p53 codon 72 polymorphism and liver cancer susceptibility: A meta-analysis of epidemiologic studies

AIM:To evaluate the association between p53 codon 72 polymorphism and liver cancer risk by means of meta-analysis. METHODS:Two investigators independently searched the Medline,Embase and Chinese Biomedicine databases.Summary odds ratios and 95%CI for p53 codon 72 polymorphism and liver cancer were calculated in fixedeffects model(Mantel-Haenszel method)and randomeffects model(DerSimonian and Laird method)when appropriate. RESULTS:This meta-analysis included 1115 liver cancer cases and 1778 controls.The combined results based on all studies showed that there was a statistically significant link between Pro/Pro genotype and liver cancer,but not between Arg/Arg or Pro/Arg genotype and liver cancer.When stratifying for race,similar results were obtained,i.e.patients with liver cancer had a significantly higher frequency of Pro/Pro genotype than non-cancer patients among Asians.After stratifying thevarious studies by control source,gender,family history of liver cancer and chronic hepatitis virus infection,we found that(1)patients among hospital-based studies had a significantly higher frequency of Pro/Pro and a significantly lower frequency of Arg/Arg genotype than individuals without cancer;(2)female patients with liver cancer had a significantly lower frequency of Arg/Arg and a higher frequency of Pro/Arg+Pro/Pro genotypes than female individuals without cancer;(3)subgroup analyses for family history of liver cancer did not reveal any significant association between p53 codon 72 polymorphism and liver cancer development;and(4) patients with negative hepatitis virus infection had a significantly higher frequency of Pro/Pro and a significantly lower frequency of Arg/Arg genotype than individuals without cancer. CONCLUSION:This meta-analysis suggests that the p53 codon 72 polymorphism may be associated with liver cancer among Asians.

Quality of life and psychological outcome of donors after living donor liver transplantation

AIM: To investigate the health related quality of life (HRQoL) and psychological outcome of donors after living donor liver transplantation. METHODS: Participants were 92 consecutive liver transplant donors who underwent hepatectomy with- out middle hepatic vein at West China Hospital of Sichuan University between January 2007 and Sep- tember 2010. HRQoL was measured using the Chinese version of the Medical Outcomes Study Short Form-36 (SF-36), and psychological symptoms were measured using the Symptom Checklist-90-Revised (SCL-90-R). Data collected from donors were compared to previ- ously published data from the general population. Clin- ical and demographic data were collected from medical records and questionnaires.RESULTS: The general health score of the SF-36 was significantly lower in females (59.78 ± 12.25) than in males (75.83 ± 22.09). Donors more than 40 years old scored higher in social functioning (85.71 ± 14.59) and mental health (82.61 ± 20.00) than those younger than 40 (75.00 ± 12.13, 68.89 ± 12.98; social func- tioning and mental health, respectively). Donors who had surgery more than two years prior to the study scored highest in physical functioning (P = 0.001) and bodily pain (P = 0.042) while those less than one year from surgery scored lowest. The health of the liver recipient significantly influenced the general health (P = 0.042), social functioning (P = 0.010), and role- emotional (P = 0.028) of donors. Donors with full-time employment scored highest in role-physical (P = 0.005), vitality (P = 0.001), social functioning (P = 0.016), mental health (P < 0.001), the physical component summary scale (P < 0.001), and the mental compo- nent summary scale (MCS) (P < 0.001). Psychological measures indicated that donors were healthier than the general population in obsessive-compulsive behav- ior, interpersonal sensitivity, phobic anxiety, and para- noid ideation. The MCS of the SF-36 was significantly correlated with most symptom scores of the SCL-90-R. CONCLUSION: HRQoL and psychological outcome were favorable in living liver transplant donors after donation. Specifically, gender, age, time since opera- tion, recipient health condition, and employment after donation, influenced postoperative quality of life.

