How Soon To Initiate Hepatitis C Therapy After Transmission
When to initiate antiviral therapy for acute hepatitis C
June 4 2013
Lancet Infect Dis. 2013;13:497-506
Deterding K, Grüner N, Buggisch P, et al.
Delayed versus immediate treatment for patients with acute hepatitis C: a randomised controlled non-inferiority trial.
Is there a role for delayed treatment?
Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%.
However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment.
In our open-label phase 3 non-inferiority trial, we enrolled adults (≥18 years) with acute hepatitis C but no HIV or hepatitis B co-infection at 72 centres in Germany. We randomly allocated patients with symptomatic acute hepatitis C (1:1) to receive immediate pegylated interferon alfa-2b treatment for 24 weeks or delayed treatment with pegylated interferon alfa-2b plus ribavirin (for 24 weeks) starting 12 weeks after randomisation if HCV RNA remained positive. We used a computer-generated
randomisation sequence and block sizes of eight, stratified by bilirubin concentration.
We assigned all asymptomatic patients to immediate treatment with pegylated interferon alfa-2b for 24 weeks. The primary endpoint was sustained HCV RNA negativity in all randomly allocated participants who completed screening (intention-to-treat analysis), with a non-inferiority margin of 10%.
For the primary analysis, we calculated the virological response of patients in the immediate and delayed
treatment groups and an absolute risk difference stratified by bilirubin status. The trial was stopped early on advice from the study advisory committee because of slow recruitment of participants. This study is registered, number ISRCTN88729946.
Between April, 2004, and February, 2010, we recruited 107 symptomatic and 25 asymptomatic patients.
37 (67%) of 55 symptomatic patients randomly allocated to receive immediate treatment and 28 (54%) of 52
symptomatic patients randomly allocated to receive delayed treatment had a sustained virological response
(difference 13·7%, 95% CI −4·6 to 32·0; p=0·071). 18 (72%) of 25 asymptomatic patients had a sustained virological response. 22 (42%) of 52 symptomatic patients allocated to receive delayed treatment did not complete follow-up compared with 20 (25%) of 80 symptomatic or asymptomatic patients assigned immediate treatment (p=0·037). 11 symptomatic patients (21%) assigned delayed treatment had spontaneous HCV clearance. 14 patients who received delayed pegylated interferon alfa-2b plus ribavirin treatment and completed follow-up achieved sustained virological response.
Delayed treatment is effective although not of equal efficacy to immediate treatment; coupled with the rate of spontaneous clearance it can reduce unnecessary treatment in closely monitored populations. Immediate treatment seems preferable in populations where loss to follow-up is great.
Some patients with HCV may benefit from delayed
Aug 17 2012
Deuffic-Burban S. J Hepatol. 2012;57:260-266.
Delayed initiation of treatment may be beneficial for patients with HCV detected more than 2 months after transmission, according to recent results.
Researchers designed a model to compare three
treatment initiation methods in patients with acute HCV:
immediate (within 2 months of transmission); early (within 3 months) and delayed (within 4 to 5 months).
The model incorporated data from a separate study which evaluated outcomes in patients with acute HCV
according to the presence of clinical symptoms; and a study in which the efficacy of early treatment was measured.
The likelihood of a patient achieving SVR was estimated at 92.6% with treatment initiated within 2 months of transmission, 76.5% within three months and 78.6% within
4 to 5 months.
A 50% frequency of the C/C genotype was assumed, along with an increased likelihood of HCV clearance among patients with this genotype (OR=0.38) compared to those without it. Investigators used this model to estimate the probability of developing chronic HCV after 18 months under each treatment method, according to the
presence of clinical symptoms and the C/C IL28B genotype.
Immediate initiation was linked to a lower probability of developing chronic HCV for both symptomatic (7.1% of those with C/C genotype, 7.3% of those without)
and asymptomatic (6.6% with and 7.1% without) patients compared with delayed initiation, for which researchers estimated probabilities of 13.5%
with C/C genotype and 18.0% without among
symptomatic patients; and 14.6% with and 18.5% without C/C among asymptomatic patients.
Higher probabilities for chronic HCV were estimated for early initiation, with 22.5% of C/C and 23.1% of non-C/C
symptomatic patients developing the illness, along with 21.1% of C/C and 22.5% of non-C/C asymptomatic patients.
“Regardless of IL28B polymorphism, in asymptomatic or symptomatic patients in whom [acute HCV] is detected within 2 months of HCV transmission, it is preferable to propose immediate antiviral therapy,” the researchers wrote. “In patients in whom acute HCV transmission is detected more than 2 months after transmission, treatment 4 or 5 months later may be preferred because of higher rates of spontaneous HCV clearance after 2 months and almost similar HCV treatment efficacy between months 3 and months 4-5; again, regardless of symptomatic or non-symptomatic nature of the disease and IL28B polymorphism.”
Disclosure: See the study for a full list of relevant financial disclosures.