Wang Gs

The Role of Liver Transplantation for Intrahepatic Cholangiocarcinoma: A Single-Center Experience

Background/Aim: Intrahepatic cholangiocarcinoma (ICC) is not a widely accepted indication for liver transplantation (LT). The present study describes our institutional experience with patients who underwent transplantation for ICC. Methods: A retrospective analysis was performed on 11 consecutive patients with ICC who underwent LT between October 2003 and November 2008 at our institution. Results: At a median patient follow-up interval of 10 months (2–56), the median survival time was 9 months (2.5–53). The perioperative mortality and the recurrence rate were 0 and 45.5%, respectively. Five patients are currently alive 10, 12, 41, 51 and 53 months after LT, respectively. One patient died 3 months after LT as a result of bile leak and toxic shock, and 5 patients died of tumor recurrences at 2.5, 8, 8, 9 and 10 months post-LT, respectively. The 1-, 2-, 3- and 4-year disease-free survival rates and overall survival rates of all the patients were 51.9, 51.9, 51.9 and 51.9%, and 50.5, 50.5, 50.5 and 50.5%, respectively. Conclusion: With better and strict patient selection, the prognosis of LT for ICC could be improved. ICC patients with lymph node involvement, vascular or bile duct invasion are contraindicated for LT.

A Single-Center Experience of Retransplantation for Liver Transplant Recipients With a Failing Graft

With the accumulation of orthotopic liver transplantation (OLT) recipients, an increased number of patients with graft failure need retransplantation (re-OLT). This study was undertaken to examine our clinical experience of re-OLT for patients with poor graft function after primary transplantation at a single center. We analyzed retrospectively, the clinical data of 32 re-OLTs in 31 patients at our center from January 2004 to February 2007, including indications and causes of death, timing of retransplantation, and surgical techniques. The indications included bile leak (2 cases), biliary stricture (16 cases), recurrence of hepatocellular carcinoma (HCC) (5 cases), hepatic artery stenosis (4 cases), hepatic artery thrombosis (HAT) (2 cases), and hepatitis B recurrence (3 cases). The rate of re-OLT was 4.29%. All patients underwent modified piggyback liver transplantations with cadaveric allografts. No intraoperative mortality and acute rejection occurred. Overall, 17 of 31 patients (54.8%) died after re-OLT with survival times ranging from 2 weeks to 28 months. Another 14 patients were cured with survival times of 4 to 32 months. The perioperative mortality rate of patients who underwent re-OLT between 8 and 30 days after their initial transplantation was highest (66.7%). The most common cause of death after re-OLT was sepsis (47.1%), multiple-organ failure (17.6%), and recurrence of HCC (17.6%), whereas the majority of deaths posttransplantation were sepsis-related (54%) within 1 year. Re-OLT is the only therapeutic option for a failing liver graft. Proper indications and optimal operative time, advanced surgical procedures, reasonable individual immunosuppression regimens, and effective perioperative anti-infection treatments contribute to the improved survival of patients after re-OLT.

Single-center experience of therapeutic management of hepatic artery stenosis after orthotopic liver transplantation. Report of 20 cases.

