Hepatitis: New York City

Hammer SM, Eron JJ, Reiss P, Schooley RT, Thompson MA, Walmsley S, Cahn P, Fischl MA, Gatell JM, Hirsch MS, Jacobsen DM, Montaner JS, Richman DD, Yeni PG, Volberding PA, Anonymous00064. · Division of Infectious Diseases, Columbia University College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA. · JAMA. · Pubmed #18677028 links to  free full text

Abstract: CONTEXT: The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection. OBJECTIVES: To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients. DATA SOURCES AND STUDY SELECTION: A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified. DATA EXTRACTION AND SYNTHESIS: Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus. CONCLUSIONS: New data and considerations support initiating therapy before CD4 cell count declines to less than 350/microL. In patients with 350 CD4 cells/microL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100,000 copies/mL) and rapidly declining CD4 cell count (>100/microL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial regimen must be individualized, particularly in the presence of comorbid conditions, but usually will include efavirenz or a ritonavir-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine). Treatment failure should be identified and managed promptly, with the goal of therapy, even in heavily pretreated patients, being an HIV-1 RNA level below assay detection limits.

Hammer SM, Saag MS, Schechter M, Montaner JS, Schooley RT, Jacobsen DM, Thompson MA, Carpenter CC, Fischl MA, Gazzard BG, Gatell JM, Hirsch MS, Katzenstein DA, Richman DD, Vella S, Yeni PG, Volberding PA, Anonymous00173. · Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. · JAMA. · Pubmed #16905788 links to  free full text

Abstract: CONTEXT: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field. OBJECTIVE: To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. DATA SOURCES AND STUDY SELECTION: A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. DATA EXTRACTION AND SYNTHESIS: Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. CONCLUSIONS: Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.

Laurence J. · Laboratory for AIDS Virus Research, Weill Cornell Medical College, New York, USA. · AIDS Read. · Pubmed #19062396 No free full text.

This publication has no abstract.

Berk PD. · The Division of Digestive Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY. · Hepatology. · Pubmed #16447279 No free full text.

This publication has no abstract.

Orsini J, Nadkarni A, Chen J, Cohen N. · Division of Critical Care Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10467-2490, USA. · Am J Health Syst Pharm. · Pubmed #19420309 No free full text.

Abstract: PURPOSE: A case of propofol infusion syndrome in a patient with respiratory failure and sepsis is reported. SUMMARY: A 36-year-old Hispanic woman was admitted to the medical intensive care unit for treatment of respiratory failure and sepsis, likely secondary to pneumonia. Her medical history included human immunodeficiency virus infection and chronic hepatitis C virus infection. She was intubated and placed on mechanical ventilation. Empirical i.v. antimicrobial therapy was initiated with vancomycin, moxifloxacin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and micafungin, along with corticosteroids and vasopressors. Propofol 1.5 mg/kg per hour i.v. and midazolam i.v. were initiated for sedation, but the dosages of both propofol and midazolam needed to be increased due to persistent agitation. On hospital day 7, the patient developed a morbilliform rash on her neck, shoulders, and chest and multiple abnormal laboratory test values, including elevated levels of alanine transaminase, aspartate transaminase, amylase, lipase, creatine kinase, and triglycerides. Serial electrocardiograms revealed sinus tachycardia. Computed tomography of the abdomen showed hepatomegaly with fatty infiltration of the liver, no gallstones, and a normal pancreas. I.V. phenobarbital was added for sedation, and propofol was tapered and discontinued on the same day. The patient responded adequately to phenobarbital maintenance therapy and was eventually weaned off all other sedatives. The patient's laboratory test values returned to normal within 72 hours after discontinuation of the propofol infusion, and the rash and tachycardia resolved. CONCLUSION: Propofol infusion syndrome developed in a patient with respiratory failure and sepsis after a prolonged infusion of high-dose propofol.

Goyal RK, Srivastava D, Lessnau KD. · Department of Internal Medicine, Lenox Hill Hospital, 100 East 77th Street, New York, NY 10021, USA. · Pharmacotherapy. · Pubmed #19397467 No free full text.

