Hepatic fibrosis and factors associated with liver stiffness in HIV mono-infected individuals.

BACKGROUND: Liver disease has become an important cause of morbidity and mortality even in those HIV-infected individuals who are devoid of hepatitis virus co-infection. The aim of this study was to evaluate the degree of hepatic fibrosis and the role of associated factors using liver stiffness measurement in HIV mono-infected patients without significant alcohol intake. METHODS: We performed a cross-sectional study of 101 HIV mono-infected patients recruited prospectively from March 1, 2014 to October 30, 2014 at the Center for HIV, St István and St László Hospital, Budapest, Hungary. To determine hepatic fibrosis, liver stiffness was measured with transient elastography. Demographic, immunologic and other clinical parameters were collected to establish a multivariate model. Bayesian Model Averaging (BMA) was performed to identify predictors of liver stiffness. RESULTS: Liver stiffness ranged from 3.0-34.3 kPa, with a median value of 5.1 kPa (IQR 1.7). BMA provided a very high support for age (Posterior Effect Probability-PEP: 84.5%), moderate for BMI (PEP: 49.3%), CD4/8 ratio (PEP: 44.2%) and lipodystrophy (PEP: 44.0%). For all remaining variables, the model rather provides evidence against their effect. These results overall suggest that age and BMI have a positive association with LS, while CD4/8 ratio and lipodystrophy are negatively associated. DISCUSSION: Our findings shed light on the possible importance of ageing, overweight and HIV-induced immune dysregulation in the development of liver fibrosis in the HIV-infected population. Nonetheless, further controlled studies are warranted to clarify causal relations.

Hepatic steatosis in individuals living with HIV measured by controlled attenuation parameter: a cross-sectional study.

OBJECTIVES: Available data on the prevalence of hepatic steatosis in an unselected HIV-infected population are limited. The aim of this study was to determine the prevalence of hepatic steatosis and assess the associated factors in HIV-infected individuals. PATIENTS AND METHODS: One hundred and thirty-six HIV-infected individuals were enrolled in this cross-sectional study. Patients underwent transient elastography and controlled attenuation parameter (CAP) measurements. We analyzed the associations between the CAP value and demographic, metabolic, and immunologic parameters. For the first time, in HIV-infected individuals, we used a continuous scale of CAP values to identify significant covariates of hepatic fat accumulation. As a result and compared with other methods, one of the main advantages of CAP was that the quantitative measurement of liver steatosis could be used for analysis. RESULTS: Using univariate analysis, CAP was significantly correlated with the following continuous variables: CD4 percentage (P=0.035), CD8 percentage (P=0.016), age (P<0.001), CD4/8 ratio (P=0.002), BMI (P<0.001), serum triglyceride (P<0.001), and serum cholesterol (P=0.004) levels, the length of known HIV positivity (P<0.001), and liver stiffness (P=0.041). With respect to categorical variables, a significant association was found for the presence of diabetes (P=0.006), hypertension (P<0.001), facial lipodystrophy (P=0.031), and the use of lopinavir (P=0.042). In multivariate analysis using linear regression, BMI (P<0.001), presence of diabetes (P=0.026), and hypertension (P=0.040) were identified as independent significant correlates. Darunavir therapy was associated negatively with the CAP value (P=0.032). CONCLUSION: Our findings reflect the importance of metabolic factors in hepatic steatosis. The strongest independent covariate was BMI.

Extensive flow cytometric characterization of plasmacytoid dendritic cell leukemia cells.