Neutrophil-lymphocyte ratio predicts the prognosis of patients with hepatocellular carcinoma after liver transplantation

AIM:To determine whether an elevated neutrophillymphocyte ratio(NLR)is negatively associated with tumor recurrence in patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)after liver transplantation(LT),and to determine the optimal predictive NLR cut-off value.METHODS:The data of HCC patients who had undergone LT came from the China Liver Transplant Registry database.We collected data from 326 liver cancer patients who had undergone LT at our medical center.We divided the patients into groups based on their NLRs(3,4 or 5).We then compared the clinicopathological data and long-time survival between these groups.Meanwhile,we used receiver operating characteristic analysis to determine the optimal NLR cut-off.RESULTS:Of 280 HCC patients included in this study,263 were HBV positive.Patients with an NLR<3 and patients with an NLR≥3 but<4 showed no significant differences in overall survival(OS)(P=0.212)or disease-free survival(DFS)(P=0.601).Patients with an NLR≥4 but<5 and patients with an NLR≥5also showed no significant differences in OS(P=0.208)or DFS(P=0.618).The 1-,3-and 5-year OS rates of patients with an NLR<4 vs an NLR≥4 were 87.8%,63.8%and 61.5%vs 73.9%,36.7%and 30.3%,respectively(P<0.001).The 1-,3-and 5-year DFS rates of patients with an NLR<4 vs NLR≥4 were 83.9%,62.9%and 60.7%vs 64.9%,30.1%and 30.1%,respectively(P<0.001).Univariate and multivariate analyses demonstrated that three factors,including NLR≥4(P=0.002),were significant predictors of tumor recurrence in HCC patients after LT.CONCLUSION:A preoperative elevated NLR significantly increased the risk for tumor recurrence in HCC patients after LT.

Bile leakage test in liver resection:A systematic review and meta-analysis

AIM:To assess systematically the safety and efficacy of bile leakage test in liver resection.METHODS:Randomized controlled trials and controlled clinical trials involving the bile leakage test were included in a systematic literature search.Two authors independently assessed the studies for inclusion and extracted the data.A meta-analysis was conducted to estimate postoperative bile leakage,intraoperative positive bile leakage,and complications.We used either the fixed-effects or random-effects model.RESULTS:Eight studies involving a total of 1253 patients were included and they all involved the bile leakage test in liver resection.The bile leakage test group was associated with a significant reduction in bile leakage compared with the non-bile leakage test group(RR=0.39,95%CI:0.23-0.67;I2=3%).The white test had superiority for detection of intraoperative bile leakage compared with the saline solution test(RR=2.38,95%CI:1.24-4.56,P=0.009).No significant intergroup differences were observed in total number of complications,ileus,liver failure,intraperitoneal hemorrhage,pulmonary disorder,abdominal infection,and wound infection.CONCLUSION:The bile leakage test reduced postoperative bile leakage and did not increase incidence of complications.Fat emulsion is the best choice of solution for the test.

Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution's experience with 398 consecutive patients

BACKGROUND: Surgical resection is an important curative treatment for hepatocellular carcinoma (HCC); however, some patients experience an unexpected recurrence even after hepatectomy. The present study aimed to investigate risk factors and predictive criteria for early and late recurrence of HCC after resection.METHODS: A retrospective analysis of 398 Chinese patients who received curative resection for HCC was conducted. Patients were divided into three groups: without recurrence, early recurrence and late recurrence. Prognostic factors and predictive criteria for early and late recurrence were statistically analyzed. RESULTS: The cumulative recurrence-free survival rates at1, 2, 3, 4, and 5 years were 75.5%, 58.2%, 54.1%, 40.5%, and28.7%, respectively. The distribution of the time to recurrence suggested that recurrence could be divided into early phase(before 2 years; n=164) and late phase (after 2 years; n=83)Cox’s multivariate proportional hazard model analysis revealed that multiplicity of tumors (P=0.004) and venous infiltration(P=0.002) were independent risk factors associated with early recurrence. In contrast, indocyanine green retention rate at 15minutes (P=0.007), serum albumin level (P=0.045), and HBeAg status ( =0.028) proved to be significant independent adverse prognostic factors for late recurrence. Patients with at least 1of the 2 early recurrence risk factors (multiplicity of tumors ≥2and venous infiltration) or with 2 or more late recurrence risk factors are often susceptible to recurrence (P=1.36e-4 and 1.0e-6respectively).CONCLUSIONS: Early and late recurrences correlate with different risk factors and predictive criteria. Early recurrence primarily results from intrahepatic metastases, while late recurrence may be multicentric in origin.

