Michael B Fallon

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Scholarly Contributions

Books

• Fallon, M. B. (2016). Cardiopulmonary Complications of Cirrhosis.
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  Nevah, MI, Kuruvilla, A and Fallon, MB. Cardiopulmonary Complications of Cirrhosis. In Zakim and Boyer’s Hepatology. T. Boyer, A. Sanyal, N. terrault and K. Lindor eds. 7th edition, Elsevier, Philadelphia, PA. in press
• Fallon, M. B. (2016). Diseases of the Liver and Biliary System.
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  Fallon, MB lead author. Diseases of the Liver and Biliary System, Chapters 39-44. In: Cecil Essentials of Medicine. I. Benjamin, R. Griggs, E. Wing and G. Fitz eds. 9th edition. Elsevier, Philadelphia, PA 2016

Journals/Publications

• Pradhan, F., Narang, N., Fallon, M. B., Pradhan, F., Narang, N., & Fallon, M. B. (2021). Tale of the Frail: Understanding Frailty in Cirrhosis.. Southern medical journal, 114(3), 186-191. doi:10.14423/smj.0000000000001224
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  Frailty is a dynamic condition that results in increased vulnerability to health stressors. Often associated with older adults, frailty is not limited to the geriatric population, although aging and disease burden often go hand in hand. This syndrome is recognized increasingly as an important factor in healthcare costs, rate of adverse outcomes, and overall resource utilization. Frailty may be reversible to a degree, and thus appropriate recognition affords a focus for efficient intervention. Notably, frailty is becoming increasingly relevant in cirrhosis, and has been noted to be an independent predictor of outcomes in patients both before and after liver transplantation. Cirrhosis is currently the 12th leading cause of death in the United States, and its incidence is anticipated to markedly increase in the coming years with the aging of our population. With the anticipated surge in disease prevalence, liver disease care will likely shift from specialist-driven to a multidisciplinary approach between primary care physicians, internists, and hepatologists to adequately care for these patients. This review serves as a guide for clinicians to learn about frailty, its role in cirrhosis, and the current tools to educate patients and families about the importance of nutrition and physical exercise within this population.
• Rangan, P., Pradhan, F., Ling, J., Kannadath, B. S., Fallon, M. B., & Al-qaisi, M. T. (2021). Su356 PORTAL VEIN THROMBOSIS IN CIRRHOTIC PATIENTS: RESULTS FROM A MULTI-CENTER HEALTH NETWORK. Gastroenterology, 160(6), S-861. doi:10.1016/s0016-5085(21)02785-2
• Sehmbey, G. S., Pradhan, F., Ling, J., Kannadath, B. S., Fallon, M. B., David, A. J., & Al-qaisi, M. T. (2021). 664 ALCOHOLIC HEPATITIS TRENDS: RESULTS FROM THE NATIONAL INPATIENT SAMPLE 2012-2017. Gastroenterology, 160(6), S-794. doi:10.1016/s0016-5085(21)02612-3
• Kannadath, B. S., Alsayed, M., Fallon, M. B., & Guha, S. (2020). Hyperthyroidism Associated With Incidence Of Acute And Chronic Pancreatitis? : Results From The National Inpatient Sample Database 2012-2016. Gastroenterology 158(6):S-871. doi:10.1016/S0016-5085(20)32863-8.
• Sehmbey, G. S., Seetharam, A. B., Patel, N., Mehta, S., Bisht, R. U., Suchartlikitwong, S., Sehmbey, G. S., Seetharam, A. B., Pradhan, F., Patel, N., Mehta, S., Koblinski, J. E., Kang, P., Fallon, M. B., Bisht, R., Al-qaisi, M. T., & Ahmed, S. (2020). 923 THE IMPACT OF TREATMENT WITH ANTICOAGULATION FOR IN CIRRHOTIC PATIENTS DIAGNOSED WITH PORTAL VEIN THROMBOSIS AT TIME OF TRANS-JUGULAR INTRAHEPATIC PORTOSYSTEMIC STENT PLACEMENT. Gastroenterology, 158(6), S-1299. doi:10.1016/s0016-5085(20)33909-3
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, K. R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2020). Su1678 IMPACT OF RACE AND ETHNICITY ON OUTCOMES IN A MULTI-CENTER NORTH AMERICAN COHORT OF INPATIENTS WITH CIRRHOSIS. Gastroenterology, 158(6), S-612. doi:10.1016/s0016-5085(20)32229-0
• Xie, K., Xie, D., Quan, M., Guha, S., Gao, Y., Fallon, M. B., Cui, J., & Chen, J. (2020). A novel KDM5A/MPC-1 signaling pathway promotes pancreatic cancer progression via redirecting mitochondrial pyruvate metabolism.. Oncogene, 39(5), 1140-1151. doi:10.1038/s41388-019-1051-8
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  Mitochondrial pyruvate carrier 1 (MPC-1) appears to be a tumor suppressor. In this study, we determined the regulation of MPC-1 expression by Lysine demethylase 5A (KDM5A) and critical impact of this novel KDM5A/MPC-1 signaling on PDA progression. TCGA database, paired PDA and adjacent normal pancreatic tissues, PDA tissue array and cell lines were used to determine the levels of MPC-1 and KDM5A expression, and their relationship with the clinicopathologic characteristics and overall survival (OS) of PDA patients. Both in vitro and in vivo models were used to determine biologic impacts of MPC-1 and KDM5A on PDA and mitochondrial pyruvate metabolism, and the mechanism underling reduced MPC-1 expression in PDA. The expression of MPC-1 was decreased in PDA cell lines and tissues, and negatively associated with tumor poorer differentiation, lymph nodes metastasis, higher TNM stages, and patients' overall survival (OS). Functional analysis revealed that restored expression of MPC-1 suppressed the growth, invasion, migration, stemness and tumorigenicity. Re-expression of MPC-1 stimulated the mitochondrial pyruvate metabolism and inhibited glycolysis, while MPC-1-specific inhibitor UK5099 attenuated these effects. Furthermore, KDM5A bound directly to MPC-1 promoter region and transcriptionally suppressed the expression of MPC-1 via demethylation H3K4. Consistently, KDM5A expression was elevated in PDA and promoted PDA cell proliferation in vitro and tumor growth in vivo via suppressing the expression of MPC-1. The expression of KDM5A was inversely correlated with that of MPC-1 in PDA. KDM5A/MPC-1 signaling promoted PDA growth, invasion, migration, and stemness via inhibiting mitochondrial pyruvate metabolism. Targeting KDM5A/MPC-1 signaling may be an effective therapeutic strategy for PDA.
• Bajaj, J. S., Tandon, P., OʼLeary, J. G., Wong, F., Biggins, S. W., Garcia-Tsao, G., Kamath, P. S., Maliakkal, B., Fallon, M. B., Lai, J. C., Thuluvath, P. J., Vargas, H. E., Subramanian, R. M., Thacker, L. R., & Reddy, K. R. (2019). Outcomes in Patients With Cirrhosis on Primary Compared to Secondary Prophylaxis for Spontaneous Bacterial Peritonitis. The American journal of gastroenterology.
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  Antibiotic prophylaxis is recommended for prevention of the first episode of spontaneous bacterial peritonitis (SBP; primary prophylaxis 1°) and subsequent episodes (secondary prophylaxis 2°). We aimed to compare outcomes in cirrhotic inpatients on 1° vs 2° SBP prophylaxis.
• Fallon, M. B., Brown, R. H., Koch, D. G., Brown, R. H., Vargas, H. E., Song, N., Sharkoski, T., Oh, J. K., Mottram, C. D., Lin, G., Levitsky, J., Krowka, M. J., Koch, D. G., Kawut, S. M., Kaplan, D. E., Gupta, S., Goldberg, D. S., Fox, A. N., Fallon, M. B., , Ellenberg, S. S., et al. (2019). Sorafenib in Hepatopulmonary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 25(8), 1155-1164. doi:10.1002/lt.25438
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  The tyrosine kinase inhibitor sorafenib improves hepatopulmonary syndrome (HPS) in an experimental model. However, the efficacy and adverse effect profile in patients with HPS are unknown. We aimed to determine the effect of sorafenib on the alveolar-arterial oxygen gradient (AaPO2 ) at 3 months in patients with HPS. We performed a randomized, double-blind, placebo-controlled parallel trial of sorafenib in patients with HPS at 7 centers. A total of 28 patients with HPS were randomized to sorafenib 400 mg by mouth daily or a matching placebo in a 1:1 ratio. We found no statistically significant difference in the median change in AaPO2 from baseline to 12 weeks between the patients allocated to sorafenib (4.5 mm Hg; IQR, -3.8 to 7.0 mm Hg) and those allocated to placebo (-2.4 mm Hg; IQR, -4.8 to 8.2 mm Hg; P = 0.70). There was also no difference between the groups in terms of degree of intrapulmonary shunting by contrast echocardiography. Sorafenib significantly reduced circulating levels of angiogenic markers, including vascular endothelial growth factor receptors (P < 0.01) and TIE2-expressing M2 monocytes (P = 0.03), but it reduced the mental component scores of the Short Form 36 (P = 0.04), indicating a worse quality of life. In conclusion, sorafenib did not change the AaPO2 or other disease markers at 3 months in patients with HPS. Alternative antiangiogenic therapies or treatments targeting other pathways should be investigated.
• Forde, K. A., Fallon, M. B., Krowka, M. J., Sprys, M., Goldberg, D. S., Krok, K. L., Patel, M., Lin, G., Oh, J. K., Mottram, C. D., Scanlon, P. D., Kawut, S. M., & , P. V. (2019). Pulse Oximetry Is Insensitive for Detection of Hepatopulmonary Syndrome in Patients Evaluated for Liver Transplantation. Hepatology (Baltimore, Md.), 69(1), 270-281.
