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.

[Alterations of immune status in liver transplant patients with sepsis].

OBJECTIVE: To explore the alterations of immune status in liver transplant recipients with sepsis so as to provide rationales for the adjustments of immunosuppressive agents. METHODS: A total of 47 cases complicated with sepsis after abdominal operations from January 2009 to December 2010 were divided into 4 groups according to the type of operations and the stage of sepsis: A. sepsis after transplantation (TS, n = 11), B. severe sepsis after transplantation (TSS, n = 10), C. sepsis without transplantation (NTS, n = 15) and D. severe sepsis without transplantation (NTSS, n = 11). Ten healthy volunteers were selected as the control group. Blood samples were collected from these patients to measure the immunological parameters associated with T lymphocyte. RESULTS: The APACHII and SOFA score of TSS group and NTSS group were both higher than TS group and NTS group respectively (all P < 0.01). In addition, SOFA score in TSS group was significantly higher than that in NTSS group (17.0 ± 4.5 vs 12.1 ± 2.8, P < 0.01). The percentages of T cell in 4 groups were all significantly lower than healthy volunteers (all P < 0.01). The CD4/CD8 ratio was slightly lower in the TSS group than those in the control group and the other three groups (P = 0.095). As compared with the control group, the IFN-γ/IL-4 ratios were significant lower in the TSS and NTSS groups (0.039 ± 0.012, 0.047 ± 0.018 vs 0.062 ± 0.006) while the level of IL-10 was higher ((32.6 ± 7.5), (25.9 ± 4.3) vs (8.2 ± 1.4) ng/L, all P < 0.05). And the difference was more significant in the TSS group. As compared with the healther, the percentage of CD4(+)CD25(+)Foxp3(+)Treg was lower in NTS group (2.21% ± 0.96% vs 4.06% ± 0.52%, P < 0.01), and significantly higher in NTSS group (8.02% ± 3.57% vs 4.06% ± 0.52%, P = 0.003). No significant difference existed in the percentage of Treg between the TS and control groups (P = 0.398). And it was significantly higher that in the TSS group (5.16% ± 0.99% vs 4.06% ± 0.52%, P = 0.006). But the magnitude of increase level was not so great as that in the NTSS group. The changes of Foxp3 mRNA demonstrated the similar trend as the percentage of Treg. CONCLUSIONS: The immune states of transplant recipients with sepsis are comparable with healthy persons during sepsis. It may subsequently develop into serious immunosuppression. Immunosuppressant should be withdrawn in severe sepsis stage so as to reconstitute the immune system.

[Reproduction after liver transplantation: a report of 13 cases from a single Chinese center].

OBJECTIVE: To explore the recipient's reproduction after liver transplantation (LT) and assess the outcomes of their offspring. METHODS: We retrospectively analyzed the reproduction status of 13 post-LT patients among 336 post-LT recipients during a follow-up period. Physical and intellectual status of their offspring were evaluated by developmental index and Denever developmental screening test. RESULTS: A total of 16 children were mothered or fathered by 13 LT patients. Two female patients mothered a boy and a girl. Ten male patients fathered 6 male and 8 female children while another male fathered a child at 28 gestational weeks. Eleven patients fathered the first gestation 21 mon (medium) since LT, and fathered 15 pregnancies. Twelve of 14 deliveries had a mean gestation age of (38.2 ± 1.8) weeks, with a mean birth weight of (3.1 ± 0.5) kg. Among 12 newborns, 3 were premature and 2 of a low birth weight. Two female patients delivered 2 babies with a gestation age of 37.3 and 40.4 weeks, a birth weight of 2.7 and 3.4 kg, and anoxia neonatorum in one case. No deformity was found. Thirteen of 16 children had almost normal developmental indices and ten had almost normal Denever developmental screening. CONCLUSION: Post-LT patients of reproductive age are able to reproduce offspring. The short-term development of their offspring is relatively normal.

[Anxiety and depression for liver transplant recipients and their impact factors].

