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Early viral load and recipient IL28B rs12979860 genotype are predictors for progression of hepatitis C after liver transplantation.

Liver Transpl. 2012 Feb 2;

Authors: Graziadei IW, Zoller HM, Schloegl A, Nachbaur K, Pfeiffer KP, Mark W, Mikuz G, Pratschke J, Margreiter R, Vogel W

Abstract

There have been few studies of detailed viral kinetics following liver transplantation (LT) and conflicting data have been reported on viral load and severity of recurrent hepatitis C virus (HCV) disease. This long-term study aimed to examine (1) the impact of HCV RNA levels at specific points in time within the first year and (2) the influence of IL28B genotype on patient outcome and severity of recurrent HCV disease. Viral load was measured at week 2, 4, 12, 24 and 48 following LT and recipient / donor IL28B genotypes of 164 patients were determined. Cox-regression analysis showed that viral load at week 2 was an independent negative predictor of recipient outcome. A week 2 viral load of = 6.0 log(10) IU/mL was significantly associated with reduced patient survival. After a mean follow-up of 6.5 years 21 patients (12.2%) developed either a cholestatic type of HCV recurrence and/or rapid progression to cirrhosis within one year. Multivariate binary regression analysis showed that HCV viremia at week 2 and a non C/C recipient IL28B genotype were independent risk factors for cholestatic recurrent hepatitis C. No predictive factors could be found for the occurrence of recurrent liver cirrhosis at 5- and 10 years following LT. Our study shows that HCV RNA levels at week 2 and recipient IL28B genotype are independent, statistically significant risk factors for post-LT cholestatic hepatitis C emphasizing the importance of viral load monitoring and of IL28B genotyping to identify HCV recipients at risk for severe hepatitis C recurrence. © 2012 American Association for the Study of Liver Diseases.

PMID: 22298465 [PubMed - as supplied by publisher]

Sinusoidal C4d deposits in liver allografts indicate an antibody mediated response: Diagnostic considerations in the evaluation of liver allografts.

Liver Transpl. 2012 Feb 2;

Authors: Kozlowski T, Andreoni K, Schmitz J, Hayashi PH, Nickeleit V

Abstract

There is a paucity of data concerning the correlation of C4d staining in liver allografts with antibody mediated rejection (AMR). Data regarding location and character of C4d deposits in native and allograft liver tissue are inconsistent. We performed C4d immunofluorescence (IF) on 141 fresh frozen liver allograft biopsies and native livers, documented the pattern of C4d IF staining and correlated the findings with the presence of donor specific antibodies (DSA). A linear/granular sinusoidal pattern of C4d IF was noted in 18 of 28 biopsies obtained post transplant in patients with positive crossmatch and detectable DSA (pos XM/DSA). In patients with negative XM/DSA none was C4d positive of 59 tested (p > 0.001). No significant association was found between positive XM/DSA and C4d IF staining in other non-sinusoidal liver compartments. To compare results of sinusoidal C4d staining using IF and two immunohistochemical (IHC) techniques, C4d IHC was performed on 19 liver allograft biopsies in which a sinusoidal pattern of C4d IF had been noted. Sinusoidal C4d IHC was negative in 17 of the 19 cases with 2 having weak and focal staining; both with pos XM/DSA. Portal vein endothelial staining was present in only 1 IF (pos XM/DSA), but 11 IHC stained biopsies (3 of 11 were neg XM/DSA). We conclude that sinusoidal C4d deposits detected in frozen tissue samples by IF in liver allograft recipients are correlated with presence of DSA and antibody mediated allo-response. These observations are similar to findings reported in other solid organ transplants and can provide relevant information for patient management. Further validation of IHC techniques for C4d detection in liver allograft tissue is required. © 2012 American Association for the Study of Liver Diseases.

PMID: 22298469 [PubMed - as supplied by publisher]

Reply.

Liver Transpl. 2012 Jan 30;

Authors: Cholongitas E, Burroughs AK

PMID: 22290606 [PubMed - as supplied by publisher]

Outcomes of living-donor liver transplantation in patients with preoperative type-1 hepatorenal syndrome and acute hepatic decompensation.