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  Screening for hepatopulmonary syndrome (HPS) using pulse oximetry is recommended in liver transplant (LT) candidates because mortality is increased, independently of the severity of the oxygenation defect. LT exception points may be afforded to those with HPS and severe hypoxemia. We assessed the screening characteristics of pulse oximetry for HPS. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study of adults undergoing their first LT evaluation. Patients underwent protocolized assessment of oxygen saturation by pulse oximetry (SpO ), arterial blood gas, spirometry, and contrast-enhanced echocardiography (CE). HPS was defined as an alveolar-arterial gradient ≥15 mm Hg (≥20 mm Hg if age >64 years), intrapulmonary vascular dilatation on CE, and absence of lung disease. The study sample included 363 patients. Of these, 75 (20.7%; 95% confidence interval [CI], 16.6%-25.2%) met the criteria for HPS. The area under the receiver operating characteristic curve (or c-statistic) for SpO in discriminating HPS was 0.59 (95% CI, 0.51-0.66). An SpO
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R. M., Reddy, K. R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2019). Targets to improve quality of care for patients with hepatic encephalopathy: data from a multi-centre cohort.. Alimentary pharmacology & therapeutics, 49(12), 1518-1527. doi:10.1111/apt.15265
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  Hepatic encephalopathy (HE) can adversely affect outcomes in both in-patients and out-patients with cirrhosis..To define targets for improving quality of care in HE management in the multi-centre North American Consortium for End-Stage Liver Disease (NACSELD) cohort..NACSELD in-patient cohort was analysed for (a) medication-associated precipitants, (b) aspiration pneumonia development, (c) HE medication changes, and (d) 90-day HE recurrence/readmissions. Comparisons were made between patients on no-therapy, lactulose only, rifaximin only or both. Ninety-day HE-readmission analysis was adjusted for MELD score..Two thousand eight hundred and ten patients (1102 no-therapy, 659 lactulose, 154 rifaximin, 859 both) were included. HE on admission, and HE rates during hospitalisation were highest in those on lactulose only or dual therapy compared to no-therapy or rifaximin only (P < 0.001). Medications were the most prevalent precipitants (32%; 21% lactulose over/underuse, 5% benzodiazepines, 4% opioids, 1% rifaximin underuse, 1% hypnotics). Patients with medication-associated precipitants had a better prognosis compared to other precipitants. A total of 23% (n = 217) reached grade 3/4 HE, of which 16% developed HE-related aspiration pneumonia. Two thousand four hundred and twenty patients were discharged alive without liver transplant (790 no-therapy, 639 lactulose, 136 rifaximin, 855 both); 12.5% (n = 99) of no-therapy patients did not receive a discharge HE therapy renewal. Ninety-day HE-related readmissions were seen in 16% of patients (9% no-therapy, 9% rifaximin only, lactulose only 18%, dual 21%,
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, K. R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2019). 573 – Predictive Factors for the Development of Acute-Onchronic Liver Failure in a North American Cohort of Hospitalized Cirrhotic Patients with Decompensation. Gastroenterology, 156(6), S-1205. doi:10.1016/s0016-5085(19)39995-0
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, K. R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2019). Su1527 – Potentially Preventable Readmissions and Complications in Hospitalized Patients with Hepatic Encephalopathy in a Large Multi-Center Cohort. Gastroenterology, 156(6), S-562. doi:10.1016/s0016-5085(19)38297-6
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2019). SAT-013-Potentially Preventable readmissions and complications in hospitalized patients with hepatic encephalopathy in a large multi-center cohort. Journal of Hepatology, 70(1), e630-e631. doi:10.1016/s0618-8278(19)31256-3
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2019). SAT-093-Underutilization of hospice in inpatients with cirrhosis: The NACSELD experience. Journal of Hepatology, 70(1), e669. doi:10.1016/s0618-8278(19)31333-7
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2019). SAT-139-Predictive factors for the development of acute-on-chronic liver failure in a North American cohort of hospitalized patients with cirrhosis and decompensation. Journal of Hepatology, 70(1), e691-e692. doi:10.1016/s0618-8278(19)31378-7
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2019). SAT-140-The natural history of stages 2 and 3 acute kidney injury in hospitalized patients with decompensated cirrhosis and ascites. Journal of Hepatology, 70(1), e692. doi:10.1016/s0618-8278(19)31379-9
• Bajaj, J. S., Tandon, P., O'Leary, J. G., Biggins, S. W., Wong, F., Kamath, P. S., Garcia-Tsao, G., Maliakkal, B., Lai, J. C., Fallon, M., Thuluvath, P., Vargas, H. E., Subramanian, R. M., Thacker, L. R., & Reddy, K. R. (2018). The Impact of Albumin Use on Resolution of Hyponatremia in Hospitalized Patients With Cirrhosis. The American journal of gastroenterology, 113(9), 1339-1344.
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  Hyponatremia is associated with poor outcomes in cirrhosis independent of MELD. While intravenous albumin has been used in small series, its role in hyponatremia is unclear. The aim of this study is to determine the effect of albumin therapy on hyponatremia.
• DuBrock, H. M., Krowka, M. J., Forde, K. A., Krok, K., Patel, M., Sharkoski, T., Sprys, M., Lin, G., Oh, J. K., Mottram, C. D., Scanlon, P. D., Fallon, M. B., & Kawut, S. M. (2018). Clinical Impact of Intrapulmonary Vascular Dilatation in Candidates for Liver Transplant. Chest, 153(2), 414-426.
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  Intrapulmonary vascular dilatations (IPVD) frequently are detected in patients with liver disease by the delayed appearance of microbubbles at contrast-enhanced echocardiography. IPVD with an elevated alveolar-arterial (A-a) gradient define hepatopulmonary syndrome (HPS); however, the importance of IPVD in the absence of abnormal gas exchange is unknown. We aimed to determine the clinical impact of IPVD in patients with liver disease.
• Frenette, C. T., Morelli, G., Shiffman, M. L., Frederick, R. T., Rubin, R. A., Fallon, M. B., Cheng, J. T., Cave, M., Khaderi, S. A., Massoud, O., Pyrsopoulos, N., Park, J. S., Robinson, J. M., Yamashita, M., Spada, A. P., Chan, J. L., & Hagerty, D. T. (2018). Emricasan Improves Liver Function in Patients With Cirrhosis and High Model for End-Stage Liver Disease Scores Compared With Placebo. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.
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  Caspase-mediated apoptosis and inflammation contribute to progression of liver disease. Emricasan is a pan-caspase inhibitor that reduced serum markers of apoptosis and liver inflammation in patients with hepatitis C and non-alcoholic steatohepatitis (NASH).
• Mendizabal, M., Goldberg, D. S., Piñero, F., Arufe, D. T., José de la Fuente, M., Testa, P., Coronel, M., Baratta, S., Podestá, L. G., Fallon, M. B., & Silva, M. O. (2018). Isolated Intrapulmonary Vascular Dilatations and the Risk of Developing Hepatopulmonary Syndrome in Liver Transplant Candidates. Annals of hepatology, 16(4), 548-554.
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  The natural history of intrapulmonary vascular dilations (IPVD) and their impact on patient outcomes in the setting of portal hypertension has only been described in small series.
• Munaaguon, P., Fallon, M. B., Bentley, C., & Ahmed, S. (2018). A Case of Simultaneous Small Cell Neuroendocrine Carcinoma of the Esophagus and Barrettʼs Adenocarcinoma: 1772. The American Journal of Gastroenterology, 113(Supplement), S1010-S1011. doi:10.14309/00000434-201810001-01772
• Nemakayala, D., Patel, P., Rahimi, E., Fallon, M. B., & Thosani, N. (2018). Use of quantitative endoscopic ultrasound elastography for diagnosis of pancreatic neuroendocrine tumors. Endoscopic ultrasound, 5(5), 342-345.
• O'Leary, J. G., Reddy, K. R., Garcia-Tsao, G., Biggins, S. W., Wong, F., Fallon, M. B., Subramanian, R. M., Kamath, P. S., Thuluvath, P., Vargas, H. E., Maliakkal, B., Tandon, P., Lai, J., Thacker, L. R., & Bajaj, J. S. (2018). NACSELD Acute-on-Chronic Liver Failure (NACSELD-ACLF) Score Predicts 30-Day Survival in Hospitalized Patients with Cirrhosis. Hepatology (Baltimore, Md.).
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  NACSELD (North American Consortium for the Study of End-Stage Liver Disease) definition of acute-on-chronic liver failure (NACSELD-ACLF) as ≥2 extra-hepatic organ failures has been proposed as a simple bedside tool to assess risk of mortality in hospitalized patients with cirrhosis. We validated NACSELD-ACLF's ability to predict 30-day survival (defined as in-hospital death or hospice discharge) in a separate multicenter prospectively enrolled cohort of both infected and uninfected hospitalized patients with cirrhosis. We utilized the NACSELD database of 14 tertiary care hepatology centers that prospectively enrolled non-elective hospitalized patients with cirrhosis (N=2675). The cohort was randomly split 60%/40% into training (N=1605) and testing (N=1070) groups. Organ failures assessed were: 1) shock, 2) hepatic encephalopathy (grade III/IV), 3) renal (need for dialysis), and 4) respiratory (mechanical ventilation). Patients were most commonly Caucasian (79%) men (62%) with a mean age of 57 years with a diagnosis of alcohol-induced cirrhosis (45%). 1079 patients had an infection during hospitalization. Mean Model for End-Stage Liver Disease (MELD) was 19 and median Child score was 10. No demographic differences were present between the 2 split groups. Multivariable modeling revealed NACSELD-ACLF score, as determined by number of organ failures, was the strongest predictor of decreased survival after controlling for admission age, white blood cell count, serum albumin, MELD score, and presence of infection. The c-statistic for the training set was 0.8073 and was 0.8532 for the validation set.
• Raevens, S., & Fallon, M. B. (2018). Potential clinical targets in hepatopulmonary syndrome: lessons from experimental models. Hepatology (Baltimore, Md.).
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  Hepatopulmonary syndrome (HPS) is a relatively common and potentially severe pulmonary complication of cirrhosis with increased risk of mortality. In experimental models, a complex interaction between pulmonary endothelial cells, monocytes and the respiratory epithelium, producing chemokines, cytokines, and angiogenic growth factors underlies alterations in the alveolar microvasculature, resulting in impaired oxygenation. Models systems are critical for evaluating mechanisms and for preclinical testing in HPS, due to the challenges of evaluating the lung in the setting of advanced liver disease in humans. This review provides an overview of current knowledge and recent findings in the rodent common bile duct ligation model of HPS, which recapitulates many features of human disease. We focus on the concepts of endothelial derangement, monocyte infiltration, angiogenesis, and alveolar type II cell dysfunction as main contributors and potential targets for therapy. This article is protected by copyright. All rights reserved.
• Raschke, R., Gerkin, R., Curry, S. C., Raschke, R., Ramos, K., Gerkin, R., Fallon, M. B., & Curry, S. (2018). The explained variance and discriminant accuracy of APACHE IVa severity scoring in specific subgroups of ICU patients. Southwest Journal of Pulmonary and Critical Care, 17(6), 153-164. doi:10.13175/swjpcc108-18
• Watt, G. P., Lee, M., Pan, J. J., Fallon, M. B., Loomba, R., Beretta, L., McCormick, J. B., & Fisher-Hoch, S. P. (2018). High Prevalence of Hepatic Fibrosis, Measured by Elastography, in a Population-Based Study of Mexican Americans. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.
