Hyung Hwan Moon

Antiviral Treatment for Hepatitis B Virus Recurrence Following Liver Transplantation

The purpose of this study was to identify the factors associated with the recurrence of hepatitis B virus (HBV) following liver transplantation (LT) for HBV‐related disease and to recognize the outcome of treatment for HBV recurrence with oral nucleos(t)ide analogues. Six hundred and sixty‐seven LTs were performed for HBsAg‐positive adult patients in our institute from 1996 to 2010. HBV prophylaxis was performed by hepatitis B immunoglobulin (HBIG) monotherapy or HBIG and entecavir combination therapy. There were 63 cases (11.4%) of HBV recurrences during a median follow‐up of 51 months. The median time to HBV recurrence was 22 months. A preoperative HBV DNA load of more than 105 IU/mL, HBIG monotherapy, and hepatocellular carcinoma in the explant liver were independent risk factors for HBV recurrence following LT in multivariate analysis. Patient survival at 10 yr was 54.2% for HBV‐recurrent patients. Among patients with HBV recurrence, HBsAg seroclearance was achieved in 13 patients (20.6%), but HBsAg seroclearance did not affect survival in these patients after the recurrence of HBV (p = 0.28). The recurrence of HBV led to graft failure in six cases. HBV recurrence should be prevented by strict management of pre‐transplant HBV viremia and an effective post‐transplant HBV prophylaxis.

Combination Therapy of Sirolimus and Sorafenibfor RecurrentHepatocellular Carcinoma after Liver Transplantation

Backgrounds: Sirolimus and sorafenib both have been used in recurrent Hepatocellular Carcinoma (HCC) patients after Liver Transplantation (LT). In the present study, we evaluated the side effects and efficacy of acombination therapy consisting of sirolimus and sorafenib. Methods: We retrospectively reviewed patients who had recurrent HCC after LT between 2005 and 2012. Toxicity was evaluated by reviewing medical records for each follow-up visit. Efficacy was evaluated according to the modified RECIST guidelines. Results: A total of 24 patients who received combination therapy were reviewed to evaluate drug toxicity. Side effects included hand-foot syndrome (n=12, 50%), diarrhea (n=7, 29.2%), fatigue (n=2, 8.3%), and alopecia (n=1, 4.2%). Among the 24 patients enrolled in this study, 19 were evaluated for efficacy. A complete response was observed in only 1 case (5.3%), while a partial response was observed in 2 cases (10.5%). Five cases (26.3%) showed disease stabilization. The median overall survival after initiation of the combination therapy was 21.6 months. In comparison, 26 recipients with recurrent HCC received non-combination therapy. The median survival of patients receiving a noncombination therapy was 12.0 months. However, there was no statistically significant difference in patient survival rate between the combination and non-combination therapy groups (P=0.101). Conclusion: Combination therapy of sorafenib and sirolimus for recurrent HCC LT recipients may be useful for disease management. However, controlled prospective study is needed to further evaluate the safety and efficacy of combined sorafenib and sirolimus therapy.

Serial ImmuKnow assay in stable kidney transplant recipients

Objectives The ImmuKnow assay (cylex Inc., Columbia, MD) has been reported to measure the global immune monitoring tool for organ transplantation recipients. We assess immuKnow ATP values in stable kidney transplant patients. Material and methods Patients who were kidney transplanted between September 2008 and May 2011 were enrolled in the prospective serial ImmuKnow assay study. The criteria of inclusion were living donor kidney transplantation (KT), no evidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and PRA less than 50%. ImmuKnow assay monitoring was performed at one day before operation, post operative weeks 4, 8, 12, 16, 20, 24, 36 and 52. We excluded patients who had undergone infectious syndrome or rejection episodes during the follow-up period. Results Among 71 patients who were enrolled in prospective serial ImmuKnow assay monitoring, 37 patients were proven to stable KT patients during the follow-up period. Two hundred and twenty-four samples from 37 patients were collected. ImmuKnow value and immunosuppression drug level were compared in post operative weeks 4, 8, 12, 16, 20, 24, 36 and 52. The value of ImmuKnow assay was significantly different depending on the length of time after transplant (p = 0.038). Interestingly, the pre-transplant ImmuKnow values were lower than those of the immediate post-transplant period. Conclusions The ImmuKnow value of stable KT recipients is different according to “time after transplant”. Therefore, “time after transplant” should be considered when applying an ImmuKnow assay in clinical practice.

