- Email: [email protected]
Model for end stage liver disease score dynamics in NASH patients awaiting liver transplantation and waitlist outcomes
POSTER PRESENTATIONS Methods: Ascites samples (n = 65), duodenal (n = 16) and bile fluids (n = 34) as well as corresponding blood samples (n = 100) were collected from patients with ACLF (n = 67) or after OLT (n = 33). In patients after OLT bile fluid was collected either during endoscopic retrograde cholangiography (ERC, n = 13, median post-OLT-time = 767 (221–4,401) days) or directly from biliary drainage (T-tube, n = 20, median post-OLT-time = 3 (1–87) days). Patients with ACLF predominantly presented with ACLF grad 1 (54.4%) and a median ACLF score of 9.5 (7–17). All samples were analyzed by standard microbiological culture and screened for fungal DNA by qPCR using universal fungal primers binding within the 18S rRNA gene and candida specific hybridization probes. Results: In duodenal samples fungal DNA was detected in 9/9 (100%) patients with ACLF and in 6/7 (85.7%) patients after OLT compared to 8/9 (88.9%) and 6/7 (85.7%) positive samples using cultural methods. Bile of OLT patients was PCR-positive in 10/33 (30.3%; ERC 8/13, T-tube 2/20) compared to 7/33 (21.2%; ERC 6/13, T-tube 1/20) of cultural positive samples. Ascites samples were positive in 0/65 by using molecular and in 2/65 (3.1%) by using cultural methods. Neither PCR-based nor culture method could detect fungal pathogens in blood samples. Candida albicans was the predominant species detected in 11/14 (78.6%) duodenal samples, in 6/7 (78.6%) bile samples and 1/2 (50%) ascites samples, followed by C. glabrata, C. krusei, C. kefyr, C. parapsilosis and Saccharomyces cerevisiae. Conclusions: We could show that our molecular based method is applicable to rapidly detect fungal pathogens in various body specimens with high sensitivity. Whereas the duodenal fluid is frequently colonized, are blood and ascites samples even in these high risk cohorts free of fungal pathogens and fungal DNA. Whether intestinal translocation can lead to invasive fungal infections need to be addressed by further studies. Importantly, fungal pathogen detection in bile fluid was, regardless of the method used, dependent on the route of collection. This questions the impact of artificial bile colonization with duodenal pathogens during endoscopic approaches. FRI-485 Model for end stage liver disease score dynamics in NASH patients awaiting liver transplantation and waitlist outcomes A. Mannalithara1, J.L. Chan2, D. Hagerty2, W.R. Kim1. 1Division of Gastroenterology and Hepatology, Stanford University, Stanford; 2 Conatus Pharmaceuticals Inc., San Diego, United States E-mail: [email protected] Background and Aims: Non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) has become a leading indication of liver transplantation (LT) in the US. The model for end stage liver disease (MELD) has been shown to predict survival of patients with decompensated cirrhosis (DC). The aim of this analysis was to compare the impact of changes in MELD score on survival of NASH DC patients at different initial MELD strata. Methods: The data used in this analysis were obtained from Organ Procurement and Transplantation Network. From the data set, we extracted adult (18 years or older) liver transplant candidates waiting for liver transplantation on or after 1 January 2010. Patients with NASH were identified by the diagnostic code. The effect of change in MELD score over 12 weeks on subsequent transplant-free survival over 2 years was assessed by the multivariable proportional hazards regression analysis. Results: There were 35,114 eligible waitlist registrants including 22,368 men and 12,746 women, of whom 4,258 had a diagnosis of NASH. The majority (36%, n = 1,534) of patients had MELD < 15, 1,455 had MELD between 15 and 20 and 1,269 had MELD of 21 or higher. In the Table, the incidence of LT or mortality among NASH patients increased according to the initial MELD score, regardless of their subsequent MELD dynamic. Moreover, for each initial MELD strata, those who experienced a decrease by 2 or more points over 12 weeks S436
had lower incidence of death or LT compared to patients whose MELD had no change, whereas those with a rising MELD score, had progressively higher incidence according to the degree of increase. NASH patients who had an initial MELD of 10–14, which then decreased by 2 or more points had a significantly lower risk of transplant or death with incidence rate ratio of 0.60 ( p = 0.02). This effect was consistent for other initial MELD strata: the incidence rate ratio was 0.56 for MELD of 15–20 and for MELD of 21–25 (both p < 0.01). Table: Patients with NASH cirrhosis
Initial MELD score
Change in MELD score
10–14
15–20
21–25
Decrease by ≥ 2 No change (±1) Increase by 2–5 Increase by 6–10 Increase by 11+
18.2 30.4 48.0 162.1 347.1
35.3 62.6 137.5 304.6 2256.1
86.6 155.2 381.0 534.8 2244.9
Incidence expressed by death or transplant per 100 people per year.
Conclusions: Reduction of MELD score by 2 or more points over 12 weeks decreases the risk of transplant or death - by approximately 40% compared to those whose MELD remains stable. Whether pharmaceutical intervention purported to reduce MELD will have the same benefit remains to be studied. FRI-486 Model for end stage liver disease score dynamics in patients awaiting liver transplantation and waitlist outcomes A. Mannalithara1, J.L. Chan2, D. Hagerty2, W.R. Kim1. 1Division of Gastroenterology and Hepatology, Stanford University, Stanford; 2 Conatus Pharmaceuticals Inc., San Diego, United States E-mail: [email protected] Background and Aims: Recent advances in hepatology therapeutics hold promises that the prognosis of patients with decompensated cirrhosis (DC) can be fundamentally altered. The model for end stage liver disease (MELD) has been shown to predict survival of patients with DC. The aim of this analysis was to correlate changes in MELD score with subsequent transplant-free survival in patients with DC awaiting liver transplantation (LT). Methods: The data used in this analysis were obtained from Organ Procurement and Transplantation Network. From the data set, we extracted adult (18 years or older) liver transplant candidates waiting for liver transplantation on or after 1 January 2010. Retransplant, multiorgan, status 1, or those receiving exception points were excluded. Four groups of patients were analyzed including hepatitis C (HCV), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD) and cryptogenic cirrhosis. The effect of change in MELD score over 12 weeks on subsequent transplant-free survival after 2 years was assessed by the multivariable proportional hazards regression analysis. Results: There were 35,114 eligible waitlist registrants including 22,368 men and 12,746 women. The majority (41%, n = 14,431) of patients had MELD <15, 9,981 had MELD between 15 and 20 and 10,702 MELD of 21 or higher. HCV was the most common diagnosis (33.6%, n = 11,804), followed by ALD (20%, n = 7,013), NASH (12.1%, n = 4,258) and cryptogenic (5.8%, n = 2,045). In the Table, among patients whose initial MELD was 10–14, those who experienced a decrease by 2 or more points over 12 weeks had lower incidence of death or LT compared to patients whose MELD had no change, whereas those with a rising MELD score had progressively higher incidence according to the degree of increase. Patients whose MELD decreased by 2 or more had a significantly lower risk of transplant or death with similar findings across different cirrhosis etiologies: incidence rate ratios of 0.60 among HCV and NASH patients (both p < 0.02), 0.75 for ALD ( p = 0.16), and 0.62 for cryptogenic patients ( p = 0.12).
Journal of Hepatology 2017 vol. 66 | S333–S542
had lower incidence of death or LT compared to patients whose MELD had no change, whereas those with a rising MELD score, had progressively higher incidence according to the degree of increase. NASH patients who had an initial MELD of 10–14, which then decreased by 2 or more points had a significantly lower risk of transplant or death with incidence rate ratio of 0.60 ( p = 0.02). This effect was consistent for other initial MELD strata: the incidence rate ratio was 0.56 for MELD of 15–20 and for MELD of 21–25 (both p < 0.01). Table: Patients with NASH cirrhosis
Initial MELD score
Change in MELD score
10–14
15–20
21–25
Decrease by ≥ 2 No change (±1) Increase by 2–5 Increase by 6–10 Increase by 11+
18.2 30.4 48.0 162.1 347.1
35.3 62.6 137.5 304.6 2256.1
86.6 155.2 381.0 534.8 2244.9
Incidence expressed by death or transplant per 100 people per year.
Conclusions: Reduction of MELD score by 2 or more points over 12 weeks decreases the risk of transplant or death - by approximately 40% compared to those whose MELD remains stable. Whether pharmaceutical intervention purported to reduce MELD will have the same benefit remains to be studied. FRI-486 Model for end stage liver disease score dynamics in patients awaiting liver transplantation and waitlist outcomes A. Mannalithara1, J.L. Chan2, D. Hagerty2, W.R. Kim1. 1Division of Gastroenterology and Hepatology, Stanford University, Stanford; 2 Conatus Pharmaceuticals Inc., San Diego, United States E-mail: [email protected] Background and Aims: Recent advances in hepatology therapeutics hold promises that the prognosis of patients with decompensated cirrhosis (DC) can be fundamentally altered. The model for end stage liver disease (MELD) has been shown to predict survival of patients with DC. The aim of this analysis was to correlate changes in MELD score with subsequent transplant-free survival in patients with DC awaiting liver transplantation (LT). Methods: The data used in this analysis were obtained from Organ Procurement and Transplantation Network. From the data set, we extracted adult (18 years or older) liver transplant candidates waiting for liver transplantation on or after 1 January 2010. Retransplant, multiorgan, status 1, or those receiving exception points were excluded. Four groups of patients were analyzed including hepatitis C (HCV), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD) and cryptogenic cirrhosis. The effect of change in MELD score over 12 weeks on subsequent transplant-free survival after 2 years was assessed by the multivariable proportional hazards regression analysis. Results: There were 35,114 eligible waitlist registrants including 22,368 men and 12,746 women. The majority (41%, n = 14,431) of patients had MELD <15, 9,981 had MELD between 15 and 20 and 10,702 MELD of 21 or higher. HCV was the most common diagnosis (33.6%, n = 11,804), followed by ALD (20%, n = 7,013), NASH (12.1%, n = 4,258) and cryptogenic (5.8%, n = 2,045). In the Table, among patients whose initial MELD was 10–14, those who experienced a decrease by 2 or more points over 12 weeks had lower incidence of death or LT compared to patients whose MELD had no change, whereas those with a rising MELD score had progressively higher incidence according to the degree of increase. Patients whose MELD decreased by 2 or more had a significantly lower risk of transplant or death with similar findings across different cirrhosis etiologies: incidence rate ratios of 0.60 among HCV and NASH patients (both p < 0.02), 0.75 for ALD ( p = 0.16), and 0.62 for cryptogenic patients ( p = 0.12).
Journal of Hepatology 2017 vol. 66 | S333–S542