Abstract: In patients undergoing percutaneous coronary intervention and in those with acute coronary syndromes, clopidogrel plus aspirin is the first-line antiplatelet therapy for reducing cardiovascular events. Although clopidogrel is generally well tolerated, with rash, indigestion, vomiting, diarrhea, and bleeding being the most common adverse effects, rare but serious complications may occur. We describe a 78-year-old woman who underwent percutaneous coronary intervention with drug-eluting stents; clopidogrel and aspirin were started as antiplatelet therapy. Three weeks later, the patient developed mixed hepatocellular and cholestatic liver injury. Clopidogrel was discontinued, and her liver profile results began to improve. Her diagnostic work-up included screening for hepatitis, infectious mononucleosis, and rheumatologic diseases, as well as ultrasonography, magnetic resonance imaging, and endoscopic retrograde cholangiopancreaticography; all results were normal. On day 5 of hospitalization, because of the patient's risk for thrombosis secondary to the drug-eluting stents, clopidogrel was reintroduced; her liver enzyme levels increased. In the absence of any biliary obstruction or other obvious causes of hepatic injury, drug-induced hepatocellular injury and cholestatic jaundice were suspected, and clopidogrel was again discontinued. The patient's liver function tests gradually improved 3 days later and showed marked improvement at her 2-week follow-up visit after discharge. Use of the Maria and Victorino scale for diagnosis of drug-induced hepatotoxicity indicated a probable (score of 14) relationship between clopidogrel and mixed hepatocellular injury and cholestatic jaundice in this patient. Although routine liver function testing is not recommended in patients who receive clopidogrel, having a high index of clinical suspicion, drug rechallenge, and excluding other obvious causes are required to establish the diagnosis of a rare drug complication such as clopidogrel-induced hepatic injury.

Lefkowitch JH. · Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. · Hum Pathol. · Pubmed #19289183 No free full text.

Abstract: Progress in liver histopathology continues to be made, as evidenced by recent publications in all areas of hepatobiliary disease. Multinucleated giant hepatocytes, known to be associated with autoimmune and drug hepatitis, now have been seen in chronic hepatitis C with or without HIV infection and in patients with infection by human herpesvirus-6A. The new term Mallory-Denk body (formerly the Mallory body) recognizes the substantial contributions to this field by Professor Helmut Denk of Austria. The problems of fatty liver and hepatic iron overload have been addressed in studies highlighting their complex pathogenesis. Genomic and immunohistochemical analysis of liver tumors provides important diagnostic information, particularly regarding the use of glypican-3 in the diagnosis of hepatocellular carcinoma.

Kotler DP. · Division of Gastroenterology and Liver Disease, St Lukes-Roosevelt Hospital Center, New York, NY 10025, USA. · Liver Int. · Pubmed #19187071 No free full text.

Abstract: Significant concerns have been raised about the metabolic effects of antiretroviral medication, including the classic triad of dyslipidaemia, insulin resistance (IR) and characteristic alterations in fat distribution (lipoatrophy and lipohypertrophy). Co-infection with hepatitis C appears to exacerbate IR, reduce serum lipids and induce prothrombotic changes in the treated human immunodeficiency virus patient. The effects of co-infection are complex. While combination antiretroviral therapy has been shown to be associated with an increased risk of cardiovascular events through promotion of dyslipidaemia, IR and fat redistribution, co-infection exacerbates IR while reducing serum lipids. Co-infection also promotes a prothrombotic state characterized by endothelial dysfunction and platelet activation, which may enhance risk for cardiovascular disease. Consideration must be given to selection of appropriate treatment regimens and timing of therapy in co-infected patients to minimize metabolic derangements and, ultimately, reduce cardiovascular risk.

Stübgen JP. · Department of Neurology and Neuroscience, Weill Medical College of Cornell University/New York Presbyterian Hospital, USA. · J Neuroimmunol. · Pubmed #19171385 No free full text.

Abstract: Interferon-alpha (IFNalpha) is a potent extracellular protein mediator of host defense and homeostasis. IFNalpha has well-established direct antiviral, antiproliferative and immunomodulatory properties. The worldwide, increasing and long-term use of IFNalpha, particularly for the treatment of chronic hepatitis C virus infection, has drawn attention to the development or exacerbation of numerous autoimmune phenomena, including a variety of neuropathy syndromes, neuromuscular junction disorders and myopathies. Management entailed withdrawal of IFNalpha therapy with supportive, immunomodulatory, and symptomatic treatment as clinically indicated. The mechanisms of IFNalpha-induced autoimmunity are incompletely understood, and likely vary depending on the inherent differences in the pathogenesis of the immune disorder on a background of patient genetic susceptibility. In addition, there is preliminary evidence from case reports and open-label studies that the immunomodulatory effects of IFNalpha may have potential as a treatment option for a spectrum of immune-mediated neuromuscular diseases, but further studies are needed.