Background/Aims: Hepatic artery stenosis (HAS) is a potentially life-threatening complication of liver transplantation because the associated mortality and morbidity rates are high. Surgical reconstruction was recommended as first choice of treatment and interventional radiologic techniques have been introduced recently. However, the mid- or long-term outcomes of HAS were unclear. The purpose of this study was to evaluate the efficacy of interventional therapy and clinical outcomes of HAS following liver transplantation. Methods: A retrospective analysis was performed for 20 cases of HAS documented by angiography from October 2003 to August 2007 at the authors’ institution. All patients underwent transluminal interventional therapy including percutaneous transluminal angioplasty and endovascular stent placement. The technical results, hepatic artery patency and clinical outcome were reviewed. Results: All patients were treated with interventional management. Technical and immediate success was 100%. Of 8 patients with early HAS (within 1 month of transplantation), 1 underwent retransplantation due to deterioration of liver function. One died of acute liver failure waiting for retransplantation. Of 12 patients with late HAS (after 1 month of liver transplantation), 1 died of severe sepsis 38 days after transplantation. Five patients underwent late retransplantation due to ischemic-type biliary strictures or recurrent attacks of cholangitis. One of these patients died 11 days after retransplantation. The median follow-up of all 20 patients was 14.4 months after liver transplantation. The Kaplan-Meier curve of patency showed that cumulated primary patency of hepatic artery interventional treatment at 3, 6 and 12 months was 94, 87 and 79%, respectively. Two patients died of causes unrelated to HAS. Three patients developed recurrent HAS and were successfully treated with second interventional therapy. Eight patients (40%) developed ischemic-type biliary strictures and 7 underwent endoscopic treatment or percutaneous transhepatic cholangiodrainage. Graft function in 5 patients improved. The Kaplan-Meier curve of survival showed that the 1- and 2-year cumulated survival rates of early and late HAS were 87.5 and 43.8% and 81.5 and 61.1%, respectively. There was no significant difference in 1- and 2-year survival rates between early and late HAS (log-rank test, p = 0.928). Conclusion: Interventional therapy is an effective treatment for both early and late HAS with excellent short- and mid-term outcomes, while without irreversible graft dysfunction resulted from HAS. However, the patients have a high incidence of ischemic-type biliary lesions.

Rapamycin‐treated mature dendritic cells have a unique cytokine secretion profile and impaired allostimulatory capacity

Rapamycin (RAPA, sirolimus) is a recently introduced immunosuppressive agent. Its effect on the differentiation and antigen uptake of immature dendritic cells (iDCs) has been studied. However, whether it can also modulate the function of mature DCs (mDCs) is unknown. We investigated the effects of RAPA on rat bone marrow‐derived DCs at different stages of maturation. RAPA affected maturation, increased apoptosis and reduced lipopolysaccharide (LPS)‐induced IL‐12 and IL‐10 production in iDCs. However, mDCs were resistant to RAPA‐induced apoptosis. RAPA‐mDCs produced significantly less IL‐10 and TNF‐α when compared with mature DCs but similar amounts of IL‐12. RAPA did not affect constitutive NF‐κB activity, but inhibited allostimulatory activity in mature DCs. In conclusion, mDCs treated with RAPA are reprogrammed to produce a unique cytokine secretion profile and exhibit low allostimulatory capacity, which may play an important role in rapamycin‐based immunomodulation.

Acute leukemia, a rare but fatal complication after liver transplantation

Little information is available about the risk factors and means to improve the survival rate of acute leukemia in a rare but often fatal complication after liver transplantation (LT). We report the development of AML-M2 in one of the 764 patients who underwent liver transplantation at our center, and review the literature on similar cases. The patient, a 42-year-old man who developed acute leukemia 38 months after liver transplantation, was successfully treated with chemotherapy and has subsequently been in remission. With appropriate adjustment of immunosuppressive agents, he was able to safely benefit from chemotherapy. Only 16 patients with acute leukemia after liver transplantation have been reported, and the mortality rate is extraordinarily high (52.94%, 9/17). More cases of acute leukemia will emerge as the rate of survival after liver transplantation increases. The patients chromosomal mutation profile, the choice of immunosuppressive agent, and infection by hepatitis virus may be the risk factors for the development of acute leukemia after LT. Our experience suggests that clinicians should adjust the immunosuppressive agents according to the immunosuppressive state of the patient and explore the option of reducing or stopping the medication as long as liver function remains stable. These measures could help reduce the high mortality rate among these patients.

