Association between donor and recipient Interleukin-18 gene polymorphisms and the risk of infection after liver transplantation.

PURPOSE: The purpose of this study was to retrospectively evaluate the association between Interleukin-18 (IL-18) gene polymorphisms of the donor and recipient in liver transplant patients with bacterial infections. METHODS: Five single nucleotide polymorphisms (SNPs) (rs7106524, rs5744247, rs1946518, rs549908 and rs187238) of the IL-18 gene from the donors were genotyped and their association with post-operative bacterial infections was evaluated in liver transplant patients (N=113). A second independent group of liver transplant patients from a different organ transplant centre was also recruited for validation purposes (N=44). RESULTS: IL-18 mRNA mean expression levels and protein levels were significantly lower in liver transplant patients with bacterial infections. For the donor SNP rs1946518, more recipients carried the A allele in the bacterial-infected group than the uninfected group (61.4% vs 39.7%; P ≤0.002). The mean IL-18 mRNA expression and protein levels were significantly lower in the transplanted livers of recipients carrying the rs1946518 AA genotype compared with those from recipients with CC genotype (3.64, 3.33 vs. 2.75, P≤0.048). The A allele of rs1946518 also resulted in lower luciferase activity than the C allele in a reporter assay. The area under ROC curve indicated that the rs1946518 SNP genotype in the donor liver predicted an increased risk of bacterial infection after liver transplantation (AUROC>0.82). CONCLUSIONS: These findings indicate that the IL-18 rs1946518 SNP in the donor liver is a risk factor for developing bacterial infection after liver transplantation.

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.

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.

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.

Effect of ursodeoxycholic acid administration after liver transplantation on serum liver tests and biliary complications: a randomized clinical trial.

BACKGROUND/AIMS: Endogenous hydrophobic bile acids are suspected to be one of the pathogenetic factors of biliary complications after orthotopic liver transplantation (OLT). This study was designed to investigate the effects of hydrophilic ursodeoxycholic acid (UDCA) administration early after OLT on serum liver tests and the incidence of biliary complications. METHODS: 112 adult patients undergoing OLT from donation after cardiac death (DCD) were randomized to UDCA (13-15 mg/kg/day for 4 weeks; 56 patients) or placebo (56 patients). Serum liver tests and serum bile acids of all patients and biliary bile acids in patients with T-tube drainage were determined during the 4 weeks after OLT. Biliary complications as well as patient and graft survival were analyzed during a mean follow-up of 41.6 months. RESULTS: UDCA treatment decreased ALT, AST and GGT (p < 0.05) during the 4 weeks after OLT and the incidence of biliary sludge and casts within the 1st year (p < 0.05). However, no differences in the incidence of other biliary complications as well as 1-, 3- and 5-year graft and patient survival were observed. CONCLUSIONS: UDCA administration early after DCD-OLT improves serum liver tests and decreases the incidence of biliary sludge and casts within the 1st postoperative year but does not affect overall outcome up to 5 years after OLT.

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.

[Effects of non-bioartificial liver support system on Gc-globulin in patients with liver failure].

OBJECTIVE: To investigate the effects of artificial liver support system(plasma exchange combined with continuous veno - venous hemodiafiltration, PE + CVVHDF) on Gc globulin in patients with liver failure. METHODS: 81 patients with liver failure were divided into 4 groups according to the treatment protocols and indicators such as liver function and clinical symptoms. Totally 29 effective cases and 14 ineffective cases in the ALSS group versus 15 effective cases and 23 ineffective cases in the medical group were included. Finally the changes of Gc globulin were observed in four subgroups before and after treatment. The correlation between Gc globulin and IL-10, IL-4, IL-18, TNFa, endotoxin, NO, sVCAM-1and sICAM-1were analyzed by Pearson correlation analysis. RESULTS: The effectiveness rate was 67.44% in ALSS group and 34.21% in the medical treatment (P less than 0.01). Gc globulin, one of liver cell protection proteins was notably increased following the artificial liver treatment as compared with the increase in the medical treatment (P less than 0.01). The time-response curve of Gc globulin level had a significant upward trend in the effective group as compared to no significant rise in the ineffective group. Moreover, the Gc globulin was negatively correlated with IL-4, IL-18, TNFa, SVCAM-1, SICAM-1 and NO. In contrast, no correlation existed between Gc globulin and IL-10. The treatment with artificial liver can improve the outcome of the patients with liver failure. The level of Gc globulin was correlated with the curative effect and thus may be used as a potential indicator for curative effect forcast in the patients with liver failure.

