Kiran Bambha

University of Colorado, Denver, Colorado, United States

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Publications (42)317.2 Total impact

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    ABSTRACT: Background and aim: Associations between pre-liver transplantation (pre-LT) BMI and post-LT survival are well described; however, there are few data assessing the associations between the commonly observed post-LT BMI changes and survival. We investigated the impact of early post-LT BMI change on post-LT patient and graft survival. Methods: Using United Network for Organ Sharing data, we identified 2968 adult primary LT recipients who were not overweight pre-LT (BMI >16 to ≤25 kg/m), and who had BMI recorded at 2 years post-LT. Delta BMI was defined as the BMI difference between pre-LT and 2 years post LT. Recipients were grouped into three categories: BMI gain (increase by >1 BMI point), BMI loss (decrease by >1 BMI point), and BMI stable (maintained BMI within 1 point). Associations between delta BMI and patient and graft survival were evaluated using Kaplan-Meier and multivariable Cox regression analyses. Results: BMI gain was common (54%) and associated with significantly greater 5-year patient and graft survival (90 and 89%, respectively), compared with recipients who had either BMI loss (77 and 74%, respectively, P<0.0001 for both) or were BMI stable (83%, P=0.04 and 82%, P=0.007, respectively). In multivariable analyses, increasing delta BMI was found to be inversely associated with risk for death and graft loss [hazard ratio 0.89 (95% confidence interval 0.86-0.91), P<0.001; and hazard ratio 0.88 (95% confidence interval 0.86-0.91), P<0.001, respectively]. Conclusion: This study of a large national liver transplant database demonstrated that post-LT BMI gain was associated with better patient and graft survival, whereas BMI loss was associated with reduced patient and graft survival.
    European journal of gastroenterology & hepatology 10/2015; DOI:10.1097/MEG.0000000000000490 · 2.25 Impact Factor
  • Kiran M Bambha · Jennifer L Dodge · Jane Gralla · Scott W Biggins ·

    Liver Transplantation 10/2015; DOI:10.1002/lt.24363 · 4.24 Impact Factor
  • Kiran M. Bambha ·

