Biomedical subjects

Sammy Saab

Publications and source records attributed to Sammy Saab.

45 records · Page 3Linked to original sources

PubMed2002

Is it cost-effective to treat recurrent hepatitis C infection in orthotopic liver transplantation patients?

Hepatitis C virus (HCV) recurs in the allograft almost universally after orthotopic liver transplantation (OLT), with a variable course ranging from mild hepatitis to frank cirrhosis. The uncertain prognosis after OLT has lead to widely increased use of antiviral therapy in the post-OLT setting. We compared two scenarios (antiviral therapy versus no antiviral therapy) using a Markov-based decision analytic model to simulate costs and health outcomes for recurrent HCV in three age and sex cohorts of post-OLT patients. Efficacy outcomes included total costs, cases of cirrhosis prevented, cases of death prevented, life-years gained, and cost per life-year saved. One-way sensitivity analyses were performed for sustained viral response; annual drug cost, discount rate, compliance, cirrhosis rate, decompensation rate, and cost of dying. Two-way sensitivity analyses were performed to compare effects of (1) changing sustained viral response and antiviral therapy costs, and (2) changing the sustained viral response and cirrhosis rate. The incremental cost-effectiveness ratio for the reference patient cohort of 1,000 men aged 55 years was $29,100 per life-year saved. The model was sensitive to drug costs, cirrhosis rate, and sustained viral response. The two-way sensitivity analysis showed that antiviral therapy remained cost-effective even if drug costs increased, as long as these increases were associated with higher sustained viral responses. The cost-effectiveness ratio also was sensitive to age and sex of cohort. The decision to treat HCV after OLT with antiviral therapy usually is based on many considerations. Such treatment can be cost-effective if baseline assumptions are met. Our model was sensitive to antiviral drug costs, cirrhosis rate, and sustained viral response. Patients with a progressive course of recurrent HCV are likely to have the greatest gain from antiviral therapy.

Antiviral Agents↗

PubMed2002

Donor and recipient outcomes in right lobe adult living donor liver transplantation.

Severe donor organ shortage has provided the impetus for adult living donor liver transplantation (ALDLT). Despite rapid implementation and expansion of the procedure, outcome analysis of ALDLT is still incomplete. This study analyzed both donor and recipient outcomes after ALDLT at a single center. ALDLT performed at UCLA between August 1999 and November 2001 were reviewed retrospectively. Twenty recipients (14 men and 6 women) with a mean age of 48.8 +/- 9.7 (29 to 66) years underwent right lobe ALDLT. By computed tomograpy (CT), graft/recipient weight ratio (GRWR) was 1.3 +/- 0.3 (1 to 2.2). Overall 1-year patient and graft survival rates were 95% and 85%, respectively. One recipient died of heart failure with normal liver function 5 months after transplantation. Three grafts (14%) were lost and all three patients underwent successful cadaveric retransplantation. Complications were classified according to the Clavien grading system with all but 3 recipients encountering at least one complication. Nine (45%) had grade 1 (minor), 10 (50%) had grade 2 (potentially life threatening without residual disease/disability), 3 (14%) had grade 4A (retransplantation) and one grade 4B (death). Right lobectomy for living donation was performed in 20 patients (12 men, 8 women). Residual left lobe volumes were 36 +/- 5.3 (23.9 to 47.9)% of total donor liver volume. No donor required intensive care unit admission and median hospital stay was 7.5 (6 to 14) days. One donor was aborted after intraoperative biopsy showed > 50% macrovesicular steatosis. No donor mortality or long-term complications were encountered. Five grade 1 minor complications, by Clavien Classification, occurred in 4 of 20 (20%) donors. ALDLT using right lobe grafts is an effective procedure to expand a severely depleted donor, but is associated with a high complication rate despite good survival outcomes. Continuous standardized reporting of ALDLT outcomes is required to allow successful and safe implementation of the procedure.

