Relationship between the genetic variation in interleukin 28B and response to antiviral therapy in patients with chronic hepatitis C / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Genetic variations at the interleukin 28B (IL-28B) locus are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. The aim of this research was to evaluate the role of IL-28B single nucleotide polymorphism (SNP) variations in Chinese patients undergoing pegylated interferon-α plus ribavirin (PEG-IFN-α/RBV) treatment.</p><p><b>METHODS</b>To determine the effect of IL-28B variation on the response to HCV therapy, these variants were genotyped in a cohort of 220 patients who were chronically infected with HCV and received combined PEG-IFN-α/RBV therapy.</p><p><b>RESULTS</b>The proportions of rs12979860 CC, CT, and TT genotypes were 71.4%, 25.0%, and 3.6% respectively, in the sustained virological response (SVR) group; 15.8%, 60.5%, and 23.7% respectively, in the null virological response (NVR) group; and 38.1%, 52.4%, and 9.5% respectively, in the relapse (Rel) group (P < 0.05). Logistic regression analysis showed that, compared to those having the CC genotype, CT heterozygotes had an increased risk of NVR and Rel (OR = 10.95, 95%CI = 4.12-29.11, P = 1.5×10(-7) and OR = 3.93, 95%CI = 1.86-8.32, P = 2.1×10(-4) respectively). The RNA quantification assay showed that patients with genotype CC exhibited much higher levels of IL-28 expression than those with genotype CT or TT (P < 0.001).</p><p><b>CONCLUSIONS</b>The IL-28B SNP rs12979860 genotype was related to the effectiveness of HCV therapy: patients with the CC rs12979860 genotype had higher rates of SVR than those with the CT or TT genotype, and the CC genotype revealed a significantly higher level of IL-28 mRNA expression.</p>

Routine use of a transanastomotic stent is unnecessary for hepatojejunostomy in liver transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The use of transanastomotic stents for Roux-en-Y hepatojejunostomy (RYHJ) in liver transplantation (LT) remains controversial. The aim of this retrospective study was to assess the role of transanastomotic stent for RYHJ in LT.</p><p><b>METHODS</b>RYHJ for biliary reconstruction in LT was performed in 52 patients. Twenty-five patients had bile duct reconstruction by RYHJ with transanastomotic stents (S group), while 27 patients underwent the same procedure without transanastomotic stents (non-S group). The two groups were compared in terms of post-LT biliary complications and survival.</p><p><b>RESULTS</b>The incidences of bile leakage, anastomotic stricture, non-anastomotic stricture, biliary sludge/lithiasis and biliary infection were 12% (3/25), 9.5% (2/21), 23.5% (4/17), 11.8% (2/17), and 24% (6/25), respectively in the S group, and 0, 0, 20.0% (5/25), 10.0% (2/20), and 16.7% (4/24), respectively in the non-S group. One and three year survival rates were 48.0% (12/25) and 34.0% (8/23), respectively, in the S group and 57.7% (15/26) and 38.9% (7/18), respectively, in the non-S group. There was no significant difference between the two groups in terms of the incidence of various biliary complications and survival (P > 0.05).</p><p><b>CONCLUSION</b>The routine use of transanastomotic stents is not necessary for RYHJ for biliary reconstruction in LT.</p>

Symptomatic osteonecrosis of the femoral head after adult orthotopic liver transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>With the increase of survival in liver transplantation recipients, more patients are at a high risk of developing osteonecrosis, especially in the femoral head, due to immunosuppressive treatment. The purpose of this study was to report the incidence, possible risk factors, and outcome of symptomatic osteonecrosis of the femoral head (ONFH) in adult patients with current immunosuppressive agents and individual protocol after liver transplantation in China.</p><p><b>METHODS</b>A retrospective analysis was performed on 226 adult patients who underwent orthotopic liver transplantation (OLT) at a single liver transplantation institution between January 2004 and December 2008. The posttransplant survival time (or pre-retransplantation survival time) of all the patients were more than 24 months. The possible pre- and post-transplantation risk factors of symptomatic ONFH were investigated and the curative effects of the treatment were also reported.</p><p><b>RESULTS</b>The incidence of ONFH was 1.33% in patients after OLT. ONFH occurred at a mean of (14 ± 6) months (range, 10 - 21 months) after transplantation. Male patients more often presented with osteonecrosis as a complication than female patients. The patients with lower pre-transplantation total bilirubin and direct bilirubin levels (P < 0.05). There was no difference in the cumulative dose of corticosteroids or tacrolimus between the patients with or without symptomatic ONFH. Patients were treated either pharmacologically or surgically. All patients showed a nice curative effect without major complications during the 18 - 63 months post-treatment follow up.</p><p><b>CONCLUSIONS</b>The symptomatic ONFH does not occur commonly after adult OLT in the current individual immunosuppressive protocol in China.</p>