OBJECTIVE: To investigate the status of anxiety and depression for liver transplant (LT) recipients and explore their impact factors. METHODS: During the period of January 2005 to December 2008, the symptoms of anxiety and depression for 53 post-LT recipients (LT group) and 48 patients with benign end-stage liver disease (BELD group) were assessed by the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS). And they were compared with that of domestic norm (Norm group). The impact factors of anxiety and depression for LT recipients were analyzed by stepwise logistic regression. RESULTS: The anxiety scores of LT, BELD and Norm groups were (42 ± 9), (47 ± 11) and (30 ± 10) and the depression scores of three groups (48 ± 11), (52 ± 11) and (33 ± 9) respectively. The anxiety score was different significantly among three groups (P < 0.01). It was higher in the LT and BELD groups than that in the Norm Group (P < 0.01) while it was lower in the LT group than that in the BELD group (P < 0.05). The depression scores were different significantly among three groups (P < 0.01). It was higher in the LT and BELD groups than that in the Norm Group. And it was lower in the LT group than that in the BELD group (P < 0.05). The impact factor of anxiety for LT recipients was patient age and that of depression per capita monthly family income. CONCLUSION: The level of anxiety and depression of post-LT recipients is higher than that of domestic norm. The main impact factor for post-LT anxiety is patient age and that of depression per capita monthly family income.

[Preoperative neutrophil-lymphocyte ratio as a prognostic predictor after liver transplantation for hepatocellular carcinoma].

OBJECTIVE: To analyze the negative impact of preoperative neutrophil-lymphocyte ratio (NLR) on the tumor recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation. METHODS: The clinical data of HBV (hepatitis B virus)-associated HCC patients undergoing liver transplantation were retrospectively analyzed. Their clinical and pathological risk factors for tumor-free survival were evaluated by univariate analysis. The analysis of Cox multiple regression was performed to determine the parameters of predicting the HCC recurrence. NLR ≥ 2.5 was considered to be elevated. RESULTS: A total of 76 patients were identified. Among them, 37 had an elevated NLR. The 1, 3 and 5-year tumor-free survival rates were 69.2%, 52.7% and 50.9% respectively. The disease-free survival for patients with high NLR was significantly worse than that for those with normal NLR (1, 3, and 5 year survivals at 56.3%, 37.6% and 37.6% vs 81.1%, 66.9% and 63.3% respectively; P = 0.011). Univariate analysis of factors revealed that tumor size > 5 cm, tumor number > 3, vascular invasion, serum α-fetoprotein level ≥ 400 µg/L and NLR ≥ 2.5 were preoperative predictors of disease-free survival. Cox regression analysis showed that the presence of vascular invasion, tumor number > 3 and NLR ≥ 2.5 were independent prognostic factors of worse disease-free survival. CONCLUSION: An elevated NLR significantly increases the risk for tumor recurrence in HCC patients undergoing liver transplantation.

[Clinical analysis between "early" versus "late" liver retransplantation].

OBJECTIVE: To compare early and late orthotopic liver retransplantation (re-OLT) for patients with poor graft function after primary transplantation at our center and sum up our clinical experience in re-OLT. METHODS: The clinical data of 36 re-OLTs from January 2004 to July 2009 were analyzed retrospectively, consisting of the first group with 17 cases of early re-OLT and the second group with 19 cases of late re-OLT. The average ages were (45 ± 13) years and (48 ± 10) years, and the time intervals were (49 ± 54) days and (514 ± 342) days in early re-OLT group and late re-OLT group, respectively. RESULTS: Biliary tract complications were the main indications for early re-OLT and late re-OLT. Other common indications were vascular complications in early re-OLT and recurrence of primary diseases in late re-OLT. No significant differences were found between the groups with regard to the volume of bleeding during operation, cold ischemia time, operative duration and perioperative mortality except the MELD score. Outcome was fatal for 8 patients in early re-OLT and 10 patients in late re-OLT. Three deaths were due to severe sepsis-related disease, 3 deaths due to multiple organ failure in early re-OLT and 4 deaths due to severe sepsis-related disease, 3 deaths due to recurrence of HCC in late re-OLT. One and 2-year actuarial survival rates after re-OLT were 52.9% and 41.2%, respectively, for patients in early re-OLT, and 63.2% and 52.6%, respectively, for patients in late re-OLT. No significant differences were found regarding survival rates between the two groups (P > 0.05). CONCLUSIONS: The similar clinical results can be achieved in early and late re-OLT. Proper indications and optimal operation timing, experienced surgical procedures and effective perioperative anti-infection strategy contribute to the improvement of the overall survival rate of the patients after re-OLT.