    Liver Transplantation 10/2015; DOI:10.1002/lt.24357 · 4.24 Impact Factor
  • A Wieland · D N Frank · B Harnke · K Bambha ·
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    ABSTRACT: The human intestinal microbiota is a key regulator of host metabolic and immune functions and alterations in the microbiome ('dysbiosis') have been implicated in several human diseases. Because of the anatomical links between the intestines and the liver, dysbiosis may also disrupt hepatic function and thereby contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). To perform a comprehensive review of the medical literature investigating associations between intestinal dysbiosis and NAFLD, with a particular emphasis on studies that characterise the microbiome in NAFLD. We conducted a search of PubMed, Embase, and Web of Science using multiple search terms including: 'NAFLD, NASH, fatty liver, steatohepatitis' combined with 'metagenome, microbiom*, microbiota*, fecal flora, intestinal flora, gut bacteria'. Results were manually reviewed and studies selected based on relevance to intestinal microbiota and NAFLD. We also included studies that addressed potential mechanistic models of pathways linking the dysbiosis to NAFLD. Nine studies (five human and four animal models) were identified in our search that assessed associations between specific intestinal microbiota composition and NAFLD. We reviewed and summarised the results of additional investigations that more broadly addressed the mechanisms by which the microbiome may impact NAFLD pathogenesis. Investigations in humans and animals demonstrate associations between intestinal dysbiosis and NAFLD; however, causality has not been proven and mechanistic links require further delineation. As the field of microbiome research matures in techniques and study design, more detailed insights into NAFLD pathogenesis and its associations with the intestinal microbiota will be elucidated. © 2015 John Wiley & Sons Ltd.
    Alimentary Pharmacology & Therapeutics 08/2015; 42(9). DOI:10.1111/apt.13376 · 5.73 Impact Factor
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    ABSTRACT: Donor age has become the dominant donor factor used to predict graft failure (GF) after liver transplantation (LT) in HCV recipients. To develop and validate a model of Corrected Donor Age (CDA) for HCV LT recipients that transforms the risk of other donor factors into the scale of donor age. We analyzed all first LT recipients with HCV in the UNOS registry from 1/1998-12/2007 (development cohort, n=14,538) and 1/2008-12/2011 (validation cohort, n=7,502) using Cox regression, excluding early GF (<90 days from LT). Accuracy in predicting 1yr GF (death or Re-LT) was assessed with the net reclassification index (NRI). In the development cohort, controlling for pre-LT recipient factors and geo-temporal trends (UNOS region, LT year), the following donor factors were independent predictors of GF (Hazard Ratio); all p<0.05; donor age (1.02/yr), circulatory death (DCD) (1.31), diabetes (1.23), height<160cm (1.13), AST>120 U/L (1.10), female (0.94), cold ischemia time (CIT) (1.02/hr), donor non-AA: recipient AA (1.65). Transforming these risk factors into the donor age scale yielded the following: DCD=+16yrs, diabetes=+12yrs, height<160cm=+7yrs, AST >120 U/L=+5yrs, female=-4yrs, CIT=+1yr/hr>8hrs and -1yr/hr<8 hrs. There was a large effect of donor-recipient race combinations; +29yrs for donor non-AA: recipient AA but only +5yrs for donor AA: recipient AA, and -2yrs for donor AA: recipient non-AA. In a validation cohort, CDA better classified risk of 1yr GF versus actual age (NRI 4.9%, p=0.009) and versus the donor risk index (9.0%, p<0.001). The CDA, compared to actual donor age, provides an intuitive and superior estimation of graft quality for HCV-positive LT recipients since it incorporates additional factors that impact LT GF rates. This article is protected by copyright. All rights reserved. © 2015 American Association for the Study of Liver Diseases.
    Liver Transplantation 06/2015; 21(8). DOI:10.1002/lt.24194 · 4.24 Impact Factor
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    ABSTRACT: With increasing attention being paid to optimizing patient outcomes, it has been proposed that liver transplant (LT) for individuals with elevated BMIs and high MELD scores may adversely affect post-LT outcomes. We investigated the impact of BMI on post-LT outcomes in the context of MELD at LT. Using UNOS data, we identified all adult (≥18 years) primary LT recipients from 3/1/02-9/30/11. BMI categories included: Underweight, Normal, Overweight, Obese Class I, II, or, III (<18.5; 18.5-24.9; 25-29.9; 30-34.9; 35-39.9; ≥40 kg/m(2) , respectively). One-year post-LT death and graft loss were modeled using Cox regression, including interactions between BMI and MELD. 45551 adult recipients were identified: 68% male; median [IQR] age 55 [49-60] years; MELD 19 [13-26]; DRI 1.39 [1.12-1.69]. Representations in the BMI categories were: (i) Underweight (n=863, 2%), (ii) Normal (n=13262, 29%), (iii) Overweight (n=16329, 36%), (iv) Obese-Class I (n=9639, 21%), (v) Obese-Class II (n=4062, 9%), and (vi) Obese-Class III (n=1396, 3%). In adjusted analyses, elevated BMI was not associated with increased risk for death or graft loss. Among the Underweight, there were significant interactions between BMI and MELD with respect to death (p=0.02) and graft loss (p=0.01), with significantly increased risks for death (HR 1.70, 95% CI 1.38-2.09, p=0.006) and graft loss (HR 1.45, 95% CI 1.21-1.74, p=0.02) among those with low MELD (≤26), compared to normal BMI recipients with low MELD. Overweight and Obese LT recipients do not have increased risk of death or graft loss regardless of MELD. Underweight patients are at increased risk for poor outcomes post-LT, specifically Underweight recipients with low MELD have increased risk for death and graft loss. Mechanisms underlying this phenomenon warrant further investigation. This article is protected by copyright. All rights reserved. © 2015 American Association for the Study of Liver Diseases.
    Liver Transplantation 06/2015; 21(10). DOI:10.1002/lt.24188 · 4.24 Impact Factor
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    ABSTRACT: Repeat liver transplantation (ReLT) is controversial due to inferior outcomes versus primary liver transplantation (LT). A minimum 1-year expected post-ReLT survival of 50% has been proposed. We aimed to identify combinations of Model for End-stage Liver Disease (MELD), donor risk index (DRI) and recipient characteristics achieving this graft survival threshold. We identified ReLT recipients listed in the US from March 2002 to January 2010 with >90 days between primary LT and listing for ReLT. Utilizing Cox regression, we estimated the expected probability of 1-year graft survival and identified combinations of MELD, DRI and recipient characteristics attaining >50% expected 1-year graft survival. ReLT recipients (n=1418) had a median MELD of 26 and median age of 52 years. Expected 1-year graft survival exceeded 50% regardless of MELD or DRI in Caucasian non-HCV-infected recipients of all ages and Caucasian HCV-infected recipients <50 years old. As age increased in HCV-infected Caucasian and non-HCV-infected African-American recipients, lower MELD scores or lower DRI grafts were needed to attain the graft survival threshold. As MELD scores increased in HCV-infected African-American recipients, lower DRI livers were required to achieve the graft survival threshold. Use of high DRI livers (>1.44) in HCV-infected recipients with MELD > 26 at ReLT failed to achieve the graft survival threshold with recipient age ≥ 60 (any race), as well as at age ≥50 for Caucasians and at age < 50 for African-Americans. Strategic donor selection can achieve >50% expected 1-year graft survival even in high-risk ReLT recipients (HCV infected, older age, African-American race, high MELD scores). Low-risk transplant recipients (age < 50, non-HCV -infected) can achieve the survival threshold with varying DRI and MELD scores. This article is protected by copyright. All rights reserved. © 2015 American Association for the Study of Liver Diseases.
    Liver Transplantation 04/2015; DOI:10.1002/lt.24138 · 4.24 Impact Factor
  • Michael Kriss · Roy Yen · Norio Fukami · Kiran Bambha · Sachin Wani ·

