Adult polycystic liver disease (PLD) is defined as a rare, benign, autosomal dominant disorder with numerous cysts scattered throughout the liver parenchyma, either in an isolated form or, more frequently, associated with polycystic kidney disease. Although liver function often remains normal until the advanced stage of the disease, a minority of patients with PLD may progress to severely handicapping hepatomegaly. Secondary cyst enlargement and compression may result in discomfort, abdominal pain and distension, anorexia, dyspnea, early satiety, malnutrition, ascites, lower extremity edema and a significant deterioration of the patient’s quality of life (QoL). It seems that therapeutic modalities dealing with massive liver size, such as aspiration with sclerotherapy, fenestration or partial liver resection, can provide satisfactory symptomatic palliation in patients with a large single dominant cyst confined to one liver lobe. However, conservative surgical intervention may pose a threat to those with the predominantly small diffuse cystic type with only temporary alleviation as well as substantial mortality and morbidity.

Cancer stem-like cells (CSCs) play a key role in maintaining the aggressiveness of hepatocellular carcinoma (HCC), but the cell-biological regulation of CSCs is unclear. In the study, we report that thyroid hormone (TH) promotes cell self-renewal in HCC cells. TH also increases the percentage of CD90 + HCC cells and promotes drug resistance of HCC cells. By analyzing primary human HCC samples, we found that TRα transcript level is significantly elevated in primary liver cancer and portal vein metastatic tumor, compared to that of adjacent normal liver tissue. Knocking down TRα not only inhibits HCC self-renewal in vitro but also suppresses HCC tumor growth in vivo. Interestingly, treatment of TH leads to activation of NF-κB, which is required for the function of TH on inducing HCC cell self-renewal. We also found TRα and p65 cooperatively drive the expression of BMI1 by co-binding to the promoter region of BMI1 gene. In summary, our study uncovers a novel function of TH signaling in regulating the CSCs of HCC and these findings might be useful for developing novel therapies by targeting TH function in HCC cells.

We investigated the overall situation of LT for BA in mainland China and analyzed their survival outcomes based on data from CLTR. Between January 1996 and December 2013, 509 liver transplants for BA were performed in mainland China and were included in this study. Patients' median age was 9.6 months (range: 4.8-175.2 months). KP was previously performed in 194 cases (38.1%). Grafts from living donors were used in 380 cases (74.7%). Era I (1996.1-2010.12) and era II (2011.1-2013.12) comprised 151 cases (29.7%) and 358 cases (70.3%), respectively. Twenty-five centers had performed at least one liver transplant for children with BA. Centers from Shanghai (197 cases), Tianjin (143 cases) and Beijing (81 cases) involved 82.7% of the 509 cases. One- and five-yr graft survival rates were 84.7% and 72.6%, respectively. Split grafts, center volume <20, GRWR ≥4.0%, and steroid-free immunosuppression regimen were independent risk factors for graft survival. In conclusion, the dramatic expansion of pediatric liver transplant programs in mainland China has enabled improved survival for those children affected by this devastating disease. However, screening of BA in neonates should be emphasized throughout the country to enhance early referrals for KP.

目的:探索IQQA(R)-Liver肝脏CT影像解读分析系统在肝脏解剖教学中的效果.方法:将两组学生先后进行常规的解剖教学和IQQA (R)-Liver系统进行教学,分析学生对不同教学方式的反应和对教学知识的掌握程度,对比两种教学方法的效果.结果:相比于常规解剖教学,IQQA(R)-Liver系统能显著提高学生对肝脏解剖的掌握程度.结论:IQQA(R)-Liver系统可显著提高肝脏解剖教学效果.

