Incidence of abdominal wall numbness post-liver transplantation and its complications.

Liver transplantation (LTx) is a life-saving procedure for end-stage liver disease. However, LTx remains a major surgical procedure with a significant amount of morbidity and mortality. Several different types of post-LTx complications have been studied and reported; however, the numbness of the abdominal skin between the subcostal incision and the umbilicus and its associated complications have not been studied in a large patient population. The aim of this study was to report the incidence of numbness in the abdominal skin post-LTx and its implications in routine life. One hundred and one post-LTx patients were questioned in the clinic about numbness. There were 52 male patients and 49 female patients with a mean age of 51.9 +/- 11.3 years at the time of LTx, and the mean time from transplant was 35.0 +/- 29.5 months (range, 3-113 months). The implications were recorded. All 101 patients (100%) had an area of numbness between the subcostal incision and the umbilicus. Four of these patients had an area of superficial-to-deep burns from hot food (accidentally dropped on the abdomen), heating pads, or a hot cup of tea. One patient had ecchymosis from blunt trauma during gardening. Out of 36 diabetic patients, more than 24 patients were insulin-dependent and used the area for subcutaneous insulin injections. In addition, some of the 43 hepatitis C virus-positive patients used the area for subcutaneous interferon therapy. In conclusion, 100% of the patients had persistent numbness up to 9 years following LTx. Five percent of the patients developed thermal injuries or blunt trauma complications that could have been prevented with better education and awareness. More then 24% of the patients used the area for subcutaneous injections of insulin and/or interferon.

Pharmacokinetics of tacrolimus in living donor liver transplant and deceased donor liver transplant recipients.

INTRODUCTION: Hepatic dysfunction is an important determinant of the clearance of tacrolimus; however, the impact of reduced hepatic mass in living donor liver transplant (LDLT) patients on the drug exposure and clearance of tacrolimus is not known. AIM.: The aim of the present study is to compare the dosage, concentration and pharmacokinetics parameters of tacrolimus between LDLT and deceased donor liver transplant (DDLT) recipients. PATIENTS AND METHODS: Daily doses used and trough concentrations measured were compared in 12 LDLT and 12 DDLT patients. Multiple blood samples were taken over one dosing interval after oral tacrolimus administration, and pharmacokinetics differences were compared. RESULTS: The mean tacrolimus dosage in first 14 postoperative days was (0.06 mg/kg/day) for LDLT and (0.09 mg/kg/day) for DDLT (P=0.0001). Despite the lower doses used, mean trough concentration was significantly greater in LDLT as compared with DDLT (8.8+/-2.5 ng/mL vs. 6.79+/-1.5 ng/mL, respectively, P=0.013). On the day of the pharmacokinetic study, minimum Concentration (Cmin), 12-hr postdose concentration (Clast), and average concentration (Cavg) were significantly greater in LDLT as compared with DDLT (LDLT: 6.6+/-2.4 ng/mL, 7.2+/-1.8 ng/mL, 8.9+/-3.0 ng/mL; DDLT: 4.3+/-1.0 ng/mL, 4.9+/-1.6 ng/mL, 5.9+/-1.4 ng/mL, P=0.02, 0.04, and 0.02, respectively). Dose normalized AUC was 37.7% greater and clearance, 47.5% lower in LDLT as compared with DDLT. CONCLUSION: Although not statistically significant, the dose normalized AUC was 37.7% greater and clearance 47.5% lower in LDLT as compared with DDLT. An initial tacrolimus dose reduction of about 30-40% may be prudent in LDLT compared with DDLT recipients.

Recurrent nonhepatic and de novo malignancies after liver transplantation.

INTRODUCTION: After Liver transplantation (LTx), recurrence of hepatic cancer, de novo cancers, and donor-transmitted cancers have been described. However, the data for patients with a prior history of nonhepatic malignancy and its recurrence post-LTx are limited. AIM: Aim of this study was to examine the patient with nonhepatic pre-LTx malignancies, and their recurrence post-LTx along with de novo cancers and recurrence of hepatic malignancy in the population. PATIENTS AND METHOD: Between March 1996 and July 2006, 1127 patients underwent LTx at our institution. Thirty patients (2.7%) (15 men and 15 women, mean age 56.9+/-12.8 years) had documented nonhepatic malignancies. There were seven colorectal, three prostatic, three cervical, three bladder, six breast, and other nine miscellaneous cancers (one patient had two cancers). Four patients had hepatocellular carcinoma at the time of LTx. All patients were followed up until 2008 with a mean follow-up period of 34.1+/-35.3 months. RESULTS: One patient with oropharyngeal cancer (3.3%), who was recurrence-free pre-LTx for 77.3 months, developed recurrence 36 months post-LTx and subsequently died 11 months postrecurrence. Two patients developed de novo cancer. One developed renal cell carcinoma 46.6 months post-LTx and other developed de novo intra-abdominal metastatic adenocarcinoma of unknown origin. Three of four patients developed recurrent hepatocellular carcinoma. CONCLUSION: The rate of recurrence of nonhepatic malignancy was 3% and de novo cancer was 6% in the present series. There is a need to develop a guideline for recurrence-free survival period for nonhepatic malignancies before LTx, based on the type and stage of cancer.

