Translational research on HGF: A phase I/II study of recombinant human HGF for the treatment of fulminant hepatic failure

Abstract

Hepatocyte growth factor (HGF) is a potential therapeutic agent for fatal liver diseases, including fulminant hepatic failure (FHF). After performing a number of preclinical tests with recombinant human HGF (rh-HGF), we started a phase I/II study in September 2005 of patients with FHF or late-onset hepatic failure (LOHF), to examine the safety and clinical efficacy of rh-HGF. We first administered rh-HGF (0.6 mg/m(2)/day) for 13 days to a 67-year-old Japanese man with FHF. All data from this patient were reviewed by the independent data monitoring committee, and the safety of rh-HGF was recognized. Finally, a clinical trial of rh-HGF was approved to be continued. As of August 2007, we have administered rh-HGF to four patients with FHF or LOHF. All patients showed a moderate decrease in systolic blood pressure during rh-HGF administration, while the urinary excretion of albumin did not increase in all cases. In the first and third patients, hepatic failure gradually progressed, and they died 66 and 29 days, respectively, after encephalopathy occurred. The second and fourth patients are presently still alive. In conclusion, we started a clinical trial that examined the effects of rh-HGF in patients with FHF or LOHF, and in the four patients with FHF or LOHF enrolled in this study, repeated doses of rh-HGF did not produce any severe side effects.

Serum levels of platelet‐derived growth factor‐BB and vascular endothelial growth factor as prognostic factors for patients with fulminant hepatic failure

“…Recently, a clinical trial of recombinant human HGF, which stimulates the proliferation of mature hepatocytes and hepatic progenitor cells, in patients with FHF was reported from Japan. 22 In the study, four patients received the administration of recombinant HGF, of whom, two died due to progression of liver failure and two were rescued. However, from the first, serum HGF levels are higher in FHF patients than AH patients or healthy controls.…”

Recombinant soluble form of heparin‐binding epidermal growth factor‐like growth factor protein therapy drastically inhibits Fas‐mediated fulminant hepatic failure: Implications in clinical application

“…The mRNA levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) increased more rapidly than those of hepatocyte growth factor (HGF), the well-studied hepatotropic factor, in regenerating livers after a partial hepatectomy and liver injury. [1][2][3][4][5][6] The membrane-anchored precursor form (proHB-EGF) is initially synthesized in non-parenchymal cells, and the extracellular domain is cleaved by a specific metalloproteinase. 7,8 The resulting soluble form of HB-EGF (sHB-EGF) acts on neighboring hepatocytes.…”

PET of c-Met in Cancer with 64Cu-Labeled Hepatocyte Growth Factor

“…However, as the only known ligand of c-Met, HGF has not been used for PET imaging to quantify c-Met abundance. Since HGF is a multifunctional growth factor involved in stimulation of hepatocyte proliferation, inhibition of apoptosis, and invasive growth of tumor cells (27), rh-HGF has been used in a clinical trial for treatment of fulminant hepatic failure (FHF) or late-onset hepatic failure (LOHF) (28). Developing a HGF-based PET tracer for imaging of c-Met expression in cancer patients may significantly facilitate patient stratification in clinical trials, as well as provide surveillance for the efficacy of c-Met-targeted therapies.…”