Prognostic factors for late mortality after liver transplantation for benign end-stage liver disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are increasing numbers of patients who survive more than one year after liver transplantation. Many studies have focused on the early mortality of these patients. However, the factors affecting long-term survival are not fully understood. This study aims to evaluate prognostic factors predicting long-term survival and to explore measures for improving the survival outcomes of patients who underwent liver transplantation for benign end-stage liver diseases.</p><p><b>METHODS</b>The causes of late death after liver transplantation and potential prognostic factors were retrospectively analyzed for 221 consecutive patients who underwent liver transplantation from October 2003 to June 2008. Twenty-seven variables were assessed using 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 identify the independent prognostic factors influencing the recipients' long-term survival.</p><p><b>RESULTS</b>Twenty-eight recipients died one year after liver transplantation. The major causes of late mortality were infectious complications, biliary complications, and Hepatitis B virus recurrence/reinfection. After Cox analysis, the five remaining co-variables were: age, ABO blood group, cold ischemia time, post-infection region, and biliary complications.</p><p><b>CONCLUSIONS</b>The major causes of late mortality were infection, biliary complications and Hepatitis B virus recurrence/reinfection. Five variables (Age, ABO blood group, cold ischemia time, infection, and biliary complications) had significant impacts on patient survival.</p>

Clinical analysis between "early" versus "late" liver retransplantation / 中华外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Inhibition of rejection in murine islet xenografts by CTLA4Ig and CD40LIg gene transfer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Costimulatory signals play a vital role in T cell activation. Blockade of costimulatory pathway by CTLA4Ig or CD40LIg have enhanced graft survival in experimental transplantation models yet mechanisms remain undetermined. We investigated the effects of CTLA4Ig and CD40LIg gene transfer on islet xenografts rejection in rats.</p><p><b>METHODS</b>Human islets were infected with recombinant adenoviruses containing CTLA4Ig and CD40LIg genes and implanted beneath the kidney capsule of diabetic rats. Levels of blood sugar, morphological changes, and survival of grafts were recorded. Expressions of CTLA4Ig, CD40LIg and insulin were detected by immunohistochemical staining and cytokines levels were quantified by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Blood glucose levels in transplant rats decreased to normal level on the 2nd day post transplantation. The mean blood glucose in the control group, CTLA4Ig transfected group, CD40LIg transfected group and CTLA4Ig + CD40LIg cotransfected group increased on days 8, 24, 21, 68, post transplantation respectively. The grafts in control group, CTLA4Ig transfected group, CD40LIg transfected group and CTLA4Ig + CD40LIg cotransfected group survived for (8 ± 1), (29 ± 4), (27 ± 3), and (74 ± 10) days, respectively. Survival in CTLA4Ig + CD40LIg cotransfected group was significantly longer. Survivals of CTLA4Ig transfected group and CD40LIg transfected group were significantly longer than control group. In control animals, serum interleukin-2 and tumor necrosis factor α concentration significantly increased within seven days post transplantation. Haematoxylin eosin staining of grafts showed live islets in situ of transplant rats without inflammatory cell infiltration. Immunohistochemical staining confirmed the expression of insulin at islets in all experimental groups.</p><p><b>CONCLUSIONS</b>Transfer of CTLA4Ig and CD40LIg genes, especially the cotransfer of both, inhibits rejection of murine islet xenografts. Downregulated expressions of Th1 cells related cytokines might be related to the beneficial effects.</p>

