Kiran Bambha

University of Colorado, Denver, Colorado, United States

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Publications (33)248.64 Total impact

  • Gastrointestinal Endoscopy 10/2014; · 4.90 Impact Factor
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    ABSTRACT: Acute intraoperative heart failure (HF) is a rare but often fatal complication of liver transplant surgery. Little is known about the clinical course or predictive variables. Our aims were to provide a detailed clinical description and conduct a systematic search for characteristics associated with intraoperative HF.
    Transplantation 09/2014; · 3.78 Impact Factor
  • Joseph R Roberts, Kiran Bambha
    JAMA Internal Medicine 09/2014; · 13.25 Impact Factor
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    ABSTRACT: Survival benefit (SB) for first liver transplantation (LT) is favorable at Model for End-Stage Liver Disease (MELD) ≥15. Herein, we identify the MELD threshold for SB from repeat liver transplantation (ReLT) by recipient hepatitis C virus (HCV) status and donor risk index (DRI). We analyzed lab MELD scores in new United Network for Organ Sharing registrants for ReLT from March 2002 to January 2010. Risk of ReLT graft failure ≤1 year versus waitlist mortality was calculated using Cox regression, adjusting for recipient characteristics. Of 3057 ReLT candidates, 54% had HCV and 606 died while listed. There were 1985 ReLT recipients, 52% had HCV and 567 ReLT graft failures by 1 year. Unadjusted waitlist mortality and post-ReLT graft failure rates were 416 (95% confidence interval [CI] 384–450) and 375 (95% CI 345–407) per 1000 patient-years, respectively. Waitlist mortality was higher with increasing waitlist MELD (p < 0.001). The MELD for SB from ReLT overall was 21 (21 in non-HCV and 24 in HCV patients). MELD for SB varied by DRI in HCV patients (MELD 21, 24 and 27 for low, medium and high DRI, respectively) but did not vary for non-HCV patients. Compared to first LT, ReLT requires a higher MELD threshold to achieve an SB resulting in a narrower therapeutic window to optimize the utility of scarce liver grafts.
    American Journal of Transplantation 09/2014; · 6.19 Impact Factor
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    ABSTRACT: MELD has reduced predictive ability in cirrhotic patients with MELD ≤ 20. We aimed to assess whether a 5-stage clinical model identifies liver transplant (LT) candidates with low MELD who are at increased risk for death. We conducted a case-control study of cirrhotic subjects with MELD ≤ 20 awaiting LT at a single academic medical center from 2/2002-5/2011. Conditional logistic regression was used to evaluate the risk of liver-related death based on cirrhosis stage. We identified 41 case subjects who died from liver-related causes with a MELD ≤ 20 within 90 days of death while waiting for LT. Cases were matched with up to 3 controls, totaling 66 controls, based on listing year, age, gender, liver disease etiology, hepatocellular carcinoma, and MELD. Cirrhosis stage (1=no varices or ascites, 2=varices, 3=variceal bleed, 4=ascites, 5=ascites and variceal bleed) was assessed for all subjects. MELD scores were similar for cases and controls. Clinical states contributing to death in cases were: sepsis 48%, spontaneous bacterial peritonitis 42%, variceal bleeding 24%, and hepatorenal syndrome 21%. In univariate analyses, variceal bleed (OR 5.6, p= 0.003), albumin (OR 0.5, p=0.041), increasing cirrhosis stage (p=0.003) and reaching stage 2, 3, or 4 cirrhosis versus lower stages (OR 3.6, p=0.048; OR 7.4, p<0.001; OR 4.1, p=0.008; respectively), sodium < 135 (OR 3.4, p=0.006), and hepatic encephalopathy (OR 2.3, p=0.082) were associated with liver-related death. In a multivariable model including cirrhosis stage, albumin, sodium, and hepatic encephalopathy, increasing cirrhosis stage (p=0.010) was independently associated with liver-related death. In conclusion, assessing the cirrhosis stage in low MELD patients awaiting LT may help select candidates for more aggressive monitoring or for living donor or extended criteria donation. Liver Transpl , 2014. © 2014 AASLD.
