Analysis of the efficacy of sleeve gastrectomy, one-anastomosis gastric bypass, and single-anastomosis sleeve ileal bypass in the treatment of metabolic syndrome.

The objective of this study was to evaluate and compare the effectiveness of three different types of bariatric surgeries, namely, sleeve gastrectomy (SG), one-anastomotic gastric bypass (OAGB), and single anastomosis sleeve ileal (SASI) bypass, in the treatment of metabolic syndrome (MS). The optimal approach for managing MS remains uncertain, and thus this study aimed to provide a recent analysis of the efficacy of these surgical procedures. This retrospective study evaluated data of individuals who underwent SG, OAGB, and SASI bypass. The primary outcome measures included weight, body mass index (BMI), glucolipid metabolic index, and the occurrence of treatment-related complications within 6 to 12 months post-surgery. A total of 324 patients were included in this study. Of these, 264 patients underwent SG, 30 underwent OAGB, and 30 underwent SASI bypass. A significant decrease in weight was observed at the 6-month and 12-month marks following all three surgical procedures. Of these, patients who underwent SASI bypass exhibited the greatest reduction in weight and BMI post-surgery. Furthermore, the SASI bypass was associated with a significantly higher percentage of total weight loss (%TWL) and excess body mass index loss (%EBMIL) compared to SG and OAGB. Patients who underwent OAGB and SASI bypass demonstrated notable improvements in type 2 diabetes mellitus (T2DM). Patients who underwent SASI bypass and OAGB experienced greater postoperative comfort and reported fewer complaints of discomfort compared to the other procedure. Based on the retrospective analysis of the data, SASI bypass was associated with greater reductions in weight and BMI, higher percentages of %TWL and %EBMIL, and better improvement in T2DM compared to SG and OAGB. Therefore, both SASI bypass and OAGB were found to be more effective than SG in the treatment of MS.

Th1 bias of liver mucosal-associated invariant T cells promotes hepatic gluconeogenesis in type 2 diabetes mellitus.

AIMS: It is acknowledged that aberrant liver immunity contributes to the development of type 2 diabetes mellitus (T2DM). Mucosal-associated invariant T (MAIT) cells, an innate-like T-cell subset, are enriched in the human liver. Nevertheless, the characterisation and potential role of hepatic MAIT cells in T2DM remain unclear. MATERIALS AND METHODS: Fourteen newly diagnosed T2DM subjects and 15 controls received liver biopsy. The frequency and cytokine production of MAIT cells were analysed by flow cytometry. The expression of genes involved in glucose metabolism was determined in HepG2 cells co-cultured with hepatic MAIT cells. RESULTS: Compared with controls, hepatic MAIT cell frequency was significantly increased in T2DM patients (24.66% vs. 14.61%, p = 0.001). There were more MAIT cells producing interferon-γ (IFN-γ, 60.49% vs. 33.33%, p = 0.021) and tumour necrosis factor-α (TNF-α, 46.84% vs. 5.91%, p = 0.021) in T2DM than in controls, whereas their production of interleukin 17 (IL-17) was comparable (15.25% vs. 4.55%, p = 0.054). Notably, an IFN-γ+ TNF-α+ IL-17+/- producing MAIT cell subset was focussed, which showed an elevated proportion in T2DM (42.66% vs. 5.85%, p = 0.021) and positively correlated with plasma glucose levels. A co-culture experiment further indicated that hepatic MAIT cells from T2DM upregulated the gene expression of pyruvate carboxylase, a key molecule involved in gluconeogenesis, in HepG2 cells, and this response was blocked with neutralising antibodies against IFN-γ and TNF-α. CONCLUSIONS: Our data implicate an increased Th1-like MAIT cell subset in the liver of newly diagnosed T2DM subjects, which induces hyperglycaemia by promoting hepatic gluconeogenesis. It provides novel insights into the immune regulation of metabolic homoeostasis. CLINICAL TRIAL REGISTRATION NUMBER: NCT03296605 (registered at www. CLINICALTRIALS: gov on 12 October 2018).

