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  1. Article ; Online: Fuel to the fire: The impact of COVID-19 on alcohol-associated hepatitis.

    Sengupta, Shreya / Dasarathy, Srinivasan

    Alcohol, clinical & experimental research

    2023  Volume 47, Issue 12, Page(s) 2223–2226

    Language English
    Publishing date 2023-10-09
    Publishing country United States
    Document type Journal Article
    ISSN 2993-7175
    ISSN (online) 2993-7175
    DOI 10.1111/acer.15204
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  2. Article ; Online: Myostatin and beyond in cirrhosis: all roads lead to sarcopenia.

    Dasarathy, Srinivasan

    Journal of cachexia, sarcopenia and muscle

    2017  Volume 8, Issue 6, Page(s) 864–869

    MeSH term(s) Fibrosis ; Humans ; Liver Cirrhosis ; Myostatin ; Sarcopenia
    Chemical Substances Myostatin
    Language English
    Publishing date 2017-11-06
    Publishing country Germany
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 2586864-0
    ISSN 2190-6009 ; 2190-5991
    ISSN (online) 2190-6009
    ISSN 2190-5991
    DOI 10.1002/jcsm.12262
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  3. Article ; Online: Are Exercise Benefits in Nonalcoholic Fatty Liver Disease Due to Increased Autophagy?

    Dasarathy, Srinivasan

    Exercise and sport sciences reviews

    2017  Volume 45, Issue 3, Page(s) 125

    MeSH term(s) Autophagy ; Exercise ; Humans ; Liver ; Non-alcoholic Fatty Liver Disease
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 187040-3
    ISSN 1538-3008 ; 0091-6331
    ISSN (online) 1538-3008
    ISSN 0091-6331
    DOI 10.1249/JES.0000000000000118
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    Se 318: Show issues Location:
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  4. Article ; Online: Nutrition and Alcoholic Liver Disease: Effects of Alcoholism on Nutrition, Effects of Nutrition on Alcoholic Liver Disease, and Nutritional Therapies for Alcoholic Liver Disease.

    Dasarathy, Srinivasan

    Clinics in liver disease

    2016  Volume 20, Issue 3, Page(s) 535–550

    Abstract: Malnutrition is the most frequent and nearly universal consequence in alcoholic liver disease (ALD) that adversely affects clinical outcomes. Sarcopenia or skeletal muscle loss is the major component of malnutrition in liver disease. There are no ... ...

    Abstract Malnutrition is the most frequent and nearly universal consequence in alcoholic liver disease (ALD) that adversely affects clinical outcomes. Sarcopenia or skeletal muscle loss is the major component of malnutrition in liver disease. There are no effective therapies to prevent or reverse sarcopenia in ALD because the mechanisms are not well understood. Consequences of liver disease including hyperammonemia, hormonal perturbations, endotoxemia and cytokine abnormalities as well as the direct effects of alcohol and its metabolites contribute to sarcopenia in ALD. This article focuses on the prevalence, methods to quantify malnutrition, specifically sarcopenia and potential therapies including novel molecular targeted treatments.
    MeSH term(s) Alcoholism/complications ; Animals ; Humans ; Liver Diseases, Alcoholic/complications ; Liver Diseases, Alcoholic/therapy ; Malnutrition/complications ; Malnutrition/epidemiology ; Malnutrition/therapy ; Metabolic Networks and Pathways ; Nutrition Therapy ; Nutritional Status ; Prevalence ; Risk Factors ; Sarcopenia/etiology ; Sarcopenia/metabolism
    Language English
    Publishing date 2016-04-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1472315-3
    ISSN 1557-8224 ; 1089-3261
    ISSN (online) 1557-8224
    ISSN 1089-3261
    DOI 10.1016/j.cld.2016.02.010
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  5. Article ; Online: Cause and management of muscle wasting in chronic liver disease.

