Hepatitis C genotype 6 is endemic in Southeast Asia[prevalence varies between 10%-60% among all hepatitis C virus(HCV) infection], as well as also sporadically reported outside the area among immigrations.The diagnosi...Hepatitis C genotype 6 is endemic in Southeast Asia[prevalence varies between 10%-60% among all hepatitis C virus(HCV) infection], as well as also sporadically reported outside the area among immigrations.The diagnosis of HCV genotype can be inaccurate with earlier methods of genotyping due to identical 5'-UTR between genotype 6 and 1b, hence the newer genotyping methods with core sequencing are preferred.Risk factors and clinical course of HCV genotype 6 do not differ considerably from other genotypes. Treatment outcome of HCV genotype 6 with a combination of pegylated interferon and ribavirin is superior to genotype 1, and nearly comparable to genotype 3, with expected sustained virological response(SVR) rates of 60%-90%. Emerging data suggests that a shorter course 24-wk treatment is equally effective as a standard 48-wk treatment, particularly for those patients who attained undetectable HCV RNA at week 4(RVR).In addition, baseline and on-treatment predictors of response used for other HCV genotypes appear effective with genotype 6. Although some pan-genotypic directacting antivirals have completed phase Ⅱ/Ⅲ studies(sofosbuvir and simeprevir) with clinical benefit demonstrated in small number of patients with genotype6, broad availability of these agents in Southeast Asia may not be expected in the near future. While awaiting the newer therapy, response-guided therapy seems appropriate for patients with HCV genotype 6. Patients with RVR(representing>70% of patients) are suitable for 24-wk treatment with expected SVR rates>80%. Patients without RVR and/or those with poor response predictors may benefit from 48 wk of therapy,and a detectable HCV RNA at week 12(with no early virological response) serves as a stopping rule. This treatment scheme is likely to have a major economic impact on HCV therapy, particularly in Southeast Asia,wherein treatment can be truncated securely in the majority of patients with HCV genotype 6.展开更多
BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model...BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model based on a response-guided therapy(RGT)strategy for predicting HBeAg seroconversion and hepatitis B surface antigen(HBsAg)clearance.METHODS In this study,75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa(PEG-IFNα)treatment and a 24-wk follow-up.Logistic regression analysis was used to assess parameters at baseline,week 12,and week 24 to predict HBeAg seroconversion at 24 wk post-treatment.The two best predictors at each time point were used to establish a prediction model for PEG-IFNαtherapy efficacy.Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0.RESULTS The two most meaningful predictors were HBsAg≤1000 IU/mL and HBeAg≤3 S/CO at baseline,HBsAg≤600 IU/mL and HBeAg≤3 S/CO at week 12,and HBsAg≤300 IU/mL and HBeAg≤2 S/CO at week 24.With a total score of 0 vs 2 at baseline,week 12,and week 24,the response rates were 23.8%,15.2%,and 11.1%vs 81.8%,80.0%,and 82.4%,respectively,and the HBsAg clearance rates were 2.4%,3.0%,and 0.0%,vs 54.5%,40.0%,and 41.2%,respectively.CONCLUSION We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNαtherapy.展开更多
Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved t...Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.展开更多
A new treatment paradigm for hepatitis C is that the treatment must include an existing direct-acting antiviral agent, namely, a protease inhibitor(PI) combined with PEGylated interferon-a and ribavirin. The currently...A new treatment paradigm for hepatitis C is that the treatment must include an existing direct-acting antiviral agent, namely, a protease inhibitor(PI) combined with PEGylated interferon-a and ribavirin. The currently mar-keted PIs and PIs in clinical trials have different mecha-nisms of action. The development of new PIs aims for an improved safety profile and higher effectiveness. This article reviews NS3/4A protease inhibitors, focusing on major criteria such as their effectiveness and safety. Specific attention is paid to dosing regimens and adverse event profiles of PIs administered in clinical settings.展开更多
AIM:To predict treatment success using only simple clinical data from peg-interferon plus ribavirin therapy for chronic hepatitis C. METHODS:We analyzed the clinical data of 176 patients with chronic hepatitis and hep...AIM:To predict treatment success using only simple clinical data from peg-interferon plus ribavirin therapy for chronic hepatitis C. METHODS:We analyzed the clinical data of 176 patients with chronic hepatitis and hepatitis C virus genotype 1 who received 48 wk standard therapy, derived a predictive formula to assess a sustained virological response of the individual patient using a logistic regression model and confirmed the validity of this formula.The formula was constructed using data from the first 100 patients enrolled and validated using data from the remaining 76 patients. RESULTS:Sustained virological response was obtained in 83(47.2%)of the patients and we derived formulae to predict sustained virological response at pretreatment and weeks 4,12 and 24.The likelihood of sustained virological response could be predicted effectively bythe formulae at weeks 4,12 and 24(the area under the curve of the receiver operating characteristic:0.821, 0.802,and 0.891,respectively),but not at baseline (0.570).The formula at week 48 was also constructed and validation by test data achieved good prediction with 0.871 of the area under the curve of the receiver operating characteristic.Prediction by this formula was always superior to that by viral kinetics. CONCLUSION:These results suggested that our formula combined with viral kinetics provides a clear direction of therapy for each patient and enables the best tailored treatment.展开更多