Folate receptor-positive circulating tumor cells predict survival and recurrence patterns in patients undergoing resection for pancreatic cancer.

Objective: To evaluate the prognostic impact of folate receptor (FR)-positive circulating tumor cells (FR+ CTCs) for patients with pancreatic cancer (PC). Background: Risk stratification before surgery for PC patients remains challenging as there are no reliable prognostic markers currently. FR+ CTCs, detected by ligand-targeted polymerase chain reaction (LT-PCR), have shown excellent diagnostic value for PC in our previous study and prognostic value in a variety of cancer types. Methods: Peripheral blood samples from 44 consecutive patients diagnosed with PC were analyzed for FR+ CTCs. 25 patients underwent tumor resection and were assigned to the surgical group. 19 patients failed to undergo radical resection because of local advance or distant metastasis and were assigned to the non-surgical group. The impact of CTCs on relapse and survival were explored. Results: For the prognostic stratification, the optimal cut-off value of CTCs analyzed by receiver operating characteristic (ROC) curve was 14.49 folate units (FU)/3 ml. High CTC levels (> 14.49 FU/3 ml) were detected in 52.0% (13/25) of the patients in the surgical group and 63.2% (12/19) in the non-surgical group. In the surgical group, median disease-free survival (DFS) for patients with high CTC levels versus low CTC levels (< 14.49 FU/3 ml) was 8.0 versus 26.0 months (P = 0.008). In multivariable analysis, CTCs were an independent risk factor for DFS (HR: 4.589, P = 0.012). Concerning the recurrence patterns, patients with high CTC levels showed a significantly frequent rate of distant and early recurrence (P = 0.017 and P = 0.011). CTC levels remained an independent predictor for both distant (OR: 8.375, P = 0.014) and early recurrence (OR: 8.412, P = 0.013) confirmed by multivariable logistic regression. However, CTCs did not predict survival in the non-surgical group (P = 0.220). Conclusion: FR+ CTCs in resected PC patients could predict impaired survival and recurrence patterns after surgery. Preoperative CTC levels detected by LT-PCR may help guide treatment strategies and further studies in a larger cohort are warranted.

Chronic intermittent hypoxia contributes to non-alcoholic steatohepatitis progression in patients with obesity.

BACKGROUND AND PURPOSE: The association between the severity of obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in patients with obesity remains unclear. We conducted this study to determine the effects of OSA on the severity of NAFLD in individuals with obesity and its link to the development of non-alcoholic steatohepatitis (NASH). METHODS: Patients were subjected to standard polysomnography up to 1 week before undergoing bariatric surgery, during which liver biopsy specimens were obtained. The apnea-hypopnea index (AHI) obtained by polysomnography was used to determine the severity of OSA. RESULTS: In total, 183 patients with obesity and biopsy-confirmed NAFLD were included; 49 (27%) had NASH. Patients with NASH had higher AHIs (p = 0.014) and oxygen desaturation indices (p = 0.031), more frequent OSA (p = 0.001), and lower minimum oxygen saturation (p = 0.035). The severity of OSA was directly correlated with the NAFLD activity score (p < 0.001), NASH activity grade (p < 0.001), semi-quantitative indices of lobular inflammation (p = 0.001), and hepatocyte ballooning (p = 0.006). The odds ratios (95% confidence intervals) for NASH and severe NASH (activity grade ≥ 3) associated with moderate-to-severe OSA were 3.85 (1.35-10.94; p < 0.05) and 5.02 (1.66-15.18; p < 0.01), respectively, after adjusting for sex, age, body mass index, waist circumference, insulin resistance values, and metabolic syndrome. CONCLUSIONS: Chronic intermittent hypoxia caused by OSA may aggravate NAFLD and lead to a higher risk of NASH in patients with obesity.

A novel insulin delivery system by ß cells encapsulated in microcapsules.

