Long-Term Outcomes of Simultaneous Liver-Kidney Transplant Patients with Hepatitis B Compared to with Liver Transplant Alone.

BACKGROUND: The number and survival rate of simultaneous liver-kidney transplant (SLKT) recipients have increased dramatically since 2002. However, the long-term effectiveness of SLKT in patients with hepatitis B is unknown. MATERIAL/METHODS: Forty-six patients who visited the Organ Transplant Center of the Shanghai First People's Hospital between January 2001 and May 2005 had hepatitis B virus infection and renal failure (any degree), and underwent organ transplantation: 21 patients underwent SLKT and 25 patients underwent liver transplant (LT) alone. RESULTS: The 1-, 3-, and 5-year survival rates of SLKT recipients were 90.5%, 81.0%, and 81.0%, respectively. Incidence of acute hepatic allograft rejection between SLKT recipients and LT recipients (33% vs. 16%) did not reach significance (P=0.170). Despite higher infection rate, more prevalent hepatitis B relapse, and longer stay in the intensive care unit, SLKT recipients experienced significantly higher 1-year survival rate (90.5%) compared with LT recipients (60%, P=0.019). Multivariate regression analysis revealed that postoperative renal failure (odds ratio (OR)=48, P=0.003) and Risk/Injury/Failure/Loss/End-stage (RIFLE) stage (OR=8, P=0.012) were independent risk factors for postoperative death after LT. CONCLUSIONS: SLKT in patients with hepatitis B had higher early-stage infection rate, but had a higher long-term survival rate compared with the LT group. Although the incidence of postoperative hepatitis B relapse in SLKT recipients was higher, timely and reasonable treatment can ensure long-term survival of patients. Worsening RIFLE stage of recipients can predict high mortality when only given LT. SLKT might be a better choice for RIFLE stage 2 or 3 patients than LT alone.

Hepatopoietin Cn reduces ethanol-induced hepatoxicity via sphingosine kinase 1 and sphingosine 1-phosphate receptors.

The hepatic growth factor hepatopoietin Cn (HPPCn) prevents liver injury induced by carbon tetrachloride in rats. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK). S1P and S1P receptors (S1PRs) are involved in liver fibrogenesis and oxidative injury. This work sought to understand the mechanism by which SphK/S1P/S1PRs are involved in the protective effects of HPPCn on ethanol-induced liver injury and fibrosis. Transgenic mice with liver-specific overexpression of HPPCn (HPPCn(liver) (+/+)) were generated. Two ethanol feeding protocols were used to assess the protective effect of HPPCn on acute and chronic liver injury in mice. Specific inhibitors of S1PR1, S1PR2 and S1PR3 and siRNA were used to examine the roles of S1PRs in hepatic stellate cell (HSC) activation and hepatocyte apoptosis. Increased HPPCn expression in transgenic mice attenuated fibrosis induced by ethanol and carbon tetrachloride (CCl4). Treatment with recombinant human HPPCn prevented human hepatocyte apoptosis and HSC activation. JTE-013 or S1PR2-siRNA attenuated the effect of HPPCn on HSC activation induced by tumour necrosis factor-α (TNF-α). Consistent with the effect of N,N-dimethylsphingosine (DMS), suramin or S1PR3-siRNA treatment blocked HPPCn-induced Erk1/2 phosphorylation in human hepatocytes. This study demonstrated that HPPCn attenuated oxidative injury and fibrosis induced by ethanol feeding and that the SphK1/S1P/S1PRs signalling pathway contributes to the protective effect of HPPCn on hepatocyte apoptosis and HSC activation.

Case report: living donor liver transplantation for giant hepatic hemangioma using a right lobe graft without the middle hepatic vein.

Hepatic hemangioma patients with Kasabach-Merritt syndrome have reportedly been cured by liver transplantation. However, liver transplantation as a potential cure for a stable patient without Kasabach-Merritt syndrome remains debatable. We report the case of a 27-year-old female patient with a giant hepatic hemangioma. The hemangioma measured 50×40×25 cm in size and weighed 15 kg, which is the largest and heaviest hemangioma reported in the literature. The patient showed jaundice, ascites, anemia, and appetite loss; but no disseminated intravascular coagulation was observed through laboratory findings. We successfully operated using a right lobe graft without the middle hepatic vein from a 55-year-old donor. At the long-term follow-up, the patient experienced two acute rejections, which were confirmed by biopsy. However, the patient still survives with good graft function after 50 months.

A new RNA-seq method to detect the transcription and non-coding RNA in prostate cancer.

