ABSTRACT
BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) develops in patients with chronic liver disease and has high mortality. Mobilization of bone marrow-derived stem cells with granulocyte colony-stimulating factor (G-CSF) could promote hepatic regeneration. METHODS: Consecutive patients with ACLF were randomly assigned to groups given 5 µg/kg G-CSF subcutaneously (12 doses; group A, n = 23) or placebo (group B, n = 24) plus standard medical therapy. We assessed survival until day 60; Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), and Sequential Organ Failure Assessment (SOFA) scores; and the development of other related complications. RESULTS: After 1 week of treatment, group A had higher median leukocyte and neutrophil counts than group B (P < .001). Sixteen patients in group A (69.6%) and 7 in group B (29%) survived; the actuarial probability of survival at day 60 was 66% versus 26%, respectively (P = .001). Treatment with G-CSF also reduced CTP scores in group A by a median of 33.3% compared with an increase of 7.1% in group B (P = .001), along with MELD (median reduction of 15.3% compared with an increase of 11.7% in group B; P = .008) and SOFA scores (median reduction of 50% compared with an increase of 50% in group B; P = .001). The percentages of patients who developed hepatorenal syndrome, hepatic encephalopathy, or sepsis were lower in group A than in group B (19% vs 71% [P = .0002], 19% vs 66% [P = .001], and 14% vs 41% [P = .04], respectively). After 1 month of treatment, G-CSF increased the number of CD34(+) cells in the liver (by 45% compared with 27.5% in group B; P = .01). CONCLUSIONS: G-CSF therapy more than doubles the percentage of patients with ACLF who survive for 2 months; it also significantly reduces CTP, MELD, and SOFA scores and prevents the development of sepsis, hepatorenal syndrome, and hepatic encephalopathy.
Subject(s)
Antigens, CD34/metabolism , Cell Movement/drug effects , End Stage Liver Disease/drug therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Liver Failure, Acute/drug therapy , Liver/drug effects , Stem Cells/drug effects , Adult , Aged , Chi-Square Distribution , End Stage Liver Disease/diagnosis , End Stage Liver Disease/immunology , End Stage Liver Disease/mortality , Female , Granulocyte Colony-Stimulating Factor/adverse effects , Humans , India , Kaplan-Meier Estimate , Liver/immunology , Liver/pathology , Liver Failure, Acute/diagnosis , Liver Failure, Acute/immunology , Liver Failure, Acute/mortality , Liver Regeneration/drug effects , Male , Middle Aged , Severity of Illness Index , Stem Cells/immunology , Stem Cells/pathology , Survival Rate , Time Factors , Treatment Outcome , Young AdultABSTRACT
The purpose of this study was to assess the effect of a motor-based, social skills intervention for two adolescents with high-functioning autism (HFA) using single-subject design. A description of the intervention is provided as a first step in the manualization process. The intervention was provided as a 7-week after-school program, once weekly to the paired participants. Intervention consisted of role-play methods in which motor behaviours were linked with their cognitive and emotional meanings. Baseline, intervention and 3-month probe data collection periods were carried out and then compared using visual inspection of graphed data, paired t-tests and a three-standard-deviation-band approach. Both participants displayed a statistically significant increase in targeted social skills behaviours from baseline to intervention and maintained this level at a 3-month post-intervention probe. These single-subject design cases illustrate that motor-based, social skills interventions may be effective for adolescents with HFA and warrant further testing.