Introduction: Diabetes is a growing epidemic worldwide and requires effective clinical therapies. In recent years, ß-cell transplantation has emerged as a promising treatment for diabetes, and an encapsulation approach has been proposed to ameliorate this treatment. Methods: Microfluidic technology had been used to generate microcapsules using a porous sodium alginate shell and a core containing ß cells. The microcapsules were transplanted into diabetic mice and the therapeutic effect was measured. Results: Porous hydrogel shell allows exchange of small molecules of nutrients while protecting beta cells from immune rejection, while the core ensures high activity of the encapsulated cells. The glucose control effect of the microcapsules were more durable and better than conventional methods. Discussion: We believe that this system, which is composed of biocompatible porous hydrogel shell and enables highly activity of encapsulated ß cells, can enhance therapeutic efficacy and has promising clinical applications.

Association of Omental Adipocyte Hypertrophy and Fibrosis with Human Obesity and Type 2 Diabetes.

OBJECTIVE: Morphological alterations including adipocyte hypertrophy and fibrosis deposition are important surrogate markers of visceral adipose tissue function, but the relationships between these morphological changes and type 2 diabetes mellitus (T2DM) and impaired insulin sensitivity are poorly defined. METHODS: Omental adipose tissue was obtained from 66 individuals with obesity but without T2DM (OB group), 93 individuals with both obesity and T2DM (T2DM group), and 15 individuals with normal BMI and normal glucose tolerance (NGT group). Adipocyte diameter and volume were measured through pathological section analysis. Pericellular and perilobular fibrosis was determined through picrosirius red staining and immunochemistry, while fibrosis-related genes were tested through gene expression and hydroxyproline content. RESULTS: Compared with the NGT and OB groups, individuals from the T2DM group displayed increased adipocyte diameter and volume levels. Increased adipocyte size (diameter and volume) was positively associated with hyperglycemia and insulin resistance and inversely correlated with insulin sensitivity (using the Matsuda whole-body insulin sensitivity index assessment of insulin sensitivity) and ß-cell function (disposition index 30 and disposition index 120). The fibrosis levels of the OB group were the highest out of the three groups, whereas the fibrosis levels of T2DM individuals were lower than the OB group but higher than the NGT group. Although fibrosis was negatively correlated with T2DM, fibrosis deposition was not remarkably associated with impaired systemic insulin sensitivity and glucose metabolism. CONCLUSIONS: Compared with fibrosis deposition, adipocyte hypertrophy is more closely associated with T2DM and impaired systemic insulin sensitivity.

Are Chinese Patients with Type 2 Diabetes and a Body Mass Index of 27.5-32.5 kg/m2 Suitable for Metabolic Surgery? A One-Year Post-Surgery Study.

INTRODUCTION: The aim of this study was to clarify the efficacy and safety of metabolic surgery in Chinese patients with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 27.5-32.5 kg/m2. METHODS: A total of 99 patients with T2DM were enrolled in this retrospective cohort study. Of these patients, 53 had a BMI of 27.5-32.5 kg/m2 and had undergone metabolic surgery (n = 21) or were on conventional antidiabetic therapy (n = 32)]; 46 had a BMI ≥ 32.5 kg/m2 and all had undergone metabolic surgery. Primary endpoints included the triple endpoint [hemoglobin A1c < 6.5%, low-density lipoprotein cholesterol (LDL-C) < 2.6 mmol/L, and systolic blood pressure (SBP) < 130 mmHg] and successful weight loss 1 year later. Remission of diabetes, glucose and lipid metabolism, medication usage, and adverse events were evaluated. RESULTS: Of patients with BMI 27.5-32.5 kg/m2 undergoing metabolic surgery, 33.33% achieved the composite endpoints, and 100% achieved successful weight loss. This result was similar to that in patients with BMI ≥ 32.5 and better than those with BMI 27.5-32.5 kg/m2 receiving conventional antidiabetic therapy. A significant and similar reduction in BMI, waist circumference, SBP, serum LDL-C, hemoglobin A1c, and uric acid, as well as similar frequency postoperative adverse events, were confirmed in both metabolic surgery groups. Patients with BMI 27.5-32.5 kg/m2 who had undergonemetabolic surgery showed more metabolic improvement than those only receiving medications but they experienced more adverse events. CONCLUSION: A BMI cutoff of 27.5 kg/m2 for metabolic surgery may be suitable for Chinese patients with T2DM.