文摘Hepatitis C genotype 6 is endemic in Southeast Asia[prevalence varies between 10%-60% among all hepatitis C virus(HCV) infection], as well as also sporadically reported outside the area among immigrations.The diagnosis of HCV genotype can be inaccurate with earlier methods of genotyping due to identical 5'-UTR between genotype 6 and 1b, hence the newer genotyping methods with core sequencing are preferred.Risk factors and clinical course of HCV genotype 6 do not differ considerably from other genotypes. Treatment outcome of HCV genotype 6 with a combination of pegylated interferon and ribavirin is superior to genotype 1, and nearly comparable to genotype 3, with expected sustained virological response(SVR) rates of 60%-90%. Emerging data suggests that a shorter course 24-wk treatment is equally effective as a standard 48-wk treatment, particularly for those patients who attained undetectable HCV RNA at week 4(RVR).In addition, baseline and on-treatment predictors of response used for other HCV genotypes appear effective with genotype 6. Although some pan-genotypic directacting antivirals have completed phase Ⅱ/Ⅲ studies(sofosbuvir and simeprevir) with clinical benefit demonstrated in small number of patients with genotype6, broad availability of these agents in Southeast Asia may not be expected in the near future. While awaiting the newer therapy, response-guided therapy seems appropriate for patients with HCV genotype 6. Patients with RVR(representing>70% of patients) are suitable for 24-wk treatment with expected SVR rates>80%. Patients without RVR and/or those with poor response predictors may benefit from 48 wk of therapy,and a detectable HCV RNA at week 12(with no early virological response) serves as a stopping rule. This treatment scheme is likely to have a major economic impact on HCV therapy, particularly in Southeast Asia,wherein treatment can be truncated securely in the majority of patients with HCV genotype 6.
基金Supported by the Anhui Provincial Natural Science Foundation,No.2108085MH298the Scientific Research Project of the Second Affiliated Hospital of Anhui Medical University,No.2019GMFY02 and 2021lcxk027the Scientific Research Project of Colleges and Universities in Anhui Province,No.KJ2021A0323.
文摘BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model based on a response-guided therapy(RGT)strategy for predicting HBeAg seroconversion and hepatitis B surface antigen(HBsAg)clearance.METHODS In this study,75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa(PEG-IFNα)treatment and a 24-wk follow-up.Logistic regression analysis was used to assess parameters at baseline,week 12,and week 24 to predict HBeAg seroconversion at 24 wk post-treatment.The two best predictors at each time point were used to establish a prediction model for PEG-IFNαtherapy efficacy.Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0.RESULTS The two most meaningful predictors were HBsAg≤1000 IU/mL and HBeAg≤3 S/CO at baseline,HBsAg≤600 IU/mL and HBeAg≤3 S/CO at week 12,and HBsAg≤300 IU/mL and HBeAg≤2 S/CO at week 24.With a total score of 0 vs 2 at baseline,week 12,and week 24,the response rates were 23.8%,15.2%,and 11.1%vs 81.8%,80.0%,and 82.4%,respectively,and the HBsAg clearance rates were 2.4%,3.0%,and 0.0%,vs 54.5%,40.0%,and 41.2%,respectively.CONCLUSION We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNαtherapy.
文摘Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.
文摘A new treatment paradigm for hepatitis C is that the treatment must include an existing direct-acting antiviral agent, namely, a protease inhibitor(PI) combined with PEGylated interferon-a and ribavirin. The currently mar-keted PIs and PIs in clinical trials have different mecha-nisms of action. The development of new PIs aims for an improved safety profile and higher effectiveness. This article reviews NS3/4A protease inhibitors, focusing on major criteria such as their effectiveness and safety. Specific attention is paid to dosing regimens and adverse event profiles of PIs administered in clinical settings.
文摘AIM:To predict treatment success using only simple clinical data from peg-interferon plus ribavirin therapy for chronic hepatitis C. METHODS:We analyzed the clinical data of 176 patients with chronic hepatitis and hepatitis C virus genotype 1 who received 48 wk standard therapy, derived a predictive formula to assess a sustained virological response of the individual patient using a logistic regression model and confirmed the validity of this formula.The formula was constructed using data from the first 100 patients enrolled and validated using data from the remaining 76 patients. RESULTS:Sustained virological response was obtained in 83(47.2%)of the patients and we derived formulae to predict sustained virological response at pretreatment and weeks 4,12 and 24.The likelihood of sustained virological response could be predicted effectively bythe formulae at weeks 4,12 and 24(the area under the curve of the receiver operating characteristic:0.821, 0.802,and 0.891,respectively),but not at baseline (0.570).The formula at week 48 was also constructed and validation by test data achieved good prediction with 0.871 of the area under the curve of the receiver operating characteristic.Prediction by this formula was always superior to that by viral kinetics. CONCLUSION:These results suggested that our formula combined with viral kinetics provides a clear direction of therapy for each patient and enables the best tailored treatment.