Adult↗

PubMed2002

New era of liver transplantation for hepatitis B: a 17-year single-center experience.

OBJECTIVE: To evaluate the variables affecting orthotopic liver transplantation (OLT) outcome for hepatitis B virus (HBV) in a large patient cohort over a 17-year period. SUMMARY BACKGROUND DATA: Historically, OLT for chronic HBV infection has been associated with aggressive reinfection and poor survival results. More recently, OLT outcome has been improved with the routine use of antiviral therapy with either hepatitis B immune globulin (HBIg) or lamivudine; however, HBV recurrence remains common. The authors studied the factors affecting HBV recurrence and outcome of transplantation, including the effects of combination viral prophylaxis with HBIg and lamivudine. METHODS: A retrospective review of 166 OLT recipients for chronic HBV over a 17-year period at a single center was performed. Median follow-up was 29 months. HBV recurrence was defined by HBsAg seropositivity after OLT. HBIg monotherapy was used in 28 (17%) patients, lamivudine monotherapy in 20 (12%), and HBIg and lamivudine combination in 89 (54%); 29 (17%) did not receive any HBV prophylaxis. Hepatocellular carcinoma (HCC) was present in 43 patients (26%) and urgent United Network for Organ Sharing (UNOS) status was assigned to 27 patients (16%). Univariate and multivariate analyses were performed to identify factors that affected OLT outcome. RESULTS: Overall 1-, 3-, and 5-year patient survival rates were 85.8%, 73.6%, and 71.8%, respectively. As expected, HBV recurrence-free survival rates were significantly lower than overall survival rates (76.4%, 58.7%, and 48.3%). When compared with a nontreated cohort, OLT recipients receiving combination viral prophylaxis with HBIg and lamivudine showed markedly reduced HBV recurrence rates and significantly improved 1- and 3-year recurrence-free survival rates. By univariate estimates, patient survival was reduced in the presence of HCC, in the Asian population, and urgent candidates by UNOS classification. Graft loss rates were significantly increased in urgent OLT candidates, Asians, patients with pretransplant positive DNA, and in the presence of HCC. Factors that were significant by univariate analysis or thought to be clinically relevant were subjected to multivariate analysis. By multivariate estimates, urgent UNOS or presence of HCC adversely affected patient and graft survival rates, whereas combination prophylactic therapy strongly predicted improved patient and graft survival rates as well as recurrence-free survival rates. CONCLUSIONS: Orthotopic liver transplantation for HBV under combination viral prophylaxis results in survival rates equivalent to other indications. Pretransplant viral replication, UNOS status, and the presence of HCC are all sensitive markers for posttransplantation outcome. Viral prophylactic therapy has effectively reduced HBV recurrence and prolonged survival outcomes. The combination of HBIg and lamivudine is the prophylactic regimen of choice.

Antiviral Agents↗

PubMed2002

Pretransplant model to predict posttransplant survival in liver transplant patients.