Ligand-targeted polymerase chain reaction for the detection of folate receptor-positive circulating tumour cells as a potential diagnostic biomarker for pancreatic cancer.

OBJECTIVES: To detect folate receptor (FR)-positive circulating tumour cells (FR+ CTCs) by using ligand-targeted polymerase chain reaction (LT-PCR) in periampullary cancer patients and to investigate the diagnostic value of FR+ CTCs in distinguishing pancreatic cancer (PC) from benign pancreatic disease. MATERIALS AND METHODS: CTCs were enriched from 3 mL of peripheral blood and portal vein blood by immunomagnetic depletion of leucocytes and were then detected by LT-PCR. The diagnostic performance of FR+ CTCs in PC was investigated by receiver-operating characteristic curve analysis. RESULTS: In total, 57 consecutive patients, including 46 patients with PC, five patients with non-pancreatic periampullary cancer (non-PC) and six patients with benign pancreatic diseases, were enrolled. FR+ CTC levels were significantly higher in patients with malignant diseases (PC and non-PC) than in patients with benign pancreatic diseases (P < .01). There was no notable difference in CTC levels between patients with PC and those with non-PC (P > .05). The combination of FR+ CTCs with carbohydrate antigen 19-9 (CA19-9) had better diagnostic efficiency than each of these two markers alone, with high sensitivity (97.8%) and specificity (83.3%). CONCLUSIONS: LT-PCR is feasible and reliable for detecting FR+ CTCs in patients with periampullary cancer. FR+ CTCs, especially when used in combination with CA19-9, have potential as a biomarker for the diagnosis of PC.

Correction to: A newly noninvasive model for prediction of non-alcoholic fatty liver disease: utility of serum prolactin levels.

Following publication of the original article [1], we have been notified that the given name of one of the authors was spelled incorrectly.

A newly noninvasive model for prediction of non-alcoholic fatty liver disease: utility of serum prolactin levels.

BACKGROUNDS: To investigate the value of prolactin (PRL) in diagnosing non-alcoholic fatty liver disease (NAFLD). METHODS: Metabolic parameters and serum PRL levels were measured in 452 males and 421 females, who were randomized to the estimation or the validation group as a 1:1 ratio. Hepatic steatosis was diagnosed via abdominal ultrasound. Variables that significantly associated with NAFLD in univariate analysis were included in multiple logistic regression. We used the receiver operator characteristic (ROC) curves to test the model performance. Besides, 147 patients underwent metabolic and liver biopsy were analyzed to validate the diagnostic value of this model. RESULTS: Body mass index, alanine aminotransferase, prolactin, high density lipoprotein cholesterol and HbA1c were included into models. In males, the area under ROC curve (AUC) was 0.86 (95%CI: 0.82-0.91) for the validation group. With two cut-off points (- 0.79 and 1.71), the sensitivity and specificity for predicting NALFD was 95.2 and 91.1% in the validation group, respectively. In females, the AUC was 0.82 (95%CI: 0.76-0.88) for the validation group. With two cut-off points (- 0.68 and 2.16), the sensitivity and specificity for predicting NALFD was 97.1 and 91.4% in the validation group, respectively. In subjects with liver pathology, the AUC was higher than that of fatty liver index. A positive correlation between the scores of the model and the severities of NAFLD was observed. Importantly, we demonstrated a potential value of this model in predicting nonalcoholic steatohepatitis. CONCLUSION: We established a mathematic model that can conveniently and effectively diagnose the existence and severities of NAFLD.

Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity.

