Therefore, it will be desirable
Lt to evaluate the clinical efficacy. Therefore, it will be desirable to examine the clinical efficacy of rh-HGF in additional clinical trials involving patients with less severe conditions. Systemic administration of potent growth factors could theoretically stimulate premalignant lesions in distant organs. Therefore, in this first clinical trial of rhHGF, it was prudent to limit systemic therapy to lifethreatening conditions. Although the two surviving patients in this study should be observed over the long term, we showed here that repeated doses of intravenous rh-HGF were well tolerated even in patients with a fatal disease. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/14445666 Recent investigations have indicated that HGF has the potential to improve treatment for intractable diseases of various PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/15139768 organs, including the nervous system [31,32], lung [33], heart [34-36], intestine [26,37], kidney [38], and vessels [39]. Therefore, the safety assessment of protein-based therapy of HGF described here sheds light on the development of new therapeutic modalities aimed at treating patients with intractable diseases.Conclusions Despite a mild BP reduction during rh-HGF infusion, intravenous rh-HGF at a dose of 0.6 mg/m 2 was well tolerated in patients with FH or LOHF. However, there was no evidence that those dose of rh-HGF was effective for the treatment of these patients. Additional studies of rh-HGF at doses higher than 0.6 mg/m2, for Boc-D-Lys-OH longer periods, or in treatment of patients with less severe conditions, will be valuable in determining the clinical efficacy of rh-HGF.Additional materialAdditional file 1: Clinical course of patient 1 with FHSA, the first patient tert-Butyl (2-bromothiazol-5-yl)carbamate receiving intravenous rh-HGF. We first administered rh-HGF to a 67-year-old Japanese man with FHSA caused by hepatitis E virus infection. On admission, he presented with hepatic encephalopathy, jaundice, ascites, edema, and microhematuria caused by bladder catheter. Although ALT had already decreased to 32 IU/L, we observed thrombocytopenia (6.1 ?104/L), increased T-Bil (11.2 mg/dL), a marked decrease in serum albumin (2.9 g/dL), and prolonged PT (33 ) (PT-INR 2.07), indicating severely impaired hepatic reserve. Serum HGF and AFP levels were 0.77 and 7.0 ng/mL, respectively, and liver volume measured by CT was 1055 mL. Following observation of general condition for two days, administration of rh-HGF (0.6 mg/m2/day) was initiated. Because of an increase in serum creatinine level of 2.0 mg/dL, caused by diuretics administration to reduce massive ascites, protocol therapy was discontinued on day 14, resulting in 13-day administration of rh-HGF. Although prolonged PT was stable during rh-HGF dosing and observation period, T-Bil gradually increased and hepatic encephalopathy did not improve. Hepatic failure gradually progressed after the observation period; the patient ultimately died 68 days after the onset of hepatic encephalopathy. PE, plasma exchange; CHDF, continuous hemodiafiltration.Ido et al. Journal of Translational Medicine 2011, 9:55 http://www.translational-medicine.com/content/9/1/Page 11 ofAdditional file 2: Clinical course of patient 2 with FHSA, who survived. The second patient (patient 2) was a 71-year-old Japanese woman with FHSA of undetermined etiology. She presented with mild hepatic encephalopathy with flapping tremor, jaundice, and urinary findings, including proteinuria and microhematuria, caused by bladder catheter. Platelet count and serum albumin level decreased to 6.9 ?104/ L, and 3.2 g/dL, respectively, and PT.