    Dasarathy, Srinivasan

    Current opinion in gastroenterology

    2016  Volume 32, Issue 3, Page(s) 159–165

    Abstract: Purpose of review: Sarcopenia or loss of skeletal muscle mass is the major component of malnutrition and occurs in the majority of patients with liver disease. Lower muscle contractile function also contributes to the adverse consequences of sarcopenia. ...

    Abstract Purpose of review: Sarcopenia or loss of skeletal muscle mass is the major component of malnutrition and occurs in the majority of patients with liver disease. Lower muscle contractile function also contributes to the adverse consequences of sarcopenia. There are no effective therapies to prevent or reverse sarcopenia in liver disease. This review will discuss the advances in diagnosis, pathogenesis, and treatment options for sarcopenia in liver disease.
    Recent findings: Sarcopenia increases mortality and risk of development of other complications of cirrhosis, and worsens postliver transplant outcomes while quality of life is decreased. Unlike other complications of cirrhosis that reverse after liver transplantation, sarcopenia may not improve and actually worsens. Impaired skeletal muscle protein synthesis and increased proteolysis via autophagy contribute to sarcopenia. Hyperammonemia is the best-studied mediator of the liver-muscle axis. Molecular studies show increased expression of myostatin whereas metabolic studies show impaired mitochondrial function and tricarboxylic acid cycle intermediates because of cataplerosis of α-ketoglutarate. Impaired skeletal muscle pyruvate and fatty acid oxidation during hyperammonemia suggest amino acids are diverted to acetyl CoA and potentially aggravate hyperammonemia. Nutritional supplementation is of limited or no benefit and suggests that cirrhosis is a state of anabolic resistance. Exercise may be beneficial but whether it overcomes anabolic resistance is not known.
    Summary: The high clinical significance of sarcopenia is well established. Current approaches to nutritional supplementation have not been effective in reversing sarcopenia because of anabolic resistance. Myostatin antagonists, specific amino acid supplementation, mitochondrial protection, and combination endurance-resistance exercise are potential future therapeutic options.
    MeSH term(s) Chronic Disease ; Humans ; Liver Cirrhosis/complications ; Liver Cirrhosis/physiopathology ; Liver Diseases/complications ; Malnutrition/diagnosis ; Malnutrition/etiology ; Sarcopenia/diagnosis ; Sarcopenia/etiology ; Sarcopenia/physiopathology ; Sarcopenia/therapy
    Language English
    Publishing date 2016-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 632571-3
    ISSN 1531-7056 ; 0267-1379
    ISSN (online) 1531-7056
    ISSN 0267-1379
    DOI 10.1097/MOG.0000000000000261
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2072: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Reply.

    Szabo, Gyongyi / Mitchell, Mack C / Dasarathy, Srinivasan / McClain, Craig

    Hepatology (Baltimore, Md.)

    2023  Volume 77, Issue 5, Page(s) E115

    Language English
    Publishing date 2023-02-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1097/HEP.0000000000000337
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    Zs.A 1660: Show issues Location:
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  7. Article: Treatment to improve nutrition and functional capacity evaluation in liver transplant candidates.

    Dasarathy, Srinivasan

    Current treatment options in gastroenterology

    2014  Volume 12, Issue 2, Page(s) 242–255

    Abstract: Opinion statement: Liver transplantation is the definitive therapy for cirrhosis, and malnutrition is the most frequent complication in these patients. Sarcopenia or loss of muscle mass is the major component of malnutrition in cirrhotics and adversely ... ...

    Abstract Opinion statement: Liver transplantation is the definitive therapy for cirrhosis, and malnutrition is the most frequent complication in these patients. Sarcopenia or loss of muscle mass is the major component of malnutrition in cirrhotics and adversely affects their outcome. In addition to the metabolic consequences, functional consequences of sarcopenia include reduced muscle strength and deconditioning. Despite nearly universal occurrence of sarcopenia and its attendant complications, there are no established therapies to prevent or reverse the same. Major reasons for this deficiency include the lack of established standardized definitions or measures to quantify muscle mass, as well as paucity of mechanistic studies or identified molecular targets to develop specific therapeutic interventions. Anthropometric evaluation, bioelectrical impedance analysis, and DEXA scans are relatively imprecise measures of muscle mass, and recent data on imaging measures to determine muscle mass accurately are likely to allow well-defined outcome responses to treatments. Resurgence of interest in the mechanisms of muscle loss in liver disease has been directly related to the rapid advances in the field of muscle biology. Metabolic tracer studies on whole body kinetics have been complemented by direct studies on the skeletal muscle of cirrhotics. Hypermetabolism and anabolic resistance contribute to sarcopenia. Reduced protein synthesis and increased autophagy have been reported in cirrhotic skeletal muscle, while the contribution of the ubiquitin-proteasome pathway is controversial. Increased plasma concentration and skeletal muscle expression of myostatin, a TGFβ superfamily member that causes reduction in muscle mass, have been reported in cirrhosis. Hyperammonemia and TNFα have been reported to increase myostatin expression and may be responsible for sarcopenia in cirrhosis. Nutriceutical interventions with leucine enriched amino acid mixtures, myostatin antagonists and physical activity hold promise as measures to reverse sarcopenia. There is even less data on muscle function and deconditioning in cirrhosis and studies in this area are urgently needed. Even though macronutrient replacement is a major therapeutic goal, micronutrient supplementation, specifically vitamin D, is expected to improve outcomes.
    Language English
    Publishing date 2014-03-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2057334-0
    ISSN 1534-309X ; 1092-8472
    ISSN (online) 1534-309X
    ISSN 1092-8472
    DOI 10.1007/s11938-014-0016-9
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    Zs.A 5533: Show issues Location:
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  8. Article ; Online: Is the adiponectin-AMPK-mitochondrial axis involved in progression of nonalcoholic fatty liver disease?

    Dasarathy, Srinivasan

    Hepatology (Baltimore, Md.)

    2014  Volume 60, Issue 1, Page(s) 22–25

    MeSH term(s) Adiponectin/blood ; Animals ; Fatty Liver/metabolism ; Male ; Mitochondria/metabolism ; Non-alcoholic Fatty Liver Disease ; Obesity/metabolism ; Receptors, Leptin/genetics ; Weight Gain/physiology
    Chemical Substances Adiponectin ; Adipoq protein, mouse ; Receptors, Leptin ; leptin receptor, mouse
    Language English
    Publishing date 2014-05-06
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.27134
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    Zs.A 1660: Show issues Location:
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  9. Article ; Online: Development and evaluation of objective trial performance metrics for multisite clinical studies: Experience from the AlcHep Network.

    Dasarathy, Srinivasan / Tu, Wanzhu / Bellar, Annette / Welch, Nicole / Kettler, Carla / Tang, Qing / Liangpunsakul, Suthat / Gawrieh, Samer / Radaeva, Svetlana / Mitchell, Mack

    Contemporary clinical trials

    2024  Volume 138, Page(s) 107437

    Abstract: Background: Recruitment and retention are critical in clinical studies but there are limited objective metrics of trial performance. We tested if development of trial performance metrics will allow for objective evaluation of study quality. Performance ... ...

