Hepatitis C virus kinetics during and immediately after liver transplantation

The study of hepatitis C virus (HCV) kinetics after liver transplantation (LT) might be important to design strategies to prevent HCV infection of the graft. We analyzed HCV kinetics during and immediately after LT in 20 consecutive patients undergoing LT for HCV-related cirrhosis. HCV RNA was quantified in blood samples obtained at regular intervals before, during, and after transplantation. HCV-RNA concentrations decreased in 18 of 20 patients during the anhepatic phase (mean decay slope -0.92, mean HCV elimination half-life 2.2 hours). We found a significant correlation between the HCV viral load decay and the blood loss during the anhepatic phase, indicating that the observed HCV clearance rates are maximum estimates. In fact, in 1 patient with an unusually long anhepatic phase of 20 hours and with minimum blood loss, the HCV elimination half-life was 10.3 hours. Eight to 24 hours after graft reperfusion a sharp decrease in HCV viral load occurred in 19 patients (mean decay slope -0.34, mean HCV elimination half-life 3.44 hours). HCV RNA became undetectable in only 1 patient. During the following days, HCV-RNA concentrations increased rapidly in 10 patients (mean HCV doubling time 13.8 hours), remained at similar levels in 4, and continued to decrease in 6. The only variable associated with a second-phase viral load decay was the absence of corticosteroids as part of the immunosuppressive regimen. In conclusion, a sharp decrease in HCV viral load occurs during the anhepatic phase and immediately after graft reperfusion, most likely owing to a lack of virion production and hepatic viral clearance. HCV infection of the graft, however, is an extremely dynamic process and viral replication begins a few hours after LT.     

Modulation of the steroidogenic activity of luteinizing hormone by insulin and insulin-like growth factor-I through interaction with the cAMP-dependent protein kinase signaling pathway in the trout ovary

In the salmonid ovary, luteinizing hormone (LH) is the major gonadotropic hormone stimulating the production of steroids during the periovulatory period and its effects are mediated by the cAMP-dependent protein kinase (PKA) signaling pathway. We have previously shown that the in vitro steroidogenic activity of LH in the salmonid ovary is inhibited by insulin-like growth factor I (IGF-I) which, like insulin, has specific receptors in both theca and granulosa layers. In the present study, we have investigated the modulatory effects of insulin on salmon LH (sLH)-stimulated steroid production in preovulatory theca layers of brown trout (Salmo trutta) and the effects of both insulin and IGF-I on the sLH-stimulated cAMP/PKA signaling pathway. Our results show that insulin, like IGF-I, blocked the stimulatory effects of sLH, dibutyryl cAMP and IBMX on testosterone (T) production but not those of sLH on cAMP production. Furthermore, insulin and IGF-I blocked the activation of PKA induced by sLH and these effects were correlated with changes in the total protein content of the catalytic (C) and type II regulatory (RII) subunits of PKA. Interestingly, insulin and IGF-I had different effects on total PKA subunit content since insulin potentiated the sLH-stimulated increase in RII subunit content whereas IGF-I blocked the sLH-stimulated increase in total C subunit content. The effects of insulin and IGF-I in trout theca layers appeared to be mediated by the mitogen-activated protein kinase (MAPK) signaling pathway because inhibition of extracellular signal-regulated kinase 1/2(ERK1/2) activity completely blocked the inhibitory effects of insulin and IGF-I on the sLH-stimulated production of T and because insulin and IGF-I increased the total protein content of ERK1/2 in trout theca layers. Therefore, our results suggest that insulin and IGF-I, probably through the MAPK pathway, block the action of sLH in trout theca layers by modulating the cAMP/PKA signaling pathway.     

Follicular lymphoma international prognostic index

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs 120 g/L), number of nodal areas (> 4 vs 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk ( 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.      

