Outcome of Liver Transplantation in Hepatocellular Carcinoma Patients at Siriraj Hospital.

BACKGROUND: Liver transplantation (LT) is one of the standard treatments for hepatocellular carcinoma (HCC), and the outcomes have become better after introduction of strict patient selection, such as the Milan criteria. However, several expanded criteria, such as the University of California San Francisco (UCSF) criteria, have demonstrated similar survival outcomes. The aim of this study was to verify survival outcomes of LT for HCC at Siriraj Hospital. METHODS: Sixty-three patients diagnosed with HCC who underwent cadaveric LT at Siriraj Hospital from 2002 to 2011 were included. All patients' characteristics, blood chemistries, size and number of tumors, bridging therapy, and survival and recurrence data were retrospectively reviewed and analyzed. RESULTS: Nearly all (62 patients, 98.4%) fulfilled the Milan criteria based on preoperative imaging. Explant pathology revealed that 40 patients (63.5%) were within Milan criteria and 50 patients (83%) within UCSF criteria. Demographic data, clinical laboratory, and bridging therapy were similar in patients within and outside both Milan and UCSF criteria. The 1-, 3-, and 5-year survival rates of patients within Milan were 85%, 75%, and 67.5%, and of those outside Milan were 69.6%, 52.2%, 52.2%, respectively (P = .25). Interestingly, with the use of the UCSF criteria, the 1-, 3-, and 5-year survival rates of patients within UCSF were significantly better than of those outside UCSF (84%, 76%, and 70% vs 61.5%, 30.8%, and 30.8%, respectively; P = .01). CONCLUSIONS: Outcome of LT in HCC patients within Milan criteria demonstrated good long-term survival. However, providing the opportunity for HCC patients by expanding from Milan to UCSF criteria revealed similar outcomes.

Correlation of Hematocrit and Tacrolimus Level in Liver Transplant Recipients.

BACKGROUND: Tacrolimus is the most widely used immunosuppressive drug after liver transplantation. Whole blood tacrolimus level is used for drug monitoring. Because of strong uptake by erythrocytes (95% to 98%), hematocrit level is an important factor for evaluation whole blood tacrolimus level. There has been no formula to calculate the effect of hematocrit on the whole blood tacrolimus level. The aim of this study is to evaluate the effect of hematocrit on the whole blood tacrolimus level. METHODS: Twenty-five patients were included in this study. Blood samples during routine follow-up were used. All patients received tacrolimus for more than 30 days after liver transplantation. Approximately half of the plasma was removed. Blood samples were remixed and remeasured for hematocrit and whole blood tacrolimus levels. Pearson correlation and linear regression were performed to generate a formula for corrected tacrolimus level. RESULTS: Thirteen male and 12 female patients participated in this study. There was a significant positive correlation between hematocrit ratio and tacrolimus ratio (r = 0.765, r(2) = 0.585, P < .001). The pattern of linear relationship between hematocrit ratio and tacrolimus ratio is defined by the regression equation, and the formula to correct tacrolimus level at hematocrit 40% is as follows: [Formula: see text] CONCLUSION: Hematocrit has a significant effect on tacrolimus level. Better dose adjustment for patients should include the consideration of hematocrit levels. Further studies are required to validate this formula and clinical significance.

Systematic Pharmaceutical Educational Approach to Enhance Drug Adherence in Liver Transplant Recipients.

BACKGROUND: Drug adherence is one of the most important factors determining graft and patient survivals after liver transplantation. A systematic pharmaceutical educational approach has been implemented to improve adherence in immunosuppressive drugs therapy at Siriraj Hospital. METHODS: This study was a single-center cross-sectional study of liver transplant patients who received pharmaceutical care from transplant pharmacists. The clinical pharmacy services, including medication review to emphasize patients' knowledge and awareness of immunosuppressive and general drug therapies with the use of various tools, were used to educate the patients. Drug-related problems (DRPs) and pre- and post-transplantation educational tests (divided into 3 parts: immunosuppressants [12 points], drug monitoring [6 points], and general drugs [2 points]) were analyzed. RESULTS: From October 2012 to September 2014, a total of 50 liver transplant recipients (86 visits) were enrolled. After the systematic pharmaceutical educational program, the average total score of post-transplantation educational test improved from 3.48 to 13.30 (P < .001). Likewise, the mean scores of all 3 parts significantly increased (part I: 2.28 vs 8.18 [P < .001]; part II: 0.75 vs 3.63 (P < .001); and part III: 0.46 vs 1.50 [P < .001]). The incidences of major DRPs, nonadherence, and adverse drug reactions were 8%, 4%, and 2%, respectively. CONCLUSIONS: A systematic pharmaceutical educational approach can significantly improve patients' knowledge and awareness concerning immunosuppressive drug usage.

