CASE PRESENTATION “Mr. K,” a 52-year-old single Caucasian man, was diagnosedwith hepatitis C virus (HCV) infection nearly two decades ago after routine testing revealed an elevated alanine transaminase (ALT) level. Additional blood work identified an HCV genotype 1 infection with a viral load of 5.2310 IU/mL. While liver biopsy demonstrated cirrhosis, esophagogastroduodenoscopy showed no varices, and ultrasonography of the liver showed nodularity but no hepatocellular carcinoma. The patient’s only risk factor for HCV infection was a 1-month period of injection drug use (cocaine) 15 years earlier. Mr. K’s psychiatric history was significant for a major depressive episode with psychotic features requiring hospitalization, 6 years before the HCV diagnosis. He had a history of alcohol dependence, consuming up to 75 drinks/week episodically over the 20 years preceding the HCV diagnosis. At the time of his admission fordepression,hehadnotusedalcohol for3months.For the next 6 years, hewas treatedwith an antidepressant, at times in combinationwith an antipsychotic. After his diagnosis of HCV infection, he achieved abstinence from alcohol and was treated with citalopram (30 mg/day). Three years after theHCV diagnosis,Mr. K started weekly pegylatedinterferonalfa-2B(IFN-a2B)injectionsanddailyoral ribavirin forHCVinfection.After the initial IFN-a injection,he experienced significant sideeffects, includingexcessive fatigue, nausea, fevers, and worsening mood symptoms. He decided to take his ribavirin every other day without notifying his care team. At week 6, his HCV therapy was stopped because of delirium caused by the interferon. After a brief hospital admission, his mental status returned to baseline and he was discharged,withoutmodificationofhispsychiatricmedication. For the next 10 years, Mr. K was followed regularly for HCV infection by a hepatologist. Treatment was deferred because of the hepatologist’s concerns about psychiatric side effects. After 10 years, Mr. K developed mild ascites, which was controlledwithdiuretics. At that time, his liver enzymes remained elevated and his liver function had declined. After attending a collaborative-care hepatology and psychiatry clinic,hewasreassessed for interferon-basedtherapy.The clinic psychiatrist monitored Mr. K closely as IFN-a was initiated. Mr. K was started on boceprevir, pegylated IFNa2A, and ribavirin, with the aim of completing 48 weeks of treatment. At week 2, he complained of fatigue and poor sleep, and mirtazapine (15 mg/day) was used to augment the citalopram. Despite attempts to further optimize the citalopram and mirtazapine dosages, Mr. K’s fatigue worsened.Atweek22,hedeveloped liver failure andpresented to the emergency department with hepatic encephalopathy. HCV therapy was stopped and the patient’s mental status soon returned to baseline and his liver function improved. For the next 3 years, Mr. K remained stable with early liver failure. Then, on the eveningnews, heheard about new treatments forHCVinfection thatdonot require IFN-a, and he asked his psychiatrist and hepatologist about them. Simeprevir/sofosbuvir therapy was started, with a planned treatment duration of 12 weeks. Mr. K experienced mild nausea but no other side effects. Hewas followedweekly to monitorandencourageadherence to thisonce-daily two-pill regimen.Hecompleted the full course andwasconfirmed to have sustained virological response. No adjustments to his psychiatric medications were needed, and his depressive symptoms remained stable throughout his treatment.