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P Sheiner

Publications and source records attributed to P Sheiner.

At least 19 recordsLinked to original sources
PubMed2000

Tuberculosis in orthotopic liver transplant patients: increased toxicity of recommended agents; cure of disseminated infection with nonconventional regimens.

BACKGROUND: Because increased hepatotoxicity was observed with first line antituberculous agents using four drug standard induction therapy in orthotopic liver transplant patients, we evaluated the efficacy and adverse effects of a novel continuation regimen for the treatment of tuberculosis in orthotopic liver transplant patients at a University Hospital in New York City. METHODS: The hospital records of all patients who were referred to Mount Sinai Hospital (n=924) and who underwent orthotopic liver transplant between September 1988 and May 1998 were reviewed. Data were collected from patient records. Nine orthotopic liver transplant patients (0.97%) developed tuberculosis over a 9.5-year period. A total of seven of nine (78%) patients had disseminated tuberculosis including two patients with meningitis. All mycobacterial isolates were sensitive to isoniazid, rifampin, pyrazinamide, and ethambutol. Standard induction therapy with three or four drugs was given for 2 months (mean). Hepatotoxicity related to the standard induction regimen developed in five of six (83.3%) patients. Liver biopsy during induction therapy revealed drug induced hepatitis in five of six (88%) patients and rejection in three of six (50%) patients. Continuation regimens consisted mainly of ethambutol and ofloxacin; mean length of therapy 9 months. RESULTS: Overall mortality was 33.3% (three of nine patients) over a 4.5-year follow-up period. Tuberculosis associated mortality was 22.2%. One patient died before therapy, another died with concomitant bacterial sepsis during induction therapy. Six of seven patients are alive and disease free. One patient died of recurrent hepatitis C and graft failure without evidence of tuberculous infection at death. Another patient retransplanted for chronic rejection, remains disease free at 1 year. The mean follow-up for six patients that completed treatment was 3.75 years (2.5-5.3 years). Six patients are free of tuberculosis. CONCLUSIONS: Our experience reveals that orthotopic liver transplant patients have poor tolerance for conventional therapy due to inherent toxicity of these agents and their concomitant bouts of organ rejection. Our nonconventional therapy yielded remarkably good results in that six patients, all with disseminated disease, were well after mean 3.5 years of follow-up. Consideration should be given to this novel follow-up therapy in patients without cavitary pulmonary disease who develop hepatotoxicity during induction.

Adult↗
PubMed2000

Th1/Th2 cytokines and ICAM-1 levels post-liver transplant do not predict early rejection.

Th1 derived cytokines IFN-gamma and IL-2, Th2 cytokine IL-4, and ICAM-1 have been implicated in liver allograft rejection. In order to determine whether monitoring of cytokine profiles during the first days post-liver transplant can predict early rejection we measured IFN-gg, IL-2, sIL-2 receptor, IL-4 and ICAM-1 in 22 patients, in plasma samples obtained within 4 h after liver perfusion (baseline) and between postoperative days (POD) 3-6. ICAM-1 and sIL-2R levels at POD 3-6 were significantly higher than at baseline but did not differ in presence or absence of rejection. Mean percentage increase of ICAM-1 levels was significantly lower in patients with Muromonab-C3 Orthoclone OKT3 (J.C. Health Care) (OKT3) whereas percentage increase of sIL-2R levels was higher in OKT3-treated patients. IFN-gamma levels at POD 3-6 increased from baseline while IL-4 levels were unchanged. Levels of IFN-gamma, IL-4 and their ratios did not correlate with rejection or immunosuppressive therapy. Thus, Th1/Th2 cytokine monitoring during the first week post-transplant does not predict early rejection and immunosuppressive therapy is the predominant factor affecting ICAM and sIL-2R levels after liver transplantation.

Female↗
PubMed2000

Serum hepatitis C virus RNA levels and histologic findings in liver allografts with early recurrent hepatitis C.

