Tian-Fu Wen

Prophylaxis Against Hepatitis B Recurrence Posttransplantation Using Lamivudine and Individualized Low-Dose Hepatitis B Immunoglobulin

Although the combination of lamivudine (LAM) and high‐dose intravenous (IV) hepatitis B immunoglobulin (HBIG) is very effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation (LT), the major limitation of this regimen is its high cost. A more cost‐effective, convenient and widely accepted regimen is urgently needed. We evaluated the safety and efficacy of another strategy using LAM and individualized low‐dose intramuscular (IM) HBIG. Between May 2002 and December 2009, a total of 254 adult patients undergoing LT for HBV‐related benign end‐stage liver diseases received this regimen in our center. The mean follow‐up of these patients was 41.2 ± 22.7 months. Their 1‐, 3‐ and 5‐year survival rates were 85.3%, 77.4% and 76.4%, respectively, and 1‐, 3‐ and 5‐year HBV recurrence rates were 2.3%, 6.2% and 8.2%. Fourteen patients experienced posttransplant HBV recurrence. Pretransplant high viral load and posttransplant prednisone withdrawal time were observed to be associated with recurrence. In conclusion, combination therapy with LAM and individualized low‐dose IM HBIG provides a safe and effective prophylaxis against HBV recurrence after LT at about 5% of the cost of conventional high‐dose IV HBIG regimens.

XRCC1 genetic polymorphism Arg399Gln and hepatocellular carcinoma risk: a meta-analysis.

Background: Studies investigating the association between X‐ray repair cross‐complementing group 1 (XRCC1) genetic polymorphism Arg399Gln and hepatocellular carcinoma (HCC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship.

Analysis of infections in the first 3-month after living donor liver transplantation

AIM To identify factors related to serious postoperative bacterial and fungal infections in the first 3 mo after living donor liver transplantation (LDLT). METHODS In the present study, the data of 207 patients from 2004 to 2011 were reviewed. The pre-, intra- and post-operative factors were statistically analyzed. All transplantations were approved by the ethics committee of West China Hospital, Sichuan University. Patients with definitely preoperative infections and infections within 48 h after transplantation were excluded from current study. All potential risk factors were analyzed using univariate analyses. Factors significant at a P < 0.10 in the univariate analyses were involved in the multivariate analyses. The diagnostic accuracy of the identified risk factors was evaluated using receiver operating curve. RESULTS The serious bacterial and fungal infection rates were 14.01% and 4.35% respectively. Enterococcus faecium was the predominant bacterial pathogen, whereas Candida albicans was the most common fungal pathogen. Lung was the most common infection site for both bacterial and fungal infections. Recipient age older than 45 years, preoperative hyponatremia, intensive care unit stay longer than 9 d, postoperative bile leak and severe hyperglycemia were independent risk factors for postoperative bacterial infection. Massive red blood cells transfusion and postoperative bacterial infection may be related to postoperative fungal infection. CONCLUSION Predictive risk factors for bacterial and fungal infections were indentified in current study. Pre-, intra- and post-operative factors can cause postoperative bacterial and fungal infections after LDLT.

Living donor liver transplantation for Budd‐Chiari syndrome using cryopreserved vena cava graft in retrohepatic vena cava reconstruction

Objective To report the authors experience with the first case of an adult-to-adult living donor liver transplantation (LDLT) for Budd-Chiari syndrome (BCS) using cryopreserved vena cava graft in postheptic vena cava reconstruction. Methods A 35-year-old male patient with a diagnosis of BCS complicated with inferior vena cava (IVC) obstruction received medical treatment and radiologic intervention for nine months, no relief of the symptoms could be achieved. Finally, the patient underwent LDLT, which required posthepatic vena cava reconstructed using cryopreserved vena cava graft. Results The patient has had an uneventful course since the LDLT. Conclusion We believe that LDLT combined with posthepatic IVC reconstruction using cryopreserved vena cava graft is considered to be a sound modality for IVC obstructed BCS.

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 AFP.

Salvage Liver Transplantation for Recurrent Hepatocellular Carcinoma within UCSF Criteria after Liver Resection

Background Salvage liver transplantation (SLT) is restricted to patients who develop hepatocellular carcinoma (HCC) recurrence within Milan criteria (MC). Little is known about outcomes for SLT in patients with recurrent HCC within University of California San Francisco (UCSF) criteria after liver resection (LR). Methods Between January 2001 and December 2011, 380 patients with HCC meeting UCSF criteria, 200 of which were resected (LR group) from a perspective of SLT in case of recurrence, and 180 directly underwent LT (PLT). We compared patient characteristics, perioperative and long-term outcomes between SLT and PLT groups. We also assessed the outcome of LR and PLT groups. Results Among the 200 patients in LR group, 86 (43%) developed HCC recurrence and 15/86 (17%) of these patients presented HCC recurrence outside UCSF criteria. Only 39 of the 86 patients underwent SLT, a transplantation rate of 45% of patients with HCC recurrence. Compared with PLT group, LR group showed lower overall survival rate (P = 0.005) and higher recurrence rate (P = 0.006). Although intraoperative blood loss and required blood transfusion were more frequent in SLT group, the perioperative mortality and posttransplant complications were similar in SLT and PLT groups. The overall survival and recurrence rates did not significantly differ between the two groups. When stratifying by graft type in the SLT group, overall survival and recurrence rates did not significantly differ between deceased donor LT (DDLT) and living donor LT (LDLT) groups. In the subgroup analysis by MC, similar results were observed between patients with recurrent HCC meeting MC and patients with recurrent HCC beyond MC but within UCSF criteria. Conclusion Our single institution experience demonstrated that prior hepatectomy and SLT for recurrent HCC within UCSF criteria was feasible and SLT could achieve the same outcome as PLT.