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  Hepatic fibrosis is a primary risk factor for cirrhosis and hepatocellular carcinoma, which affect a disproportionate number of Hispanics in the United States. We aimed to determine the prevalence of significant fibrosis, measured by point shear-wave elastography (pSWE), and determine characteristics of hepatic fibrosis and simple steatosis in a population-based study of Mexican American Hispanics in south Texas.
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, K. R., O'leary, J. G., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., & Bajaj, J. S. (2018). 499 - Primary SBP Prophylaxis is Associated with Higher ICU Admission and 30-Day Mortality Compared to Secondary SBP Prophylaxis. Gastroenterology, 154(6), S-1091. doi:10.1016/s0016-5085(18)33633-3
• Zucker, K., Munaaguon, P., Fallon, M. B., & Ahmed, S. (2018). A Case of Salmonella Enterocolitis Unmasking Crohnʼs Disease: 3006. The American Journal of Gastroenterology, 113(Supplement), S1651-S1652. doi:10.14309/00000434-201810001-03005
• Bajaj, J. S., Garcia-tsao, G., Kamath, P. S., Maliakkal, B., Thacker, L., Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2017). Albumin use and acute kidney injury in a large real-world analysis of cirrhotic inpatients. Journal of Hepatology, 66(1), S378. doi:10.1016/s0168-8278(17)31103-0
• Bajaj, J. S., O'Leary, J. G., Tandon, P., Wong, F., Garcia-Tsao, G., Kamath, P. S., Maliakkal, B., Biggins, S. W., Thuluvath, P. J., Fallon, M. B., Subramanian, R. M., Vargas, H. E., Lai, J., Thacker, L. R., & Reddy, K. R. (2017). Hepatic Encephalopathy Is Associated With Mortality in Patients With Cirrhosis Independent of Other Extrahepatic Organ Failures. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 15(4), 565-574.e4.
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  Although survival times have increased for patients with cirrhosis, hepatic encephalopathy (HE) remains a major complication and its relative contribution toward mortality in North America is unclear. We investigated whether HE is associated with mortality independent of extrahepatic organ failures (EHOFs).
• Mills, M. R., Fallon, M. B., Mills, M. R., Jondle, D. M., Fallon, M. B., & Cole, L. S. (2017). Are pathologists missing adenomas? Novel Polyp Analysis Protocol Boosts Adenoma Detection rate. Gastroenterology, 152(5), S174. doi:10.1016/s0016-5085(17)30899-5
• O'Leary, J. G., Wong, F., Reddy, K. R., Garcia-Tsao, G., Kamath, P. S., Biggins, S. W., Fallon, M. B., Subramanian, R. M., Maliakkal, B., Thacker, L., & Bajaj, J. S. (2017). Gender-Specific Differences in Baseline, Peak, and Delta Serum Creatinine: The NACSELD Experience. Digestive diseases and sciences, 62(3), 768-776.
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  Women have lower serum creatinine values than men for similar renal function.
• Tandon, P., Reddy, K. R., O'Leary, J. G., Garcia-Tsao, G., Abraldes, J. G., Wong, F., Biggins, S. W., Maliakkal, B., Fallon, M. B., Subramanian, R. M., Thuluvath, P., Kamath, P. S., Thacker, L. R., Bajaj, J. S., & , N. A. (2017). A Karnofsky performance status-based score predicts death after hospital discharge in patients with cirrhosis. Hepatology (Baltimore, Md.), 65(1), 217-224.
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  Identification of patients with cirrhosis at risk for death within 3 months of discharge from the hospital is essential to individualize postdischarge plans. The objective of the study was to identify an easy-to-use prognostic model based on the Karnofsky Performance Status (KPS). The North American Consortium for the Study of End-Stage Liver Disease consists of 16 tertiary-care hepatology centers that prospectively enroll nonelectively admitted cirrhosis patients. Patients enrolled had KPS assessed 1 week postdischarge. KPS was categorized into low (score 10-40), intermediate (50-70), and high (80-100). Of 954 middle-aged patients (57 ± 10 years, 63% men) with a median Model for End-Stage Liver Disease (MELD) score of 17 (interquartile range 13-21), the mortality rates for the low, intermediate, and high performance status groups were 23% (36/159), 11% (55/489), and 5% (15/306), respectively. Low, intermediate, and high performance status was seen in 17%, 51%, and 32% of the cohort, respectively. Low performance status was associated with older age, dialysis, hepatic encephalopathy, longer length of stay, and higher white blood cell count or MELD score at discharge. A model was derived using the three independent predictors of 3-month mortality: KPS, age, and MELD score. This score had better discrimination (area under the receiver operating characteristic curve = 0.74) than a model using MELD (area under the receiver operating characteristic curve = 0.62) or MELD and age (area under the receiver operating characteristic curve = 0.67) to predict 3-month mortality.
• Wong, F., O'Leary, J. G., Reddy, K. R., Garcia-Tsao, G., Fallon, M. B., Biggins, S. W., Subramanian, R. M., Thuluvath, P. J., Kamath, P. S., Patton, H., Maliakkal, B., Tandon, P., Vargas, H., Thacker, L., & Bajaj, J. S. (2017). Acute Kidney Injury in Cirrhosis: Baseline Serum Creatinine Predicts Patient Outcomes. The American journal of gastroenterology, 112(7), 1103-1110.
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  The International Ascites Club (IAC) recently defined Stage 1 acute kidney injury (AKI) for cirrhosis as an acute increase in serum creatinine (SCr) by ≥0.3 mg/dl or by ≥50% in
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, K. R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2017). Albumin Use and Acute Kidney Injury in a Large Real-World Analysis of Cirrhotic Inpatients. Gastroenterology, 152(5), S906. doi:10.1016/s0016-5085(17)33097-4
• Bajaj, J. S., Reddy, K. R., Tandon, P., Wong, F., Kamath, P. S., Garcia-Tsao, G., Maliakkal, B., Biggins, S. W., Thuluvath, P. J., Fallon, M. B., Subramanian, R. M., Vargas, H., Thacker, L. R., O'Leary, J. G., & , N. A. (2016). The 3-month readmission rate remains unacceptably high in a large North American cohort of patients with cirrhosis. Hepatology (Baltimore, Md.), 64(1), 200-8.
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  In smaller single-center studies, patients with cirrhosis are at a high readmission risk, but a multicenter perspective study is lacking. We evaluated the determinants of 3-month readmissions among inpatients with cirrhosis using the prospective 14-center North American Consortium for the Study of End-Stage Liver Disease cohort. Patients with cirrhosis hospitalized for nonelective indications provided consent and were followed for 3 months postdischarge. The number of 3-month readmissions and their determinants on index admission and discharge were calculated. We used multivariable logistic regression for all readmissions and for hepatic encephalopathy (HE), renal/metabolic, and infection-related readmissions. A score was developed using admission/discharge variables for the total sample, which was validated on a random half of the total population. Of the 1353 patients enrolled, 1177 were eligible on discharge and 1013 had 3-month outcomes. Readmissions occurred in 53% (n = 535; 316 with one, 219 with two or more), with consistent rates across sites. The leading causes were liver-related (n = 333; HE, renal/metabolic, and infections). Patients with cirrhosis and with worse Model for End-Stage Liver Disease score or diabetes, those taking prophylactic antibiotics, and those with prior HE were more likely to be readmitted. The admission model included Model for End-Stage Liver Disease and diabetes (c-statistic = 0.64, after split-validation 0.65). The discharge model included Model for End-Stage Liver Disease, proton pump inhibitor use, and lower length of stay (c-statistic = 0.65, after split-validation 0.70). Thirty percent of readmissions could not be predicted. Patients with liver-related readmissions consistently had index-stay nosocomial infections as a predictor for HE, renal/metabolic, and infection-associated readmissions (odds ratio = 1.9-3.0).
• Boyer, T. D., Sanyal, A. J., Wong, F., Frederick, R. T., Lake, J. R., O'Leary, J. G., Ganger, D., Jamil, K., Pappas, S. C., & , R. S. (2016). Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1. Gastroenterology, 150(7), 1579-1589.e2.
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  Hepatorenal syndrome type 1 (HRS-1) in patients with cirrhosis and ascites is a functional, potentially reversible, form of acute kidney injury characterized by rapid (
• Fallon, M. B. (2016). International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation.
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  Krowka MJ, Fallon MB, Kawut SM, Fuhrmann V, Heimbach JK, Ramsay MA, Sitbon O, Sokol RJ. International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation. 2016 100(7):1440-52. PMID: 27326810.
• Fallon, M. B. (2016). Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation in experimental hepatopulmonary syndrome. J Gastroenterol Hepatol. 2016 31(11):1888-1894. PMID: 27029414.
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  Wu W, Zhang J, Yang W, Hu B, Fallon MB. Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation in experimental hepatopulmonary syndrome. J Gastroenterol Hepatol. 2016 31(11):1888-1894. PMID: 27029414
• Fallon, M. B. (2016). Use of quantitative endoscopic ultrasound elastography for diagnosis of pancreatic neuroendocrine tumors. Use of quantitative endoscopic ultrasound elastography for diagnosis of pancreatic neuroendocrine tumors.
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  Nemakayala D, Patel P, Rahimi E, Fallon MB, Thosani N. Use of quantitative endoscopic ultrasound elastography for diagnosis of pancreatic neuroendocrine tumors. Endosc Ultrasound. 2016 5(5):342-345. PMID: 27803909
• Fallon, M. B. (2016). Vapreotide Study Group.. Child-Turcotte-Pugh Class is Best at Stratifying Risk in Variceal Hemorrhage: Analysis of a US Multicenter Prospective Study.. J Clin Gastroenterol. 2016 [epub ahead of print] PMID: 27779613.
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  Fortune BE, Garcia-Tsao G, Ciarleglio M, Deng Y, Fallon MB, Sigal S, Chalasani NP, Lim JK, Reuben A, Vargas HE, Abrams G, Lewis MD, Hassanein T, Trotter JF, Sanyal AJ, Beavers KL, Ganger D, Thuluvath PJ, Grace ND, Groszmann RJ; Vapreotide Study Group.. Child-Turcotte-Pugh Class is Best at Stratifying Risk in Variceal Hemorrhage: Analysis of a US Multicenter Prospective Study. J Clin Gastroenterol. 2016 [epub ahead of print] PMID: 27779613
• Fortune, B. E., Garcia-Tsao, G., Ciarleglio, M., Deng, Y., Fallon, M. B., Sigal, S., Chalasani, N. P., Lim, J. K., Reuben, A., Vargas, H. E., Abrams, G., Lewis, M. D., Hassanein, T., Trotter, J. F., Sanyal, A. J., Beavers, K. L., Ganger, D., Thuluvath, P. J., Grace, N. D., , Groszmann, R. J., et al. (2016). Child-Turcotte-Pugh Class is Best at Stratifying Risk in Variceal Hemorrhage: Analysis of a US Multicenter Prospective Study. Journal of clinical gastroenterology.