AIM:To summarize our single-center experience with liver transplantation (LT) for biliary atresia (BA).METHODS:From October 2006 to December 2012, 188 children with BA were analyzed retrospectively. The stage I group (from October 2006 to December 2010) comprised the first 74 patients, and the stage II group (from January 2011 to December 2012) comprised the remaining 114 patients. Finally, 123 liver transplants were performed in 122 (64.9%) patients, whereas 66 patients did not undergo LT due to denial by their parents or lack of suitable liver grafts. The selection of graft types depended on the patients' clinical status and whether a suitable living donor was available. The characteristics of patients in stages I and II were described, and the surgical outcomes of LT recipients were compared between the two stages. The Kaplan-Meier method was used to estimate the cumulative patient and graft survival rates, and the equality of survival distributions was evaluated using the log-rank test.RESULTS:The 188 children consisted of 102 boys and 86 girls. Their ages ranged from 3 to 144 mo with a median of 8 mo. One hundred and fifteen (61.2%) patients were born in rural areas. Comparing stage I and stage II patients, the proportion of patients referred by pediatricians (43.2% vs 71.1%, respectively; P < 0.001) and the proportion of patients who previously received a Kasai procedure (KP) (32.4% vs 44.7%, respectively; P = 0.092) obviously increased, and significantly more parents were willing to treat their children with LT (73% vs 86%, respectively; P = 0.027). Grafts from living donors (102/122, 83.6%) were the most commonly used graft type. Surgical complications (16/25, 64.0%) were the main reason for posttransplant mortality. Among the living donor liver transplantation recipients (n = 102), the incidence of surgical complications was significantly reduced (34.1% vs 15.5%, respectively; P = 0.029) and survival rates of patients and grafts were greatly improved (81.8% vs 89.7%, respectively, at 1 year; 75.0% vs 87.8%, respectively, at 3 years; P = 0.107) from stage I to stage II.CONCLUSION:The status of surgical treatments for BA has been changing in mainland China. Favorable midterm outcomes after LT were achieved as centers gained greater technical experience.

Split liver transplantation (SLT) has proven to be an effective technique to reduce the mortality of children on the waiting list, but whether creating 2 split grafts from 1 standard‐criteria whole liver would compromise outcomes of adult recipients remains uncertain. We conducted this meta‐analysis to compare outcomes of right lobe SLT and whole liver transplantation (WLT) in adult patients. PubMed, Embase, and the Cochrane Library were searched for relevant articles published before December 2014. Outcomes assessed were patient survival (PS), graft survival (GS), and major surgical complications after transplantation. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to synthesize the results. Seventeen studies with a total of 48,457 patients met the full inclusion criteria. PS and GS rates were all found to be equivalent between SLT and WLT recipients. However, SLT was associated with higher rates of overall biliary complications (OR = 1.66; 95% CI = 1.29‐2.15; P < 0.001), bile leaks (OR = 4.30; 95% CI = 2.97‐6.23; P < 0.001), overall vascular complications (OR = 1.81; 95% CI = 1.29‐2.53; P < 0.001), hepatic artery thromboses (OR = 1.71; 95% CI = 1.17‐2.50; P = 0.005), and outflow tract obstructions (OR = 4.17; 95% CI = 1.75‐9.94; P = 0.001). No significant difference was observed in incidences of biliary stricture, portal vein complications, postoperative bleeding requiring surgical treatments, primary nonfunction, and retransplantations. In subgroup analyses, biliary and vascular complications only increased after ex vivo SLT rather than in situ SLT, and SLT recipients had more retransplantations if they matched with WLT recipients in terms of urgent status. In conclusion, adult right lobe SLT was associated with increased biliary and vascular complications compared with WLT, but it did not show significant inferiority in PSs and GSs. Liver Transpl 21:928‐943, 2015. © 2015 AASLD.

Regeneration of the partial allograft and the growth of children may cause kinking of the biliary tract after pediatric living donor liver transplantation (LDLT), but bile duct kinking after adult LDLT is rarely reported. We herein presented two patients who suffered from anastomotic strictures caused by severe bile duct kinking after LDLT. The first patient was a 57-year-old woman with hepatitis B virus (HBV)-related liver cirrhosis, who developed biliary stricture 5 months after receiving right-lobe LDLT. Subsequently, endoscopic and percutaneous treatments were attempted, but both failed to solve the problem. The second was a 44-year-old woman also having HBV-related liver cirrhosis. Biliary stricture occurred 14 months after LDLT. Likewise, the guide wire failed to pass through the stricture when endoscopic interventions were conducted. Afterwards, both of the two cases underwent reexploration, showing that compensatory hypertrophy of the allografts resulted in kinking and sharp angulation of the bile ducts, and the anastomotic sites were found to be severely stenotic. Finally, re-anastomosis by Roux-en-Y procedure was successfully performed, and long-term stenosis-free survival was achieved in both of them. Our experience suggests that bile duct kinking after LDLT may play a role in the high incidence of anastomotic strictures in adult LDLT recipients, which may also result in the treatment failure of the non-surgical techniques for anastomotic strictures. Re-anastomosis in the form of Roux-en-Y hepaticojejunostomy is an effective surgical option for the treatment of such a condition.