    Gastrointestinal Endoscopy 10/2014; 81(5). DOI:10.1016/j.gie.2014.08.003 · 5.37 Impact Factor
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    ABSTRACT: Background: 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. Methods: A matched case-control study of adults undergoing primary liver transplant from 2009 to 2011 was conducted. Cases showed new onset HF with an ejection fraction less than 50% during liver transplant surgery. Controls were recipients without signs or symptoms of HF. Matching was based on: age, sex, model for end-stage liver disease at the time of transplant, type 2 diabetes, and β-blocker use. Conditional logistic regression analyses were conducted. Results: From 2009 to 2011, seven (3%) of 256 recipients developed intraoperative HF with one resulting death. All survivors regained normal systolic function within 6 months of surgery. Decreasing preoperative serum sodium (odds ratio, 1.41; 95% confidence interval, 1.02-1.94; P = 0.039) and increasing number of units of packed red blood cells transfused intraoperatively (odds ratio=1.2, 95% confidence interval, 1.001-1.467, P = 0.048) were associated with HF. Conclusion: No preoperative echocardiographic parameter predicted HF in affected patients. Two possible explanations are: our patients suffered from stress cardiomyopathy and therefore had no evidence of impaired contraction before the event or echocardiographic predictors of HF were masked by circulatory changes in patients with cirrhosis. Lower serum sodium and more red blood cell transfusions were associated with intraoperative HF. Lower mortality of our intraoperative cases compared to others may be influenced by earlier diagnosis and intervention.
    Transplantation 09/2014; 99(4). DOI:10.1097/TP.0000000000000387 · 3.83 Impact Factor
  • Joseph R Roberts · Kiran Bambha ·

    JAMA Internal Medicine 09/2014; 174(11). DOI:10.1001/jamainternmed.2014.4023 · 13.12 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; 14(11). DOI:10.1111/ajt.12867 · 5.68 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; 20. DOI:10.1002/lt.23929 · 4.24 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; 49(1). DOI:10.1097/MCG.0000000000000075 · 3.50 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; 34(8). DOI:10.1111/liv.12379 · 4.85 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). DOI:10.1007/s10620-013-2740-8 · 2.61 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 at evaluating 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 of 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) were 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; 58(5). DOI:10.1016/j.jhep.2012.12.027 · 11.34 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). DOI:10.1002/lt.23551 · 4.24 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 10/2012; 56(4):1214-22. DOI:10.1002/hep.25771 · 11.06 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(1):65. DOI:10.1186/1471-230X-12-65 · 2.37 Impact Factor
  • Kiran Bambha · Nathan M Bass ·

    Hepatology 05/2012; DOI:10.1002/hep.25838 · 11.06 Impact Factor

Publication Stats

801 Citations
317.20 Total Impact Points


  • 2011-2015
    • University of Colorado
      • • Division of Gastroenterology and Hepatology
      • • Department of Medicine
      Denver, Colorado, United States
  • 2012
    • College of Charleston
      Charleston, South Carolina, United States
  • 2008-2009
    • University of California, San Francisco
      • Division of Gastroenterology
      San Francisco, California, United States
  • 2003-2008
    • Mayo Clinic - Rochester
      • Department of Gastroenterology and Hepatology
      Рочестер, Minnesota, United States