BACKGROUND/AIMS: When combined with pegylated interferon alpha-2b (Peg-IFN alpha-2b) for the treatment of genotype 1 chronic hepatitis C (CHC) in Korea, the current guideline for the initial ribavirin (RBV) dose is based on body weight. However, since the mean body weight is lower for Korean patients than for patients in Western countries, current guidelines might result in Korean patients being overdosed with RBV. METHODS: We retrospectively reviewed the medical records of patients with genotype 1 CHC who were treated with Peg-IFN alpha-2b and RBV combination therapy. We divided the patients into groups A (> or =15 mg/kg/day, n=23) and B (<15 mg/kg/day, n=26), given that the standard dose is 15 mg/kg/day. The clinical course in terms of the virologic response, adverse events, and dose modification rate was compared between the two groups after therapy completion. RESULTS: The early response rates (92.0% vs. 83.3%, P=0.634) and sustained virologic response rates (82.6% vs. 73.1%, P=0.506) did not differ significantly between the two groups. During the treatment period, the RBV dose reduction rate was significantly higher in group A than in group B (60.9% vs. 23.1%, P=0.01). CONCLUSIONS: RBV dose reduction is performed frequently when patients are treated according to the current Korean guidelines. Given that lowering the RBV dose did not appear to decrease the virologic response during therapy, reducing RBV doses below the current Korean guideline may be effective for treatment, especially in low-weight patients.
Antiviral Agents/pharmacology/*therapeutic use ; Body Mass Index ; Body Weight ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/drug effects ; Hepatitis C, Chronic/*drug therapy/virology ; Humans ; Interferon-alpha/pharmacology/*therapeutic use ; Male ; Polyethylene Glycols/pharmacology/*therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/pharmacology/therapeutic use ; Retrospective Studies ; Ribavirin/pharmacology/*therapeutic use ; Sex Factors ; Treatment Outcome

OBJECTIVETo investigate the prevalence and distribution of HCV genotypes and the clinical effect of interferon-alpha combined with ribavirin treatment in chronic hepatitis C patients in Kunming.

METHODS60 patients were divided into two groups based on drug therapies: PEG-interferon-a plus ribavirin treatment group for HCV 1b and interferon-a plus ribavirin treatment group for non-HCV-1b. Serum ALT levels and HCV RNA quantitations of the patients were detected during treatment and follow-up.

RESULTSThe HCV genotypes of 60 patients were determined by type specific probe assay, and five different types were found. Their overall prevalence were 21.7% for type 1b, 5% for type 2a, 16.7% for type 3a, 48.3% for type 3b, and 8.3% for type 6a. Sustained viral response rates for PEG-interferon treatment group were 46.1%, for interferon treatment group were 74.4%. The abnormal rate of serum ALT after the treatment had no significant difference between HCV-1b and non-HCV-1b patients (P>0.05). All patients with early viral responses got sustained viral response.

CONCLUSIONHCV-3b is the most dominant genotype in Kunming. The effect of PEG-interferon-a plus ribavirin treatment for genotype 1b is unsatisfactory. The early viral response is a good predictor for the responses to antiviral therapy in chronic hepatitis C patients.

Adult ; Aged ; Antiviral Agents ; pharmacology ; therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Genotype ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; RNA, Viral ; Ribavirin ; therapeutic use ; Young Adult

BACKGROUND/AIMS: Lipid profile and insulin resistance (IR) are associated with hepatitis C virus (HCV) and may predict the chronic hepatitis C (CHC) treatment response. The aim of this study was to determine the association between CHC treatment response and lipid profile and IR change during treatment. METHODS: In total, 203 CHC patients were reviewed retrospectively between January 2005 and December 2011 at Soon Chun Hyang University Hospital. The lipid profile, homeostasis model for assessment (HOMA) of IR (HOMA-IR), and HOMA of beta cells (HOMA-beta) were evaluated before interferon plus ribavirin therapy (BTx), at the end of treatment (DTx), and 24 weeks after the end of treatment (ATx). RESULTS: A sustained virologic response (SVR) was achieved by 81% of all patients (49/60), 60% (n=36) of whom possessed genotype 1, with the remainder being non-genotype-1 (40%, n=24). Apart from age, which was significantly higher in the non-SVR group (SVR, 48.0+/-11.2 years, mean+/-SD; non-SVR, 56.6+/-9.9 years; P<0.01), there were no significant differences in the baseline characteristics between the SVR and non-SVR groups. In the SVR group, low density lipoprotein-cholesterol (LDL-C) had significantly changed at DTx and ATx compared to BTx. In addition, HOMA-IR and HOMA-beta were significantly changed at DTx in the SVR group. Among those with a high baseline insulin resistance (HOMA-IR >2.5), HOMA-IR was significantly changed at DTx in the SVR group. CONCLUSIONS: LDL-C appears to be associated with HCV treatment in SVR patients. Furthermore, eradication of HCV may improve whole-body IR and insulin hypersecretion, as well as high baseline insulin resistance (HOMA-IR >2.5).
Adult ; Aged ; Antiviral Agents/pharmacology/*therapeutic use ; Cholesterol/blood ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/genetics ; Hepatitis C, Chronic/*drug therapy ; Humans ; *Insulin Resistance ; Interferon-alpha/pharmacology/*therapeutic use ; Lipid Metabolism/drug effects ; Male ; Middle Aged ; Polyethylene Glycols/pharmacology/*therapeutic use ; Recombinant Proteins/pharmacology/therapeutic use ; Ribavirin/*therapeutic use ; Treatment Outcome ; Triglycerides/blood

