Hepatitis: Cohen M

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

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

Rotman Y, Katz L, Cohen M, Cohen-Ezra O, Manhaim V, Braun M, Ben-Ari Z, Tur-Kaspa R. · Liver Institute, Rabin Medical Center, Bellinson Hospital, Petach-Tiqwa, Israel. · J Viral Hepat. · Pubmed #19220735 No free full text.

Abstract: Treatment-induced neutropenia frequently complicates the treatment course of patients treated with pegylated interferon alfa and ribavirin for chronic hepatitis C. We investigated the effect of weight on the risk for dose reductions caused by neutropenia in patients treated with a weight-independent dose of peginterferon alfa-2a. We retrospectively analysed single centre data for 172 patients enrolled in a multi-centre, open-label trial of peginterferon alfa-2a and ribavirin for chronic hepatitis C. Low body weight was significantly associated with dose reductions due to neutropenia. Patients weighing less than 62 kg had a 35% risk for significant neutropenia as opposed to a 12% risk for heavier patients (P = 0.001), and this side-effect occurred earlier during treatment. Low weight was an independent risk factor by multivariate analysis (hazard ratio 0.956/kg). The risk for treatment-induced neutropenia was associated with body surface area more than with the body mass index. In conclusion, a low pre-treatment weight strongly predicts the need for peginterferon alfa-2a dose reductions. This apparently reflects overall body size more than body fat content. It is prudent to frequently monitor blood counts for smaller-sized patients, especially during the first weeks of treatment.

Feldman DN, Feldman JG, Greenblatt R, Anastos K, Pearce L, Cohen M, Gange S, Leanza S, Burk R. · Department of Pathology, University of Arizona College of Medicine, Tucson, AZ 85724, USA. · AIDS Educ Prev. · Pubmed #19537956 No free full text.

Abstract: We have recently shown that cigarette smoking is associated with lesser responses to potent antiretroviral therapies. Certain Cytochrome P-450 enzymes activate compounds derived from tobacco smoke into toxic forms that may promote HIV-1 gene expression through promotion of DNA-adduct formation by the oxidation of chemical constituents of cigarette smoke, such as polyaromatic hydrocarbons and dioxins. To explore the association between environmental and genetic factors to viral replication in women who smoke and receive highly active anti-retroviral therapy (HAART), we assessed the impact of polymorphisms in a panel of four Cytochrome P-450 genes (CYP1A1, CYP2A6, CYP2D6, and CYP2E1) and two Glutathione S-transferase genes (GSTM1 and GSST1) in 924 participants of the Women's Interagency HIV Study (WIHS). Our findings showed that GSTM1 and GSST1 deletions were not associated with HAART effectiveness. By contrast, homozygosity for the CYP1A1-m1 polymorphism, was associated with impaired viral response to treatment among smokers (relative hazard (RH) = 0.54; 95% confidence interval = 0.31-0.94) after adjustment for pretreament viral load, CD4 count, age, hepatitis C infection, prior HAART therapy and race, although it had no effect among nonsmokers. We conclude that the association of the CPY1A1-m1 variant with a reduced response to HAART therapy in HIV infected smokers is consistent with this enzyme's role in the metabolic conversion of environmental toxins to DNA adducts, which may directly promote HIV-1 gene expression.

Tien PC, Schneider MF, Cole SR, Levine AM, Cohen M, DeHovitz J, Young M, Justman JE. · Department of Medicine, University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA. · J Acquir Immune Defic Syndr. · Pubmed #19186350 No free full text.

