March/April - West Virginia State Medical Association

| Scientific Articleif patient weighs less than 75kg, then800mg/daily as 400 bid is utilized;however, if the patient weighs morethan 75kg, then 1000mg should beused daily, given in two divideddoses: 400 in the morning and 600 atnight. If the patient weighs more than100kg, the maximum dose of ribavirinof 1200mg/daily could be attemptedwith careful monitoring of the CBC.For HCV genotype 1 (mostcommon in the US); if there isa RVR, the duration of therapycan be shortened to 24 weeksinstead of 48 weeks. If there isa slow viral response (meaningthat the qualitative PCR becomesnegative at 24 weeks rather than12 weeks, or if there is a twologdrop in the viral titer but thequalitative test is still positive at12 weeks) then it is recommendedthat the duration of treatment beextended to 72 weeks (Figure 1).Preceding therapy, patients,both male and female should becounseled to prevent pregnancyduring and up to six months aftertherapy. Furthermore, all patientsshould have a baseline evaluationthat includes the following:a) Psychiatric evaluation andclearance. If patient is takinganti-depressants, requirefour weekly follow-ups totheir psychiatrist for theduration of therapy.b) Baseline retinal examinationby an ophthalmologist, dueto the effects of interferon.c) Blood work should includeCBC with differential,LFT, KFT, and TSH.During therapy, a weekly CBC forthe first month and every four weeksthereafter should be maintained.Any change in the dosage of eitherribavirin or interferon shouldrevert patient to a weekly cycleuntil blood counts are stable.What new therapies are coming?The investigational agentsfor HCV infection can bedivided into three areas:a) Treatments targeting HCVencodedproteins.b) Treatments targeting hostencodedproteins.c) Therapeutic andpreventive vaccines.In addition, there are ongoingdiscussions among the liver expertsabout triple therapy rather thandual therapy. There are somepromising reports with triple therapyusing interferon, ribavirin, plusnitazoxanide “an anti-protozoaldrug” or triple therapy withinterferon, ribavirin, plus one of theprotease inhibitors such as Telapreviror Boceprevir; and or the additionof the antiviral agent Silibinin. 6-15Telaprevir and Boceprevir areprotease inhibitors which belong toa class of agents known as DAA’s(Direct-Acting Anti-virals), and arethe two products currently in phasethree development. Hopefully,these medications will soon beavailable on the market. 16 Oncethese products are readily available,they will be used in conjunctionwith ribavirin and peginterferon forthe initial 8 to 12 weeks of therapyfollowed by another 12 weeksof ribavirin and peginterferon ifnecessary. Due to their excellentanti-viral effects, many physiciansare withholding therapy for newlydiagnosed HCV patients till thesedrugs are available on the market.SummaryThe take home message is that itis our duty as treating physiciansto keep people on therapy byeliminating drop-outs, keeping inmind that it is no longer acceptableto think of genotype 1 and 4 as“difficult to treat” or that genotype 2and 3 are “easy to treat”. Treatmentshould be tailored to the specificpatient and to the specific virus thatinfected that particular patient.Although the genotype is animportant driver of responseand is useful in designing theinitial treatment plan, it is clearthat once treatment is initiated,RVR is the most important andpowerful predictor of SVR. 3It is our opinion that HCV is apotentially treatable disease, buttreatment is not a “one size fits all”,but rather should be tailored andindividualized for each patient.However, if there is a responseat week four of therapy [RVR],treat the patient for 24 weeksonly, regardless of the genotype.If there is a response at week 12 oftherapy [EVR], treat for 48 weeks,regardless of the genotype. If thereis a response at 24 weeks of therapy[Slow Virologic Response], treat for72 weeks regardless of the genotype.Chronic HCV is a potentiallytreatable disease with thefollowing response rates“Sustained Virologic Response”:a) SVR of approximately 70---75% if RVR is achievedb) SVR of approximately 55---63% if EVR is achievedc) SVR of approximately30---33% if there was aSlow Viral ResponseThe most recent and detailedrecommendations about treatmentof HCV can be found in theAmerican Association for the Studyof Liver Diseases (AASLD) practiceguidelines that were published inthe Hepatology Journal in April2009, (2); or at their web site: www.aasld.org/practiceguidelines.Since the preparation of thismanuscript, Incivek [Telaprevir]and Victrelis [Boceprevir] havebecome available on the marketfor the treatment of Hepatitis CGenotype 1 as triple therapy-March/April 2012 | Vol. 108 23