Liver Transpl. 2012 Jan 30;

Authors: Chok KS, Fung JY, Chan SC, Cheung TT, Sharr WW, Chan AC, Fan ST, Lo CM

Abstract

This study was to investigate the outcomes of living-donor liver transplantation in patients with preoperative type-1 hepatorenal syndrome (HRS) and acute hepatic decompensation. Prospectively collected data of 104 patients who had fulminant hepatic failure, acute decompensation of cirrhosis, or acute flare of chronic hepatitis B were analyzed. Thirty-three patients (31.7%) had HRS (HRS group) and 71 (68.3%) did not (non-HRS group). The median follow-up period was 60 months. The HRS group had significantly more preoperative intensive care unit admissions (84.8 vs. 60.6%, p=0.01), worse preoperative blood test results (creatinine, 248 vs. 88 umol/L, p>0.001; total bilirubin, 630 vs. 555 umol/L, p=0.001), more hemodialysis (48.5 vs. 0%, p>0.001), more blood transfusion (9 vs. 4 units, p>0.001), longer postoperative intensive care unit stay (8 vs. 4 days, p>0.001), worse postoperative blood test results (creatinine at one year, 108 vs. 96 umol/L, p=0.006), and poorer overall survival (p>0.001). On multivariable analysis, only HRS was associated with poorer overall survival (HR: 8.592, 95% CI: 1.782-41.431, p=0.007). In conclusion, HRS patients, compared with non-HRS patients, had worse postoperative renal function and overall survival. However, their five-year overall survival rate was still nearly 80%, which is satisfactory. Therefore, living-donor liver transplantation can be considered for patients who have acute hepatic decompensation with or without HRS. © 2012 American Association for the Study of Liver Diseases.

PMID: 22290625 [PubMed - as supplied by publisher]

Activation of cyclic adenosine monophosphate-dependent protein kinase a signaling prevents liver ischemia/reperfusion injury in mice.

Liver Transpl. 2012 Jan 30;

Authors: Ji H, Shen X, Zhang Y, Gao F, Huang CY, Chang WW, Lee C, Ke B, Busuttil RW, Kupiec-Weglinski JW

Abstract

Hepatic ischemia and reperfusion injury (IRI) occurs in multiple clinical settings including liver transplantation. Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway inhibits hepatocellular apoptosis and regulates TLR4-triggered inflammation responses in vitro. Here, we examined the function and therapeutic potential of cAMP-PKA activation in a murine (C57/BL6) model of liver warm ischemia (90 min) followed by reperfusion. Liver IRI triggered cAMP-PKA activation, whereas administration of its specific inhibitor, H-89, exacerbated hepatocellular damage. Conversely, Forskolin therapy, which activates PKA by elevating cAMP levels, protected livers from IRI, evidenced by diminished serum ALT and well-preserved tissue architecture. Liver protection rendered by cAMP-PKA stimulation was accompanied by diminished neutrophil and macrophage infiltration/activation, reduced hepatocyte necrosis/apoptosis, yet increased cAMP response element-binding protein (CREB) and augmented IL-10 expression. Neutralization of IL-10 restored liver damage in otherwise IR-resistant Forskolin-treated mice. In vitro, cAMP-PKA activation diminished macrophage TNF-α/IL-6/IL-12 in an IL-10-dependent manner, and prevented necrosis/apoptosis in primary mouse hepatocyte cultures. Our novel findings in a mouse model of liver IRI document the importance of cAMP-PKA signaling in hepatic homeostasis and cytoprotection in vivo. Activation of cAMP-PKA signaling differentially regulates local inflammation and prevents hepatocyte death, providing the rationale for novel therapeutic approaches to combat liver IRI in transplant recipients. © 2012 American Association for the Study of Liver Diseases.

PMID: 22290937 [PubMed - as supplied by publisher]

Development of organ-specific donor risk indices.

Liver Transpl. 2012 Jan 28;

Authors: Akkina SK, Asrani SK, Peng Y, Stock P, Kim R, Israni AK

Abstract

Due to the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival using various combinations of donor and recipient characteristics. We will review the kidney donor risk index (KDRI) and liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The Kidney Donor Risk Index has a potential role in developing new kidney allocation algorithms. The Liver Donor Risk Index allows for greater appreciation of the importance of donor factors, particularly for hepatitis C-positive recipients; as the donor risk index increases, rates of allograft and patient survival among these recipients decrease disproportionately. Use of livers with high donor risk index is associated with increased hospital costs independent of recipient risk factors, and transplanting livers with high donor risk index into patients with Model for End-Stage Liver Disease scores < 15 is associated with lower allograft survival; use of the Liver Donor Risk Index has limited this practice. Significant regional variation in donor quality, as measured by the Liver Donor Risk Index, remains in the United States. We also review other potential indices for liver transplant, including donor-recipient matching and the retransplant donor risk index. While substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival. © 2012 American Association for the Study of Liver Diseases.

PMID: 22287036 [PubMed - as supplied by publisher]

To split or not to split: That is the question.

Liver Transpl. 2012 Jan 28;

Authors:

PMID: 22287492 [PubMed - as supplied by publisher]

Comparison of the 2-step tuberculin skin test and the quantiFERON-TB Gold In-Tube Test for the screening of tuberculosis infection before liver transplantation.

