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Biomedical subjects

Sammy Saab

Publications and source records attributed to Sammy Saab.

At least 37 records · Page 2Linked to original sources
PubMed2004

Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings.

PURPOSE: To assess degree of macrovesicular steatosis with unenhanced computed tomography (CT) and correlate it with histologic findings in potential donors for living related liver transplantation. MATERIALS AND METHODS: Forty-two candidates underwent unenhanced CT within 4 weeks of core liver biopsy. An experienced liver pathologist, blinded to both CT and surgical findings, retrospectively reviewed biopsy specimens and determined degree of macrovesicular steatosis. A radiologist blinded to histologic grading calculated mean hepatic attenuation in each donor liver by averaging 25 region-of-interest (ROI) measurements on five sections (five ROIs per section). Mean splenic attenuation was calculated with three separate ROI measurements. Liver attenuation index (LAI) was derived and defined as the difference between mean hepatic and mean splenic attenuation. Body mass index (BMI) was determined for each patient. Linear regression analysis was used to correlate degree of macrovesicular steatosis with both LAI and BMI. RESULTS: LAI correctly predicted degree of macrovesicular steatosis in 38 (90%) of 42 cases. In four of four livers, LAI below -10 HU correlated with greater than 30% macrovesicular steatosis (unacceptable for liver transplantation). In nine of 11 livers, LAI was between -10 and 5 HU and correctly predicted 6%-30% steatosis (relative contraindication). In two of 11 cases, LAI overestimated degree of hepatic steatosis. LAI above 5 HU correctly predicted 0%-5% steatosis in 25 of 27 livers. In two of 27 cases, parenchymal hemosiderin deposition led to an increase in LAI into the normal range, despite mild histologically confirmed steatosis. Degree of histologic macrovesicular steatosis correlated well with LAI (r = 0.92) and marginally with BMI (r = 0.45). Of 27 potential donors with normal livers at CT and acceptable LAI levels, four (15%) were deemed poor donor candidates because core biopsy revealed subtle hepatic necrosis and nonspecific hepatitis. CONCLUSION: Although unenhanced CT quantifies the degree of macrovesicular steatosis relatively well, it may preclude a liver biopsy only in a small percentage of potential donors with low LAI (unacceptable degree of steatosis). Core liver biopsy is still necessary in the majority of donors with normal LAI to identify those with both fatty liver and coexistent hemosiderin deposition or radiologically occult diffuse liver diseases.

Adult↗
PubMed2004

Primary prevention of cirrhosis. Public health strategies that can make a difference.

Cirrhosis is associated with high morbidity and mortality and often affects persons during the most productive years of life. In the United States, alcoholic liver disease is the leading contributor to the overall prevalence of cirrhosis, followed by infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). In this article, Drs Karsan, Rojter, and Saab examine lifestyle behaviors that can lead to cirrhosis and enumerate public health strategies aimed at primary prevention.

Alcohol Drinking↗
PubMed2003

Fulminant Hepatic Failure.

Fulminant hepatic failure is a rapidly progressive and often fatal syndrome, and the only definitive treatment is liver transplantation. However, given the scarcity of available grafts, the mainstay of therapy remains supportive care until there is spontaneous recovery or until a suitable donor liver becomes available. After initial assessment and stabilization, patients should be transferred to the nearest liver transplant center as soon as possible, as they can deteriorate rapidly. All patients with fulminant hepatic failure must be monitored closely and treated for hepatic encephalopathy, coagulopathy, gastrointestinal bleeding, renal failure, cerebral edema, and metabolic derangement.

Journal Article↗
PubMed2003

A model to predict the development of mental status changes of unclear cause after liver transplantation.

Postoperative mental status changes are common after liver transplantation (LT). A clear cause of these mental status changes cannot be identified in a significant proportion of patients. In adult liver transplant recipients, our goals are to: (1) identify independent predictors for the development of post-LT mental status changes of unclear cause and (2) derive a practical formula to predict the risk for developing this complication by using simple clinical parameters. Eligible patients had documented mental status changes of at least 3 days' duration, occurring within 1 month of LT. Exclusion criteria were known structural brain disorders, major organ dysfunction, or metabolic causes of altered mentation. Age- and sex-matched controls were liver transplant recipients without post-LT neurological sequelae. Data were collected on preoperative, intraoperative, and postoperative variables. Univariate and multivariate analyses were performed to detect factors predictive of the development of post-LT mental status of unclear cause. There were 40 cases and 40 controls. Independent predictors of mental status changes of unclear cause included alcoholic and metabolic liver diseases; pre-LT mechanical ventilation; Model for End-Stage Liver Disease (MELD) score greater than 15; and nonelective LT. Using these four preoperative factors, a simple predictive rule was developed. Risk for developing altered mental status of unclear cause after LT was 78% to 89% if all four predictors were present versus 0.8% to 2.4% if no predictors were present. In conclusion, alcoholic and metabolic liver diseases, pre-LT mechanical ventilation, MELD score greater than 15, and nonelective LT are independent predictive factors for post-LT altered mental status changes of unclear cause. A simple model can be used to calculate the risk for developing altered mental status post-LT.

