Granulocyte colony‐stimulating factor with or without stem or progenitor cell or growth factors infusion for people with compensated or decompensated advanced chronic liver disease

Plain language summary Granulocyte colony‐stimulating factor with or without stem or progenitor cell or growth factors infusion for people with compensated or decompensated advanced chronic liver disease Key messages In people with chronic liver disease with diffuse scarring (called cirrhosis) and impairment of liver function, the infusion of granulocyte colony‐stimulating factor (G‐CSF) may reduce the risk of death in comparison with standard treatment. Unexpected effects were either poorly reported, or the information was unclear. G‐CSF is a protein that stimulates the growth and spread of undifferentiated cells (immature cells that do not have specialised structures or functions) or partially differentiated (incompletely specialised) cells into the bloodstream and organs, such as the liver. G‐CSF may be administered alone or in combination with another drug. As we are not confident in the evidence provided by the available studies that assessed G‐CSF, the results of this review are likely untrustworthy. Also, the included studies in the review were too different from each other to allow us to draw firm conclusions based on the evidence. Why is it important to treat people with advanced chronic liver disease? A wide range of diseases can cause continuous and repeated damage to the liver, which leads to progressive scarring and impairment of the liver function. When damage to the liver is irreversible, it is defined as chronic. Globally, advanced chronic liver disease is considered responsible for more than one million deaths every year. No treatment is available to specifically target liver scarring, and liver transplantation remains the only curative option. Many researchers are investigating strategies to restore the functions of the liver to avoid or slow progression towards end‐stage liver disease (that is, the final stage of a progressive liver condition, such as cirrhosis of the liver, progressive hepatitis (for example, viral hepatitis type C), or liver cancer), which ultimately requires a rescue liver transplantation. What is granulocyte colony‐stimulating factor? Granulocyte colony‐stimulating factor is a protein that stimulates the bone marrow to produce white blood cells and immature cells and release them into the bloodstream. This protein can be produced with recombinant DNA technology (DNA molecules formed by laboratory methods) and is currently used to preserve a safe level of white blood cells in people on chemotherapy for cancer. Also, G‐CSF might regulate inflammation and improve the capacity of the liver to replace lost cells and survival in people with advanced chronic liver disease. What did we want to find out? We wanted to find out if G‐CSF, administered alone or in combination with other drugs to people with advanced chronic liver disease, compared with sham treatment or no treatment, is able to improve survival. We were also interested in assessing unwanted or harmful effects of this treatment, complications due to the liver disease, and the treatment effect on well‐being. What did we do? We searched for randomised clinical trials that assessed the effect of multiple courses of G‐CSF alone or in combination with other drugs in people with advanced chronic liver disease. In randomised controlled trials, study participants are assigned to groups that receive different treatments by chance (that is, at random). What did we find? We included a total of 20 studies with 1419 participants. A total of 188 out of 738 (25.4%) participants randomised to the G‐CSF group, compared with 302 out of 681 (44.3%) participants in the control group, died. (The control group received standard medical therapy and other supportive measures.) The follow‐up in the studies varied between 2 and 12 months. The studies were conducted from 2008 to 2022: 15 in Asia, 4 in Europe, and 1 in the USA. Eight studies included only people with alcoholic liver disease, and the other studies included people with different causes of liver disease, mainly chronic hepatitis B or C. Only few studies reported data on unwanted or harmful effects of the treatment and well‐being. G‐CSF seemed to reduce the proportion of participants with liver‐related complications that may increase the risk of dying. We could not draw any firm conclusions for any of the studied outcomes because of the poor study designs, as this resulted in no confidence in the evidence. Therefore, we cannot be sure if there is a beneficial, harmful, or neutral effect of G‐CSF compared with no treatment or sham treatment on the risk of death, unwanted or harmful effects of the treatment, and complications due to liver disease. What are the limitations of the evidence? Our confidence in the evidence is very low because the studies show many limitations, which can potentially lead to prejudiced results. There are not enough studies to be certain about the result estimates. Therefore, we need further randomised clinical studies of high quality. How up to date is this evidence? The evidence is up to date to 4 October 2022.