Potential immunological advantage of intravenous mycophenolate mofetil with tacrolimus and steroids in primary deceased donor liver transplantation and live donor liver transplantation without antibody induction.

With the current immunosuppressive regimens, graft loss secondary to immunological reasons after successful liver transplantation is a rarity; acute rejections, however, do occur, with the majority of them being steroid-responsive. The aim of the present study is to examine the rate of acute rejection with tacrolimus, intravenous (IV) mycophenolate mofetil (MMF), and steroids in primary deceased donor liver transplant (DDLT) and live donor liver transplant (LDLT) recipients. During the year 2005, 130 patients (mean age: 54.9 +/- 10.8, males: 84, females: 46, 112 DDLT and 18 LDLT) received primary liver transplantation. They were followed up for the incidence of acute rejection in the first 12 months. Liver biopsies were performed as clinically indicated; protocol liver biopsies were never performed. A total of 127 liver biopsies were performed. Thirty-two had a rejection activity index (RAI) score of > or =3, of which 24 biopsies in 20 patients were not treated with a steroid bolus. Eight (6.1%) patients (mean RAI score: 5.1 +/- 1.4) received 750 to 1500 mg of methylprednisolone over 3 days. Out of these, 2 were noncompliant, 4 were off MMF, and 1 was on cyclosporine. All patients responded to steroid therapy. None of the patients required any antibody preparation. In conclusion, IV MMF with tacrolimus and steroids is useful and required antirejection therapy in 6.1% of liver transplant recipients.

Pharmacokinetics of mycophenolic acid in liver transplant patients after intravenous and oral administration of mycophenolate mofetil.

The bioavailability of mycophenolic acid (MPA) after oral administration of mycophenolate mofetil (MMF) has been reported to be more than 90% in healthy volunteers, and in kidney and thoracic organ transplant patients. Such information is limited in liver transplant (LTx) patients. The present study compares the pharmacokinetics of MPA after intravenous (IV) and oral administrations of MMF in LTx recipients. Pharmacokinetic parameters were calculated using WinNonlin software. A total of 12 deceased donor LTx patients initially received IV MMF and were switched to oral MMF after 2-7 days (mean, 3.3 +/- 1.7) when oral feeds were started. Multiple blood samples were drawn immediately prior to and after IV or oral MMF and the plasma concentration of MPA was measured. The mean peak plasma concentrations and the area under the plasma concentration vs. time curve (AUC) were significantly higher after IV MMF compared to oral MMF (peak plasma concentrations of 10.7 +/- 2.1 microg/mL for IV vs. 4.5 +/- 2.8 microg/mL for oral; P = 0.0001; and AUC of 28.9 +/- 7.1 microg . hr/mL for IV vs. 12.8 +/- 4.2 microg . hr/mL for oral; P = 0.0001). The oral bioavailability of MPA was 48.5 +/- 18.7%. The systemic clearance, half-life, and steady state volume of distribution of MPA were 26.9 +/- 6 L/hour, 5.5 hours, and 85 liters, respectively. The terminal disposition half-life was not significantly different between the 2 routes of administration. In conclusion, during the early postoperative period, LTx recipients have MPA exposure with oral MMF of less than half that of IV MMF. Use of IV MMF immediately post-LTx may provide an immunological advantage.

Characterization of CD4, CD8, CD56 positive lymphocytes and C4d deposits to distinguish acute cellular rejection from recurrent hepatitis C in post-liver transplant biopsies.

INTRODUCTION: Hepatitis C viral (HCV) infection is the most common cause for liver transplantation (LTx) in USA. Hepatitis C viral recurrence in liver allograft is almost universal, which is often difficult to distinguish from acute cellular rejection (ACR). AIM: Aim of the present study is to examine the differences between distribution of CD4, CD8, CD56 positive lymphocytes, and C4d deposits in patients with ACR and recurrent HCV. PATIENTS AND METHODS: As a pilot project, a group of five post-LTx HCV RNA negative patients, strongly suspicious for ACR based on clinical findings and history of medication non-compliance and another group of five post-LTx HCV positive, medication compliant patients with abnormal liver function were retrospectively selected. Liver biopsies of these patients were stained with monoclonal CD4, CD8, CD56, and polyclonal C4d antibodies and compared. RESULTS: Mean CD4, CD8, and CD56 counts in ACR group were 156.7 +/- 17.6, 35.4 +/- 8.8, and 1.0 +/- 1.8/HPF, respectively and were 89.7 +/- 41.3, 20.3 +/- 23.2, and 0.6 +/- 0.9/HPF, respectively in HCV recurrence group. Biopsies of four of five patients with ACR demonstrated moderate to strong C4d staining, whereas all patients with recurrent HCV had none to mild C4d staining. CONCLUSION: Mean CD4, CD8, and CD56 were similar for acute rejection and recurrent HCV infection. However, 80% of patients with ACR showed moderate to strong staining for C4d and all recurrent HCV patients showed none to mild C4d staining.