Immunosuppressive Medication Adherence in Liver Transplant Recipients.

BACKGROUND: Immunosuppressive medication is one of the pivotal factors in the outcome of liver transplant patients. Nonadherence to immunosuppressive therapy is a common problem after transplantation and affects graft and patient survival. This study aimed to assess immunosuppressive medication adherence in liver transplant recipients. METHODS: Liver transplant recipients who underwent the Siriraj-Support Medication Adherence in Organ Transplantation (S-SMAOT) program were included in this cross-sectional study. Immunosuppressive medication adherence was assessed with the use of the Immunosuppressive Therapy Adherence Scale (ITAS, which is scored from 0 to 12; very poor to excellence adherence). The correlations between ITAS scores and the clinical profiles of the patients, duration after transplantation, and transplant educational scores post-test were also analyzed. RESULTS: From October 2012 to September 2014, a total of 50 liver transplant recipients (86 visits) were enrolled in this study. The ratio of male to female patients was 48:52. The proportions of patients with ITAS scores of 12, 10-11, and 0-9 were 82.6%, 16.3% and 1.2%, respectively. ITAS score was significantly correlated with the duration after transplantation (P < .001) and the educational scores (P = .009). CONCLUSIONS: Consistent assessment of patients' immunosuppressive medication adherence is essential to avoid problems of noncompliance and to improve the outcome after liver transplantation. The S-SMAOT program was an effective approach to significantly improve the medication adherence in liver transplant recipients.

Murine typhus in a liver transplant recipient: report of a first case.

Zoonoses, especially rickettsial diseases, are rarely reported in solid organ transplant recipients. We report here a case of murine typhus in a 69-year-old liver transplant recipient, who presented with acute febrile illness 5 years post transplantation. Although receiving treatment with broad-spectrum antibiotics, he was still febrile and developed progressive dyspnea. Laboratory results showed elevated transaminases and his chest radiograph revealed bilateral interstitial infiltration. The diagnosis of murine typhus was made by a 4-fold rise in specific Rickettsia typhi antibody, using indirect immunofluorescent assay. He dramatically improved after treatment with doxycycline for 7 days. To our knowledge, this is the first case report of murine typhus in a liver transplant recipient.

Outcomes of orthotopic liver transplantation in non-malignant end-stage liver diseases.

BACKGROUND: Orthotopic liver transplantation (OLT) is an effective treatment for patients who have end-stage liver disease. The aim of this study is to compare outcomes of OLT in fulminant hepatic failure (FHF) and non-fulminant hepatic failure (non-FHF) patients. METHODS: A retrospective review of adult patients who underwent OLT for non-malignant end-stage liver diseases between 2002 and 2011 at Siriraj Hospital was performed. All explanted liver histopathology results were reviewed. The clinical factors and overall results of OLT were analyzed. RESULTS: Of the 137 patients, 72 patients had non-malignant diagnoses. Eleven patients were diagnosed with FHF, whereas 61 patients were in the non-FHF group. The most common indication for liver transplantation was chronic viral hepatitis. One- and 5-year survival rates (95% confidence interval) in the FHF group were 91% (51%-99%) and 91% (51%-99%), respectively, whereas those in the non-FHF group were 74% (61%-83%) and 66% (52%-77%), respectively. Multivariate cox regression analysis revealed no statistically significant difference of survival between both groups (P = .34). CONCLUSIONS: The post-OLT outcomes in non-malignant patients were comparable between FHF and non-FHF groups in terms of survival. OLT remains the only therapeutic option for the FHF patients.

Renal dysfunction after orthotopic liver transplantation.