Case-Control Studies↗
PubMed2003

Discordance between ALT values and fibrosis in liver transplant recipients treated with ribavirin for recurrent hepatitis C.

Hepatitis C virus (HCV) recurrence is a serious problem after orthotopic liver transplantation (OLT). The role of ribavirin as a single agent to treat recurrent HCV is controversial. Our aim was to evaluate the correlation between alanine aminotransferase (ALT) levels and histological findings in OLT recipients treated with ribavirin monotherapy for recurrent HCV. The mean [+/- standard error (SE)] age of 11 patients was 50.1 (SE +/- 8.6) years. The estimated mean dose and duration of ribavirin treatment (+/- SE) was 661.5 (+/- 52.5) mg and 20.4 (+/- 1.7) months, respectively. Five patients required either dose reduction or erythropoietin. We found a significant decrease of mean (+/- SE) ALT value from 246 +/- 44.8 U/L to 109.4 +/- 49.1 U/L (p = 0.002) in patients treated with ribavirin. However, there was also significant worsening of interface activity (p = 0.03) and fibrosis (p = 0.02). No significant association was found between ALT values and (i) stage of hepatic fibrosis, (ii) interface activity, (iii) lobular activity and (iv) HCV RNA values. Our results suggest that HCV disease can progress despite a significant decrease in ALT values. ALT values are inadequate markers of the ribavirin monotherapy and can lead to erroneous conclusions of efficacy.

Adult↗
PubMed2003

Hepatitis C positive grafts may be used in orthotopic liver transplantation: a matched analysis.

Hepatitis C (HCV)-positive liver grafts have been increasingly used in patients with decompensated liver disease from HCV because of critical shortage of available organs. Fifty-nine recipients of HCV-positive grafts were matched to patients who received HCV-negative grafts. All recipients were transplanted for HCV liver disease. Matching variables were (1) status, (2) pre-transplant creatinine, (3) recipient age, (4) donor age, (5) warm ischemia time, and (6) year of transplantation. Both unmatched and matched analyses were performed on patient survival, graft survival, and time to HCV recurrence. There was no significant statistical difference in patient, graft, or HCV recurrence-free survival between recipients of HCV-positive and HCV-negative grafts with matched and unmatched analyses (p > 0.05). The 3-year estimates of HCV disease-free survival were 12% (+/- 9%) and 19% (+/- 7%) using HCV-positive and -negative grafts, respectively. The use of HCV-positive grafts in recipients with HCV does not appear to affect patient survival, graft survival, or HCV recurrence when compared with the use of HCV-negative grafts. Our results suggest that HCV-positive grafts can be used in a HCV liver transplant recipient.

Adult↗
PubMed2003

Conversion from intravenous to intramuscular hepatitis B immune globulin in combination with lamivudine is safe and cost-effective in patients receiving long-term prophylaxis to prevent hepatitis B recurrence after liver transplantation.

Recurrent hepatitis B infection after liver transplantation was previously frequent and associated with significant allograft failure and mortality. Recurrence rates of hepatitis B were improved with the use of passive immunoprophylaxis with hepatitis B immune globulin, and later, lamivudine monotherapy. Combination prophylaxis with intravenous hepatitis B immune globulin and lamivudine substantially decreased rates of hepatitis B recurrence, but intravenous administration of hepatitis B immune globulin was expensive and associated with significant adverse effects. In the current study, 59 patients receiving primary liver transplantation for chronic hepatitis B infection were prospectively followed up after converting from intravenous to intramuscular hepatitis B immune globulin in combination with lamivudine. All patients tolerated intramuscular hepatitis B immune globulin well. At a median follow-up of 511 days after conversion to intramuscular hepatitis B immune globulin, 58 of 59 patients (98.3%) were hepatitis B surface antigen-negative. Twenty-one patients (35.6%) required a median of one supplemental intravenous hepatitis B immune globulin infusion to maintain therapeutic antibody levels. Economic analysis showed an average cost-effectiveness ratio for combination intramuscular hepatitis B immune globulin plus lamivudine of $52,600 per recurrence prevented, which was far below the cost of lamivudine monotherapy and of intravenous hepatitis B immune globulin alone or in combination with lamivudine. These results suggest that intramuscular administration of hepatitis B immune globulin in combination with lamivudine offers a safe, effective, and cost-effective approach to preventing hepatitis B recurrence after orthotopic liver transplantation.