Frieden TR, Myers JE, Krauskopf MS, Farley TA. · New York City Department of Health and Mental Hygiene, New York, NY 10013 USA. · Oncologist. · Pubmed #19091779 links to  free full text

Abstract: The "war on cancer" in the United States has been viewed primarily as an effort to develop and disseminate cancer cures, but cancer is far more easily prevented than cured. There are three major approaches to cancer prevention: Primary prevention, through reduction in risk factors and changes to the environment that reduce human exposure to widely-consumed cancer-promoting agents. The most important actions for primary prevention of cancer are those that reduce tobacco use through taxation, smoke-free environment policies, advertising restrictions, counter-advertising, and cessation programs. The World Health Organization's MPOWER package outlines these actions, each of which covered less than 5% of people in the world in 2007. Similarly, cancer can be prevented by reducing alcohol consumption through policies such as alcohol taxes and limits on alcohol sales, and restoring caloric balance through policies such as creating healthier food environments and engineering the built environment to increase opportunities for physical activity. Vaccination is an effective approach to preventing specific virus-associated cancers, such as using human papillomavirus vaccine to prevent cervical cancer and hepatitis B virus vaccine to prevent hepatocellular cancer. Secondary prevention reduces cancer mortality through screening and early treatment; this approach has been used successfully for breast and cervical cancer but is still underused against colon cancer. Progress can be made in all three approaches to cancer prevention, but will require a greater emphasis on public health programs and public policy. Winning the war on cancer will require a much larger investment in prevention to complement efforts to improve treatment.

Lelutiu-Weinberger C, Pouget ER, Des Jarlais DD, Cooper HL, Scheinmann R, Stern R, Strauss SM, Hagan H. · Center for Drug Use and HIV Research, National Development and Research Institutes, 71 West 23rd Street, 8th Floor, New York, NY 10010 United States. · Soc Sci Med. · Pubmed #19062148 No free full text.

Abstract: Hepatitis C virus (HCV) is mostly transmitted through blood-to-blood contact during injection drug use via shared contaminated syringes/needles or injection paraphernalia. This paper used meta-analytic methods to assess whether HCV prevalence and incidence varied across different racial/ethnic groups of injection drug users (IDUs) sampled internationally. The 29 prevalence and 11 incidence studies identified as part of the HCV Synthesis Project were categorized into subgroups based on similar racial/ethnic comparisons. The effect estimate used was the odds or risk ratio comparing HCV prevalence or incidence rates in racial/ethnic minority groups versus those of majority status. For prevalence studies, the clearest disparity in HCV status was observed in the Canadian and Australian Aboriginal versus White comparison, followed by the US non-White versus White categories. Overall, Hispanic IDUs had greater HCV prevalence, and HCV prevalence in African-Americans was not significantly greater than that of Whites in the US. Aboriginal groups showed higher HCV seroconversion rates when compared to others, and African-Americans had lower seroconversion rates compared to other IDUs in the US. The findings suggest that certain minority groups have elevated HCV rates in comparison to other IDUs, which may be a consequence of stigma, discrimination, different risk behaviors or decreased access to health care, services and preventive education. Future research should seek to explicitly explore and explain racial/ethnic variations in HCV prevalence and incidence, and define the groups more precisely to allow for more accurate detection of possible racial/ethnic differences in HCV rates.

Kalim S, Szczech LA, Wyatt CM. · Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. · Semin Nephrol. · Pubmed #19013326 No free full text.

