[show abstract][hide abstract] ABSTRACT: Acute-on-chronic liver failure (ACLF) is one of the most deadly, prevalent, and costly diseases in Asia. However, no prognostic model has been developed that is based specifically on data gathered from Asian patients with ACLF. The aim of the present study was to quantify the survival time of ACLF among Asians and to develop a prognostic model to estimate the probability of death related to ACLF.
We conducted a retrospective observational cohort study to analyze clinical data from 857 patients with ACLF/pre-ACLF who did not undergo liver transplantation. Kaplan-Meier and Cox proportional hazards regression model were used to estimate survival rates and survival affected factors. The area under the receiver operating characteristic curve (auROC) was used to evaluate the performance of the models for predicting early mortality.
The mortality rates among patients with pre-ACLF at 12 weeks and 24 weeks after diagnosis were 30.5% and 33.2%, respectively. The mortality rates among patients with early-stage ACLF at 12 weeks and 24 weeks after diagnosis were 33.9% and 37.1%, respectively. The difference in survival between pre-ACLF patients and patients in the early stage of ACLF was not statistically significant. The prognostic model identified 5 independent factors significantly associated with survival among patients with ACLF and pre-ACLF: the model for end-stage liver disease (MELD) score; age, hepatic encephalopathy; triglyceride level and platelet count.
The findings of the present study suggest that the Chinese diagnostic criteria of ACLF might be broadened, thus enabling implementation of a novel model to predict ACLF-related death after comprehensive medical treatment.
PLoS ONE 01/2013; 8(6):e64379. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: An immortalized human hepatocyte cell line, HepLi5, was established via transfection of Simian virus 40 large T antigen (SV40 LT) into primary human hepatocytes. The morphologic and functional characteristics of HepLi5 cells were evaluated. The expression of SV40 LT in HepLi5 cells was detected by reverse transcription-PCR (RT-PCR) and western blotting. mRNA expression of liver-enriched genes, including glutamine synthetase, albumin, and cytochrome P450 was detected via RT-PCR in HepLi5 cells. Activity of CYP1A2, one of the drug-metabolizing P450 enzymes, was detected. Subcutaneous injection of HepLi5 cells into nude mice did not induce tumors within 3 months. Short Tandem Repeat results confirmed the authenticity of the cell line. Clinical-grade quantities of HepLi5 cells could be harvested using large-scale culture in roller bottles after which their cellular function was significantly enhanced. Therefore, the immortalized HepLi5 cells are a suitable cell source for applications in bioartificial livers.
[show abstract][hide abstract] ABSTRACT: Bioartificial liver (BAL) support system has been proposed as potential treatment method for end-stage liver diseases. We described an improved BAL system based on a choanoid fluidized bed bioreactor containing alginate-chitosan encapsulated primary porcine hepatocytes. The feasibility, safety, and efficiency of this device were estimated using an allogeneic fulminant hepatic failure (FHF) model. FHF was induced with intravenous administration of D-galactosamine. Thirty FHF pigs were divided into three groups: (1) an FHF group which was only given intensive care; (2) a sham BAL group which was treated with the BAL system with empty encapsulation, and (3) a BAL group which was treated with the BAL system containing encapsulated freshly isolated primary porcine hepatocytes. The survival times and biochemical parameters of these animals were measured, and properties of the encapsulations and hepatocytes before and after perfusion were also evaluated. Compared to the two control groups, the BAL-treated group had prolonged the survival time and decreased the blood lactate levels, blood glucose, and amino acids remained stable. No obvious ruptured beads or statistical decline in viability or function of encapsulated hepatocytes were observed. This new fluidized bed BAL system is safe and efficient. It may represent a feasible alternative in the treatment of liver failure.
Biotechnology and Bioengineering 03/2011; 108(9):2229-36. · 3.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background/introduction: Artificial liver support treatment is a promising alternative to liver transplantation. An ideal artificial liver support system (ALSS) should be a combination of a nonbiological liver (NBL) device and a bioreactor based bioartificial liver (BAL). Material and methods: A novel ALSS which can not only fulfill toxin-removal functions of NBL but also provide biotransformation and synthetic functions of BAL is constructed. The unique dual-chamber reservoir can improve the efficiency of material exchange. The funnel-shaped fluidized bed bioreactor can provide an ideal physiological environment for hepatocytes. Quick bubble handling function improves the security during treatment. The software design provides error correction function. Our control center is an industrial personal computer and most components are integrated via the RS485 buses. The whole control system consists of three parts: a pump drive module, a sensor network and a human-machine communication interface. To verify our design, we test the system on miniature pigs. Results: The system runs normally in all treatment modes and meets the clinical requirements. Functions of all components are verified. Conclusions: The system provides a reliable research platform for artificial liver support treatment.
4th International Conference on Biomedical Engineering and Informatics, BMEI 2011, Shanghai, China, October 15-17, 2011; 01/2011
[show abstract][hide abstract] ABSTRACT: A modular novel bioartificial liver support system was designed and constructed in order to simplify tedious operation of artificial liver treatment and to improve the applicability in the system. The design ideas, structure composition, system function, and etc, were described in detail. In this system, the variety of the therapy modes could be conveniently connected by the interface of modular structure. Industrial control computer was used as the main control platform, and physical of control parameters such as pressure, pump speed, dissolved oxygen, temperature, and etc, were transmitted into computer, then according to the instruction, process of the treatment was accomplished by the executing units implemented by main control system. Touch screen of human-computer interface was adopted, which made the system better operational and more comfortable. The system has passed the spot function test, and all indexes can meet requirements for the clinical treatment requested. It has the character such as modular design, systematic distribution, building-block structure, and etc, which supports a great novel operation platform for artificial therapy.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:3095-8.