AIM:To examined the efficacy and safety of treatment with boceprevir,PEGylated-interferon and ribavirin(PR)in hepatitis C virus genotype 1(HCVGT1) PR treatmentfailures in Asia.METHODS:The Boceprevir Named-Patient Prog...AIM:To examined the efficacy and safety of treatment with boceprevir,PEGylated-interferon and ribavirin(PR)in hepatitis C virus genotype 1(HCVGT1) PR treatmentfailures in Asia.METHODS:The Boceprevir Named-Patient Program provided boceprevir to HCVGT1 PR treatment-failures.Participating physicians were invited to contribute data from their patients:baseline characteristics,ontreatment responses,sustained virological response at week 12(SVR12),and safety were collected and analysed.Multivariate analysis was performed to determine predictors of response.RESULTS:150 patients were enrolled from Australia,Malaysia,Singapore and Thailand(Asians = 86,Caucasians = 63).Overall SVR12 was 61%(Asians= 59.3%,Caucasians = 63.5%).SVR12 was higher in relapsers(78%) compared with non-responders(34%).On-treatment responses predicted SVR,with undetectable HCVRNA at week 4,8 and 12 leading to SVR12 s of 100%,87%,and 82%respectively,and detectable HCVRNA at week 4,8 and 12,leading to SVR12 s of 58%,22%and 6%respectively.Asian patients were similar to Caucasian patients with regards to on-treatment responses.Patients with cirrhosis(n= 69) also behaved in the same manner with regards to on-treatment responses.Those with the IL28 B CC genotype(80%) had higher SVRs than those with the CT/TT(56%) genotype(P = 0.010).Multivariate analysis showed that TW8 and TW12 responses were independent predictors of SVR.Serious adverse events occurred in 18.6%:sepsis(2%),decompensation(2.7%) and blood transfusion(14%).Discontinuations occurred in 30.7%,with 18.6%fulfilling stopping rules.CONCLUSION:Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80%if they have good on-treatment responses;however,discontinuations occurred in 30%because of virological failure or adverse events.展开更多
BACKGROUND Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biom...BACKGROUND Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein(AFP), protein induced by vitamin K absence/antagonist-Ⅱ(PIVKA-Ⅱ) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs(miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including HCC.AIM To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein biomarkers.METHODS Our prospective, multicenter, case-control study recruited 660 participants(354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR(n = 60) and next-generation sequencing(n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs(including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-Ⅱ via real-time quantitative PCR in training(n = 200) and validation cohorts(n = 300).RESULTS We identified 26 miRNAs that differentiated chronic liver disease controls from(early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p(miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423could significantly distinguish(Q < 0.05) between the HCC and chronic liver disease control groups. In the multivariate setting, miR-21 with PIVKA-Ⅱ was selected as the best combination,resulting in an area under the curve of 0.87 for diagnosis and area under the curve of 0.74 for early diagnosis of HCC. In the validation cohort, only miR-21 and miR-423 could be confirmed as potential HCC biomarkers. A combination of miRNAs did not perform better than any single miRNA. Improvement of PIVKA-Ⅱ performance through combination with miRNAs could not be confirmed in the validation panel. Two putative miRs, put-miR-6 and put-miR-99, were tested in the training and validation panels, but their expression could only be detected in very few samples and at a low level(cycle threshold between 31.24 and 34.97).CONCLUSION miRNAs alone or as a signature in combination with protein biomarkers AFP and PIVKA-Ⅱ do not improve the diagnostic performance of the protein biomarkers.展开更多
Background and Aims:The impact of drug-induced liver injury(DILI)on patients with chronic liver disease(CLD)is unclear.There are few reports comparing DILI in CLD and non-CLD patients.In this study,we aimed to determi...Background and Aims:The impact of drug-induced liver injury(DILI)on patients with chronic liver disease(CLD)is unclear.There are few reports comparing DILI in CLD and non-CLD patients.In this study,we aimed to determine the incidence and outcomes of DILI in patients with and without CLD.Methods:We collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies,causes,and the severity of DILI.We compared the causative agents,clinical features,and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry.Subjects with definite,or highly likely DILI were included in the analysis.Results:A total of 200 subjects diagnosed with DILI were found in the registry.Of those,41 had CLD and 159 had no evidence of CLD in their background.Complementary and alternative medicine(CAM)products were identified as the most common class of DILI agents.Approximately 59%of DILI in the CLD and 40%in non-CLD group were associated with CAM use.Individuals with pre-existing CLD had similar severity including mortality.Twelve patients(6%)developed adverse outcomes related to DILI including seven(3.5%)deaths and five(2.5%)with liver failure.Mortality was 4.88%in CLD and 3.14%in non-CLD subjects over median periods of 58(8–106)days and 22(1–65)days,respectively.Conclusions:In this liver disease registry,the causes,clinical presentation,and outcomes of DILI in subjects with CLD and without CLD patients were not different.Further study is required to confirm our findings.展开更多