BACKGROUND: Identification of risk factors of acute renal failure (ARF) after orthotopic liver transplantation (OLT) may avoid the development and attenuate the impact on patient outcome. Therefore, the incidence and risk factors of ARF after OLT at Siriraj Hospital were analyzed. METHODS: The study was retrospectively analyzed from the OLT patients at the Siriraj Hospital between January 2002 and December 2009. ARF was defined as an increased in serum creatinine level more than 1.5 times within the first week postoperation compared with the preoperative level. RESULTS: A total of 81 liver transplant patients were analyzed. The mean age was 52.45 years (range, 22 to 71) and there were 25 women (30.86%) and 56 men (69.14%). Indications for OLT were end-stage liver cirrhosis (n = 43, 53.09%), hepatocellular carcinoma (n = 36, 44.44%), and fulminant hepatic failure (n = 2, 2.47%). Fifty-eight patients (71.60%) developed ARF, and the perioperative mortality of these was 18.97%. The univariate analysis identified the presence of preoperative coagulopathy, prolonged intraoperative hypotension, more blood loss, and postoperative hypotension as the risk factors of ARF. By the multivariate analysis, prolonged intraoperative hypotension more than 30 minutes and presence of postoperative hypotension were the independent risk factors of ARF. During the intraoperative and postoperative periods, ARF group required more blood and blood components transfusion, longer intensive care unit stay, and higher in-hospital mortality. Seven patients (12.07%) in the ARF group required postoperative renal replacement therapy. Four patients (9.52%) developed chronic renal failure, and one of them required long-term hemodialysis. CONCLUSIONS: ARF was a common complication after OLT, which caused increased morbidity and mortality. Although some patients required dialysis, most of them recovered normal renal function. Prolonged intraoperative hypotension and presence of postoperative hypotension were the independent risk factors of ARF after OLT.

Analysis of donor risk factors associated with graft outcomes in orthotopic liver transplantation.

BACKGROUND: In orthotopic liver transplantation (OLT), the critical shortage of organ donors is the reason for accepting marginal donors. Although the outcome of OLT does not entirely seem to have been affected by the use of such donors identification of predictive risk factors is challenging. This study sought to identify significant risk factors associated with graft outcomes in our institute. METHODS: We retrospectively analyzed donor-associated factors for recipients who underwent liver transplantation from January 2002 to December 2009 for displaying primary dysfunction (PDF) as primary nonfunction (PNF) and initial poor function (IPF). RESULTS: We examined 97 post-liver transplant patients (male:female 70:27) whose average age was 52.74 years. The majority of indications for OLT were hepatitis B and/or C cirrhosis, alcoholic cirrhosis, and hepatocellular carcinoma. The incidence of PDF was 31.9% (31/97) including 7.2% PNF (7/97) and 24.7% IPF (24/97), versus 68.1% (66/97) with immediate function. The donors last serum alanine aminotransferase value being more than 65 IU/L was the only risk factor for poor graft function (P=.034). Donor peak and last serum sodium were potential risk factors. CONCLUSION: Although many factors including a high serum sodium level are associated with a marginal liver graft, Last donor alanine aminotransferase level was the only significant factor that predicted the PDF.

Recipient and perioperative risk factors associated with liver transplant graft outcomes.

BACKGROUND: Orthotopic liver transplantation (OLT) is currently considered to be the ultimate form of therapy for most patients with end-stage liver diseases. The identification of recipient and various perioperative factors that may affect the graft outcomes is critical. This study sought to analyze the preoperative and perioperative factors associated with graft outcomes in our institute. METHODS: This retrospective study of liver transplanted patients from January 2002 to December 2009 determined the incidence of 2 forms of primary dysfunction (PDF): Primary nonfunction (PNF) and initial poor function (IPF). RESULTS: The 97 posttransplant patients included in the study had an average age of 52.74 years. The majority of indications for OLT were hepatitis B and/or C cirrhosis, alcoholic cirrhosis, and hepatocellular carcinoma. The incidence of PDF was 31.9% (31/97) with 7.2% (7/97) PNF and 24.7% (24/97) IPF. Additionally, we observed 68.1% (66/97) to display immediate function (IF). Warm ischemic time (WIT) and operative time were significantly longer in the PDF compared with the IF group. The logistic regression model showed a WIT of >45 minutes to be a risk factor leading to PDF (odds ratio, 11.74; P<.05). An operative time of >6 hours and operative blood loss of >2 L were possible risk factors. CONCLUSION: Prolonged WIT (>45 minutes) was the only significant risk factor among other established parameters for graft function. Nevertheless, reduced operative times and blood loss may improve the outcomes of OLT.

