The hepatitis C virus(HCV) is one of the most common causes of chronic liver disease and the leading indication for liver transplantation worldwide. Every aspect of the HCV life cycle is closely tied to human lipid me...The hepatitis C virus(HCV) is one of the most common causes of chronic liver disease and the leading indication for liver transplantation worldwide. Every aspect of the HCV life cycle is closely tied to human lipid metabolism. The virus circulates as a lipid-rich particle, utilizing lipoprotein cell receptors to gain entry into the hepatocyte. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation and circulating hypocholesterolemia. Patients with chronic hepatitis C(CHC) are at increased risk of hepatic steatosis, fibrosis, and cardiovascular disease including accelerated atherosclerosis. HMG Co A Reductase inhibitors, or statins, have been shown to play an important role in the modulation of hepatic steatosis and fibrosis, and recent attention has focused upon their potential therapeutic role in CHC. This article reviews the hepatitis C viral life cycle as it impacts host lipoproteins and lipid metabolism. It then describes the pathogenesis of HCV-related hepatic steatosis, hypocholesterolemia and atherosclerosis, and finally describes the promising anti-viral and anti-fibrotic effects of statins, for the treatment of CHC.展开更多
AIMTo evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial. METHODSA prospective, multicenter, ...AIMTo evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial. METHODSA prospective, multicenter, phase 3, open-label, single-arm study of PEG-IFN alfa, weight-based RBV, and boceprevir, with a PEG-IFN/RBV lead-in phase was performed. The HCV/human immunodeficiency virus coinfected study population included treatment naïve (TN) and treatment experienced (TE) patients. Treatment duration ranged from 28 to 48 wk dependent upon response-guided criteria. All patients had HCV Genotype 1 with a viral load > 10000 IU/mL. Compensated cirrhosis was allowed. Sample size was determined to establish superiority to historical (PEG-IFN plus RBV) rates in sustained viral response (SVR). RESULTSA total of 257 enrolled participants were analyzed (135 TN and 122 TE). In the TN group, 81.5% were male and 54.1% were black. In the TE group, 76.2% were male and 47.5% were white. Overall SVR12 rates (HCV RNA P = 0.002). Among the TN, SVR12 was 42.1% among whites and 27.4% among blacks (P = 0.09). CONCLUSIONThe trial met its hypothesis of improved SVR compared to historical controls but overall SVR rates were low. All-oral HCV treatments will mitigate these difficulties.展开更多
文摘The hepatitis C virus(HCV) is one of the most common causes of chronic liver disease and the leading indication for liver transplantation worldwide. Every aspect of the HCV life cycle is closely tied to human lipid metabolism. The virus circulates as a lipid-rich particle, utilizing lipoprotein cell receptors to gain entry into the hepatocyte. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation and circulating hypocholesterolemia. Patients with chronic hepatitis C(CHC) are at increased risk of hepatic steatosis, fibrosis, and cardiovascular disease including accelerated atherosclerosis. HMG Co A Reductase inhibitors, or statins, have been shown to play an important role in the modulation of hepatic steatosis and fibrosis, and recent attention has focused upon their potential therapeutic role in CHC. This article reviews the hepatitis C viral life cycle as it impacts host lipoproteins and lipid metabolism. It then describes the pathogenesis of HCV-related hepatic steatosis, hypocholesterolemia and atherosclerosis, and finally describes the promising anti-viral and anti-fibrotic effects of statins, for the treatment of CHC.
基金Princy N Kumar MD and Susan Vajda RN - Georgetown University (Site 1008) Grant N/ADonna Mc Gregor and Richard Green - Northwestern University CRS (Site 2701) Grant AI 069471, UL1 RR02574+43 种基金Metro Health CRS (Site 2503) Grant 1U01AI069501-01Mark A Rodriguez RN BSN and Geyoul Kim RN BS - Washington University Therapeutics CRS (Site 2101) Grant AI69439Graham Ray and Jacob Langness - University of Colorado CRS (Site 6101) Grant2UM1AI069432, UL1 TR001082Roger Bedimo and Holly Wise - Trinity Health and Wellness Center CRS (Site 31443) Grant U01 AI069471Michelle Saemann RN BSN and Carl J Fichtenbaum MD - University of Cincinnati (Site 2401) Grant UM1AI068636Jorge L Santana Bagur MD FIDSA and Daniel Casiano RN BSN - Puerto Rico AIDS/CRS (Site 5401) Grant 5UM1AI069415UCSD Antiviral Research Center