    Liver Transplantation 06/2014; · 3.79 Impact Factor
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    ABSTRACT: To assess awareness of nonalcoholic fatty liver disease (NAFLD) as a disease entity among individuals with and without metabolic risk factors in an outpatient clinical setting, and to evaluate interest in patient-centered education on NAFLD. NAFLD is the most common chronic liver disease in the United States with up to 30% of the adult population affected. Individuals with metabolic risk factors, particularly, insulin resistance, diabetes, and overweight/obesity, have a high prevalence of NAFLD estimated up to 70%, yet little is known about the understanding and perceptions of NAFLD in these high-risk patients. A self-administered paper questionnaire was given to 368 adult patients presenting to an outpatient endocrinology clinic from February 2012 to October 2012. A total of 302 surveys were completed for a response rate of 82%. Overall, 18% of all respondents reported awareness of NAFLD. Even among patients with self-reported major risk factors for NAFLD (overweight/obese, insulin resistant, or both overweight/obese and insulin resistant), the rates of awareness of NAFLD were low (19%, 23%, and 24%, respectively). A majority of survey respondents expressed interest in receiving patient-centered education on NAFLD (73%). Among high metabolic risk individuals there is low awareness of NAFLD. The majority of those surveyed expressed interest in learning about NAFLD. These findings suggest opportunities to raise public awareness of NAFLD, particularly among patients at high metabolic risk, and to provide education to high-risk individuals with the goal of implementing early prevention strategies and optimizing care.
    Journal of clinical gastroenterology 01/2014; · 2.21 Impact Factor
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    ABSTRACT: Coffee has inverse relationships with both type 2 diabetes and hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Relationships were explored between coffee intake and insulin resistance (IR) with respect to NAFLD histologic severity. We analyzed data from 782 adults (≥18 years) in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) from 2004 to 2008. IR was assessed using the HOMA-IR. We modeled associations between coffee intake and NAFLD histologic severity using multiple logistic regression; and interactions between coffee and IR on NAFLD histology were explored. Among 782 participants, 38% (n = 295) were men, 12% (n = 97) were Latino, mean age (± standard deviation) was 48 ± 12 years. Median BMI was 33.5 kg/m(2) [interquartile range, 29.7-38.3] and median HOMA-IR was 4.3 [2.7-7.2]. Diabetes was present in 24% (n = 189). NASH was present in 79% (n = 616), and 25% (n = 199) had advanced fibrosis. The frequency of coffee intake (cups/day, cpd) was as follows: 0 cpd, n = 230 (29%); <1 cpd, n = 219 (28%); 1 to <2 cpd, n = 116 (15%); ≥2 cpd, n = 217 (28%). The effect of coffee on fibrosis varied with degree of IR (interaction P = 0.001). Coffee consumers with less IR, defined as HOMA-IR<4.3, had a lower odds of advanced fibrosis [OR = 0.64; 95% CI, (0.46-0.88), P = 0.001]. There was no protective effect of coffee on advanced fibrosis among individuals with higher HOMA-IR [OR = 1.06, 95% CI (0.87-1.28), P = 0.6]. Coffee intake is inversely associated with advanced fibrosis among NAFLD patients with lower HOMA-IR. Our findings warrant further investigation given the worldwide ubiquity of coffee intake.
    Liver international: official journal of the International Association for the Study of the Liver 11/2013; · 4.41 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. Primary care providers (PCPs), in contrast to gastroenterology/hepatology (GI/Hep) providers, are the first medical contact for the majority of patients with, or at risk for, NAFLD. PCP awareness of and facility with NAFLD is critical for management of these patients. The purpose of this study was to assess understanding and practice patterns of PCPs and non-GI/Hep subspecialty providers with respect to the diagnosis and management of NAFLD. We administered an online, 61-question survey to 479 providers in internal medicine, family medicine, endocrinology, cardiology, and obstetrics and gynecology (ObGyn) across three health systems: academic medical center, safety-net health system and managed care health system. There were 246 respondents (51 %), with the majority (87 %) being PCPs (internal medicine, family medicine, ObGyn). Only 31 % of providers identified NAFLD as a clinically important diagnosis in their practice. Although 65 % of providers reported some degree of facility in diagnosing NAFLD, less than half (47 %) were comfortable managing NAFLD. Only 33 % refer patients with suspected NAFLD to GI/Hep. Subspecialists in endocrinology and cardiology reported greater clinical concern over NAFLD and were more likely (67 %) to refer patients with suspected NAFLD to GI/Hep. The majority of providers do not identify NAFLD as a clinically important diagnosis and do not refer to GI/Hep. However, 83 % expressed a need for education on NAFLD. Our data reveal practice gaps within NAFLD care and identify opportunities for targeted education to guide PCPs in the evaluation and management of NAFLD.