Adult↗
PubMed2003

MELD score predicts 1-year patient survival post-orthotopic liver transplantation.

The Model for End-Stage Liver Disease (MELD) is an important predictor in patients awaiting orthotopic liver transplantation (OLT). However, the model's association with posttransplant patient survival is unclear. We studied 1-year patient survival in 404 adult patients who underwent OLT at the University of California Los Angeles. The hazard rates of patient survival according to the MELD strata and United Network for Organ Sharing (UNOS) statuses were assessed by Proportional Hazard Cox regression analysis. The difference in survival for MELD strata and UNOS status were compared using the Cox model. There was a significant difference in 1-year patient (P =.0006) survival using different MELD strata, whereas there was a trend according to UNOS status (P =.051). Increased rate of death was observed in recipients of OLT with higher MELD scores (> 36, hazard ratio 3.9; 95% CI 1.55, 10.27) and more urgent UNOS status (2A; hazard ratio, 1.99; 95% CI 1.07, 3.7). The MELD stratum is better associated with 1-year patient survival in liver transplant recipients than UNOS statuses. Patient survival was worse with higher MELD scores.

Bilirubin↗
PubMed2003

Hepatocellular carcinoma screening in patients waiting for liver transplantation: a decision analytic model.

De novo hepatocellular carcinoma (HCC) may have a large impact on patients waiting for liver transplantation. The presence of HCC can lead to a status upgrade or removal from the waitlist. Our aim is to compare costs and outcomes of different liver cancer surveillance strategies. A Markov-based decision analytic model is created to simulate costs and health outcomes for a hypothetical cohort awaiting liver transplantation undergoing HCC screening. Three strategies of HCC screening are compared with the referent strategy of using alphafetaprotein (AFP) level alone: (1) ultrasound (U/S), (2) AFP plus U/S, and (3) computed tomography (CT). Screening is performed for all strategies at 6-month intervals. Selected tumors are treated locally. Costs and clinical outcomes are discounted. Using baseline assumptions, incremental cost-effectiveness ratios (ICERs) for U/S, U/S plus AFP, and CT are $60,300/life-year saved (LY), $74,000/LY, and $101,100/LY, respectively. The most cost-effective strategy was dependent on the relative costs of each screening modality. U/S screening becomes the dominant strategy when the cost of an AFP test is decreased. Our results show that screening with CT is associated the greatest gain in life expectancy and greatest costs. U/S screening strategy is the preferred screening strategy based on the lowest ICER. Ultimately, costs of the screening modalities determine the most cost-effective strategy.

Carcinoma, Hepatocellular↗
PubMed2003

Outcomes of hepatitis C- and hepatitis B core antibody-positive grafts in orthotopic liver transplantation.

The use of hepatitis B core antibody (HBcAb)- and hepatitis C virus antibody (HCV+) liver grafts for transplantation in selected populations has not affected patient and graft survival. We reexamined the clinical outcomes of using these HBcAb+ and HCV+ grafts at our institution, in addition to studying recipients of combined HBcAb+/HCV+ grafts. We identified 377 patients who underwent transplantation for either hepatitis B and/or hepatitis C, or received both HBcAb+ and HCV+ grafts. Patient and graft survival at 5 years posttransplantation was 73% and 71%, respectively, in the HBcAb+ grafts compared with 81% and 75% in the HBcAb- grafts (P =.65; P =.94). For HCV+ grafts, patient and graft survival at 5 years posttransplantation was 89% and 73%, respectively, compared with 69% and 59% in the HCV- grafts; (P =.22; P =.77). The 5-year patient and graft survival rate in those who received combined HBcAb+/HCV+ grafts was 74% and 69%, respectively, and there was no statistical difference compared with the HBcAb+ and HCV+ grafts (P =.76; P =.90). The 5-year patient and graft survival rate in patients who received dual HBV prophylaxis with hepatitis B immunoglobulin (HBIg) and lamivudine was 88% and 84%, respectively, which was significantly higher than for patients who received single prophylaxis or no prophylaxis (P <.01; P =.02). Our study supports previous observations that patient and graft survival is not affected with the use of HBcAb+ and HCV+ grafts, and that dual prophylaxis with HBIg and lamivudine offers substantial survival benefits. Furthermore, the use of combined HBcAb+/HCV+ grafts did not impact patient or graft survival. This provides a potential new pool of donor livers that can be used for transplantation in select patients.