Risk factors predicting late mortality after liver transplantation for benign end-stage liver disease / 中华外科杂志

<p><b>OBJECTIVES</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Effects of sirolimus on the growth of transplanted hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the effects of sirolimus (SRL) on the growth of transplanted human hepatocellular carcinoma (HCC) in nude mice.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>SRL inhibits transplanted HCC tumor growth by reducing tumor angiogenesis, inhibiting tumor proliferation and inducing tumor apoptosis.</p>

Prospective evaluation of postoperative outcome after liver transplantation in hepatopulmonary syndrome patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Only a few reviews of small case series and individual case reports including a relatively small number of adult patients undergoing liver transplantation for hepatopulmonary syndrome (HPS) are available, and there has been no prospective evaluation of the long-term outcome of HPS patients after orthotopic liver transplantation (OLT). The aim of this study was to determine the frequency of HPS in OLT patients with chronic end-stage liver-disease, and the short-term and long-term postoperative outcome of HPS patients after OLT.</p><p><b>METHODS</b>This prospective study included 31 HPS and 30 control, non-HPS patients. The preoperative conditions were similar between the two groups. Twenty-six of 31 HPS patients and all of the non-HPS patients underwent OLT. Standardized methods, such as arterial blood gas at room air and 99m-technetium macroaggregated albumin ((99m)Tc MAA) lung and brain perfusion scanning were performed for the diagnosis of HPS. Patients were followed after OLT.</p><p><b>RESULTS</b>The incidence of HPS in OLT patients was 9.3% (26/279). Hypoxemia in HPS was obviously improved with a normalized shunt of (99m)Tc MAA in the lungs after OLT. The immediate postoperative survival rate (within 28 days after OLT) of HPS was 76.9% (20/26). The one year survival was 61.5% (16/26) and four-year survival was 57.7% (15/26); much higher than HPS patients without OLT (0). But high postoperative morbidity and mortality were observed in HPS patients whose death occurred within 3 months of OLT due to complications summarized in this study.</p><p><b>CONCLUSIONS</b>Liver transplantation was an effective treatment for HPS. But the postoperative mortality rate following OLT in HPS patients was still much higher than that of patients without HPS.</p>

Transplantation of human thioredoxin gene-modified hepatocytes for treatment of acute liver failure in rat model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mostly because of the limited number and proliferative ability of the transplanted hepatocytes, hepatocyte transplantation offers only temporary support to the hepatic function with rather poor functional replacement of the damaged liver parenchyma. This study aimed to observe the therapeutic effect of human thioredoxin (hTrx) gene-modified hepatocytes on experimental acute liver failure in rats.</p><p><b>METHODS</b>hTrx cDNA was obtained by reverse transcription-polymerase chain reaction (RT-PCR) from human osteosarcoma 143 (TK-) cells to construct the recombinant retrovirus vector pLEGFP/hTrx, which was packaged into PA317 cells to collect the recombinant retrovirus containing hTrx gene. After titration and characterization, the recombinant retrovirus was applied to primary cultured rat hepatocyte for infection to generate hTrx gene-modified rat hepatocytes, whose viability and antioxidative capacity were examined by immunohistochemistry and MTT assay, respectively. In a Sprague-Dawley (SD) rat model of acute liver failure, the modified hepatocytes were injected into the spleen, and the hepatic function and survival rate of the recipient rats were evaluated at different time points after the transplantation.</p><p><b>RESULTS</b>NIH3T3 cells infected by the recombinant retrovirus were capable of expressing bioactive hTrx in the form of fusion proteins. Immunohistochemistry demonstrated normal function of the hTrx gene-modified hepatocytes, which possessed strong antioxidative capacity as shown by MTT assay. Transplantation of the modified hepatocytes in rats with acute liver failure resulted in significantly lowered serum alanine aminotransferase (ALT) and total bilirubin (TBIL) levels (P < 0.05). The hepatocytes exhibited long-term survival and efficient proliferation after transplantation. Fourteen days after the operation, the rat models receiving hTrx gene-modified hepatocytes had significantly higher survival rate than those without the transplantation.</p><p><b>CONCLUSION</b>hTrx gene-modified hepatocyte transplantation can effectively alleviate acute liver failure in rats.</p>

