all chronic hepatitis biopsy specimens include iron (which may represent hereditary hemochromatosis or secondary uptake) and neoplasia-associated changes, namely large cell change and small cell change; these findings and their clinical import are updated and reviewed. Sample approaches to composing useful diagnostic reports are also presented.

Rivkin A. · Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, New York, New York, USA. · Drugs Today (Barc). · Pubmed #17460784 No free full text.

Abstract: Infection with hepatitis B virus (HBV) is extremely widespread - it infects two billion people out of the six billion world population. It is estimated that between 350 and 400 million people are chronically infected with HBV. Chronic HBV infection leads to development of complications, such as cirrhosis and hepatocellular carcinoma (HCC), which arise in 15-40% of patients. HBV-related liver disease and its complications result in approximately one million deaths each year. The ultimate goals of chronic hepatitis B (CHB) therapy are decreases in the incidence of cirrhosis, end-stage liver disease and HCC. The following six medications are currently approved by the U.S. Food and Drug Administration for the treatment of CHB: interferon (INF)-alpha2b, pegylated INF-alpha2a, lamivudine, adefovir dipivoxil, entecavir and, recently, telbivudine. Interferon therapy has many contraindications and commonly causes multiple intolerable adverse effects. Lamivudine therapy leads to increased development of resistant mutations with each year of use. Entecavir, a new guanosine nucleoside analogue with specific activity against HBV DNA polymerase, represents a third agent within the nucleoside/nucleotide HBV polymerase inhibitor class. It has distinct advantages over lamivudine and adefovir dipivoxil: it has a three-step mechanism of action, is the most potent inhibitor of HBV DNA polymerase, is not associated with any major adverse effects and has a limited potential for resistance. In clinical trials, entecavir was superior to lamivudine in all primary endpoints in both nucleoside-naive and lamivudine-refractory hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. Preliminary data support entecavir efficacy in patients with cirrhosis and HIV/HBV coinfected patients. No resistance occurred after two years of entecavir therapy in nucleoside-naive patients. Up to 9% resistance developed in patients with documented prior lamivudine resistance during 96 weeks of entecavir therapy. Currently, entecavir should be considered a first- or second-line treatment option for the management of HBeAg-positive or -negative nucleoside-naive or lamivudine-refractory CHB patients.

Chang CY, Schiano TD. · The Division of Liver Diseases, Department of Internal Medicine, The Mount Sinai School of Medicine, New York, NY 10029-6574, USA. · Aliment Pharmacol Ther. · Pubmed #17451560 No free full text.

Abstract: BACKGROUND: Drug toxicity is the leading cause of acute liver failure in the United States. Further understanding of hepatotoxicity is becoming increasingly important as more drugs come to market. AIMS: (i) To provide an update on recent advances in our understanding of hepatotoxicity of select commonly used drug classes. (ii) To assess the safety of these medications in patients with pre-existing liver disease and in the post-liver transplant setting. (iii) To review relevant advances in toxicogenomics which contribute to the current understanding of hepatotoxic drugs. METHODS: A Medline search was performed to identify relevant literature using search terms including 'drug toxicity, hepatotoxicity, statins, thiazolidinediones, antibiotics, antiretroviral drugs and toxicogenomics'. RESULTS: Amoxicillin-clavulanic acid is one of the most frequently implicated causes of drug-induced liver injury worldwide. Statins rarely cause clinically significant liver injury, even in patients with underlying liver disease. Newer thiazolidinediones are not associated with the degree of liver toxicity observed with troglitazone. Careful monitoring for liver toxicity is warranted in patients who are taking antiretrovirals, especially patients who are co-infected with hepatitis B and C. Genetic polymorphisms among enzymes involved in drug metabolism and HLA types may account for some of the differences in individual susceptibility to drug hepatotoxicity. CONCLUSIONS: Drug-induced hepatotoxicity will remain a problem that carries both clinical and regulatory significance as long as new drugs continue to enter the market. Future results from ongoing multicentre collaborative efforts may help contribute to our current understanding of hepatotoxicity associated with drugs.

Lamster IB, Ahlo JK. · Columbia University College of Dental Medicine, New York, New York 10032, USA. · Ann N Y Acad Sci. · Pubmed #17435131 No free full text.

Abstract: Gingival crevicular fluid (GCF), a serum transudate or inflammatory exudate, can be collected from the gingival crevice surrounding the teeth. As such, the fluid reflects the constituents of serum, the cellular response in the periodontium, and contributions from the gingival crevice. The study of GCF has focused on defining the pathophysiology of periodontal disease, and identification of a potential diagnostic test for active periodontitis. The majority of markers that have been identified as potential candidates for such a test are measures of inflammation (i.e., prostaglandin E2 (PGE2), neutrophil elastase, and the lysosomal enzyme beta-glucuronidase). Further, analysis of inflammatory markers in GCF may assist in defining how certain systemic disorders (e.g., diabetes mellitus) can modify periodontal disease, and how periodontal disease/periodontal inflammation can influence certain systemic disorders (i.e., cardiovascular/cerebrovascular diseases). Methodological concerns related to the collection and analysis of GCF are important factors that need to be considered when studying GCF. Practical concerns argue against the widespread clinical application of GCF as an adjunct to periodontal diagnosis. Rather, analysis of GCF-derived mediators in saliva may serve as a means of rapid screening for periodontal disease.