Regeneration of the partial allograft and the growth of children may cause kinking of the biliary tract after pediatric living donor liver transplantation (LDLT), but bile duct kinking after adult LDLT is rarely reported. We herein presented two patients who suffered from anastomotic strictures caused by severe bile duct kinking after LDLT. The first patient was a 57-year-old woman with hepatitis B virus (HBV)-related liver cirrhosis, who developed biliary stricture 5 months after receiving right-lobe LDLT. Subsequently, endoscopic and percutaneous treatments were attempted, but both failed to solve the problem. The second was a 44-year-old woman also having HBV-related liver cirrhosis. Biliary stricture occurred 14 months after LDLT. Likewise, the guide wire failed to pass through the stricture when endoscopic interventions were conducted. Afterwards, both of the two cases underwent reexploration, showing that compensatory hypertrophy of the allografts resulted in kinking and sharp angulation of the bile ducts, and the anastomotic sites were found to be severely stenotic. Finally, re-anastomosis by Roux-en-Y procedure was successfully performed, and long-term stenosis-free survival was achieved in both of them. Our experience suggests that bile duct kinking after LDLT may play a role in the high incidence of anastomotic strictures in adult LDLT recipients, which may also result in the treatment failure of the non-surgical techniques for anastomotic strictures. Re-anastomosis in the form of Roux-en-Y hepaticojejunostomy is an effective surgical option for the treatment of such a condition.

BACKGROUND:Portal vein thrombosis (PVT) is one of the main vascular complications after liver transplantation (LT), especially in pediatric patients with biliary atresia (BA). This study aimed to assess the preoperative hepatic hemodynamics in pediatric patients with BA using Doppler ultrasound and determine whether ultrasonographic parameters may predict early PVT after LT.METHODS:One hundred and twenty-eight pediatric patients with BA younger than 3 years of age underwent Doppler ultrasound within seven days before LT, between October 2006 and June 2013. The preoperative hepatic hemodynamic parameters were then compared between patients with early PVT (within 1 month following LT) and those without PVT. Receiver operating characteristic analysis was performed to determine the optimal cutoff value for predicting early PVT.RESULTS:Of the 128 transplant recipients, 41 (32.03%) had a hypoplastic portal vein (PV), 52 (40.63%) had hepatofugal PV flow and 40 (31.25%) had a high hepatic artery resistance index (HARI) of ≥1. Nine cases (7.03%) experienced early PVT. A PV diameter ≤4 mm (sensitivity 88.89%, specificity 72.27%), and a hepatofugal PV flow (sensitivity 77.78%, specificity 62.18%) with a high HARI ≥1 (sensitivity 77.78%, specificity 72.27%) were hepatic hemodynamic risk factors for early PVT.CONCLUSIONS:Hepatic hemodynamic disturbances in pediatric recipients with BA were more common. Small PV diameter (≤4 mm) and hepatofugal PV flow combined with high HARI (≥1) are strong warning signs of early PVT after LT in pediatric patients with BA. Intense monitoring of vascular patency and prophylactic thrombolytic therapy should be considered in pediatric patients undergoing LT for BA.

