Outcomes after multiple courses of granulocyte colony‐stimulating factor and growth hormone in decompensated cirrhosis: A randomized trial

Verma, Nipun; Kaur, Amritjyot; Sharma, Ratiram; Bhalla, Ashish; Sharma, Navneet; De, Arka; Singh, Virendra

doi:10.1002/hep.29763

Cited by 49 publications

(64 citation statements)

References 48 publications

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“…Transplant free survival at 12 months was significantly improved in both groups of G-CSF-treated patients, associated with decreased measures of liver disease severity and a significant reduction in the odds of developing a bacterial infection (including ~88% reduction in the odds of developing sepsis). GH treatment did not show any additional benefit in reducing infections or in survival (120). In contrast to these promising results, G-CSF treatment for 5 consecutive days or G-CSF treatment followed by 3 doses of autologous CD133+ hematopoietic stem cells in patients with compensated cirrhosis did not improve liver disease severity (MELD score, the primary outcome), and there was evidence to suggest G-CSF treatment, with or without stem cells, was associated with an increased frequency of adverse events compared to standard care ( n = 26–28 per group) (121).…”

Section: Immunotherapeutic Approaches To Reduce Susceptibility To Infmentioning

confidence: 99%

Causes and Consequences of Innate Immune Dysfunction in Cirrhosis

et al. 2019

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Liver cirrhosis is an increasing health burden and public health concern. Regardless of etiology, patients with cirrhosis are at risk of a range of life-threatening complications, including the development of infections, which are associated with high morbidity and mortality and frequent hospital admissions. The term Cirrhosis-Associated Immune Dysfunction (CAID) refers to a dynamic spectrum of immunological perturbations that develop in patients with cirrhosis, which are intimately linked to the underlying liver disease, and negatively correlated with prognosis. At the two extremes of the CAID spectrum are systemic inflammation, which can exacerbate clinical manifestations of cirrhosis such as hemodynamic derangement and kidney injury; and immunodeficiency, which contributes to the high rate of infection in patients with decompensated cirrhosis. Innate immune cells, in particular monocytes/macrophages and neutrophils, are pivotal effector and target cells in CAID. This review focuses on the pathophysiological mechanisms leading to impaired innate immune function in cirrhosis. Knowledge of the phenotypic manifestation and pathophysiological mechanisms of cirrhosis associated immunosuppression may lead to immune targeted therapies to reduce susceptibility to infection in patients with cirrhosis, and better biomarkers for risk stratification, and assessment of efficacy of novel immunotherapies.

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Section: Immunotherapeutic Approaches To Reduce Susceptibility To Infmentioning

confidence: 99%

Causes and Consequences of Innate Immune Dysfunction in Cirrhosis

et al. 2019

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“…Protein energy malnutrition can contribute to the onset and progression of the withdrawal of anabolism in states in liver cirrhosis . Furthermore, anabolic resistance is correlated with factors including hormonal abnormalities, such as testosterone and insulin‐like growth factor imbalances, and persistent chronic inflammatory cytokines, such as interleukin‐6 and tumor necrosis factor‐α . According to the molecular mechanisms responsible for the LSMM in cirrhotic patients, researchers have reported the roles of myostatin, adenosine monophosphate kinase, and the impaired mechanistic target of rapamycin signaling in anabolic resistance in animal models.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for loss of skeletal muscle mass in patients with cirrhosis

Sung

Uojima

Hidaka

et al. 2019

Hepatology Research

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Aim The present study aimed to assess the correlation between loss of skeletal muscle mass (LSMM) and the clinical characteristics of patients with liver cirrhosis. Methods This multicenter, prospective study was undertaken at five locations in Japan and involved a 12‐month observation period. After baseline assessment, the change in the skeletal muscle index per year (ΔSMI/y) was evaluated in the enrolled patients; LSMM was defined as ΔSMI/y < 0. We evaluated the relationships between LSMM and baseline clinical characteristics in patients with liver cirrhosis. Results A total of 166 patients with cirrhosis were enrolled and, of these, 123 patients (74.1%) showed LSMM. Multivariate analysis confirmed that hepatic encephalopathy, Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA+‐M2BP) (≥1.86), age (≥60 years), and grip strength (<18 kg for women and <26 kg for men) were independent predictors of skeletal muscle decline (P = 0.042, odds ratio [OR] 8.997, 95% confidence interval [CI] 1.083–74.71; P = 0.023, OR 3.970, 95% CI 1.468–6.177; P = 0.037, OR 2.526, 95% CI 1.056–6.045; and P = 0.002, OR 3.970, 95% CI 1.691–9.322, respectively). Conclusions Advanced age, low grip strength, hepatic encephalopathy, and high WFA+‐M2BP might be risk factors for LSMM in liver cirrhosis patients.

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“…Explanations for such robust fibrosis reversal and improvement in synthetic liver function was not supported by strong research data in the discussion. Reasons for GCSF related to 'liver regeneration' as discussed by the Verma et al 59 remain hypothetical.…”

Section: Critical Appraisal Of Gcsf In Decompensated Cirrhosismentioning

confidence: 99%

Role of Granulocyte Colony-stimulating Factor Therapy in Cirrhosis, ‘Inside Any Deep Asking Is the Answering’

Philips¹,

Augustine²,

Ahamed³

et al. 2019

Journal of Clinical and Translational Hepatology

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Liver cirrhosis progresses through multiple clinical stages which culminate in either death or liver transplantation. Availability of organs, timely listing and prompt receipt of donor-livers pose difficulties in improving transplant-listed and transplant outcomes. In this regard, regenerative therapies, particularly with granulocyte colony-stimulating factor (GCSF), has become a lucrative option for improving transplant-free survival. However, the literature is confusing with regards to patient selection and real outcomes. In this exhaustive review, we describe the basics of liver fibrosis and cirrhosis through novel insights from a therapeutic point of view, discuss preclinical studies on GCSF in advanced liver disease to improve on clinical utility, shed light on the pertinent literature of GCSF in advanced cirrhosis, and provide astute inputs on growth factor therapy in decompensated cirrhosis.

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Outcomes after multiple courses of granulocyte colony‐stimulating factor and growth hormone in decompensated cirrhosis: A randomized trial

Cited by 49 publications

References 48 publications

Causes and Consequences of Innate Immune Dysfunction in Cirrhosis

Causes and Consequences of Innate Immune Dysfunction in Cirrhosis

Risk factors for loss of skeletal muscle mass in patients with cirrhosis

Role of Granulocyte Colony-stimulating Factor Therapy in Cirrhosis, ‘Inside Any Deep Asking Is the Answering’

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