Salvage liver transplantation in the treatment of hepatocellular carcinoma:A Meta-analysis

AIM:To evaluate survival and recurrence after salvage liver transplantation(SLT) for the treatment of hepatocellular carcinoma(HCC) compared with primary liver transplantation(PLT) using a meta-analysis.METHODS:Literature on SLT versus PLT for the treatment of HCC published between 1966 and July 2011 was retrieved.A meta-analysis was conducted to estimate pooled survival and disease-free rates.A fixed or random-effect model was established to collect the data.RESULTS:The differences in overall survival and disease-free survival rates at 1-year,3-year and 5-year survival rates were not statistically significant between SLT group and PLT group(P > 0.05).After stratifying the various studies by donor source and Milan criteria,we found that:(1) Living donor liver transplantation recipients had significantly higher 1-year survival rate,lower 3-year and 5-year survival rates compared with deceased-donor liver transplantation(DDLT) recipients.And in DDLT recipients they had better 1-year and 5-year disease-free survival rate in SLT group;and(2) No difference was seen in 1-year,3-year and 5-year survival rates between two groups who beyond Milan criteria at the time of liver transplantation.CONCLUSION:SLT can be effectively performed for patients with recurrence or deterioration of liver function after hepatectomy for HCC.It does not increase the perioperative mortality and has a similar long-term survival rates compared to PLT.

Unsuccessful treatment of four patients with acute graft-vs-host disease after liver transplantation

AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed. RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.CONCLUSION: New and effective treatments are re-quired for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.

Health-related quality of life of 256 recipients after liver transplantation

AIM:To investigate health-related quality of life(HRQoL) and psychological outcomes in 256 adults who had undergone liver transplantation(LT).METHODS:A stratified random sampling method was used in this follow-up multicenter study to select a representative sample of recipients undergoing either living donor liver transplantation(LDLT) or deceased donor liver transplantation(DDLT).HRQoL was measured by using the Chinese version of Medical Outcome Study Short Form-36(SF-36),and psychological outcomes by using the beck anxiety inventory(BAI) and the self-rating depression scale(SDS).Clinical and demographic data were collected from the records of the Chinese Liver Transplant Registry and via questionnaires.RESULTS:A total of 256 patients were sampled,including 66(25.8%) receiving LDLT and 190(74.2%) undergoing DDLT;15(5.9%) recipients had anxiety and four(1.6%) developed severe depression after the operation.Compared with LDLT recipients,DDLT patients had higher scores in general health(60.33 ± 16.97 vs 66.86 ± 18.42,P = 0.012),role-physical(63.64 ± 42.55 vs 74.47 ± 36.46,P = 0.048),roleemotional(61.11 ± 44.37 vs 78.95 ± 34.31,P = 0.001),social functioning(78.60 ± 22.76 vs 88.16 ± 21.85,P = 0.003),vitality(70.30 ± 15.76 vs 75.95 ± 16.40,P = 0.016),mental health(65.88 ± 12.94 vs 71.85 ± 15.45,P = 0.005),physical component summary scale(PCS,60.07 ± 7.36 vs 62.58 ± 6.88,P = 0.013) and mental component summary scale(MCS,52.65 ± 7.66 vs 55.95 ± 10.14,P = 0.016).Recipients > 45 years old at the time of transplant scored higher in vitality(77.33 ± 15.64 vs 72.52 ± 16.66,P = 0.020),mental health(73.64 ± 15.06 vs 68.00 ± 14.65,P = 0.003) and MCS(56.61 ± 10.00 vs 54.05 ± 9.30,P = 0.037) than those aged ≤ 45 years.MCS was poorer in recipients with than in those without complications(52.92 ± 12.21 vs 56.06 ± 8.16,P = 0.017).Regarding MCS(55.10 ± 9.66 vs 50.0 ± 10.0,P < 0.05) and PCS(61.93 ± 7.08 vs 50.0 ± 10.0,P < 0.05),recipients scored better than the Sichuan general and had improved overall QoL compared to patients with chronic diseases.MCS and PCS significantly correlated with scores of the BAI(P < 0.001) and the SDS(P < 0.001).CONCLUSION:Age > 45 years at time of transplant,DDLT,full-time working,no complications,anxiety and depression were possible factors influencing postoperative HRQoL in liver recipients.