OBJECTIVES: Accumulating evidence suggests that non-T, non-B cell CD4+CD56+ neoplasms with lymphoblastic morphology include clinically and immunophenotypically diverse entities. Although their cells of origin or classification are still controversial several entities clearly represent a distinct type of neoplasms that are clinically aggressive. METHODS: In this work we present the immunophenotypic and genotypic features of bone marrow (BM), peripheral blood (PB), lymph node and skin lymphocytes from a patient diagnosed as plasmacytoid dendritic cell leukemia involving the skin, BM, PB, lymph nodes, liver and spleen. For determination of immunophenotypic characteristics of malignant plasmacytoid dendritic cells 73 monoclonal antibodies detecting lineage markers, chemokine receptors, cytokine receptors, activation, and co-stimulatory molecules were used. RESULTS AND CONCLUSION: The malignant cells proved to express CD4+, CD56+ lineage negative leukemia phenotype characteristically positive for CD36, CD38, CD40, CD45, CD45RA, CD68, CD123, CD184, HLA-DR, BDCA2, and granzyme-B corresponding to the preplasmacytoid dendritic cell developmental stage. The presence of CD11a/CD18, CD84, CD91, CD95, alphavbeta5, CDw197, and the absence of CD52 and CD133 in this case can be regarded as additional features of malignant cells. Completing the immunophenotypes with multidrug resistance function can provide additional information for characterizing pDC leukemia.

Reactivity of new adhesion molecules on lymphocytes from patients with chronic graft versus host disease.

Reaction patterns of the 7th Human Leukocyte Differentiation Antigen Workshop blind panel adhesion molecules were studied on CD3/CD4, CD3/CD8, CD3/TCR gamma delta double positive T cells from peripheral blood of patients with chronic graft versus host disease (n = 8) and healthy controls (n = 4). Reactivity of 14 adhesion antibodies was tested by three-colour immunophenotyping. The mean proportion of CD3+ T cells (69 +/- 19%). CD3/CD8++ (31 +/- 13%) and CD3/TCR gamma delta++ (4 +/- 2%) T sub-populations of patients were comparable with the healthy controls. However, the mean percentage of CD3/CD4++ T cell subset in patients (14 +/- 12%) proved to be significantly decreased in comparison with the normal control value (34 +/- 16%) presumably due to secondary immunodeficiency. The workshop antibodies proved to be reactive with three T cell subsets expressing the examined antigens. Based on the results of the adhesion molecule workshop new CD categories have been introduced: CD156b as a transmembrane protein, CD167a as an epithelial tyrosin kinase receptor, CD168 as a receptor for hyaluronan mediated motility (RHAMM) and CD171 as a co-stimulatory adhesion molecule. There were significant differences in the expression of the CD167a and CD156b antigens on the CD3/CD4++ subset between the samples of patients compared with the controls characterizing the CD4+ T lymphocyte subpopulation in chronic graft versus host disease.

Functional significance of genetic abnormalities in multiple myeloma.

Multiple myeloma (MM) is a B-cell neoplasm characterized by infiltration of the bone marrow with malignant plasma cells, synthesizing and secreting monoclonal immunoglobulin fragments. The malignant transformation of this terminally differentiated plasma cell is the result of a multistep transformation process. In spite of recent advances in this field, the cause and the exact molecular genetic basis of MM remain obscure. In this review, an attempt has been made to summarize the genetic alterations having functional significance in the generation and progression of MM, and also the existing relationship between genetic abnormalities and chemosensitivity, as well as the typical genetic alterations in various MM subgroups. Factors known to have a role in the conversion of monoclonal gammopathy of unknown significance (MGUS) to MM are also reviewed.

Telomere length analysis on cord blood cells by the flow-FISH method.

Telomerase is the enzyme responsible for synthesizing telomeric repeats at the ends of chromosomes to maintain telomere length. Recent studies have suggested that telomere shortening may serve as a surrogate marker of the progression of malignant disorders and seems to be accelerated in allogeneic bone marrow transplant recipients. In this study, the results of the telomere length of nine cord blood mononuclear cell samples are presented. Telomere length was measured by the flow-FISH method, using a peptide nucleic acid probe. The proportion of cord blood cell subsets (CD19/CD34/CD3) was also evaluated. The telomere length of the internal control 1301 cell line was estimated to be 100%. The mean telomere length of cord blood cells was 18.5 +/- 3.9%, compared with the internal control. The progenitor CD34+ cells were detected as 2.6 +/- 0.7% in the lymphoid gate measured. Linear correlation analysis did not find any connection between the cell subsets (CD3+, CD34+, CD19+) and the telomere length. The findings confirm that the telomere flow-FISH method is sufficient for estimation of the telomere length. Assessment of the current procedures of collection, manipulation, and ex vivo expansion of cord blood cells in terms of their effect on telomere shortening might be important.