[Show abstract][Hide abstract] ABSTRACT: The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013.
The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report.
Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004-2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively.
The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR).
[Show abstract][Hide abstract] ABSTRACT: Research related to primary sclerosing cholangitis (PSC) has since 1980 been a major activity at the Oslo University Hospital Rikshospitalet. The purpose of this publication is to describe the development of this research, the impact of this research on the clinical handling of the patients, and finally to describe what we believe are the most urgent, remaining problems to be solved. During the early years, our research dealt primarily with clinical aspects of the disease. The concomitant inflammatory bowel disease (IBD) seen in most patients with PSC was a major interest and we also started looking into genetic associations of PSC. Prognosis, malignancy development and treatment with special emphasis on transplantation have later been dealt with. These activities has had impact on several aspects of PSC management; when and how to diagnose PSC and variant forms of PSC, how to handle IBD in PSC and how to deal with the increased rate of malignancy? The problems remaining to be solved are many. What is the role of the gut and the gut microbiota in the development of PSC? Do the PSC patients have an underlying disturbance in the bile homeostasis? And how does the characteristic type of fibrosis in PSC develop? The genetic studies have supported a role for the adaptive immune system in the disease development, but how should this be dealt with? Importantly, the development of malignancy in PSC is still not understood, and we lack appropriate medical treatment for our patients.
Scandinavian Journal of Gastroenterology 04/2015; DOI:10.3109/00365521.2015.1028996 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a need to determine biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC). We aimed to evaluate the prognostic utility of the enhanced liver fibrosis (ELF) score in Norwegian PSC patients. Serum samples were available from 305 well-characterized large-duct PSC patients, 96 ulcerative colitis patients, and 100 healthy controls. The PSC patients constituted a derivation panel (recruited 1992-2006 [n=167]; median age 41 years, 74% male) and a validation panel (included 2008-2012 [n=138]; median age 40 years, 78% male). We used commercial kits to analyze serum levels of hyaluronic acid, TIMP1 and PIIINP and calculated ELF scores by the previously published algorithm. Results were also validated by analysis of ELF®Tests using the ADVIA Centaur XP system and its commercially available reagents. We found that PSC patients stratified by the ELF score tertiles exhibited significantly different transplant-free survival in both panels (P<0.001), with higher scores associated with shorter survival, further confirmed in the validation panel stratified by ELF®Test tertiles (P=0.003). The ELF®Test distinguished between mild and severe disease defined by clinical outcome (transplantation or death) with an area under the curve (AUC) of 0.81 (95% confidence interval [CI] [0.73, 0.87]) and optimal cut-off 10.6 (sensitivity 70.2%, specificity 79.1%). In multivariate Cox regression analysis in both panels, ELF score (hazard ratio [HR] 1.9; 95% CI [1.4, 2.5] and 1.5; 95% CI [1.1, 2.1], respectively) was associated with transplant-free survival independently from the Mayo risk score (HR 1.3; 95% CI [1.1, 1.6]) and 1.6; 95% CI [1.2, 2.1], respectively). The ELF®Test correlated with ultrasound elastography in separate assessments. Conclusion: The ELF score is a potent prognostic marker in PSC, independent from the Mayo risk score. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: ABO-incompatible (ABOi) liver transplantation (LT) with deceased donor organs is performed occasionally when no ABO-compatible (ABOc) graft is available. From 1996 to 2011, 61 ABOi LTs were performed in Oslo and Gothenburg. Median patient age was 51 years (range 13-75); 33 patients were transplanted on urgent indications, 13 had malignancy-related indications, and 8 received ABOi grafts for urgent retransplantations. Median donor age was 55 years (range 10-86). Forty-four patients received standard triple immunosuppression with steroids, tacrolimus, and mycophenolate mofetil, and forty-four patients received induction with IL-2 antagonist or anti-CD20 antibody. Median follow-up time was 29 months (range 0-200). The 1-, 3, 5-, and 10-year Kaplan-Meier estimates of patient - (PS) and graft survival (GS) were 85/71%, 79/57%, 75/55%, and 59/51%, respectively, compared to 90/87%, 84/79%, 79/73%, and 65/60% for all other LT recipients in the same period. The 1-, 3-, 5-, and 10-year GS for A2 grafts were 81%, 67%, 62%, and 57%. In conclusion, ABOi LT performed with non-A2 grafts is associated with inferior graft survival and increased risk of rejection, vascular and biliary complications. ABOi LT with A2 grafts is associated with acceptable graft survival and can be used safely in urgent cases. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Transplant International 03/2015; 28(7). DOI:10.1111/tri.12552 · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have previously shown that gastrointestinal cancers display similar epigenetic aberrations. In a recent study, we identified frequently methylated genes for cholangiocarcinoma (CDO1, DCLK1, SFRP1 and ZSCAN18), where one of these genes, DCLK1, was also confirmed to be highly methylated in colorectal cancer. The aim of the present study was to determine whether these four genes, in addition to one gene found to be methylated in colon cancer cell lines (ZNF331), are commonly methylated across gastrointestinal malignancies, as well as explore their role as potential biomarkers. Quantitative methylation specific PCR (qMSP) of colorectal cancer (n = 164) and normal colorectal mucosa (n = 106) samples showed that all genes were frequently methylated in colorectal cancer (71-92%) with little or no methylation in normal mucosa (0-3%). Methylation of minimum two of these five genes identified 95% of the tumors with a specificity of 98%, and an area under the receiver operating characteristics curve (AUC) of 0.98. For gastric (n = 25) and pancreatic (n = 20) cancer, the same panel detected 92% and 90% of the tumors, respectively. Seventy-four cancer cell lines were further analyzed by qMSP and real time RT-PCR. In addition to the previously reported DCLK1, a high negative correlation between promoter DNA methylation and gene expression was observed for CDO1, ZNF331 and ZSCAN18. In conclusion, the high methylation frequency of these genes in colorectal- as well as in gastric-, pancreatic- and bile duct cancer confirmed an epigenetic similarity between gastrointestinal cancer types, and simultaneously demonstrated their potential as biomarkers, particularly for colorectal cancer detection.
International Journal of Cancer 02/2015; 136(4). DOI:10.1002/ijc.29039 · 5.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased serum levels of immunoglobulin (Ig)G4 have been reported in 9%–15% of patients with primary sclerosing cholangitis (PSC); it is not clear whether this increase contributes to pathogenesis. We performed genetic analyses of the HLA complex in patients with PSC from Norway, Sweden, and the United States. We found an association between levels of IgG4 above the upper reference limit and specific HLA haplotypes. These patients had a significantly lower frequency of the strongest PSC risk factor, HLA-B*08, than patients without increased IgG4, and significantly higher frequencies of HLA-B*07 and DRB1*15. HLA genotype might therefore affect the serum concentration IgG4, and increased IgG4 might be a marker of a distinct phenotype of PSC.