Pretransplant Elevated Plasma Fibrinogen Level is a Novel Prognostic Predictor for Hepatocellular Carcinoma Recurrence and Patient Survival Following Liver Transplantation

BACKGROUND Elevated plasma fibrinogen is associated with tumour progression and poor outcomes in several cancers. The present study investigated the prognostic value of preoperative fibrinogen in hepatocellular carcinoma (HCC) patients after liver transplantation (LT). MATERIAL AND METHODS We analyzed the preoperative plasma fibrinogen levels of 41 patients who underwent LT for HCC. The cut-off value for elevated level of fibrinogen was determined by using a receiver operating characteristic (ROC) curve analysis. Cox regression analysis was performed to analyze the relationship between elevated fibrinogen level and HCC recurrence. The disease-free survival (DFS) and overall survival (OS) rate after transplantation were calculated by Kaplan-Meier method and compared by log-rank test. RESULTS The fibrinogen levels were significantly higher in patients with tumor recurrence (3.31±0.98 g/L) compared with those in patients without recurrence (2.39±0.89 g/L) (P<0.01). A cut-off value for elevated fibrinogen level of 2.675 g/L was defined. Cox regression analysis showed that the relative risk for tumor recurrence increased by 6.871 times for patients with elevated fibrinogen. Eleven patients in the elevated fibrinogen group (21 cases) developed recurrence, while only 2 in the normal fibrinogen group (20 cases) developed recurrence. There were significant differences in DFS and OS between the elevated fibrinogen group and normal fibrinogen group (5-year DFS and OS of 44.0% and 42.9% vs. 89.2% and 80.0%, respectively, P<0.05). Vascular invasion and fibrinogen level ≥2.675 g/L were the independent prognostic predictors of tumor recurrence and poor outcome. CONCLUSIONS Pretransplant elevated fibrinogen levels are associated with tumor recurrence and poor prognosis in hepatocellular carcinoma patients after liver transplantation.

Liver transplant may improve erectile function in patients with benign end-stage liver disease: single-center Chinese experience.

OBJECTIVES No investigation in mainland China concerning erectile function in men with liver transplant for benign end-stage liver disease has been performed. MATERIALS AND METHODS Sixty men with a liver transplant for benign end-stage liver disease (post-liver transplant group) between October 2003 and December 2008 were invited to evaluate erectile dysfunction with the Chinese version of the 5-item international index of erectile function. Fifty-seven patients with benign end-stage liver disease (pre-liver transplant group) on the waiting list also were investigated. RESULTS The proportion of sexually active patients in the post-liver transplant group was higher than it was in the pre-liver transplant group (80% [48/60] vs 47.7% [21/44]; P < .01). The mean International Index of Erectile Function-5 score of responders was significantly higher in the post-liver transplant group than it was in the pre-liver transplant group (15.9 ± 8.5 vs 8.5 ± 9.1; P < .01). The incidences of no erectile dysfunction, mild, mild-moderate, moderate, and severe erectile dysfunction and total erectile dysfunction were 15.9% (7/44), 9.1% (4/44), 15.9% (7/44), 0% (0/44), 59.1% (26/44), and 84.1% (37/44) in the pre-liver transplant group, and 33.3% (20/60), 20% (12/60), 25% (15/60), 0 (0/60), 21.7% (13/60), and 66.7% (40/60) in the post-liver transplant group. The pre-liver transplant group had higher incidence of severe erectile dysfunction and total erectile dysfunction and a lower incidence of no erectile dysfunction than did the post-liver transplant group (P < .05). There was a comparable incidence of mild and mild-moderate erectile dysfunction with the post-liver transplant group (P > .05). Variables associated with International Index of Erectile Function-5 score of the post-liver transplant patients included age, profession, and immunosuppressive protocol. CONCLUSIONS Liver transplant may improve erectile function in persons with benign end-stage liver disease, but erectile dysfunction remains a problem in the post-liver transplant patients.