Assessment of islet graft survival using a 3.0-Tesla magnetic resonance scanner.

Some studies have recently described a magnetic resonance (MR) method for detection of iron-labeled islets transplanted into the liver. The aim of this work was to assess the survival of islet graft using a clinical 3.0-T scanner. Islets from Lewis rats were cultured in the presence of iron oxide nanoparticles. One thousand iron-labeled islets were transplanted into the portal vein of diabetic rats. Blood glucose levels were measured daily through day 14 post-transplantation. MR imaging of the same section of the liver was performed on 1, 3, 7, 10, and 14 days post-transplantation. The labeled islets were visualized by MR as distinct hypointensive spots distributed in the liver. There was a linear correlation between the relative value of delta R2* relaxometry multiplied by the cubic diameter (relative value of the iron volume, Ir) and blood glucose level on 14 days post-transplantation in allograft and isograft (P<0.05). The relative value of delta R2* relaxometry, diameter, and number of hypointensive spots could be calculated to assess the survival of the iron-labeled islet grafts. Assessment of iron-labeled islet grafts using a clinical 3.0-T magnetic resonance scanner represents a useful method that has potential for clinical use.

[Therapeutic effect of liver transplantation on acute liver failure].

OBJECTIVE: To evaluate the short-term and long-term outcomes of emergent liver transplantation recipients with acute liver failure and to identify factors that influenced these outcomes. METHODS: 318 consecutive patients who underwent liver transplantations between January 2001 and December 2004 were analyzed retrospectively (all the cases were followed up to December 2005). According to UNOS grading scale, all recipients preoperative status were evaluated. 54 patients were acute liver failure (Group I, UNOS 1 and 2A), and the other 264 cases were chronic liver diseases (Group II, UNOS 2B and 3). The postoperative effects in different groups were compared, including the survival rates, incidences of complications, rates and causes of retransplantation, rates and causes of death. RESULTS: Comparing UNOS2B/3 to UNOS1/2A, the perioperative mortality were 3.7%; 22.6%, the rate of complications 16.7%; 55.6%, 1 year survival rate 91.3%; 74.1%, 3 year survival rate 86.4%; 68.5%, the retransplantation rate 1.1%; 18.5% respectively. CONCLUSION: Since the technique of liver transplant is very advanced, the effect of surgery is mainly depended on the function of liver and other organs in patients. The recipients with UNOS2B/3 have better short-term and long-term outcomes as comparing to UNOS1/2A. In addition, the recipients with UNOS1/2A are burdened with much higher mortality.

[The effects of p16 and Rb protein expression and NF-kappaB activity on hepatocarcinogenesis].

OBJECTIVE: To study the relation between the expression of p16 protein and Rb (retinoblastoma) protein and the transcription activity of nuclear factor-kappaB (NF-kappaB) and their roles in hepatocarcinogenesis. METHODS: p16 protein and Rb protein in 35 hepatocellular carcinoma (HCC) tissues and the peritumoral areas (more than 3 cm away from the tumor) were examined by Western blot analysis. The transcription activity of NF-kappaB in these tissues was detected by electrophoretic mobility shift assays (EMSA) and super-shift assays. RESULTS: The expression rates of p16 protein in the HCC tissues and peritumoral areas were 37% (13/35) and 48% (17/35) respectively (P < 0.01). The expression rates of Rb protein in the HCC tissues and peritumoral areas were 34% (12/35) and 74% (26/35) respectively (P < 0.01). The emergence rates of NF-kappaB with transcription activity in the HCC tissues and peritumoral areas were 77% (27/35) and 85% (30/35) respectively (P > 0.05). Four out of the 10 (40%) HCC tissues expressing p16 protein and Rb protein simultaneously turned up NF-kappaB with transcription activity, while 18 out of the 20 (90%) HCC tissues not expressing both p16 and Rb proteins turned up NF-kappaB with transcription activity (P < 0.05). 13 out of the 17 (76%) peritumoral areas expressing two kinds of proteins simultaneously turned up NF-kappaB with transcription activity and the emergence rate of NF-kappaB with transcription activity in the peritumoral areas not expressing the two kinds of proteins was 89% (8/9) (P > 0.05). CONCLUSION: Dysfunction of p16 is the early event of hepatocarcinogenesis and dysfunction of Rb is the later event in this course. There is a positive correlation between p16 protein and Rb protein in HCC tissues. The loss of expression of p16 and Rb proteins plays important roles in the carcinogenesis and progression of HCC by affecting NF-kappaB transcription activity which may prevent hepocyctes from apoptosis, besides disturbing cell cycle.