    Digestive Diseases and Sciences 07/2013; 58(10). · 2.26 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: IL28B single nucleotide polymorphisms are strongly associated with spontaneous HCV clearance and treatment response in non-transplant populations. A DDX58 single nucleotide polymorphism is associated with the antiviral response of innate lymphocytes. We aimed to evaluate the associations of donor and recipient IL28B (rs12979860 and rs8099917) and DDX58 (rs10813831) genotypes with severity of HCV recurrence after liver transplantation. METHODS: In a case-control study of 523 liver transplantation recipients with HCV, we matched severe with mild recurrent HCV based on 2-year clinical and histologic follow-up. A total 440 liver transplantation recipients (severe, n=235; mild, n=205) with recipient DNA and 225 (severe, n=123; mild, n=102) with both recipient and donor DNA were analyzed. RESULTS: IL28B [rs12979860, non-CC (vs.CC) and rs8099917, non-TT (vs.TT)] in the recipient-only analysis had higher risk of severe recurrent HCV [OR 1.57 and 1.58, p<0.05]. However, for the 225 with donor and recipient DNA, IL28B rs12979860 CC (vs. non-CC) and rs8099917 TT (vs.non-TT) and DDX58 rs10813831 non-GG (vs. GG) was associated with more (not less) severe recurrent HCV. The greatest risk of severe recurrent HCV was for rs12979860 CC donors in non-CC recipients (OR 7.02, p<0.001,vs. non-CC donor/recipient) and for rs8099917 TT donors in non-TT recipients (OR 5.78, p=0.001, vs. non-TT donor/recipient). These associations persisted after controlling for donor age, donor race and donor risk index. CONCLUSIONS: IL28B and DDX58 single nucleotide polymorphisms that are favorable when present in the non-transplant setting or in the recipient are unfavorable when present in a donor liver graft.
    Journal of Hepatology 01/2013; · 9.86 Impact Factor
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    ABSTRACT: In the United States, the peak hepatitis C virus (HCV) antibody prevalence of 4% occurred in persons born in the calendar years 1940-1965. The goal of this study was to examine observed and projected age-specific trends in the demand for liver transplantation (LT) among patients with HCV-associated liver disease stratified by concurrent hepatocellular carcinoma (HCC). All new adult LT candidates registered with the Organ Procurement and Transplantation Network for LT between 1995 and 2010 were identified. Patients who had primary, secondary, or text field diagnoses of HCV with or without HCC were identified. There were 126,862 new primary registrants for LT, and 52,540 (41%) had HCV. The number of new registrants with HCV dramatically differed by the age at calendar year, and this suggested a birth cohort effect. When the candidates were stratified by birth year in 5-year intervals, the birth cohorts with the highest frequency of HCV were as follows (in decreasing order): 1951-1955, 1956-1960, 1946-1950, and 1941-1945. These 4 birth cohorts, spanning from 1941 to 1960, accounted for 81% of all new registrants with HCV. A 4-fold increase in new registrants with HCV and HCC occurred between the calendar years 2000 and 2010 in the 1941-1960 birth cohorts. By 2015, we anticipate that an increasing proportion of new registrants with HCV will have HCC and be ≥60 years old (born in or before 1955). In conclusion, the greatest demand for LT due to HCV-associated liver disease is occurring among individuals born between 1941 and 1960. This demand appears to be driven by the development of HCC in patients with HCV. During the coming decade, the projected increase in the demand for LT from an aging HCV-infected population will challenge the transplant community to reconsider current treatment paradigms. Liver Transpl, 2012. © 2012 AASLD.