In order to explore the expression of TRAIL in primary acute leukemic cells and the effect of chemotherapeutic drug on TRAIL expression in acute leukemic cells, the expression of TRAIL was assessed by flow cytometry on day 0, day 1, day 3 and day 5 in 16 patients with acute leukemia received chemotherapy. Meanwhile, the bone marrow mononuclear cells of acute leukemia patients were cultured in vitro with VP-16 and INFalpha-2a. Expression of TRAIL was analyszed by flow cytometry at 24, 48 and 72 hours after treatment. The results showed that the expression of TRAIL in the peripheral blood mononuclear cells was upregulated significantly from day 1 after chemotherapy (P < 0.05). In in vitro culture test, VP-16 upregulated the expression of TRAIL on acute leukemia bone marrow mononuclear cells (P < 0.05). Compared with VP-16 alone, the combination of VP-16 with IFNalpha-2a showed no synergic effects on the expression of TRAIL. It is concluded that the expression of TRAIL increases after chemotherapy in vivo and after treatment with VP-16 and IFN in vitro, which suggests that the apoptosis induced by TRAIL may play an important role in chemotherapy of leukemia.
Acute Disease ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Bone Marrow Cells ; metabolism ; Etoposide ; pharmacology ; Humans ; Interferon-alpha ; pharmacology ; Leukemia ; drug therapy ; metabolism ; pathology ; TNF-Related Apoptosis-Inducing Ligand ; biosynthesis ; genetics ; Tumor Cells, Cultured

OBJECTIVETo explore the therapeutic mechanisms of interferon-beta (IFN-beta) and intravenous immunoglobulin (IVIG) for experimental peripheral neuropathy induced by Campilobacter jejuni (Cj) lipopolysaccharide (LPS).

METHODForty healthy Wistar rats weighing 205 - 230 g were divided into IFN-beta, IVIG, IFN-beta plus IVIG and control groups. After the immune neuropathy was induced in the rats by Cj LPS, IFN-beta (1.3 microg/kg) was given by subcutaneous injection to the rats every other day for 6 weeks; IVIG [400 mg/(kg x d)] was given to the rats for five days, every other week for two times and IFN-beta [1.3 microg/(kg x d)] and IVIG [400 mg/(kg x d)] were given to the rats on the same days. Meanwhile, the control group was given PBS. The sera were collected in the 2nd, 4th and 6th week after therapy, the titers of anti-GM(1) IgG, MMP-9 and TNF-alpha in sera of immunized rats were measured by ELISA; histological study of sciatic nerve was performed and IgG on sciatic nerve was detected by immunohistochemistry in the 6th week.

RESULTS(1) There were no significant differences in titers of anti-GM(1) IgG, MMP-9 and TNF-alpha among the 3 therapeutic groups and control group after therapy for 2 weeks (P > 0.05). (2) The titers of anti- GM(1) IgG, MMP-9 or TNF-alpha in the control group were much higher than those of the IFN-beta group, the IVIG group or the IFN-beta and IVIG group after therapy for 4 weeks (P > 0.01) and there were no significant differences in titers of antibody among the 3 therapeutic groups (P > 0.05); the titers of MMP-9 or TNF-alpha in the IFN-beta and IVIG group were lower than those of the IFN-beta group or the IVIG group (P < 0.05). (3) The titers of anti-GM(1) IgG, MMP-9 or TNF-alpha in the control group were much higher than those of the IFN-beta group, the IVIG group or the IFN-beta with IVIG group after therapy for 6 weeks (P > 0.01); the IFN-beta with IVIG group had much lower levels of all indexes than the IFN-beta group or the IVIG group (P < 0.01).

