Granulocyte Colony-Stimulating Factor in Severe Alcoholic Hepatitis: A Randomized Pilot Study

Singh, Virendra; Sharma, Arun; Narasimhan, R; Bhalla, Ashish; Sharma, Navneet; Sharma, Ratiram

doi:10.1038/ajg.2014.154

Cited by 206 publications

(205 citation statements)

References 34 publications

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“…The authors' medical center did not use corticosteroids as standard medical therapy for severe alcoholic hepatitis. The survival rate in the standard care alone group was lower than previous studies of pentoxifylline most likely secondary to higher mDF/MELD scores in the study of Singh et al (5).…”

contrasting

confidence: 52%

“If a fake friend stays in your vodkabulary as a stem friend”: Granulocyte colony-stimulating factor promoted stem cell therapy in severe alcoholic hepatitis

Tahan

Tahan²

2015

Turk J Gastroenterol

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contrasting

confidence: 52%

“If a fake friend stays in your vodkabulary as a stem friend”: Granulocyte colony-stimulating factor promoted stem cell therapy in severe alcoholic hepatitis

Tahan

Tahan²

2015

Turk J Gastroenterol

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“…31 An alternative strategy is to combine the use of steroids with granulocyte colony stimulating factor, which has previously been evaluated in a small recently published trial. 64 The STOPAH trial results do not demonstrate any benefit from the use of PTX in severe AH. The low incidence of acute kidney injury in the STOPAH trial prevents a definitive conclusion being drawn on the ability of PTX to prevent hepatorenal syndrome.…”

Section: Discussionmentioning

confidence: 99%

The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial

Thursz

Forrest

Roderick

et al. 2015

Health Technol Assess

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BackgroundAlcoholic hepatitis (AH) is a distinct presentation of alcoholic liver disease arising in patients who have been drinking to excess for prolonged periods, which is characterised by jaundice and liver failure. Severe disease is associated with high short-term mortality. Prednisolone and pentoxifylline (PTX) are recommended in guidelines for treatment of severe AH, but trials supporting their use have given heterogeneous results and controversy persists about their benefit.ObjectivesThe aim of the clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis trial was to resolve the clinical dilemma on the use of prednisolone or PTX.DesignThe trial was a randomised, double-blind, 2 × 2 factorial, multicentre design.SettingSixty-five gastroenterology and hepatology inpatient units across the UK.ParticipantsPatients with a clinical diagnosis of AH who had a Maddrey’s discriminant function value of ≥ 32 were randomised into four arms: A, placebo/placebo; B, placebo/prednisolone; C, PTX/placebo; and D, PTX/prednisolone. Of the 5234 patients screened for the trial, 1103 were randomised and after withdrawals, 1053 were available for primary end-point analysis.InterventionsThose allocated to prednisolone were given 40 mg daily for 28 days and those allocated to PTX were given 400 mg three times per day for 28 days.OutcomesThe primary outcome measure was mortality at 28 days. Secondary outcome measures included mortality or liver transplant at 90 days and at 1 year. Rates of recidivism among survivors and the impact of recidivism on mortality were assessed.ResultsAt 28 days, in arm A, 45 of 269 (16.7%) patients died; in arm B, 38 of 266 (14.3%) died; in arm C, 50 of 258 (19.4%) died; and in arm D, 35 of 260 (13.5%) died. For PTX, the odds ratio for 28-day mortality was 1.07 [95% confidence interval (CI) 0.77 to 1.40;p = 0.686)] and for prednisolone the odds ratio was 0.72 (95% CI 0.52 to 1.01;p = 0.056). In the logistic regression analysis, accounting for indices of disease severity and prognosis, the odds ratio for 28-day mortality in the prednisolone-treated group was 0.61 (95% CI 0.41 to 0.91;p = 0.015). At 90 days and 1 year there were no significant differences in mortality rates between the treatment groups. Serious infections occurred in 13% of patients treated with prednisolone compared with 7% of controls (p = 0.002). At the 90-day follow-up, 45% of patients reported being completely abstinent, 9% reported drinking within safety limits and 33% had an unknown level of alcohol consumption. At 1 year, 37% of patients reported being completely abstinent, 10% reported drinking within safety limits and 39% had an unknown level of alcohol consumption. Only 22% of patients had attended alcohol rehabilitation treatment at 90 days and 1 year.ConclusionsWe conclude that prednisolone reduces the risk of mortality at 28 days, but this benefit is not sustained beyond 28 days. PTX had no impact on survival. Future research should focus on interventions to promote abstinence and on treatments that suppress the hepatic inflammation without increasing susceptibility to infection.Trial registrationThis trial is registered as EudraCT 2009-013897-42 and Current Controlled Trials ISRCTN88782125.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 102. See the NIHR Journals Library website for further project information. The NIHR Clinical Research Network provided research nurse support and the Imperial College Biomedical Research Centre also provided funding.

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“…G-CSF has been evaluated in the context of SAH in two RCTs performed in India [7,8]. There were limitations: open label, corticosteroids were not used, the presence of ACLF was not assessed, and the RCTs have been performed in a single center (Postgraduate Institute of Medical Education and Research (PGIMER) in Chandigarh), raising the question of generalizability.…”

Section: Question 6: Do You Apply Any Experimental Drugs Such As N-acmentioning

confidence: 99%

Acute-on-Chronic Liver Failure

et al. 2018

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Granulocyte Colony-Stimulating Factor in Severe Alcoholic Hepatitis: A Randomized Pilot Study

Abstract: G-CSF is safe and effective in the mobilization of hematopoietic stem cells and improves liver function as well as survival in patients with severe alcoholic hepatitis.

Cited by 206 publications

References 34 publications

“If a fake friend stays in your vodkabulary as a stem friend”: Granulocyte colony-stimulating factor promoted stem cell therapy in severe alcoholic hepatitis

“If a fake friend stays in your vodkabulary as a stem friend”: Granulocyte colony-stimulating factor promoted stem cell therapy in severe alcoholic hepatitis

The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial

Acute-on-Chronic Liver Failure

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