[Show abstract][Hide abstract] ABSTRACT: Purpose: Early detection of the highly aggressive malignancy, cholangiocarcinoma (CCA), remains a challenge, but has the potential to render the tumor curable by surgical removal. This study evaluates a biomarker-panel for the diagnosis of CCA by DNA methylation analyses of biliary brush samples.Experimental design: The methylation status of 13 candidate genes (CDO1, CNRIP1, DCLK1, FBN1, INA, MAL, SEPT9, SFRP1, SNCA, SPG20, TMEFF2, VIM, and ZSCAN18), were investigated in 93 tissue samples (39 CCAs and 54 non-malignant controls) using quantitative methylation specific PCR. The 13 genes were further analyzed in a test series of biliary brush samples (15 CCAs and 20 non-malignant primary sclerosing cholangitis (PSC) controls), and the methylation status of the four best performing markers were validated (34 CCAs and 34 PSC controls). Receiver operating characteristics (ROC) curve analyses were used to evaluate the performance of the individual and combination of biomarkers.Results: The 13 candidate genes displayed a methylation frequency of 26-82% in tissue samples. The four best performing genes (CDO1, CNRIP1, SEPT9, and VIM) displayed individual methylation frequencies of 45-77% in biliary brushes from CCA patients. Across the test and validation biliary brush series, this four-gene biomarker-panel achieved a sensitivity of 85% and specificity of 98%, with an area under the ROC curve of 0. 944.Conclusions: We report a straightforward biomarker assay with high sensitivity and specificity for CCA, outperforming standard brush cytology. We suggest that the biomarker-panel, potentially in combination with cytological evaluation, may improve CCA detection, particularly among PSC patients. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Genetic variants within the major histocompatibility complex (MHC) represent the strongest genetic susceptibility factors for primary sclerosing cholangitis (PSC). Identifying the causal variants within this genetic complex represents a major challenge due to strong linkage disequilibrium and an overall high physical density of candidate variants. We aimed to refine the MHC association in a geographically restricted PSC patient panel.
A total of 365 PSC cases and 368 healthy controls of Scandinavian ancestry were included in the study. We incorporated data from HLA typing (HLA-A, -B, -C, -DRB3, -DRB1, -DQB1) and single nucleotide polymorphisms across the MHC (n = 18,644; genotyped and imputed) alongside previously suggested PSC risk determinants in the MHC, i.e. amino acid variation of DRβ, a MICA microsatellite polymorphism and HLA-C and HLA-B according to their ligand properties for killer immunoglobulin-like receptors. Breakdowns of the association signal by unconditional and conditional logistic regression analyses demarcated multiple PSC associated MHC haplotypes, and for eight of these classical HLA class I and II alleles represented the strongest association. A novel independent risk locus was detected near NOTCH4 in the HLA class III region, tagged by rs116212904 (odds ratio [95% confidence interval] = 2.32 [1.80, 3.00], P = 1.35×10-11).
Our study shows that classical HLA class I and II alleles, predominantly at HLA-B and HLA-DRB1, are the main risk factors for PSC in the MHC. In addition, the present assessments demonstrated for the first time an association near NOTCH4 in the HLA class III region.
PLoS ONE 12/2014; 9(12):e114486. DOI:10.1371/journal.pone.0114486 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dramatic improvement in first-year outcomes post-liver transplantation (LT) has shifted attention to long-term survival, where efforts are now needed to achieve improvement. Understanding the causes for premature death is a prerequisite for improving long-term outcome. Overall and cause-specific mortality of 3299 Nordic LT patients (1985-2009) having survived 1 year post-LT were divided by expected rates in the general population, adjusted for age, sex, calendar time, and country to yield standardized mortality ratios (SMRs). Data came from the Nordic Liver-Transplant Registry and WHO mortality-indicator database. Stagnant patient survival rates >1 year post-LT were 21% lower at 10 years than expected survival for the general population. Overall SMR for death before age 75 (premature mortality) was 5.8 (95%CI 5.4-6.3), with improvement from 1985-1999 to 2000-2010 in hepatitis C (HCV) (SMR change 23.1-9.2), hepatocellular carcinoma (HCC) (SMR 38.4-18.8), and primary sclerosing cholangitis (SMR 11.0-4.2), and deterioration in alcoholic liver disease (8.3-24.0) and acute liver failure (ALF) (5.9-7.6). SMRs for cancer and liver disease (recurrent or transplant-unrelated disease) were elevated in all indications except primary biliary cirrhosis (PBC). Absolute mortality rates underestimated the elevated premature mortality from infections (SMR 22-693) and kidney disease (SMR 13-45) across all indications, and from suicide in HCV and ALF. SMR for cardiovascular disease was significant only in PBC and alcoholic liver disease, owing to high mortality in the general population. Transplant-specific events caused 16% of deaths.Conclusion: standardized premature mortality provided an improved picture of long-term post-LT outcome, showing improvement over time in some indications, not revealed by overall absolute mortality rates. Causes with high premature mortality (infections, cancer, kidney and liver disease, and suicide) merit increased attention in clinical patient follow-up and future research. (Hepatology 2014;)
[Show abstract][Hide abstract] ABSTRACT: To investigate influence of human leukocyte antigen (HLA) and killer immunoglobuline-like receptor (KIR) genotypes on risks of acute rejection (AR) after liver transplantation (LTX).