CONCLUSIONIFN-beta and IVIG showed therapeutic effects on immune peripheral neuropathy through inhibiting the humoral and cellular immunity simultaneously in the peripheral neuropathy induced by CJ LPS, treatment with combined IFN-beta and IVIG was more effective.

Animals ; Enzyme-Linked Immunosorbent Assay ; Immunoglobulins, Intravenous ; therapeutic use ; Immunotherapy ; Interferon Type I ; therapeutic use ; Interferon-beta ; immunology ; therapeutic use ; Lipopolysaccharides ; pharmacology ; Peripheral Nervous System Diseases ; therapy ; Rats ; Rats, Wistar ; Recombinant Proteins ; Sciatic Nerve ; drug effects ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVESTo study the relationship between HBV genotypes and the efficacy of antiviral therapies.

METHODSHBV genotypes of 90 hepatitis B e antigen positive patients with chronic hepatitis B (CHB) were determined by PCR sandwich hybridization-ELISA technique. Forty-one patients with CHB were treated with lamivudine (100 mg/day) for 48 weeks and 49 patients with CHB were given alpha-interferon (3 MU/QOD) therapy for 48 weeks. The serological, biochemical and virological symbols were measured before, during and after treatment for all the patients.

RESULTSOf the 90 patients, genotype B HBV was found in 16 and C in 74. There was no difference in the rate of response to lamivudine treatment between patients with genotype B or C HBV (33.3% vs. 20.0%) after 48 weeks treatment with lamivudine in the 41 patients. Of the 49 HBeAg positive CHB patients treated with alpha-interferon for 48 weeks, in HBV genotype B and C patients the rates of normalization of ALT were 60.0% and 20.5%; the rate of HBeAg turning to negativity was 50.0% and 17.9%; and the rate of HBV DNA undetectability was 50.0% and 17.9%. The rate of response to the interferon treatment was significantly higher in patients with HBV genotype B compared to those with genotype C.

CONCLUSIONSOur study shows that there is no influence on the lamivudine treatment effects for the HBV genotype B and C CHB patients, but the alpha-interferon treatment for HBV genotype B CHB patients is more effective than that for the genotype C ones.

Adolescent ; Adult ; Antiviral Agents ; pharmacology ; therapeutic use ; Female ; Genome, Viral ; Genotype ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; pharmacology ; therapeutic use ; Lamivudine ; pharmacology ; therapeutic use ; Male ; Young Adult

OBJECTIVETo evaluate the effects of antiviral agents on intrahepatic HBV covalently closed circular DNA (cccDNA) in HBeAg-positive chronic hepatitis B patients.

METHODSSeventy-one HBeAg positive chronic hepatitis B patients were enrolled in this study. Lamivudine was administered to 35 patients for 48 weeks, sequential therapy with lamivudine-IFN alpha-2b to 24 of the 71 patients for 48 weeks, and interferon alpha (IFN alpha-2b) was administered to 12 for 24 weeks. All subjects were followed-up for 24 weeks. Serum HBV DNA, intrahepatic HBV DNA and cccDNA were measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP.

RESULTSForty-eight weeks of sequential lamivudine-IFN alpha-therapy and lamivudine monotherapy and 24 weeks of IFN alpha monotherapy reduced the intrahepatic HBV DNA to (4.7+/-1.1) log10, (4.6+/-1.5) log10 and (5.6+/-1.5) log10, and cccDNA to (3.4+/-1.3) log10, (3.8+/-1.1) log10 and (5.0+/-1.5) log10, significantly lower than therapy (P < 0.05). Seventeen of the 71 patients developed HBeAg seroconversion, and the reduction of cccDNA in the HBeAg seroconverted patients was significantly more than that of the HBeAg positive patients (P < 0.05). After 24 weeks of antiviral therapy withdrawal, 18 patients achieved sustained virological response, and the baseline intrahepatic cccDNA in the patients with sustained virological response was significantly lower than that of patients with virological rebound (P < 0.05). The change in intrahepatic cccDNA correlated positively with the reduction in intrahepatic HBV DNA (P < 0.05). The cccDNA levels correlated with the serum HBeAg titers at the end of the treatment (P < 0.01). Of the total 71 cases, HBV genotype C accounted for 85.9% (n = 61), and genotype B for 14.1% (n = 10). There was no significant difference in the changes of intrahepatic HBV DNA and cccDNA levels between HBV genotypes C and B (P >0.05).

