Joseph J. Larson

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (46)529.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Little is known in the United States (US) about the epidemiology of liver diseases that develop only during (are unique to) pregnancy. We investigated the incidence of liver diseases unique to pregnancy in Olmsted County, MN and long-term maternal and fetal outcomes. We identified 247 women with liver diseases unique to pregnancy from 1996 through 2010 using the Rochester Epidemiology Project database. The crude incidence rate was calculated by the number of liver disease cases divided by 35,101 pregnancies. Of pregnant women with liver diseases, 134 had preeclampsia with liver dysfunction, 72 had hemolysis-associated increased levels of liver enzymes and low-platelet (HELLP) syndrome, 26 had intrahepatic cholestasis of pregnancy, 14 had hyperemesis gravidarum with abnormal liver enzymes, and 1 had acute fatty liver of pregnancy. The crude incidence of liver diseases unique to pregnancy was 0.77%. Outcomes were worse among women with HELLP or preeclampsia than the other disorders-of women with HELLP, 70% had a premature delivery, 4% had abruptio placentae, 3% had acute kidney injury, and 3% had infant death. Of women with preeclampsia, 56.0% had a premature delivery, 4% had abruptio placentae, 3% had acute kidney injury, and 0.7% had infant death. After 7 median years of follow up (range, 0-18 years), 14% of the women developed recurrent liver disease unique to pregnancy; the proportions were highest in women with initial hyperemesis gravidarum (36%) or intrahepatic cholestasis of pregnancy (35%). Women with preeclampsia were more likely to develop subsequent hepatobiliary diseases. We found the incidence of liver disease unique to pregnancy in Olmsted County, MN to be lower than that reported from Europe or US tertiary referral centers. Maternal and fetal outcomes in Olmsted County were better than those reported from other studies, but fetal mortality was still high (0.7%-3.0%). Women with preeclampsia or HELLP are at higher risk for peri-partum complications and subsequent development of comorbidities. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 08/2015; DOI:10.1016/j.cgh.2015.08.022 · 7.90 Impact Factor
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    ABSTRACT: Background Isotretinoin (13-cis retinoic acid) is a metabolite of vitamin A and has anti-inflammatory and immunoregulatory effects; however, a recent publication by DePaolo et al. demonstrated that in the presence of IL-15, retinoic acid can act as an adjuvant and promote inflammation against dietary proteins. Objective To evaluate the risk of overt and latent celiac disease (CD) among users of isotretinoin. Material and Methods Medical records of patients from 1995 to 2011 who had a mention of isotretinoin in their records (N = 8393) were searched for CD diagnosis using ICD-09CM codes. Isotretinoin exposure was compared across overt CD patients and their age- and gender-matched controls from the same pool. To evaluate the risk of latent CD with isotretinoin exposure, patients were overlapped with a community-based list of patients with waste serum samples that were tested for CD serology, excluding those with overt CD (2006–2011). Isotretinoin exposure was defined as the use of isotretinoin prior to CD diagnosis or serology. Results Of 8393 patients, 25 had a confirmed CD diagnosis. Compared to matched controls (N = 75), isotretinoin exposure was not significantly different between overt CD patients versus controls (36% versus 39%, respectively; P = 0.712). Likewise, latent CD defined as positive serology was not statistically different between isotretinoin exposed (N = 506) versus non-exposed (N = 571) groups (1.8% versus 1.4%, respectively; P = 0.474). Conclusions There was no association between isotretinoin use and risk of either overt or latent CD.