[Risk factors predicting late mortality after liver transplantation for benign end-stage liver disease].

OBJECTIVES: To find out the risk factors predicting long-term survival, and to explore the measures for further improving the survival outcome of whom underwent liver transplantation (LT) for benign end-stage liver disease. METHODS: The common causes of late death after LT and risk factors were retrospectively analyzed in 221 consecutive patients, who underwent LT from October 2003 to June 2007 and survived more than one year. Twenty-six potential risk factors were assessed by the Kaplan-Meier method, and those variables found to be univariately significant at P < 0.10 were entered into a backward step down Cox proportional hazard regression analysis to screen the independent risk factors influencing the recipient's long-term survival. RESULTS: There were 28 recipients died one year later after LT during the follow-up period. The major causes of late mortality were related to infectious complications 5.0% (11/221), biliary complications 3.6% (8/221) and HBV recurrence/reinfection 1.4% (3/221). After Cox proportional hazard regression analysis, 5 covariables finally retained in the formula were: age (RR = 2.325, P = 0.009), ABO blood group (RR = 2.206, P = 0.015), cold ischemia time (RR = 3.001, P = 0.000), post-infection region (RR = 1.665, P = 0.007) and biliary complications (RR = 2.655, P = 0.004). CONCLUSION: Age (≥ 60 years), ABO blood group (incompatible), cold ischemia time (> 12 h), infectious complications (lung infection) and biliary complications (diffuse biliary stricture) significantly impact patient's survival time.

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-alpha when compared with mature DCs but similar amounts of IL-12. RAPA did not affect constitutive NF-kappaB 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.

[Immunization with dendritic cells infected with mTERT adenovirus vector effectively elicits immunity against mouse H22 hepatoma in vivo].

OBJECTIVE: To investigate the effects of dendritic cells (DCs) infected with adenovirus vector encoding mTERT on induction of mTERT antigen specific immunity against H22 hepatoma in vivo. METHODS: Forty Bal B/c mice were subcutaneously immunized with Ad-mTERT infected DC. Cytotoxicity of mTERT specific CTL was determined by 51Cr release assay. IL-2 and IFN-gamma were tested by ELISA. IFN-gamma ELISPOT assays were performed for measuring antigen specific IFN-gamma production by T cells. Tumor size and survival of the immunized mice were recorded and evaluated whether preexisting hepatoma metastases could be supressed after immunization with mTERT-expressing DCs. RESULTS: The lytic activity of CTL, IL-2 (871.25 pg/ml), IFN-gamma (169.15 ng/ml) and IFN-gamma secreting cells (378/10(6) spleen cells) elicited by the Ad-mTERT infected DCs were much stronger and higher than that by Ad-GFP group (131.6 pg/ml, 15.4 ng/ml, 36/10(6) spleen cells, P<0.05), DC group (71.3 pg/ml, 10.5 ng/ml, 21/10(6) spleen cells, P<0.05), PBS group (65.8 pg/ml, 7.4 ng/ml, 18/10(6) spleen cells, P<0.05). In prophylaxis and treatment experiment the Ad-mTERT/DCs immunized mice lived significantly longer than other groups, demonstrating that primary DCs were genetically modified to express the mTERT antigen and could suppress the tumor growth. CONCLUSION: Adenovirus vector mediated mTERT infected DCs can effectively induce mTERT antigen specific antitumor activity, and can induce protective and therapeutic antitumor immunity.

[Significance of lipopolysaccharides, toll-like receptor and inducible nitric oxide synthase in hepatopulmonary syndrome].