Abstract: BACKGROUND: Evidence suggesting an increased risk of cardiovascular disease in HIV-infected individuals has heightened the need to understand the relation of HIV infection, antiretroviral therapy use, and non-HIV-related factors with insulin resistance (IR). METHODS: Prospective study of 1614 HIV-infected and 604 HIV-uninfected participants from the Women's Interagency HIV Study between October 2000 and March 2007. Homeostasis model assessment (HOMA)-estimated IR at 11,019 semiannual visits. RESULTS: HIV-infected women reporting highly active antiretroviral therapy (HAART) had higher median HOMA than HIV-uninfected women {1.20 [95% confidence interval (CI): 1.11 to 1.30] times higher for those reporting protease inhibitor-containing HAART; 1.10 (95% CI: 1.01 to 1.20) times higher for those reporting non-protease inhibitor-containing HAART}. Among HIV-infected, cumulative exposure to nucleoside reverse transcriptase inhibitors (NRTIs) of > 3 years was associated with HOMA 1.13 (95% CI: 1.02 to 1.25) times higher than the HOMA without any cumulative NRTI exposure. Cumulative exposure to the NRTI stavudine of > 1 year was associated with HOMA 1.15 (95% CI: 1.05 to 1.27) times higher than the HOMA without any cumulative stavudine use. Family history of diabetes, hepatitis C virus seropositivity, higher body mass index, or reporting menopause was associated with higher HOMA. CINCLUSIONS: Longer cumulative exposure to NRTI; in particular, stavudine is associated with greater IR in HIV-infected women.

Kovacs A, Al-Harthi L, Christensen S, Mack W, Cohen M, Landay A. · Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California, USA. · J Infect Dis. · Pubmed #18444798 links to  free full text

Abstract: Immune activation is a hallmark of human immunodeficiency virus type 1 (HIV-1) infection and impacts innate and adaptive immunity. Individuals coinfected with HIV-1 and hepatitis C virus (HCV) may have increased immune activation early in HIV disease because of a high HCV antigen load in tissues such as the liver. We evaluated T cell markers of activation and maturation in women with or without HIV-1 infection, by HCV antibody and HCV RNA status. We found increased percentages of activated CD8(+) T cells (i.e., CD8(+)HLA-DR(+)38(+) cells and CD8(+)CD28(+)HLA-DR(+) cells) but not of CD4(+) T cells among women who tested positive for HIV-1, HCV antibody, and HCV RNA, compared with HIV-1-positive women who tested negative for HCV antibody. Because CD8(+) T cell activation is related to HIV-1 disease progression, these data may have implications for the medical management of patients coinfected with HIV-1 and HCV.

Wolff FH, Fuchs SC, Barcellos NT, Falavigna M, Cohen M, Brandão AB, Fuchs FD. · Post-Graduate Program in Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. · Dig Liver Dis. · Pubmed #18096448 No free full text.

Abstract: BACKGROUND: Except for injecting drug use, other routes of transmission for hepatitis C virus among HIV-AIDS patients have not been consistently described, and risk estimates are often not adjusted for confounding factors. AIMS: To evaluate characteristics associated with hepatitis C virus infection in individuals infected with the HIV. PATIENTS: Cases were patients co-infected by HIV and hepatitis C virus, and controls were infected only by HIV. METHODS: Cases and controls were consecutively enrolled at a public health care outpatient HIV-AIDS reference centre in Porto Alegre, Southern Brazil. RESULTS: A total of 227 cases (63% men; 40.3+/-8.7 years) and 370 controls (44.6% men; 38.9+/-9.8 years) were enrolled in the study. In a multiple logistic regression model, male gender (odds ratio 1.9; 95% confidence interval 1.3-2.7), age between 30 and 49 years (odds ratio 2.1; 95% confidence interval 1.2-3.7), elementary school education (odds ratio 4.2; 95% confidence interval 1.9-9.6), lower family income (odds ratio 1.7; 95% confidence interval 1.1-2.7), sharing personal hygiene objects (odds ratio 2.0; 95% confidence interval 1.3-3.3), using injected drugs (odds ratio 21.6; 95% confidence interval 10.8-43.0) and crack cocaine (odds ratio 2.8; 95% confidence interval 1.1-6.9) were independently associated with co-infection by hepatitis C virus. CONCLUSION: These results confirm the risk profile for hepatitis C virus-HIV infection and suggest that sharing personal hygiene objects might explain the transmission of virus C to those not infected by the usual routes, which may be of relevance for developing preventive strategies.

Shemer-Avni Y, Cohen M, Keren-Naus A, Sikuler E, Hanuka N, Yaari A, Hayam E, Bachmatov L, Zemel R, Tur-Kaspa R. · Clinical Virology Unit, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel. · Clin Infect Dis. · Pubmed #17638183 No free full text.

