Hepatitis: New York area

Epstein NE. · Long Island Neurosurgical Associates, New Hyde Park, NY 11042, USA. · Surg Neurol. · Pubmed #18423553 No free full text.

Abstract: BACKGROUND: "Bloodless spinal surgery" predominantly refers to NH, a procedure that minimizes blood transfusion requirements. By limiting or eliminating allogeneic transfusions, NH reduces the risk of transmitting HIV or hepatitis, and the need for predonating autologous blood with the risks of blood bank contamination, misidentification, or the removal of coagulation factors (fresh frozen plasma, platelets). METHODS: The NH technique technically requires the controlled removal of a volume of whole blood at the beginning of surgery. The quantity removed is dependent upon the preoperative hematocrit and varies from 1 to 3 U. Each 1 mL of whole blood removed is then replaced with 3 to 4 mL of colloid or crystalloid. Intraoperatively, NH typically reduces the hematocrit to 28%, taking care to avoid hemodynamic compromise through adequate volume replacement. RESULTS: For adolescents undergoing scoliosis/spinal fusions, NH reduced allogeneic transfusion requirements from 79% to 37% [Cha CW, Deible C, Muzzonigro T, et al. Allogeneic transfusion requirements after autologous donations in posterior lumbar surgeries. Spine. 2002; 27(1) 99-104]. Without NH, 40% of patients undergoing instrumented lumbar spine fusions in one series required allogeneic blood transfusions [Catoire P, Saada M, Liu N, et al. Effect of preoperative normovolemic hemodilution on left ventricular segmental wall motion during abdominal aortic surgery. Anesth Analg (US). 1992; 75(5): 654-9.]. With the use of NH in a comparable series, this frequency was reduced to 23.5% [Epstein NE, Peller A, Korsh J, et al. Impact of intraoperative normovolemic hemodilution on transfusion requirements for 68 patients undergoing lumbar laminectomies with instrumented posterolateral fusion. Spine. 2006; 31(19): 2227-2230]. CONCLUSIONS: This study reviews how NH may be safely and effectively used by spinal surgeons, particularly for those who perform multilevel lumbar laminectomies with or without fusion.

Novick DM, Kreek MJ. · Rockefeller University, New York, NY, USA. · Addiction. · Pubmed #18422827 No free full text.

Abstract: AIMS: Hepatitis C virus (HCV) infection is a common chronic complication of injection drug use. Methadone maintenance programs contain large numbers of patients infected with HCV. This paper reviews HCV infection with emphasis on the medical care of HCV-infected, or HCV and human immunodeficiency virus co-infected, patients on methadone or buprenorphine maintenance. METHODS: Literature searches using PubMed, PsycINFO and SocINDEX were used to identify papers from 1990-present on antiviral therapy for HCV in methadone maintenance patients and on liver transplantation in methadone maintenance patients. RESULTS: Injection drug use is the most significant risk factor for HCV infection in most western countries. The prevalence of HCV antibody is high in injection drug users (53-96%) and in patients enrolled in methadone maintenance programs (67-96%). Studies of antiviral therapy for HCV in methadone maintenance patients show rates of sustained virological response (SVR), defined as negative HCV-RNA 24 weeks after the end of treatment, of 28-94%. In studies with contrast groups, no significant differences in SVR between methadone and contrast groups were found. Excellent completion rates of antiviral therapy (72-100%) were found in five of six studies. There are many barriers to methadone maintenance patients' receiving antiviral therapy, and research on overcoming barriers is discussed. Liver transplantation has been successful in methadone maintenance patients but has not been utilized widely. CONCLUSION: High quality medical care for all aspects of HCV infection can be provided to methadone maintenance patients. The literature supports the effectiveness of such services, but the reality is that most patients do not receive them.

Lefkowitch JH. · Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, USA. · Curr Opin Gastroenterol. · Pubmed #18408454 No free full text.

Abstract: PURPOSE OF REVIEW: Studies are reviewed from the past year concerning the histopathology of liver and biliary diseases and their pathogenesis. RECENT FINDINGS: Several cases of acute hepatitis E showed portal and periportal hepatitis, with polarization of neutrophils to the interface region and lymphocytes more centrally in the portal tracts. Transfection of hepatitis C virus into cultured fetal hepatocytes resulted in sustained growth of 50-90 nm diameter viral particles. The ductular reaction in nonalcoholic steatohepatitis appears to evolve with fibrosis in response to hepatocyte replicative senescence. Hepatocellular release of hepcidin is critical for iron homeostasis in a manner analogous to pancreatic insulin for glucose homeostasis; this 'endocrine' focus was elaborated in an overview of hemochromatosis. Specific microscopic features of liver-cell adenomas combined with genetic analysis for hepatocyte nuclear factor 1alpha and beta-catenin mutations allows differentiation into four variants. Steroid-sensitive biliary strictures resembling primary sclerosing cholangitis but with increased serum immunoglobulin G4 and infiltrating immunoglobulin G4-positive plasma cells ('immunoglobulin associated cholangitis') are part of a spectrum of disorders including autoimmune pancreatitis and inflammatory pseudotumor. SUMMARY: Pathologic features of viral hepatitis C and E, immunohistochemistry for the ductular reaction and malignant liver tumors and several systemic disorders are among recent important pathology studies.

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.

Njoroge FG, Chen KX, Shih NY, Piwinski JJ. · Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. · Acc Chem Res. · Pubmed #18193821 No free full text.