Quality of life among liver transplantation patients.

BACKGROUND: Orthotopic liver transplantation (OLT) is the treatment of choice for end-stage disease. It offers a chance to return to an active and prolonged life. Recently, more attention is being paid to the health-related quality of life (HRQoL) of patients and their spouses or caregivers after OLT. The aim of this study was to analyze the pre- versus posttransplantation HRQoL of patients and their spouses or caregivers using generic and disease-specific health questionnaires. MATERIAL AND METHODS: The study was performed between October 2010 and January 2011 using the Short Form-36 (SF-36) and the Chronic Liver Disease Questionnaire (CLDQ) to evaluate the HRQoL. RESULTS: Posttransplantation patients (N=59, mean age 53.39 [range, 23 to 76] years, male 63.2%, female 36.8%) and their spouses and caregivers showed significantly better generic SF-36 HRQoL scores, namely, physical and social functioning, role limitations because of physical or emotional problems, bodily pain, vitality, as well as general and mental health compared with pretransplantation patients (N=57, mean age 54.56 (range, 22 to 69) years, male 71.2%, female 28.8%). Similarly, the posttransplantation group showed significantly improved CLDQ scores in all domains: fatigue, activity, abdominal symptoms, systemic symptoms, emotional function, and worry. CONCLUSION: OLT improved HRQoL of end-stage liver patients and their spouses or caregivers.

The 37-year kidney transplantation experience at Siriraj Hospital.

With 37-years of experience, a total of 801 kidney transplantations (59.4% were deceased donors and 40.6% were living donors) performed at Siriraj hospital were reported. The point system parallel to OPTN/UNOS for waitlists was utilized. Most of the recipients of deceased donor kidney transplantations had 3 HLA mismatches. Due to the point allocation system, none of them had 6 HLA mismatches. Extended criteria donor comprised 7.8% of all deceased donors. Mean duration of dialysis prior to deceased donor transplant was 53 +/- 34 months. Delayed graft function (DGF) was found in 54% of deceased donor kidney transplantation and resulted in significantly higher rate of 1 year biopsy-proven acute rejection, longer duration of kidney transplant admission, higher admission cost and lower patient survival compared to those with immediate graft function. Most of living donor kidney transplant recipient had 1 haplotype match. Mean donor age was 35.9 +/- 9.8 years. 95.6% of the recipients were on hemodialysis prior to transplantation. The current standard regimen includes calcineurin inhibitor, Mycophenolic acid and prednisolone. Interleukin-2 receptor monoclonal antibody has been used in the high immunological risk or high risk for DGF recipients that were 50% of the recipients. There was no statistically significant difference in the biopsy-proven acute rejection (BPAR) free survival between deceased and living donor transplantation. Proportion of cases with the diagnosis of acute rejection according to Banff 2007 classification is as follows: 32.4% acute cellular rejection (ACR), 39.4% antibody-mediated rejection (AMR) and 21.1% mixed cellular and antibody-mediated rejection. Seventy two patients, 35 deceased donor and 37 living donor kidney transplant recipients, had biopsy-proven glomerular disease after transplantation which IgA nephropathy is the most common form of glomerulonephritis. Median graft survival was 7.6 and 13.2 years and median patient survival was 12.1 and 15.5 years for recipient of deceased and living donor transplant respectively. The follow up program of living donors was introduced in 2003 and there were not any donors who required renal replacement therapy.

The minimal flush volume for washout of preservation fluid in liver transplantation.

