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Hepatitis C virus (HCV)-related cirrhosis is an extremely heterogeneous pathological condition with a wide spectrum of clinical manifestations, ranging from pre-clinical to compensated and decompensated stages, each of which is characterized by a different clinical outcome. To measure the benefit of a sustained virological response (SVR) with interferon (IFN)-based therapy, several studies have been performed in patients with compensated disease, while only a few have been performed in decompensated disease. Nevertheless, these studies have certain methodological weaknesses that may limit the accuracy of results. Access to new, more effective and safe direct acting antivirals (DAAs) has significantly changed these outcomes, with SVR rates that were not seen previously, making antiviral treatment available to patients with end-stage liver disease. However, the clinical benefit of treating patients with late stage disease is still poorly understood and must be investigated. The existence of a point of no return beyond which a SVR is not beneficial has not yet been determined. All of these issues are discussed in this review.