OBJECTIVE: To develop a prognostic model that determines patient survival outcomes after orthotopic liver transplantation (OLT) using readily available pretransplant variables. SUMMARY BACKGROUND DATA: The current liver organ allocation system strongly favors organ distribution to critically ill recipients who exhibit poor survival outcomes following OLT. A severely limited organ resource, increasing waiting list deaths, and rising numbers of critically ill recipients mandate an organ allocation system that balances disease severity with survival outcomes. Such goals can be realized only through the development of prognostic models that predict survival following OLT. METHODS: Variables that may affect patient survival following OLT were analyzed in hepatitis C (HCV) recipients at the authors' center, since HCV is the most common indication for OLT. The resulting patient survival model was examined and refined in HCV and non-HCV patients in the United Network for Organ Sharing (UNOS) database. Kaplan-Meier methods, univariate comparisons, and multivariate Cox proportional hazard regression were employed for analyses. RESULTS: Variables identified by multivariate analysis as independent predictors for patient survival following primary transplantation of adult HCV recipients in the last 10 years at the authors' center were entered into a prognostic survival model to predict patient survival. Accordingly, mortality was predicted by 0.0293 (recipient age) + 1.085 (log10 recipient creatinine) + 0.289 (donor female gender) + 0.675 urgent UNOS - 1.612 (log10 recipient creatinine times urgent UNOS). The above variables, in addition to donor age, total bilirubin, prothrombin time (PT), retransplantation, and warm and cold ischemia times, were applied to the UNOS database. Of the 46,942 patients transplanted over the last 10 years, 25,772 patients had complete data sets. An eight-factor model that accurately predicted survival was derived. Accordingly, the mortality index posttransplantation = 0.0084 donor age + 0.019 recipient age + 0.816 log creatinine + 0.0044 warm ischemia (in minutes) + 0.659 (if second transplant) + 0.10 log bilirubin + 0.0087 PT + 0.01 cold ischemia (in hours). Thus, this model is applicable to first or second liver transplants. Patient survival rates based on model-predicted risk scores for death and observed posttransplant survival rates were similar. Additionally, the model accurately predicted survival outcomes for HCV and non-HCV patients. CONCLUSIONS: Posttransplant patient survival can be accurately predicted based on eight straightforward factors. The balanced application of a model for liver transplant survival estimate, in addition to disease severity, as estimated by the model for end-stage liver disease, would markedly improve survival outcomes and maximize patients' benefits following OLT.

Adult↗

PubMed2002

Hepatitis B surface antigenemia in chronic hemodialysis patients: effect of hepatitis B immunization.

OBJECTIVE: Hemodialysis patients with hepatitis B surface antigen (HBsAg) are considered to have the hepatitis B virus (HBV) and are segregated to limit transmission. However, transient de novo HBsAg has been identified in hemodialysis patients shortly after vaccination. Our hypothesis is that immunization rather than actual HBV infection is the most common cause of de novo HBsAg among hemodialysis patients. METHODS: We performed a prospective study between January, 1998 and June, 2000 of de novo HBV infection in over 2400 hemodialysis patients who were screened monthly for HBsAg using a standard enzyme immunoassay. Positive results were confirmed with a neutralization assay. If the confirmatory test was positive, anti-hepatitis B core antibody IgM testing was performed. RESULTS: We identified nine patients with de novo HBsAg confirmed with the neutralization assay. In eight of the nine patients with de novo HBsAg (89%), HBsAg was temporally related to HBV immunization. In none of these eight patients was there a detectable anti-hepatitis B core antibody IgM, an elevated ALT level, or clinical history suggestive of recent hepatitis. The mean age (+/- SD) of the four men and four women was 56.4 +/- 18.8 yr. HBsAg was detectable within 3 days of immunization in most patients. CONCLUSION: Our results suggest that HBV immunization is the most common cause of detectable HBsAg in hemodialysis patients. Hemodialysis patients should not be screened for HBV within a week of immunization, and caution should be exercised when interpreting HBsAg seropositivity within 4 wk of HBV immunization.

Adult↗

PubMed2002

Presence and predictors of hepatitis C virus RNA in the semen of homeless men.

Although the possibility of sexual transmission of the hepatitis C virus (HCV) remains controversial, little is known of the associations ofpositive semen specimens with potential demographic and behavioral risk factors. Knowledge of these predictors may suggest factors that increase risk of HCV RNA in the semen. Semen and bloodfrom 80 HCV-infected homeless men were evaluatedfor the presence of HCVRNA by means of branch DNA and transcription-mediated amplification analyses. Associations of selected demographic and behavioral characteristics of the participants with presence or absence of HCV in their semen were also assessed. HCV RNA was detected in the semen of 36% of the sample. Associations were found with HCV RNA in semen and older age, higher viral loads of HCV in blood, current alcohol and lifetime methamphetamine use, and having been vaccinated for the hepatitis B virus. Findings suggest that sexual transmission of HCV is plausible and shed light on the need to conduct more in-depth investigations.