Effects of Rapamycin on angiogenesis and tumor progression in human hepatocellular carcinoma implantation mice / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effects of Rapamycin (RPM) on angiogenesis and tumor progression in human hepatocellular carcinoma (HCC) implantation mice.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>(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).</p><p><b>CONCLUSION</b>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.</p>

Immunization with dendritic cells infected with mTERT adenovirus vector effectively elicits immunity against mouse H22 hepatoma in vivo / 中华肿瘤杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Adenovirus vector mediated mTERT infected DCs can effectively induce mTERT antigen specific antitumor activity, and can induce protective and therapeutic antitumor immunity.</p>

Risk factors predicting the prognosis of orthotopic liver transplantation in hepatopulmonary syndrome / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the effect of orthotopic liver transplantation (OLT) on hepatopulmonary syndrome (HPS) and investigate risk factors predicting the prognosis of OLT.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Post-transplant prophylaxis of the recurrence of lamivudine-resistant YMDD mutant hepatitis B virus in liver recipients / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the prophylactic efficacy of adefovir dipivoxil (ADV) for post-transplant recurrence of hepatitis B virus (HBV) with lamivudine-resistant YMDD mutation in liver recipients.</p><p><b>METHODS</b>From March 2004 to May 2006, 20 patients with chronic hepatitis B associated with YMDD mutant HBV prior to liver transplantation received treatment with ADV and additional intramuscular hepatitis B immunoglobulin (HBIG) for prevention of post-transplant graft reinfection. The liver function, serum HBsAg, anti-HBs (HBIG), HBeAg, anti-HBc, anti-HBe, HBV DNA and creatinine were examined in all the patients before and after the transplantation.</p><p><b>RESULTS</b>The median follow-up duration of these patients after the transplantation was 33.5 months. Nineteen patients survived and one patient died of recurrent hepatocellular carcinoma. There was significant difference in YMDD mutation rate between the patients with HBV-DNA over 10(6) copies/ml and those with HBV-DNA less than 10(6) copies/ml (12.4% vs 2.5%, P < 0.05). HBV-DNA was undetectable at 4 weeks after the transplantation in 95.0% of the patients (19/20) and at 6 months in one case. No recurrence of hepatitis B was detected by long-term regular testing of HBsAg, HBeAg and HBV-DNA. Serum creatinine increased in 1 case 1 year after the use of ADV.</p><p><b>CONCLUSION</b>ADV offers protection against recurrence of HBV with YMDD mutation after liver transplantation with only mild nephrotoxicity, but renal function monitoring during the use of ADV is still necessary.</p>

Application of somatostatin combined with oral vancomycin in the treatment of intestinal obstruction after liver transplantation / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of somatostatin combined with oral vancomycin in the treatment of intestinal obstruction after liver transplantation.</p><p><b>METHODS</b>Fifty-eight cases of intestinal obstruction after liver transplantation from Jan. 2005 to Dec. 2006 were divided into two groups: Group A (from Jan. 2005 to Dec. 2005) received traditional treatment, including fasting,gastrointestinal decompression, maintaining electrolyte and acid-base balance, enteral and parenteral nutrition support and antibiotics; Group B (from Jan. 2006 to Dec. 2006) received somatostatin combined oral vancomycin in addition to the above mentioned traditional treatment.</p><p><b>RESULTS</b>Fifty-eight cases out of 441 patients (13%) suffered from intestinal obstruction after liver transplantation. Group B had a better outcome as compared with Group A, including a quick recovery of flatus and stool, [(7.1+/-2.0) d and (8.4+/-2.4) d vs (9.1+/-3.0) d and (10.8+/-3.4) d] (P<0.05), less amount of gastric drainage [(298+/-58) ml/d vs (485+/-106) ml/d](P<0.05). The rate of intestinal flora imbalance in Group B was 55%, which was significantly less than the 77% in Group A(P<0.05).</p><p><b>CONCLUSION</b>The application of somatostatin combined with oral vancomycin can improve the symptoms of intestinal obstruction after liver transplantation and decrease the rate of intestinal flora imbalance.</p>