    Liver Transplantation 12/2012; 18(12). · 3.79 Impact Factor
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    David Sprague, Kiran Bambha
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    ABSTRACT: Liver injury due to prescription and nonprescription medications is an expanding public health concern in the United States, with drug-induced liver injury (DILI) being the single most common reason for regulatory actions instituted by the Food and Drug Administration against certain medications and supplements. A 69-year-old Latino man was referred to Hepatology Clinic for urgent evaluation of new onset jaundice, nausea and fatigue associated with a >40-fold increase in his transaminase levels and elevated INR and alkaline phosphatase. The patient had received a new prescription for varenicline to aid with smoking cessation approximately 3 weeks prior to his evaluation in Hepatology Clinic. Within 5 days of starting the varenicline, the patient developed new onset of nausea, vomiting, malaise and deep jaundice. The varenicline was discontinued on day 5 by the patient. Hepatologic evaluation revealed no evidence of acute viral hepatitis, autoimmune, metabolic or alcohol-related liver disorders. The patient's past medical history was notable, however, for chronic hepatitis C. His liver enzymes and synthetic function completely normalized 9 weeks after discontinuation of the varenicline. This report represents the second documented cases of drug-induced liver injury related to varenicline therapy, highlighting the need for clinician awareness regarding potential hepatotoxicity of varenicline, particularly among patients with pre-existing liver disease.
    BMC Gastroenterology 06/2012; 12:65. · 2.11 Impact Factor
  • Kiran Bambha, Nathan M Bass
    Hepatology 05/2012; · 11.19 Impact Factor
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    ABSTRACT: Major racial and gender differences have been documented in the natural history and treatment responses of chronic hepatitis C virus (HCV) infection; however, distinct mechanisms have remained enigmatic. We hypothesized that racial- and gender-related differences in natural killer (NK) cell populations may explain altered natural history and treatment responses. Our study cohort consisted of 29 African-American (AA; 55% male) and 29 Caucasian-American (CA; 48% male) healthy uninfected control subjects. Multiparameter flow cytometric analysis was used to characterize levels, phenotype with respect to 14 NK receptors, and lymphokine-activated killing (LAK) function. Gene expression was assessed by real-time reverse-transcriptase polymerase chain reaction after 6-hour in vitro stimulation with Toll-like receptor (TLR) ligands. The ability to control HCV infection was assessed in the Huh-7.5/JFH-1 coculture system. NK expression of natural cytotoxicity receptor NKp46 was strongly associated with CA race and female gender and correlated positively with LAK activity (P = 0.0054). NKp46(high) NKs were more efficient at controlling HCV than their NKp46(low) counterparts (P < 0.001). Similarly, ligation of NKp46 on isolated NK cells resulted in a significant reduction in the HCV copy number detected in Huh-7.5/JFH-1 coculture (multiplicity of infection: 0.01) at an effector:target ratio of 5:1 (P < 0.005). After TLR stimulation, genes involved in cytotoxicity, but not cytokine genes, were significantly up-regulated in NKp46(high) NKs. Cytokine stimulation (interleukin [IL]-12 and IL-15) demonstrated that NKp46(high) NK cells have significantly higher interferon-gamma production than NKp46(low) cells. TLR stimulation significantly induced degranulation as well as tumor necrosis factor alpha (TNF-α)-related apoptosis-inducing ligand, Fas, and TNF-α protein expression in NKp46(high) NKs. NKp46 ligand was induced on HCV-infected hepatocytes. Conclusions: NKp46 expression may contribute to differential HCV responses. NKp46 expression correlates with anti-HCV activity in vitro and thus may prove to be a useful therapeutic target. (HEPATOLOGY 2012).
