Does the donor mannose-binding lectin genotype really predict the risk of bacterial infections after liver transplantation?

Abstract

We read with interest the reviews by Ghouri et al. 1 and Martinez et al. 2 Ghouri et al. analyzed the association of nonalcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) and concluded that although a diagnosis of NAFLD should prompt diabetes screening, it is insufficient for considering patients to be at high risk for CVD. Martinez et al. evaluated noninvasive methods for assessing liver fibrosis and recommended that those tests with the highest diagnostic accuracy be validated against liver biopsy to facilitate their implementation in clinical practice.We meta-analyzed prospective data regarding the natural history of NAFLD and studies assessing the diagnostic accuracy of noninvasive methods for liver disease severity against liver biopsy in NAFLD, and we reached the following conclusions 3 :1. The two NAFLD histological subtypes, simple steatosis (SS) and nonalcoholic steatohepatitis (NASH), have different risks of liver-related complications: SS progresses to cirrhosis in less than 5% of cases; NASH progresses to cirrhosis in 10% to 15% of cases over 10 years and in 25% to 30% of cases in the presence of advanced fibrosis. 2. NAFLD patients have a 1.44-to 2.05-fold higher rate of CVD (depending on whether the diagnosis is based on an aminotransferase elevation or radiological/histological criteria) than the general population; restricting the analysis to studies adjusting for metabolic syndrome did not change the risk. Importantly, CVD mortality did not differ among NAFLD histological subtypes. ; restricting the analysis to studies adjusting for metabolic syndrome did not change the risk. Whether the risk of diabetes differs among NAFLD histological subtypes remains unclear: in a communitybased study, the 13-year incidence of diabetes was 2.98-fold higher in NASH patients versus SS patients. 3According to our analysis, a diagnosis of NAFLD should prompt a thorough three-focus assessment of cardiovascular, metabolic, and liver-related risks (Table 1). 4 Liver-related risk assessment remains problematic because it requires liver histology. Three noninvasive methods have been extensively validated: enzyme-linked immunosorbent assay-detected cytokeratin 18 fragments (9 studies enrolling 856 participants) for the detection of NASH and the NAFLD fibrosis score (13 studies enrolling 3064 participants) and FibroScan (6 studies enrolling 563 participants) for the detection of advanced fibrosis. We believe that these methods should be promptly implemented in diagnostic algorithms to select patients for liver biopsy in routine clinical practice while we continue to search for the ideal noninvasive marker.

Genetic polymorphisms in innate immunity receptors do not predict the risk of bacterial and fungal infections and acute rejection after liver transplantation

“…In conclusion, our data together with a previously published study show that neither risk of bacterial and fungal infections nor risk of acute rejection after LT is significantly influenced by 50 common genetic polymorphisms in innate immunity receptors. Transplant‐related variables may play a superior role as risk factors for bacterial and fungal infections and acute rejection, compared to the genetic polymorphisms tested.…”

“…To prevent the pitfall of false‐positive associations caused by a type I error, we repeated the observed associations in a second cohort from the same liver transplant center. We did not include MBL polymorphisms in this study, as we have previously observed that these are not associated with infections in LT patients from our center . Several polymorphisms were significantly associated with the risk of bacterial or fungal infection or acute rejection after LT in our identification cohort, but none of these associations was confirmed in the validation cohort.…”

Impact of MBL2 gene polymorphisms on the risk of infection in solid organ transplant recipients: A systematic review and meta-analysis

“…After removing of duplicate studies and detailed evaluation of titles and abstracts, 45 articles were fully assessed for eligibility . Eleven studies (Table ) fulfilled the inclusion and exclusion criteria and were finally included in the present study (PRISMA flow chart shown in Figure ). Two further studies had to be excluded due to the lack of relevant data despite repeated attempts to contact corresponding authors to obtain additional details.…”

“…These 11 studies comprised a total of 1858 SOT recipients: 1494 (80.4%) liver transplant (LT) recipients, 317 (17.1%) kidney or kidney‐pancreas (KT), recipients and 47 (2.5%) lung transplant (LuT) recipients. Although only one study detailed the ethnicity of the genotyped participants, most patients (87.9% [1634/1858]) came from studies performed in countries with predominant Caucasian populations . All but two studies assessed the impact of polymorphisms in both the promoter and exon 1 regions of the MBL2 gene (Table ).…”

“…The presence of low or deficient serum MBL levels has been associated with an increased risk of infectious complications after SOT, particularly for cytomegalovirus (CMV) infection, although discrepant results can be also found . In view of the major role played by genetic determinants, the potential impact of variant alleles or haplotypes of SNPs located in the MBL2 gene has also been investigated, with most but not all studies reporting an association with the occurrence of posttransplant infection.…”