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  Data on acute variceal hemorrhage (AVH) in the United States is limited and the best method to stratify risk is not clear. Taking advantage of a prospective US cohort study, we aimed to (1) describe clinical outcomes of AVH and their predictors; (2) compare predictors of 6-week mortality.
• Garza, A. L., Vatcheva, K. P., Pan, J. J., Rahbar, M. H., Fallon, M. B., McCormick, J. B., & Fisher-Hoch, S. P. (2016). Liver and Other Gastrointestinal Cancers Are Frequent in Mexican Americans. Journal of racial and ethnic health disparities, 3(1), 1-10.
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  Disease patterns in Mexican American health-disparity populations differ from larger US populations.
• Jiao, J., Watt, G. P., Lee, M., Rahbar, M. H., Vatcheva, K. P., Pan, J. J., McCormick, J. B., Fisher-Hoch, S. P., Fallon, M. B., & Beretta, L. (2016). Cirrhosis and Advanced Fibrosis in Hispanics in Texas: The Dominant Contribution of Central Obesity. PloS one, 11(3), e0150978.
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  Liver cirrhosis is a leading cause of death in Hispanics and Hispanics who live in South Texas have the highest incidence of liver cancer in the United States. We aimed at determining the prevalence and associated risk factors of cirrhosis in this population. Clinical and demographic variables were extracted for 2466 participants in the community-based Cameron County Hispanic Cohort in South Texas. Aspartate transaminase to Platelet Ratio Index (APRI) was used to predict cirrhosis in Cameron County Hispanic Cohort. The prevalence of cirrhosis using APRI≥2 was 0.94%, which is nearly 4-fold higher than the national prevalence. Using APRI≥1, the overall prevalence of cirrhosis/advanced fibrosis was 3.54%. In both analyses, highest prevalence was observed in males, specifically in the 25-34 age group. Risk factors independently associated with APRI≥2 and APRI≥1 included hepatitis C, diabetes and central obesity with a remarkable population attributable fraction of 52.5% and 65.3% from central obesity, respectively. Excess alcohol consumption was also independently associated with APRI≥2. The presence of patatin-like phospholipase domain-containing-3 gene variants was independently associated with APRI≥1 in participants >50 years old. Males with both central obesity and excess alcohol consumption presented with cirrhosis/advanced fibrosis at a young age. Alarmingly high prevalence of cirrhosis and advanced fibrosis was identified in Hispanics in South Texas, affecting young males in particular. Central obesity was identified as the major risk factor. Public health efforts are urgently needed to increase awareness and diagnosis of advanced liver fibrosis in Hispanics.
• Krowka, M. J., Fallon, M. B., Kawut, S. M., Fuhrmann, V., Heimbach, J. K., Ramsay, M. A., Sitbon, O., & Sokol, R. J. (2016). International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation, 100(7), 1440-52.
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  Two distinct pulmonary vascular disorders, hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) may occur as a consequence of hepatic parenchymal or vascular abnormalities. HPS and POPH have major clinical implications for liver transplantation. A European Respiratory Society Task Force on Pulmonary-Hepatic Disorders convened in 2002 to standardize the diagnosis and guide management of these disorders. These International Liver Transplant Society diagnostic and management guidelines are based on that task force consensus and should continue to evolve as clinical experience dictates. Based on a review of over 1000 published HPS and POPH articles identified via a MEDLINE search (1985-2015), clinical guidelines were based on, selected single care reports, small series, registries, databases, and expert opinion. The paucity of randomized, controlled trials in either of these disorders was noted. Guidelines are presented in 5 parts; I. Definitions/Diagnostic criteria; II. Hepatopulmonary syndrome; III. Portopulmonary hypertension; IV. Implications for liver transplantation; and V. Suggestions for future clinical research.
• Watt, G. P., Vatcheva, K. P., Beretta, L., Pan, J. J., Fallon, M. B., McCormick, J. B., & Fisher-Hoch, S. P. (2016). Hepatitis C virus in Mexican Americans: a population-based study reveals relatively high prevalence and negative association with diabetes. Epidemiology and infection, 144(2), 297-305.
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  This study aimed to estimate the prevalence and risk factors for hepatitis C virus (HCV) infection in Mexican Americans living in South Texas. We tested plasma for the presence of HCV antibody from the Cameron County Hispanic Cohort (CCHC), a randomized, population-based cohort in an economically disadvantaged Mexican American community on the United States/Mexico border with high rates of chronic disease. A weighted prevalence of HCV antibody of 2·3% [n = 1131, 95% confidence interval (CI) 1·2-3·4] was found. Participants with diabetes had low rates of HCV antibody (0·4%, 95% CI 0·0-0·9) and logistic regression revealed a statistically significant negative association between HCV and diabetes (OR 0·20, 95% CI 0·05-0·77) after adjusting for sociodemographic and clinical factors. This conflicts with reported positive associations of diabetes and HCV infection. No classic risk factors were identified, but important differences between genders emerged in analysis. This population-based study of HCV in Mexican Americans suggests that national studies do not adequately describe the epidemiology of HCV in this border community and that unique risk factors may be involved.
• Watt, G. P., Vatcheva, K. P., Griffith, D. M., Reininger, B. M., Beretta, L., Fallon, M. B., McCormick, J. B., & Fisher-Hoch, S. P. (2016). The Precarious Health of Young Mexican American Men in South Texas, Cameron County Hispanic Cohort, 2004-2015. Preventing chronic disease, 13, E113.
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  Hispanic men have higher rates of illness and death from various chronic conditions than do non-Hispanic men. We aimed to characterize the health of Mexican American men living on the US-Mexico border in South Texas and elucidate indications of chronic disease in young men.
• Wong, F., Vargas, H. E., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R., Reddy, K. R., O'leary, J. G., Maliakkal, B., Lai, J. C., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2016). Su1513 In-Hospital Mortality Related to Hepatic Encephalopathy Is Independent of ACLF and Varies Significantly Across North America: NACSELD Experience. Gastroenterology, 150(4), S1117. doi:10.1016/s0016-5085(16)33769-6
• Wu, W., Zhang, J., Yang, W., Hu, B., & Fallon, M. B. (2016). Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation in experimental hepatopulmonary syndrome. Journal of gastroenterology and hepatology, 31(11), 1888-1894.
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  Pulmonary monocyte infiltration plays a significant role in the development of angiogenesis in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Hepatic monocytes are also increased after CBDL, but the origins remain unclear. Splenic reservoir monocytes have been identified as a major source of monocytes that accumulate in injured tissues. Whether splenic monocytes contribute to monocyte alterations after CBDL is unknown. This study evaluates monocyte distributions and assesses effects of splenectomy on monocyte levels and pulmonary vascular and hepatic abnormalities in experimental HPS.
• Younes, M., Rubin, M. I., Katz-agranov, N. S., Fallon, M. B., & Bynon, S. J. (2016). A Case of Post Infantile Giant Cell Hepatitis: 1890. The American Journal of Gastroenterology, 111, S905. doi:10.14309/00000434-201610001-01890
• Feldstein, A. E., Pan, J. J., Rahbar, M. H., Pan, J. J., Mccormick, J. B., Fisher-hoch, S. P., Feldstein, A. E., Fallon, M. B., Chen, C., & Beretta, L. (2015). Burden of nonalcoholic fatty liver disease and advanced fibrosis in a Texas Hispanic community cohort.. World journal of hepatology, 7(11), 1586-94. doi:10.4254/wjh.v7.i11.1586
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  To investigate the potential burden of nonalcoholic steatohepatitis (NASH) and advanced fibrosis in a hispanic community..Four hundred and forty two participants with available ultrasonography data from the Cameron County Hispanic Cohort were included in this study. Each participant completed a comprehensive questionnaire regarding basic demographic information, medical history, medication use, and social and family history including alcohol use. Values of the nonalcoholic fatty liver disease fibrosis score (NFS), FIB4 index, BARD score, and Aspartate aminotransferase to Platelet Ratio Index (APRI) were computed using the blood samples collected within 6 mo of liver ultrasonography from each participant. Hepatic steatosis was determined by ultrasonography. As part of univariable analysis, for continuous variables, comparisons among groups were performed with student-t test, one way analysis of variance, and Mann-Whitney test. Pearson χ(2) and the Fisher exact test are used to assess differences in categorical variables. For multivariable analyses, logistic regression analyses were performed to identify characteristics associated with hepatic steatosis. All reported P values are based two-sided tests, and a P value of less than 0.05 was considered to indicate statistical significance..The mean age and body mass index (BMI) of the study participants were 49.1 years and 31.3 kg/m(2), respectively. Among them, 65.6% were females, 52% had hepatic steatosis, 49.5% had metabolic syndrome, and 29% had elevated aminotransferases. Based on established cut-offs for diagnostic panels, between 17%-63% of the entire cohort was predicted to have NASH with indeterminate or advanced fibrosis. Participants with hepatic steatosis had significantly higher BMI (32.9 ± 5.6 kg/m(2) vs 29.6 ± 6.1 kg/m(2), P < 0.001) and higher prevalence rates of elevation of ALT (42.2% vs 14.6%, P < 0.001), elevation of aspartate aminotransferase (38.7% vs 18.9%, P < 0.001), and metabolic syndrome (64.8% vs 33%, P < 0.001) than those without hepatic steatosis. The NFS scores (P = 0.002) and the APRI scores (P = 0.002) were significantly higher in those with steatosis but the scores of the FIB4 index and BARD were similar between the two groups. After adjusting for age, gender and BMI, elevated transaminases, metabolic syndrome and its components, intermediate NFS and APRI scores were associated hepatic steatosis in multivariable analysis..The burden of NASH and advanced fibrosis in the Hispanic community in South Texas may be more substantial than predicted from referral clinic studies.