Abstract: Acute kidney injury is common in human immunodeficiency virus (HIV)-infected patients, and has been associated with increased morbidity and mortality. Before the introduction of effective antiretroviral therapy, acute kidney injury in HIV-positive patients was most commonly the result of volume depletion, septicemia, or nephrotoxic medications. Acute kidney injury remains a significant problem in the antiretroviral era, and still commonly is attributed to infection or nephrotoxic medications. Less common causes such as direct infectious insults, immune restoration inflammatory syndrome, rhabdomyolysis, and obstruction should be considered when the underlying process is not obvious. In addition to advanced HIV disease, several other patient characteristics have emerged as potential risk factors for acute kidney injury in the antiretroviral era, including older age, diabetes, pre-existing chronic kidney disease, and hepatitis co-infection or liver disease.

Cohen SD, Chawla LS, Kimmel PL. · Division of Nephrology, Department of Medicine, College of Physicians and Surgeons, Columbia University, Washington, District of Columbia, USA. · Curr Opin Crit Care. · Pubmed #19005305 No free full text.

Abstract: PURPOSE OF REVIEW: To present an overview of the epidemiology and etiology of acute kidney injury (AKI) in patients infected with human immunodeficiency virus (HIV). RECENT FINDINGS: HIV-infected patients are at an increased risk of developing AKI. Potential risk factors for the development of AKI in this patient population include increased HIV viral loads, reduced CD4 cell counts, hepatitis C virus coinfection, a history of diabetes, black race, male gender, and baseline chronic kidney and hepatic disease. Observational studies have found an increased morbidity and mortality in HIV-infected patients who develop AKI. There are diverse etiologies of AKI in HIV-infected patients, with increasing reports of highly active antiretroviral therapy-related nephropathy secondary to tenofovir nephrotoxicity. There have also been recent case reports of HIV-infected patients who develop a unique form of acute interstitial nephritis secondary to diffuse infiltrative lymphocytosis syndrome. SUMMARY: There are a variety of etiologies of AKI in HIV-infected patients. Prompt diagnosis and treatment of AKI is critical to help prevent morbidity and mortality in this patient population.

Wilkin TJ, Gulick RM. · Division of International Medicine and Infectious Diseases, Weill-Cornell Medical College, New York, New York 10011, USA. · Clin Infect Dis. · Pubmed #18990069 No free full text.

Abstract: The optimal time to start antiretroviral therapy (ART) for human immunodeficiency virus (HIV)-infected individuals remains uncertain. Although current ART regimens are effective in suppressing viremia and enhancing immune function and are increasingly convenient and well tolerated, ongoing concerns remain about adherence, drug-related toxicities, drug resistance, and cost. Although few clinical trials results are currently available to inform the question of when to start ART, large clinical cohorts clearly have demonstrated the benefits of earlier initiation of ART for reducing both HIV-related and non-HIV-related clinical events. Additional data suggest that the strategy of earlier initiation of ART is cost-effective and efficient. Consequently, many antiretroviral guidelines from around the world now recommend routine initiation of ART when the CD4 cell count decreases to <350 cells/microL or at higher CD4 cell counts for certain subgroups of HIV-infected individuals, such as pregnant and/or breast-feeding women and persons with HIV-related nephropathy or hepatitis virus coinfection. Additional cohort and clinical trials data are needed.

Levy B, Arnason JE, Bussel JB. · Platelet Research & Treatment Program, Division of Pediatric Hematology Oncology, Weill Cornell Medical College, New York, New York, USA. · Curr Opin Oncol. · Pubmed #18841052 No free full text.

Abstract: PURPOSE OF REVIEW: This review summarizes the history of the development of thrombopoietic agents and discusses their potential use in chemotherapy-induced thrombocytopenia. RECENT FINDINGS: A new generation of thrombopoietic agents have had preliminary success in the treatment of thrombocytopenia. The initial thrombopoietic agents were recombinant and pegylated human megakaryocyte growth factor. These agents showed promise in the treatment of chemotherapy-induced thrombocytopenia but had the unfortunate side effect of promoting the development of antibodies against endogenous thrombopoietin and subsequent refractory thrombocytopenia. Now, a second generation of synthetic thrombopoietic agents including AMG 531 and eltrombopag have shown promise in the treatment of thrombocytopenia in patients with immune thrombocytopenia purpura and hepatitis C without the development of an immunological response. As these new agents see broader use, many questions regarding their safety and their most effective administration need to be answered. SUMMARY: The second generation of thrombopoietic agents has been shown to correct thrombocytopenia in selected diseases with a minimum of side effects. Looking forward, there is great potential for their use in other forms of thrombocytopenia, including chemotherapy-induced thrombocytopenia, but there are also many questions remaining regarding their best and safest use.