OBJECTIVE: To investigate the role of lipopolysaccharides (LPS), toll-like receptor 2 (TLR2) and inducible nitric oxide synthase (iNOS) in the development of hepatopulmonary syndrome (HPS). METHODS: Seventy-one patients were divided into 3 groups: end-stage liver disease with HPS (HPS group, n = 31), end-stage liver disease without HPS (non-HPS group, n = 30) and healthy volunteers (n = 10). Blood was collected at pre-OLT and Days 3, 7, 14, 21 and 28 post-OLT to detect the plasma LPS level, TLR2mRNA and iNOSmRNA in peripheral blood monocytes. RESULTS: The LPS, TLR2mRNA and iNOSmRNA at pre-OLT in HPS group were 4.31 +/- 3.267 ng/L, 336,594.10 +/- 366,901.14 and 63,982.24 +/- 74,127.47 copies/microg RNA respectively; 1.62 +/- 1.34 ng/L, 336,321.53 +/- 222,317.17 and 44,169.9 +/- 24,993.00 copies/microg RNA respectively in non-HPS group and 0.94 +/- .69 ng/L, 10,338.28 +/- 3,814.64 and 19,168.49 +/- 2,417.35 copies/microg RNA in normal control group. LPS, TLR2mRNA and iNOSmRNA at pre-OLT in HPS group were higher than those in non-HPS group without significance (P > 0.05), but significantly higher than those in control group (P < 0.05). The TLR2mRNA decreased in all end-stage liver disease patients at post-OLT with the improvement of liver function and oxygenation. CONCLUSION: The dysfunction of intestinal barrier and intestinal endotoxemia may be the important mechanisms of HPS through the elevation of LPS level and the expressions of TLR2mRNA and iNOSmRNA.

[Multimodality interventional treatments for biliary complications after orthotopic liver transplantation: a preliminary study].

OBJECTIVE: To describe the technique, efficacy, and safety of multimodality interventional treatments for biliary complications after orthotopic liver transplantation (OLT). The core of multimodality interventional treatments is percutaneous transhepatic biliary drainage (PTBD). METHODS: From January 2006 to May 2008, seventy-two patients with biliary complications afte OLT were closed in our study. On the basis of the cholangiographic appearance, patients were classified into 4 groups: anastomotic biliary strictures (n = 19), hilar biliary strictures (n = 16), multifocal/diffuse biliary strictures (n = 31), and anastomotic biliary fistulae (n = 6). All patients were treated in our hospital, including PTBD only in 6 patients, PTBD combined with balloon dilation in 50 patients, balloon dilation and plastic stent implantation in 10 patients, balloon dilation and metallic stent implantation in 6 patients. Their data were analyzed retrospectively, including serum hemobilirubin, cholangiographic appearance and complications. RESULTS: PTBD were successful in all cases. The clinical symptoms improved or eliminated were observed in 66 cases, the effective rate was 91.7% (66/72). Among 72 patients, 26 patients were free of drainage tube, 8 patients underwent second PTBD for the obstruction of biliary stents, and 38 patients maintained drainage tube for long-term. In 66 patients with biliary obstruction, the direct bilirubin was (145 +/- 106) micromol/L before treatments and 76 micromol/L +/- 59 micromol/L one month after PTBD (t = 3.78, P < 0.001). The rate of biliary tract infection was 14.3% and 43.8% respectively with the tip of drainage tube placed in biliary duct and in duodenum. There was a significantly statistical difference between these two items (chi(2) = 4.886, P = 0.027). CONCLUSION: PTBD combined with balloon dilation and biliary stent implantation is a effective therapeutic modality for biliary complications after OLT, which can improve patients' clinical symptoms, elevate patients' quality of life. The tip of drainage tube being placed in biliary duct can decrease the rate of biliary tract infection significantly.

[Effects of sirolimus on the growth of transplanted hepatocellular carcinoma].

OBJECTIVE: To study the effects of sirolimus (SRL) on the growth of transplanted human hepatocellular carcinoma (HCC) in nude mice. METHODS: HepG2 cells were Implanted into the liver of nude mice. The implanted mice were then treated with SRL and tacrolimus (FK506). The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was detected by immunohistology, microvessel density (MVD) was counted by immunostaining with anti-CD34 antibody for endothelial cells. Tumor apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. RESULTS: The tumor weight was (352+/-38) mg, (683+/-53) mg and (675+/-45) mg in SRL, FK506 and control group respectively. The tumor weight was significantly decreased in SRL group (P < 0.01), and there was no difference between FK506 group and control group. The expression of VEGF and PCNA protein was remarkably down-regulated in SRL group compared to control group (P < 0.05), and it was not significantly different between FK506 group and control group (P > 0.05). Compared to the control group, MVD was significanly decreased in SRL group, and the apoptosis index of tumor cell was significantly higher in SRL group (P < 0.01). CONCLUSION: SRL inhibits transplanted HCC tumor growth by reducing tumor angiogenesis, inhibiting tumor proliferation and inducing tumor apoptosis.

[Effects of Rapamycin on angiogenesis and tumor progression in human hepatocellular carcinoma implantation mice].