Background & Aims: Distinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence.Methods: A prospective single-center study investigated 174 patients undergoing liver transplantation due to acute decompensation of hepatitis B virus (HBV)-associated liver cirrhosis. Two groups were distinguished by the presence or absence of submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant). Core clinical features of ACLF were compared between these groups. Disease severity scoring systems were applied to describe liver function and organ failure. Serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes were used to study systemic and local inflammatory responses.Results: SMHN was identified in 69 of 174 patients proven to have cirrhosis by histological means. Characteristic features of SMHN were extensive necrosis along terminal hepatic veins and spanning multiple adjacent cirrhotic nodules accompanied by various degrees of liver progenitor cell-derived regeneration, cholestasis, and ductular bilirubinostasis. Patients with SMHN presented with more severely impaired hepatic function, a higher prevalence of multiple organ failure (as indicated by higher CLIF-SOFA and SOFA scores) and a shorter interval between acute decompensation and liver transplantation than those without SMHN (p < 0.01 for all parameters). Further analyzes based on serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes revealed higher levels of anti-inflammatory cytokines in patients with SMHN.Conclusions: SMHN is a critical histological feature of HBV-associated ACLF. Identification of a characteristic pathological feature strongly supports that ACLF is a separate entity in end-stage liver disease. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

We aimed to assess the impact of size mismatching between grafts and recipients on outcomes of infants or small children after LDLT. Between October 2006 and December 2014, 129 LDLT recipients weighing no more than 8 kg were retrospectively analyzed. The entire cohort was categorized into three groups by GRWR: GRWR < 3.0% (group A, n = 38), 3.0% ≤ GRWR < 4.0% (group B, n = 61), and GRWR ≥ 4.0% (group C, n = 30). Baseline characteristics were similar among groups A, B, and C. Compared with groups A and B, post-transplant alanine aminotransferase and aspartate aminotransferase within seven days were significantly higher in group C; however, differences between total bilirubin and albumin after transplantation were not prominent. Moreover, incidences of surgical complications, perioperative deaths, infections, and acute rejections were all comparable among the three groups. Five-yr patient survival rates for groups A, B, and C were 89.5%, 88.9%, and 81.6%, respectively (p = 0.872), and the graft survival rates were 89.5%, 86.6%, and 81.6%, respectively (p = 0.846). In conclusion, GRWR between 1.9% and 5.8% would not cause noticeable adverse events for infantile LDLT recipients ≤ 8 kg. However, there is still a role for considering reduction in the graft mass as an applicable strategy in selected cases.

Objective To discuss the preoperative donor and recipient assessments and clinical outcomes of living donor liver transplantation (LDLT) using right posterior sector (RPS) grafts.Method We retrospectively analyzed the clinical data and postoperative outcomes of a pediatric patient who underwent living-related liver transplantation (LT) using the RPS graft.The patient was an 8-year-old girl weighing 28 kg.She was diagnosed with cholestasis disease and liver cirrhosis and was admitted to our department for LDLT.The standard liver volume (SLV) of this patient was 727 cm3,and the minimum required graft volume for LDLT was 291 cm3.The donor was her mother,who was 38 years old and weighed 53 kg.Preoperative volumetric assessments showed that the donor's total liver volume was 1071 cm3.Computer tomography angiography (CTA) of the donor liver indicated that the RPS portal vein was branching off separately from the main portal vein (type Ⅲ portal vein),and the branching point of the RPS hepatic artery located outside the liver parenchyma.Further volumetric analysis showed that the volume of RPS graft was 403 cm3,accounting for 55.4％ of recipients SLV.Then,LDLT using RPS graft was performed for this child in January 2015.Result The donor and the recipient both recovered smoothly.Initial immunosuppressive therapy consisted of a dual drug regimen of tacrolimus combined with methylprednisolone,and the recipient was discharged 22 days after LT.The CTA images 3 months after LT showed that the liver graft was working well.The patient has been followed up for more than 7 months.Conclusion Favorable outcomes after LDLT using RPS graft could be obtained in pediatric patients through strict volumetric and anatomical assessment of the donor liver.

Acute liver failure (ALF) is a life-threatening end-stage liver disease, causing high mortality all over the world. Here, we presented a 54-year-old male patient, suffering from drug-induced ALF on the basis of hepatitis B virus (HBV) infection. At that time, the only available donor we could find was his 44-year-old sister. We performed living donor auxiliary partial orthotopic liver transplantation (APOLT) on the second day of admission. The right lobe of the donor liver was implanted into the recipient orthotopically. The actual graft-to-recipient weightratio (GRWR) was 0.85% and the postoperative immunosuppression was a combination of tacrolimus, mycophenolate mofetil (MMF) and steroids. The patient recovered consciousness on the third post-operative day and was discharged with normal liver function after 43 days of transplantation. After a 48-month follow-up, the recipient has been restored to normal life and the immunosuppression has been tapered off (tacrolimus, 1 mg/d). Besides, the size of the native liver has extended to 29% of standard liver volume (SLV) and the native liver cells have returned to normal pathological condition. In conclusion, APOLT is a life-saving treatment for ALF with excellent post-operative outcomes.

