Peginterferon alfa plus ribavirin is standard treatment for most chronic HCV infections . Substance use, even active alcohol or injection drug use, is not an absolute contraindication to treatment , and despite potential adverse psychiatric effects of interferon use (e.g., irritability, depression, and mood swings), people with serious mental illness are able to complete treatment safely and achieve outcomes comparable to those of patients without serious mental illness , particularly when treated in multidisciplinary integrated settings with close psychiatric follow-up . Additionally, recently approved and newly emerging direct-acting HCV antiviral agents, such as boceprevir and telaprevir, allow for highly effective, shorter-duration treatment regimens that may eventually obviate the need for interferon. The improved efficacy and lowered treatment burdens may rebalance the risk-benefit ratio overwhelmingly in favor of treatment under most, if not all, circumstances. While most HCV-infected patients without cirrhosis or with compensated cirrhosis are eligible for treatment, decompensated cirrhosis, as seen in Mr. H at the time of his presentation, is often a contraindication to treatment, as side effects are more burdensome and success rates lower, making liver transplantation the treatment of choice