Abstract: More than 170 million people worldwide are affected by the hepatitis C virus (HCV). The disease has been described as a "silent epidemic" and "a serious global health crisis". HCV infection is a leading cause of chronic liver disease such as cirrhosis, carcinoma, or liver failure. The current pegylated interferon and ribavirin combination therapy is effective in only 50% of patients. Its moderate efficacy and apparent side effects underscore the need for safer and more effective treatments. The nonstructural NS3 protease of the virus plays a vital role in the replication of the HCV virus. The development of small molecule inhibitors of NS3 protease as antiviral agents has been intensively pursued as a viable strategy to eradicate HCV infection. However, it is a daunting task. The protease has a shallow and solvent-exposed substrate binding region, and the inhibitor binding energy is mainly derived from weak lipophilic and electrostatic interactions. Moreover, lack of a robust in vitro cell culture system and the absence of a convenient small animal model have hampered the assessment of both in vitro and in vivo efficacy of any antiviral compounds. Despite the tremendous challenges, with access to a recently developed cell-based replicon system, major progress has been made toward a more effective small molecule HCV drug. In our HCV program, facing no leads from our screening effort, a structure-based drug design approach was carried out. An alpha-ketoamide-type electrofile was designed to trap the serine hydroxyl of the protease. Early ketoamide inhibitors mimicked the structures of the peptide substrates. With the aid of X-ray structures, we successfully truncated the undecapeptide lead that had a molecular weight of 1265 Da stepwise to a tripeptide with a molecular weight of 500 Da. In an attempt to depeptidize the inhibitors, various strategies such as hydrazine urea replacement of amide bonds and P2 to P4 and P1 to P3 macrocyclizations were examined. Further optimization of the tripeptide inhibitors led to the identification of the best moieties for each site: primary ketoamide at P', cyclobutylalanine at P1, gem-dimethylcyclopropylproline at P2, tert-leucine at P3, and tert-butyl urea as capping agent. The combination of these led to the discovery of compound 8 (SCH 503034, boceprevir), our clinical candidate. It is a potent inhibitor in both enzyme assay (Ki* = 14 nM) and cell-based replicon assay (EC 90 = 0.35 microM). It is highly selective (2200x) against human neutrophil elastase (HNE). Boceprevir is well tolerated in humans and demonstrated antiviral activity in phase I clinical trials. It is currently in phase II trials. This Account details the complexity and challenges encountered in the drug discovery process.

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.

Venkatraman S, Njoroge FG. · MS 3545, K15, Schering Plough Research Institute, Kenilworth, NJ 07033, USA. · Curr Top Med Chem. · Pubmed #17627558 No free full text.

Abstract: HCV NS3, a serine protease, that when bound to NS-4A cofactor facilitates development of mature virons by catalyzing cleavage of a single polyprotein to form functional and structural proteins of HCV. X-ray structure of the enzyme reveal a very shallow binding pocket at the catalytic site which makes development of inhibitors a daunting task. Various novel approaches have been used to design, preorganized, depeptidized macrocyclic inhibitors linking the P(2)-P(4) residues and P(1)-P(3) groups. The design and structure activity relationship of these macrocyclic inhibitors are reviewed in the following article. X-ray structure of inhibitor bound to the active site of the enzyme is also discussed. Macrocyclization proved to be an effective tool for depeptidization of peptidic inhibitors, imparting enhanced metabolic stability and improved pharmacokinetic properties in the resultant molecules.

Ben-Menachem T. · UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA. · Eur J Gastroenterol Hepatol. · Pubmed #17625428 No free full text.

Abstract: Cholangiocarcinoma occurs with a varying frequency in different areas of the world. Some of the variations in incidence rates can be explained by the distribution of risk factors in different geographic regions and ethnic groups. Several accepted risk factors for cholangiocarcinoma include infestation with liver flukes, primary sclerosing cholangitis, hepatolithiasis, choledochal cysts, cirrhosis, and infusion of certain chemical agents. Approximately, 90% of patients diagnosed with cholangiocarcinoma do not have a recognized risk factor for the malignancy. The study by Ahrens et al. [16] finds that obesity and gallstones are risk factors for developing extrahepatic cholangiocarcinoma in men patients. Obesity was found to have a 'dose-effect' relationship with the strength of statistical association. No significant association was reported for tobacco or alcohol use, hepatitis, cirrhosis, diabetes, or inflammatory bowel disease. Although the author's definition of extrahepatic cholangiocarcinoma was unusual, the association of obesity with the risk of developing cholangiocarcinoma persisted for all anatomic subsites.

Kalia H, Lopez PM, Martin P. · Division of Gastroenterology, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA. · Arch Med Res. · Pubmed #17613354 No free full text.

Abstract: There continues to be a high prevalence of hepatitis C virus infection in patients with chronic kidney disease (CKD) on maintenance hemodialysis, despite screening of blood products and precautions to prevent the transmission of viral hepatitis within dialysis units. In addition, an increased rate of mortality from liver disease has been observed in infected patients on long-term dialysis, despite the frequent absence of biochemical dysfunction. Hepatitis C-infected renal transplant recipients have diminished patient and graft survivals compared to uninfected controls. Treatment with interferon in renal transplant candidates has resulted in sustained viral responses that have been long lasting even after subsequent renal transplant. A major concern limiting the use of interferon following renal transplant is graft dysfunction due to rejection. Ribavirin's induction of hemolytic anemia is the major reason why it is avoided in patients with CKD. Cautious use of reduced-dose ribavirin in small studies has been promising in these patients with close monitoring of hematocrit and additional measures to enhance compensatory erythropoiesis.