Abstract: BACKGROUND: Transmission of hepatitis C virus (HCV) from infected health care workers to patients rarely occurs. In 2003, a cluster of patients with HCV infection was identified at a medical center in Israel. All patients had a common history of various surgical procedures performed during the period 2001-2003. All patients had been anesthetized by an anesthesiologist who was an injection drug user and was infected with genotype 2a HCV. Screening was initiated by the hospital to identify newly infected patients with HCV infection and to determine the source of the iatrogenic HCV infection outbreak using comparative molecular analysis of the HCV E1 and HCV E2 hypervariable regions (HVR1 and HVR2). METHODS: A total of 1200 patients who were anesthetized by the anesthesiologist (the related group) and 873 hospital personnel and patients anesthetized by other anesthetists (the unrelated group) were examined. Serum samples were screened for anti-HCV antibodies, HCV RNA, and genotype. Sequence analysis of HVR1 and HVR2 was performed after reverse-transcriptase polymerase chain reaction. RESULTS: HCV type 2a was found in 33 patients in the related group but in only 1 patient in the unrelated group. The differences between the sequences isolated from the related group serum samples and the sequences isolated from genotype 2a control group serum samples (obtained from 15 patients) were highly statistically significant. The genetic distances from the anesthesiologist sequence were 1.4%-4.4% in the HVR1 and 0%-3% in the HVR2 in the related group serum samples, whereas in the HCV genotype 2a control group serum samples, the genetic distances were 22%-45% and 10%-35%, respectively. CONCLUSIONS: Molecular analysis revealed sequence similarity of HVR1 and HVR2 in the related group, suggesting that the anesthesiologist with chronic HCV infection may have transmitted HCV to 33 patients.

Schmilovitz-Weiss H, Cohen M, Pappo O, Sulkes J, Braun M, Tur-Kaspa R, Ben-Ari Z. · Gastroenterology Unit, Hasharon-Golda Campus, Tel Aviv University, Tel Aviv, Israel. · Clin Transplant. · Pubmed #17488390 No free full text.

Abstract: The progression of HCV-related disease is particularly aggressive in the post-transplantation setting. Recipients with recurrent HCV infection undergo repeated liver biopsies in order to estimate disease progression. A strong association was found between serum immunoglobulins levels and hepatic fibrosis in non-transplanted patients with chronic HCV infection. The aim of this study was to determine if serum globulin and immunoglobulins levels can predict the extent of fibrosis in patients with recurrent HCV infection. The records of 45 patients (mean age 51.6 +/- 10.5 yr; 53.3% men) with biochemical, serologic, virologic, and histological evidence of recurrent HCV infection were reviewed. Recurrence developed after a median interval of 11.7 months (range: 3-106); in 14 patients (31.1%), the recurrent infection was severe. The mean duration of follow-up was 51.4 +/- 35.4 months. A total of 96 liver biopsies were performed. The mean fibrosis score increased significantly with an increase in the number of biopsies (p < 0.0001, r = 0.44). On multivariate analysis, the only predictors of severe fibrosis were serum levels of globulin (OR: 5.97, 95% CI: 1.82-19.53; p = 0.0004) and IgG (OR: 1.003, 95% CI: 1.001-1.006; p = 0.018). On linear regression analysis, for each 0.5-g/dL increase in serum globulin level, there was a 0.22-point increase in fibrosis stage. In conclusion, serum levels of globulin and IgG can serve as a noninvasive marker of the extent of hepatic fibrosis in patients with post-transplant recurrent HCV infection, thus avoiding the need for repeated liver biopsies. These findings, if confirmed, have important implications for the prevention and treatment of fibrosis in this patient group.

Nowicki MJ, Karim R, Mack WJ, Minkoff H, Anastos K, Cohen M, Greenblatt RM, Young MA, Gange SJ, Levine AM. · Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. · Hum Immunol. · Pubmed #17462501 No free full text.