    PLoS ONE 08/2015; 10(8). DOI:10.1371/journal.pone.0135881 · 3.23 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-397-S-398. DOI:10.1016/S0016-5085(15)31337-8 · 16.72 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-1061. DOI:10.1016/S0016-5085(15)33623-4 · 16.72 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-776. DOI:10.1016/S0016-5085(15)32647-0 · 16.72 Impact Factor
  • Disha Khemani · Joseph J. Larson · Michael D. Leise
    Gastroenterology 04/2015; 148(4):S-1063. DOI:10.1016/S0016-5085(15)33632-5 · 16.72 Impact Factor
  • Alimentary Pharmacology & Therapeutics 03/2015; 41(6). DOI:10.1111/apt.13094 · 5.73 Impact Factor
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    ABSTRACT: Chronic kidney disease (CKD) is an important comorbidity after liver transplantation (LT); however, reliable tools with which to evaluate these patients are limited. In this work, we examine the extent to which the addition of serum cystatin C improves glomerular filtration rate (GFR) estimation and mortality prediction, in comparison to various GFR-estimating equations. The GFR was measured in LT recipients by iothalamate clearance. Concurrent serum cystatin C was assayed in banked serum samples. Performance of GFR-estimating equations with and without cystatin C, including the modification of diet in renal disease and CKD-epidemiology collaboration formulas was assessed. The proportional hazards regression analysis was performed to determine the association between serum cystatin C and mortality. A total of 586 iothalamate results were obtained in 401 patients after a mean of 4 years after LT. When compared to measured GFR, the formula with both creatinine and cystatin C, namely, CKD-epidemiology cr-cys, outperformed those with either marker alone. Performance of creatinine-based models was similar to one another. Serum cystatin C, by itself or as a part of an estimated GFR, was a significant predictor of mortality. Serum cystatin C has an important role in enhancing accuracy of GFR estimation and predicting mortality in LT recipients.
    Transplantation 01/2015; 99(7). DOI:10.1097/TP.0000000000000552 · 3.83 Impact Factor
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    ABSTRACT: Chemotherapy of patients with inactive hepatitis B virus (HBV) infection can lead to viral reactivation and flares of hepatitis. We investigated the proportions of patients screened for HBV infection before chemotherapy over time and outcomes of screened patients. In a retrospective study, we collected data from a pharmacy database on patients who underwent cytotoxic chemotherapy for solid or hematologic malignancies at the Mayo Clinic in Rochester, Minnesota, from January 1, 2006 through September 30, 2011. Laboratory data were collected from electronic medical records. Screening was identified based on tests for HB surface antigen, for any reason at any time before chemotherapy. Of 8005 patients undergoing chemotherapy, 1279 (16%) were screened for HBV infection before chemotherapy, including 668/1805 patients with hematologic malignancies (37%). The proportion of patients screened for HBV increased from 14.3% in 2006-2008 to 17.7% in 2009-2011 (P<.01). This trend was attributed mostly to an increase the proportion of patients with hematologic malignancies, from 32.7% in 2006-2008 to 40.6% in 2009-2011 (P<.01). Of 13 patients who tested positive for HBV, 5 did not receive prophylactic antiviral therapy; HBV infection was reactivated in 2 of these patients. None the 8 patients who received an antiviral agent before chemotherapy experienced HBV reactivation. Of 58 unscreened patients who had increases in levels of alanine aminotransferase (>300 U/L), only 1 appeared to have an undiagnosed HBV infection. Only a small percentage of patients receiving chemotherapy are screened for HBV infection. However, a larger proportion was screened during 2009-2011 than 2006-2008, especially of patients with hematologic malignancies. Strategies are needed to ensure that patients receiving chemotherapy are protected from the consequences of undiagnosed HBV infection. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Clinical Gastroenterology and Hepatology 11/2014; 13(5). DOI:10.1016/j.cgh.2014.10.032 · 7.90 Impact Factor
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    Journal of Hepatology 09/2014; 62(1). DOI:10.1016/j.jhep.2014.09.021 · 11.34 Impact Factor
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    ABSTRACT: Importance Isotretinoin is the standard treatment for refractory severe nodulocystic acne. A true association between prior isotretinoin use and development of inflammatory bowel disease (IBD) is uncertain. Addressing the reality of this association is important in decision making for both the clinician and the patient when isotretinoin treatment is indicated.Objective To assess the risk of IBD mainly in patients with acne with and without isotretinoin exposure.Design, Setting, and Participants In this retrospective, single-center study, the electronic medical records of patients who were primarily seeking acne treatment were reviewed for isotretinoin exposure. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to search for IBD diagnosis. participants included 1078 patients from 1995 to 2011, with isotretinoin referenced in their medical records, and who had ongoing local medical care defined as having had a serum sample collected between 2006 to 2011 for any reason while an Olmsted County, Minnesota, resident at the time of serum sample collection.Exposures The exposed group included the patients with confirmed prior isotretinoin exposure (n = 576), and the nonexposed group were defined as patients who never received isotretinoin or received it after the diagnosis of IBD (n = 502).Main Outcomes and Measures Risk of IBD among isotretinoin-exposed vs nonexposed patients.Results Both groups were comparable by race, prior systemic antibiotic use, and systemic tetracycline use. Inflammatory bowel disease developed less frequently in the isotretinoin-exposed group vs the nonexposed group (0.9% vs 2.6%; P = .03; unadjusted odds ratio [OR], 0.33; 95% CI, 0.12-0.93; P = .04). The negative association between isotretinoin exposure and IBD remained after adjusting for sex (OR, 0.28; 95% CI, 0.10-0.80; P = .02) and for sex and nonacne indication (OR, 0.28; 95% CI, 0.10-0.79; P = .02).Conclusions and Relevance Our study did not show an increased risk of IBD with prior isotretinoin use. If anything, the risk seemed to be decreased. Although these results may be due to chance given the small number of IBD cases, the anti-inflammatory and immune-modulating effects of isotretinoin may be worth exploring.