CONCLUSIONSBoth 48 weeks of sequential lamivudine-IFN alpha and lamivudine monotherapy strongly reduced intrahepatic HBV DNA and cccDNA more than 24 weeks of IFN alpha monotherapy. Low baseline intrahepatic cccDNA levels might predict a good long-term efficacy of antiviral treatment. The reduction of intrahepatic cccDNA correlated positively with the changes of intrahepatic HBV DNA, and intrahepatic cccDNA levels correlated with serum HBeAg titers. HBV genotypes had no obvious influence on intrahepatic HBV DNA load or cccDNA load.

Adult ; Antiviral Agents ; pharmacology ; therapeutic use ; DNA, Circular ; DNA, Viral ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; pharmacology ; therapeutic use ; Lamivudine ; pharmacology ; therapeutic use ; Male ; Middle Aged ; Recombinant Proteins ; Young Adult

OBJECTIVETo evaluate the effect of antiviral agents on intrahepatic HBV DNA and histology in HBeAg-positive chronic hepatitis B patients.

METHODSThirty-five patients were treated with lamivudine, 16 with interferon alfa (INF-alpha), 24 with sequential Lamivudine and INF-alpha. The total duration of therapy was 12 months. Intrahepatic HBV DNA was measured quantitatively by real-time polymerase chain reaction.

RESULTSThere was significant change in all parameters of the groups of patients at the end of treatment (P < 0.05). The patients treated with sequential treatment had slightly higher HBeAg seroconversion rate (38.1%) than that of the other patients (P=0.1352). The baseline levels of intrahepatic HBV DNA in the patients with HBeAg seroconversion or undetectable serum HBV DNA were significantly lower than that of the other patients (P < 0.05).

CONCLUSIONAntiviral agents could effectively inhibit intrahepatic HBV DNA and improve hepatic histology. The patients with low baseline intrahepatic HBV DNA level may achieve better antiviral efficacy. Sequential treatment might produce high HBeAg seroconversion rate.

Adolescent ; Adult ; Antiviral Agents ; pharmacology ; therapeutic use ; DNA, Viral ; blood ; metabolism ; Drug Therapy, Combination ; Female ; Hepatitis B e Antigens ; immunology ; metabolism ; Hepatitis B, Chronic ; drug therapy ; immunology ; pathology ; virology ; Humans ; Interferon-alpha ; pharmacology ; therapeutic use ; Lamivudine ; pharmacology ; therapeutic use ; Liver ; drug effects ; metabolism ; pathology ; virology ; Male ; Middle Aged ; Time Factors

Antiviral Agents ; pharmacology ; therapeutic use ; DNA, Viral ; blood ; Hepatitis B ; blood ; drug therapy ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; physiology ; Humans ; Interferon-alpha ; pharmacology ; therapeutic use ; Kinetics ; Lamivudine ; pharmacology ; therapeutic use ; Models, Statistical ; Viral Load

In the present study, the effects of Pleurotus nebrodensis polysaccharide (PN-S) on the immune functions of immunosuppressed mice were determined. The immunosuppressed mouse model was established by treating the mice with cyclophosphamide (40 mg/kg/2d, CY) through intraperitoneal injection. The results showed that PN-S administration significantly reversed the CY-induced weight loss, increased the thymic and splenic indices, and promoted proliferation of T lymphocyte, B lymphocyte, and macrophages. PN-S also enhanced the activity of natural killer cells and increased the immunoglobulin M (IgM) and immunoglobulin G (IgG) levels in the serum. In addition, PN-S treatment significantly increased the phagocytic activity of mouse peritoneal macrophages. PN-S also increased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), and nitric oxide (NOS) in splenocytes. qRT-PCR results also indicated that PN-S increased the mRNA expression of IL-6, TNF-α, INF-γ, and nitric oxide synthase (iNOS) in the splenocytes. These results suggest that PN-S treatment enhances the immune function of immunosuppressed mice. This study may provide a basis for the application of this fungus in adjacent immunopotentiating therapy against cancer and in the treatment of chemotherapy-induced immunosuppression.
Animals ; Antineoplastic Agents, Alkylating ; Biological Products ; pharmacology ; therapeutic use ; Cell Line ; Cyclophosphamide ; Immunity ; drug effects ; Immunologic Factors ; pharmacology ; therapeutic use ; Immunosuppression ; Interferon-gamma ; metabolism ; Interleukin-6 ; metabolism ; Macrophages ; drug effects ; metabolism ; Male ; Mice, Inbred BALB C ; Neoplasms ; drug therapy ; immunology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Phagocytosis ; drug effects ; Pleurotus ; chemistry ; Polysaccharides ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism