Abstract: We included seven trials with 1369 participants. All trials had high risk of bias. Five trials used our first definition of slow responders, and three other trials (including one that used both definitions) used the second definition. None of the included trials mentioned our primary outcomes. However, regarding the secondary outcomes, extension of the treatment period to 72 weeks increased the sustained virological response according to both definitions (71/217 (32.7%) versus 52/194 (26.8%); risk ratio (RR) 1.43, 95% confidence interval (CI) 1.07 to 1.92, P = 0.02, I2 = 8%; and 265/499 (53.1%) versus 207/496 (41.7%); RR 1.27, 95% CI 1.07 to 1.50, P = 0.006, I2 = 38%), with a risk difference of 0.11 and calculated number needed to treat of nine. The end of treatment response was not significantly different between the two treatment groups. The number of participants who relapsed virologically was found to be lower in the groups that had been treated for 72 weeks using both definitions (27/84 (32.1%) versus 46/91 (50.5%); RR 0.59, 95% CI 0.40 to 0.86, P = 0.007, I2 = 18%, 3 trials; and 85/350 (24.3%) versus 146/353 (41.4%); RR 0.59, 95% CI 0.47, 0.73, P < 0.000001, I2 = 0%, 3 trials). The length of treatment did not significantly affect the adherence (247/279 (88.5%) versus 252/274 (92.0%); RR 0.95, 95% CI 0.84 to 1.07, P = 0.42, I2 = 69%, 3 trials). In the single trial that reported adverse events, no significant difference was seen between the two treatment groups. This review demonstrates higher a proportion of sustained virological response after extension of treatment from 48 weeks to 72 weeks in HCV genotype 1 infected patients in whom HCV RNA was still detectable but decreased by ≥ 2 log after 12 weeks and became negative after 24 weeks of treatment, and in patients with detectable HCV RNA after four weeks of treatment with peginterferon plus ribavirin. The observed intervention effects can be caused by both systematic error (bias) and random errors (play of chance). There was no reporting on mortality and the reporting of clinical outcomes and adverse events was insufficient. More data are needed in order to recommend or reject the policy of extending the treatment period for slow responders.

Plain-language summary: We found seven randomised clinical trials that compared a treatment duration of 72 weeks with 48 weeks in 1369 participants. The quality of all trials was low. Mortality and liver-related morbidity were not reported in any of the included trials. Sustained virological response (that is, undetectable hepatitis C virus RNA after six months from the end of an entire course of treatment) was increased when the decision to prolong treatment was taken based on viral load after 12 weeks of treatment (RR 1.43, 95% CI 1.07 to 1.92) as well as when the decision to prolong treatment was taken based on the results of the viral load after four weeks of treatment (RR 1.27, 95% CI 1.07 to 1.50). The calculated number needed to treat to achieve an increase in sustained virological response proportions was nine (meaning that among nine participants treated for 72 weeks instead of 48 weeks, only one more will achieve a sustained virological response compared to the participants treated for 48 weeks). The higher sustained virological response after 72 weeks of treatment was caused by a reduction in the number of patients in this group who experienced a virological relapse after treatment. Adherence to treatment was not different between the two groups. Serious adverse events were mentioned in only one trial, and they were not different in the two treatment groups. The findings may be influenced by both risks of systematic errors (bias) and the risk of random errors (play of chance). Further large-scale, randomised trials with reporting of patient relevant outcomes are warranted.