Significance of true-positive and false-positive pretransplantation lymphocytotoxic crossmatch in primary liver allograft outcomes.

Background At the time of transplantation, a recipient’s serum is tested against the prospective donor’s lymphocytes to identify specific reactivity and to look for a donor-specific crossmatch (CXM). Here, we investigated the relationship between the pretransplantation lymphocytotoxic CXM results and the long-term outcome of liver transplantation at a single center. Methods From October 1998 to April 2011, medical records, laboratory data, and pretransplantation lymphocytotoxic CXM results were collected from 1133 consecutive liver transplant recipients. Results We performed liver transplantations on 80 (7.1%) patients after a true-positive CXM (t+CXM). The t+CXM group exhibited higher initial aminotransferase levels immediately after transplantation compared with a negative CXM group. However, no significant differences in rejection, biliary or vascular complications, viral disease recurrence, or de novo malignancies were found. Although overall graft and patient survival did not differ between the groups, liver-specific graft survival was inferior in the t+CXM group. It was also found that, in 42 (3.7%) recipients, initially positive results converted to final negative results after the elimination of immunoglobulin M autoantibodies. We defined this subpopulation as a false-positive CXM. Significantly decreased posttransplantation aminotransferase levels with a higher incidence of de novo malignancies were observed in this group compared with negative controls. Conclusion Our findings demonstrate that t+CXM transplants show increased aspartate aminotransferase and alanine aminotransferase peak immediately after transplantation, which influences liver-specific graft outcomes. Additionally, the presence of circulating immunoglobulin M autoantibodies against recipients’ own antigens may be protective in liver grafts. However, this may be a predisposing factor for de novo malignancies.

A new technique for complete portal vein and superior mesenteric vein thrombosis in a liver transplant recipient.

We describe a deceased-donor liver transplant recipient with grade 3 complete portal vein and superior mesenteric vein thromboses, which was successfully managed with an extensive thrombectomy through the venotomy site of superior mesenteric vein. In this case report, we suggest our method as an option for grade 3 portal vein thromboses, and discuss other options available for recipients with portal vein thromboses.

Different Etiologies and Prognostic Factors after Liver Transplantation for Fulminant Hepatic Failure in Korea: 1605

Background: Recently, much effort was put into improvement of the liver waiting list allocation system. Still obviously, none of the newly developed scores is significantly beneficent in compare to MELD score. The new LiMAx test might have a potential to improve the prediction of mortality by patients with liver cirrhosis. Methods: A prospective observational single center study has been conducted in our department. In the on-going study 400 patients with different stages of cirrhosis are to be included and followed at 6, 12 and 24 months. Standard clinical parameters, biochemical blood tests as well as the LiMAx test were performed by inclusion. The end points are: death or liver transplantation. T-test comparison between the groups, as well as a multivariate logistic Regression was performed. Results: Up to now 240 patients are included in the study. After excluding patients who became liver transplantation 148 and 96 patients reached 6 and 12 months follow up respectively. 54% of the patients suffer of alcohol cirrhosis, 20% was HCV positive. The Child-B stadium was observed in 41%, Child-C in 27% of cases. The 6 and 12 month mortality was 13.5 and 31.3% respectively. The patients who died at 6 and 12 month had significantly lower LiMAx value (91 and 99 μg/kg/h) than those who survived (132 and 147μg/kg/h, p=.008). LiMAx value, creatinineand sodium serum level were the only significant parameters in the multivariate regression analysis including also other laboratory parameters like total bilirubin or coagulation factors. Conclusions: The LiMAx test might predict a liver dependent death by patients with liver cirrhosis. Final results of the study are needed to estimate the exact value of LiMAx test in evaluation of patient with liver cirrhosis. 1605