Browsing by Author "Orloff, Mark"

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Effect of Liver Transplant on Pulmonary Functions in Adult Patients with Alpha 1 Antitrypsin Deficiency: 7 Cases
(Başkent Üniversitesi, 2010-03) Kashyap, Randeep; Orloff, Mark; Jain, Ashokkumar B.; Patil, Vrishali; Sheikh, Baber; Apostolakos, Michael; Ryan, Charlotte
Objectives: Alpha 1 antitrypsin (A1A) is a 52 kD glycoprotein that is mainly synthesized in the liver. As a major protease inhibitor, it binds to and neutralizes neutrophil elastase, thereby limiting the damage to the normal tissues after an inflammatory response. A deficiency in A1A leads to end-stage liver disease, both in children and in adults. In addition, the deficiency also has a detrimental effect in the lungs of the adult population. Alpha 1 antitrypsin deficiency is corrected with hepatic replacement; however, the changes in pulmonary functions have not been studied before and after liver transplant. The purpose of this study was to observe the changes in the pulmonary functions of patients who underwent liver transplant for the treatment of A1A deficiency. Materials and Methods: Nine patients underwent liver transplant for A1A deficiency. Seven patients (5 men, 2 women; mean age, 49.95 ± 7.09 years) had their pulmonary function tests available before the liver transplant (mean, 5.6 ± 3.4; range, 0.9-10.1 months) and after the liver transplant (mean, 30.3 ± 18.4, range 7.8-48.1 months) for analysis. Results: The mean, preliver, transplant, FEV1 was 2.69 ± 0.9 L, which was nearly unchanged after the liver transplant to a mean of 2.7 ± 1.2 L. During the mean total interval of nearly 3 years, an estimated decline of 250 mL in FEV1 was expected. Conclusions: It appears from the results of our study that liver transplant probably prevented the progression of pulmonary disease in A1A-deficient patients. Further study and close, postliver, transplant follow-up is warranted to support our initial findings.
HCV Antibody Quantitative Levels in Liver Transplant Patients: Do They Have Any Relevance in Clinical Practice?
(Başkent Üniversitesi, 2006-06) Jain, Ashok; Menegus, Marilyn; Mohanka, Ravi; Orloff, Mark; Abt, Peter; Mantry, Parvez; Bozorgzadeh, Adel
Objectives: Hepatitis C virus (HCV) is not directly cytopathic to the hepatocytes; however, host immune response against the virus does cause hepatic injury. Production of the HCV antibody is a host immune response to a viral antigen. The currently used HCV antibody assay is a qualitative, not quantitative, assessment. In this study, we sought to quantitatively estimate HCV antibody levels in patients who had undergone liver transplantations at the University of Rochester Medical Center, Rochester, New York, and correlate these levels with HCV RNA viral load, genotype, severity of recurrence, and anti-HCV treatment. Materials and Methods: From 39 liver transplantation patients, we obtained 141 blood samples for quantitative HCV RNA to measure HCV antibody levels quantitatively. Results: Most antibody levels were within a narrow range with a mean of 32.9 ± 5.1. Samples with undetectable RNA had a mean antibody level of 31.4 ± 8.0, and samples with a positive RNA had mean level of 33.0 ± 4.6. The mean antibody levels were significantly higher for patients with genotype 1 (n = 33) compared with those with genotype 2 (n = 5) (33.2 vs 29.1; P = .007). No correlation was found between antibody levels and severity of hepatic injury with regard to hepatitis activity index or fibrosis score. Six patients with no response to anti-HCV treatment had no change in their mean antibody levels (33.7 vs 34.5). Ten patients who responded to anti-HCV therapy had lower mean levels after therapy, but the changes were not significant (34.2 vs 30.4). Conclusions: Antibody levels in this study did not correlate with viral load or hepatic injury. However, genotype-2 patients had significantly lower levels compared with genotype-1 patients, and patients who responded to anti-HCV therapy demonstrated decreased antibody levels.