Hepatitis B reactivation during ruxolitinib treatment

Annals of Hematology -     

Plasma leptin and TNF-alpha levels in chronic hepatitis C patients and their relationship to hepatic fibrosis

The aim of this study was to examine the possible relationship between the plasma levels of leptin and tumor necrosis factor (TNF)- and the stage of hepatic fibrosis in a cohort of patients with chronic hepatitis C. Leptin and TNF levels were measured by RIA in 135 patients and in 75 age- and sex-matched controls. Liver disease was evaluated by the stage of fibrosis and the extent of inflammatory infiltrate in the liver biopsy. Leptin levels correlated with BMI values in healthy controls and in patients with chronic hepatitis C (men, r = 0.61, P = 0.0001; women, r = 0.68, P = 0.003). Leptin levels increased as hepatic fibrosis stage progressed both in male and in female patients (P < 0.001); also, TNF levels were higher in patients with an advanced stage of fibrosis (P = 0.006). In these patients, levels of leptin increased according to the progression of the stage of fibrosis; these data suggest that leptin may play a role in the regulation of hepatic fibrosis.     

A study of prognostic factors in blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia

In 80 patients with Ph-positive chronic myelogenous leukaemia the main clinical, haematological and cytogenetical data were recorded at diagnosis of blast crisis and evaluated for prognostic significance. At the time of the analysis 73 patients had died, with a median survival of 4-8 months from diagnosis of blast crisis for the whole series. When analysed as a time-dependent variable, the achievement of a favourable response to chemotherapy resulted in a longer patient's survival. On the other hand, the univariate analysis identified six pretreatment characteristics associated with a poorer prognosis: a longer chronic phase, presence of extramedullary blastic involvement, a platelet count below 200 x 10(9)/l, a less marked leucocytosis, a blood blast cell percentage higher than 10%, and presence of trisomy 8. The latter parameters were included in a multiple regression model together with the blast cell phenotype (lymphoid versus non-lymphoid), and only four of them (trisomy 8, duration of chronic phase, platelet count, and leucocyte count) retained their prognostic influence. When the therapeutical response was also included in the regression model, it proved to be the most important prognostic variable, followed by trisomy 8, length of chronic phase, extramedullary disease, and platelet count, whereas the leukocyte count lost its predictive value. Thus, in spite of the short overall survival of blast crisis patients, the identification of prognostic factors in such a haematological condition may be of interest, especially in the interpretation of new therapeutical approaches.     

Presenting features and prognosis of chronic lymphocytic leukemia in younger adults

We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.     

Cardiac damage in hypertensive patients with inverse white coat hypertension. Hospitalet study

BACKGROUND: Few studies have assessed the relationship between ambulatory blood pressure (BP) and cardiac damage in essential hypertensive patients with inverse white coat hypertension (IWCH). OBJECTIVES: To determine the frequency of IWCH in untreated grade 1-2 hypertension and to assess possible differences in cardiac damage among patients with IWCH, white coat hypertension (WCH) and the rest of patients with grade 1-2 hypertension. PATIENTS AND METHODS: Two hundred and eleven patients with grade 1-2 hypertension were sequentially included. A good quality 24-h ambulatory BP monitoring was obtained in 204 patients (age: 41 +/- 12 years, 56% males). IWCH was defined as a daytime systolic and/or diastolic BP higher than diagnostic office systolic and/or diastolic BP, respectively. WCH was defined as a daytime BP < 135/85 mmHg. A good quality echocardiogram was obtained in 174 patients. We considered left ventricular hypertrophy a left ventricular mass index (LVMI) > or = 125 g/m2. RESULTS: We found IWCH in 29 subjects (14%), and WCH in 68 (33%). Office BP in patients with IWCH was in an intermediate position between WCH and the rest of grade 1-2 hypertension patients. The IWCH patients showed 24-h, daytime and night-time BP higher than the other groups. Left ventricular mass was significantly greater in patients with IWCH than in the other grade 1-2 hypertension patients after adjusting for age, gender, body mass index, smoking and office BP (regression coefficient 28.14, 95%CI: 7.36-48.91). CONCLUSION: IWCH is independently associated with higher values of left ventricular mass in patients with grade 1-2 hypertension.