Pathogenic factors driving obesity to type 2 diabetes (T2D) are not fully understood. Group 1 innate lymphoid cells (ILC1s) are effectors of innate immunity and enriched in inflamed tissues. Here we show that the number of adipose ILC1s increases in obese T2D patients and correlates with glycemic parameters and with the number of ILC1s in the blood; circulating ILC1 numbers decrease as a result of metabolic improvements after bariatric surgery. In vitro co-culture experiments show that human adipose ILC1s promote adipose fibrogenesis and CD11c+ macrophage activation. Reconstruction of the adipose ILC1 population in Prkdc-/-IL2rg-/- mice by adoptive transfer drives adipose fibrogenesis through activation of TGFß1 signaling; however, transfer of Ifng-/- ILC1s has no effect on adipose fibrogenesis. Furthermore, inhibiting adipose accumulation of ILC1s using IL-12 neutralizing antibodies attenuates adipose tissue fibrosis and improves glycemic tolerance. Our data present insights into the mechanisms of local immune disturbances in obesity-related T2D.

Metabolic effects and safety of Roux-en-Y gastric bypass surgery vs. conventional medication in obese Chinese patients with type 2 diabetes.

AIM: To assess metabolic effects and safety of Roux-en-Y gastric bypass (RYGB) versus conventional medication (CM) in obese Chinese patients with type 2 diabetes (T2DM). METHODS: This retrospective cohort study included 40 patients who underwent RYGB (mean age 44.1 years, body mass index [BMI] 33.3 kg/m2 ) and 36 patients administered CM (mean age 49.4 years, BMI 32.1 kg/m2 ). The primary endpoint was achievement of the triple endpoint (haemoglobin A1C [HbA1c] < 7.0%, low-density lipoprotein cholesterol < 2.6 mmol/L, and systolic blood pressure < 130 mmHg). Changes in weight, BMI, medication usage, complications, and adverse events were assessed. RESULTS: After 1-year follow-up, 35% of RYGB patients and 8% of CM patients achieved the triple endpoint (P = 0.005). More patients in the RYGB group achieved complete (48% vs 3%, P < 0.001) and partial (23% vs 0%, P = 0.007) remission of diabetes, and complete remission of hypertension (58% vs 24%, P = 0.019). Patients in the RYGB group had greater weight loss and decrease in BMI, waist circumference, fasting and postprandial of blood glucose and insulin levels, HbA1c, blood pressure, triglycerides, and increased high-density cholesterol (P < 0.001- < 0.05). A lower proportion of the RYGB group received antidiabetics, antihypertensives, or antilipemic treatments, and had non-alcoholic fatty liver disease (NAFLD) than the CM group during follow-up. More patients had nutrient deficiency-related diseases in the RYGB group over 1-year follow-up. CONCLUSIONS: For obese Chinese patients with T2DM, RYGB resulted in better metabolic control, greater weight loss, and lower medication usage and NAFLD, but more frequently resulted in diseases related to nutrient deficiency.

The chromatin remodeling protein BRG1 regulates APAP-induced liver injury by modulating CYP3A11 transcription in hepatocyte.

Acetaminophen (APAP) overdose represents the most frequent cause of acute liver failure. The underlying epigenetic mechanism is not fully understood. In the present study we investigated the mechanism whereby the chromatin remodeling protein brahma related gene 1 (Brg1) regulates APAP induced liver injury in mice. We report that hepatocyte-specific deletion of Brg1 attenuated APAP induced liver injury in mice as evidenced by reduced plasma ALT and AST levels, decreased liver necrosis, amelioration of GSH depletion, and prolonged survival. Brg1 regulated APAP-induced liver injury likely by stimulating the transcription of Cyp3a11, a key cytochrome enzyme involved in APAP metabolism. Immunoprecipitation coupled with DNA affinity microarray identified hepatocyte nuclear factor 4 (HNF4) as a novel binding partner for Brg1. HNF4 recruited Brg1 to the Cyp3a11 promoter and formed a complex with Brg1 to trans-activate Cyp3a11. In contrast, BRG1 deficiency attenuated HNF4 binding to the Cyp3a11 promoter and dampened Cyp3a11 transcription. Therefore, our data suggest that Brg1 might play an essential role mediating APAP induced liver injury in vivo.

