Early prediction of survival in hepatocellular carcinoma patients treated with transarterial chemoembolization plus sorafenib

AIM To identify clinical biomarkers that could early predict improved survival in patients with advanced-stage hepatocellular carcinoma(HCC) treated with transarterial chemoembolization combined with sorafenib(TACE-S).METHODS We retrospectively evaluated the medical records of consecutive patients with advanced-stage HCC who underwent TACE-S from January 2012 to December 2015. At the first follow-up 4-6 wk after TACE-S(median, 38 d; range, 33-45 d), patients exhibiting the modified Response Evaluation Criteria in Solid Tumors(m RECIST)-evaluated complete response, partial response, and stable disease were categorized as early disease control. At this time point, multiple variables were analyzed to identify the related factors affecting survival.RESULTS Ninety-five patients were included in this study, and 60 of these patients achieved early disease control, with an overall disease control rate(DCR) of 63.2%. Patients who got sorafenib at the first TACE(no previous TACE) and patients without portal vein tumor thrombus(PVTT) had a higher DCR than those who underwent previous TACE before TACE-S(72.4% vs 48.6%, P = 0.019) and those with PVTT(75.5% vs 50.0%, P = 0.010). Early disease control after TACE-S, no previous TACE, and no PVTT were the independent prognostic factors for survival in the uni-and multivariate analyses.CONCLUSION The first follow-up 4-6 wk after TACE-S can be used as the earliest time point to assess the response to TACE-S, and patients with m RECIST-evaluated early disease control, no previous TACE, and no PVTT had better survival.

Generation of functional hepatocyte-like cells from human bone marrow mesenchymal stem cells by overexpression of transcription factor HNF4α and FOXA2

Background: Our previous study showed that overexpression of hepatocyte nuclear factor 4α(HNF4α) could directly promote mesenchymal stem cells(MSCs) to differentiate into hepatocyte-like cells. However, the efficiency of hepatic differentiation remains low. The purpose of our study was to establish an MSC cell line that overexpressed HNF4α and FOXA2 genes to obtain an increased hepatic differentiation efficiency and hepatocyte-like cells with more mature hepatocyte functions. Methods: Successful establishment of high-level HNF4α and FOXA2 co-overexpression in human induced hepatocyte-like cells(hi Hep cells) was verified by flow cytometry, immunofluorescence and RT-PCR. Measurements of albumin(ALB), urea, glucose, indocyanine green(ICG) uptake and release, cytochrome P450(CYP) activity and gene expression were used to analyze mature hepatic functions of hi Hep cells. Results: hi Hep cells efficiently express HNF4α and FOXA2 genes and proteins, exhibit typical epithelial morphology and acquire mature hepatocyte-like cell functions, including ALB secretion, urea production, ICG uptake and release, and glycogen storage. hi Hep cells can be activated by CYP inducers. The percentage of both ALB and α-1-antitrypsin(AAT)-positive cells was approximately 72.6%. The expression levels of hepatocyte-specific genes( ALB, AAT, and CYP1A1) and liver drug transport-related genes( ABCB1, ABCG2, and SLC22A18) in hi Hep cells were significantly higher than those in MSCs-Vector cells. The hi Hep cells did not form tumors after subcutaneous xenograft in BALB/c nude mice after 2 months. Conclusion: This study provides an accessible, feasible and efficient strategy to generate hi Hep cells from MSCs.

Renal aspergillosis after liver transplantation: Clinical and imaging manifestations in two cases

Renal aspergillosis(RAsp)is a rare complication in liver transplant(LT)recipients.Here we report RAsp in two LT recipients.In both patients,RAsp occurred more than 90 d after allogenetic orthotropic LT,and all the clinical findings were unspecific.RAsp involved unilateral kidney in Case one and bilateral kidneys in Case two.Both computed tomography(CT)and magnetic resonance imaging(MRI)revealed renal abscesses,with progressively enhanced walls and separationsand unenhanced alveolate areas after contrast agent administration.On unenhanced CT images they showed inhomogeneous hypo-attenuation.On fat-suppressed T2-weighted images(T2WIs),the walls and separations of the abscesses showed slightly low signal intensity and the central parts of the lesions showed slightly high signal intensity.Both on CT and MRI,there were some hints of renal infarction or chronic ischemia.Both cases were treated by radical nephrectomy followed by adjuvant antifungal treatment.They all recovered well.

Role of interventional therapy in hepatic artery stenosis and non-anastomosis bile duct stricture after orthotopic liver transplantation

AIM： To analyze the clinical manifestations and the effectiveness of therapy in patients with orthotopic liver bansplantation （OLT）-associated hepatic artery stenosis （HAS） and non-anastomosis bile duct stricture.METHODS： Nine cases were diagnosed as HAS and non-anastomosis bile duct stricture. Percutaneous transluminal angioplasty （PTA） was performed in four HAS cases, and expectant treatment in other five HAS cases, percutaneous transhepatic bile drainage, balloon dilation, stent placement were performed in all nine cases.RESULTS： Diffuse intra- and extra-bile duct stricture was observed in nine cases, which was associated with bile mud siltation and biliary infection. Obstruction of the bile duct was improved obviously or removed. Life span/ follow-up period was 13-30 mo after PTA of four HAS cases, 6-23 mo without PTA of other five cases.CONCLUSION： Progressive, non-anastomosis, and diffuse bile duct stricture are the characteristic manifestations of HAS and non-anastomosis bile duct stricture after OLT. These are often associated with bile mud siltation, biliary infection, and ultimate liver failure. Interventional therapy is significantly beneficial.

Role of multi-detector computed tomography for biliary complications after liver transplantation

AIM: To investigate the diagnostic performance of multi-detector computed tomography (MDCT) in detecting biliary complications after orthotopic liver transplantation (OLT).