BACKGROUND: Histopathologic features of early recurrent hepatitis C after orthotopic liver transplantation (OLTx) may be modified by immunosuppressive therapy or complicated by other conditions. Hepatitis C virus (HCV) RNA level usually increases after OLTx, but its correlation to histologic findings is not clear. OBJECTIVE: To evaluate the histologic findings of early recurrent hepatitis C in liver allografts and its correlation to serum HCV RNA level. METHODS: We studied 14 patients who underwent OLTx for chronic HCV infection. Thirty liver biopsy specimens and HCV RNA levels of 22 corresponding plasma samples obtained during the first 6 months following OLTx were analyzed. The control group (9 patients, 25 biopsy specimens) was chosen at random from patients with chronic liver disease other than HCV who were undergoing OLTx, and all tested negative for HCV RNA by polymerase chain reaction after OLTx. RESULTS: Statistically significant pathological features of early recurrent HCV infection were the number of acidophilic bodies, piecemeal necrosis, lymphocyte predominance in the portal tracts, and fibrous septum. These findings and histologic activity index scores increased with time after OLTx. The HCV RNA levels determined by branched DNA assay showed no significant correlation with histologic features. However, patients with higher histologic activity index scores tended to have higher RNA levels. CONCLUSIONS: Liver biopsy specimens are helpful for the diagnosis or confirmation of early recurrent hepatitis C in liver allografts, but serial biopsy specimens are sometimes required for definite diagnosis. The HCV RNA levels are usually higher in patients who display signs of more severe liver damage.

Biopsy↗
PubMed1998

Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation.

PURPOSE: To review the treatment of cirrhotic patients with hepatocellular carcinoma in the era of liver transplantation and to determine the most appropriate approach to the treatment of patients at different stages of disease. DATA SOURCES: A MEDLINE search of English-language articles published between 1981 and 1997 and the clinical experience of the Mount Sinai Liver Transplant Program. STUDY SELECTION: Selected studies were 1) original articles reporting results of resection and transplantation in the treatment of hepatocellular carcinoma in cirrhotic patients and 2) initial reports from major transplantation centers of multimethod therapies combining chemotherapy with transplantation. DATA EXTRACTION: Study designs were assessed with careful attention to methods and aims. Relevant data on patient population, tumor stage distribution, treatment, survival, and rate of recurrent disease were extracted and analyzed. DATA SYNTHESIS: Options for the treatment of hepatocellular carcinoma in cirrhotic patients vary according to tumor stage and severity of underlying liver disease. Resection remains an important method primarily in eastern countries, where the screening of high-risk populations has been associated with early detection of small asymptomatic lesions. Long-term survival after resection, however, is low. In western countries, liver transplantation is becoming the treatment of choice in patients with advanced cirrhosis and small, unresectable lesions; resection is reserved for cirrhotic patients with small, peripheral lesions and preserved hepatic function. Minimally invasive procedures (such as percutaneous ethanol injection and transarterial chemoembolization) have been developed to treat unresectable tumors. Transarterial chemoembolization may also be effective in patients with advanced cirrhosis and unresectable lesions who are awaiting transplantation. CONCLUSIONS: The efficacy of liver transplantation for hepatocellular carcinoma has been proven mainly in patients with advanced cirrhosis and small lesions. Future studies may clarify the role of approaches combining neoadjuvant chemotherapy with transplantation for large (stage III) tumors.

Algorithms↗
PubMed1997

Assessment of liver allograft function by hyaluronic acid and endothelin levels.