In this retrospective study we included 143 adult donor-recipient pairs with a minimum of 6 mo follow-up after LTX for whom DNA was available from both donor and recipients. Clinical data, all early complications including episodes and severity of AR and graft/patient survival were registered. The diagnosis of AR was based on clinical, biochemical and histological criteria. All suspected episodes of AR were biopsy confirmed. Key classical HLA loci (HLA-A, HLA-B, HLA-C and HLA-DRB1) were genotyped using Sanger sequencing. 16 KIR genes were genotyped using a novel real time PCR approach which allows for determination of the diploid copy number of each KIR gene. Immunohistochemical staining for T (CD3), B (CD20) and natural killer (NK) cells (CD56 and CD57) were performed on liver biopsies from 3 different patient groups [primary sclerosing cholangitis (PSC), primary biliary cirrhosis and non-autoimmune liver disease], 10 in each group, with similar grade of AR.
Fourty-four (31%) patients were transplanted on the basis of PSC, 40% of them had AR vs 24% in the non-PSC group (P = 0.04). No significant impact of donor-recipient matching for HLA and KIR genotypes was detected. In the overall recipient population an increased risk of AR was detected for HLA-B*08 (P = 0.002, OR = 2.5; 95%CI: 1.4-4.6), HLA-C*07 (P = 0.001, OR = 2.4; 95%CI: 1.4-4.0) and HLA-DRB1*03 (P = 0.03, OR = 1.9; 95%CI: 1.0-3.3) and a decreased risk for HLA-DRB1*04 (P = 0.001, OR = 0.2; 95%CI: 0.1-0.5). For HLA-B*08, HLA-C*07 and DRB1*04 the associations remained evident in a subgroup analysis of non-PSC recipients (P = 0.04, P = 0.003 and P = 0.02, respectively). In PSC recipients corresponding P values were 0.002, 0.17 and 0.01 for HLA-B*08, HLA-C*07 and DRB1*04, respectively. A dosage effect of AR prevalence according to the PSC associated HLA alleles was also notable in the total recipient population. For HLA-B*08 the frequency of AR was 56% in HLA-B*08 homozygous recipients, 39% in heterozygous recipients and 21% in recipients lacking HLA-B*08 (P = 0.02). The same was observed for the HLA-C*07 allele with AR in 57%, 27% and 18% in recipients being homozygous, heterozygous and lacking HLA-C*07 respectively (P = 0.003). Immunohistochemical analysis showed similar infiltration of T, B and NK cells in biopsies with AR in all three groups.
We found significant associations between the PSC-associated HLA-B*08, HLA-C*07, HLA-DRB1*03 and HLA-DRB1*04 alleles and risk of AR in liver transplant recipients.
World Journal of Gastroenterology 04/2014; 20(14):3986-4000. DOI:10.3748/wjg.v20.i14.3986 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Small duct primary sclerosing cholangitis (PSC) is phenotypically a mild version of large duct PSC, but it is unknown whether these phenotypes share aetiology. We aimed to characterize their relationship by investigating genetic associations in the HLA complex, which represent the strongest genetic risk factors in large duct PSC.
Four classical HLA loci (HLA-A, HLA-B, HLA-C, HLA-DRB1) were genotyped in 87 small duct PSC patients, 485 large duct PSC patients and 1117 controls across three geographical regions.