Abstract: Studies of human immunodeficiency virus (HIV) infection often compare values from HIV-uninfected controls, including CD4 and CD8 lymphocyte counts. Nonetheless, little is known regarding factors associated with CD4 and CD8 cell numbers in HIV-uninfected individuals. To ascertain potential factors associated with differences in CD4 and CD8 cells among HIV negative women, we studied these cells in a group of 953 women, enrolled as HIV-negative comparators in the Women's Interagency HIV Study. Using standard techniques, we measured CD4 and CD8 cells obtained during study-related visits every six months through visit 20 (maximum of 9.5 years). Results were correlated with demographic and behavioral factors, and data were analyzed using a multiple linear regression approach with generalized estimating equations. At baseline, the median age was 32.4 years, body mass index (BMI) was 26.4 kg/m(2), CD4 cell count was 1010 (range 214-2705)/microL, and CD8 cell count was 542 (range 72-2448)/microL. African-Americans comprised 54%, 24% were Hispanic, and 19% were Caucasian. In multivariate analysis, increasing age (p = 0.0006), increasing BMI (p = 0.001), and current smoking status (p = 0.03) were independent predictors of higher CD4 counts. Multivariate analyses of CD8 cells revealed that lower age (p = 0.001), higher BMI (p = 0.03), Hispanic race/ethnicity (p = 0.01); current smoking (p = 0.006), injection drug use (p = 0.02), and Hepatitis C infection (p = 0.01) were independent predictors of higher CD8 cell counts. Multiple demographic and behavioral factors may influence CD4 and CD8 counts in HIV negative women. These factors must be considered in future analyses comparing lymphocyte subsets in HIV positive and negative women.

Cohen M, Bachmatov L, Ben-Ari Z, Rotman Y, Tur-Kaspa R, Zemel R. · Molecular Hepatology Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel. · Dig Dis Sci. · Pubmed #17436105 No free full text.

Abstract: The hepatitis C virus (HCV) F protein is a recently described, frameshift product of HCV core encoding sequence with unknown biological function. In this study we sought to characterize the prevalence of specific anti-F antibodies in patients with chronic HCV infection and to analyze the anti-F antibody profile before, during, and after antiviral treatment in order to gain a better understanding of the role of F protein in HCV pathogenesis.Serum samples were collected from 44 patients with chronic HCV infection and from 19 healthy controls. Consecutive samples from 27 patients taken before, during, and after treatment with antiviral therapy. The F and the core proteins were cloned from the HCV genome. The recombinant proteins were expressed in Escherichia coli and affinity purified. A sensitive and specific enzyme-linked immunosorbent assay was developed to assess the prevalence of anti-F antibodies. Eighty-nine percent of chronic HCV patients had evidence of anti-F antibodies, and 95% of them had anti-core antibodies. No correlation of anti-F antibodies was found with response to treatment, genotype, or seroconversion. We conclude that the F protein elicits specific antibodies in most individuals chronically infected with HCV with no correlation with response to treatment. Our results confirm the expression of F protein during natural HCV infection.

Feldman JG, Minkoff H, Schneider MF, Gange SJ, Cohen M, Watts DH, Gandhi M, Mocharnuk RS, Anastos K. · SUNY Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY 11203, USA. · Am J Public Health. · Pubmed #16670229 links to  free full text

Abstract: OBJECTIVE: We assessed the association of cigarette smoking with the effectiveness of highly active antiretroviral therapy (HAART) among low-income women. METHODS: Data were analyzed from the Women's Interagency HIV Study, a multisite longitudinal study up to 7.9 years for 924 women representing 72% of all women who initiated HAART between July 1, 1995, and September 30, 2003. RESULTS: When Cox's regression was used after control for age, race, hepatitis C infection, illicit drug use, previous antiretroviral therapy, and previous AIDS, smokers on HAART had poorer viral responses (hazard ratio [HR]=0.79; 95% confidence interval [CI]=0.67, 0.93) and poorer immunologic response (HR=0.85; 95% CI=0.73, 0.99). A greater risk of virologic rebound (HR=1.39; 95% CI=1.06, 1.69) and more frequent immunologic failure (HR=1.52; 95% CI=1.18, 1.96) were also observed among smokers. There was a higher risk of death (HR=1.53; 95% CI=1.08, 2.19) and a higher risk of developing AIDS (HR=1.36; 95% CI=1.07, 1.72) but no significant difference between smokers and nonsmokers in the risk of death due to AIDS. CONCLUSIONS: Some of the benefits provided by HAART are negated in cigarette smokers.