BACKGROUND: Sinusoidal endothelial cells are considered the primary site of preservation-reperfusion injury occurring during cold storage and reperfusion. Hyaluronic acid (HA) and endothelin-1 (ET) are markers of endothelial cell integrity. The aim of this study was to evaluate the possible correlation between these markers and early graft function following liver transplantation. MATERIALS AND METHODS: Blood samples were collected from 85 adult orthotopic liver transplant recipients at the following time points: before surgery, just before reperfusion, first and last 20 cc of caval effluent, 30, 60, and 120 min after reperfusion, and on postoperative day (POD) 1. Levels of both HA and ET were measured by sandwich enzyme-binding assay. HA uptake was also defined for every sample as the ratio of the actual measurement to the value obtained just before reperfusion. RESULTS: Patients with severe liver disease displayed significantly higher pretransplant HA and ET levels compared with those of less advanced illness. Poor early graft function (PEGF) was defined as peak enzyme levels on the first three PODs higher than 2500 U/L and prothrombin time longer than 16 s on POD 2. Patients with PEGF (n = 9) showed significantly lower HA uptake than patients with good graft function (n = 76) at 60 and 120 min after reperfusion. There was also a significant difference in the average uptake values measured in the last 20 cc of caval effluent between the two groups. We could not find any difference in ET levels between these two groups. CONCLUSIONS: Perioperative HA uptake measurement may be an additional marker to evaluate early graft function.

Adult↗
PubMed1997

Infectious ocular complications in orthotopic liver transplant patients.

We report the frequency and type of infectious ocular complications following orthotopic liver transplantation (OLT) and review diagnostic and therapeutic strategies. During the period September 1988 through November 1994, 684 patients underwent OLT at Mount Sinai Hospital (New York). Nine orthotopic liver transplant patients (1.3%) developed ocular infections: Candida albicans endophthalmitis (2), Aspergillus fumigatus endophthalmitis (1), cytomegalovirus retinitis (4), herpes simplex virus keratitis (1), and varicella-zoster virus panophthalmitis (1). The mean time from OLT to ocular symptoms was 42 days for patients with fungal infections and 128 days for patients with viral infections. Blurred vision was the commonest symptom (five of nine cases). The mean duration of follow-up was 2 years (range, 33 days to 5 years). Permanent loss of vision occurred in three patients, five had improvement in visual acuity, and one died of disseminated aspergillosis 33 days after OLT. Infectious ocular complications following OLT may occur as isolated events or with disseminated disease. Fungal infections occur earlier (mean, 42 days after OLT) than viral infections (mean, 4 months after OLT). The clinical presentation may be atypical; aggressive vitreoretinal procedures and serial examinations may be required to establish the diagnosis. Cytomegalovirus retinitis in orthotopic liver transplant patients may not require life-long maintenance therapy with antiviral agents.

Adult↗
PubMed1997

Effluent levels of thrombomodulin predict early graft function in clinical liver transplantation.

Thrombomodulin is a surface protein on vascular endothelial cells that serves as a binding site for thrombin and plays an important role as an anticoagulant factor. We correlated plasma thrombomodulin levels with early graft function after liver transplant in 58 recipients. Blood samples were collected at the following time points: before surgery, just before reperfusion, 30, 60, 120 min after reperfusion, and post-operative day 1. The first and last 20 cc of caval effluent were also collected. Plasma thrombomodulin levels were measured by a sandwich enzyme-binding assay in the blood samples; tissue expression was determined by immunohistochemistry. Poor early graft function was defined as peak aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2500 U/l during the first 3 post-operative days and prothrombin time >16 s on post-operative day 2. Thrombomodulin levels in the first 20 cc of caval effluent ranged from 1.33 to 91 FU/ml and showed a significant positive correlation with ischemic time, intra-operative blood transfusion requirement, and early graft function. In grafts with high effluent thrombomodulin (>20 FU/ml, n=12), the incidence of poor early graft function and primary nonfunction was 66.7% and 25.0%, respectively; in grafts with low effluent thrombomodulin (<20 FU/ml, n=46), graft function was not impaired. By immunohistochemistry, thrombomodulin was detected in large vessels of every donor liver. Sinusoidal cells, however, showed positive staining only in livers with poor early graft function. Effluent thrombomodulin levels reflect the extent of preservation injury and might be a useful marker for predicting graft function after liver transplantation.

Adult↗
PubMed1997

Differential contribution of graft and recipient to perioperative TNF-alpha, IL-1 beta, IL-6 and IL-8 levels and correlation with early graft function in clinical liver transplantation.