• Goldberg, D. S., & Fallon, M. B. (2015). The Art and Science of Diagnosing and Treating Lung and Heart Disease Secondary to Liver Disease.. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 13(12), 2118-27. doi:10.1016/j.cgh.2015.04.024
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  Patients with chronic liver disease are at risk of extrahepatic complications related to cirrhosis and portal hypertension, as well as organ-specific complications of certain liver diseases. These complications can compromise quality of life, while also increasing morbidity and mortality before and after liver transplantation. Patients with chronic liver disease are at risk for pulmonary complications of hepatopulmonary syndrome and portopulmonary syndrome; the cardiac complication fall under the general concept of cirrhotic cardiomyopathy, which can affect systolic and diastolic function, as well as cardiac conduction. In addition, patients with certain diseases are at risk of lung and/or cardiac complications that are specific to the primary disease (ie, emphysema in α-1-antitrypsin deficiency) or occur with increased incidence in certain conditions (ie, ischemic heart disease associated with nonalcoholic steatohepatitis). This article focuses on the epidemiology, clinical presentation, pathogenesis, treatment options, and role of transplantation for lung and heart diseases secondary to liver disease, while also highlighting select liver diseases that directly affect the lungs and heart.
• Kanwal, F., Fallon, M. B., & El-serag, H. B. (2015). The Art and Science of Managing Liver Disease.. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 13(12), 2029-30. doi:10.1016/j.cgh.2015.08.031
• Wong, F., Thuluvath, P. J., Thacker, L. R., Subramanian, R. M., Reddy, K. R., O'leary, J. G., Maliakkal, B., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2015). 575 The 3-Month Readmission Rate Remains Unacceptably High in a Large Multi-Center Cohort of Cirrhotic Patients. Gastroenterology, 148(4), S-982-S-983. doi:10.1016/s0016-5085(15)33360-6
• Wong, F., Thuluvath, P. J., Thacker, L. R., Tandon, P., Subramanian, R. M., Reddy, K. R., Patton, H., O'leary, J. G., Maliakkal, B., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2015). 591 Validation of Infection-Related Acute-on-Chronic Liver Failure (I-ACLF) Definition for 30-Day Mortality Prediction in Infected and Uninfected Hospitalized Cirrhotic Patients. Gastroenterology, 148(4), S-988. doi:10.1016/s0016-5085(15)33376-x
• Mehta, S., Zacks, S., Trotter, J. F., Tanikella, R., Roberts, K. E., Mehta, S., Machicao, V. I., Krowka, M. J., Kawut, S. M., Fallon, M. B., Bynon, J. S., Brown, R. S., & Batra, S. (2014). The impact of left ventricular hypertrophy on survival in candidates for liver transplantation.. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 20(6), 705-12. doi:10.1002/lt.23875
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  Left ventricular hypertrophy (LVH) occurs in 12% to 30% of patients with cirrhosis; however, its prognostic significance is not well studied. We assessed the association of LVH with survival in patients undergoing a liver transplantation (LT) evaluation. We performed a multicenter cohort study of patients undergoing an evaluation for LT. LVH was defined with transthoracic echocardiography. The outcome of interest was all-cause mortality. LVH was present in 138 of 485 patients (28%). Patients with LVH were older, more likely to be male and African American, and were more likely to have hypertension. Three hundred forty-five patients did not undergo transplantation (212 declined, and 133 were waiting): 36 of 110 patients with LVH (33%) died, whereas 57 of 235 patients without LVH (24%) died (P = 0.23). After LT, 8 of 28 patients with LVH (29%) died over the course of 3 years, whereas 9 of 112 patients without LVH (8%) died (P = 0.007). This finding was independent of conventional risk factors for LVH, and all deaths for patients with LVH occurred within 9 months of LT. No clinical or demographic characteristics were associated with mortality among LVH patients. In conclusion, the presence of LVH is associated with an early increase in mortality after LT, and this is independent of conventional risk factors for LVH. Further studies are needed to confirm these findings and identify factors associated with mortality after transplantation to improve outcomes.
• Wong, F., Thacker, L. R., Subramanian, R. M., Reddy, K. R., Patton, H., O'leary, J. G., Malik, R., Maliakkal, B., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Biggins, S. W., & Bajaj, J. S. (2014). Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures.. Hepatology (Baltimore, Md.), 60(1), 250-6. doi:10.1002/hep.27077
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  Infections worsen survival in cirrhosis; however, simple predictors of survival in infection-related acute-on-chronic liver failure (I-ACLF) derived from multicenter studies are required in order to improve prognostication and resource allocation. Using the North American Consortium for Study of End-stage Liver Disease (NACSELD) database, data from 18 centers were collected for survival analysis of prospectively enrolled cirrhosis patients hospitalized with an infection. We defined organ failures as 1) shock, 2) grade III/IV hepatic encephalopathy (HE), 3) need for dialysis and mechanical ventilation. Determinants of survival with these organ failures were analyzed. In all, 507 patients were included (55 years, 52% hepatitis C virus [HCV], 15.8% nosocomial infection, 96% Child score ≥ 7) and 30-day evaluations were available in 453 patients. Urinary tract infection (UTI) (28.5%), and spontaneous bacterial peritonitis (SBP) (22.5%) were the most prevalent infections. During hospitalization, 55.7% developed HE, 17.6% shock, 15.1% required renal replacement, and 15.8% needed ventilation; 23% died within 30 days and 21.6% developed second infections. Admitted patients developed none (38.4%), one (37.3%), two (10.4%), three (10%), or four (4%) organ failures. The 30-day survival worsened with a higher number of extrahepatic organ failures, none (92%), one (72.6%), two (51.3%), three (36%), and all four (23%). I-ACLF was defined as ≥ 2 organ failures given the significant change in survival probability associated at this cutoff. Baseline independent predictors for development of ACLF were nosocomial infections, Model for Endstage Liver Disease (MELD) score, low mean arterial pressure (MAP), and non-SBP infections. Independent predictors of poor 30-day survival were I-ACLF, second infections, and admission values of high MELD, low MAP, high white blood count, and low albumin..Using multicenter study data in hospitalized decompensated infected cirrhosis patients, I-ACLF defined by the presence of two or more organ failures using simple definitions is predictive of poor survival.
• Zhang, J., Yang, W., Wu, W., Hu, B., Fallon, M. B., Blackburn, M. R., Batra, S., & Alcorn, J. L. (2014). Alveolar type II epithelial cell dysfunction in rat experimental hepatopulmonary syndrome (HPS).. PloS one, 9(11), e113451. doi:10.1371/journal.pone.0113451
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  The hepatopulmonary syndrome (HPS) develops when pulmonary vasodilatation leads to abnormal gas exchange. However, in human HPS, restrictive ventilatory defects are also observed supporting that the alveolar epithelial compartment may also be affected. Alveolar type II epithelial cells (AT2) play a critical role in maintaining the alveolar compartment by producing four surfactant proteins (SPs, SP-A, SP-B, SP-C and SP-D) which also facilitate alveolar repair following injury. However, no studies have evaluated the alveolar epithelial compartment in experimental HPS. In this study, we evaluated the alveolar epithelial compartment and particularly AT2 cells in experimental HPS induced by common bile duct ligation (CBDL). We found a significant reduction in pulmonary SP production associated with increased apoptosis in AT2 cells after CBDL relative to controls. Lung morphology showed decreased mean alveolar chord length and lung volumes in CBDL animals that were not seen in control models supporting a selective reduction of alveolar airspace. Furthermore, we found that administration of TNF-α, the bile acid, chenodeoxycholic acid, and FXR nuclear receptor activation (GW4064) induced apoptosis and impaired SP-B and SP-C production in alveolar epithelial cells in vitro. These results imply that AT2 cell dysfunction occurs in experimental HPS and is associated with alterations in the alveolar epithelial compartment. Our findings support a novel contributing mechanism in experimental HPS that may be relevant to humans and a potential therapeutic target.
• Kamath, P. S., Garcia-tsao, G., Maliakkal, B., Thacker, L. R., Wong, F., Thacker, L. R., Subramanian, R. M., Reddy, K. R., Patton, H., O'leary, J. G., Maliakkal, B., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Fallon, F., & Bajaj, J. S. (2013). 83 THE NEW CONSENSUS DEFINITION OF ACUTE KIDNEY INJURY IS VALID IN PREDICTING MORTALITY IN HOSPITALIZED INFECTED CIRRHOTIC PATIENTS: THE NACSELD EXPERIENCE. Journal of Hepatology, 58, S37. doi:10.1016/s0168-8278(13)60085-9
• Kamath, P. S., Thacker, L. R., Bajaj, J. S., Wong, F., Thacker, L. R., Subramanian, R. M., Reddy, K. R., Patton, H. M., O'leary, J. G., Malik, R., Kamath, P. S., Garcia-tsao, G., Fallon, M. B., Fallon, F., Brown, G., Biggins, S. W., & Bajaj, J. S. (2013). 226 LONG-TERM ANTIBIOTIC AND PROTON-PUMP INHIBITOR USE ARE STRONG PREDICTORS OF RECURRENT INFECTIONS IN CIRRHOSIS: A PROSPECTIVE MULTI-CENTER STUDY FROM NACSELD. Journal of Hepatology, 58, S97. doi:10.1016/s0168-8278(13)60228-7
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  (type V collagen), C6M (type VI collagen), BGM (Biglycan), ELM (Elastin), and CRPM (CRP)), and ECM formation markers (P3NP (type III collagen) and P4NP7S (type IV collagen)) were measured. Results: The markers measured in hepatic venous blood correlated to the level measured in arterial blood (R=0.89–0.98; p < 0.0001). In hepatic venous blood, all markers correlated directly to Child Score and MELD, and inversely to ICG clearance and serum albumin, strongest with P3NP (R=0.46, 0.48, −0.53, and −0.46; respectively, p < 0.0001). All markers except ELM were inversely correlated to hematocrit and to hemoglobin, especially C4M and C1M showed strongest correlations (R = −0.31; −0.40; respectively, p = 0.001p < 0.0001). In both arterial and hepatic venous blood all markers except CRPM correlated to HVPG (e.g. P3NP for both sites R =0.47, p < 0.0001). A multiple regression analysis including P3NP, C6M and MELD improved the correlation (R =0.62, p < 0.0001). P3NP could clearly separate controls from HVPG levels
• Zhang, J., & Fallon, M. B. (2013). The lung in liver disease: old problem, new concepts.. Transactions of the American Clinical and Climatological Association, 124, 250-62.
