The patient, who was a 52-year-old male of Mongolian origin, had cyanotic congenital heart disease. He was born with a large ventricular septal defect that was not repaired in childhood. Over the years, he developed severe shunt-induced pulmonary hypertension leading to shunt reversal (Eisenmenger syndrome) with a resting oxygen saturation of 85-90%. He was in functional NYHA class II-III and suffered from recurrent sustained supraventricular tachycardia. Therefore, he was under continuous treatment with amiodarone 200 mg/day, metoprolol 75 mg/day, and sildenafil 60 mg/day. From a clinical point of view the patient's cardiovascular symptoms were well controlled with the given medication. Being dependent on both medication and regular medical checkups, he was able to work and lead a more or less normal life.
His further medical record consisted of a chronic hepatitis C (genotype 1B), primary biliary cholangiopathy, condition after hepatitis B and tuberculosis, hypothyroidism, and chronic kidney disease (see Table 1 for an overview). He first presented to our Hepatology Outpatient Clinic in 2013.
For his chronic hepatitis C he had been treated twice elsewhere with pegylated interferon and ribavirin in 2003 and 2006, but had shown viral relapse both of these times. In December 2015, we intended to treat the patient with a combination of sofosbuvir 400 mg and ledipasvir 60 mg (Harvoni ). Since the FDA Drug Safety Communication and the EMA had warned about serious bradycardia when amiodarone was combined with sofosbuvir-containing drugs like Harvoni , we wanted the patient to stop amiodarone before and during antiviral therapy. Before the patient was seen by a cardiologist to decide whether amiodarone could be stopped or switched to an alternative drug, the patient took a dose of Harvoni  accidentally at home while still taking amiodarone. He developed symptomatic bradycardia with a heart rate of 30 bpm. An emergency physician applied 50 microg fentanyl and 1 mg midazolam i.v. and started external provisional pacing. The patient was then admitted to our emergency department by air rescue. At admission, his resting ECG showed sinus arrest. With isoprenaline i.v., he developed a frequency-dependent AV block type II and remained with a bradycardic heart rate. Finally, a temporary pacemaker wire had to be placed in the atrium, despite his markedly increased risk for paradoxical systemic embolism as an Eisenmenger patient. After 1 day his condition improved and the majority of heartbeats were self-triggered, resulting in a frequency of 61 bpm. Two days after hospitalization the temporary pacemaker was removed and the patient was discharged in a stable condition.
Because of the language barrier, the patient's complex heart disease that definitely required continuous amiodarone treatment, and his presentation of highly dangerous drug interactions, we decided against further treatment attempts with an antiviral therapy containing sofosbuvir. Due to a lack of treatment alternatives at that time, we saw him for regular follow-ups to monitor his liver function, FibroScan, and viral activity.
In 2016, a new class of antiviral drugs was approved in Switzerland, amongst others Zepatier  (MSD Merck Sharp & Dohme AG), a combination of elbasvir, an NS5A inhibitor, and grazoprevir, an NS3/4A protease inhibitor, for oral treatment of chronic hepatitis C virus (HCV) genotypes 1 and 4.
In the end of 2016, the patient presented with progressive liver disease graded Child A6, MELD 13, demonstrated by elevated liver enzymes (Fig. 1a; Table 2), a FibroScan of 16.5 kPa, CAP 300 dB/m, and an ultrasound showing progressive fibrotic changes in the liver. We conducted a liver biopsy that revealed steatotic and fibrotic parenchyma graded METAVIR A2F3, SAF score S2 A2 F3, the latter score confirming nonalcoholic steatohepatitis. The patient complained about being increasingly tired and about intermittent pain in the upper right quadrant of his abdomen resulting in recurrent sick days and inability to partake in everyday life. Considering these progressive findings and his augmented hepatological risk profile due to his primary biliary cholangiopathy, manifesting with positive AMA-M2 antibodies (1: 1,280), and nonalcoholic steatohepatitis shown in his ultrasound and biopsy, we were urged to reconsider antiviral therapy. Because of his other comorbidities, foremost his kidney disease and hypothyroidism, we decided for a treatment attempt with elbasvir/grazoprevir. Due to the patient's history of cardiac complications under antiviral treatment, we hospitalized him for 2 days in February of 2017 to introduce the medication under telemetric control while he continued using amiodarone. The surveillance and therapy introduction worked without any incident, demonstrated by stable ECG results, so that the patient was discharged after 2 days.
During the 12-week therapeutic period we did regular follow-ups every 2-3 weeks in close collaboration with the cardiologists. Apart from palpitations uttered by the patient, which were without any ECG correlate, the patient showed an improving general state. He reported being less tired and a decrease in the above-mentioned abdominal pain. Palpitations are described as frequent side effects of Zepatier  by the producer, therefore we regarded them as such.
Liver enzymes started to normalize as early as 2 weeks after the beginning of the elbasvir/grazoprevir treatment (Fig. 1a; Table 2). The hepatitis C viremia decreased over the first few weeks, with an undetectable virus content 1 month after therapy induction (Fig. 1c; Table 2). During the first few weeks the patient's kidney values increased but returned to a stable level towards the end of therapy (Fig. 1b; Table 2).
With a sustained virological response 12 weeks after the end of antiviral treatment with elbasvir/grazoprevir, our patient was considered cured of his hepatitis C. With regard to the comorbidities and the complicated history including two viral relapses following interferon therapy and cardiac complications under sofosbuvir, we consider this a big success.