Cytokines, produced by both the recipient and the newly vascularized allograft, are central mediators in the inflammatory response to allografted tissue. This study examines the relationship between pre- and intraoperative levels of TNF, IL-1, IL-6, and IL-8 and hepatic allograft function in the early postoperative period and also determines which cytokines are produced in a significant amount by the newly vascularized allograft. Baseline levels of IL-6 and IL-8 tended to be higher in patients with more advanced disease and showed an increase during the anhepatic period. TNF and IL-1 remained stable from baseline to anhepatic phase. IL-1 showed an increase from portal vein to effluent samples, suggesting that the graft has an important contribution to circulating IL-1 levels. Analysis of the data according to early graft performance revealed extremely high levels of effluent IL-1, IL-6 and IL-8, and the prolonged elevation of the latter two cytokines in patients with poor early graft function. Our findings demonstrate that sequential perioperative measurements of proinflammatory cytokines can be useful in monitoring graft function.

Adult↗
PubMed1996

Nosocomial infections with vancomycin-resistant Enterococcus faecium in liver transplant recipients: risk factors for acquisition and mortality.

The risk factors for acquisition of and mortality due to nosocomial infection with vancomycin-resistant Enterococcus faecium (VREF) in orthotopic liver transplant (OLT) recipients were studied at a tertiary care hospital; 32 VREF-infected OLT patients (cases) were compared with 33 randomly selected OLT recipients (controls). More antibiotics were administered preoperatively to cases (mean, 4 antibiotics per patient for 474 antibiotic-days) than to controls (mean, 1.8 antibiotics per patient for 131 antibiotic-days). Cases were more likely than controls to have received vancomycin therapy preoperatively and to have been hospitalized in the intensive care unit (ICU) preoperatively. Logistic regression revealed that the risk factors for acquisition of VREF infection were surgical reexploration and a prolonged stay in the surgical ICU postoperatively. In the cases, the risk factors for mortality were admission to the ICU preoperatively and hemodialysis. The mortality rate associated with polymicrobial bloodstream infections was 100% despite appropriate therapy. Sixteen and 18 cases received parenteral chloramphenicol and doxycycline, respectively, for treatment of VREF infection. There were no hematologic adverse effects attributed to chloramphenicol treatment. DNA analysis of selected E. faecium isolates suggested that infections were due to multiple clones. In summary, the source of VREF infection in OLT patients is the gastrointestinal tract. Antibiotic selective pressure may contribute to colonization. Infection with VREF is a predictor of morbidity and mortality in OLT patients.

Anti-Bacterial Agents↗
PubMed1995

A multidisciplinary approach to hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: A multidisciplinary approach has been developed to evaluate and treat patients with cirrhosis and hepatocellular carcinoma (HCC). STUDY DESIGN: We evaluated 153 patients with cirrhosis and HCC. Fourteen patients with Child's A cirrhosis underwent resection. Transplantation was performed in 40 patients with HCC less than 5 cm (32 incidental, eight recognized preoperatively), in six patients with HCC 5 cm or greater not recognized preoperatively, and in 11 patients with recognized HCC 5 cm or greater; the latter 11 underwent transplantation in a multimodality protocol using pretransplant chemoembolization and intraoperative and postoperative chemotherapy. RESULTS: Among the 14 patients who underwent resection, the three-year survival rate was 39 percent. Among the 40 patients with HCC less than 5 cm who underwent transplantation, no tumor recurrence was observed. Among the six with HCC 5 cm or greater unrecognized preoperatively, three had tumor recurrence. Among the 11 with HCC 5 cm or greater enrolled in the protocol, there were no deaths and one recurrence at a mean of 433 days follow-up. The four-year survival rate for all patients who underwent transplantation with HCC was 56 percent (66 percent excluding the six patients with unrecognized HCC 5 cm or larger). CONCLUSIONS: Hepatocellular carcinoma less than 5 cm in patients with cirrhosis (Child's B or C) is an indication for hepatic transplantation. Hepatocellular carcinoma less than 5 cm in patients with cirrhosis (Child's A), although resectable, may in some cases be better treated by hepatic transplantation. Transplantation for HCC 5 cm or greater within a multimodality protocol has yielded excellent results at two years.

Aged↗