Liver Transpl. 2011 Oct;17(10):1205-11

Authors: Casas S, Muñoz L, Moure R, Castellote J, Guerra MR, Gonzalez L, Andreu A, Rafecas AG, Alcaide F, Santin M

Abstract

The ability of interferon-gamma release assays (IGRAs) to detect latent tuberculosis (TB) infection before liver transplantation (LT)is not well established. The aims of this study were (1) to compare the ability of the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-IT) test (a whole-blood IGRA) to diagnose latent TB infections in patients awaiting LT and (2) to correlate the results with the severity of liver disease. We conducted a prospective, cross-sectional study of patients who were evaluated for LT between July 2008 and July 2010. The 95 patients who were included underwent the 2-step TST and the QFT-IT test. The mean Model for End-Stage Liver Disease (MELD) score was 13.8. Forty-four patients (46.3%) had positive TST results, 42 (44.2%) had positive QFT-IT results, and 2 (2.1%) had indeterminate QFT-IT results. Simultaneous TST and QFT-IT testing yielded a positivity rate of 55.8% [95% confidence interval (CI) = 45.3-65.9] with either test, and the 2-step TST yielded a positivity rate of 46.3% (95% CI = 36.1-56.8); the difference was 9.5% (P = 0.004). In an adjusted analysis, the rates for positive TST results were lower in patients with MELD scores > or = 18 [odds ratio (OR) = 0.2, 95% CI = 0.04-0.7], lower in Child-Pugh-Turcotte (CPT) class C patients versus CPT class A patients (OR = 0.1, 95% CI = 0.02-0.6), and higher in males (OR = 6.4, 95% CI = 1.9-22.0). In contrast, only being male (OR = 3.5, 95% CI = 1.1-11.0) was associated with positive QFT-IT results; no association was found with the MELD score (OR = 0.8, 95% CI = 0.2-2.8) or the CPT class (OR = 0.3; 0.05-1.4). In conclusion, the QFT-IT test is better than the TST for detecting latent TB infection in patients with more advanced liver disease. Our results support the regular use of the QFT-IT test for screening patients with end-stage liver disease for latent TB infection before LT.

PMID: 22279622 [PubMed - in process]

Response to “Comparison of SOFA score to King’s criteria and MELD score in the prognosis of acetaminophen-induced acute liver failure”

Liver Transpl. 2012 Jan 19;

Authors: Craig DG, Simpson KJ

PMID: 22262580 [PubMed - as supplied by publisher]

Pulmonary function in individuals with cystic fibrosis from the U.S. cystic fibrosis foundation registry who had undergone liver transplant.

Liver Transpl. 2012 Jan 23;

Authors: Miller MR, Sokol RJ, Narkewicz MR, Sontag MK

Abstract

Severe liver disease (cirrhosis) affects between 4.5-10% of individuals with cystic fibrosis (CF) and is the third leading cause of death and a significant cause of morbidity. Liver transplantation is an accepted therapy for severe liver disease, but the effects of liver disease and liver transplant on pulmonary function in CF are controversial. The aim of this study was to characterize changes in pulmonary function in liver transplanted CF patients. Using mixed effect models, we analyzed pulmonary function pre- and post-transplant in 168 liver transplanted patients with CF versus 840 non-transplanted CF patients, matched on age, gender, pancreatic status, and bacterial infections from the U.S. CF Foundation Patient Registry Data from 1989-2007. The primary outcome was change in forced expiratory volume in one second (FEV(1) ; percent predicted) in liver transplanted and non-liver transplanted groups for three years prior- and post-transplant. We also compared change in FEV(1) pre- versus post-transplant. In the three years prior to transplant, the liver transplant group had lower initial FEV(1) (p<0.0001) and slower decline (p=0.0003), (71.5±1.9%, +0.1±0.4%/year) compared to the non-transplanted group (79.6±1.3%, -1.3±0.2%/year). There was no difference in FEV(1) decline post-transplant (liver transplant: -1.4±0.4%/year vs. non-liver transplant: -2.1±0.2%/year; p=0.135). Both transplanted (p=0.002) and non-transplanted groups (p=0.001) had a slower FEV(1) decline in the pre-transplant/matched period compared to post-transplant period. Pulmonary function is lower and declines more slowly in CF patients prior to liver transplant compared to their peers who do not receive a transplant, but parallels the decline in non-transplanted individuals after transplant. Liver transplant is neither beneficial nor detrimental to pulmonary function in CF, but returns FEV(1) decline to the same trajectory as matched non-transplanted CF individuals. © 2012 American Association for the Study of Liver Diseases.

PMID: 22271602 [PubMed - as supplied by publisher]