Hepatitis C virus therapy in advanced liver disease: Outcomes and challenges.

While for many years investigators had worked on highly effective direct-acting antiviral agent (DAA) therapy, we are now encountering challenges on the appropriate timing of DAA therapy in patients with decompensated cirrhosis. Improvement in hepatic function and quality of life can be achieved following successful therapy but not in all patients. Predictors of improvement or failure to improve have been noted but these are currently not robust enough to ubiquitously apply them to clinical practice. The lowest probability of improvement in hepatic function and avoidance of Model for End-stage Liver Disease (MELD) "purgatory" appears to be in those with MELD >20 while the more likely scenario of improvements is in those with MELD <15. Ideally, patients with a MELD score >20 should be transplanted first and treated for hepatitis C virus (HCV) infection after liver transplantation (LT). Those with MELD score <15 should be considered readily for treatment while in those with MELD of 15-20, treatment has to be individualized with full discussion of the pros and cons of treating them pre- or post-LT. However, it is to be appreciated that the majority of patients with decompensated cirrhosis across the world may not be eligible for liver transplant or may not have access to LT; thus, these patients should be considered for HCV therapy with the hope and expectation that they still gain variable degrees of benefit from successful DAA therapy.