OBJECTIVE: To study the effects of Rapamycin (RPM) on angiogenesis and tumor progression in human hepatocellular carcinoma (HCC) implantation mice. METHODS: Tumor tissues of HCC were implanted into the liver of nude mice. Then, nude mice were treated with RPM and cyclosporine A (CsA). Real-time PCR was used to detect the mRNA expression of vascular endothelial growth factor (VEGF). Immunohistochemical stain and image analysis were used to detect the protein expression of VEGF and proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) was counted by endothelial cells immunostained by anti-CD34 antibody. The concentration of VEGF in the peripheral blood was detected by ELISA. RESULTS: (1) The tumor weights were (372 +/- 35) mg, (769 +/- 39) mg and (751 +/- 42) mg in RPM, CsA and control group respectively. The tumor weight was significantly decreased in RPM group and no difference in CsA group compared with control group. (2) The expression of VEGF mRNA, VEGF and PCNA protein in tumor tissues and concentration of VEGF in the peripheral blood were remarkably down-regulated in RPM group compared with control group (P < 0.05) and were not remarkably different in CsA group from in control (P > 0.05).(3) Comparing with the control, the tumor MVD was remarkably decreased in RPM group (P < 0.05), and no difference in CsA group (P > 0.05). CONCLUSION: RPM can inhibit angiogenesis and tumor progression of HCC by down-regulated the gene and protein expression of VEGF and inhibited the growth of tumor.

[Risk factors predicting the prognosis of orthotopic liver transplantation in hepatopulmonary syndrome].

OBJECTIVE: To observe the effect of orthotopic liver transplantation (OLT) on hepatopulmonary syndrome (HPS) and investigate risk factors predicting the prognosis of OLT. METHODS: Twenty-six cases of HPS and 30 cases of non-HPS were analyzed treated from April 2004 to January 2006. Survival rates after OLT were compared and risk factors predicting the prognosis of OLT in HPS were researched by univariant and COX analysis. RESULTS: The 28 days survival rate in HPS after OLT was 76.9% (20/26), half a year survival rate and one year survival rate were both 61.5% (16/26). Whereas the one year survival rate of patients without HPS was 100%(P < 0.05). By univariant analysis, shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs, PaO2 and PaO2/FiO2 in room air before operation were relative to the prognosis of peri-operative period and half a year outcome after OLT in HPS (P < 0.05). Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs (OR = 1.182, P = 0.001), and mechanical ventilation time (OR = 1.003, P = 0.053) after OLT were independent risk factors predicting the prognosis of OLT in HPS by COX analysis. Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs > or = 28.4%, or PaO2 < or = 56 mm Hg (1 mm Hg = 0.133 kPa) before OLT predicted the poor outcome of OLT in HPS. The sensitivity were 83.3% and 85.0% respectively, and the specificity were 95.0% and 83.3% respectively. CONCLUSIONS: OLT is an effective treatment for HPS.Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs before OLT and mechanical ventilation time after OLT were independent risk factors for the prognosis of OLT in HPS.

Feasibility of laparoscopic isolated caudate lobe resection for rare hepatic mesenchymal neoplasms.

BACKGROUND: Mesenchymal tumors such as perivascular epithelioid cell neoplasm (PEComa) and inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDC sarcoma) are relatively uncommon in the liver and are particularly rare in the caudate lobe. The clinical manifestations and available imaging tests lack specificity for hepatic mesenchymal tumors. To the best of our knowledge, no caudate PEComa or IPT-like FDC sarcoma has been completely resected by laparoscopy. The standard laparoscopic technique, surgical approaches, and tumor margins for potentially malignant or malignant caudate mesenchymal tumors are still being explored. AIM: To assess both the safety and feasibility of laparoscopic resection for rare caudate mesenchymal neoplasms. METHODS: Eleven patients who underwent isolated caudate lobe resection from 2003 to 2017 were identified from a prospective database. Three consecutive patients with rare caudate mesenchymal tumors underwent laparoscopic resection. Patient demographic data, intraoperative parameters, and postoperative outcomes were assessed and compared with the open surgery group. RESULTS: All procedures for the three resection patients with caudate mesenchymal tumors were completed using a total laparoscopic technique by two different approaches. The average operative time was 226 min, and the estimated blood loss was 133 mL. The average length of postoperative hospital stay was 6.3 ± 0.3 d for the laparoscopy group and 15.5 ± 2.3 d for the open surgery group (P < 0.05). There were no perioperative complications or patient deaths in this series. CONCLUSION: Laparoscopic isolated caudate lobe resection for rare mesenchymal neoplasms is a feasible and curative surgical option in selected patients.