    Hepatology 04/2012; 56(4):1214-22. · 11.19 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the United States; however, few data are available about racial and ethnic variation. We investigated relationships between ethnicity, NAFLD severity, metabolic derangements, and sociodemographic characteristics in a well-characterized cohort of adults with biopsy-proven NAFLD. Data were analyzed from 1,026 adults (≥18 years) in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) from 2004 to 2008, for whom liver histology data were available within 6 months of enrollment. Associations between ethnicity (i.e., Latino versus non-Latino white) and NAFLD severity (i.e., NASH versus non-NASH histology and mild versus advanced fibrosis) were explored with multiple logistic regression analysis. We also investigated effect modification of ethnicity on metabolic derangements for NAFLD severity. Within the NASH CRN, 77% (N = 785) were non-Latino white and 12% (N = 118) were Latino. Sixty-one percent (N = 628) had NASH histology and 28% (N = 291) had advanced fibrosis. Latinos with NASH were younger, performed less physical activity, and had higher carbohydrate intake, compared to non-Latino whites with NASH. Gender, diabetes, hypertension, hypertriglyceridemia, aspartate aminotransferase (AST), platelets, and the homeostasis model assessment of insulin resistance (HOMA-IR) were significantly associated with NASH. Age, gender, AST, alanine aminotransferase, alkaline phosphatase, platelets, total cholesterol, hypertension, and HOMA-IR, but not ethnicity, were significantly associated with advanced fibrosis. The effect of HOMA-IR on the risk of NASH was modified by ethnicity: HOMA-IR was not a significant risk factor for NASH among Latinos (odds ratio [OR] = 0.93; 95% confidence interval [CI]: 0.85-1.02), but was significant among non-Latino whites (OR, 1.06; 95% CI: 1.01-1.11). CONCLUSION: Metabolic risk factors and sociodemographic characteristics associated with NASH differ by ethnicity. Additional insights into NASH pathogenesis may come from further studies focused on understanding ethnic differences in this disease.
    Hepatology 03/2012; 55(3):769-80. · 11.19 Impact Factor
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    ABSTRACT: Natural killer (NK) cells constitute a first line of defense against viral infections; their function is governed by the integration of signals from multiple activating and inhibitory surface receptors. We hypothesized that because NKs become rapidly activated by cytokines, response to anti-hepatitis C virus (HCV) therapy would be predicted by the phenotype and function of NKs. We used a cohort of 101 patients (55 African, 46 Caucasian-American) who received pegylated-interferon (IFN) and ribavirin for 48 weeks. Multiparameter FACS analysis was used to examine relative expression of 14 different inhibitory/activating receptors. Interleukin (IL)-28B genotyping (rs12979860) was also performed. Pretreatment levels of inhibitory receptors CD158a, CD158b, and CD158e were higher in patients who demonstrated poor viral decline within the first 28 days of therapy. Higher expression levels of inhibitory receptors NKG2A, CD158b, and CD158e were demonstrable in patients who failed to achieve sustained virologic response (SVR). Patients carrying the IL-28B T allele had higher NKG2A expression on effector NKs. We created a mathematical regression model incorporating race, viral level, and two inhibitory receptors. The area-under-the curve was 0.88, which is highly predictive of SVR. Moreover, the model performed complementarily with IL-28B across the CC, CT, and TT genotypes. Purified NKG2Aneg NKs treated with pegylated-IFN-α for 4 hours demonstrated higher levels of IFN-γ-inducible protein-10 (IP-10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) compared with their NKG2Apos counterparts. Conclusions: These results provide novel insights into the associations of NK phenotype with IL-28B genotype and gene expression patterns, as well as the role of NKs in mediating IFN-induced viral clearance of chronic HCV infection. (HEPATOLOGY 2011;)
    Hepatology 08/2011; 54(5):1559 - 1569. · 11.19 Impact Factor
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
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    ABSTRACT: To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT). This study consists of a cohort of adult (> or =18 years) primary-LT recipients who had normal renal function before LT and who survived 1 year or more after LT at a high-volume US LT program between January 1, 1990, and December 31, 2000. Patients with adequate renal function (estimated glomerular filtration rate, > or =40 mL/min per 1.73 m(2) during follow-up; n=308) and patients with incident CKD (estimated glomerular filtration rate, <40 mL/min per 1.73 m(2) after LT; n=92) were identified. To investigate the association of 6 candidate genes with post-LT CKD, we selected SNPs that have been associated with renal function in the literature. Hazard ratios were estimated using Cox regression, adjusted for potential confounding variables. The variant allele (298Asp) of the Glu298Asp SNP in the endothelial nitric oxide synthase gene (NOS3) was significantly associated with CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp) compared with 42% among those not homozygous for the NOS3 variant allele. Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold increased risk of developing CKD after LT (P=.005, adjusted for confounding variables). Homozygosity for the variant allele of NOS3 (298Asp) is associated with CKD after LT and may be useful for identifying recipients at higher risk of post-LT CKD.