HLA-DRB1*13:01 (OR=2.0, 95% CI 1.2-3.4, P=0.01) and HLA-B*08 (OR=1.6, 95% CI 1.1-2.4, P=0.02) were significantly associated with small duct PSC compared with healthy controls. Based on the observed frequency of HLA-B*08 in small duct PSC, the strongest risk factor in large duct PSC, an estimated 32% (95% CI 4%-65%) of this population can be hypothesized to represent early stages or mild variants of large duct PSC. This subgroup may be constituted by small duct PSC patients with inflammatory bowel disease (IBD), which greatly resembled large duct PSC in its HLA association. In contrast, small duct PSC without IBD was only associated with HLA-DRB1*13:01(P=0.03) and was otherwise distinctly dissimilar from large duct PSC.
Small duct PSC with IBD resembles large duct PSC in its HLA association and may represent early stages or mild variants of large duct disease. Different HLA associations in small duct PSC without IBD could indicate that this subgroup is a different entity. HLA-DRB1*13:01 may represent a specific risk factor for inflammatory bile duct disease. This article is protected by copyright. All rights reserved.
Liver international: official journal of the International Association for the Study of the Liver 02/2014; 34(10). DOI:10.1111/liv.12492 · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite considerable advances over the last two decades in the molecular understanding of cholestasis and cholestatic liver disease, little improvement has been made in diagnostic tools and therapeutic strategies.
To critically review controversial aspects of the scientific basis for common clinical practice in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and to discuss key ongoing challenges to improve patient management.
We performed a literature search using PubMed and by examining the reference lists of relevant review articles related to the clinical management of PBC and PSC. Articles were considered on the background of the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) practice guidelines and clinical experience of the authors.
Ongoing challenges in PBC mainly pertain to the improvement of medical therapy, particularly for patients with a suboptimal response to ursodeoxycholic acid. In PSC, development of medical therapies and sensitive screening protocols for cholangiocarcinoma represent areas of intense research. To rationally improve patient management, a better understanding of pathogenesis, including complications like pruritis and fatigue, is needed and there is a need to identify biomarker end-points for treatment effect and prognosis. Timing of liver transplantation and determining optimal regimens of immunosuppression post-liver transplantation will also benefit from better appreciation of pre-transplant disease mechanisms.
Controversies in the management of PBC and PSC relate to topics where evidence for current practice is weak and further research is needed.
[Show abstract][Hide abstract] ABSTRACT: Primary sclerosing cholangitis (PSC) occurs in 2%-8% of patients who suffer from ulcerative colitis (UC). For patients who require colectomy, ileal pouch-anal anastomosis (IPAA) or ileorectal anastomosis (IRA) is employed to preserve continence.We evaluated the outcomes after IPAA and IRA for patients with UC-PSC, using patients with UC but without PSC as controls (UC-only group).
In a case-control study conducted at Sahlgrenska University Hospital, Sweden, patients with UC-PSC (N=48; 31 IPAA and 17 IRA) were compared to patients with UC only (N=113; 62 IPAA and 51 IRA). Functional outcomes (Öresland score), pouchitis, surgical complications, and failure were evaluated.
For patients with IPAA, the median Öresland scores were similar for the two groups: 5 (range, 0-13) for the UC-PSC group and 5 for the UC-only group (range, 0-12; p>0.05). However, the IRA scores were significantly different at 7 (range, 2-11) and 3 (range, 0-11) for the respective groups (p=0.005). Pouchitis was more frequent in patients with UC-PSC. Complication rates did not differ. For patients with IPAA, the failure rate was 16% for those in the UC-PSC group versus 6% for those in the UC-only group (p>0.05); the corresponding results for IRA were 53% versus 22% (p=0.03).
For cases of IPAA, pouchitis seems to be more common in patients with UC-PSC. However, the functional outcomes and failure rates are unaffected by concurrent PSC. For patients with UC-PSC, functional outcome is poor and the failure rate is high after IRA.