Prolactin improves hepatic steatosis via CD36 pathway.

BACKGROUND & AIMS: Prolactin (PRL) is a multifunctional polypeptide with effects on metabolism, however, little is known about its effect on hepatic steatosis and lipid metabolism. Herein, we aimed to assess the role of PRL in the development of non-alcoholic fatty liver disease (NAFLD). METHODS: The serum PRL levels of 456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and 85 individuals with liver histology obtained during metabolic surgery (44 female and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals) were evaluated. The expression of the gene encoding the prolactin receptor (PRLR) and signalling molecules involved in hepatic lipid metabolism were evaluated in human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were tested in free fatty acid (FFA)-treated HepG2 cells. RESULTS: Circulating PRL levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9 [range, 5.9-10.3] µg/L; women: 8.7 [range, 6.1-12.4] µg/L) than those with non-NAFLD (men: 9.1 [range, 6.8-13.0] µg/L, p = 0.002; women: 11.6 [range, 8.2-16.1] µg/L, p <0.001). PRL levels in patients with biopsy-proven severe hepatic steatosis were lower compared with those with mild-to-moderate hepatic steatosis in both men (8.3 [range, 5.4-9.5] µg/L vs. 9.7 [range, 7.1-12.3] µg/L, p = 0.031) and women (8.5 [range, 4.2-10.6] µg/L vs. 9.8 [range, 8.2-15.7] µg/L, p = 0.027). Furthermore, hepatic PRLR gene expression was significantly reduced in patients with NAFLD and negatively correlated with CD36 gene expression. In FFA-induced HepG2 cells, PRL treatment or PRLR overexpression significantly reduced the expression of CD36 and lipid content, effects that were abrogated after silencing of PRLR. Furthermore, overexpression of CD36 significantly reduced the PRL-mediated improvement in lipid content. CONCLUSIONS: Our results reveal a novel association between the central nervous system and the liver, whereby PRL/PRLR improved hepatic lipid accumulation via the CD36 pathway. LAY SUMMARY: Our clinical study suggests a negative association between prolactin (PRL)/prolactin receptor (PRLR) and the presence of non-alcoholic fatty liver disease (NAFLD). Using cell experiments, we found that PRL ameliorates hepatic steatosis via the hepatic PRLR and fatty acid translocase (FAT)/CD36, a key transporter of free fatty acid uptake in liver. Our findings suggest a novel approach to improving NAFLD using PRL and PRLR. Clinical trial number: NCT03296605.

[Development of Magnetic Anastomosis Device for Colostomy].

Introduction of a new magnetic anastomosis device for colostomy including its design and operaging principal. The anastomosis device is composed of magnetic base and anastomosis ring. It is convenient for colon and abdominal subcutaneous tissue going together through the magnetic attraction. The colostomy completes with magnetic compression anastomosis. The device has the advantage of making operation easer, reducing the operation steps and can better solve the colostomy ischemic necrosis, colostomy retraction, colostomy joint complications of skin mucous membrane and the skin diease around the colostomy. Patients can real y benefit from this device.

Evaluation of a novel hybrid bioartificial liver based on a multi-layer flat-plate bioreactor.