    JAMA Dermatology 09/2014; 150(12). DOI:10.1001/jamadermatol.2014.1540 · 4.43 Impact Factor
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    ABSTRACT: Hyponatremia is associated with an increased risk of mortality on the liver transplant (LTx) waiting list. Though incorporation of the serum sodium into the MELD score may reduce wait list mortality, concerns remain about a potential association between pre-LTx hyponatremia and decreased post-LTx survival. Furthermore, the relationship between pre-LTx hypernatremia and post-LTx survival remains unexplored. The purpose of this study was to investigate the impact of the entire spectrum pre-LTx serum sodium (Na) on post-LTx outcomes. We identified 19,537patients with serum Na that was available immediately before LTx from 2003-20010. Patients were divided into three groups including hyponatremic (Na ≤ 130 mEq/L), normonatremic (Na=131-145mEq/L) and hypernatremic (Na >145 mEq/L) groups and their post-LTx outcomes compared. There was no difference in in-hospital mortality or 90-day survival between patients with hyponatremia and normonatremia. A fraction (2.4%) of patients had hypernatremia, which was associated with increased in-hospital death (11.2% vs. 4.2%, p<0.001) and diminished 90 day survival (86.4% vs. 94.0.%, p<0.001). After adjusting for important clinical variables, the association of preLTx hypernatremia with post-transplant mortality remained significant with a HR=1.13 for each unit increase in sodium >145mEq/L (p<0.001). Length of hospitalization after LTx was significantly longer in hypernatremic patients (p < 0.001). In conclusion, hyponatremia per se does not affect post-LTx survival. Pre-LTx hypernatremia is a highly significant risk factor for post-LTx mortality. Liver Transpl , 2014. © 2014 AASLD.
    Liver Transplantation 06/2014; 20(6). DOI:10.1002/lt.23860 · 4.24 Impact Factor
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    ABSTRACT: Background The etiology of irritable bowel syndrome (IBS) is not been fully elucidated, but childhood trauma may disturb the brain–gut axis and therefore be important. Thus, we conducted a family based case–control study of IBS cases and their relatives with the aims to (i) determine the frequency of childhood trauma among IBS cases and controls as well as their relatives, and (ii) assess childhood trauma among IBS cases with affected relatives (familial IBS).Methods Outpatients with IBS, matched controls, and their first-degree relatives completed a self-report version of Bremner' Early Trauma Inventory. Percent of cases and controls with a family history were compared and odds ratios were computed using chi-squared test; recurrence risks to relatives were computed using logistic regression and generalized estimating equations.Key ResultsData were collected from 409 cases, 415 controls, 825 case relatives, and 921 control relatives. IBS cases had a median age of 50 and 83% were women. Of IBS cases, 74% had experienced any general trauma compared to 59% among controls, yielding an odds ratio of 1.56 (95% CI: 1.13–2.15, p < 0.008). There were no statistical differences between IBS relatives and control relatives with regards to lifetime trauma.Conclusions & InferencesIBS is associated with childhood trauma, and these traumas often occur prior to onset of IBS symptoms. This provides further insight into how traumatic childhood events are associated with development of adult IBS.
    Neurogastroenterology and Motility 05/2014; 26(7). DOI:10.1111/nmo.12353 · 3.59 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-966. DOI:10.1016/S0016-5085(14)63519-8 · 16.72 Impact Factor
  • Amanda M. Lynn · Joseph J. Larson · Michael D. Leise
    Gastroenterology 05/2014; 146(5):S-943. DOI:10.1016/S0016-5085(14)63425-9 · 16.72 Impact Factor
  • Amanda M. Lynn · Joseph J. Larson · Michael D. Leise
    Gastroenterology 05/2014; 146(5):S-1003. DOI:10.1016/S0016-5085(14)63648-9 · 16.72 Impact Factor
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    ABSTRACT: Objective To examine the effectiveness and tolerability of triple therapy with pegylated interferon (p-IFN), ribavirin (RBV), and telaprevir in patients with chronic hepatitis C receiving treatment in an academic practice setting and in a more clinically diverse population compared with patients receiving treatment in phase 3 trials. Patients and Methods A prospective database of all patients with viral hepatitis undergoing antiviral therapy from January 1, 2006, to July 1, 2012, was queried to identify treatment-naive and -experienced patients with chronic hepatitis C receiving dual and triple therapies. On-treatment response categories included rapid virologic response, extended rapid virologic response, early virologic response, and sustained virologic response. These patients were compared with matched controls, namely, patients who underwent dual therapy with p-IFN and RBV. Matching was performed for age, cirrhosis status, and prior treatment. Results There were 55 patients who received triple therapy and met the eligibility criteria, consisting of treatment-naive (n=35) and -experienced patients (n=20: those with relapse, 9; those with nonresponse, 9; and those who terminated the treatment early, 2). Rapid virologic response was achieved in 41% of the patients, extended rapid virologic response in 41%, and early virologic response in 75%. Sustained virologic response was observed in 51% (18/35) of treatment-naive patients, 67% (6/9) of the patients with prior nonresponse, and 56% (5/9) of those with prior relapse. Corresponding results after dual therapy were 37% (23/62), 11% (2/18), and 27% (3/11), respectively. The mean decrease in the hemoglobin level at weeks 4, 8, and 24 of triple therapy was 2.8, 3.8, and 3.2 mg/dL compared with 2.4, 2.6, and 2.4 mg/dL with dual therapy (to convert mg/dL to mmol/L, multiply values by 0.0259). Conclusion Telaprevir-based triple therapy in clinical practice is considerably more effective than dual therapy with p-IFN and RBV despite the significant degree of anemia that complicated therapy, requiring RBV dose reduction and erythropoietin support.
    Mayo Clinic Proceedings 05/2014; 89(5). DOI:10.1016/j.mayocp.2014.01.024 · 6.26 Impact Factor
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    ABSTRACT: The accuracy of creatinine-based estimated GFR (eGFR) in assessing the prevalence of chronic kidney disease (CKD) and associated mortality after liver transplantation (LTx) is unknown. Using measured GFR (mGFR) by iothalamate clearance, we determined the prevalence of the entire spectrum of renal dysfunction and the impact of CKD on mortality after LTx. A database that prospectively tracks all LTx recipients at this academic transplant program from 1985 to 2012 was queried to identify all adult primary LTx recipients. Our post-LTx protocol incorporates GFR measurement by iothalamate clearance at regular intervals. A multistate model was used to assess the prevalence of CKD, kidney transplant and death after LTx. Time-dependent Cox regression analysis was performed to evaluate the impact of mGFR and eGFR changes on survival. A total of 1,211 transplant recipients were included. At the time of LTx, the median age was 54 years, 60% were male and 86% were Caucasian. At 25 years after LTx, 54% of patients died, 9% underwent kidney transplantation, whereas 7%, 21% and 18% had mGFR >60, 59-30 and <30 ml/min/1.73m(2) respectively. The risk of death increased when mGFR decreased below 30 ml/min/1.73m(2): HR=2.67 (95% CI=1. 80-3.96) for GFR=29-15 ml/min/1.73m(2) and HR=5.47(95% CI=3.10-9.65) for GFR<15 ml/min/1.73m(2). Compared to mGFR, eGFR underestimated mortality risk in LTx recipients with an eGFR of 30-90 ml/min/1.73m(2). An overwhelming majority of LTx recipients develop CKD. The risk of death increases exponentially when GFR<30 ml/min/1.73m(2). Creatinine-based eGFR underestimates the mortality risk in a large proportion of patients.
    Journal of Hepatology 04/2014; 61(2). DOI:10.1016/j.jhep.2014.03.034 · 11.34 Impact Factor
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    ABSTRACT: The hospital at which liver transplantation (LT) is performed has a substantial impact on post-LT outcomes. Center-specific outcome data are closely monitored not only by the centers themselves but also by patients and government regulatory agencies. However, the true magnitude of this center effect, apart from the effects of the region and donor service area (DSA) as well as recipient and donor determinants of graft survival, has not been examined. We analyzed data submitted to the Organ Procurement and Transplantation Network for all adult (age ≥ 18 years) primary LT recipients (2005-2008). Using a mixed effects, proportional hazards regression analysis, we modeled graft failure within 1 year after LT on the basis of center (de-identified), region, DSA, and donor and recipient characteristics. At 115 unique centers, 14,654 recipients underwent transplantation. Rates of graft loss within a year varied from 5.9% for the lowest quartile of centers to 20.2% for the highest quartile. Gauged by a comparison of the 75th and 25th percentiles of the data, the magnitude of the center effect on graft survival (1.49-fold change) was similar to that of the recipient Model for End-Stage Liver Disease (MELD) score (1.47) and the donor risk index (DRI; 1.45). The center effect was similar across the DRI and MELD score quartiles and was not associated with a center's annual LT volume. After stratification by region and DSA, the magnitude of the center effect, though decreased, remained significant and substantial (1.30-fold interquartile difference). In conclusion, the LT center is a significant predictor of graft failure that is independent of region and DSA as well as donor and recipient characteristics. Liver Transpl, 2013. © 2013 AASLD.
    Liver Transplantation 09/2013; 19(9). DOI:10.1002/lt.23685 · 4.24 Impact Factor
  • Alina M Allen · W Ray Kim · Joseph Larson · Edward V Loftus
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    ABSTRACT: There is uncertainty about the efficacy and safety of treatment for hepatitis C virus (HCV) infection in patients with inflammatory bowel disease (IBD). IBD can become exacerbated during treatment with interferon (IFN) and serious adverse events, such as pancytopenia or hepatotoxicity, can be compounded by drug interactions. We investigated the risk of exacerbation of IBD during HCV therapy and the rate of adverse effects of concomitant therapy for HCV and IBD. We also evaluated the efficacy of HCV treatment in the IBD population. We conducted a retrospective review of all patients who underwent IFN-based treatment for HCV at the Mayo Clinic in Rochester, Minnesota from 2001 through 2012. Exacerbation of IBD was evaluated by clinical, endoscopic, and histologic parameters during antiviral therapy and the ensuing 12 months. Hematologic toxicity was assessed by levels of all 3 cell lineages at baseline and during therapy. Efficacy of antiviral treatment was assessed by serum levels of HCV RNA until 24 weeks after completion of therapy. We also conducted a detailed Medline database search and reviewed the literature on this topic. We identified 15 subjects with concomitant IBD (8 with ulcerative colitis and 7 with Crohn's disease). Only 1 patient experienced an exacerbation of the disease during therapy; symptoms were controlled with mesalamine enemas. Another patient developed a flare shortly after completing antiviral therapy; symptoms returned spontaneously to baseline 2 weeks later. All subjects experienced an anticipated degree of pancytopenia while on IFN-based therapy. The rate of sustained virologic response was 67 %. A concise review of available literature regarding the safety and efficacy of HCV treatment in IBD patients is also presented; although limited, the published data appears to support the safety of treatment with IFN in patients whose IBD is under control. In conjunction with data from the literature, our findings indicate that the efficacy and safety of HCV therapy with IFN and ribavirin for patients with IBD are comparable to those of subjects without IBD.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 07/2013; 11(12). DOI:10.1016/j.cgh.2013.07.014 · 7.90 Impact Factor