Intravenous Mycophenolate Mofetil with Low-Dose Oral Tacrolimus and Steroid Induction for Live Donor Liver Transplantation
(Başkent Üniversitesi, 2005-12) Jain, Ashok; Mohanka, Ravi; Orloff, Mark; Abt, Peter; Kashyap, Randeep; Kelley, Mark; Burlee, Kari; Bozorgzadeh, Adel
Objectives: Mycophenolate mofetil (MMF) is used in liver transplantation (LTx) to reduce rejection, nephrotoxicity, neurotoxicity, and the need for steroids. Lower trough concentrations and bioavailability have been reported with oral MMF in first week after LTx. These parameters improve after the first month postoperatively. Previously published studies have used oral formulations of MMF. In this study, we sought to examine survival, rejection, and nephrotoxicity rates using IV MMF in live donor liver transplantation (LDLT). Patients and Methods: Twenty-eight patients (mean age, 50.1 years; 15 men, 13 women) were examined between January 2000 and January 2004 with a mean follow-up of 17 months for survival, rejection, and renal function. Results: Four patients died at 2, 5, 8, and 18 months after LDLT from sepsis (n = 3) and recurrent hepatocellular carcinoma (n = 1). There were no retransplants; hence, patient and graft survival rates were the same (82.4%). Three patients (10.7%) experienced acute cellular rejection requiring treatment. The mean serum creatinine level prior to LDLT was 0.9 ± 0.4 mg/dL, which remained stable throughout the study. One patient required hemodialysis during the perioperative period for 8 days. Conclusions: In the current study, we demonstrate a new strategy of IV MMF administration with low-dose tacrolimus that provides for lower rates of acute rejection, better preservation of renal function, and one that is better tolerated compared with historical treatments after LTx.
Polysubstance abuse in liver transplant patients and its impact on survival outcome
(Başkent Üniversitesi, 2007-12) Nickels, Mark; Bozorgzadeh, Adel; Kashyap, Randeep; Tsoulfas, Georgios; Orloff, Mark; Sharma, Rajeev; Jain, Ashok
Background: Alcohol-related end-stage liver disease was the most common reason for liver transplant in the 1990s. Currently, hepatitis C virus (HCV) is the most common reason for transplant. The major HCV risk factor is intravenous drug abuse, which often includes other forms of substance abuse. It is important to understand posttransplant survival outcomes in patients with multiple substance abuse and pretransplant factors that predict relapse. Methods: The medical records of patients referred to the transplant psychiatrist were retrospectively reviewed to identify posttransplant patients with pretransplant multisubstance abuse issues including cannabis, cocaine, opioids, and alcohol. Survival outcomes and drug relapse were assessed in relation to demographic variables including age, race, sex, legal history, psychiatric diagnoses or need for psychiatric hospitalization, and substance abuse diagnosis. Results: Twenty-seven patients with polysubstance abuse disorders were identified: substance abuse (n=41), substance dependence (n=33), and other (n=8); a mean of 3.03 substances was used per patient. Eight patients relapsed (29.6%) and 10 patients died (33%) between 2 and 60 months after transplant. Patients were divided into relapse and no-relapse groups, and 1-year patient survival rates in patients were 100% and 83.9%, respectively. No between-group differences were found for age, race, sex, legal history, psychiatric diagnoses or need for psychiatric hospitalization, or having first-degree relatives with substance abuse issues. Conclusions: The rate of recidivism was 26.9%; however, it did not affect survival. No predictors of relapse were identified. Patients with polysubstance abuse issues should not be categorically denied access to liver transplant. Further research regarding these issues is essential.