AIM: To evaluate the efficacy and safety of a hybrid bioartificial liver (HBAL) system in the treatment of acute liver failure. METHODS: Canine models with acute liver failure were introduced with intravenous administration of D-galactosamine. The animals were divided into: the HBAL treatment group (n = 8), in which the canines received a 3-h treatment of HBAL; the bioartificial liver (BAL) treatment group (n = 8), in which the canines received a 3-h treatment of BAL; the non-bioartificial liver (NBAL) treatment group (n = 8), in which the canines received a 3-h treatment of NBAL; the control group (n = 8), in which the canines received no additional treatment. Biochemical parameters and survival time were determined. Levels of xenoantibodies, RNA of porcine endogenous retrovirus (PERV) and reverse transcriptase (RT) activity in the plasma were detected. RESULTS: Biochemical parameters were significantly decreased in all treatment groups. The TBIL level in the HBAL group was lower than that in other groups (2.19 ± 0.55 µmol/L vs 24.2 ± 6.45 µmol/L, 12.47 ± 3.62 µmol/L, 3.77 ± 1.83 µmol/L, P < 0.05). The prothrombin time (PT) in the BAL and HBAL groups was significantly shorter than the NBAL and control groups (18.47 ± 4.41 s, 15.5 ± 1.56 s vs 28.67 ± 5.71 s, 21.71 ± 3.4 s, P < 0.05), and the PT in the HBAL group was shortest of all the groups. The albumin in the BAL and HBAL groups significantly increased and a significantly higher level was observed in the HBAL group compared with the BAL group (27.7 ± 1.7 g/L vs 25.24 ± 1.93 g/L). In the HBAL group, the ammonia levels significantly decreased from 54.37 ± 6.86 to 37.75 ± 6.09 after treatment (P < 0.05); there were significant difference in ammonia levels between other the groups (P < 0.05). The levels of antibodies were similar before and after treatment. The PERV RNA and the RT activity in the canine plasma were all negative. CONCLUSION: The HBAL showed great efficiency and safety in the treatment of acute liver failure.

Microbiological safety of a novel bio-artificial liver support system based on porcine hepatocytes: a experimental study.

BACKGROUND: Our institute has developed a novel bio-artificial liver (BAL) support system, based on a multi-layer radial-flow bioreactor carrying porcine hepatocytes and mesenchymal stem cells. It has been shown that porcine hepatocytes are capable of carrying infectious porcine endogenous retroviruses (PERVs) into human cells, thus the microbiological safety of any such system must be confirmed before clinical trials can be performed. In this study, we focused on assessing the status of PERV infection in beagles treated with the novel BAL. METHODS: Five normal beagles were treated with the novel BAL for 6 hours. The study was conducted for 6 months, during which plasma was collected from the BAL and whole blood from the beagles at regular intervals. DNA and RNA in both the collected peripheral blood mononuclear cells (PBMCs) and plasma samples were extracted for conventional PCR and reverse transcriptase (RT)-PCR with PERV-specific primers and the porcine-specific primer Sus scrofa cytochrome B. Meanwhile, the RT activity and the in vitro infectivity of the plasma were measured. RESULTS: Positive PERV RNA and RT activity were detected only in the plasma samples taken from the third circuit of the BAL system. All other samples including PBMCs and other plasma samples were negative for PERV RNA, PERV DNA, and RT activity. In the in vitro infection experiment, no infection was found in HEK293 cells treated with plasma. CONCLUSIONS: No infective PERV was detected in the experimental animals, thus the novel BAL had a reliable microbiological safety profile.

[New evidence of porcine endogenous retrovirus transmission with new bio-artificial liver system: a experimental study].

OBJECTIVE: To investigate the potential transmissibility of porcine endogenous retrovirus (PERV) from a newly-developed porcine hepatocyte bioartificial liver (BAL) system prior to human clinical trial by using a live canine model. METHODS: Five normal beagles were treated with the new BAL support system for six hours. Samples of plasma from the BAL system and whole blood from the beagles were collected at regular intervals over the six month study period. DNA and RNA were isolated from both the peripheral blood mononuclear cells (PBMCs) and plasma for evaluation by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR, respectively, to detect PERV and the Sus scrofa cytochrome B normalization standard. In addition, RT activity and the in vitro infectivity of the plasma were detected in HEK293 cells. RESULTS: All five beagles remained in stable physical health throughout the treatment and survived until the end of the study. PERV RNA-positivity and RT activity were only detected in the plasma samples from the 3rd BAL treatment cycle. All other samples, including PBMCs and plasma, were negative for PERV RNA, PERV DNA, and RT activity. In addition, none of the sera samples showed in vitro infectivity. CONCLUSION: Application of our BAL system does not lead to PERV transmission.