Outcome of patients undergoing right lobe living donor liver transplantation with small-for-size grafts

AIM: To investigate the outcome of living donor liver transplantation (LDLT) recipients transplanted with small-for-size grafts (SFSGs). METHODS: Between November 2001 and December 2010, 196 patients underwent LDLT with right lobe liver grafts at our center. Recipients were divided into 2 treatment groups: group A with an actuarial graft-to-recipient weight ratio (aGRWR) < 0.8% (n = 45) and group B with an aGRWR = 0.8% (n = 151). We evaluated serum liver function markers within 4 wk after transplantation. We also retrospectively evaluated the outcomes of these patients for potential effects related to the recipients, the donors and the transplantation procedures based upon a review of their medical records. RESULTS: Small-for-size syndrome (SFSS) developed in 7 of 45 patients (15.56%) in group A and 9 of 151 patients (5.96%) in group B (P = 0.080). The levels of alanine aminotransferase and aspartate aminotransferase in group A were higher than those in group B during early period after transplantation, albeit not sig-nificantly. The cumulative 1-, 3-and 5-year liver graft survival rates were 82.22%, 71.11% and 71.11% for group A and 81.46%, 76.82%, and 75.50% for group B patients, respectively (P = 0.623). However, univariate analysis of risk factors associated with graft survival in group A demonstrated that the occurrence of SFSS after LDLT was the only significant risk factor affecting graft survival (P < 0.001). Furthermore, multivariate analysis of our data did not identify any additional significant risk factors accounting for poor graft survival. CONCLUSION: Our study suggests that LDLT recipients with an aGRWR < 0.8% may have liver graft outcomes comparable to those who received larger size grafts. Further studies are required to ascertain the safety of using SFSGs. (c) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Management of venous stenosis in living donor liver transplant recipients

AIM:To retrospectively evaluate the management and outcome of venous obstruction after living donor liver transplantation(LDLT).METHODS:From February 1999 to May 2009,1 intraoperative hepatic vein(HV) tension induced HV obstruction and 5 postoperative HV anastomotic stenosis occurred in 6 adult male LDLT recipients.Postoperative portal vein(PV) anastomotic stenosis occurred in 1 pediatric left lobe LDLT.Patients ranged in age from 9 to 56 years(median,44 years).An air balloon was used to correct the intraoperative HV tension.Emergent surgical reoperation,transjugular HV balloon dilatation with stent placement and transfemoral venous HV balloon dilatation was performed for HV stenosis on days 3,15,50,55,and 270 after LDLT,respectively.Balloon dilatation followed with stent placement via superior mesenteric vein was performed for the pediatric PV stenosis 168 d after LDLT.RESULTS:The intraoperative HV tension was corrected with an air balloon.The recipient who underwent emergent reoperation for hepatic stenosis died of hemorrhagic shock and renal failure 2 d later.HV balloon dilatation via the transjugular and transfemoral venous approach was technically successful in all patients.The patient with early-onset HV stenosis receiving transjugular balloon dilatation and stent placement on the 15th postoperative day left hospital 1 wk later and disappeared,while the patient receiving the same interventional procedures on the 50th postoperative day died of graft failure and renal failure 2 wk later.Two patients with late-onset HV stenosis receiving balloon dilatation have survived for 8 and 4 mo without recurrent stenosis and ascites,respectively.Balloon dilatation and stent placement via the superior mesenteric venous approach was technically successful in the pediatric left lobe LDLT,and this patient has survived for 9 mo without recurrent PV stenosis and ascites.CONCLUSION:Intraoperative balloon placement,emergent reoperation,proper interventional balloon dilatation and stent placement can be effective as a way to manage hepatic and PV stenosis during and after LDLT.

