{"id":1821,"date":"2008-04-01T16:58:29","date_gmt":"2008-04-01T15:58:29","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=1821"},"modified":"2013-08-30T10:44:13","modified_gmt":"2013-08-30T10:44:13","slug":"no-effect-of-interferon-maintenance-therapy-on-fibrosis-progression-in-non-responders","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/1821","title":{"rendered":"No effect of interferon maintenance therapy on fibrosis progression in non-responders"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong><\/p>\n

One aspect of HCV management that is informed by little data, is whether continued treatment of virologic non-responders with maintenance peg-IFN therapy can reduce the rate of clinical HCV progression.<\/strong><\/p>\n

This question was addressed in a study presented by Kenneth Sherman and colleagues in a multicentered US study that treated a mixed group of 329 patients (68% naive and 32% refractory to previous treatment) with peg-IFN-alpha-2a plus weight-based ribavirin for 12-18 weeks. Median age was 48 years; 83% male; 43% white, 37% black, non-Hispanic and 15% Hispanic; baseline median HCV viral load was 6.6 log IU; CD4 was 498 cells\/mm3; 74% had HIV RNA <50 copies\/mL.<\/p>\n

Early virologic response (EVR) was defined as achieving undetectable HCV viral load (<600 IU) or 2-log drop at week 12. Patients without an EVR received biopsy and were randomised to peg-IFN 180ug alone or observation for 72 weeks.<\/p>\n

Liver biopsies obtained at start and end of therapy were blinded, and read by a single pathologist. The study design required 134 subjects to show whether maintenance treatment produced 0.18 unit\/year reduction in the rate of Metavir fibrosis progression.<\/p>\n

EVR was observed in 55.6% patients (95%CI 50 to 61%; ITT analysis) and was strongly associated with expected factors (gender, race, degree of fibrosis, AST, absolute neutrophil and heamoglobin levels.<\/p>\n

86 patients without EVR were then randomised to peg-IFN vs observation. Median entry Metavir score was 2; 28% had advanced fibrosis (F3, F4).<\/p>\n

However, lack of fibrosis progression in both groups, lead to DSMB-recommended early closure of the study, when 62 patients had completed 72 weeks of follow-up, only 45 of who had paired biopsy results for this analysis (24 in the IFN, 21 in observation arm).<\/p>\n

Compared to the expected rate of 0.18 units\/year, median fibrosis change was 0.0 (Q1,Q3: 0.0, 0.69) in the maintenance groups and 0.0 units\/year (Q1,Q3: \u00960.69, 0.61) in the control group.<\/p>\n

The authors concluded that, in contrast to recent reports, this randomised controlled trial failed to identify significant change in hepatic fibrosis among untreated non-early virologic responses over 72 weeks. They also commented that weight-based ribavirin achieved higher levels of EVR (55.6% vs. 41%) than the ACTG 5071 study, which used lower doses of ribavirin, and that race (Causaian>Hispanic>Black) appears to be an important independent factor in early virologic response.<\/p>\n

Comment<\/h3>\n

Right from the early registration studies for interferon and ribavirin, investigators had noted a slight reduction in hepatic fibrosis scores and also decreases in activity\/inflammation, which drives fibrosis in patients who did not have a virological response to therapy. A question that had been asked was does this therapy have an anti-fibrotic effect over and above its anti-viral effect?<\/strong><\/p>\n

This phenomenon was recently explored in the HALT-C study (AASLD 2007, De Bisceglie et al), where HCV mono-infected patients with Child-Pugh A cirrhosis and previous non-response, were randomised to continue pegIFN-alpha 2a at half-dose (90mg) or placebo over 3.5 years. The end-points were death, de-compensation, HCC or an increase in fibrosis by two points. The results, presented by the authors at AASLD, suggested that for all individual end-points, there was no significant difference between the pegIFN arm and the placebo arm, thus suggesting that in clinical terms, pegIFN maintenance therapy did not prevent progression in cirrhotic patients.<\/strong><\/p>\n

This study, also called the SLAM-C study, included HIV\/HCV co-infected patients, 15% of whom had cirrhosis. \u00a0After a lead in period of treatment with pegIFN and weight-based ribavirin, patients with no EVR were randomised to maintenance therapy with pegIFN 180mcgs\/week or no therapy. Liver biopsies were evaluated after 72 weeks. There was no fibrosis progression in either arm. However, there was a greater reduction in inflammatory scores in patients on pegIFN arm. Clearly this begs the question of whether maintenance therapy will help reduce fibrosis progression in non-virological responders. From this study, evidently not, although these were small numbers, therapy and follow-up was only for 72 weeks and that these patients had good CD4 counts and well-controlled HIV disease, and were therefore likely to have slow progression of HCV related fibrosis.<\/strong><\/p>\n

Taking HALT-C and SLAM-C results into account, current evidence does not support pegIFN maintenance in patients with no virological response.<\/strong><\/p>\n

Reference:<\/p>\n

Sherman K, et al. Sustained Long-term Antiviral Maintenance with Pegylated Interferon in HCV\/HIV-co-infected Patients: Early Viral Response and Effect on Fibrosis in Treated and Control Subjects.15th CROI, Boston 2008. Abstract 59.
\nhttp:\/\/www.retroconference.org\/2008\/Abstracts\/31871.htm<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base One aspect of HCV management that is informed by little data, is whether continued treatment of virologic non-responders with maintenance peg-IFN therapy can reduce the rate of clinical HCV progression. This question was addressed in a …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,24],"tags":[62],"class_list":["post-1821","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-hepatitis-coinfection","tag-croi-2008"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1821","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=1821"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1821\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=1821"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=1821"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=1821"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}