Prostate cancer is a big killer in many regions especially American men, and this year, the diagnosed rate rises rapidly. We aimed to find the biomarker or any changing in prostate cancer patients. With the development of next generation sequencing, much genomic alteration has been found. Here, basing on the RNA-seq result of human prostate cancer tissue, we tried to find the transcription or non-coding RNA expressed differentially between normal tissue and prostate cancer tissue. 10 T sample data is the RNA-seq data for prostate cancer tissue in this study, we found the differential gene is TFF3-Trefoil factor 3, which was more than seven fold change from prostate cancer tissue to normal tissue, and the most outstanding transcript is C15orf21. Additionally, 9 lncRNAs were found according our method. Finally, we found the many important non-coding RNA related to prostate cancer, some of them were long non-coding RNA (lncRNA).

Comparison of clinical outcome of low-dose and high-dose rabbit antithymocyte globulin induction therapy in renal transplantation: a single-center experience.

BACKGROUND: To explore a better balance between efficacy and complications, we respectively compared the clinical outcome of low-dose and high-dose rATG induction therapy with a control group in renal transplantations from March 2009 to March 2012. MATERIAL AND METHODS: 281 kidney transplant recipients were included in 3 groups. The low-dose group (n=39) received rATG 1 mg/kg on the first day and 0.5 mg/kg on the next consecutive 3 days post-transplantation. The high-dose group (n=30) received rATG 1 mg/kg for 6 days. The control group (n=212) received no induction therapy. All patients were treated with Prednisolone, Mycophenolate mofetil, cyclosporine A, or tacrolimus capsules. Acute rejection rates, renal function, CMV infection, patient survival, and the adverse effects of rATG were reviewed. RESULTS: The acute rejection rate was significantly lower in the rATG group compared with the control group (low-dose 17.9% vs. control 35.4%, P=0.03, and high-dose 16.7% vs. control 35.4%, P=0.038). There was no statistically significant difference in 3-year survival and graft survival rates among the groups. Renal function early recovery was similar in the rATG and the control group. The CMV infection rate in the high-dose rATG group was higher than the low-dose rATG and the control group (p=0.037 and p=0.002, respectively). rATG induction therapy was associated with thrombocytopenia in our series, especially in the high-dose rATG group. CONCLUSIONS: Low-dose rATG induction may be superior to high-dose rATG induction therapy in renal transplantation.

Prevalence and risk factor for MDR-GNB infection in liver transplantation.

Liver transplantation (LT) has emerged as a viable therapy for various end-stage liver diseases. Multi-drug resistant Gram-negative bacilli (MDR-GNB) have emerged as predominant pathogens. The prevalence of MDR-GNB infection has been increasing in LT recipients, especially in early post-LT stages. MDR-GNB infection has become a main cause of death following LT. Since key elements of MDR-GNB infection after LT mainly include the pre-LT severity of underlying disease, technical problems, acute rejection, and so on, appropriate measures, such as improvement of LT technology and management, restriction of antibiotic use and immunosuppressive therapy advancement, should be commenced to prevent and control the occurrence of MDR-GNB infection. A better understanding of the prevalence of and risk factors for MDR-GNB infection complications is needed to improve quality of life and survival rate after LT.

Multidrug-resistant gram-negative bacterial infections after liver transplantation - spectrum and risk factors.

OBJECTIVES: Gram-negative bacilli infections, especially multidrug-resistant gram-negative bacilli infections, are the leading cause of high mortality after liver transplantation. This study sought to investigate the type of infection, infection rate, pathogenic spectrum, antibiotic-resistance profile, risk factors, and epidemiology of multidrug-resistant gram-negative bacterial infection. METHODS: A retrospective cohort study was conducted and data of 217 liver transplant patients receiving cadaveric livers between January 2007 and April 2010 were analyzed. Antibiotic susceptibility was determined by minimum inhibitory concentration test. Extended-spectrum and metallo-ß-lactamase assays were used to analyze ß-lactamase-produced isolates, and repetitive-sequence polymerase chain reaction was used to differentiate bacterium subspecies. RESULTS: Sixty-seven isolates of multidrug-resistant gram-negative bacteria were isolated from 66 infected liver transplant patients. Stenotrophomonas maltophilia (100%, 8/8), Klebsiella pneumoniae (61.5%, 8/13), Enterobacter cloacae (75%, 3/4) and Escherichia coli (81.3%, 13/16) were the most common extended-spectrum ß-lactamase-producing bacilli. Metallo-ß-lactamase expressing isolates were identified as S. maltophilia (100%, 8/8), Pseudomonas aeruginosa (83.3%, 5/6), Acinetobacter baumannii (95%, 19/20). Significant independent risk factors for multidrug-resistant gram-negative infection were extended use of pre-transplant broad-spectrum antibiotics (OR 9.027, P=0.001) and prolonged (≧72h) endotracheal intubation (OR 3.537, P=0.033). CONCLUSIONS: To reduce the risk of acquiring MDR gram-negative bacillus infections after liver transplant, control measures are required to limit the use of prophylactic antibiotic in preventing infection during liver transplant and to shorten endotracheal intubation time.