Role of microRNA in liver regeneration

BACKGROUND： Liver regeneration is a complex process. micro RNAs（mi RNAs） are short, single-stranded RNAs that modify gene expression at the post-transcriptional level. Recent investigations have revealed that mi RNAs are closely linked to liver regeneration.DATA SOURCES： All included studies were obtained from Pub Med, Embase, the Science Direct databases and Web of Science, with no limitation on publication year. Only studies published in English were considered.RESULTS： We grouped studies that involved mi RNA and liver regeneration into two groups： mi RNAs as promoters and as inhibitors of liver regeneration. We summarized the relevant mi RNAs separately from the related pathways.CONCLUSIONS： Blocking or stimulating the pathways of mi RNAs in liver regeneration may be novel therapeutic strategies in future regeneration-related liver managements. We may discover additional chemotherapy targets of mi RNA.

Interleukin-10-1082G/A polymorphism and acute liver graft rejection:A meta-analysis

AIM: To investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in liver transplant (LT) recipients. METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% CIs for IL-10-1082 G/A polymorphism and AR were calculated in a fixed and a random-effects model as appropriate. RESULTS: This meta-analysis included seven casecontrol studies, which comprised 652 cases of LT recipients in which 241 cases developed AR and 411 cases did not develop AR. Overall, the variant A allele was not associated with AR risk when compared with the wild-type G allele (OR = 0.94, 95% CI: 0.64-1.39). Moreover, similar results were observed when the AA genotype was compared with the AG/GG genotype (OR = 1.05, 95% CI: 0.55-2.02). When stratifying for eth-nicity, no significant association was observed among either Caucasians or Asians. Because only one study was performed in Asian patients, the result of subgroup analysis by ethnicity would not be reliable for Asians. Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. CONCLUSION: This meta-analysis suggests that IL-10-1082 G/A polymorphism may be not associated with AR risk in LT recipients among Caucasians.

Value of α-fetoprotein in association with clinicopathological features of hepatocellular carcinoma

AIM:To explore the relationship between α-fetoprotein(AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma(HCC) thoroughly.METHODS:A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study.The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis,such as status of hepatitis B virus(HBV) infection,tumor size,tumor number,vascular invasion and degree of tumor differentiation.Also,patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP(≤ 20 μg/L,21-400 μg/L,401-800 μg/L,and ≥ 801 μg/L),to compare the positive rate of patient among four groups stratified by various clinicopathological variables.And the correlation of different kinds of tumor staging systems,such as TNM,Barcelona Clinic Liver Cancer(BCLC) staging classification and China staging,were compared with the serum concentration of AFP.RESULTS:A total of 2304 HCC patients were enrolled in this study totally;the mean serum level of AFP was 555.3 ± 546.6 μg/L.AFP levels were within the normal range(< 20 μg/L) in 27.4%(n = 631) of all the cases.81.4%(n = 1875) patients were infected with HBV,and those patients had much higher serum AFP level compared with non-HBV infection ones(573.9 ± 547.7 μg/L vs 398.4 ± 522.3 μg/L,P < 0.001).The AFP level in tumors ≥ 10 cm(808.4 ± 529.2 μg/L) was significantly higher(P < 0.001) than those with tumor size 5-10 cm(499.5 ± 536.4 μg/L) and with tumor size ≤ 5 cm(444.9 ± 514.2 μg/L).AFP levels increased significantly in patients with vascular invasion(694.1 ± 546.9 μg/L vs 502.1 ± 543.1 μg/L,P < 0.001).Patients with low tumor cell differentiation(559.2 ± 545.7 μg/L) had the significantly(P = 0.007) highest AFP level compared with high differentiation(207.3 ± 420.8 μg/L) and intermediate differentiation(527.9 ± 538.4 μg/L).In the multiple variables analysis,low tumor cell differentiation [OR 6.362,95%CI:2.891-15.382,P = 0.006] and tumor size(≥ 10 cm)(OR 5.215,95%CI:1.426-13.151,P = 0.012) were independent predictors of elevated AFP concentrations(AFP > 400 μg/L).Serum AFP levels differed significantly(P < 0.001) in the D stage of BCLC(625.7 ± 529.8 μg/L) compared with stage A(506.2 ± 537.4 μg/L) and B(590.1 ± 551.1 μg/L).CONCLUSION:HCC differentiation,size and vascular invasion have strong relationships with AFP,poor differentiation and HCC size ≥ 10 cm are independent predictors of elevated AFP.BCLC shows better relationship with