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  Liver dysfunction has been recognized to influence the lung in many different clinical situations, although the mechanisms for these effects are not well understood. One increasingly recognized interaction, the hepatopulmonary syndrome (HPS) occurs in the context of cirrhosis and results when alveolar microvascular dilation causes arterial gas exchange abnormalities and hypoxemia. HPS occurs in up to 30% of patients with cirrhosis and significantly increases mortality in affected patients. Currently, liver transplantation is the only curative therapy. Experimental biliary cirrhosis induced by common bile duct ligation (CBDL) in the rat reproduces the pulmonary vascular and gas exchange abnormalities of human HPS and has been contrasted with other experimental models of cirrhosis in which HPS does not develop. Microvascular dilation, intravascular monocyte infiltration, and angiogenesis in the lung have been identified as pathologic features that drive gas exchange abnormalities in experimental HPS. Our recent studies have identified biliary epithelium and activation and interaction between the endothelin-1 (ET-1)/endothelial endothelin B (ETB) receptor and CX3CL1/CX3CR1 pathways as important mechanisms for the observed pathologic events. These studies define novel interactions between the lung and liver in cirrhosis and may lead to effective medical therapies.
• Gitlin, N., Fontana, D., Zeuzem, S., Yoffe, B., Xu, D., Vierling, J. M., Vargas, H. E., Sulkowski, M. S., Sola, R., Shiffman, M. L., Sherman, M., Serfaty, L., Rustgi, V. K., Rodriguez-torres, M., Pockros, P. J., Nelson, D. R., Mur, R. E., Muir, A. J., Lueth, S., , Lopez-talavera, J. C., et al. (2012). 10 PEGINTERFERON LAMBDA-1A (LAMBDA) COMPARED TO PEGINTERFERON ALFA-2A (ALFA) IN TREATMENT-NAIVE PATIENTS WITH HCV GENOTYPES (G) 2 OR 3: FIRST SVR24 RESULTS FROM EMERGE PHASE IIB. Journal of Hepatology, 56, S5-S6. doi:10.1016/s0168-8278(12)60024-5
• Mehta, S., Guha, S., Wolf, D. S., Thosani, N., Mehta, S., Guha, S., Fallon, M. B., & Dupont, A. W. (2012). Su1020 Nonmelanoma Skin Cancers in Inflammatory Bowel Disease Patients Treated With Thiopurines: A Systematic Review and Meta-Analysis. Gastroenterology, 142(5), S-401-S-402. doi:10.1016/s0016-5085(12)61522-4
• Thosani, N., Pan, J. J., & Fallon, M. B. (2012). Sclerosing encapsulating peritonitis. Gastroenterology Insights, 4(1), 3. doi:10.4081/gi.2012.e3
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  Sclerosing encapsulating peritonitis (SEP) is a rare cause of intestinal obstruction. This entity has been reported as either primary idiopathic or secondary to other diseases. We report SEP in 2 cirrhotic patients and review the literature. Both patients had decompensated cirrhosis and episodes of spontaneous bacterial peritonitis. One patient underwent a Denver shunt placement before developing SEP. This patient remains alive and is managed conservatively. The other patient deceased from multi-organ failure after the resection of gangrened small bowel. The manifestations of SEP are often nonspecific that leads to misdiagnosis and/or delayed diagnosis. Early diagnosis of SEP is difficult but not impossible. Surgical treatment is often required when intestinal obstruction is present. Nevertheless, patients with this problem can be treated conservatively with immunosuppressive therapy with or without total parenteral nutrition (TPN) before going for surgery.
• Wolf, D. C., Thosani, N., Spinn, M., Nevah, M. I., Machicado, J. D., Khanijow, V., Fallon, M. B., Dupont, A. W., & Batra, S. (2012). Bleeding Risk Associated with Uninterrupted Clopidogrel Therapy during PEG Tube Placement: Largest Single Center Experience Presidential Poster: 1907. The American Journal of Gastroenterology, 107, S777. doi:10.14309/00000434-201210001-01907
• Diago, M., Gitlin, N., Gladysz, A., Fontana, D., Zeuzem, S., Yoffe, B., Xu, D., Vierling, J. M., Vargas, H. E., Sulkowski, M. S., Sola, R., Shiffman, M. L., Sherman, M., Serfaty, L., Rustgi, V. K., Rodriguez-torres, M., Ramos, E., Pockros, P. J., Nelson, D. R., , Mur, R. E., et al. (2011). 1360 PEGYLATED INTERFERON-LAMBDA (PEGIFN-λ) SHOWS SUPERIOR VIRAL RESPONSE WITH IMPROVED SAFETY AND TOLERABILITY VERSUS PEGIFNα-2A IN HCV PATIENTS (Gl/2/3/4): EMERGE PHASE IIB THROUGH WEEK 12. Journal of Hepatology, 54, S538-S539. doi:10.1016/s0168-8278(11)61362-7
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  1359 FIRST SVR DATA WITH THE NUCLEOSIDE ANALOGUE POLYMERASE INHIBITOR MERICITABINE (RG7128) COMBINED WITH PEGINTERFERON/RIBAVIRIN IN TREATMENT-NAIVE HCV G1/4 PATIENTS: INTERIM ANALYSIS FROM THE JUMP-C TRIAL P. Pockros, D. Jensen, N. Tsai, R.M. Taylor, A. Ramji, C. Cooper, R. Dickson, A. Tice, S. Stancic, D. Ipe, J.A. Thommes, J.M. Vierling. Scripps Clinic Research Center, La Jolla, CA, Center for Liver Diseases, University of Chicago Hospitals, Chicago, IL, Hawaii Medical Center, Honolulu, HI, The University of Kansas Hospital Medical Center, Kansas City, KS, USA; Division of Gastroenterology, University of British Columbia, Vancouver, BC, The Ottawa Hospital, Ottowa, ON, Canada; Dartmouth-Hitchcock Medical Center, Lebanon, NH, Infections Limited Hawaii, Honolulu, HI, Roche, Nutley, NJ, Genentech, South San Francisco, CA, Baylor College of Medicine, Houston, TX, USA E-mail: pockros.paul@scrippshealth.org Introduction: Mericitabine (RG7128, MCB) is a potent, selective nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase with activity across all HCV genotypes. MCB has demonstrated a high barrier to resistance without treatmentemergent resistance observed to date. Methods: JUMP-C is an ongoing randomised, double-blind, placebocontrolled phase 2b study in treatment naive patients infected with HCV G1/4. The trial objective was to compare a response guided therapy regimen of MCB plus peginterferon alfa-2a/ribavirin (P/R) with P/R alone. Patients randomised to arm A achieving an extended RVR (eRVR; HCVRNA
• Tanikella, R., Kochar, R., & Fallon, M. B. (2011). Serial pulse oximetry in hepatopulmonary syndrome.. Digestive diseases and sciences, 56(6), 1862-8. doi:10.1007/s10620-011-1600-7
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  The natural history of hepatopulmonary syndrome (HPS) is poorly characterized and how hypoxemia develops and progresses over time is unclear. We evaluated oxygenation over time in advanced liver disease patients with and without HPS using serial pulse oximetry..Data from a prospective cohort of patients evaluated for liver transplantation were analyzed. All patients with significant cardiopulmonary disease were excluded and patients with and without HPS were compared. Arterial oxygen saturation measurements with pulse oximetry (SpO(2)) were recorded serially from initial evaluation until transplantation or last clinic visit on record. Patients with SpO(2) measurements at ≥ 2 visits were included..A total of 22 HPS patients were compared to 32 non-HPS patients (18 with intrapulmonary vasodilation on contrast echocardiography, CE) over a mean duration of 20 months and 4 SpO(2) measurements. HPS patients had lower SpO(2) at baseline (96.8 vs. 98.4%, P = 0.02) and at end of follow-up (95.8 vs. 98.2%, P = 0.02), and were more likely to have a ≥ 2% reduction (P = 0.04) and faster decline in SpO(2) as compared to non-HPS patients (F = 2.2, P = 0.04). HPS patients with lower SpO(2) and/or PO(2) at baseline appeared more likely to worsen over time. There was no difference in SpO(2) over time between the 2 non-HPS subgroups (- or +CE)..HPS patients have a significant decline in SpO(2) over time compared to non-HPS patients, and therefore, pulse oximetry may be useful for monitoring cirrhotics for development or worsening of HPS. Presence of intrapulmonary vasodilation in the absence of hypoxemia does not appear to affect SpO(2) over time.
• Wolf, D. S., Thosani, N., Tanikella, R., Nevah, M. I., Lukens, F., Ko, T. C., & Fallon, M. B. (2011). 172 ERCP for Suspected Choledocholithiasis: Evaluating the ASGE Guidelines. Gastrointestinal Endoscopy, 73(4), AB116. doi:10.1016/j.gie.2011.03.023
• Mehta, S., Mehta, S., Fallon, M. B., & Arora, G. (2010). Severe Chronic Ductopenic Rejection Related to Successful Treatment of Recurrent Hepatitis C infection in a Liver Transplant Recipient.: 783. The American Journal of Gastroenterology, 105, S284. doi:10.14309/00000434-201010001-00783
• Saggi, R., Rubin, M. N., Mieles, L., Machicao, V. I., Liaw, J. V., Kyriakides, P., Fallon, M. B., Cohen, A. M., Cen, P., Bryant, K. W., & Anderson, F. (2010). Abstract No. 194: Local regional intervention in hepatocellular carcinoma (HCC): pathological complete response (pCR) to pre-transplant treatment correlates with improved survival. Journal of Vascular and Interventional Radiology, 21(2), S75. doi:10.1016/j.jvir.2009.12.355
• Zhao, Y., Yoder, M. C., Weinshilboum, R. M., Voelkel, N. F., Tuder, R. M., Sullivan, E. J., Stevens, T., Stenmark, K. R., Shizuru, J., Schumacker, P. T., Rounds, S. I., Rodman, D. M., Rabinovitch, M., Polgar, P., Oka, M., Nicolls, M. R., Newman, J. H., Moore, T. M., Mcmurtry, I. F., , Mcdonald, D. M., et al. (2010). Strategic plan for lung vascular research: An NHLBI-ORDR Workshop Report.. American journal of respiratory and critical care medicine, 182(12), 1554-62. doi:10.1164/rccm.201006-0869ws
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  The Division of Lung Diseases of the National Heart, Lung, and Blood Institute, with the Office of Rare Diseases Research, held a workshop to identify priority areas and strategic goals to enhance and accelerate research that will result in improved understanding of the lung vasculature, translational research needs, and ultimately the care of patients with pulmonary vascular diseases. Multidisciplinary experts with diverse experience in laboratory, translational, and clinical studies identified seven priority areas and discussed limitations in our current knowledge, technologies, and approaches. The focus for future research efforts include the following: (1) better characterizing vascular genotype-phenotype relationships and incorporating systems biology approaches when appropriate; (2) advancing our understanding of pulmonary vascular metabolic regulatory signaling in health and disease; (3) expanding our knowledge of the biologic relationships between the lung circulation and circulating elements, systemic vascular function, and right heart function and disease; (4) improving translational research for identifying disease-modifying therapies for the pulmonary hypertensive diseases; (5) establishing an appropriate and effective platform for advancing translational findings into clinical studies testing; and (6) developing the specific technologies and tools that will be enabling for these goals, such as question-guided imaging techniques and lung vascular investigator training programs. Recommendations from this workshop will be used within the Lung Vascular Biology and Disease Extramural Research Program for planning and strategic implementation purposes.