Postoperative Impact of Intraoperative Biochemical Changes at the Completion of Parenchymal Division in Living-Donor Liver Transplantat
(Başkent Üniversitesi, 2006-12) Jain, Ashok; Orloff, Mark; Abt, Peter; Kashyap, Randeep; Mantry, Parvez; Bozorgzadeh, Adel
Objectives: Biochemical abnormalities after living-donor hepatectomy are attributed to the loss of liver volume and steatosis or fibrosis. In this study, we evaluated the intraoperative biochemical changes caused by the separation of the hepatic lobes before removal and the impact of those changes on postoperative biochemical abnormalities in patients who underwent adult-to-adult living-donor liver transplantation (LDLT). Materials and Methods: The extent and postoperative impact of the biochemical changes that occur during hepatic parenchymal transection in adult-to-adult LDLT were studied in 38 patients who underwent that procedure (14 men and 24 women; mean age, 39.6 years; age range, 19.5-58.9 years). Preoperative, intraoperative, and postoperative biochemical values for the first 8 postoperative days were compared. Results: The mean total hepatic volume was 1703.0 mL, the mean weight of the resected mass was 887.0 g (52.6%), and the mean weight of the residual mass was 816.0 g (47.4%). The mean total bilirubin, aspartate amino transferase (AST), and amino alanine transferase (ALT) values were 8.6 U/L, 21.4 U/L, and 27.6 U/L, respectively, before surgery, compared with 27.4 U/L (an increase of 3.2 times), 257.9.2 U/L (an increase of 12.0 times), and 224.64 U/L (an increase of 8.1 times), respectively, after separation of the hepatic lobes. Patients (n = 21) with an intraoperative ALT value of >= 200 had a significantly higher peak postoperative ALT (P = .001) than did those (n = 17) with an ALT value of < 200. Conclusions: A significant increase in hepatic biochemical parameters occurs at the completion of hepatic parenchymal transection and before the removal of the right hepatic lobe from the donor. This has an impact on postoperative peak enzyme levels in the donor.
University of Wisconsin Versus Histidine-Tryptophan-Ketoglutarate for Tissue Preservation in Live-Donor Liver Transplantation
(Başkent Üniversitesi, 2006-06) Jain, Ashok; Mohanka, Ravi; Orloff, Mark; Abt, Peter; Kashyap, Randeep; Cullen, Jackie; Lansing, Kerrie; Bozorgzade, Adel
Objectives: University of Wisconsin solution has twice the cold hepatic preservation time as does Euro-Collins solution. Histidine-tryptophan-ketoglutarate has a lower potassium content than does University of Wisconsin solution and is used more frequently. To date, however, studies comparing University of Wisconsin and histidine-tryptophan-ketoglutarate in live-donor liver transplantation are lacking. We therefore sought to examine the hepatic function of live-donor liver transplantation allografts preserved in University of Wisconsin solution as compared with those preserved in histidine-tryptophan-ketoglutarate solution. Materials and Methods: Between July 2003 and August 2004, 33 live-donor liver transplantations were performed at the University of Rochester Medical Center, Rochester, NY, USA. University of Wisconsin solution was used for the first 9 allografts, and histidine-tryptophan-ketoglutarate was used for the subsequent 24 allografts. Daily total bilirubin, aspartate amino transferase, amino alanine transferase, alkaline phosphatase, gamma glutamyl transpeptidase, and international normalized ratio levels were measured for the first 8 postoperative days. Peak values were compared between the groups. Results: There was no primary graft nonfunction in either group. Two patients in the histidine-tryptophan-ketoglutarate group developed hepatic artery thromboses and underwent a retransplantation. Mean peak aspartate amino transferase and amino alanine transferase levels were higher in patients in the histidine-tryptophan-ketoglutarate group (aspartate amino transferase, 661 ± 801 U/L; amino alanine transferase, 696 ± 964 U/L) than they were in patients in the University of Wisconsin group (aspartate amino transferase, 439 ± 415 U/L; amino alanine transferase, 464 ± 376 U/L); however, this difference was not significant. Mean total bilirubin, alkaline phosphatase, and gamma glutamyl transpeptidase levels, and international normalized ratios were similar in both groups. Conclusions: University of Wisconsin and histidine-tryptophan-ketoglutarate solutions are both effective in preserving live-donor liver allografts. In the current study, patients in the histidine-tryptophan-ketoglutarate group had higher peak aspartate amino transferase and amino alanine transferase levels initially, but these became almost identical by postoperative day 8.