Current prophylactic strategies against hepatitis B virus recurrence after liver transplantation

Prophylactic strategies against hepatitis B virus(HBV) recurrence after liver transplantation(LT) are essential for patients with HBV-related disease.Before LT, lamivudine(LAM) was proposed to be down-graded from first-to second-line therapy.In contrast, adefovir dipivoxil(ADV) has been approved not only as first-line therapy but also as rescue therapy for patients with LAM resistance.Furthermore, combination of ADV and LAM may result in lower risk of ADV resistance than ADV monotherapy.Other new drugs such as entecavir, telbivudine and tenofovir, are probably candidates for the treatment of hepatitis-B-surface-antigen-positive patients awaiting LT.After LT, low-dose intramuscular hepatitis B immunoglobulin(HBIG), in combination with LAM, has been regarded as the most cost-effective regimen for the prevention of post-transplant HBV recurrence in recipients without pretransplant LAM resistance and rapidly accepted in many transplant centers.With the introduction of new antiviral drugs, new hepatitis B vaccine and its new adjuvants, post-transplant HBIG-free therapeutic regimens with new oral antiviral drug combinations or active HBV vaccination combined with adjuvants will be promising, particularly in those patients with low risk of HBV recurrence.

Primary graft dysfunction after liver transplantation

BACKGROUND: Primary graft dysfunction (PGD) causes complications in liver transplantation, which result in poor prognosis. Recipients who develop PGD usually experience a longer intensive care unit and hospital stay and have higher mortality and graft loss rates compared with those without graft dysfunction. However, because of the lack of universally accepted definition, early diagnosis of graft dysfunction is difficult. Additionally, numerous factors affect the allograft function after transplantation, making the prediction of PGD more difficult. The present review was to analyze the literature available on PGD and to propose a definition.DATA SOURCE: A search of PubMed (up to the end of 2012) for English-language articles relevant to PGD was performed to clarify the characteristics, risk factors, and possible treatments or interventions for PGD.RESULTS: There is no pathological diagnostic standard; many documented definitions of PGD are different. Many factors such as donor status, procurement and transplant process and recipient illness may affect the function of graft, and ischemia reperfusion injury is considered the direct cause. Potentia managements which are helpful to improve graft function were investigated. Some of them are promising.CONCLUSIONS: Our analyses suggested that the definition of PGD should include one or more of the following variables: (1)bilirubin ≥10 mg/dL on postoperative day 7; (2) internationa normalized ratio ≥1.6 on postoperative day 7; and (3) alanine aminotransferase or aspartate aminotransferase 】2000 IU/L within 7 postoperative days. Reducing risk factors may decrease the incidence of PGD. A majority of the recipients could recover from PGD; however, when the graft progresses intoprimary non-function, the patients need to be treated with retransplantation.