Journal of Crohn s and Colitis 11/2013; 8(5). DOI:10.1016/j.crohns.2013.10.008 · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary sclerosing cholangitis (PSC) remains one of the most challenging conditions of clinical hepatology. There has been a steady growth in research to overcome this fact and the present review aims at summarizing the most recently published literature. The main emphasis will be put on the link of recent pathogenetic insights to clinical characteristics and patient management. With regard to pathogenesis, there is no consensus yet as to whether immune mediated injury or factors related to bile acid physiology are the most important. It also remains to be clarified whether PSC is a mixed bag of various secondary etiologies yet to be defined, or a disease entity predominantly represented by sclerosing cholangitis in the context of inflammatory bowel disease. Most important, there is no available medical therapy with proven influence on clinical end points, and timing of liver transplantation and patient follow-up are challenging due to the unpredictable and high risk of cholangiocarcinoma.
[Show abstract][Hide abstract] ABSTRACT: Little is known about nongenetic risk factors for primary sclerosing cholangitis (PSC), except a possible protective effect of smoking. We investigated the relationship between environmental risk factors and susceptibility to PSC.
A questionnaire was distributed to patients with PSC, recruited from Oslo University Hospital Rikshospitalet in Norway through 2011, and randomly chosen individuals from the Norwegian Bone Marrow Donor Registry (controls). Data were analyzed from 240 patients with PSC and 245 controls, matched for sex and age.
A lower proportion of patients with PSC were daily coffee drinkers than controls, both currently (76% vs 86%; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.32-0.82; P=.006) and at the age of 18 y (35% vs 49%; OR, 0.58; 95% CI, 0.40-0.83; P=.003). The associations were mainly attributed to differences observed in men. Twenty percent of the patients were ever (current or former) daily smokers compared with 43% of controls (OR, 0.33; 95% CI, 0.22-0.50; P<.001). Ever daily smoking before PSC diagnosis was associated with older age at diagnosis (42 y vs 32 y, P<.001). Ever daily smoking (P<.001) and being a coffee drinker at the age of 18 y (P=.048) were independently and negatively associated with PSC. Fewer female patients with PSC than controls reported ever use of hormonal contraception (51% vs 85%, P<.001). Among female patients, there was a strong correlation between increasing number of children before the diagnosis of PSC and increasing age at diagnosis (r=0.63; P<.001).
Coffee consumption and smoking might protect against development of PSC. In women, the disease might be influenced by hormonal factors.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 09/2013; 12(6). DOI:10.1016/j.cgh.2013.09.024 · 6.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Allelic variants of fucosyltransferases 2 and 3 (FUT2/3) influence serum levels of CA19-9, a screening parameter commonly used for detection of biliary malignancy in PSC. We aimed to improve diagnostic accuracy of CA19-9 by determining the impact of FUT2/3 genotypes.
CA19-9 levels were measured in 433 PSC patients, 41 of whom had biliary malignancy. Genotypes for FUT3 and FUT2 were used to assign patients to one of three groups: A, no FUT3 activity regardless of FUT2 activity; B, both FUT2 and FUT3 activity and C, no FUT2 activity without loss of FUT3 activity. Group-specific cut-off values were determined by Youden's index.
The median CA19-9 values of cancer-free patients were significantly different (p < 0.001) in Groups A (2.0 U/mL), B (17.0 U/mL), and C (37.0 U/mL). Biliary malignancy patients in Groups B and C had significantly higher CA19-9 values than cancer-free patients (p < 0.001). The optimal cut-off, as determined by ROC analysis, for all patients was 88.5 U/mL. Optimal cut-off values in Groups A, B, and C were 4.0 U/mL, 74.5 U/mL, and 106.8 U/mL, respectively. Use of these values improved sensitivity of CA19-9 in Groups B and C. Further, use of group-dependent cut-off values with 90% sensitivity resulted in a 42.9% reduction of false positive results.
Use of FUT2/3 genotype-dependent cut-off values for CA19-9 improved sensitivity and reduced the number of false positive results.
Journal of Hepatology 08/2013; 59(6). DOI:10.1016/j.jhep.2013.08.005 · 10.40 Impact Factor