The present study was aimed to isolate the active compounds from the fermentation products of Fusarium oxysporum, which had hepatitis C virus (HCV) NS3 protease inhibitory activity. A bioactive compound was isolated by reverse-phase silica-gel column chromatography, silica-gel column chromatography, semi-preparative reverse-phase High Performance Liquid Chromatography (HPLC), and then its molecular structure was elucidated based on the spectrosopic analysis. As a result, the compound (H1-A, 1) Ergosta-5, 8 (14), 22-trien-7-one, 3-hydroxy-,(3β, 22E) was isolated and identified. To the best of our knowledge, this was the first report on the isolation of H1-A from microorganisms with the inhibitory activity of NS3 protease.
Enzyme Inhibitors ; chemistry ; isolation & purification ; metabolism ; Fusarium ; chemistry ; metabolism ; Hepacivirus ; drug effects ; enzymology ; genetics ; Hepatitis C ; virology ; Humans ; Magnetic Resonance Spectroscopy ; Viral Nonstructural Proteins ; antagonists & inhibitors ; metabolism

OBJECTIVETo explore the retreatment of CHC patients with initial treatment failure and how to achieve SVR.

METHODS54 patients who had experienced treatment failure were enrolled and retreated with standard treatment of pegylated interferon and ribavirin or intensive treatment, respectively. Their SVR rates were statistically compared, to decide two therapies' application.

RESULTS54 patients had been retreated, and total SVR rate was up to 75.92%, with 88.46% in relapsed patients and 64.29% in non-responders. After retreatment with pegylated interferon and ribavirin, SVR rate was 95.45% in patients with prior interferon monotherapy, and 64.71% in patients with prior interferon and ribavirin, and 60% in patients with prior pegylated interferon alpha-2a monotherapy. SVR rate of relapsed patients was significantly higher than that of non-responders.

CONCLUSIONSIn CHC patients with treatment failure, SVR rate of retreatment with standard treatment or intensive treatment still can be up to 60%-90%. Retreatment with standard therapy can be applied to patients who had received interferon monotherapy or interferon plus ribavirin. Three types of patients who need intensive retreatment were as following: patients nonresponsive to interferon plus ribavirin or pegylated interferon alpha-2a monotherapy, and patients with treatment failure who had received prior standard treatment.

Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Female ; Hepacivirus ; drug effects ; genetics ; isolation & purification ; physiology ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Retreatment ; Ribavirin ; therapeutic use ; Treatment Failure ; Viral Load ; drug effects ; Young Adult

BACKGROUND AND AIMS: Hepatitis C virus (HCV)-associated cirrhosis is an increasingly frequent indication for liver transplantation (LT). However, HCV recurrence is universal and this immediately occurs following LT, which endangers both the graft and patient survival. We investigated the frequency of posttransplant recurrence of HCV infection and the patient-graft survival, and we analyzed the responses to ribavirin and interferon therapy in the patients with recurrent HCV infection after living donor liver transplantation (LDLT). METHODS: We retrospectively reviewed the clinical outcomes of 39 HCV-associated cirrhosis patients who underwent LDLT at Asan Medical Center between August 1992 and June 2006. In this study, the diagnosis of recurrent HCV was made on the basis of increased transaminases and serum HCV RNA levels greater than 10 million IU/mL because protocol liver biopsy was not performed. RESULTS: HCV recurrence was seen in 26 of the 39 LDLT patients (66.7%). 86.7% of recurrence occurred within the first postoperative year. Antiviral treatment was used for all patients with recurrence of HCV. None of the 10 patients receiving ribavirin alone and 9 of 16 patients who received combination therapy with pegylated interferon alpha-2a plus ribavirin became HCV RNA negative and they remained persistently negative during the median follow-up of 24.9 months. Our data indicates that there is no significant factor influencing HCV recurrence except for the recipient's age. The 2-year patient survival for the HCV patients with HCC and those patients without HCC were 81.2% and 81.3%, respectively (P=0.85) and the 2-year graft survival rates were 81.2% and 68.2%, respectively (P=0.29). No patient died from HCV recurrence during the follow-up period. CONCLUSIONS: Combination therapy with ribavirin and interferon appears to improve the outcome of recurrent HCV infected patients after LDLT.
Adult ; Aged ; Antiviral Agents/therapeutic use ; Combined Modality Therapy ; Female ; Graft Survival ; Hepacivirus/drug effects/isolation & purification ; Hepatitis C, Chronic/complications/diagnosis/*drug therapy ; Humans ; Interferon Alfa-2a/therapeutic use ; Liver Cirrhosis/mortality/*surgery/*virology ; Liver Neoplasms/mortality ; *Liver Transplantation ; Living Donors ; Male ; Middle Aged ; Polyethylene Glycols/therapeutic use ; Recurrence ; Retrospective Studies ; Ribavirin/therapeutic use ; Severity of Illness Index ; Treatment Outcome

BACKGROUND/AIMS: The relationship between patient survival and biopsy-proven acute rejection (BPAR) in liver transplant recipients with hepatitis C remains unclear. The aims of this study were to compare the characteristics of patients with and without BPAR and to identify risk factors for BPAR. METHODS: We retrospectively reviewed the records of 169 HCV-RNA-positive patients who underwent LT at three centers. RESULTS: BPAR occurred in 39 (23.1%) of the HCV-RNA-positive recipients after LT. The 1-, 3-, and 5-year survival rates were 92.1%, 90.3%, and 88.5%, respectively, in patients without BPAR, and 75.7%, 63.4%, and 58.9% in patients with BPAR (P<0.001). Multivariate analyses showed that BPAR was associated with the non-use of basiliximab and tacrolimus and the use of cyclosporin in LT recipients with HCV RNA-positive. CONCLUSION: The results of the present study suggest that the immunosuppression status of HCV-RNA-positive LT recipients should be carefully determined in order to prevent BPAR and to improve patient survival.
Antibodies, Monoclonal/therapeutic use ; Biopsy ; Cyclosporine/therapeutic use ; Drug Therapy, Combination ; Genotype ; Graft Rejection/mortality/*prevention & control ; Hepacivirus/genetics/isolation & purification ; Hepatitis C/drug therapy/*virology ; Humans ; Immunosuppressive Agents/*therapeutic use ; *Liver Transplantation/adverse effects ; Polymerase Chain Reaction ; RNA, Viral/blood ; Recombinant Fusion Proteins/therapeutic use ; Recurrence ; Retrospective Studies ; Survival Rate ; Tacrolimus/therapeutic use