Hepatoblastoma (HB) is the most common primary liver tumor in children. Mutations in the β‐catenin gene that lead to constitutive activation of the Wnt pathway have been detected in a large proportion of HB tumors. To identify novel mutations in HB, we performed whole‐exome sequencing of six paired HB tumors and their corresponding lymphocytes. This identified 24 somatic nonsynonymous mutations in 21 genes, many of which were novel, including three novel mutations targeting the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) genes in the Wnt pathway, and genes previously shown to be involved in the ubiquitin ligase complex (SPOP, KLHL22, TRPC4AP, and RNF169). Functionally, both the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) were observed to be gain‐of‐functional mutations, and the CAPRIN2 (R968H/S969C) was also shown to activate the Wnt pathway in HB cells. These findings suggested the activation of the Wnt pathway in HB, which was confirmed by immunohistochemical staining of the β‐catenin in 42 HB tumors. We further used short hairpin RNA (shRNA)‐mediated interference to assess the effect of 21 mutated genes on HB cell survival. The results suggested that one novel oncogene (CAPRIN2) and three tumor suppressors (SPOP, OR5I1, and CDC20B) influence HB cell growth. Moreover, we found that SPOP S119N is a loss‐of‐function mutation in HB cells. We finally demonstrated that one of the mechanisms by which SPOP inhibits HB cell proliferation is through regulating CDKN2B expression. Conclusion: These results extend the landscape of genetic alterations in HB and highlight the dysregulation of Wnt and ubiquitin pathways in HB tumorigenesis. (Hepatology 2014;;60:1686–1696)

To establish a prognostic prediction system for patients with hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation (LT).

Little information is available regarding the impact of cytochrome P450 (CYP) 3A5 on the metabolism of TAC in infant LTx. Therefore, the CYP3A5 genotype of Chinese pediatric recipients (intestine) as well as donors (graft liver) was performed for the purpose of establishing an optimal dosage regimen in children. Sixty-four patients were divided according to CYP3A5 genotype (expression of *1 allele: EX and NEX) for each recipient (R) and donor (D), EX-R/EX-D (n=21), EX-R/NEX-D (n=8), NEX-R/EX-D (n=8) and NEX-R/NEX-D (n=27). Results indicated that initial TAC daily dose requirement was higher among EX-R/EX-D children compared with those who did not express CYP3A5 (0.28 +/- 0.10 vs. 0.19 +/- 0.08mg/kg/day, p<0.01). CYP3A5 expression contributed an overall of 38.35% to its C/D ratios, and graft liver was a key determinant. Additionally, the EX-R/EX-D group showed significantly higher incidence of infectious complications, lower immune response and was an independent risk factor for the development of infections (odds ratio 3.86, p=0.025). Donor CYP3A5 expression partially explains TAC dose requirement, the effect of CYP3A5 variation may influence clinical outcomes; therefore, monitoring immune response may be important for preventing risks associated with under- and over-immunosuppression.

目的 建立肝脏切除术前风险预测模型.方法 回顾性分析2012年6月至2013年9月我科连续性完成52例半肝切除的临床资料,采用Logistic回归分析模型明确术后肝功能不全发生的预测因素.结果 术前吲哚菁绿15分钟滞留率(ICG R15)、残余肝脏体积/标准肝脏体积(RLV/SLV)、脾脏体积增大倍数(△SV/SSV)均为半肝切除术后肝功能不全发生的独立危险因素(P=0.001,P=0.003和P=0.002),风险系数R=3.545×(ICG R15)-5.743×(RLV/SLV) +8.982×(△SV/SSV).结论 相对较高的ICG15R和△SV/SSV,以及较低的RLV/SLV可能影响肝脏切除术后患者肝功能不全的发生.