Inhibitory effect of RNAi targeting human telomerase reverse transcriptase against human hepatocellular carcinoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a recombinant retrovirus vector expressing small interfering RNA (siRNA) targeting human telomerase reverse transcriptase (hTERT), and assess its effect on proliferation and apoptosis of human hepatocellular carcinoma cells.</p><p><b>METHODS</b>The sequence of the siRNA targeting hTERT, U6 promoter and EGFP gene were amplified by PCR and inserted into the mammalian retroviral expression vector pLXSN to construct the recombinant retroviral vector pLXSN-EGFP-U6-siTERT. The vector was then used to infect human hepatocellular carcinoma cell HepG2. The telomerase activity of the infected cells was detected by telomerase repeat amplification protocol-silver staining, and the cell apoptosis was examined using flow cytometry. The inhibition rate of HepG2 cell proliferation was analyzed by MTT assay.</p><p><b>RESULTS</b>Sequence analysis and restriction enzyme digestion showed confirmed successful construction of the recombinant expression vector pLXSN-EGFP-U6-siTERT. The telomerase activity of the infected HepG2 cells was reduced by 23.84%, 58.03% and 85.01% at 24, 48 and 72 h after the infection, respectively (P<0.05). The cell apoptosis rate of the infected cells was 29.05% at 24 h after the infection. The cell proliferation was markedly inhibited by the infection with the vector in comparison to that of the control group.</p><p><b>CONCLUSION</b>hTERT siRNA can effectively silence hTERT gene and suppress the telomerase activity and proliferation of HepG2 cells.</p>

Retransplantation for hepatic artery complications after orthotopic liver transplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and timing of re-transplantation for hepatic artery complications after orthotopic liver transplantation.</p><p><b>METHODS</b>Between December 2003 and December 2006, the clinical data of 13 patients diagnosed as hepatic artery complications after liver transplantation were retrospectively analyzed.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Early liver retransplantation versus late liver retransplantation: analysis of a single-center experience / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Hepatic artery complications after orthotopic liver transplantation: interventional treatment or retransplantation? / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Prophylaxis of hepatitis B recurrence in post-liver transplantation patients with lamivudine-resistant YMDD mutant / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The most frequently used therapy for post-transplantation recurrence of hepatitis B virus (HBV) infection is lamivudine, but this drug is associated with a high resistance rate due to YMDD mutant. In preliminary reports, adefovir dipivoxil (ADV) has been shown to have activity against lamivudine-resistant strains of HBV. However, clinical experience in treatment of HBV infection after liver transplantation (LT) is still not entirely clear. This study was aimed to evaluate the prophylactic efficacy of ADV plus hepatitis B immunoglobulin (HBIG) in patients with YMDD mutant before LT.</p><p><b>METHODS</b>From March 2004 to March 2006, 16 patients with chronic hepatitis B had lamivudine-resistant YMDD mutants detected prior to liver transplantation and received treatment with ADV plus additional intramuscular HBIG after LT as prophylaxis against graft reinfection. Tests for liver function, serum HBsAg, anti-HBs (HBIG), HBeAg, anti-HBc, anti-HBe, HBV-DNA, and creatinine were assessed pre- or post-liver transplantation.</p><p><b>RESULTS</b>The median follow-up of these patients post-liver transplantation was 19.4 months. Fifteen patients survived and one patient died of recurrence of hepatocellular carcinoma (HCC). There was significant difference (10.98% vs. 2.26%, P < 0.05) in YMDD mutant rate between the patients with HBV-DNA over 10(6) copies/ml and those with HBV-DNA less than 10(6) copies/ml. Fifteen patients (93.8%) had undetectable HBV-DNA at 4 weeks and 1 (6.3%) at 6 months after LT. No hepatitis B recurrence was detected by persistent testing of HBsAg, HBeAg, and HBV-DNA and no increase of serum creatinine level associated with ADV was observed in any of the patients.</p><p><b>CONCLUSION</b>ADV combined with intramuscular HBIG can effectively prevent patients with pre-transplantation YMDD mutant from HBV recurrence after LT.</p>