Stern RK, Hagan H, Lelutiu-Weinberger C, Des Jarlais D, Scheinmann R, Strauss S, Pouget ER, Flom P. · Center for Drug Use and HIV Research, National Development and Research Institutes (NDRI), 71 West 23rd Street, 8th Floor, New York, NY 10010, USA. · BMC Med Res Methodol. · Pubmed #18789163 links to  free full text

Abstract: BACKGROUND: The hepatitis C virus (HCV) is hyper-endemic in injecting drug users. There is also excess HCV among non-injection drug users who smoke, snort, or sniff heroin, cocaine, crack, or methamphetamine. METHODS: To summarize the research literature on HCV in drug users and identify gaps in knowledge, we conducted a synthesis of the relevant research carried out between 1989 and 2006. Using rigorous search methods, we identified and extracted data from published and unpublished reports of HCV among drug users. We designed a quality assurance system to ensure accuracy and consistency in all phases of the project. We also created a set of items to assess study design quality in each of the reports we included. RESULTS: We identified 629 reports containing HCV prevalence rates, incidence rates and/or genotype distribution among injecting or non-injecting drug user populations published between January 1989 and December 2006. The majority of reports were from Western Europe (41%), North America (26%), Asia (11%) and Australia/New Zealand (10%). We also identified reports from Eastern Europe, South America, the Middle East, and the Caribbean. The number of publications reporting HCV rates in drug users increased dramatically between 1989 and 2006 to 27-52 reports per year after 1998. CONCLUSION: The data collection and quality assurance phases of the HCV Synthesis Project have been completed. Recommendations for future research on HCV in drug users have come out of our data collection phase. Future research reports can enhance their contributions to our understanding of HCV etiology by clearly defining their drug user participants with respect to type of drug and route of administration. Further, the use of standard reporting methods for risk factors would enable data to be combined across a larger set of studies; this is especially important for HCV seroconversion studies which suffer from small sample sizes and low power to examine risk factors.

Abou-Alfa GK, Venook AP. · Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10022, USA. · Curr Oncol Rep. · Pubmed #18765149 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, causing 500,000 deaths yearly. The risk factors mostly responsible for the rising incidence of HCC in the Western hemisphere are hepatitis C, alcoholic cirrhosis, and nonalcoholic steatohepatitis, which most commonly leads to HCC in the setting of cirrhosis. Over the past 30 years, several chemotherapeutic single agents and combinations have been tested in HCC, yet none have demonstrated any improvement in survival. Recently, the multitargeted anti-angiogenic and Raf kinase inhibitor sorafenib has shown a survival advantage as a single agent and improved outcomes in combination with doxorubicin. Other novel agents have also shown intriguing outcomes as single agents (sunitinib) or in combination (bevacizumab and erlotinib). The encouraging results and clinical information gathered in recent trials are generating important clinical questions regarding which patients to treat, how to accommodate concurrent cirrhosis, and which parameters to use to monitor efficacy and the potential benefit from therapy.

Wyatt CM, Malvestutto C, Coca SG, Klotman PE, Parikh CR. · Department of Medicine, Division of Nephrology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA. · AIDS. · Pubmed #18753863 No free full text.

Abstract: BACKGROUND: In the era of antiretroviral therapy, non-AIDS complications such as kidney disease are important contributors to morbidity and mortality. OBJECTIVE: To estimate the impact of hepatitis C coinfection on the risk of kidney disease in HIV patients. DESIGN AND METHODS: Two investigators identified English-language citations in MEDLINE and Web of Science from 1989 through 1 July 2007. References of selected articles were reviewed. Observational studies and clinical trials of HIV-related kidney disease and antiretroviral nephrotoxicity were eligible if they included at least 50 subjects and reported hepatitis C status. Data on study characteristics, population, and kidney disease outcomes were abstracted by two independent reviewers. RESULTS: After screening 2516 articles, 27 studies were eligible and 24 authors confirmed or provided data. Separate meta-analyses were performed for chronic kidney disease outcomes (n = 10), proteinuria (n = 4), acute renal failure (n = 2), and indinavir toxicity (n = 5). The pooled incidence of chronic kidney disease was higher in patients with hepatitis C coinfection [6.2 versus 4.0%; relative risk 1.49, 95% confidence interval (CI) 1.08-2.06]. In meta-regression, prevalence of black race and the proportion of patients with documented hepatitis C status were independently associated with the risk of chronic kidney disease. The relative risk associated with hepatitis C coinfection was significantly increased for proteinuria (1.15; 95% CI 1.02-1.30) and acute renal failure (1.64; 95% CI 1.21-2.23), with no significant statistical heterogeneity. The relative risk of indinavir toxicity was 1.59 (95% CI 0.99-2.54) with hepatitis C coinfection. CONCLUSION: Hepatitis C coinfection is associated with a significant increase in the risk of HIV-related kidney disease.