文摘AIM:To examined the efficacy and safety of treatment with boceprevir,PEGylated-interferon and ribavirin(PR)in hepatitis C virus genotype 1(HCVGT1) PR treatmentfailures in Asia.METHODS:The Boceprevir Named-Patient Program provided boceprevir to HCVGT1 PR treatment-failures.Participating physicians were invited to contribute data from their patients:baseline characteristics,ontreatment responses,sustained virological response at week 12(SVR12),and safety were collected and analysed.Multivariate analysis was performed to determine predictors of response.RESULTS:150 patients were enrolled from Australia,Malaysia,Singapore and Thailand(Asians = 86,Caucasians = 63).Overall SVR12 was 61%(Asians= 59.3%,Caucasians = 63.5%).SVR12 was higher in relapsers(78%) compared with non-responders(34%).On-treatment responses predicted SVR,with undetectable HCVRNA at week 4,8 and 12 leading to SVR12 s of 100%,87%,and 82%respectively,and detectable HCVRNA at week 4,8 and 12,leading to SVR12 s of 58%,22%and 6%respectively.Asian patients were similar to Caucasian patients with regards to on-treatment responses.Patients with cirrhosis(n= 69) also behaved in the same manner with regards to on-treatment responses.Those with the IL28 B CC genotype(80%) had higher SVRs than those with the CT/TT(56%) genotype(P = 0.010).Multivariate analysis showed that TW8 and TW12 responses were independent predictors of SVR.Serious adverse events occurred in 18.6%:sepsis(2%),decompensation(2.7%) and blood transfusion(14%).Discontinuations occurred in 30.7%,with 18.6%fulfilling stopping rules.CONCLUSION:Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80%if they have good on-treatment responses;however,discontinuations occurred in 30%because of virological failure or adverse events.
文摘BACKGROUND Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein(AFP), protein induced by vitamin K absence/antagonist-Ⅱ(PIVKA-Ⅱ) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs(miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including HCC.AIM To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein biomarkers.METHODS Our prospective, multicenter, case-control study recruited 660 participants(354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR(n = 60) and next-generation sequencing(n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs(including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-Ⅱ via real-time quantitative PCR in training(n = 200) and validation cohorts(n = 300).RESULTS We identified 26 miRNAs that differentiated chronic liver disease controls from(early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p(miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423could significantly distinguish(Q < 0.05) between the HCC and chronic liver disease control groups. In the multivariate setting, miR-21 with PIVKA-Ⅱ was selected as the best combination,resulting in an area under the curve of 0.87 for diagnosis and area under the curve of 0.74 for early diagnosis of HCC. In the validation cohort, only miR-21 and miR-423 could be confirmed as potential HCC biomarkers. A combination of miRNAs did not perform better than any single miRNA. Improvement of PIVKA-Ⅱ performance through combination with miRNAs could not be confirmed in the validation panel. Two putative miRs, put-miR-6 and put-miR-99, were tested in the training and validation panels, but their expression could only be detected in very few samples and at a low level(cycle threshold between 31.24 and 34.97).CONCLUSION miRNAs alone or as a signature in combination with protein biomarkers AFP and PIVKA-Ⅱ do not improve the diagnostic performance of the protein biomarkers.
文摘Background and Aims:The impact of drug-induced liver injury(DILI)on patients with chronic liver disease(CLD)is unclear.There are few reports comparing DILI in CLD and non-CLD patients.In this study,we aimed to determine the incidence and outcomes of DILI in patients with and without CLD.Methods:We collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies,causes,and the severity of DILI.We compared the causative agents,clinical features,and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry.Subjects with definite,or highly likely DILI were included in the analysis.Results:A total of 200 subjects diagnosed with DILI were found in the registry.Of those,41 had CLD and 159 had no evidence of CLD in their background.Complementary and alternative medicine(CAM)products were identified as the most common class of DILI agents.Approximately 59%of DILI in the CLD and 40%in non-CLD group were associated with CAM use.Individuals with pre-existing CLD had similar severity including mortality.Twelve patients(6%)developed adverse outcomes related to DILI including seven(3.5%)deaths and five(2.5%)with liver failure.Mortality was 4.88%in CLD and 3.14%in non-CLD subjects over median periods of 58(8–106)days and 22(1–65)days,respectively.Conclusions:In this liver disease registry,the causes,clinical presentation,and outcomes of DILI in subjects with CLD and without CLD patients were not different.Further study is required to confirm our findings.