Early liver retransplantation versus late liver retransplantation: analysis of a single-center experience.

BACKGROUND: Orthotopic liver retransplantation (re-OLT) is the only effective therapy for irreversible failure of a liver graft. Early and late graft failure gives way to two different clinical conditions that should be discussed separately. This study was designed to compare early and late re-OLT for patients with poor graft function after primary transplantation at our center and sum up our clinical experience in re-OLT. METHODS: The clinical data of 31 re-OLTs at our center from January 2004 to February 2007 were analyzed retrospectively, consisting of the first group with 14 cases of early re-OLT and the second group with 17 cases of late re-OLT. RESULTS: Biliary tract complications were the main indications for early re-OLT (57.1%) and late re-OLT (52.9%). Other common indications were vascular complications in early re-OLT and recurrence of primary diseases in late re-OLT. No significant differences were found between the groups with regard to the volume of bleeding during operation, cold ischemia time, operative duration, and perioperative mortality; except for the model of end-stage liver disease (MELD) score. Outcome was fatal for 7 patients in early re-OLT and 9 patients in late re-OLT. Two deaths were due to multiple organ failure with 3 deaths due to severe sepsis-related disease in early re-OLT, and 4 deaths were due to severe sepsis-related disease with 3 deaths due to recurrence of hepatocellular carcinoma (HCC) in late re-OLT. One and 2-year actuarial survival rates after re-OLT were 55.2% and 36.9%, respectively, for patients in early re-OLT, and 65.1% and 52% respectively, for patients in late re-OLT. No significant differences were found regarding survival rates between the two groups. CONCLUSIONS: Similar clinical results can be achieved in early and late re-OLT. Proper indications and optimal operation timing, adequate preoperative preparation, experienced surgical procedures, and effective perioperative anti-infection strategy contribute to the improvement of overall survival rates of patients after re-OLT.

Hepatic artery complications after orthotopic liver transplantation: interventional treatment or retransplantation?

BACKGROUND: The main therapeutic treatments for hepatic artery complications after orthotopic liver transplantation (OLT) include thrombolysis, percutaneous transluminal angioplasty, stent placement, and liver retransplantation. The prognosis of hepatic artery complications after OLT is not only related to the type, extent, and timing but also closely associated with the selection and timing of the therapeutic methods. However, there is no consensus of opinion regarding the treatment of these complications. The aim of this study was to determine optimal treatment for hepatic artery complications after OLT. METHODS: The clinical data of 25 patients diagnosed with hepatic artery thrombosis (HAT) and hepatic artery stenosis (HAS) between October 2003 and March 2007 were retrospectively reviewed. Treatments included liver retransplantation and interventions which contain thrombolysis, percutaneous transluminal angioplasty and stent placement. RESULTS: Among five patients with HAT, 3 were treated with thrombolysis. One recovered, one died after thrombolysis and another one died of multi-organ failure after retransplantation because of recurrent HAT. The remaining 2 patients underwent successful retransplantation and have survived after that. Among 12 patients presented with HAS within 1 month postoperatively, 2 patients underwent retransplantation due to irreversible liver failure and another 10 patients were treated with interventions. The liver function failed to improve in 3 patients and retransplantations were performed in 4 patients after stent placement because of ischemic cholangitis. Among 6 patients undergoing liver retransplantations, two died of intracranial hemorrhage and infection respectively. Eight patients presented with HAS after 1 month postoperatively, 5 patients were treated with interventional management and recovered after stent placement. Among another 3 patients presented with HAS, 2 patients' liver function was stable and one patient received late liver retransplantation due to ischemic bile duct lesion. CONCLUSIONS: Individualized therapeutic regimens should be adopted in treating hepatic artery complications after OLT, according to postoperative periods, types and whether ischemic bile duct lesion exists or not. Liver retransplantation is the best treatment for patients with hepatic artery thrombosis. Interventional treatments of late HAS without irreversible liver failure or bile duct ischemia are appropriate, whereas retransplantation is recommended for early HAS.

