Granulocyte colony stimulating factor improves liver function in alcoholic hepatitis

Granulocyte colony-stimulating factor improves liver function in alcoholic hepatitis

Tuesday, September 23, 2014. A pilot study reported in the September, 2014 issue of The American Journal of Gastroenterology found a benefit for the administration of granulocyte colony-stimulating factor (G-CSF) in patients with severe alcoholic hepatitis, a condition with high short-term mortality.

"Both animal and human studies have suggested that CD34 + cells might contribute to hepatic regeneration and repair after various forms of acute liver injury," write authors Virendra Singh, MD, and colleagues. "In animal models of liver injury, bone marrow–derived circulating pluripotent cells [stem cells] are reported to participate in hepatic regeneration, which may be dependent on the type of liver injury and experimental conditions. Several studies have demonstrated the safety and efficacy of granulocyte colony-stimulating factor in promoting the mobilization of bone marrow stem cells, leading to improved histology and survival after liver injury. Recent studies using G-CSF as a treatment modality in patients with acute-on-chronic liver failure (ACLF) have shown clinical, biochemical, and histological improvement in liver function."

Among 46 men who received standard medical therapy for severe alcoholic hepatitis, 23 received subcutaneous G-CSF twice daily for five days. CD34+ cells (whose mobilization in peripheral blood is a marker for hematopoietic stem cell mobilization) and white blood cells were measured in peripheral blood samples, and liver function was assessed before and after treatment, and at one, two and three months.

Treatment with G-CSF resulted in an increase in white blood cell counts and a trend toward higher CD34+ cells on the sixth day of the study in comparison with levels measured prior to treatment. Median changes in clinical scores that evaluated liver failure and prognosis were reduced at one, two and three months in G-CSF patients in comparison with those who did not receive it. At day 90 of the study, eighteen patients who received standard medical treatment alone had died in comparison with five among those who also received G-CSF. No major side effects were observed in association with G-CSF.

The authors conclude that G-CSF is safe and effective in mobilizing hematopoietic stem cells as well as improving liver function and patient survival. They observe that G-CSF has also reduced the rate of acute rejection and sepsis-related death in liver transplant patients. The positive outcome of this pilot study could lead to larger trials of G-CSF in patients suffering from alcoholic hepatitis or other conditions.

What's Hot

N-acetylcysteine protects transplanted livers

The February, 2013 issue of the journal Liver Transplantation reports the finding of researchers in Padua, Italy of a benefit for the amino acid N-acetylcysteine (NAC) in transplanted livers. The organs undergo damage following restoration of blood flow after transplantation, which affects their viability in transplant recipients.

"Liver transplantation is the standard treatment for end-stage liver disease," lead author Francesco D'Amico of Padova University noted. "Antioxidants such as NAC could potentially reduce damage to deceased donor livers, improving graft function."

Acting on the results of studies of animal livers which determined a benefit for NAC in reducing injury following blood flow restoration, Dr D'Amico's team tested the effect of NAC in human livers. Sixty-nine non-living donors were infused with a solution containing NAC one hour prior to liver removal and transplant. Seventy-one patients who received standard liver transplants served as controls.

At three months, participants who received NAC-infused livers had graft survival rates of 93 percent in comparison with 82 percent of the control group. The complication rate among those whose livers were treated with NAC was less than half that of the controls. At one year, organ failure had occurred in 10 percent of the treatment group and 30 percent of the control subjects. In a separate analysis of patients who received suboptimal liver tissue, liver dysfunction occurred in 15 percent of the NAC group in comparison with 32 percent of the controls.

"Our study was the first randomized trial to investigate the use of NAC antioxidant infusion during the liver procurement procedure," Dr D'Amico announced. "We propose that NAC be used during organ harvesting to improve liver transplantation outcomes, particularly with the increased use of suboptimal organs. NAC has a good safety profile and the very low cost per patient, make this protocol highly cost-effective in consideration of grafts survival, length of hospital stays and post operative complications. Moreover we are performing further analyses to determine beneficial effects on the other organ procured with NAC protocol."

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Health Concern

Liver Degenerative Disease

Compared to other health conditions, it is striking how little attention is given to diseases of the liver, particularly considering the rising level of concern about health and health-related environmental issues. Hepatoprotection (or protection of the liver) should be of intense interest because the liver plays a critical role in all aspects of metabolism and overall health.

This protocol will present intriguing information about the role of the liver and why a well-functioning liver is essential for overall health and quality of life. Additionally, you will learn about ways to support healthy liver function, identify environmental hazards that constantly challenge the detoxification capacity of the liver, and the effects of alcohol on the liver.

Some beneficial herbs will also be described. In Europe and Asia, herbal liver remedies have been in common use for decades--perhaps even centuries. The effectiveness of the herbs used in these remedies has been validated through research and clinical studies. These herbs generally contain antioxidants, membrane-stabilizing and bile-enhancing compounds, or substances that prevent depletion of sulfhydryl compounds, such as glutathione.