The patient with compensated HCV cirrhosis has an advanced form of HCV infection and is at risk of developing complications that may require LTx. As the necroinflammatory activity driven by ongoing HCV infection continues to cause apoptosis and fibrosis, decompensation of the cirrhosis eventually occurs and/or HCC develops. For both of these late complications of end-stage cirrhosis, liver transplantation is the only curative therapy at the present time. Therefore, antiviral therapy with DAAs is considered a high priority for patients with compensated HCV cirrhosis, as the cure of a cirrhotic patient has the greatest impact on patient’s life expectancy and on consumption of health care resources. It is now clear that patients who are cured from HCV have substantially improved survival due to reduction in liver- and non-liver-related causes of death (van der Meer et al. 2012).

Although the presence of cirrhosis was a negative predictor of response in the interferon era, the effect of cirrhosis on response rates to DAAs is greatly diminished. In fact, in most of the DAAs large clinical trials, patients with cirrhosis responded equally well compared to those with early disease (Nelson et al. 2015; Zeuzem et al. 2014; Lawitz et al. 2013, 2014; Afdhal et al. 2014; Poordad et al. 2014; Feld et al. 2014; Sulkowski et al. 2014; Jacobson et al. 2013). Thus, cirrhosis has now essentially vanished as a predictor of response in the DAA era, just as ethnicity, HIV coinfection, and obesity have also proved to be no longer predictors of lower response to DAA therapy. A notable exception remains that of genotype 3 cirrhosis, in which response rates with the currently approved therapy are only 60 %. However, noncirrhotic patients with genotype 3 currently enjoy very high cure rates, as shown in recent studies (Nelson et al. 2015).

A large, recent clinical trial enrolled only compensated cirrhotic patients, who were treated with 3 DAAs plus or minus ribavirin depending on the subtype of genotype 1 (1a or 1b) for durations between 3 and 6 months (Poordad et al. 2014). Between 90 % and 100 % of patients achieved a cure (SVR12), a rate similar to those with early, noncirrhotic disease. The response to modern DAA therapy in patients with HCV cirrhosis can be summarized by stating that over 90 % of these patients are now able to achieve a cure, with the exception of HCV genotype 3 patients, who achieve a cure in 60–80 % of cases (Poordad et al. 2014).

The onset of ascites , hepatic encephalopathy, jaundice, or variceal hemorrhage in a patient with HCV cirrhosis signals the final stages of the disease, commonly referred as decompensation. The onset of decompensation is associated with markedly decreased survival at 1 and 2 years and constitutes a clinical indication to determine if the patient is a viable liver transplant candidate. Antiviral treatment with alpha-interferon of patients with decompensated HCV cirrhosis was fraught with risks and frequent severe complications, on occasion fatal. The allure of inducing sustained virological response (SVR) in patients with decompensated cirrhosis lies in the potential to avoid liver transplantation. One of the first DAA developed was the nucleoside analog lamivudine for hepatitis B virus infection back in 1995. Although not very potent and limited by frequent emergence of resistant variants, lamivudine had a profound impact on transplantation for HBV cirrhosis, decreasing the frequency of HBV by approximately 70 %. Refractory ascites, encephalopathy, and other manifestations of decompensated HBV cirrhosis often substantially improved on lamivudine, leading to removal of many patients from the transplant waiting list. In the case of HCV cirrhosis, the introduction of safe and very effective DAA antiviral therapy has raised the hopes that a similar phenomenon could potentially be observed. In this regard, a multicenter study of sofosfuvir/ledipasvir and ribavirin in decompensated Childs B and C cirrhotics recently reported SVR rates of nearly 90 % (Charlton et al. 2015a).