    Abstract Background: Recruitment and retention are critical in clinical studies but there are limited objective metrics of trial performance. We tested if development of trial performance metrics will allow for objective evaluation of study quality. Performance metrics were developed using data from the observational cohort (OBS) and randomized clinical trial (RCT) arms of the prospective Alcoholic Hepatitis Network.
    Methods: Yield-rate (%YR; eligible/screened), recruitment index (RI; mean recruitment time/patient), completion index (CI; average number of days to complete the follow-up/patient), and protocol adherence index (AI; average number of deviations/subject recruited) were determined.
    Results: 2250 patients (1168 for OBS; 1082 for RCT) were screened across 8 sites. Recruitment in the RCT (57% target) was similar to that in the OBS (59% target). Of those screened, 743 (63.6%) subjects in the OBS and 147 (13.6%) subjects in the RCT were enrolled in the study. In OBS study, 253 (34.1%) subjects, and in the RCT, 68 (46.3%) subjects, completed the study or reached a censoring event. Across all sites (range), YR for OBS was 63.6% (41.3-98.3%) and for RCT was 13.6% (5.5-92.6%); RI for OBS was 1.66 (8.79-19.85) and for RCT was 4.05 (19.76-36.43); CI for OBS was 4.87 (22.6-118.3) and for RCT was 8.75 (27.27-161.5); and AR for OBS was 0.56 (0.08-1.04) and for RCT was 1.55 (0.39-3.21. Factors related to participants, research design, study team, and research sponsors contributed to lower performance metrics.
    Conclusions: Objective measures of clinical trial performance allow for strategies to enhance study quality and development of site-specific improvement plans.
    Trial registration number: ClinicalTrials.gov NCT4072822 NCT03850899.
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2182176-8
    ISSN 1559-2030 ; 1551-7144
    ISSN (online) 1559-2030
    ISSN 1551-7144
    DOI 10.1016/j.cct.2024.107437
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    Zs.A 1581: Show issues Location:
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  10. Article ; Online: Emergency services utilization by patients with alcohol-associated hepatitis: An analysis of national trends.

    Sengupta, Shreya / Anand, Akhil / Lopez, Rocio / Weleff, Jeremy / Wang, Philip R / Bellar, Annette / Attaway, Amy / Welch, Nicole / Dasarathy, Srinivasan

    Alcohol, clinical & experimental research

    2024  Volume 48, Issue 1, Page(s) 98–109

    Abstract: Background: Hospitalization and mortality in patients with alcohol-associated hepatitis (AH), a severe form of liver disease, continue to increase over time. Given the severity of the illness, most hospitalized patients with AH are admitted from the ... ...

    Abstract Background: Hospitalization and mortality in patients with alcohol-associated hepatitis (AH), a severe form of liver disease, continue to increase over time. Given the severity of the illness, most hospitalized patients with AH are admitted from the emergency department (ED). However, there are no data on ED utilization by patients with AH. Thus, the Nationwide Emergency Department Sample (NEDS) dataset was analyzed to determine the ED utilization for AH.
    Methods: Temporal trends (2016-2019) and outcomes of ED visits for AH were determined. Primary or secondary AH diagnoses were based on coding priority. Numbers of patients evaluated in the ED, severity of disease, complications of liver disease, and discharge disposition were analyzed. Crude and adjusted rates were examined, and temporal trends evaluated using logistic regression with orthogonal polynomial contrasts for each year.
    Results: There were 466,014,370 ED visits during 2016-2019, of which 448,984 (0.096%) were for AH, 85.0% of which required hospitalization. The rate of visits for AH (primary and secondary) between 2016 and 2019 increased from 85 to 106.8/100,000 ED visits. The rate of secondary AH increased more than the rate of primary AH (from 68.6 to 86.5 vs. from 16.4 to 20.3/100,000 ED visits). Patients aged 45-64 years had the highest rate of ED visits for AH, which decreased during the study period, while the rate of ED visits for AH increased in those aged 25-44 years (from 38.5% to 42.9%). The severity of disease (ascites, hepatic encephalopathy, and acute kidney injury) also increased over time. Medicaid and private insurance were the most common payors for patients seeking care in the ED for AH.
    Conclusions: Temporal trends show an overall increase in ED utilization rates for AH, more patients requiring hospitalization, and an increase in the proportion of younger patients presenting to the ED with AH.
    Language English
    Publishing date 2024-01-09
    Publishing country United States
    Document type Journal Article
    ISSN 2993-7175
    ISSN (online) 2993-7175
    DOI 10.1111/acer.15223
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