Adult↗

PubMedDate not supplied

An economic assessment of pre-vaccination screening for hepatitis A and B.

OBJECTIVE: The availability of a single vaccine active against hepatitis A and B may facilitate prevention of both infections, but complicates the question of whether to conduct pre-vaccination screening. The authors examined the cost-effectiveness of pre-vaccination screening for several populations: first-year college students, military recruits, travelers to hepatitis A-endemic areas, patients at sexually transmitted disease clinics, and prison inmates. METHODS: Three prevention protocols were examined: (1) screen and defer vaccination until serology results are known; (2) screen and begin vaccination immediately to avoid a missed vaccination opportunity; and (3) vaccinate without screening. Data describing pre-vaccination immunity, vaccine effectiveness, and prevention costs borne by the health system (i.e., serology, vaccine acquisition, and administration) were derived from published literature and U.S. government websites. Using spreadsheet models, the authors calculated the ratio of prevention costs to the number of vaccine protections conferred. RESULTS: The vaccinate without screening protocol was most cost-effective in nine of 10 analyses conducted under baseline assumptions, and in 69 of 80 sensitivity analyses. In each population considered, vaccinate without screening was less costly than and at least equally as effective as screen and begin vaccination. The screen and defer vaccination protocol would reduce costs in seven populations, but effectiveness would also be lower. CONCLUSIONS: Unless directed at vaccination candidates with the highest probability of immunity, pre-vaccination screening for hepatitis A and B immunity is not cost-effective. Balancing cost reduction with reduced effectiveness, screen and defer may be preferred for older travelers and prison inmates.

Adolescent↗

PubMedDate not supplied

Preoperative imaging in adult-to-adult living related liver transplant donors: what surgeons want to know.

Because of an overwhelming demand for cadaveric livers in the United States that far outstrips supply, living related liver transplantation is increasingly being performed to help treat a cohort of patients with severe end-stage liver disease. This procedure demands careful preoperative evaluation to minimize morbidity to the healthy donor and recipient, however. As a part of the workup, radiologic assessment of the donor hepatic vascular and biliary anatomy, hepatic volume, and hepatic parenchyma (with regard to focal and diffuse liver disease) is essential. In this pictorial essay, the experience of a group of investigators at the University of California at Los Angeles is reviewed, and the essential radiologic components of the preoperative evaluation of hepatic vascular and biliary anatomy, hepatic parenchyma, and lobar volume are described. The roles of high-field magnetic resonance (MR) imaging, MR angiography, MR cholangiopancreatography, multidetector-row computed tomography (CT) angiography, and CT cholangiography in the workup are discussed.

Angiography↗

PubMedDate not supplied

Myosin mediates contractile force generation by hepatic stellate cells in response to endothelin-1.

Although endothelin-1-stimulated contractile force generation by stellate cells is believed to play an important role in hepatic pathophysiology, the molecular signals that mediate this process are incompletely understood. The aim of this study was to test the hypothesis that myosin mediates the contractile force generated by stellate cells in response to endothelin-1. Contractile force generation by primary and immortalized stellate cells was directly and quantitatively measured. Myosin phosphorylation and reorganization, and actin stress fiber formation were investigated in immortalized stellate cells. Endothelin-1 stimulated a rapid and robust generation of contractile force by primary and immortalized stellate cells with a similar dose dependence. Myosin phosphorylation, actin stress fiber assembly, and reorganization of myosin to stress fibers were induced by concentrations of endothelin-1 that also stimulated stellate cell contraction. BQ-123, a selective endothelin receptor antagonist, inhibited myosin phosphorylation and contractile force generation. Y-27632, which selectively inhibits rho-associated kinase, also blocked endothelin-1-stimulated myosin phosphorylation and contractile force generation with a similar dose dependence. These results suggest that endothelin-1-stimulated contractile force generation by stellate cells is mediated by myosin.

Actins↗