A Molecular Adsorbent Recycling System in Treating Posthepatectomy Acute Hepatic Failure Patients with Hepatocellular Carcinoma:a Bridge to Liver Transplantation

OBJECTIVE To evaluate the effect and safety of a Molecular Adsorbent Recycling System (MARS) in treating posthepatoectomy hepatic failure (AHF) patients surgically treated for primary hepatocellular carcinoma (HCC). METHODS 12 AHF patients induced by resection of HCC were treated with MARS before orthotopic liver transplantation (OLT). Their vital signs, urine volume, APACHEⅢand Glasgow scores were monitored. Routine laboratory blood tests, measurements of coagulatory function, liver and kidney function, serum ammonia, lactic acid and blood gas were conducted before and after treatment with MARS. All of the patients were followed up for a period of 6 months after OLT for prognosis and complication assessment. RESULTS Each patient was treated with MARS for 2-5 times (average of 3.6) with a length of 8-24 h each time. Their mean arterial blood pressure and urine volume were improved, APACHEⅢand Glasgow scores were better. Liver function was improved with the following alterations before and after treatment with MARS: serum ammonia (127.1±21.4 umol/L vs. 77.4±19.7 umol/L, P<0.05), lactic acid (6.53±0.45 mmol/L vs. 3.75±0.40 mmol/L, P<0.05) and total bilirubin (452.3±153.7 umol/L vs. 230.9±115.2 umol/L, P<0.05). However, there was no significant change in platelet count (44.25±3.60×109/L vs. 43.19±8.26×109/L, P>0.05) on international normalized ratio (INR) (2.74±0.50 us. 2.82±0.60, P>0.05), which showed the safety of MARS. For all patients no serious adverse effects occurred during the treatment with MARS. CONCLUSION MARS is effective and safe for treatment of AHF patients with HCC, especially as a bridge to OLT when a donor organ is not available.

miR-30b inhibits autophagy to alleviate hepatic ischemiareperfusion injury via decreasing the Atg12-Atg5 conjugate

AIM: To explore the role and potential mechanism of miR-30 b regulation of autophagy in hepatic ischemiareperfusion injury(IRI).METHODS: An animal model of hepatic IRI was generated in C57BL/6 mice. For in vitro studies, AML12 cells were immersed in mineral oil for 1 h and then cultured in complete Dulbecco's Modified Eagle's Medium(DMEM)/F12 to simulate IRI. Mice and cells were transfected with miR-30 b agomir/mimics or antagomir/inhibitor to examine the effect of miR-30 b on autophagy to promote hepatic IRI. The expression of miR-30 b was measured by real-time polymerase chain reaction. Apoptotic cells were detected by terminal uridine nickend labeling(TUNEL) staining, and cell viability was detected by methylthiazole tetrazolium assay. The expression of light chain 3, autophagy-related gene(Atg)12, Atg5, P62, and caspase-3 were detected by western blotting analysis.RESULTS: miR-30 b levels were significantly downregulated after hepatic IRI, and the numbers of autophagosomes were increased in response to IRI both in vivo and in vitro. These findings demonstrate that low levels of miR-30 b could promote hepatic IRI. Furthermore, we found that miR-30 b interacted with Atg12-Atg5 conjugate by binding to Atg12. Overexpression of miR-30 b diminished Atg12 and Atg12-Atg5 conjugate levels, which promoted autophagy in response to IR. In contrast, downregulation of miR-30 b was associated with increased Atg12-Atg5 conjugate levels and increased autophagy.CONCLUSION: miR-30 b inhibited autophagy to alleviate hepatic ischemia-reperfusion injury via decreasing the Atg12-Atg5 conjugate.

Pediatric liver transplantation in 31 consecutive children

Background Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements. Methods Thirty-one children （≤18 years old） underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old （ranged from 5 months to 18 years） with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson＇s disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard （without venovenous bypass）, 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug （FK506, steroid, and mycophenolate mofetil） immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months. Results Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus （HBV） or hepatitis C virus （HCV） infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively. Conclusions The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients＇ age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher surgical skills. The early postoperative management is the key to success. Postoperative bile leak was common, but most patients underwent liver transplantation had a better prognosis.