Adolescent↗
PubMed2003

The cost effectiveness of hepatitis immunization for US college students.

Hepatitis B immunization is recommended for all American children, and hepatitis A immunization is recommended for children who live in areas with elevated disease rates. Because hepatitis A and B occur most commonly in young adults, the authors examined the cost effectiveness of college-based vaccination. They developed epidemiologic models to consider infection risks and disease progression and then compared the cost of vaccination with economic, longevity, and quality of life benefits. Immunization of 100,000 students would prevent 1,403 acute cases of hepatitis A, 929 cases of hepatitis B, and 144 cases of chronic hepatitis B. Hepatitis B vaccination would cost the health system $7,600 per quality-adjusted life year (QALY) gained but would reduce societal costs by 6%. Hepatitis A/B vaccination would cost the health system dollar 8,500 per QALY but would reduce societal costs by 12%. Until childhood and adolescent vaccination can produce immune cohorts of young adults, college-based hepatitis immunization can reduce disease transmission in a cost-effective manner.

Adolescent↗
PubMed2003

Recurrent hepatitis C following liver transplant: diagnosis, natural history, and therapeutic options.

Hepatitis C virus (HCV) related cirrhosis is the most common indication for orthotopic liver transplantation (OLT). Updated data suggest worse long-term outcomes for those transplanted with HCV than those transplanted for other indications. Re-infection with HCV post-OLT is universal, therefore diagnosis of recurrence should be based on histological findings in the setting of persistent viremia. Variables associated with worse outcome of recurrent disease include early recurrence, degree of immunosuppression, and donor age. Antiviral therapy has been used in the prevention and treatment of recurrent disease, and can be initiated prior to transplantation, prophylactically after transplantation, and during recurrence. Preliminary studies of pre-transplantation treatment demonstrate virological responses, but tolerance is common. Higher efficacy has been associated with combination therapy for recurrent disease. Adverse effects limit its widespread use.

Antiviral Agents↗
PubMed2003

Regional variation in the cost effectiveness of childhood hepatitis A immunization.

BACKGROUND: Routine childhood hepatitis A immunization is recommended in regions with incidence rates twice the national average, but it may be cost-effective in a wider geographic area. OBJECTIVE: To evaluate the costs and benefits of potential hepatitis A immunization of healthy US children in regions with varying hepatitis A incidences. METHODS: We considered vaccination of the 2000 US birth cohort in states defined by historic hepatitis A incidence rates. Infections among potential vaccinees and their personal contacts were predicted from age 2 through 85 years. Net vaccination costs were estimated from health system and societal perspectives and were compared with life-years saved and quality-adjusted life years (QALYs) gained using a 3% discount rate. RESULTS Nationally vaccination would prevent >75 000 cases of overt hepatitis A disease. Approximately two-thirds of health benefits would accrue to personal contacts rather than to vaccinees themselves. In states with incidence rates of > or =200%, 100 to 199%, 50 to 99% and <50% the national average, societal costs per QALY gained would be <0, <0, 13,800 and 63,000 US dollars, respectively. Nationally vaccination would cost 9100 US dollars per QALY gained from the perspective of the health system and 1400 US dollars per QALY gained from society's perspective. Results are most sensitive to vaccination costs and rates of disease transmission through personal contact. CONCLUSION: Childhood hepatitis A vaccination is most cost-effective in areas with the highest incidence rates but would also meet accepted standards of economic efficiency in most of the US. A national immunization policy would prevent substantial morbidity and mortality, with cost effectiveness similar to that of other childhood immunizations.

Adolescent↗
PubMed2003

Liver transplantation for fulminant hepatic failure: experience with more than 200 patients over a 17-year period.