CRS (Site 701) Grant UM1AI069432Valery Hughes FNP and Todd Stroberg RN - Weill Cornell Chelsea CRS (Site 7804) Grant 5UM1 AI069419, UL1 TR000457Roberto C Arduino and Martine Diez - Houston AIDS Research Team CRS (Site 31473) Grant 2UM1 AI069503Pola de la Torre MD and Yolanda Smith BA - Cooper University Hospital (Site 31476) Grant AI069503-01Ioana Bica MD and Betsy Adams RN - Boston Medical Center (Site 104) Grant 5U01A1069472Ilene Wiggins RN and Andrea Weiss BPharm - Johns Hopkins University CRS (Site 201) Grants 2UM1 AI069465 and UL1TR001079Institute for Clinical and Translational ResearchUniversity of Washington AIDS CRS (Site 1401) Grant UM1AI069481Pamela Poethke RN and Deborah Perez RN - the Miriam Hospital CRS (Site 2951) Harvard/Boston/Providence CTU Grant UM1-AI069412Mary Adams RN and Christine Hurley RN - University of Rochester (Site 31787) Grant UM1 AI069511, UL1 TR000042Debbie Slamowitz RN and Sandra Valle PA-C - Stanford University (Site 501) Grant AI 069556Ramakrishna Prasad MD MPH and Lisa Klevens RN BSN - University of Pittsburgh (Site 1001) Grant UM1AI069494Dr. Susan Koletar, MD and Kathy Watson RN - Ohio State University (Site 2301) Grant UM1AI069494Benigno Rodriguez MD MSc FIDSA and Kristen Allen RN BSN - Case CRS (Site 2501) Grant AI69501Peter Gordon MD and Jolene Noel-Connor RN - Columbia University P and S CRS (Site 30329) Grant 5UM1AI069470-10Supported in part by Columbia University's CTSA grant UL1 TR000040 from NCATS/ NIHBronx-Lebanon Hosp. Ctr. CRS (Site 31469) Grant 1U01AI069503-01Daniel Nixon DO Ph D and Vicky Watson RN - Virginia Commonwealth University CRS (Site 31475) Grant UM1-AI069503Shobha Swaminathan and Baljinder Singh - Rutgers New Jersey Medical School CRS (Site 31786) Grant AI069419-10Connie Funk RN MPH and Fred R Sattler MD - University of Southern California CRS (Site 1201) Grants AI069428 and AI27673Beverly E Sha MD and Tondria Green RN BSN ACRN - Rush University Medical Center CRS (Site 2702) Grant U01 AI069471Linda Makohon RN BSN and Leslie Faber RN BSN - Henry Ford Health System (Site 31472) Grant 5UM1A1069503, B40465Susan Blevins RN MS ANP-C and Catherine Kronk BA - Chapel Hill CRS (Site 3201) Grants UM1 AI069423, CTSA: 1UL1TR001111, CFAR: P30 AI50410Vicki Bailey RN and Fred Nicotera Vanderbilt Therapeutics CRS (Site 3652) Grant 2UM1AI069439-08supported in part by the Vanderbilt CTSA grant TR000445 from NIHAlabama CRS (Site 31788) Grant 1U01AI069452-01Dr. Debika Bhattacharya MD and Maria Palmer PA - UCLA Care Center CRS (Site 601) Grant AI069424Jacquelin Granholm and Susanna Naggie- Duke University (Site 1601) Grant U01-AI069484Eric S Daar and Sadia Shaik - Harbor-UCLA (Site 603) Grant AI 069424, UL1 TR000124Denver Public Health CRS (Site 31470)Wayne State Univ. CRS (Site 31478) Grant 1U01AI069503-01Annie Luetkemeyer MD and Anna Smith RN - UCSF AIDS CRS (Site 801) CTU Grant 5UM1AI069496Pablo Tebas MD and Yan Jiang RN Penn Therapeutics CRS (Site 6201) Grant ACTG: UMIA-069534-08, CFAR: 5-P30-AI-045008-15Amy Sbrolla RN and Teri Flynn ANP-BC - Massachusetts General Hospital CRS (Site 101) Grant UM1AI068636Paul Sax MD and Cheryl Keenan RN BC - Brigham and Women’s Hospital (Site 107) Grant UM1AI069412Clifford Gunthel MD and Ericka R Patrick RN MSN - Emory-CDC CTU The Ponce de Leon CRS (Site 5802) Grant 1U01AI069418-01Emory University Center For AIDS Research P30AI050409Weill Cornell Uptown CRS (Site 7803) Grant UM1AI069419
文摘AIMTo evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial. METHODSA prospective, multicenter, phase 3, open-label, single-arm study of PEG-IFN alfa, weight-based RBV, and boceprevir, with a PEG-IFN/RBV lead-in phase was performed. The HCV/human immunodeficiency virus coinfected study population included treatment naïve (TN) and treatment experienced (TE) patients. Treatment duration ranged from 28 to 48 wk dependent upon response-guided criteria. All patients had HCV Genotype 1 with a viral load > 10000 IU/mL. Compensated cirrhosis was allowed. Sample size was determined to establish superiority to historical (PEG-IFN plus RBV) rates in sustained viral response (SVR). RESULTSA total of 257 enrolled participants were analyzed (135 TN and 122 TE). In the TN group, 81.5% were male and 54.1% were black. In the TE group, 76.2% were male and 47.5% were white. Overall SVR12 rates (HCV RNA P = 0.002). Among the TN, SVR12 was 42.1% among whites and 27.4% among blacks (P = 0.09). CONCLUSIONThe trial met its hypothesis of improved SVR compared to historical controls but overall SVR rates were low. All-oral HCV treatments will mitigate these difficulties.
