BACKGROUND The hepatitis C virus(HCV) NS5A inhibitor ABT-267(ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450(paritaprevir, PTV), the CYP3A inhibitor ritonavir(r) and the non-nucleoside NS5B polymerase inhi...BACKGROUND The hepatitis C virus(HCV) NS5A inhibitor ABT-267(ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450(paritaprevir, PTV), the CYP3A inhibitor ritonavir(r) and the non-nucleoside NS5B polymerase inhibitor ABT-333(dasabuvir, DSV)(OBV/PTV/r + DSV) with or without ribavirin(RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1(GT1) infected patients. Patients with HCV who are considered "hard-to-cure" have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures.AIM To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials.METHODS Patients were ≥ 18 years old and chronically infected with HCV GT1(GT1a, GT1b or GT1a/1b). Patients were treatment-na?ve or previously failed a regimen including pegylated interferon/RBV +/-telaprevir, boceprevir, or simeprevir.One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/-RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment.RESULTS Many of the patients studied had comorbidities(44.2% hypertensive, 33.7%obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority(88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue(12%), headache(10%),insomnia(9%) and diarrhea(8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all(98%) patients were treatment compliant.CONCLUSION In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/-RBV is highly effective and tolerable and results in better mental and physical health following treatment.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the hepatic manifestation of the metabolic syndrome(MetS)and is characterized by steatosis in the absence of significant alcohol consumption.However,MetS and signif...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the hepatic manifestation of the metabolic syndrome(MetS)and is characterized by steatosis in the absence of significant alcohol consumption.However,MetS and significant alcohol intake coexist in certain individuals which may lead to the development of BAFLD.AIM To assess the clinical characteristics of patients with both alcoholic and NAFLD(BAFLD)in a large cohort in the United States.METHODS Adults from the National Health and Nutrition Examination Survey between 2003-2014 were included.NAFLD was diagnosed based on elevated alanine aminotransferase(ALT)and being overweight or obese in the absence of other liver diseases.BAFLD patients met the criteria for NAFLD but also had either MetS or type 2 diabetes and consumed excessive amounts of alcohol.Univariable and multivariable analysis were performed to assess differences between NAFLD and BAFLD and to compare severity based on a validated fibrosis score(FIB4 index).RESULTS The prevalence of NAFLD was at 25.9%(95%CI;25.1-26.8)and that of BAFLD was 0.84%(0.67,1.02)which corresponds to an estimated 1.24 million Americans affected by BAFLD.Compared to NAFLD,patients with BAFLD were more likely to be male,smokers,have higher ALT,aspartate aminotransferase,triglycerides,and lower platelets;P<0.01 for all.More importantly,after adjusting for MetS components,BAFLD patients were significantly more likely to have advanced fibrosis[adjusted OR(95%CI)based on FIB4 index>2.67 was 3.2(1.4,7.0),P=0.004].CONCLUSION A significant percentage of the American general population is afflicted by BAFLD and these patients tend to have more advanced liver fibrosis.展开更多
基金an investigatorinitiated grant from AbbVie(B15-791)
文摘BACKGROUND The hepatitis C virus(HCV) NS5A inhibitor ABT-267(ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450(paritaprevir, PTV), the CYP3A inhibitor ritonavir(r) and the non-nucleoside NS5B polymerase inhibitor ABT-333(dasabuvir, DSV)(OBV/PTV/r + DSV) with or without ribavirin(RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1(GT1) infected patients. Patients with HCV who are considered "hard-to-cure" have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures.AIM To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials.METHODS Patients were ≥ 18 years old and chronically infected with HCV GT1(GT1a, GT1b or GT1a/1b). Patients were treatment-na?ve or previously failed a regimen including pegylated interferon/RBV +/-telaprevir, boceprevir, or simeprevir.One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/-RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment.RESULTS Many of the patients studied had comorbidities(44.2% hypertensive, 33.7%obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority(88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue(12%), headache(10%),insomnia(9%) and diarrhea(8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all(98%) patients were treatment compliant.CONCLUSION In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/-RBV is highly effective and tolerable and results in better mental and physical health following treatment.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the hepatic manifestation of the metabolic syndrome(MetS)and is characterized by steatosis in the absence of significant alcohol consumption.However,MetS and significant alcohol intake coexist in certain individuals which may lead to the development of BAFLD.AIM To assess the clinical characteristics of patients with both alcoholic and NAFLD(BAFLD)in a large cohort in the United States.METHODS Adults from the National Health and Nutrition Examination Survey between 2003-2014 were included.NAFLD was diagnosed based on elevated alanine aminotransferase(ALT)and being overweight or obese in the absence of other liver diseases.BAFLD patients met the criteria for NAFLD but also had either MetS or type 2 diabetes and consumed excessive amounts of alcohol.Univariable and multivariable analysis were performed to assess differences between NAFLD and BAFLD and to compare severity based on a validated fibrosis score(FIB4 index).RESULTS The prevalence of NAFLD was at 25.9%(95%CI;25.1-26.8)and that of BAFLD was 0.84%(0.67,1.02)which corresponds to an estimated 1.24 million Americans affected by BAFLD.Compared to NAFLD,patients with BAFLD were more likely to be male,smokers,have higher ALT,aspartate aminotransferase,triglycerides,and lower platelets;P<0.01 for all.More importantly,after adjusting for MetS components,BAFLD patients were significantly more likely to have advanced fibrosis[adjusted OR(95%CI)based on FIB4 index>2.67 was 3.2(1.4,7.0),P=0.004].CONCLUSION A significant percentage of the American general population is afflicted by BAFLD and these patients tend to have more advanced liver fibrosis.