    Mayo Clinic Proceedings 09/2010; 85(9):814-20. · 5.79 Impact Factor
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    ABSTRACT: Organ procurement in China has been criticized because of its reliance on executed prisoners as donors. We aimed to assess the influence of perceptions about organ procurement practices in China on domestic patient-care decisions. Methods: An anonymous internet administered case-based questionnaire was used to survey a sample of healthcare professionals with affiliations to hepatology and transplantation professional societies. Results: Of 674 completed surveys, the vast majority (93%) of the respondents were physicians, surgeons or allied transplant professionals actively caring for liver transplant patients and 81% practiced in the US. A strong majority believed procurement practices were ethically sound in the US and Europe (87% and 73%) but fare fewer believed that procurement practices were ethically sound in China (4%, p < 0.001). In case-based questions, lack of confidence in the ethical standards of organ procurement in China predicted patient-care decisions. The majority would provide post-transplantation care for patients who underwent liver transplantation at another domestic center, in a foreign country and in China (90%, 78%, and 63%, respectively, p < 0.001) yet respondents who suspected unethical procurement practices in China were more reluctant to do so (p < 0.001). Conclusions: Transplant professionals expressed concern about organ procurement practices in China which influenced their patient-care decision-making.
    Clinical Transplantation 11/2009; 23(6):831-8. · 1.49 Impact Factor
  • Kiran Bambha, Hal F Yee
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    ABSTRACT: (Am J Gastroenterol 2008;103:1380–1382)
    The American Journal of Gastroenterology 07/2008; 103(6):1380-2. · 9.21 Impact Factor
  • Kiran M Bambha, Scott W Biggins
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    ABSTRACT: The aim of this article is to examine the limitations of the Model for End-Stage Liver Disease (MELD) components and summarize data on promising new predictor variables. Promising modifications to MELD have been aimed at identifying more accurate measurements of the current MELD components and at improving survival prediction in earlier stages of cirrhosis. Incorporation of new measurements of cholestasis, coagulopathy and renal dysfunction should improve accuracy and reliability of MELD in predicting mortality in end stage liver disease. Direct bilirubin may be a more specific surrogate marker of liver disease than total bilirubin and further investigation of its use in liver mortality risk models in warranted. The recently developed liver-specific international normalized ratio may mitigate thromboplastin-related variation in international normalized ratio measurements. The incorporation of more accurate assessments of renal function into MELD should improve prognostic accuracy and would avert systematic biases associated with serum creatinine. Hepatic venous pressure gradient and serum sodium are promising predictors of liver-related mortality that may warrant further consideration. Modification to MELD, particularly if intended for use in liver transplant allocation, should be based upon objective, reliable, reproducible and readily available predictors; and be able to withstand rigorous model development and validation.
    Current opinion in organ transplantation 07/2008; 13(3):227-33. · 3.27 Impact Factor

Publication Stats

484 Citations
248.64 Total Impact Points


  • 2010–2014
    • University of Colorado
      • Division of Gastroenterology and Hepatology
      Denver, Colorado, United States
  • 2006–2008
    • University of California, San Francisco
      • • Division of Hospital Medicine
      • • Division of Gastroenterology
      San Francisco, California, United States
    • Mayo Foundation for Medical Education and Research
      • Division of Gastroenterology and Hepatology
      Scottsdale, AZ, United States
  • 2003–2004
    • Mayo Clinic - Rochester
      • Department of Gastroenterology and Hepatology
      Rochester, MN, United States