OBJECTIVES: Organ preservation is one of the important steps that predicts the patient outcome. However, after revascularization, the high concentration of potassium that influxes into the circulation might cause immediate postreperfusion hyperkalemia. To prevent this complication, the portal vein has been washed out with flush fluid to remove preservation fluid before reperfusion. Up to now, it has not been established what exact amount volume of albumin provides washout of the UW solution. METHODS: Eleven of 20 patients who underwent orthotopic liver transplantation (OLT) between December, 2003, and June, 2005, were enrolled in this study. OLT was performed following the standard technique. Five percent albumin (1000 mL) was flushed through the portal vein canula before reperfusion of the donor liver. Every 100 mL of flush fluid effluent was collected from an incomplete infrahepatic inferior vena cava anastomosis for electrolyte measurement. The 10 flushed fluid samples were measured for potassium concentration. Mean arterial pressure was monitored preoperatively, at 1-minute intervals after reperfusion and at 60 minutes after reperfusion. RESULTS: We observed that 61.5% of potassium was removed after only 100 mL of flush fluid, and 90.8% after 500 mL. Only one patient in this study had an effluent potassium reduction that did not achieved 90% after 500- or 1000-mL flush. However, this patient did not develop either postreperfusion syndrome or hyperkalemia. One patient did experience postreperfusion hyperkalemia (6.20 mEq) with severe hypothermia and cardiac arrest. Five patients had stable hemodynamic profiles and five patients, transient, reversible hypotension without postreperfusion hyperkalemia. DISCUSSION AND CONCLUSIONS: We propose that the minimal flush volume for washout of preservation fluid in liver transplantation is 500 mL, to reduce the risk of postreperfusion syndrome and hyperkalemia.

Anti-CD20 monoclonal antibody (rituximab) for the treatment of membranous nephropathy after living-unrelated kidney transplantation: a case report.

A 41-year-old Thai male with end-stage renal disease of uncertain etiology started chronic hemodialysis in November 2001. Two years later, he underwent a living unrelated, four HLA mismatched, kidney transplantation from his wife. Pretransplant class I panel reactive antibody was 80% and the cross-match was positive for immunoglobulin (Ig)M. There was no complication until 30 months after transplantation, when he developed frank nephrotic syndrome with 12.9 g/day of proteinuria. Serum creatinine was 1.5 mg/dL. Allograft biopsy showed membranous nephropathy and mild acute cellular rejection with plasma cell infiltration. In addition to enalapril, valsartan, and simvastatin, a single dose of rituximab (375 mg/m2) and a 3-day course of pulse methylprednisolone were prescribe for the acute rejection episode. The patient was maintained on the same immunosuppressive regimen: cyclosporine, azathioprine, and prednisolone. Five months after the therapy, proteinuria was reduced to 0.5 g/day with a normalized serum albumin level. At 4 years post transplantation, his renal function remains stable. His serum albumin is 4.5 g/dL and urine protein-to-creatinine ratio 0.2.

Hepatic resection: effective treatment for primary and secondary tumors.

BACKGROUND: Hepatic resection is an accepted therapeutic modality for isolated colorectal metastases (CRM) and primary hepatobiliary cancers (PC). Controversy continues regarding the safety, efficacy, and appropriateness of resection for noncolorectal metastases (NCM). METHODS: A retrospective review of 167 resections in 160 patients was performed to evaluate the impact of demographics and perioperative data on survival and recurrence. Statistical analyses were performed by Student t test, analysis of variance, and Kaplan-Meier survival estimates. RESULTS: Resections were performed for CRM, 110 of 167 (66%), NCM, 31 of 167 (19%), and PC, 26 of 167 (15%). The interval from primary to metastases was significantly longer in the NCM group than the CRM group (34.7+/-45.1 vs. 18.7+/-23.7 months; P<.01). Mean number of lesions was not different between groups; however, NCM were larger than CRM (5.9+/-4.5 vs 4.5+/-2.9 cm; P<.05). Operative complications were significantly greater for PC (54%) versus CRM and NCM (21% and 19%, respectively; P<.01), although length of stay was similar between groups. Perioperative mortality was 2%. Actuarial survival at 1 year, 3 years, and 5 years was CRM 91%, 54%, and 40%, PC 75%, 60%, and 38%, and NCM 68%, 36%, and not available, respectively (CRM vs. NCM; P<.01 at 3 years). CONCLUSIONS: Hepatic resection for primary and secondary malignancy can be performed with minimal morbidity and mortality. Resection of NCM is associated with a lower overall survival compared with CRM and PC. The disease-free interval from resection of the primary to metastasectomy is prolonged and hepatic recurrence infrequent after resection in the NCM group. These results suggest that tumor biology is a critical determinant of outcome after hepatic resection of primary and secondary hepatic tumors.