Direct antiviral agents in hepatitis C virus related liver disease:Don’t count the chickens before they’re hatched

Since molecules with direct-acting antiviral(DAA)became available,the landscape of the treatment of hepatitis C virus(HCV)infection has completely changed.The new drugs are extremely effective in eradicating infection,and treatment is very well tolerated with a duration of 8-12 wk.This review aims to report the outstanding clinical benefits of DAA and to highlight their critical disadvantages,identifying some clinically relevant hot topics.First,do the rates of virological response remain as high when patients with more advanced cirrhosis are considered?Large studies have shown slightly lower but still satisfactory rates of response in these patients.Nevertheless,modified schedules with an extended treatment duration and use of ribavirin may be necessary.Second,does the treatment of HCV infection affect the risk of occurrence and recurrence of liver cancer?Incidence is reduced after viral eradication but remains high enough to warrant periodic surveillance for an early diagnosis.In contrast,the risk of recurrence seems to be unaffected by viral clearance;however,DAA treatment improves survival because of the reduced risk of progression of liver disease.Third,can HCV treatment also have favorable effects on major comorbidities?HCV eradication is associated with a reduced incidence of diabetes,an improvement in glycemic control and a decreased risk of cardiovascular events;nevertheless,a risk of hypoglycemia during DAA treatment has been reported.Finally,is it safe to treat patients with HCV/hepatitis B virus(HBV)coinfection?In this setting,HCV is usually the main driver of viral activity,while HBV replication is suppressed.Because various studies have described HBV reactivation after HCV clearance,a baseline evaluation for HBV coinfection and a specific follow-up is mandatory.

Antiviral therapy for ＂difficult-to-treat＂ hepatitis C virus-infected patients

Objective To review the updated research on direct antiviral agents （DAAs）-including regimens for hepatitis C virus （HCV）,and focus on ＂difficult-to-treat＂ HCV-infected patients.Data sources The literature concerning DAAs and hepatitis C cited in this review was collected from PubMed and Google Scholar databases published in English up to July 2013.Study selection Data from published articles regarding HCV and DAAs in clinical trials and in clinical use were identified and reviewed.Results It was recognized that some ＂difficult-to-treat＂ patients would still exist,even though stronger treatments using such as DAAs,including telaprevir and boceprevir,which lead to higher sustained virological response rates,are available.Such patients include those with advanced fibrosis/cirrhosis,elderly persons,children,HCV-human immunodeficiency virus co-infected patients,HCV-infected recipients,and so on.Conclusions Certain ＂difficult-to-treat＂ patients would still exist,even though stronger treatment is available.Although evidence from clinical trials is still lacking,interferon-sparing regimens could have stronger effects for eradicating HCV in such cases.