[Long-term survival after liver transplantation for benign end-stage liver disease in adults].

OBJECTIVE: To evaluate the long-term survival rates of the adults with benign end-stage liver disease (BELD) after liver transplantation (LT) and the causes of death. METHODS: The common causes of late death (after more than 1 year) after LT were retrospectively analyzed in 203 consecutive patients with BELD who underwent LT from Oct. 2003 to May.2006. RESULTS: The 1, 2 and 3-year survival rates were 88.7%, 85.5%, and 81.2% respectively. The 2-year and 3-year survival rates of the patients with HBV-related liver disease were 88.4% and 84.5% respectively, not significantly different from those of patients with non-HBV-related liver disease (75.6% and 64.0% respectively, P = 0.144). 165 recipients survived for more than 1 year and 21 recipients died during the period between 12 and 48 months after LT with a mean of (22.7 +/- 6.6) months. The common causes of late death included related to infectious complications (4.8%, 8/165), biliary tract complications (3.6%, 6/165), HBV re-infection (1.8%, 3/165), chronic rejection (1.2%, 2/165), renal functional lesion (0.6%, 1/165), and hepatic arterial complication (0.6%1/165). CONCLUSION: Satisfactory long-term survival can be achieved in most adult recipients with BELD after LT and the major causes that influence the long-term survival are infectious complications, biliary tract complications, and HBV re-infection. Prevention of these complications, rational use of immunosuppressant, and regular follow-up are essential to improve long-term survival.

[Retransplantation for hepatic artery complications after orthotopic liver transplantation].

OBJECTIVE: To evaluate the efficacy and timing of re-transplantation for hepatic artery complications after orthotopic liver transplantation. METHODS: Between December 2003 and December 2006, the clinical data of 13 patients diagnosed as hepatic artery complications after liver transplantation were retrospectively analyzed. RESULTS: There were no significant difference in duration of operation and anhepatic phase between the initial transplantation and the second transplantation (P = 0.291, P = 0.312). However, intra-operative blood loss [(3.1 +/- 1.1) L vs. (1.5 +/- 0.9) L, P = 0.005] and intensive care unit stays [(4.3 +/- 1.8) d vs. (3.2 +/- 2.5) d, P = 0.015] were significantly increased in the re-transplant patients. No perioperative mortality occurred. The postoperative mortality of liver re-transplantation was 38.5% (5/13) including acute renal failure in two patients, severe infection in two and heart infarction in one. The other 8 patients were followed from 6 months to 51 months, with a median survival time of 22.5 months. CONCLUSIONS: Liver re-transplantation is the only viable option for patients with irreversible graft dysfunction secondary to hepatic artery complications after liver transplantation. Proper indication and optimum time of re-transplantation, reasonable individual immunosuppression regime and effective perioperative care program contribute to the increase of the survival rate of the patients performed liver re-transplantation.

Aging aggravates hepatic ischemia-reperfusion injury in mice by impairing mitophagy with the involvement of the EIF2α-parkin pathway.

Hepatic ischemia-reperfusion (I/R) injury fundamentally influences the performance of aged liver grafts. The significance of mitophagy in the age dependence of sensitivity to I/R injury remains poorly understood. Here, we show that aging aggravated hepatic I/R injury with decreased mitophagy in mice. The enhancement of mitophagy resulted in significant protection against hepatic I/R injury. Parkin, an E3 ubiquitin ligase, was found depleted by I/R in aged livers. In oxygen-glucose deprivation reperfusion (OGD-Rep.)-treated L02 cells, parkin silencing impaired mitophagy and aggravated cell damage through a relative large mitochondrial membrane potential transition. The phosphorylation of the endoplasmic reticulum stress response protein EIF2α, which was also reduced in the aged liver, induced parkin expression both in vivo and vitro. Forty-six hepatic biopsy specimens from liver graft were collected 2 hours after complete revascularization, followed by immunohistochemical analyses. Parkin expression was negatively correlated to donor age and the peak level of aspartate aminotransferase within first week after liver transplantation. Our translational study demonstrates that aging aggravated hepatic I/R injury by impairing the age-dependent mitophagy function via an insufficient parkin expression and identifies a new strategy to evaluate the capacity of an aged liver graft in the process of I/R through the parkin expression.