Gambarin-Gelwan M, Jacobson IM. · Weill Cornell Medical College, New York, NY 10021, USA. · J Viral Hepat. · Pubmed #18637069 No free full text.

Abstract: Chronic hepatitis C affects 170 million people worldwide, including up to 4 million people in the United States. The current standard of care therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV) while highly successful in patients with genotype 2 and 3 infection, allows for sustained virologic response in 42-46% of treatment-naïve genotype 1 patients, comprising about 70% of cases of chronic hepatitis C in the USA. While awaiting approval of Specifically Targeted Antiviral Therapy for HCV (STAT-C) agents, which will require the completion of additional clinical trials, it is important to optimize the dose and duration of currently available treatment modalities, namely PEG-IFN and RBV, for treatment of CHC. Results of several recent trials evaluating optimal dosing of RBV and higher than standard dosing of PEG-IFN in treatment-naïve genotype 1 patients, as well as data from retreatment trials with "induction" doses of PEG-IFN or high-dose RBV in prior non-responders to IFN-based therapy will be reviewed here. The possibility of shorter duration of therapy for genotype 2 and 3 patients based on recent publications and presentations will be discussed as well.

Verna EC, Brown RS. · Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA. · Clin Liver Dis. · Pubmed #18625432 No free full text.

Abstract: Hepatitis C (HCV)-related end-stage liver disease is the most common indication for liver transplantation. Safe expansion of the donor pool with improved rates of deceased donation and more widespread use of living and extended criteria donation are likely to decrease wait list mortality. In addition, improved antiviral treatments and a better understanding of the delicate balance between under- and over-immunosuppression in this population are needed. Finally, when recurrent advanced fibrosis occurs, the criteria for patient selection for retransplantation remain widely debated. This article reviews the literature on these topics and the work being done in each area to maximize outcomes in patients receiving transplants for HCV-related cirrhosis.

Marsch LA, Bickel WK, Grabinski MJ. · Center for Drug Use and HIV Research, National Development and Research Institutes, 71 West 23rd Street, 8th Floor, New York, NY 10010, USA. · Adolesc Med State Art Rev. · Pubmed #18605650 No free full text.

Abstract: This article provides an overview of several interactive, computer-based substance abuse-prevention and -treatment interventions that we have developed for adolescents, including an interactive substance abuse-prevention multimedia program for middle school-aged youth and a customizable program focused on prevention of HIV, hepatitis, and sexually transmitted infections among youth in substance abuse treatment. The content in these programs is grounded in a scientific understanding of the types of skills and information that are critical to effective prevention. The programs also use several evidence-based informational technologies that have been shown to be critical in effectively training key skills and information. Our evaluations to date have underscored the effectiveness of these programs in producing desired health-behavior change. Applying information technologies to the delivery of science-based interventions may allow for unique opportunities to provide widespread dissemination of cost-effective interventions with consistency and in a manner that is engaging and acceptable to youth.

Kobos R, Bussel JB. · Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Clin Lymphoma Myeloma. · Pubmed #18501086 No free full text.

Abstract: Pharmaceutical advances in the field of hematology have led to promising new options for the management of thrombocytopenia. This overview provides both a brief review of historical management of thrombocytopenia and a more detailed look at the novel thrombopoietic agents currently being investigated for their utility in treating thrombocytopenia. Specific agents that enhance thrombopoiesis will alter the overall approach to immune thrombocytopenia purpura. Development of these agents might also improve the management of diseases such as cancer and hepatitis C, whose current regimens are limited by the occurrence of thrombocytopenia.

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.