A 56-year-old Chinese woman presented with tea-colored urine, malaise and loss of appetite for 2 weeks. She does not drink alcohol. The diagnosis of acute exacerbation of chronic viral hepatitis B infection was supported by the presence of HBV ("hepatitis B virus") surface antigen and e antigen. Other investigation results revealed total bilirubin 16 μmol/L, ALT ("alanine transaminase") 460 IU/L, and HBV DNA level > 20000 IU/mL. The ultrasound scan of liver revealed no evidence of liver cirrhosis. The treating physician is considering antiviral agents for treatment of HBeAg ("hepatitis B e-antigen") positive chronic HBV infection. She also had a past medical history of seizures, diabetes mellitus, hypertension, supraventricular tachycardia, hyperlipidaemia, and GERD (“gastroesophageal reflux disease”). Her medications included phenytoin, metformin, lisinopril, verapamil, simvastatin, and lansoprazole. 

(a) Discuss the PROS and CONS of various antiviral treatment options for the patient: Entecavir (“ETV”), Tenofovir disoproxil fumarate (“TDF”), Tenofovir alafenamide (“TAF”) and Peginterferon (“PEG-INF”). (8 marks) 

(b) Describe the pharmacokinetic changes in severe liver cirrhosis (Child- Pugh Class C) and the impact on phenytoin metabolism. (3 marks) 

(c) As her liver disease progresses to the stage of severe cirrhosis (decompensated), how would you advise to adjust her medications for treatment of diabetes mellitus, hypertension and supraventricular tachycardia, hyperlipidaemia and GERD, and explain the reasons for changes? (9 marks)