Predictors of patient survival following living donor liver transplantation

BACKGROUND Living donor liver transplantation (LDLT) is considered to be the alterative choice in light of the great shortage of cadaveric donors. However, the characteristics of the patients who will benefit from LDLT have not been well identified. The aim of this study was to define the pre- and intra-operative factors that may influence patient outcome. METHODS The data from 102 LDLT patients who had operations between 2002 and 2009 were collected and analyzed retrospectively. Data were analyzed using uni- and multi-variate analysis according to factors that are known to be associated with outcome in these patients. RESULTS Overall, the accurate survival rate of recipients at 1, 3, and 5 years was 84%, 76%, and 70%, respectively. The independent risk factors, preoperative renal dysfunction, intraoperative red blood cell transfusions of greater than 5 units, and female to male match (donor to recipient matching), were identified by Cox regression analysis. The pre-transplant model for end-stage liver disease score and a graft to recipient weight ratio of less than 0.8% were not predictive of outcome. The overall 1-, 3-, and 5-year survival of patients with one or no risk factors and two or more risk factors were 91%, 86%, and 83% and 67%, 56%, and 47%, respectively (P<0.0001). CONCLUSIONS In our retrospective study, preoperative renal dysfunction, intraoperative red blood cell transfusions of greater than 5 units, and female to male gender match were independent risk factors for LDLT recipient outcome. Two or more of these risk factors may contribute to poor outcome.

Systematic Review and Meta-Analysis of the Relationship between EPHX1 Polymorphisms and Colorectal Cancer Risk

Background Microsomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk. Methods Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before June 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for EPHX1 Tyr113His (rs1051740) and His139Arg (rs2234922) polymorphisms and CRC were calculated in a fixed-effects model and a random-effects model when appropriate. Results This meta-analysis yielded 14 case-control studies, which included 13 studies for Tyr113His (6395 cases and 7893 controls) and 13 studies for His139Arg polymorphisms (5375 cases and 6962 controls). Overall, the pooled results indicated that EPHX1 Tyr113His polymorphism was not associated with CRC risk; while the His139Arg polymorphism was significantly associated with decreased CRC risk (Arg/His vs. His/His, OR = 0.90, 95%CI = 0.83–0.98; dominant model, OR = 0.92, 95%CI = 0.85–0.99). The statistically significant association between EPHX1 His139Arg polymorphism and CRC was observed among Caucasians and population-based case-control studies. This association showed little heterogeneity and remained consistently strong when analyses were limited to studies in which genotype frequencies were in Hardy–Weinberg equilibrium, or limited to studies with matched controls. When cumulative meta-analyses of the two associations were conducted by studies’ publication time, the results were persistent and robust. Conclusion This meta-analysis suggests that EPHX1 Tyr113His polymorphism may be not associated with CRC development; while the EPHX1 His139Arg polymorphism may have a potential protective effect on CRC.

A single institution experience with living donor liver transplantation for acute-on-chronic hepatitis B liver failure.

BACKGROUND/AIMS This study reports our preliminary experience of living donor liver transplantation (LDLT) for patients with acute-on-chronic liver failure (AoCLF) caused by hepatitis B. METHODOLOGY 47 patients who demonstrated Ao- CLF caused by hepatitis B with mean (±SD) Model for End-Stage Liver Disease scores of 39.2±5.1 were divided by the transplantation group (n=19) and the non-transplantation group (n=28) according to whether or not undergoing LDLT. At the same time, 30 hepatitis B cirrhosis recipients who underwent LDLT and did not reach the criteria of AoCLF were selected as the control group (n=30). In the transplantation group, veno-venous bypass, molecular adsorbent recirculating system (MARS) and continuous renal replacement therapy (CRRT) were introduced. The intraoperative data, post-transplant complications and mortality were analyzed retrospectively. RESULTS There were no significant differences in survival rates of 1, 6 and 12 months and the postoperative complications except for pneumonia and diabetes, between the control group and the transplantation group (p>0.05). Recurrence of hepatitis B was not found in the recipients of the control group and the transplantation group. CONCLUSIONS Right-lobe LDLT may be an effective therapeutic option for patients with acute-on-chronic hepatitis B liver failure.

Estimation of Standard Liver Volume for Liver Transplantation in the Chinese Population

INTRODUCTION The accurate assessment of standard liver volume (SLV) is necessary for the safety of both the donor and the recipient in living donor liver transplantation. However, the accuracy of SLV formulas relates to cohorts or races. This study examined the accuracy of a simple linear formula versus previous formulas of SLV for Chinese adults. METHODS Among 112 patients with normal liver, we created a new formula for SLV with stepwise regression analysis using the following variables: age, gender, body weight, body height, body mass index, and body surface area. The agreement between the actual liver volume (LV) and calculated LV using various formulas was prospectively evaluated among 63 living donors by paired-sample students t-test and Lins concordance correlation coefficient. RESULTS A new formula was developed SLV (mL) = 949.7 x BSA (m(2)) - 48.3 x age - 247.4 where age was counted as 1 for those <40, 2 if 41-60, and 3 if >60 years old. The calculated LV using our formula showed no significant difference from the actual LV using the paired-samples students t-test (P = .653). Lins concordance correlation coefficient showed substantial agreement between estimated LV using our formula and actual LV. Furthermore, this study also observed an almost perfect agreement between our formula and the Yoshizumi et al formula. CONCLUSION Our formula, which accurately estimated LV among Chinese adults, may be applicable to adults of other ethnicitis.