Zinc finger protein A20 protects rats against chronic liver allograft dysfunction

AIM： To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats. METHODS： AIIogeneic liver transplantation from DA rats to Lewis rats was performed. Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day （POD） 5. Hepatic overexpression of A20 was achieved by recom- binant adenovirus （rAd.）-mediated gene transfer ad- ministered intravenously every 10 d starting from POD 10. The recipient rats were injected with physiologi- cal saline, rAdEasy-A20 （1 × 109 pfu/30 g weight） or rAdEasy （1 × 109 pfu/30 g weight） every 10 d through the tail vein for 3 mo starting from POD 10. Liver tissue samples were harvested on POD 30 and POD 60. RESULTS： Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis. A20 overexpression ameliorated the effects on liver function, attenuated liver allograft fibrosis and prolonged the survival of the recipient rats. Treatment with A20 suppressed hepatic protein pro- duction of tumor growth factor （TGF）-β1, interleukin- 113, caspase-8, CD40, CD40L, intercellular adhesion molecule-i, vascular cell adhesion molecule-1 and E-selectin. A20 treatment suppressed liver cell apopto- sis and inhibited nuclear factor-KB activation of Kupffer cells （KCs）, liver sinusoidal endothelial cells （LSECs） and hepatic stellate cells （HSCs）, and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs. CONCLUSION： A20 might prevent chronic liver allogra- ft dysfunction by re-establishing functional homeostasis of KCs, LSECs and HSCs.

Adult-to-adult living donor liver transplantation for acute liver failure in China

AIM:To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation(AALDLT) for acute liver failure(ALF).METHODS:Between January 2005 and March 2010,170 living donor liver transplantations were performed at West China Hospital of Sichuan University.All living liver donor was voluntary and provided informed consent.Twenty ALF patients underwent AALDLT for rapid deterioration of liver function.ALF was defined based on the criteria of the American Association for the Study of Liver Diseases,including evidence of coagulation abnormality [international normalized ratio(INR) ≥ 1.5] and degree of mental alteration without pre-ex-isting cirrhosis and with an illness of < 26 wk duration.We reviewed the clinical indications,operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors.The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis.Survival rates after operation were analyzed using the Kaplan-Meier method.Receiver operator characteristic(ROC) curve analysis was undertaken to identify the threshold of potential risk factors.RESULTS:The causes of ALF were hepatitis B(n = 18),drug-induced(n = 1) and indeterminate(n = 1).The score of the model for end-stage liver disease was 37.1 ± 8.6,and the waiting duration of recipients was 5 ± 4 d.The graft types included right lobe(n = 17) and dual graft(n = 3).The mean graft weight was 623.3 ± 111.3 g,which corresponded to graft-torecipient weight ratio of 0.95% ± 0.14%.The segment Ⅴor Ⅷ hepatic vein was reconstructed in 11 right-lobe grafts.The 1-year and 3-year recipient's survival and graft survival rates were 65%(13 of 20).Postoperative results of total bilirubin,INR and creatinine showed obvious improvements in the survived patients.However,the creatinine level of the deaths was increased postoperatively and became more aggravated compared with the level of the survived recipients.Multivariate analysis showed that waiting duration was independently correlated with increased mortality(P = 0.014).Furthermore,ROC curve revealed the cut-off value of waiting time was 5 d(P = 0.011,area under the curve = 0.791) for determining the mortality.The short-term creatinine level with different recipient's waiting duration was described.The recipients with waiting duration ≥ 5 d showed the worse renal function and higher mortality than those with waiting duration < 5 d(66.7% vs 9.1%,P = 0.017).In addition,all donors had no residual morbidity.Furthermore,univariate analysis did not show that short assessment time induced the high morbidity(P = 0.573).CONCLUSION:Timely AALDLT for patients with ALF greatly improves the recipient survival.However,further systemic review is needed to investigate the optimal treatment strategy for ALF.

Liver transplantation for hepatic metastatic pancreatic insulinoma with a survival over five years

Pancreatic neuroendocrine tumors （NETs） are one subgroup of gastroenteropancreatic NETs. Its main characteristics are slow growth, frequent metastasis to the liver, and limited to the liver for long periods. In patients with irresectable liver metastatic NET, liver transplantation is the only radical treatment. About 160 cases of liver transplantation for liver metastatic NET have been reported worldwide. However, there is no such report of liver transplantation for hepatic metastatic NET in China by now. We herein report a case of liver transplantation for hepatic metastatic pancreatic insulinoma with a survival of over 5 years.