Symptom Experienced Three Years after Liver Transplantation under Immunosuppression in Adults

Background & Aims Immunosuppression-related symptom experience has not been covered thoroughly in long-term liver transplant recipients. The aim of this study was to assess the symptom experience of immunosuppressive therapy three years after liver transplantation and to correlate it with adherence to medications and sociodemographic or disease-related characteristics. Methods This study included 94 liver transplant recipients who had survived for more than 3 years after liver transplantation. Symptom experience was measured by the 59-Item Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) at the outpatient visits. Adherence to immunosuppressive drugs was assessed using the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS). Results Itching, concentration or memory problems, and fatigue were the three most frequent or most distressing symptoms. Factors significantly associated with a higher level of symptom frequency and distress were 3- to 5-year time cohort (i.e., time post-transplantation), and younger age. At the item level, concentration or memory problems were the most frequent and distressing symptoms in the 3- to 5-year time cohort. Itching was the most frequent and distressing symptom in the 5- to 9-year time cohort. Finally, relationship was found between symptom experience and nonadherence to immunosuppressive drugs. Conclusions Symptoms related to physical complaints or impairments were more often perceived and more distressing for liver transplant recipients 3 years after transplantation. Furthermore, the 3- to 5-year time cohort and younger age were associated with a higher degree of perceived symptom occurrence and symptom distress. Finally, recipients who perceived higher levels of symptom frequency and symptom distress reported higher levels of nonadherence.

Survival analysis of sirolimus-based immunosuppression in liver transplantation in patients with hepatocellular carcinoma.

AIM To investigate the effect of a sirolimus-based immunosuppressive protocol on tumor recurrence and survival after liver transplantation (LT) in hepatocellular carcinoma (HCC) patients. METHODS We retrospectively analyzed 142 HCC patients who underwent LT in our hospital from January 2006 to January 2012. The patients were divided into the sirolimus (SRL) group (62 cases) and non-sirolimus (control) group (80 cases). Disease-free survival (DFS) and tumor-bearing survival after tumor recurrence were compared using the Kaplan-Meier method. RESULTS No significant difference in DFS was observed between the two groups. Furthermore, DFS showed no significant differences in the subgroups of patients who met the Milan criteria, exceeded the Milan criteria but met the University of California, San Francisco (UCSF) criteria, or exceeded the UCSF criteria between the two groups. In the control group, 21 patients who were administered SRL after tumor recurrence had a median tumor-bearing survival time of 12months (3-34months), while 14 patients who did not experience a change in their immunosuppressive protocol after tumor recurrence had a median tumor-bearing survival time of 8months (6-22months). There was a significant difference in the tumor-bearing survival time between these patients (P=0.039). CONCLUSIONS Not all HCC patients benefited from the sirolimus-based immunosuppressive protocol after LT. However, sirolimus may prolong the survival time of patients after tumor recurrence.

Health-related quality of life after liver transplantation: the experience from a single Chinese center

BACKGROUND Few studies have been performed to assess health-related quality of life (HRQOL) in liver transplantation (LT) patients in the mainland of China. This study aimed to investigate the HRQOL of post-LT patients in a single center. METHODS HRQOL was evaluated by the SF-36 (Chinese version) questionnaire in 60 patients (LT group) who had received LT for benign end-stage liver disease (BELD). Fifty-five patients with BELD (BELD group) and 50 healthy volunteers from the general population (GP group) were also evaluated, and the results were compared among the three groups. RESULTS There was a significant difference among the three groups in terms of the scores of eight domains in the SF-36 (P<0.01). Patients in the BELD group had lower scores in each domain of the SF-36 in comparison with those in the GP group (P<0.025). The LT group had mental health scores equivalent to those of the BELD group (P>0.025), but higher scores for the remaining seven domains (P<0.025). Compared with the GP group, the LT group scored equivalently for role physical, body pain, vitality, social function and role emotion (P>0.025), but had lower scores for the remaining three domains (P<0.025). Lower family income was found to be associated with reduced physical function and mental health scores (P<0.05). Better education was associated with increased mental health scores (P<0.05). CONCLUSIONS LT patients generally have a good HRQOL although some respects of their HRQOL remains to be improved. Lower family income and poor education are important factors relating to the poor HRQOL of LT patients.