O10 Granulocyte-Colony Stimulating Factor (G-CSF) to treat acute-on-chronic liver failure; results of the first multicenter randomized trial (GRAFT study)

Engelmann, Cornelius; Herber, Adam; Ildh, Tony; Schiefke, Ingolf; Zipprich, Alexander; Schmiedeknecht, Anett; Zeuzem, Stefan; Goeser, Tobias; Canbay, Ali; Berg, Christoph; Trebicka, Jonel; Uschner, Frank Erhard; Mueller, Tobias; Aehling, Niklas; Schmelzle, Moritz; Splith, Katrin; Lammert, Frank; Lange, Christian; Sarrazin, Christoph; Manns, Michael P.; Häussinger, Dieter; Pfeiffenberger, Jan; Galle, Peter R.; Franke, Annegret; Berg, Thomas

doi:10.1136/gutjnl-2021-basl.10

Cited by 5 publications

(3 citation statements)

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“…On the contrary, a recent European multicenter clinical trial reveals that G-CSF does not have any superior benefits than the standard medical treatment. The findings unveil that G-CSF is ineffective in improving patient survival and other clinical endpoints including MELD score, CLIF-C organ failure score, and the occurrence of infection, recommending G-SCF not be used as a standard treatment for ACLF ( 168 ).…”

Section: Strategies For the Management Of Aclfmentioning

confidence: 99%

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Khanam

Kottilil

2021

Front. Med.

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Acute-on-chronic liver failure (ACLF) is a multifaceted condition with poor treatment options and high short-term mortality. ACLF can develop in patients with or without liver cirrhosis, where patients with decompensated cirrhosis display a higher risk of short-term mortality. Pathophysiological mechanisms include systemic inflammation due to bacterial and fungal infections and acute hepatic insult with drug, alcohol, and viral hepatitis. Cryptogenic factors also contribute to the development of ACLF. The clinical outcome of patients with ACLF gets further complicated by the occurrence of variceal hemorrhage, hepatorenal syndrome, hepatic encephalopathy, and systemic immune dysfunction. Regardless of the better understanding of pathophysiological mechanisms, no specific and definitive treatment is available except for liver transplantation. The recent approach of regenerative medicine using mesenchymal stem cells (MSCs) could be advantageous for the treatment of ACLF as these cells can downregulate inflammatory response by inducing antiinflammatory events and prevent hepatic damage and fibrosis by inhibiting hepatic stellate cell activation and collagen synthesis. Moreover, MSCs are involved in tissue repair by the process of liver regeneration. Considering the broad therapeutic potential of MSCs, it can serve as an alternative treatment to liver transplant in the near future, if promising results are achieved.

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Section: Strategies For the Management Of Aclfmentioning

confidence: 99%

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Khanam

Kottilil

2021

Front. Med.

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“…106 In a recently published “GRAFT” randomized trial on 176 patients with ACLF (52% ALD), G-CSF 5 μg/kg for 5 days in 88 patients failed to improve liver disease and achieve primary endpoint of 90-day transplant-free survival (34.1 vs. 37.5%, p = 0.80). 107 Clearly, more data are needed on the role of G-CSF in the management of AH before recommending its routine use in clinical practice ( Table 6 ).…”

Section: Management Of Liver Diseasementioning

confidence: 99%

Therapeutic Pipeline in Alcohol-Associated Liver Disease

2022

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Alcohol-associated liver disease is a leading cause of mortality and morbidity worldwide. Patients with alcohol-associated liver disease are often diagnosed at advanced stage and disease spectrum including alcoholic hepatitis, a severe manifestation with a high short-term mortality. Corticosteroid, recommended first-line treatment for patients with alcoholic hepatitis, is a very suboptimal treatment. Although the use of early liver transplantation has increased with consistent benefit in select patients with alcoholic hepatitis, its use remains heterogeneous worldwide due to lack of uniform selection criteria. Over the last decade, several therapeutic targets have evolved of promise with ongoing clinical trials in patients with cirrhosis and alcoholic hepatitis. Even with availability of effective medical therapies for alcohol-associated liver disease, long-term outcome depends on abstinence from alcohol use in any spectrum of alcohol-associated liver disease. However, alcohol use disorder treatment remains underutilized due to several barriers even in patients with advanced disease. There is an urgent unmet need to implement and promote integrated multidisciplinary care model with hepatologists and addiction experts to provide comprehensive management for these patients. In this review, we will discuss newer therapies targeting liver disease and therapies targeting alcohol use disorder in patients with alcohol-associated liver disease.

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“…In total, seven drug-related serious adverse reactions occurred in the G-CSF group. 65 A recently meta-analysis, aimed to resolve some aspects regarding the discrepancy in outcome in Asian versus European studies, assessing the effects of G-CSF in alcoholic hepatitis. Data of the effect of G-CSF on the 90-day mortality rate and risk of infection from patients with ASH were analyzed.…”

Section: Human Mesenchymal Stem Cellsmentioning

confidence: 99%

Mesenchymal Stem Cell Transplantation in Liver Diseases

Nevens

Merwe

2022

Semin Liver Dis

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Promising preclinical data suggested that bone marrow–derived mesenchymal stem cells (BM-MSC) can reduce hepatic fibrosis and stimulate liver regeneration. Preclinical studies moreover suggested that the immunomodulatory and anti-inflammatory functions of MSCs may reduce hepatic inflammation, improve liver function, and decrease infection incidences which are deemed especially important in the case of acute-on-chronic liver failure (ACLF). Studies in patients with decompensated cirrhosis demonstrated that injection of BM-MSC resulted in an improvement of biochemical tests and led to a survival benefit in ACLF. Most of these studies were performed in hepatitis B virus infected patients. However, two adequately powered studies performed in Europe could not confirm these data. A possible alternative to mobilize BM-MSC into the liver is the use of granulocyte colony-stimulating factor (G-CSF) which has proregenerative and immunomodulatory effects. In Indian studies, the use of G-CSF was associated with improvement of survival, although this finding could not be confirmed in European studies. Human allogeneic liver-derived progenitor cell therapy represents a potential treatment for ACLF, of which the main action is paracrine. These human liver–derived MSC can perform various functions, including the downregulation of proinflammatory responses. The clinical beneficial effect of these cells is further explored in patients with alcoholic cirrhosis and ACLF in Europe.

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O10 Granulocyte-Colony Stimulating Factor (G-CSF) to treat acute-on-chronic liver failure; results of the first multicenter randomized trial (GRAFT study)

Cited by 5 publications

References 0 publications

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Therapeutic Pipeline in Alcohol-Associated Liver Disease

Mesenchymal Stem Cell Transplantation in Liver Diseases

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