title: Recurrent hepatitis C after liver transplantation: on-treatment prediction of response to peginterferon/ribavirin therapy.
abstract: Sustained virologic response (SVR) in the treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) remains suboptimal. We evaluated efficacy of pegylated interferon alfa (PEG) and ribavirin (RBV) (PEG/RBV) combination therapy in LT recipients with recurrent HCV and predictive values of rapid virological response (RVR) and early virologic response (EVR). Between January 2001 and October 2005, LT recipients with recurrent HCV were intended to be treated for 48 weeks with PEG/RBV combination therapy independent of genotype or virologic response [53 patients (79% genotype 1)]. On-treatment predictor of response at week 4 (RVR) was defined as undetectable HCV RNA, and at week 12 (EVR) as undetectable HCV RNA or a >2 log(10) drop from pretreatment viral load. SVR was seen in 19 (35%) patients. Patients with genotype 2/3 were more likely to achieve SVR than those with genotype 1 (87% versus 23%; P = 0.001). The highest rate of SVR was seen in patients with RVR [specificity and positive predictive value (PPV) = 100%] while the highest rate of treatment failure was seen in those who did not have EVR [sensitivity and negative predictive value (NPV) = 100%]. The NPV of RVR to identify those who will not achieve SVR was also very high (88%). EVR had low PPV (63%) to identify those with SVR. In conclusion, PEG/RBV combination therapy is effective in the treatment of post-LT recurrent HCV. On-treatment virologic monitoring is highly predictive of SVR and may optimize the virologic response and minimize toxicity. Given its high PPV and NPV, RVR appears to be the most appropriate decision time point for continuation of therapy.
authors.affiliation: Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Hanouneh
authors.forename: Charles
authors.initials: C
authors.lastname: Miller
authors.forename: Federico
authors.initials: F
authors.lastname: Aucejo
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Quinn
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Zein
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D017093:Liver Failure / Q000209:etiology / Q000601:surgery*; D016031:Liver Transplantation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012008:Recurrence; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a