• Zacks, S., Trotter, J. F., Taichman, D. B., Roberts, K. E., Krowka, M. J., Knowles, J. A., Kawut, S. M., Horn, E. M., Fallon, M. B., Brown, R. S., Benza, R. L., & Badesch, D. B. (2009). Serotonin transporter polymorphisms in patients with portopulmonary hypertension.. Chest, 135(6), 1470-1475. doi:10.1378/chest.08-1909
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  The long allele of a functional promoter polymorphism in the serotonin transporter (SERT) is associated with an increased risk of some forms of pulmonary arterial hypertension. We hypothesized that the long allele or other polymorphisms in SERT would be associated with an increased risk of portopulmonary hypertension (PPHTN) in patients with advanced liver disease..We performed a multicenter case-control study. Subjects undergoing liver transplant evaluation at seven centers were prospectively screened for the presence of PPHTN using transthoracic echocardiography. PPHTN was confirmed by right heart catheterization using standard criteria..The study sample included 30 case patients with PPHTN and 109 control subjects with advanced liver disease. There was no significant association between the long allele and case status in an adjusted additive model (odds ratio, 0.63; 95% confidence interval, 0.33 to 1.21; p = 0.17). If anything, LL genotype tended to be associated with a lower risk of PPHTN. There were no associations between other SERT polymorphisms and PPHTN..SERT polymorphisms are not associated with the risk of PPHTN in patients with advanced liver disease. Other clinical or genetic risk factors may play a role in this complication of portal hypertension.
• Zhang, J., Tang, L., Pollock, D. M., Luo, B., Ling, Y., & Fallon, M. B. (2009). Attenuation of experimental hepatopulmonary syndrome in endothelin B receptor-deficient rats.. American journal of physiology. Gastrointestinal and liver physiology, 296(4), G704-8. doi:10.1152/ajpgi.90627.2008
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  Experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL) in rat is accompanied by increased lung vascular endothelial endothelin B (ETB) receptor expression and increased circulating levels of endothelin-1 (ET-1). The onset of HPS is hypothesized to be triggered by ET-1/ETB receptor activation of endothelial nitric oxide synthase (eNOS)-derived NO production in the pulmonary endothelium. However, whether functional pulmonary vascular ETB receptors are required for the development of experimental HPS is not defined. We evaluated the effects of vascular ETB receptor deficiency on the development of experimental HPS. The molecular and physiological alterations of HPS were compared in 2-wk CBDL wild-type and ETB receptor-deficient (transgenic sl/sl) rats. Relative to wild-type rats, basal hepatic and plasma ET-1 levels were elevated in sl/sl controls although, unlike wild-type animals circulating ET-1 levels, did not increase further after CBDL in sl/sl animals. In contrast to wild-type animals, ETB receptor-deficient rats did not develop increased Akt and eNOS expression and activation and did not develop gas exchange abnormalities of HPS after CBDL. There was a similar degree of pulmonary intravascular monocyte accumulation in both 2-wk CBDL sl/sl and wild-type animals. In conclusion, ETB receptor deficiency inhibits lung Akt/eNOS activation and prevents the onset of experimental HPS after CBDL. This effect is independent of inhibition of pulmonary intravascular monocyte accumulation. These results demonstrate that ET-1/ETB receptor signaling plays a key role in the initiation of experimental HPS.
• Palma, D. T., & Fallon, M. B. (2006). The hepatopulmonary syndrome.. Journal of hepatology, 45(4), 617-25. doi:10.1016/j.jhep.2006.07.002
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  Respiratory symptoms are exceedingly common in patients who have chronic liver disease with estimates ranging as high as 50–70% of patients complaining of shortness of breath [1]. The differential diagnosis of dyspnea is extensive in such patients and numerous causes should be considered. Over the last 15 years, pulmonary vascular abnormalities have been increasingly recognized as important clinical entities that influence survival and liver transplant candidacy in affected patients. The most common such abnormality, the hepatopulmonary syndrome (HPS), occurs when intrapulmonary vasodilatation impairs arterial oxygenation. This syndrome is now recognized as many as 15–20% of patients undergoing evaluation for orthotopic liver transplantation (OLT) [2]. The presence of HPS increases mortality in the setting of cirrhosis and may influence the frequency and severity of complications of portal hypertension [3]. The purpose of this review is to provide an update on HPS, including the pathophysiology and clinical features, and to provide guidelines for diagnosis and treatment.
• Vitello, A. M., Morris, K. G., Limbird, J. N., Klemm, D. J., Ivy, D. D., Imamura, M., Fallon, M. B., Crossno, J. T., & Carter, E. P. (2005). Attenuation of hypoxia-induced pulmonary artery remodeling by a peroxisome proliferator-activated receptor-gamma agonist.. Chest, 128(6 Suppl), 580S. doi:10.1378/chest.128.6_suppl.580s
• Fallon, M. B., Eloubeidi, M. A., Chen, V. K., & Arguedas, M. R. (2003). Screening for hepatocellular carcinoma in patients with hepatitis C cirrhosis: a cost-utility analysis.. The American journal of gastroenterology, 98(3), 679-90. doi:10.1111/j.1572-0241.2003.07327.x
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  Screening for hepatocellular carcinoma (HCC) is advocated in cirrhotic patients to optimize early detection and treatment. However, the cost-effectiveness is not well defined. Our objective was to perform a cost-utility analysis from a third-party payer's perspective of no screening, alpha-fetoprotein (AFP) concentration measurement alone, abdominal ultrasound (US) and AFP, abdominal three-phase CT and AFP, and abdominal magnetic resonance imaging (MRI) and AFP..A Markov model was constructed simulating the natural history of hepatitis C-related cirrhosis in a cohort of patients age 50 yr over a time horizon of their remaining life expectancy. Transition probabilities were obtained from published data and U.S. vital statistics. Costs represented Medicare reimbursement data. Costs and health effects were discounted at a 3% annual rate..Screening with ultrasonography and AFP concentration measurement was associated with an incremental cost-utility ratio of 26,689 US dollars per quality-adjusted life year, whereas screening with abdominal three-phase CT and AFP concentration measurement was associated with an incremental cost-utility ratio of 25,232 US dollars per quality-adjusted life year compared with no screening. Compared with three-phase CT and AFP, magnetic resonance and AFP imaging costs 118,000 US dollars per quality-adjusted life year. Sensitivity analysis demonstrated that the results are most sensitive to the annual incidence of HCC, proportion of tumors amenable to treatment, and to transplant candidacy, whereas the choice of screening strategy is most sensitive to the test characteristics and cost..Screening for HCC with CT is a cost-effective strategy in transplant-eligible patients with cirrhosis secondary to chronic hepatitis C viral (HCV) infection, comparable with other commonly accepted screening interventions such as mammography and colonoscopy.
• Song, D., Ku, D. D., & Fallon, M. B. (2003). 496 Enhanced ETB receptor mediated vasodilatation in response to ET-1 in pulmonary artery segments from animals with prehepatic portal hypertension and experimental HPS. Hepatology, 38, 398-399. doi:10.1016/s0270-9139(03)80538-4
• Zhang, J., Tang, L., Luo, B., Ling, Y., & Fallon, M. B. (2003). 544 Effects of selective endothelin receptor antagonists on the molecular and physiologic alterations in experimental HPS. Hepatology, 38, 421-421. doi:10.1016/s0270-9139(03)80586-4
• Zhang, J., Tang, L., Luo, B., Ling, Y., & Fallon, M. B. (2003). 90 Endothelin-1 in experimental hepatopulmonary syndrome: evaluation in prehepatic portal hypertension, billiary and nonbiliary cirrhosis. Hepatology, 38, 199-199. doi:10.1016/s0270-9139(03)80133-7
• Zhang, J., Tang, L., Stockard, C. R., Ryter, S. W., Luo, B., Ling, Y., Grizzle, W. E., & Fallon, M. B. (2003). Analysis of pulmonary heme oxygenase-1 and nitric oxide synthase alterations in experimental hepatopulmonary syndrome.. Gastroenterology, 125(5), 1441-51. doi:10.1016/j.gastro.2003.07.005
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  Cirrhosis and portal hypertension due to chronic common bile duct ligation reproduce the features of human hepatopulmonary syndrome, whereas portal hypertension alone due to partial portal vein ligation does not. Nitric oxide contributes to experimental hepatopulmonary syndrome, but the nitric oxide synthase forms involved remain controversial. Recently, increased pulmonary heme oxygenase-1 expression and carbon monoxide production have also been found after common bile duct ligation. Our aim was to explore the role of the heme oxygenase-1/carbon monoxide pathway in the pathogenesis of experimental hepatopulmonary syndrome..Pulmonary heme oxygenase-1 expression and distribution were assessed in sham; 3-week partial portal vein ligation; and 1-, 2-, 3-, 4-, and 5-week common bile duct ligation animals by Northern, Western and immunohistochemical analysis relative to endothelial and inducible nitric oxide synthase levels and to hepatopulmonary syndrome development. In vivo heme oxygenase enzyme inhibition with tin protoporphyrin IX in common bile duct ligation animals was used to define effects on intrapulmonary vasodilatation and arterial blood gases..Heme oxygenase-1 expression in pulmonary intravascular monocytes/macrophages and arterial carboxyhemoglobin levels increased progressively from 3 to 5 weeks after common bile duct ligation relative to controls (5-week protein levels were 15.94 +/- 1.75-fold those of sham animals; P < 0.001). Inducible nitric oxide synthase increased transiently in pulmonary intravascular monocytes/macrophages in 3-week common bile duct ligation animals, whereas pulmonary microvascular endothelial nitric oxide synthase increases began at 2 weeks and correlated with the onset of hepatopulmonary syndrome. Tin protoporphyrin treatment normalized carboxyhemoglobin and improved arterial blood gases and intrapulmonary vasodilatation, reflecting partial reversal of hepatopulmonary syndrome..The heme oxygenase-1/carbon monoxide system is an important contributor to the progression of experimental hepatopulmonary syndrome in addition to alterations in the endothelial nitric oxide synthase/nitric oxide pathway.