OBJECTIVE: To analyze outcomes after liver transplantation (LT) in patients with fulminant hepatic failure (FHF) with emphasis on pretransplant variables that can potentially help predict posttransplant outcome. SUMMARY BACKGROUND DATA: FHF is a formidable clinical problem associated with a high mortality rate. While LT is the treatment of choice for irreversible FHF, few investigations have examined pretransplant variables that can potentially predict outcome after LT. METHODS: A retrospective review was undertaken of all patients undergoing LT for FHF at a single transplant center. The median follow-up was 41 months. Thirty-five variables were analyzed by univariate and multivariate analysis to determine their impact on patient and graft survival. RESULTS: Two hundred four patients (60% female, median age 20.2 years) required urgent LT for FHF. Before LT, the majority of patients were comatose (76%), on hemodialysis (16%), and ICU-bound. The 1- and 5-year survival rates were 73% and 67% (patient) and 63% and 57% (graft). The primary cause of patient death was sepsis, and the primary cause of graft failure was primary graft nonfunction. Univariate analysis of pre-LT variables revealed that 19 variables predicted survival. From these results, multivariate analysis determined that the serum creatinine was the single most important prognosticator of patient survival. CONCLUSIONS: This study, representing one of the largest published series on LT for FHF, demonstrates a long-term survival of nearly 70% and develops a clinically applicable and readily measurable set of pretransplant factors that determine posttransplant outcome.

Adolescent↗
PubMed2003

Costs and clinical outcomes of primary prophylaxis of variceal bleeding in patients with hepatic cirrhosis: a decision analytic model.

OBJECTIVE: Current guidelines recommend upper endoscopic screening for patients with hepatic cirrhosis and primary prophylaxis with a nonselective beta-blocker for those with large varices. METHODS: However, only 25% of cirrhotics develop large varices. Thus, the aim of this study is to evaluate the most cost-effective approach for primary prophylaxis of variceal hemorrhage. RESULTS: Using a Markov model, we compared the costs and clinical outcomes of three strategies for primary prophylaxis of variceal bleeding. In the first strategy, patients were given a beta-blocker without undergoing upper endoscopy. In the second strategy, patients underwent upper endoscopic screening; those found to have large varices were treated with a beta-blocker. In the third strategy, no prophylaxis was used. Selected sensitivity analyses were performed to validate outcomes. Our results show screening prophylaxis was associated with a cost of $37,300 and 5.72 quality-adjusted life yr (QALYs). Universal prophylaxis was associated with a cost of $34,100 and 6.65 QALYs. The no prophylaxis strategy was associated with a cost of $36,600 and 4.84 QALYs. The incremental cost-effectiveness ratio was $800/QALY for the endoscopic strategy relative to the no prophylaxis strategy. Screening endoscopy was cost saving when the compliance, bleed risk without beta-blocker, and variceal bleed costs were increased, and when the discount rate, bleed risk on beta-blockers, and cost of upper endoscopy were decreased. In contrast, the universal prophylaxis strategy was persistently cost saving relative to the no prophylaxis strategy. In comparing the strategies, sensitivity analysis on the death rates from variceal hemorrhage did not alter outcomes. CONCLUSIONS: Our results provide economic and clinical support for primary prophylaxis of esophageal variceal bleeding in patients with hepatic cirrhosis. Universal prophylaxis with beta-blocker is preferred because it is consistently associated with the lowest costs and highest QALYs.

Adrenergic beta-Antagonists↗
PubMed2003

A parathyroid hormone-related protein-secreting metastatic epithelioid leiomyosarcoma. A case report and review of the literature.

A diagnosis of parathyroid hormone-related protein (PTH-rP)-secreting metastatic uterine epithelioid leiomyosarcoma was made in a 61-year-old woman with humoral hypercalcemia of malignancy. A primary uterine tumor had been removed 10 years previously, which had been associated with a short history of hypercalcemia. The original uterine tumor was diagnosed as a smooth muscle tumor of uncertain malignant potential. To the best of our knowledge, this is the first reported case of a PTH-rP-secreting uterine leiomyosarcoma. We demonstrate the dramatic changes in serum calcium, phosphorus, PTH, and PTH-rP levels after tumor resection. Extensive biochemical analysis and detailed immunohistochemical and ultrastructural characterization demonstrate several features of this tumor.

Calcium↗
PubMed2002

Comparison of the cost and effectiveness of two strategies for maintaining hepatitis B immunity in hemodialysis patients.

A decision-analysis model was developed to compare the strategies to maintain hepatitis B virus (HBV) immunity in hemodialysis patients who responded to the primary HBV vaccine. Our hypothesis is that the routine, annual administration of the vaccine booster to all hemodialysis patients (non-screening strategy) is more cost-effective than the current strategy of vaccination based on anti-HBs titers (screening strategy). Under baseline assumptions, the screening strategy was less costly and was associated with fewer HBV infections than the non-screening strategy. The results of our model did not support our hypothesis, and indicate that regularly screening patients for HBV immunity before revaccination is less costly and more effective than the empiric vaccination of hemodialysis patients.

Algorithms↗