• Stinnett, A. A., Heudebert, G. R., Fallon, M. B., & Arguedas, M. R. (2002). The cost-effectiveness of hepatitis A vaccination in patients with chronic hepatitis C viral infection in the United States.. The American Journal of Gastroenterology, 97(3), 721-728. doi:10.1016/s0002-9270(01)04116-8
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  Abstract OBJECTIVE: Hepatitis A vaccination is recommended for patients with chronic hepatitis C. Our aim was to analyze the cost-effectiveness of hepatitis A vaccination in these patients. The specific strategies evaluated were: no vaccination, targeted vaccination, and universal vaccination. METHODS: Clinical estimates were based on published data. Costs estimates were based on published data and institutional Medicare reimbursement rates. Health-related quality-of-life weights were derived from published data and expert estimates. The target population consisted of patients 45 yr of age with chronic hepatitis C followed every 6 months until death. We adopted a societal perspective. RESULTS: Compared with no vaccination, targeted vaccination was associated with an incremental cost-effectiveness ratio of $51,000 per quality-adjusted life-year. The incremental cost-effectiveness ratio of universal vaccination compared with targeted vaccination was $3,900,000 per quality-adjusted life-year. The results were particularly sensitive to the incidence of hepatitis A, probability of fulminant hepatic failure, and costs of hepatitis A antibody screening and vaccination. CONCLUSIONS: Targeted vaccination for hepatitis A in patients with chronic hepatitis C may be a cost-effective strategy to decrease the morbidity and mortality associated with hepatitis A superinfection. Universal vaccination is not a cost-effective alternative to targeted vaccination in this target population.
• Sood, G. K., Fallon, M. B., Crowe, D. R., & Blackard, W. G. (1998). Tacrine. A cause of fatal hepatotoxicity?. Journal of clinical gastroenterology, 26(1), 57-9. doi:10.1097/00004836-199801000-00015
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  Tacrine, an acetyl cholinesterase inhibitor used in the treatment of Alzheimer's disease, often causes reversible abnormalities in liver enzymes, but significant hepatotoxicity is uncommon. We describe fatal hepatic failure associated with tacrine administration. A 75-year-old woman with Alzheimer's disease, taking tacrine for 14 months, developed progressive jaundice. Liver function abnormalities developed during tacrine treatment and led to hepatic failure and death. An extensive evaluation for other etiologies of liver disease was negative. Other potentially hepatotoxic medicines had been administered for at least 2 years before beginning tacrine, and postmortem examination of the liver was consistent with drug-induced hepatotoxicity. Approximately half the patients treated with tacrine have liver enzyme abnormalities develop, primarily in the first 12 weeks of therapy, that resolve with discontinuation of drug or dosage adjustment. Our case of tacrine-associated hepatotoxicity 14 months after the initiation of treatment despite regular biochemical evaluation suggests the potential for delayed and fatal hepatotoxicity with tacrine.
• Fallon, M. B., & Abrams, G. A. (1997). The hepatopulmonary syndrome.. Clinics in liver disease, 1(1), 185-200, xiii. doi:10.1016/s1089-3261(05)70263-4
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  The hepatopulmonary syndrome occurs in subjects with chronic liver disease and/or portal hypertension who develop intrapulmonary vasodilation resulting in arterial deoxygenation. Clinical and basic science studies investigating the pathophysiology of HPS are presented. A diagnostic algorithm is provided using contrast echocardiography, the lung perfusion scan, and pulmonary angiography. Medical therapy and experience with liver transplantation are reviewed.
• Fallon, M. B., & Abrams, G. A. (1996). Scenario number one: hepatopulmonary syndrome.. Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2(4), 313-9. doi:10.1002/lt.500020413
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  HPS is an increasingly recognized clinical entity resulting from intrapulmonary vasodilatation in patients with liver disease and/or portal hypertension. The pathogenesis of alterations in the pulmonary vascular bed in affected patients is poorly understood and the subject of ongoing investigation. The differential diagnosis of pulmonary symptoms and gas-exchange abnormalities in patients with liver disease being evaluated for transplantation is broad and should be focused on differentiating pulmonary causes that significantly increase the risk for transplantation from HPS where transplantation has emerged as a useful treatment. Specific contraindications to transplantation in patients with HPS have not been identified, though unique postoperative complications have been observed and may be treatable during the frequently prolonged resolution of intrapulmonary vasodilatation. The development of a database of information on patients with HPS undergoing transplantation will provide insight into potential contraindications, prognostic features, and postoperative complications unique to these patients.
• Matter, K., Fallon, M. B., Brecher, A. R., Balda, M. S., & Anderson, J. M. (1995). Altered hepatic localization and expression of occludin after common bile duct ligation.. The American journal of physiology, 269(4 Pt 1), C1057-62. doi:10.1152/ajpcell.1995.269.4.c1057
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  Epithelial tight junctions form a regulated barrier that seals the paracellular space and prevents mixing of luminal contents with the interstitium. This barrier is composed of a group of proteins including the putative "sealing" protein occludin that appears to bind directly to a cytoplasmic junction protein, ZO-1. To study the interaction and regulation of these two components when paracellular integrity is altered, we assessed protein expression and immunofluorescent (IF) localization of ZO-1 and occludin in a rat model of hepatocyte tight junction damage induced by common bile duct ligation (CBDL). Protein levels were detected in liver by immunoblotting and IF localization by 3-dimensional reconstruction of serial 0.5-micron confocal microscopic optical sections. As previously described, ZO-1 protein levels progressively increased to threefold control levels 9 days after CBDL. In contrast, occludin protein levels decreased by 50% within 2 days after CBDL and returned to control values by 9 days. In control IF sections, ZO-1 and occludin colocalized, forming thin continuous staining outlining canaliculi. After CBDL, ZO-1 staining appeared discontinuous, and a punctate pericanalicular accumulation of signal developed around junctional areas. Occludin staining was also discontinuous after CBDL, but, in contrast to ZO-1, was not punctate and remained localized either in a linear fashion along canalicular margins or in a homogeneous fashion in immediately surrounding areas. CBDL results in changes in the expression and localization of the putative tight junction sealing protein occludin in hepatocytes that are distinct from those observed for the peripheral membrane tight junction protein ZO-1.(ABSTRACT TRUNCATED AT 250 WORDS)
• Saez, J. C., Saez, J. C., Nathanson, M. H., Mennone, A., Fallon, M. B., Burgstahler, A. D., & Anderson, J. M. (1995). Altered expression and function of hepatocyte gap junctions after common bile duct ligation in the rat.. The American journal of physiology, 268(5 Pt 1), C1186-94. doi:10.1152/ajpcell.1995.268.5.c1186
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  Gap junction channels allow intercellular exchange of ions and small molecules between adjacent cells. Such communication coordinates cellular and organ function in tissues, although it is unclear if altered gap junction expression and communication contribute to organ dysfunction in pathological states. We examined the immunofluorescent (IF) localization and mRNA and protein levels of the two hepatocyte gap junction proteins connexin 32 and connexin 26, after hepatic injury induced by common bile duct ligation (CBDL) in the rat. Intercellular communication was measured by comparing gap junction-mediated coordination of hormone-induced Ca2+ signals in isolated rat hepatocyte couplets from control and CBDL animals. Connexin 32 plasma membrane IF, protein, and mRNA levels decreased markedly early after CBDL and remained low at 14 days. Connexin 26 plasma membrane IF and protein levels also decreased markedly after CBDL, but mRNA levels rose, and a partial return in membrane IF and protein levels was noted at 9 and 14 days. Coordination of vasopressin-induced Ca2+ signals between cells in isolated rat hepatocyte couplets 1 day after CBDL was significantly impaired compared with controls. These results demonstrate that hepatocyte gap junction communication is impaired early after CBDL because of decreased connexin protein levels. Disruption of gap junctions after CBDL may contribute to loss of hepatic functions that depend on gap junction communication.
• Mennone, A., Fallon, M. B., & Anderson, J. M. (1993). Altered expression and localization of the tight junction protein ZO-1 after common bile duct ligation.. The American journal of physiology, 264(6 Pt 1), C1439-47. doi:10.1152/ajpcell.1993.264.6.c1439
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  Hepatocyte tight junctions form the intercellular barrier between bile and blood. Cholestasis due to common bile duct ligation (CBDL) results in structural changes in the tight junction (TJ) and an overt paracellular leak, although the molecular basis for these alterations is undefined. Using the epithelial isoform of the TJ protein ZO-1 (ZO-1 alpha +) as a marker for molecular changes in hepatocyte TJs, we investigated the effects of CBDL on ZO-1 alpha + immunofluorescence (IF) localization and on ZO-1 alpha + mRNA and protein expression over 2 wk of CBDL. ZO-1 alpha + IF staining was altered after 2 days of CBDL and appeared to accumulate in pericanalicular regions after 7 and 9 days. Quantitative immunoblotting and ribonuclease protection revealed a marked increase in hepatic ZO-1 alpha + protein expression and ZO-1 alpha + mRNA levels, respectively. In contrast to changes in ZO-1 alpha + IF, which occurred throughout the lobule, and changes in mRNA and protein expression, which were maximal after 9 days of ligation, the maximal hepatocyte proliferation occurred within 2 days after CBDL and was confined to periportal regions. CBDL results in altered hepatic localization and increased expression of the TJ protein ZO-1 alpha + and appears to represent a specific response by hepatocytes to pathological junction injury independent of cell proliferation.
• Itallie, C. M., Fallon, M. B., Balda, M. S., & Anderson, J. M. (1992). Structure, regulation, and pathophysiology of tight junctions in the gastrointestinal tract.. The Yale journal of biology and medicine, 65(6), 725-35; discussion 737-40.
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  The tight junction, or zonula occludens, forms an intercellular barrier between epithelial cells within the gastrointestinal tract and liver and, by limiting the movement of water and solutes through the intercellular space, maintains the physicochemical separation of tissue compartments. The paracellular barrier properties of junctions are regulated and quite different among epithelia. The junction also forms an intramembrane barrier between the apical and basolateral membrane domains, contributing to segregation of biochemically distinct components of these plasma membrane surfaces. Here we briefly review three rapidly developing areas of medically relevant basic knowledge about the tight junction. First, we describe the presently incomplete knowledge of the molecular structure of the tight junction as a framework for understanding its functional properties. Second, we consider experimental evidence defining how the barrier properties of junctions are physiologically regulated and, third, how barrier properties are specifically altered in, and contribute to, pathologic processes affecting epithelia.